Judith A. Wisneski’s research while affiliated with Case Western Reserve University and other places

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Publications (64)


Table 2 . Regional blood flow 
Table 3 . Arterial glucose, FFA, lactate, insulin, and P-hydroxybutyrate 
Table 4 . Glucose, FFA, and P-hydroxybutyrate uptake measurements 
Table 5 . ?)-acer-measured lactate uptake and output 
Impaired pyruvate oxidation but normal glucose uptake in diabetic pig heart during dobutamine-induced work
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January 1997

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131 Reads

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83 Citations

American Journal of Physiology-Legacy Content

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W C Stanley

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G D Lopaschuk

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J G McCormack

We tested the hypothesis that diabetes impairs myocardial glucose uptake and pyruvate oxidation under normal conditions and during a dobutamine-induced increase in work. We also tested the hypothesis that an increase in work would result in a decrease in the levels of malonyl CoA, a potent inhibitor of carnitine palmitoyltransferase I (CPT I). Streptozotocin-diabetic micropigs were compared with a nondiabetic control group (n = 8 per group). Triglyceride emulsion, glucose, and somatostatin were infused into the nondiabetic group to create an acute diabetic-like state. In accord with our hypothesis, malonyl CoA decreased significantly with dobutamine in both groups, providing a possible mechanism for increased fatty acid oxidation through relieved inhibition on CPT I. In the absence of dobutamine, glucose uptake and tracer-measured lactate uptake were decreased by 57 and 80%, respectively, in the diabetic group. Dobutamine infusion resulted in similar increases in cardiac contractility, oxygen consumption, and glucose uptake in both groups despite reductions of 50-65% in GLUT-4 and GLUT-1 protein in the diabetic group. Diabetic animals possessed a defect in myocardial pyruvate oxidation, as reflected in increased lactate production, and depressed lactate uptake and pyruvate dehydrogenase activity under control and dobutamine conditions. In conclusion, the major derangement in carbohydrate metabolism in diabetic myocardium was not in glycolysis but, rather, in pyruvate oxidation.

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Myocardial High-Energy Phosphate and Substrate Metabolism in Swine With Moderate Left Ventricular Hypertrophy

March 1995

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8 Reads

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85 Citations

Circulation

Although left ventricular hypertrophy (LVH) is frequently associated with impaired coronary vasodilator reserve, it is uncertain whether this leads to myocardial ischemia under physiological conditions. The goal of the present study was to determine whether swine with moderate LVH exhibit metabolic evidence of ischemia when myocardial oxygen requirements are increased. Myocardial metabolism was evaluated in an open-chest anesthetized preparation at baseline and during dobutamine infusion in 13 adolescent pigs with moderate LVH induced by supravalvular aortic banding and 12 age-matched control pigs. Transmural myocardial blood flow was quantified with radioactive microspheres; the ratio of phosphocreatine to ATP (PCr/ATP) in the anterior LV free wall was measured by 31P-nuclear magnetic resonance; and anterior wall lactate release was quantified from the arterial-coronary venous difference in 14C- or 13C-labeled lactate. In a subset of 5 animals from each group, the metabolic fate of exogenous glucose was determined from the transmyocardial difference in 6-14C-glucose and its metabolites 14C-lactate and 14CO2. Coronary reserve, as assessed by the ratio of blood flow during adenosine infusion to baseline blood flow, was significantly lower in the LVH pigs compared with controls (3.5 +/- 0.4 versus 5.5 +/- 0.4 mL/g.min, P < .05); however, transmural myocardial blood flow was similar in both groups of pigs, both at baseline and with dobutamine stimulation, probably reflecting the higher coronary perfusion pressure in the LVH pigs. At baseline, PCr/ATP tended to be lower in the LVH pigs (P = .09) but decreased similarly with dobutamine infusion in both groups. Isotopically measured anterior wall lactate release did not differ between the groups at baseline, nor did the increase in lactate release differ during dobutamine stimulation. The uptake of glucose, lactate, and free fatty acids did not differ between the groups in the basal state. However, during dobutamine stimulation, glucose uptake was greater in the LVH group (0.84 +/- 0.09 mumol/g.min versus 0.59 +/- 0.08 mumol/g.min, P < .05). In a subset of animals, 14C-glucose was used to assess glucose oxidation. These data showed that the LVH animals had a greater rate of glucose oxidation (0.6 +/- 0.10 versus 0.28 +/- 0.08 mumol/g.min, P < .05) and a greater rate of glucose conversion to lactate (0.20 +/- 0.04 versus 0.09 +/- 0.02 mumol/g.min, P < .05) compared with the control pigs. These results suggest that despite their reduced coronary vasodilator reserve and the absence of a greater rise in myocardial blood flow to compensate for a substantially higher LV double product, pigs with this model of moderate LVH do not exhibit a greater susceptibility to myocardial ischemia during dobutamine stress. However, LVH pigs exhibit significantly greater use of exogenous glucose during dobutamine stress, as evidenced by increases in both glucose oxidation and anaerobic glycolysis.


