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Coronary Insufficiency: Relations Between Hemodynamic, Electrical, and Biochemical Parameters
Abstract
Perfusion of the left coronary artery of open chest dogs at fixed control and ischemic flow rates demonstrated that ST alterations in the electrocardiogram were always associated with significant hemodynamic and metabolic changes. Decreased pressure time per minute, atrial hypertension, increased myocardial oxygen extraction, and the presence of excess lactate accompanied ischemia. In three dogs, hemodynamic changes, the presence of "excess lactate," or both, preceded significant electrocardiographic changes.
Whenever coronary flow was insufficient to meet myocardial oxygen demands, a series of metabolic shifts occurred. The most significant of these was inadequate aerobic energy production and stimulation of anaerobic glycolysis. This acceleration of anaerobic myocardial metabolism may be present without notably altering the surface electrocardiogram. The absence of ST shifts does not rule out the presence of concomitant and potentially severe myocardial ischemia.
... A resposta a essas questões tem sido procurada em trabalhos experimentais por uma série de autores. Vários deles estudaram os efeitos da oclusão coronária no eletrocardiograma epicárdico, considerando as variações do segmento ST [15][16][17][18][19][20][21][22] . Outros procuraram comprovar a importância dessa variação, comparando-a com as determinações da atividade da creatinofosfoquinase 23,24 e da pressão parcial de oxigênio 25,26 , nos mesmos locais. ...
... Embora vários trabalhos referentes à oclusão coronária e revascularização miocárdica procurem estabelecer a viabilidade das fibras miocárdicas e a reversibilidade de suas alterações, os resultados são controversos e os meios de avaliação não uniformes. Vários autores têm se referido às alterações do segmento ST como reflexo fiel da lesão miocárdica após oclusão coronariana [15][16][17][18][19][20][21][22][23][24][25][26] . No presente trabalho, além desses parâmetros, foram consideradas também, as alterações da onda Q, como evidência de necrose das fibras; procurou-se, assim, estudar a influência de revascularização miocárdica na extensão e intensidade das alterações eletrocardiográficas consequentes à oclusão coronária experimental. ...
... Nesse particular, há também discordância entre os vários autores que estudaram tais áreas em experimentos de oclusão coronária. Alguns realmente não encontraram alterações nas mesmas 23,30,31 outros relataram diminuição do fluxo coronário nestes locais, de 10 a 15% [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]34,35 , tentando explicar esse fato como decorrente de angioespasmo reflexo 14,35 , aumento da resistência coronariana por hipercontração compensadora na zona ocluída 14,35 , aumento da tensão muscular desta zona 14 ou aumento da impedância aórtica 35 . ...
... Ischemia was defined as the sum of the tissue samples with less than 50% of the mean activity over the total myocardium, expressed in cpm/g. The 50% level was chosen because it has been shown that biochemical evidence of ischemia does not appear until flow is 50% or less of normal (Scheuer and Brachfeld 1966;Becket et al. 1973). The preparation of radioactively labeled FFA was performed as reported earlier (Westera et al. 1980;. ...
In an experimental study, the influence of propranolol on myocardial uptake of radioiodinated heptadecanoic acid (131I-HDA) and thallium-201 (201Tl) in the dog heart was assessed. Uptake of 131I-HDA and 201Tl was evaluated in ten control dogs and in ten dogs 20 min after IV administration of propranolol (0.15 mg/kg). In both groups, four healthy dogs were studied and six dogs were studied after coronary artery occlusion. It was shown that both total uptake of 131I-HDA and 201Tl did not alter significantly, regardless of significant changes in hemodynamic parameters and total arterial plasma FFA levels. However, distribution of both 131I-HDA and 201Tl was markedly affected by propranolol, since the endocardial to epicardial ratio showed significantly higher values in the ischemic myocardial regions.
The results of our study indicate that propranolol (1) preserves myocardial perfusion in the normal and acutely ischemic dog heart, and (2) gives a more favorable distribution in the ischemic myocardial region towards the subendocardial layers.
... ST-segment changes or angina during ischemia. [3][4][5][6][7][8][9][10][11][12] During ischemia induced by percutaneous coronary intervention (PCI), about 40% of patients developed ventricular dysfunction without ischemic ST changes. [6][7][8] In about 40% of patients who released excessive lactate that can damage the myocardial cells, angina did not develop during ischemia. ...
Previous studies have suggested that ventricular function may be impaired without or prior to electrocardiographic changes or angina during ischemia. Understanding of temporal sequence of electrical and functional ischemic events may improve the detection of myocardial ischemia.
A prospective study was performed in 21 subjects undergoing percutaneous coronary intervention (PCI) who had both ST amplitude changes >2 standard deviations above baseline on 12-lead electrocardiography (ECG), and new or increased third or fourth heart sound (S3 or S4) intensity measured by computerized acoustic cardiography. The sequence of the onset and resolution of these signs of ischemia were examined following coronary balloon inflation and deflation.
Electrocardiographic ST amplitude and diastolic heart sound changes occurred contemporaneously, shortly after coronary occlusion (mean onset from balloon inflation; ST changes, 21 +/- 17 seconds; S4, 25 +/- 26 seconds; S3, 45 +/- 43 seconds). In 40% of patients, a new or increased S3 or S4 developed earlier than ST changes. Anginal symptoms occurred in only 2 of the 21 subjects during ischemia with a mean onset time of 68 seconds. ST-segment changes resolved earliest (33 seconds after balloon deflation) while diastolic heart sounds (89 +/- 146 seconds) and angina (586 +/- 653 seconds) resolved later.
A new or intensified S3 and/or S4 occurred contemporaneously with electrocardiographic changes during ischemia. These diastolic heart sounds persisted longer than ST changes following coronary reperfusion. Acoustic cardiographic assessment of diastolic heart sounds may aid in the early detection of myocardial ischemia, particularly in those patients with an uninterpretable ECG.
... Depression of the ST segment and inversion of the T waves on the surface electrocardiogram are regarded as features of subendocardial ischaemia. However, experimental evidence and studies using intracavity electrodes (Scheuer and Brachfeld, 1966; Monroe et al., 1972) have suggested that the changes on a surface electrocardiogram may be a relatively insensitive and late manifestation. The subendocardial flow index in our patients was compared with the resting electrocardiogram, and though 6 patients had evidence of subendocardial ischaemia on the surface electrocardiogram and also had abnormal subendocardial flow indices, 4 patients had low indices with normal electrocardiograms. ...
The evidence for subendocardial ischaemia was studied in 12 patients with discrete subvalvar aortic stenosis. Symptomatology, electrocardiographic criteria, and pressure difference across the left ventricular outflow tract were compared with the subendocardial flow index (diastolic pressure time index systolic pressure time index). All symptomatic patients had a large pressure difference and abnormal index, but 4 asymptomatic patients had pressure differences greater than 60 mmHg and a low index. One of these 4 patients had a normal resting electrocardiogram. In patients with borderline accepted indications for surgery, calculation of the subendocardial flow index may be an additional useful variable in the timing of surgery.