Dichloroacetate stimulates carbohydrate metabolism but does not improve systolic function in ischemic pig heart

March 1995

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7 Reads

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29 Citations

American Journal of Physiology-Legacy Content

Increased carbohydrate utilization may protect the heart during ischemia and reperfusion. Dichloroacetate (DCA) stimulates pyruvate dehydrogenase, which is the rate-limiting step in oxidation of lactate and pyruvate. The purpose of this study was to determine if the myocardial metabolic changes induced by intracoronary DCA during myocardial ischemia were accompanied by improvement in systolic function. A perfusion circuit was created from the carotid to left anterior descending coronary artery (LAD) in 11 anesthetized Yorkshire swine. Data were obtained under strict hemodynamic control at baseline, after 15 min of moderate (30%) LAD flow reduction, and after an additional 15 min of ischemia with either intracoronary DCA (3 mM, n = 6) or saline (n = 5) infusion. DCA decreased lactate release and increased lactate uptake during ischemia as measured by glucose and lactate carbon-labeled tracers. Despite these metabolic changes, no improvement in systolic shortening, microsphere blood flow, or oxygen consumption occurred. Thus, although DCA stimulated carbohydrate metabolism during myocardial ischemia, it did not directly improve systolic function.


Inhibition of fatty acid metabolism alters myocardial high energy phosphates in vivo

July 1994

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19 Reads

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41 Citations

American Journal of Physiology-Legacy Content

We previously observed that isoproterenol (ISO) stimulation of the in situ porcine right ventricle (RV) increases the ratio of phosphocreatine (PCr) to ATP, accompanied by marked augmentation of myocardial free fatty acid (FFA) uptake. We hypothesized that increased FFA uptake and utilization cause the increase in PCr/ATP and that inhibition of FFA metabolism during ISO would prevent such an increase. In open-chest pigs, myocardial oxygen consumption (MVO2) of the RV free wall was increased with ISO (0.15 microgram.kg-1.min-1 iv) in the absence (n = 6) and presence (n = 6) of oxfenicine (65 mg/kg iv), an inhibitor of carnitine palmitoyltransferase I. ISO caused twofold increases in MVO2 and arterial FFA concentration. In the absence of oxfenicine, ISO increased RV FFA uptake from a control of 0.01 +/- 0.01 to 0.11 +/- 0.02 (SE) mumol.g-1.min-1. The PCr/ATP, measured by 31P-nuclear magnetic resonance spectroscopy, rose from 1.75 +/- 0.05 to 2.22 +/- 0.10 (P < 0.05). In the presence of oxfenicine, FFA uptake did not increase with ISO, despite elevated arterial FFA concentration. PCr/ATP fell from 1.65 +/- 0.05 to 1.53 +/- 0.07 (P < 0.01 vs. response without oxfenicine). In four additional pigs, arterial FFA concentration was increased in the absence of ISO by infusion of Intralipid and heparin sodium. PCr/ATP increased in each pig. When oxfenicine was administered with Intralipid, PCr/ATP decreased in each pig. We conclude that increased utilization of FFA raises the RV PCr/ATP ratio in vivo. Inhibition of FFA metabolism prevents the rise in PCr/ATP otherwise observed with ISO or with high arterial FFA.(ABSTRACT TRUNCATED AT 250 WORDS)