In an attempt to provide more accurate and inclusive information regarding the physiological significance of
cardiac disease, nuclear myocardial perfusion imaging has evolved into a very sensitive and accurate modality. MPI
has the advantage of being able to detect even mild ischemia when only flow heterogeneity is present. All the data
available today indicate that a normal stress MPI means <1% chances of hard cardiac events per year and this
figure has particular relevance for certification of aviators. Stress MPI has a high negative predictive value for
death up to 10 yrs. There is a need to analyze the present trends of its usage in Air force. Hence we undertook this
study of retrospectively analyzing 50 consecutive Air force officers referred to our centre for MPI. 50 consecutive
Air force officers who were referred for MPI to nuclear medicine centre of command hospital Air force were
retrospectively analyzed. Single day protocol was used and Bruce protocol was used for physical stress. Siemens
ECAM dual headed gamma camera was used for imaging. Stress gated images were obtained and Emory tool box
auto cardiac software was used for processing the image. QGS and QPS software was used for scoring and
functional analysis. 26 cases were referred for ECG abnormality out of which 4 cases were detected to have
perfusion defects and later underwent coronary angiography followed by revascularization. All these 4 MPIs were
true positive. 5 cases were referred for having positive TMT to exclude false positivity. Only one out them (20%)
was detected to be positive. There were 7 cases referred for atypical chest pain out of which one case turned out to
have RPD in inferior segments. Three MPIs were done for patients who underwent primary PTCA to check for the
success of revascularization. Nine cases were follow-up cases of CAD. 7 out of these 9 cases had abnormal MPI, out
of which 1 had reversible defect and the others had fixed defects. Among the non-invasive methods of cardiac
evaluation MPI has emerged as one of the most important modality in the past few years. It has the advantage of
detection of CAD at a very early stage when only flow heterogeneity is present. MPI has a much better diagnostic
accuracy than stress ECG alone and hence this leads to avoiding unnecessary angiographies. Although coronary
angiography provides clinically valuable information, its invasive nature and costs precludes its routine use in the
evaluation of patients after intervention. MPI with its ability to provide information about the physiological significance
of stenosis, extent of ischemia and scar, global LV function, viability and prognosis is hence ideally suited to
assess patients after intervention also. Myocardial perfusion imaging has a high diagnostic accuracy in the
detection, prognosis and follow-up of patients of coronary artery disease. The aviators are a special group of people
in whom we need to use MPI more liberally due to its high negative predictive value, non-invasive nature and lower
costs
Few would question the desirability of increasing blood flow to jeopardized ischemic tissues. Since an infarct is the direct result of an insufficient blood supply, it is almost self-evident that increasing flow should provide a potent means for reducing cell damage, by both increasing the supply of oxygen and metabolic substrates and enhancing the washout of toxic products of anaerobic metabolism. Complete protection should theoretically be possible if blood flow can be increased to a level compatible with cell survival before irreversible injury begins.
Under normal circumstances there is a balance between myocardial oxygen supply and demand. A schematic illustration of current concepts of this relationship is shown in Fig. 1. In the presence of a normal coronary circulation any increase in oxygen demands is met by a concomitant increase in oxygen delivery. If, however, oxygen demands should exceed delivery ischemia results. The factors controlling oxygen demand have been recently reviewed [1] and will not be discussed further. Oxygen delivery is dependent upon the extraction of oxygen across the myocardium and coronary blood flow. Since oxygen extraction is near maximal in the myocardium, any major increase in oxygen demands must be met by an increase in coronary blood flow.
Die Angina pectoris ist das wichtigste Leitsymptom der koronaren Herzerkrankung und das Symptom, an dem sich die Auswahl der Therapie in erster Linie orientiert (Roskamm u. Schmuziger 1979; Rahimtoola 1982; Reeves 1982).
Die Nitrate fanden im 19. Jahrhundert Eingang in die Therapie. Die ersten Substanzen, die medizinisches Interesse erlangten, waren Glyceryltrinitrat (Nitroglycerin), welches von Sobrero synthetisiert wurde und Amylnitrit, dessen Darstellung durch Balard erfolgt war (Sobrero 1847; Balard 1844). Beide Substanzen wurden zun?chst bei einer Vielzahl von Erkrankungen eingesetzt, bis die g?nstige Beeinflussung des Angina pectoris-Schmerzes durch Amylnitrit durch Brunton und durch Glyceryltrinitrat durch Murrell beschrieben wurde (Brunton 1857; Murrell 1879). Glyceryltrinitrat wurde wegen seiner l?ngeren Wirkung in den folgenden Jahren dem Amylnitrit vorgezogen und hat bis in die Gegenwart seine wichtige Bedeutung in der Therapie der Angina pectoris beibehalten. Die Einf?hrung der sogenannten Langzeitnitrate, wie sie in erster Linie durch die Nitratester von Isosorbid, Erythrit, Pentaerythrit und Mannit repr?sentiert werden, geht auf Untersuchungen von Krantz et al. (1940) zur?ck. Ihre Einf?hrung erweiterte die Anwendungsm?glichkeiten der Nitrate auf die prophylaktische Therapie der Angina pectoris, w?hrend bis dahin nur eine Kupierung des Anfalles ?blich war. Nach anf?nglicher Ablehnung fanden die oralen Darreichungsformen bald einen festen Platz in der Behandlung der Angina pectoris und stellen heute einen wichtigen Bestandteil der medikament?sen Therapie dar. Die Indikation der Nitratbehandlung wurde in den letzten Jahren auf die Herzinsuffizienz und das kardiale Lungen?dem erweitert (Bussmann et al. 1975 a; Cohn et al. 1977; Bussmann u. Schupp 1977).
One of the major problems in finding relevant experimental methods to assess substances of potential therapeutic value is the fact that it is very difficult to mimic human disease in animal experiments. Human disease is, in most instances, a multifactorial event, which runs an individual course in each patient, with a variable outcome. The aim of an experimental model of a disease should, therefore, be to include the main pathogenetic factors for this disease. Animal models used for drug testing are mostly artificially induced diseases or disturbances of normal physiologic function and are very seldom naturally occurring diseases in animals displaying symptoms similar to human disease. The natural occurrence of cardiac insufficiency in dogs, for example, is not sufficiently frequent to allow the complete testing of potentially useful drugs in a relevant setup. The Syrian golden hamster, on the other hand, would fulfill some criteria for drug testing, but has the big disadvantage of being too small to allow complete hemodynamic assessment of the dysfunction or of drug effects. Another great problem is the availability of the experimental animals and the legal restrictions which further limit the species available for use in establishing the therapeutic efficacy of a drug.
Establishing prognosis in individual coronary heart disease patients is difficult because of the complex pathophysiologic interactions inherent to the disease procers. This difficulty applies as much to specific prognostic information derived from electrocardiography as it does to any other clinical or laboratory method of evaluation. While electrocardiography alone, during and after myocardial infarction, has limitations primarily related to the dynamic characteristics of evolving and healing infarction, there are, nonetheless, valuable prognostic clues which can be recognized. As long as the clinician recognizes the limitations, the electrocardiogram in conjunction with other clinical information does have distinct value both for general and for specific prognostic indices. In this chapter, we summarize the electrocardiographic indices for establishing prognosis in patients with ischemic heart disease, with particular emphasis on myocardial infarction. We analyze available information in three clinical settings: (a) during the acute phase of myocardial infarction, (b) during the convalescent (late hospital) and early posthospital phase, and (c) during the phase of stable ischemic heart disease after surviving myocardial infarction.