Relation among regional O2 consumption, high-energy phosphates, and substrate uptake in porcine right ventricle

March 1994

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13 Reads

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29 Citations

American Journal of Physiology-Legacy Content

Changes in phosphate metabolites may play a role in the regulation of myocardial oxidative phosphorylation in vivo. We tested the hypothesis that changes in phosphate metabolites with increased myocardial oxygen consumption (MVO2) depend on the mechanism by which MVO2 is increased. In 17 open-chest pigs, regional MVO2 of the right ventricular (RV) free wall was increased from control by isoproterenol infusion (Iso) and by pulmonary artery constriction (PAC). The phosphocreatine-to-ATP ratio (PCr/ATP), which is inversely related to free ADP concentration ([ADP]), was determined by 31P-nuclear magnetic resonance (NMR) spectroscopy. Regional MVO2 and lactate, glucose, and free fatty acid (FFA) uptake were determined in the myocardium directly beneath the NMR coil. Iso and PAC increased MVO2 nearly equally, to approximately twice control, but produced directionally opposite changes in PCr/ATP: a significant decrease with PAC (control 1.52 +/- 0.06, PAC 1.35 +/- 0.06, means +/- SE) but a significant increase with Iso (to 1.72 +/- 0.07). Thus increased [ADP] may have stimulated oxidative phosphorylation during PAC but could not have done so during Iso. With Iso, uptake of FFA was more than three times that with PAC, and the sum of the oxygen extraction ratios for lactate, glucose, and FFA was more than double that with PAC. Enhanced substrate uptake during Iso may have increased mitochondrial NADH, which in turn may have provided an alternative stimulus to the rate of oxidative phosphorylation. These results support multifactorial control of RV oxidative phosphorylation in vivo.


Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine

February 1994

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9 Reads

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40 Citations

Metabolism

We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)


Myocardial metabolism during increased work states in the porcine left ventricle in vivo

January 1994

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14 Reads

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59 Citations

Circulation Research

It is not known whether myocardial energy requirements can be increased to the degree that they exceed myocardial O2 availability in the absence of abnormalities of coronary blood flow or coronary reserve. To determine whether this form of "demand ischemia" occurs, 10 swine were subjected to pressure overload induced by aortic constriction, inotropic and chronotropic stimulation by dobutamine, and the combination of these interventions. In an additional 9 animals, intravenous adenosine was administered during the combination of constriction and dobutamine to determine whether further increases in coronary flow could be achieved and if they would attenuate the metabolic changes. Left ventricular anterior wall transmural blood flow was measured by radioactive microspheres. Energy phosphates were assessed by 31P magnetic resonance spectroscopy using the Fourier series window technique to increase the proportion of signal derived from the subendocardium. Myocardial lactate release was quantified independent of net lactate uptake using an isotopic tracer technique. The three interventions produced 39% to 195% increases in myocardial O2 uptake from control measurements. The phosphocreatine to ATP ratio (PCr/ATP), uncorrected for partial saturation, fell significantly, from 1.39 +/- 0.10 at control conditions to 1.25 +/- 0.10 with dobutamine alone and 1.15 +/- 0.08 with dobutamine plus constriction (P < .05 for both). Myocardial lactate release rose from 0.21 +/- 0.03 mumol.g-1.min-1 at control conditions to 0.45 +/- 0.05 and 0.59 +/- 0.10 mumol.g-1.min-1, respectively (P < .05 for both), with these two interventions. Although transmurally averaged left ventricular blood flow rose from 0.97 +/- 0.09 mL.g-1.min-1 at control conditions to 3.25 +/- 0.47 mL.g-1.min-1 (P < .001) and subendocardial blood flow increased from 1.02 +/- 0.09 to 2.92 +/- 0.45 mL.g-1.min-1 (P < .001) at the highest of the three increased work states, the subendocardial to subepicardial flow ratio declined progressively from 1.13 +/- 0.08 to 0.87 +/- 0.04 (P < .05). With a further increase in aortic constriction, myocardial O2 uptake and subepicardial blood flow rose, whereas subendocardial blood flow did not change, and there was a further decline in PCr/ATP and a rise in lactate release. Although adenosine increased the average myocardial blood flow during high work state from 3.79 +/- 0.91 to 6.29 +/- 1.08 mL.g-1.min-1 (P < .001), the further rise in subendocardial flow from 3.08 +/- 0.62 to 3.78 +/- 0.68 mL.g-1.min-1 was not significant, nor were the accompanying changes in PCr/ATP or lactate metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)


Diagnostic Accuracy of Exercise Thallium-201 Scintigraphy in Men With Asymptomatic Essential Hypertension

August 1992

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9 Reads

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15 Citations

American Journal of Hypertension

Coronary artery disease is responsible for much of the morbidity and mortality in patients with essential hypertension, and these complications have proven to be relatively resistant to antihypertensive therapy. However, the diagnosis of coronary disease in the hypertensive population has been considered problematic. In the present study, 30 asymptomatic patients with mild to moderate hypertension with positive exercise electrocardiograms (ECG) or stress thallium-201 scintigrams underwent coronary angiography to determine the accuracy of these tests for coronary artery disease. The exercise ECG was positive in 25 subjects, of whom 15 had significant coronary lesions and 10 did not. Thallium-201 scintigraphy proved more accurate: 17 of 18 patients with reversible abnormalities had significant obstructive coronary disease anatomically corresponding to the defect, one patient with a fixed defect had normal coronary arteries and was found to have an idiopathic cardiomyopathy, and 9 of 11 without defects had no significant lesions. The results were similar in populations with and without echocardiographic criteria for left ventricular hypertrophy. These findings indicate that despite previous suggestions to the contrary, thallium-201 scintigraphy can accurately diagnose coronary artery disease in most patients with asymptomatic essential hypertension, and that most asymptomatic hypertensive patients with physiologic evidence of myocardial ischemia have associated coronary artery disease. Am J Hypertens 1992;5:465–472


Adverse reactions of low osmolality contrast media during cardiac angiography: A prospective randomized multicenter study

May 1992

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15 Reads

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37 Citations

Journal of the American College of Cardiology

A multicenter study was performed to determine the incidence of adverse reactions to two contrast media with similar low osmolality during cardiac angiography. The study was of a randomized double-blind design comparing ioxaglate (an ionic dimer) and iopamidol (a nonionic compound) and included 500 patients; 250 patients received ioxaglate and 250 iopamidol. There were 58 adverse reactions attributed to the contrast media in the ioxaglate group and 29 in the iopamidol group (p less than 0.001). Chest pain occurred in 11 patients in the ioxaglate group compared with 5 in the iopamidol group (p = 0.123). Nausea or vomiting was present in 20 and 2 patients, respectively (p less than 0.0003). Allergic adverse reactions, such as bronchospasm, urticaria and itching, occurred in 15 of the ioxaglate group and only 1 of the patients receiving iopamidol (p less than 0.0007). Fifty-two patients in the ioxaglate group had a known allergic history (not to contrast medium) or asthma, whereas 77 receiving iopamidol had a similar history. Seven of the 52 ioxaglate-treated patients developed an allergic adverse reaction compared with none of the 77 in the iopamidol group (p = 0.001). Of 41 patients receiving ioxaglate who were premedicated with diphenhydramine, 4 had an allergic adverse event. In the iopamidol group 45 patients received similar premedication and none had an allergic adverse reaction (p less than 0.03). Thus, this multicenter study shows that adverse reactions occur more often with ioxaglate than with iopamidol and that patients with an allergic history have a greater risk with ioxaglate therapy compared with iopamidol.