The effects of increased heart rate upon the physical and metabolic determinants of coronary blood flow in coronary heart disease provide a physiologic basis for the use of this investigative tool in cardiovascular studies. Heart rate increased by electrical pacing has minimal effects upon other hemodynamic indexes and arterial substrate concentrations, thus providing a considerable advantage over exercise and isoproterenol as a relatively uncomplicated myocardial stress. Atrial pacing represents a significant myocardial stress. Pressure-time per minute (PTM) increases with a nearly linear increase in myocardial oxygen consumption (MV̇O2). This probably represents a balance between 2 unmeasured determinants of myocardial oxygen consumption, left ventricular size and contractility. If left ventricular failure supervenes, MV̇O2/PTM may rise rapidly. Although total coronary blood flow increases in a manner adequate to meet oxygen demand even in coronary heart disease, the presence of regional lactate production implies that this vasodilating capacity is exceeded in some areas or depths of the coronary vascular bed.
A model of partial thickness ischemia has been developed using subendocardial S-T elevation without epicardial S-T elevation to detect partial thickness ischemia which is sufficient to cause subsequent necrosis. Subendocardial blood flow in this model (measured with radioactive microsphere techniques) may be reduced to 25 percent of normal (P < 0.001) by coronary stenosis and tachycardia while subepicardial flow remains normal. Epicardial S-T depression seems to indicate reciprocally subendocardial S-T elevation as long as a layer of nonischemic epicardial muscle is present, but when ischemia becomes transmural, epicardial S-T elevation occurs. Regional pressure-flow relations were determined as distal coronary pressure was reduced at a constant aortic pressure, heart rate and cardiac output. These relations revealed remarkably effective autoregulation of epicardial blood flow concomitant with progressive subendocardial ischemia.
The pacing stress test has been shown to be useful in evaluating the severity and extent of coronary insufficiency in patients with a history of ischemic heart disease. Inducing an increase in heart rate by stimulating the right atrium via an electrode catheter an elevation of the left ventricular filling pressure and ischemic ECG changes could be observed often preceding the onset of anginal pain (Friesinger et al.;Pitt et al.;).
Assuming that also in patients with aortic valvular disease the pacing stress test might prove helpful in assessing the coronary reserve and thus the surgical risk, the right atrium was stimulated with an increasing rate.
It could be observed however, that in spite of a history of angina pectoris and coronary insufficiency the 9 patients with severe aortic stenosis as well as those 7 of the control group without any left ventricular pressure load showed a decrease and no increase in left ventricular enddiastolic pressure with higher rates. Only in one instance precordial pain occurred without the corresponding hemodynamic changes. — Systolic left ventricular pressure dropped in the patients with aortic stenosis, whereas it stayed constant or even increased slightly in the control group. — The rate of pressure rise (d P/dt) remained about constant in the patients with aortic stenosis, while an increase in this parameter up to 50% above the initial values resulted in the control group. — In both patient groups with the rising rate of stimulation the P-R interval was prolonged.
According to these results the pacing stress test does not permit to demonstrate the coronary insufficiency by hemodynamic criteria that must be assumed to exist for anamnestic and pathological-anatomical reasons in patients with severe valvular aortic stenosis. — The possible causes for these unexspected findings are discussed.
The development of therapeutic strategies to ensure a favorable balance between myocardial oxygen delivery (SUPPLY) and myocardial oxygen consumption (DEMAND) is mandatory for patients with coronary artery disease. Myocardial ischemia can lead to clinically significant circulatory impairment. Slogoff and Keats emphasized the importance of detection of perioperative ischemia in a study that related the incidence of ischemia to postoperative myocardial infarction.1 Calculation of myocardial oxygen supply and consumption (MVO2) requires the direct of measurement coronary blood flow.
26 mongrel dogs were given a single dose of 0.03 mg/kg tritium-labelled digoxin, β-methyldigoxin, digitoxin or ouabain 2 hrs or 95 hrs following experimental coronary occlusion. Examination of the epicardial ECG was performed by moving from intact to ischemic or necrotic zones. 60 min after glycoside administration the animals were sacrificed and tissue samples from the marked heart muscles areas and from the skeletal muscle were analysed for glycoside content. The early glycoside uptake in acute ischemic or necrotic myocardium was diminished independently of the physicochemical properties of the glycoside. Significantly higher glycoside concentrations (ng/g wet weight) were measured in the injured myocardium 3 hrs after coronary occlusion than 96 hrs afterward (p<0.005). The values in acute ischemic myocardium varied considerably. This non-homogeneity of glycoside uptake in the acute ischemic heart muscle may partly explain the increased sensitivity to glycosides in myocardial infarction. The decline of glycoside concentration correlates with the alterations in the epicardial ECG. The cardiac effects of cardenolides 60 min after intravenous administration was caused by the unchanged glycoside.
In contrast to the myocardium, glycoside accumulation could not be found in the skeletal muscle. The concentrations of digoxin, β-methyldigoxin and digitoxin in the skeletal muscle were significantly higher than the concentration of ouabain, which was rapidly eliminated via the urine.
The regional myocardial distribution of 131I-16-iodo-9-hexadecenoic acid (131I-HA) and 201Tl-thallium chloride (201TlCl) was determined in normal dogs and after occlusion of a coronary artery. The uptake of 131I-HA was about 20% lower than that of 201TlCl but the ratio 201Tl/131I was the same for the whole myocardium within narrow limits for normal as well as infarcted tissue. The potential of 123I-HA as a radiopharmaceutical for diagnosis of myocardial defects is discussed.
The ECG was taken of adult, non-arteriosclerotic (virgin) male and female rats (20 each) and arteriosclerotic (breeder) male and female rats (20 each). Although similar to the human ECG the rat ECG exhibits Q waves only in leads AVR and AVL, there is no definitive ST segment and its T wave is asymmetrical. The arteriosclerotic rats have slower heart rates and elevated R waves and J points. Female breeders exhibited the most advanced arteriosclerosis and have calcified coronary arteries associated with dilated epicardial arteries in contrast to male breeders whose epicardial branches are less calcified. The male breeders are particularly prone to die of myocardial infarction. The abnormal ECG tracings in the arteriosclerotic subjects are believed to be due to myocardial ischemia caused by the calcified coronary arteries.
The dynamic and metabolic performance of rats conditioned by a swimming program (CH) and hearts of sedentary rats (SH) was studied in an isolated working rat heart apparatus. Heart rate, filling pressure, and afterload were controlled or kept constant, and heart weights were comparable in both groups. When compared with SH, CH had increased cardiac output and cardiac work. Atrial pacing at more rapid rates caused greater differences in these functions, and left ventricular pressure and maximal rate of pressure rise (dp/dt) became higher in CH than in SH. Atrial pacing was associated in CH with increased oxygen consumption but in SH by increased lactate and pyruvate production. When atrial filling pressure was elevated in order to perform ventricular function curves, CH showed greater dynamic responses than SH. There were also greater increments in oxygen consumption, and the ratio of aerobic to anaerobic energy production was also higher in CH. The mechanism of increasing oxygen consumption during stress in CH was mainly by improved coronary flow. In SH coronary flow did not change, but extraction of oxygen from the perfusing fluid increased. The results indicate that in physically trained rats the function of the heart as a pump is improved. These hearts have greater aerobic and mechanical reserve than hearts of sedentary animals. These effects appear to be at least partially due to improved mechanisms of oxygen delivery.