Effects of high arterial oxygen tension on function, blood flow distribution, and metabolism in ischemic myocardium

March 1992

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11 Reads

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29 Citations

Circulation

Although oxygen inhalation therapy has long been used in the treatment of acute myocardial ischemia, experimental evidence that increased arterial PO2 has any beneficial effect in the absence of hypoxemia is equivocal. In this study, we used a swine model of subendocardial myocardial ischemia to determine the effects of arterial hyperoxia on regional myocardial contractile function (sonomicrometry), myocardial blood flow distribution (microspheres), and regional myocardial glycolytic metabolism (carbon isotope-labeled substrates). In 10 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery was strictly controlled via a roller pump in the perfusion circuit. Arterial PO2 was controlled by manipulating inspired oxygen concentration (FIO2). Low-flow myocardial ischemia was induced by reducing pump flow to 50% of the control value, which diminished regional endocardial systolic shortening to 30-50% of normal. After a 15-minute period of flow stability, each animal was exposed in randomized order to two additional 15-minute experimental periods: coronary normoxia (PO2 = 90-110 mm Hg) and coronary hyperoxia (PO2 greater than 400 mm Hg). At each level of oxygenation, we measured regional myocardial function, regional myocardial blood flow and metabolism, and hemodynamic indexes of myocardial oxygen demand. Myocardial ischemia during normoxia reduced systolic shortening to 10.9 +/- 5.3% in the ischemic zone. Hyperoxia increased ischemic zone systolic shortening substantially to 15.2 +/- 4.6%. During myocardial ischemia, endocardial blood flow was decreased to 0.26 +/- 0.06 ml.g-1.min-1 in the ischemic zone. During hyperoxia, endocardial blood flow rose to 0.34 +/- 0.10 ml.g-1.m-1. The endocardial: epicardial flow ratio was 0.45 +/- 0.18 in the initial ischemia period and rose to 0.61 +/- 0.23 in the hyperoxic period. Myocardial ischemia increased regional uptake of glucose, conversion of glucose to released lactate, and net myocardial lactate release. In the ischemic myocardium, coronary hyperoxia decreased both chemically measured lactate production and isotopically measured lactate release and decreased glucose extraction and the conversion of glucose to lactate. These data demonstrate for the first time that increasing arterial PO2 to high levels during acute low-flow myocardial ischemia improves both function and flow distribution in the ischemic myocardium and decreases glycolytic metabolism in the ischemic zone. The degree of improvement in contractile function (5% absolute increase in systolic shortening or 25% change normalized to preischemic values) is consistent with the observed increase in subendocardial blood flow.


Citations (45)


... The conundrum with this concept is that the variables, rate of disposal (R d ) and concentration (C), are interdependent. This interdependency is illustrated by the fact that a high R d reduces concentration [6,43], and yet concentration reciprocally drives R d [16,44]. Since MCR indicates a blood volume cleared of lactate per minute, the physiological meaning of MCR can be interpreted as the efficiency with which lactate is removed from the circulation. ...

Reference:

Concepts of Lactate Metabolic Clearance Rate and Lactate Clamp for Metabolic Inquiry: A Mini-Review
Systemic lactate kinetics during graded exercise in man
  • Citing Article
  • December 1985

AJP Endocrinology and Metabolism

... The mechanism surrounding this is believed to be a result of increased vasomotor tone and mechanical stimulation from the catheter tip [2, 4]. There are many adverse reactions that can occur during coronary angiography, involving both the catheterization process and the use of radiocontrast dye [5] . Catheterinduced vasospasm is uncommon but important to recognize and distinguish from atherothrombotic disease [6]. ...

Adverse reactions with arterial administration of low osmolality contrast media: Prospective randomized multicenter study
  • Citing Article
  • February 1990

Journal of the American College of Cardiology

... On the other hand, a generalized arterial oxygen desaturation has been found during angiography of the aorta or of one of its larger branches (1 5). During ventriculography both ionic and non-ionic monomeric contrast media caused a decreased sinus 0: difference with a tendency to increased myocardial oxygen consumption (8). Also, during percutaneus transluminal coronary angioplasty (PTCA), the decrease in ejection fraction caused by the lack of blood supply when inflating the PTCA balloon was reduced by perfusing the myocardium distal to the inflated balloon with oxygenated perfluorocarbon solution (I). ...