To investigate whether diastolic third or fourth heart sounds (S3 or S4) detect myocardial ischemia independently or in combination with the 12-lead electrocardiogram (ECG), a prospective comparison study was conducted in a group with ischemia induced by percutaneous coronary intervention (n=19) and a non-ischemia group (n=18) without coronary artery disease or ischemic ECG evidence. Diastolic heart sounds were detected by computerized acoustic cardiography.
Of 37 patients, the mean age was 59.4+/-11.8 years. An S4 was more sensitive (74%) in detecting ischemia than an S3 (47%) or standard ST-T criteria (53%). All subjects with standard ST-T wave criteria for PCI-induced ischemia had an S3 or S4. All subjects without an S3 or S4 did not have ST-T wave criteria for ischemia. Using logistic regression, both an S3 and S4 were shown to detect ischemia (P<0.05), independent of ST-T criteria. The detection of ischemia was improved by 32% when the presence of an S3 or S4 was added to ST-T wave criteria. The absence of an S3 and S4 was helpful to rule out myocardial ischemia.
The use of computerized acoustic cardiography to detect an S3 or S4 may augment the ECG detection of ischemia.
Although the standard 12-lead electrocardiogram (ECG) is considered the gold standard to diagnose acute myocardial ischemia, nearly half of ECGs are nondiagnostic in patients who present with chest pain and have subsequent confirmation of infarction with positive serum biomarkers.
A prospective study was performed to investigate the frequency and intensity of diastolic third and fourth heart sounds (S3 and S4), as measured by computerized acoustic cardiography, with myocardial ischemia induced by balloon occlusion during percutaneous coronary intervention.
In our 24 subjects, during percutaneous coronary intervention-induced ischemia, a new or increased intensity S3 or S4 developed in 67%. Ten (67%) of 15 patients without clinical ST criteria for ischemia also developed new or increased-intensity diastolic heart sounds.
The combined use of diastolic heart sounds, as a measurement of ventricular dysfunction, with the standard ECG may improve the noninvasive diagnosis of myocardial ischemia that is likely to develop into infarction.
The effect of phosvitin (1 g kg(-1), i.p.) on ecg changes induced in rats by a reduction of partial oxygen pressure in the respiratory mixture was studied. Phosphocreatine, phosphoserine, ATP and Na2HPO42H2O were also administered intraperitoneally for comparison. Phosvitin alone was found to prevent the hypoxia-induced T-wave changes (flattening or disappearance), which were also temporarily aggravated by injection of noradrenaline. As to the metabolic, hypoxia-induced myocardial changes, two hypotheses are discussed: a release of phosvitin phosphate radicals ready for immediate utilization or a drug action mediated via a membrane-bound intrinsic proteinkinase system.
Postextrasystolic potentiation after a single closely coupled extrasystole may identify residual ventricular contractile performance in acutely ischemic myocardium without producing sustained secondary ischemic depression of myocardial function. Postextrasystolic potentiation was systematically used in eight open chest dogs to assess the progression of regional contraction abnormalities during a 10 minute occlusion of the left anterior descending coronary artery. Segment function was determined from pressure-length loop areas inscribed during right ventricular pacing at 128 +/- 3 (mean +/- standard error of the mean) beats/min, and after single closely coupled (179 +/- 3 msec) extrasystoles. Despite a 50 percent decrease in border zone segment function, postextrasystolic potentiation consistently augmented mechanical performance to control levels throughout the ischemic period. Central ischemic zone segment function deteriorated more profoundly, with the development of holosystolic aneurysmal bulging within 30 seconds after occlusion. Nonetheless, postextrasystolic potentiation produced marked inotropic augmentation, but not to control levels, for up to 10 minutes of ischemia. These results suggest that latent viability and contractile reserve may exist during brief periods of coronary occlusion.
The effects of verapamil on epicardial ST segment elevation, regional myocardial metabolism and collateral blood flow were studied in open-chest anesthetized dogs following left anterior descending coronary artery occlusion. Collateral blood flow was measured by radioactive microspheres (15 +/- 5 micron diameter) and regional metabolism was studied by measuring lactate concentration in venous blood draining the infarcting myocardium. Verapamil (0-2 mg/kg intravenously) produced a significant reduction (50-60%) in the epicardial ST elevation when it was given before coronary occlusion; when administered 15 minutes after coronary occlusion and infusion continued for two hours, it minimized (30-40%) ST segment elevation, and prevented the fall in cardiac index and rise in systemic resistance found in the untreated animals in which the ST segment remained persistently elevated. Changes in epicardial ST segment occurred without alterations in the QRS duration. Verapamil had no effect on either the total collateral blood flow or the relative distribution of flow to the endocardial and epicardial halves of the ischemic ventricular myocardium. No significant differences were found between the levels of lactate in blood sampled from small epicardial veins at the center of the infarct when the control animals were compared with those treated with verapamil.
Twentyfour male patients with sustained myocardial infarction (MI) were studied with 12-lead ECG and systolic time intervals (STI) 5 months after the acute episode. From the ECGs were calculated the summed voltages of the R wave (σR), the Q wave (σQ), and the ST segment deviation (σST). These ischaemic ECG variables were correlated with the STI parameters of left ventricular function: LVETI, PEP and PEP/LVET. Statistically significant regression equations relating the ECG changes to the STI variables were found in anterior MI, for σST in the entire series, but not in inferior MI. Thus a simple and rapid inspection of the resting 12-lead ECG gives an indirect but reliable quantitative estimate of left ventricular function in patients with a sustained myocardial infarction.
Experimental studies have shown a relation between QRS changes in the ECG and the size of myocardial infarction (MI) (11, 21). As the extent of myocardial damage after MI determines the impairment of left ventricular (LV) function (14, 20, 25), a correlation between QRS changes and the LV performance would be expected. Linear correlation between the summed R wave voltages (σR) and the number of Q waves (Q index), and the angiographically determined LV ejection fraction has been reported in patients with chronic ischaemic heart disease (2, 4). This study looked for a quantitative correlation between the LV performance, as reflected by various systolic time intervals (STI), and ischaemic ECG changes (σR, σQ, and σST) in a group of patients with previous MI.
Controversy and confusion surround many aspects of TQ-ST segment mapping today. Technical standards pertaining to the recording and measurement of the TQ-ST deflection have not been uniformly established nor has the correlative value of the deflection as an indicator of myocardial injury been clearly ascertained. The TQ-ST deflection is believed to originate primarily although not exclusively as a result of extracellular potassium accumulation in the ischemic region and subsequent establishment of a transmembrane potential gradient during diastole and systole at the ischemic boundary. Nonspatial factors (including electrolytes, antiarrhythmic agents, heart rate) influence the TQ-ST deflection by altering this gradient. Spatial factors (including ischemic area and shape, electrode location) alter the relative position of the ischemic boundary to the electrode site and as such can be analyzed with the solid angle theorem. Further study of the complex behavior of the TQ-ST segment deflection, particularly in the presence of pharmacologic intervention, is necessary before mapping techniques can be used reliably in clinical studies designed to quantitate and modify ischemic damage.
The quantity of myocardium which becomes necrotic following coronary occlusion has been shown to influence both the acute and long-term consequences of myocardial infarction. Fortunately, experiments now indicate that the size of a myocardial infarct is not irrevocably determined immediately following a coronary occlusion, but can be altered substantially by a number of interventions. However, the clinical assessment of interventions designed to protect ischemic myocardium has posed considerable difficulty. Precordial electrocardiographic mapping, including analysis of both the ST segment and the QRS complex, which has been developed over the past several years, is now being used in studies on patients with acute myocardial infarction. In this review evidence will be presented which indicates that electrocardiographic mapping, when employed properly and with appropriate awareness of its limitations, can yield valid results and indicate whether or not an intervention modifies either the severity of ischemia itself or the eventual size of an infarction.
Serial precordial ST-segment ECG mapping with a grid consisting of 49 recording marks made on the anterior thorax of patients with acute anterior transmural myocardial infarction has been applied in the study of usefulness of this technique. It has been found that a pattern of variable devolution of the magnitude of ST-segment elevations is seen in uncomplicated myocardial infarction. Extension of the infarct has been characterized by re-elevation of ST-segments. Beneficial therapeutic interventions have resulted in reduction of the magnitude of ST-segment elevation. However, the technique cannot be applied in patients with inferior transmural myocardial infarction or in patients with functioning pacemakers, bundle branch blocks, or pericarditis. The significance of adherence to strict guidelines in performing ST-segment mapping and the analysis of mapping data in the light of the total clinical picture at the time of recordings is emphasized.
Limitation of myocardial injury after coronary occlusion is an exciting, recently recognised, but as yet unconfirmed, possibility in the treatment of myocardial infarction. Review of the experimental basis for the concept indicates that although manipulation of the ST segment of the electrocardiogram is not sufficient proof that myocardial necrosis can be limited, more robust experimental methods have confirmed the efficacy of a variety of interventions in experimental coronary occlusion. The effect of myocardial infarct size in determining acute prognosis and complications has been confirmed in clinical studies though the importance of infarct size lessens after recovery. Reported attempts at limiting myocardial necrosis in patients with myocardial infarction have so far not been sufficiently convincing to merit universal clinical application. Results of large scale randomised trials currently underway are awaited with interest.
Electrocardiography is an evolving clinical diagnostic modality for detection of acute myocardial infarction. Animal studies and electrocardiographic-clinical-pathological correlations have provided experience currently used for detection and rough localization of myocardial infarcts. Additions to the conventional 12 electrocardiographic leads have been utilized to increase the diagnostic sensitivity of the ECG in the setting of myocardial infarction. Mapping of ST-segment elevation an QRS complex from several chest wall loci have been employed for purposes of quantitating serially myocardial ischemic injury and eventual necrosis. These multiple lead electrocardiographic systems have also been utilized in assessing therapeutic interventions in the Coronary Care Unit. Usefulness of standard and multiple-lead recording systems is enhanced by awareness of their limitations when applied to patients with acute myocardial infarction.
Carbocromen prevents to some extent, particularly in subendocardial layer, carbohydrate cardiac metabolism alterations induced by the ischemia obtained by intermittent occlusion of left coronary artery.
Myocardial ischemia has been associated with dispersion of ventricular refractory periods and this dispersion has been related to the ventricular arrhythmias seen with coronary occlusion. This study relates the degree of change in measured ventricular refractory period with the degree of regional myocardial blood flow abnormality after coronary occlusion. When regional myocardial blood flow is less than 70% of that of nonischemic areas, refractory periods are significantly (P less than 0.001) shortened. The greatest change in refractory periods occurs in areas with a regional myocardial blood flow that is 21 to 40% of that of nonischemic areas. Marked (less than 20%) and minimal (61 to 80%) reductions in regional myocardial blood flow are associated with less, but still significant, shortening of ventricular refractory periods. Thus dispersion of refractoriness can be related to the inhomogeneity of regional myocardial blood flow after acute coronary occlusion. Interventions designed to salvage ischemic myocardium by increasing regional myocardial blood flow may affect dispersion of ventricular refractory periods in complex and divergent ways.
A radioautographic method was adapted to assess regional blood flow in focal myocardial infarction produced experimentally in dogs with ligation of a branch of the left circumflex artery. Twenty-four hours later, the dogs were given an infusion of 1 millicurie of 14C-antlpyrine and killed. Radloautograms were prepared from 20 μ full thickness sections Of the infarcted segment of each left ventricle. Adjacent tissue sections were also prepared for histopathologic study and comparison. Photodensltometric scanning of radioautograms in transverse and transmural planes permitted quantification of regional blood flow, measurement of dimensions of the zones of blood flow reduction and construction of profiles of Ischemic blood flow within a cubic reference system. Thus, transverse plane scans showed symmetric profiles of decreasing blood flow from each normal margin (mean ± standard error of the mean 0.75 ± 0.11 ml/g per min) to the center of the Infarct (mean 0.08 ± 0.02 ml/g per min or 11.7 ± 3.5 percent of normal flow); transmural plane scans showed an asymmetric profile of decreasing blood flow from the epicardlum (mean 0.36 ± 0.06 ml/g per min) to the center of the infarct and a subsequent increase to 0.22 ± 0.03 ml/g per min near the endocardial surface. From a comparative analysis of radioautograms with corresponding adjacent histologie sections we determined that (1) myocardial necrosis was first evident at the point of blood flow reduction that averaged 45.2 ± 3.2 percent of normal values; (2) a border zone of intermediate flow reduction where cell viability was maintained 24 hours after infarction averaged 4.5 ± 0.5 mm and encompassed 30.4 ± 3.0 percent of total ischemic zone width; and (3) on the basis of various geometric models, the size of the myocardial infarct in these experiments was approximately 40 percent of that of the ischemic zone.
The detection of regional asynergy provides strong evidence for a critical reduction of coronary blood flow to that zone. In the present study, the usefulness of combining computer-assisted radionuclide angiography and isometric handgrip exercise testing to detect coronary heart disease (CHD) was evaluated. One hundred twenty-nine patients with chest pain undergoing cardiac catheterization were evaluated using radionuclide angiography. Thirty-four patients were found to have severe contraction abnormalities during the initial radionuclide angiographic study. Of these, 33 had significant CHD. Ninety-five patients had normal or borderline normal left ventricular contraction and therefore underwent a second radionuclide angiogram during handgrip. Radionuclide angiogram data were quantitatively analyzed by computer to determine regional left ventricular contribution to ejection fraction during handgrip stress. Of the 95 patients, 30 had normal coronary arteries of whom 26 (87%) had normal relative regional ejection fraction. Sixty-five patients had CHD; 20 had single and 45 had two or three vessel obstructive disease. Overall, of the 95 patients who underwent isometric handgrip stress, sensitivity was 86% for detection of CHD and specificity was 87% for accurately defining the patients with normal coronary arteries. The results of the present study suggest that the radionuclide angiographic assessment of relative regional ejection fraction during isometric handgrip exercise may provide a useful new diagnostic approach for patients with suspected CHD as well as providing important additional data concerning its location and severity.