The Effects of Iopamidol on Myocardial Metabolism A Comparison with Renografin-76
  • Citing Article
  • September 1984

Investigative Radiology

... It is well documented that blood lactate concentration is a result of the production in the working muscle and removal of lactate in the blood (Moxnes and Sandbakk, 2012). Lactate is produced by tissues during exercise or even at rest and formation and removal of the lactate is highly related to metabolic rate (Myers and Ashley, 1997;Stanley et al., 1988;Connett et al., 1984). For moderate constant work rates, the aerobic power increases towards a steady state condition. ...

Lactate Kinetics During Submaximal Exercise in Humans
  • Citing Article
  • September 1988

Journal of Cardiopulmonary Rehabilitation

... The stiffness of the left atrium (LA) and left ventricle (LV) has been demonstrated to be a crucial index for assessing and predicting various conditions, such as hypertension, atrial fibrillation, coronary artery disease, and heart failure (10)(11)(12)(13)(14). Additionally, the left atrioventricular coupling index (LACI) is considered one of the indices that can predict the likelihood of atrial fibrillation, heart failure, and other cardiovascular events early in life (15)(16)(17). ...

Left Ventricular Stiffness
  • Citing Article
  • February 1978

Annual Review of Medicine

... Typical electrocardiographic changes are often nonspecific and myocardial biomarkers always elevated. As Q-waves on the electrocardiogram (ECG) have been traditionally considered a sign of major myocardial tissue damage, the appearance of new Q-waves following cardiac surgery has been accepted as the most reliable criterion for PMI diagnosis [1,2]. The recent finding of a higher rate of Q-waves after coronary artery bypass surgery (CABG) than after PTCA has raised the question of whether these Qwaves represent the same entity in the two groups [3,4]. ...

Significance of new Q waves after aortocoronary bypass surgery. Correlation with changes in ventricular wall motion
  • Citing Article
  • January 1976

Circulation

... The reported hospital mortality in large series for bypass grafting alone varies from 0-7 per cent (Ullyot et al., 1975) to 7 per cent (Anderson et al., 1974). Our figure of 4 per cent is comparable. ...

Improved survival after coronary artery surgery in patients with extensive coronary artery disease
  • Citing Article
  • October 1975

Journal of Thoracic and Cardiovascular Surgery

... There are many adverse reactions that can occur during coronary angiography, involving both the catheterization process and the use of radiocontrast dye [5]. Catheterinduced vasospasm is uncommon but important to recognize and distinguish from atherothrombotic disease [6]. ...

Adverse reactions of low osmolality contrast media during cardiac angiography: A prospective randomized multicenter study
  • Citing Article
  • May 1992

Journal of the American College of Cardiology

... Nel paziente iperteso la SPECT di perfusione ha una sensibilità dell'85-90% e una specificità del 70% circa. L'accuratezza diagnostica complessiva, che è sovrapponibile a quella dell'ecocardiografia da stress, ma con specificità maggiore per l'ecocardiografia e sensibilità superiore per la SPECT 172,173 , tuttavia si riduce in presenza di IVS 174 . ...

Diagnostic Accuracy of Exercise Thallium-201 Scintigraphy in Men With Asymptomatic Essential Hypertension
  • Citing Article
  • August 1992

American Journal of Hypertension

... For example, troponin, neuron-specific enolase and creatine kinase-MB fraction can be detected several hours after patients are resuscitated (Scolletta et al. 2012, Devaux et al. 2015. On the other hand, lactic acid levels, the most common marker of ischaemia, correlate with ischaemia during the early stage but becomes saturated after about 10 min ischaemia (Apstein et al. 1979, Schaefer et al. 1992. This saturation limits the usage of lactate also to an afterward marker with moderate prediction power (Karagiannis et al. 2012, Starodub et al. 2013. ...

Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo

Circulation