The effect of sublingual nitroglycerin (NTG) on myocardial ischemic injury was evaluated in eleven patients with acute anterior myocardial infarction. Precordial 35-lead ST-segment maps were obtained in each patient immediately before and 3-10 minutes after 0.4 mg sublingual NTG. The following measurements were made from each ST map: N-ST (number of leads showing ST elevation greater than 1mm), sigmaST (total ST elevation in all leads), ST (average ST-segment elevation in those leads with less than 1mm elevation). Following 0.4 mg sublingual NTG evidence of myocardial ischemic injury as assessed by ST-segment mapping decreased in association with reduction of heart rate X systolic blood pressure product (10.80 X 10(3) to 9.49 X 10(3), P less than 0.001). Group mean values diminished significantly for N-ST (18.1 to 14.4, P less than 0.001), sigma ST (37.9 to 30.1 P less than 0.005) and ST (1.7 to 1.4, P less than 0.001). Evaluation performed by the technique of precordial ST-segment mapping suggests that sublingual nitroglycerin in a commonly employed clinical dose is associated with evidence of reduced ischemic cardiac injury in patients with acute myocardial infarction. This effect appears to be related to reduction of myocardial oxygen demand by the nitrate.
To determine the sequence of changes in segmental myocardial function, regional lactate metabolism and global left ventricular function induced by mild regional ischemia, blood flow in the left anterior descending coronary artery of 10 dogs was reduced by 10 percent decrements with use of a screw clamp. At each level of flow, segmental mechanical function and regional metabolism were assessed, the former with use of a mercury-in-Silastic length gauge and the latter with transmyocardial lactate balance measurements obtained with sampling from the anterior interventricular vein. Coronary arterial flow at the onset of regional lactate production was 48 +/- 4 percent (mean +/- standard error of the mean) of the control value. The onset of segmental mechanical dysfunction coincided with the onset of lactate production. Epicardial S-T segment abnormalities over the ischemic zone usually could not be detected until coronary flow was further reduced. After the onset of regional ischemia there was a linear correlation between coronary arterial flow and regional lactate production. At the onset of mild regional ischemia, defined as the onset of regional lactate production, no significant or directionally consistent changes were noted in standard measurements of global left ventricular performance, including heart rate, mean aortic pressure, left ventricular end-diastolic pressure, cardiac output, stroke volume, stroke work and peak positive dP/dt (maximal rate of rise of pressure). However, peak negative dP/dt (maximal rate of pressure decrease) decreased from 99 +/- 2 to 89 +/- 3 percent of the control value (P less than 0.0005) coincident with the onset of ischemia. It is hypothesized that dyssynchronous wall motion in the ischemic zone during isometric relaxation accounts for this decrease in peak negative dP/dt.
A new method is described for measuring the unipolar left ventricular cavitary electrogram by means of a standard pigtail ventriculography catheter. Experiences with this technique in 30 patients are described with particular reference to changes in the S-T segment of the cavitary electrogram during cardiac stress by atrial pacing. This method allows convenient recording of His bundle potentials from the left ventricular outflow tract in most patients.
The purpose of this editorial is to review the electrophysiologic basis for deviation of the ST segment and to place into perspective its potential value and limitations in assessing the efficacy of interventions designed to limit infarct size.
Using epicardial electrograms others have established that infusion of isoproterenol increases myocardial injury after acute coronary occlusion. To define the contribution of alterations in collateral blood flow to this increased ischemia, isoproterenol was administered to 10 dogs. After pretreatment with practolol in doses that successfully block inotropic but not vascular effects of beta adrenergic stimulants, intracoronary isoproterenol continued to enhance the magnitude of S-T segment elevation in ischemic areas. Thus, vasodilation induced by isoproterenol appears to divert flow from the ischemic area. To test this hypothesis, intracoronary adenosine was given to cause coronary vasodilation without enhancing inotropy. S-T segment elevation at ischemic and adjacent sites was significantly increased. Neither agent had systemic effects, but each increased coronary blood flow while concomitantly decreasing collateral flow as evidenced by a reduction in retrograde coronary flow and peripheral coronary pressure. In addition, adenosine significantly diminished the rate of xenon-133 clearance from the ischemic myocardium. Thus, isoproterenol, in addition to its positive inotropic effect, increases myocardial injury by its vascular action. Collateral blood flow to acutely ischemic myocardium is diminished by the production of a coronary steal. Intravenously administered isoproterenol additionally diminishes collateral flow by decreasing coronary perfusion pressure. It is postulated that any agent that causes either a primary or secondary coronary vasodilation may cause a coronary steal and subsequently enhance myocardial injury.
The effect of intravenous administration of propranolol (3 to 10 mg) was studied in 12 patients with acute anterior transmural myocardial infarction within the first 8 hours from the onset of pain. Criteria for inclusion in the study were persistence of ischemic pain, S-T segment elevation of 0.3 or more mg in at least two standard precordial leads, heart rate of 80 or more beats/min, mean arterial pressure of 75 or more mm Hg and cardiac index of 2.5 or more liters/min per m2. Within 30 minutes of administration of propranolol, the sum of S-T segment elevations from leads V1 through V6 (sigmaST6) and the average S-T segment elevation over the left precordium recorded from multiple unipolar leads (ST) decreased significantly by 40 and 39%, respectively. At the same time, there was a significant reduction in heart rate (from 100+/-3 [standard error of the mean] to 79+/-4 beats/min), mean arterial pressure (from 112+/-6 to 95+/-5 mm Hg) and cardiac output (from 6.1+/-0.3 to 4.1+/-0.3 liters/min). Pulmonary capillary wedge pressure remained unaltered. Four hours later the hemodynamic variables had returned to control level, but the beneficial effect on myocardial injury persisted. These electrocardiographic changes were accompanied by resolution of ischemic pain and cessation of ventricular arrhythmias. The effects of propranolol were more pronounced in patients with angiographically demonstrable flow to the affected area of myocardium. Thus, administration of propranolol in the early hours of myocardial infarction can significantly reduce the signs of myocardial ischemic injury without excessively depressing myocardial function.
Lacate concentrations were measured in blood from (a) coronary veins within ischaemic myocardium and (b) veins nearer to the coronary vein, for periods of up to 2 1/2 hours after ligation of the left anterior descending artery in dogs. Concentrations at (a) were three to four times higher than at (b), while blood sampled simultaneously from two veins at (a) yielded similar concentrations of lactate. At 2 1/2 hours after ligation the veno-arterial difference of lactate concentration in blood from (a) was about one half of the difference at 15 minutes. Lactate concentration at (a) was approximately twice as great when the area of ischaemic myocardium drained by the vein was large (18 not equal to 1% of heart weight) than when it was small (6 not equal to 1% of heart weight). No close correlation was apparent between the height of epicardial ST-segment elevation and the level of lactate release. These experiments extend previous observations that changes in lactate concentration at a given site may reflect changes in venous dilution, rather than in the rate of production of lactate, and emphasize that caution is necessary in interpretation of changes in concentrations of metabolites in coronary sinus blood after acute myocardial infarction in man.
In anesthetized open chest dogs, hydrocortisone (50 mg/kg body weight administered 30 minutes after occlusion and 25 mg/kg 12 hours later) substantially reduced the size of myocardial infarcts, as reflected by both myocardial creatine phosphokinase activity and histologic appearance 24 hours later. Similarly, hyaluronidase, which increases diffusion through the extracellular space and presumably facilitates delivery of substrate to ischemic cells, also reduced the extent of myocardial necrosis after coronary occlusion in the dog. In view of the salutary effects of hyaluronidase and the absence of serious side effects, this agent was administered clinically to two groups of patients, who were compared with two groups of untreated control subjects. Hyaluronidase (500 National Formulary units/kg X 8) was shown to result in a significantly more rapid reduction in the magnitude and the extent of precordial S-T segment elevations, and in patients treated within 4 hours a tendency to a lower incidence rate of Q waves and a smaller reduction of R waves.
Intracoronary administration of complement component C5a induces transient decreases in coronary blood flow and regional left ventricular segment shortening, associated with intramyocardial granulocyte trapping. We evaluated the influence of a cyclooxygenase inhibitor (acetylsalicylic acid, n = 8) or a thromboxane A2/prostaglandin H2 receptor antagonist (SQ29548, n = 6) on these C5a-induced cardiovascular responses. Open-chest anesthetized pigs were instrumented to monitor heart rate, arterial blood pressure, left anterior descending coronary blood flow, regional left ventricular segment shortening, and dP/dt. Oxygen content, lactate concentration, leukocyte count, and thromboxane B2, the stable metabolite of thromboxane A2, were measured in arterial and regional coronary venous blood. Repetitive injections of intracoronary C5a (500 ng) given 60 minutes apart showed no tachyphylaxis of the hemodynamic response. However, tachyphylaxis was seen in coronary blood flow changes when injections were spaced 30 minutes apart. An increase in myocardial oxygen extraction and lactate production was observed after intracoronary C5a. Administration of acetylsalicylic acid (50 mg/kg i.v.) attenuated C5a-induced decreases in coronary blood flow (-8 +/- vs. -3 +/- 1 ml/min) and regional left ventricular segmental shortening (-10 +/- 3% vs. -2 +/- 1%) and blocked the maximal increase in coronary venous thromboxane B2 (2.0 +/- 0.1 vs. 0.2 +/- 0.1 pmol/ml plasma). Furthermore, SQ29548 (30 micrograms/kg/min) reduced C5a-induced changes in coronary blood flow (-13 +/- 2 vs. -4 +/- 2 ml/min) and segmental shortening (-14 +/- 2% vs. -3 +/- 1%). Neither cyclooxygenase inhibition nor thromboxane A2/prostaglandin H2 antagonism blocked the decrease in coronary venous granulocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)
Forty-three ambulatory patients with angina of increasing frequency underwent continuous monitoring of left ventricular (LV) function for an average of 2.9 +/- 1.9 hours to determine the incidence and temporal sequence of LV dysfunction, ST-segment depression and chest pain. Indicators of ischemia were: a decrease in ejection fraction greater than 5% lasting greater than 1 minute; horizontal or downsloping ST-segment depression of greater than or equal to 1 mm; or onset of the patient's typical chest pain complex, or a combination of these. During the monitoring interval, subjects performed daily activities such as sitting, walking, climbing stairs and eating. In 11 patients, 22 episodes of chest pain or ST-segment depression, or both, were observed. Eighteen episodes were accompanied by a decrease in ejection fraction (9 patients); chest pain accompanied the decrease in ejection fraction during 13 episodes, whereas ST-segment changes occurred during 7. In 12 of 13 episodes the decrease in ejection fraction began earlier than the onset of chest pain, whereas in 1 patient ejection fraction decrease and chest pain onset started at the same time. The average interval from a decrease in ejection fraction to the onset of chest pain was 56 +/- 41 seconds (range 0 to 120). ST changes occurred after the onset of a decrease in ejection fraction in 6 of 7 episodes. The average interval from the onset of ejection fraction decrease and the onset of ST change was 99 +/- 91 seconds. These data suggest that LV dysfunction manifested by a decrease in ejection fraction is an earlier indicator of myocardial ischemia than is angina pectoris or electrocardiographic evidence of ischemia.
The role of thromboxane A2 (TXA2) in the control of O2 supply/consumption variables during pacing-induced ischemia was examined using the TXA2 receptor antagonist SQ 29,548. Anesthetized, open-chest dogs were subjected to left anterior descending coronary artery (LAD) stenosis that produced significant epicardial S-T segment elevation (12 mV) only when superimposed on atrial pacing. Regional myocardial blood flow was determined using radioactive microspheres, and O2 consumption was determined by measuring O2 saturation of venous blood draining the ischemic region. The dogs were treated with saline or 0.2 mg/kg + 0.2 mg/kg/hr SQ 29,548, and the effect on ischemia was determined during 5-minute pacing-induced ischemic episodes at 10, 40, and 70 minutes postdrug or saline treatment. SQ 29,548 significantly reduced S-T elevation at 40 and 70 minutes postdrug compared with saline values and at all times measured compared with its paired predrug pace+stenosis values. SQ 29,548 reduced S-T elevation approximately 45% compared with its paired predrug values at 70 minutes. SQ 29,548 resulted in a significantly higher subendocardial-to-subepicardial flow ratio (0.70 +/- 0.10, p less than 0.05) compared with saline-treated animals (0.42 +/- 0.06), with an overall increase of flow to the ischemic region of approximately 40%. This increased flow was matched by a proportional increase in O2 consumption without a change in O2 extraction. The O2 supply/consumption balance was also unchanged by SQ 29,548 implying that despite the increase in blood flow, the ischemic region was still flow-limited.(ABSTRACT TRUNCATED AT 250 WORDS)
Except for hibernating myocardium, other manifestations of silent ischemia appear to be favorably affected by the usual therapeutic approaches to patients with suspected or documented coronary heart disease. However, it appears that in severe stable angina and unstable angina pharmacologic therapy may not be effective in controlling all or nearly all episodes of silent ischemia. There is no data to determine indications for or efficacy of therapy directed primarily at silent ischemia. Although elimination of silent ischemia would seem to be a desirable goal, there are no data to support that it can be achieved or that it is a clinically practical approach to treatment of patients.
During a 15-minute period of myocardial ischemia, glycogen concentration fell. This decrease was roughly accounted for by increases in hexosemonophosphate and lactic acid. Fructose 1,6-diphosphate, dihydroxyace-tone-phosphate and pyruvate did not accumulate. The myocardial concentration of adenosinetriphosphate declined. Reperfusion of the ischemie heart with oxygenated blood was accompanied by inconstant changes in myocardial glycogen and by rapid lowering of hexosemonophosphate. The hexosemonophosphate decrease occurred even when the ischemie myocardium was perfused with a deoxygenated buffered salt solution and is attributed in part at least to lactic acid washout. Adeno-sinetriphosphate rose steadily when the heart was perfused with oxygenated blood containing 15 mmoles KCl to prevent cardiac activity. When KCl was not added, fibrillation and irregular contractions occurred within 1 to 2 minutes. In these instances, the rise in adenosinetriphosphate was irregular and inconstant.
Innumerable hypotheses have been proposed to explain the mechanism of an attack of angina pectoris. Huchard1 collected about eighty such hypotheses in his monograph. It is not within the scope of this paper to enumerate or to discuss the great majority of these. However, the two that seem to be commanding most attention at the present time merit a brief outline.1. The "coronary hypothesis," stated first by Parry,2 holds that the attack of angina pectoris is dependent on a temporary interference with the blood supply of a part of the heart muscle. This hypothesis is based on the following points: (a) the frequency with which advanced coronary disease is found post mortem in patients who have died from angina pectoris; (b) the similarity of the syndromes of angina pectoris and coronary occlusion in regard to the character and location of the pain; (c) the adequate explanation of the mechanism
The electrolyte shifts occurring in myocardial cells irreversibly injured by ischemia were compared in two groups of dogs; one given 40 minutes of transient ischemia followed by 20, 50, 80, and 200 minutes of restored coronary arterial flow and the other 30, 60, 90, 130, and 240 minutes of permanent ischemia. Each interval of restored arterial flow in the transient ischemia group was associated with marked changes in the electrolyte content of the injured myocardium. Sodium, chloride, and water were increased and potassium and phosphorus were decreased. These changes occurred much more quickly in dogs exposed to transient ischemia than in dogs with comparable periods of permanent ischemia. These data indicate that objective chemical evidence of the death of myocardial cells develops slowly in areas of permanent ischemia primarily because of the reduced flow of blood through the ischemic injured tissue.
1.1. Two types of primary S-T deviation, primary S-T depression and primary S-T elevation, have been observed clinically and demonstrated in experiments on animals.2.2. Experiments in dogs demonstrated that S-T segment elevation is associated with more severe ischemia than S-T segment depression, confirming clinical impressions in patients with myocardial infarction and/or angina pectoris.3.3. Release of the tie on a large coronary artery resulted in reduced severity of ischemia; S-T elevation was diminished and in most instances replaced by transient S-T depression. This parallels clinical observations in patients during a severe attack of the variant form of angina pectoris.4.4. Hemorrhagic hypotension following ligation of a large coronary artery resulted in further increase in S-T segment elevation over the cyanotic area and widely scattered “islands” of S-T depression appeared over both ventricles. S-T elevation over the cyanotic area decreased and the “islands” of S-T depression disappeared upon restoration of normal blood pressure. This illustrates the deleterious effect of shock in acute coronary occlusion and underlines the importance of maintaining adequate systemic blood pressure.5.5. Primary S-T depression, as demonstrated in different experiments, occurs with ischemia and under nonischemic conditions due to chemical alterations. Primary S-T depression is in no way at variance with the principle of reciprocity or other fundamental laws of electrocardiography.6.6. S-T segment depression and S-T segment elevation are due to two different types of cellular response.7.7. The experimental findings suggest that development of ischemia and recovery from ischemia may occur along different metabolic pathways.8.8. The effect of collateral circulation was studied by means of two artificial coronary artery circuits providing independent control of the blood supply to the central part of the ischemic area and its periphery. It was demonstrated that collateral circulation diminishes the extent and degree of ischemia simultaneously with the appearance of primary S-T depression from the periphery of the ischemic area.
A dissertation presented to the graduate school of the State University of New York College of Medicine at New York City, in candidacy for the degree of Doctor of Philosophy. Thesis (Ph. D.)--State University of New York, College of Medicine at New York City, 1960. Includes bibliographical references (p. 142-148).
The authors devised a method that allows the gradual occlusion of the descending branch of the left coronary artery of nonanesthetized dogs with closed thorax. These experimental conditions try to reproduce what happens in human beings. A continuous electrocardiographic recording in V3 disclosed that the first sign of a coronary occlusion is an increase of the T-wave voltage. Changes of the rhythm, the QRS complex, and of the auricular complex were also seen. These T-wave changes are quite similar to those recently described in the very early stages of a human myocardial infarction.
This study is the first attempt to correlate myocardial oxygen availability by the polaro-graphic method with direct electrocardiographic leads and cinematographic records of muscle contraction during experimental acute coronary branch occlusion and narrowing. The comparative insensitivity and slowness of the epicardial electrocardiogram as an index of acute regional ischemia is demonstrated. Special attention is given to the rates of myocardial oxygen change immediately following attainment of a significant degree of coronary obstruction, the effects of pure oxygen inhalation on the experimental situations, and alterations in coronary vein color following release of arterial occlusion.
The experimental data here reported indicate that ST deviation is related largely to a change in the balance between intra- and extracellular electrolytes. This change in intra- and extracellular electrolyte balance occurs in ischemic heart disease as well as in a wide variety of noncardiac conditions.
Veno-arterial differences of pyruvate and lactate across the myocardium in chloralose-anesthetized dogs were very variable; in any one animal they changed continually with time despite constant blood flow and arterial blood concentrations. There was a systematic tendency of v-a lactate to vary with v-a pyruvate, as expressed in the calculated "Δ excess lactate," which remained nearly constant (or, if blood flow changed, bore a constant ratio to (a-v)O 2 ). No change in Δ excess lactate from control values occurred in nonhypoxic experiments despite marked changes in v-a differences, arterial blood composition, and coronary flow. Cardiac Δ excess lactate became positive in most animals breathing 10% O 2 in N 2 ; output of excess lactate was also observed in all those in which moderate muscular exercise was induced. This anaerobic metabolism, or change in the relationship between pyruvate and lactate exchanges, was interpreted as an indication that O 2 delivery response was not adequate to meet cardiac tissue requirements during such mild stresses when judged by the standards of adequacy of the basal state.
Absence of enzymatic hydrogen-carrying systems is a factor in aerobic glycolysis of malignant tissue.
Metabolic changes occurring during coronary insufficiency were studied in ten dogs by progressively reducing the rate of blood flow to the perfused left main coronary artery, while maintaining aortic pressure constant. Seven animals exhibited a net myocardial lactate production at low coronary flows, averaging 2.8 mg/min. The remaining animals showed a decreased lactate uptake which fell from an average 40 to 1.8% at the lowest flows. A rise in left atrial pressure occurred coincident with the alteration of lactate metabolism in all animals. Calculated coronary vascular resistance fell from an average 2.33 to 1.24 units, and in each case reached the minimum value at the onset of the metabolic changes. These results indicate that left ventricular failure, anaerobic myocardial metabolism, and maximal coronary arteriolar dilatation occur at the same time during inadequate myocardial blood flow.
Conventional electrocardiographie equipment (capacitance-coupled amplification) cannot distinguish between RS-T segment and baseline shifts of the ventricular complex. The so-called RS-T segment displacement is the net difference between the undetermined levels of those components. Using direct-coupled amplification, the absolute changes of baseline and RS-T segment on the surface of the exposed left ventricle during levarterenol administration and during regional ischemia, and release-recovery were studied in dogs. Ten significant patterns of displacement were observed. These permitted clear differentiation of the effects of levarterenol injection and hyperperfusion from those of ischemia. The centers and borders of an ischemic area could be distinguished and the change with prolonged ischemia described. The relationship of these observations to the literature and pertinent studies of intracellular action potentials are discussed.
Electrocardiograms were obtained on 52 normal dogs before and after ; cardiac irradiation with 1,300, 2,000, and 2,500 r. No ectopic cardiac ; arrhythmias were noted on electrocardiograms obtained 7 to 90 days following the ; completion of the course of irradiation. A mean increase in the ventricular rate ; was noted 7 days following the completion of the course of irradiation, but was ; not present 30 to 60 days later. There was no prolongation of PR interval or QRS ; duration following cardiac irradiation. At the dosage levels employed, ; irradiation of the normal canine heart produced no electrocardiographic changes ; indicative of gross myocardial damage. This was noted to be true as long as 90 ; days following the completion of the course of irradiation. (auth);
Experimental studies on the effects of temporary occlusion of the coronary arteries
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