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T J Anderson
Coronary Artery Disease 10/2001; 12(6):431-3. · 1.24 Impact Factor
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ABSTRACT: To determine the effect of angiotensin-converting enzyme (ACE) inhibition on brachial flow-mediated vasodilation.
Quinapril, an ACE inhibitor with high affinity, has been shown to improve coronary endothelial dysfunction in patients with coronary artery disease. The effectiveness of different vasoactive agents to improve human endothelial function is unknown.
High resolution ultrasound was used to assess endothelium-dependent brachial artery flow-mediated vasodilation (FMD) in patients with coronary disease. We studied 80 patients (mean age 58 +/- 0.9 years) in a partial-block, cross-over design trial. Patients were randomized to one of four different drug sequences to receive quinapril 20 mg, enalapril 10 mg, losartan 50 mg or amlodipine 5 mg daily. Each patient received three drugs with a two-week washout period between treatments. The primary end point was the absolute difference in FMD after eight weeks of each study drug compared with their respective baselines analyzed in a blinded fashion.
There was mild impairment of FMD at baseline (7.3 +/- 0.6%). The change in FMD from baseline was significant only for quinapril (1.8 +/- 1%, p < 0.02). No change was seen with losartan (0.8 +/- 1.1%, p = 0.57), amlodipine (0.3 +/- 0.9%, p = 0.97) or enalapril (-0.2 +/- 0.8%, p = 0.84). No significant change in nitroglycerin-induced dilation occurred with drug therapy. The improvement in quinapril response was not seen in those with the DD ACE genotype (0.5 +/- 2.1%) but was seen in those with the ID and II genotype (3.3 +/- 1.2 and 3.2 +/- 1.9%, respectively, p = 0.03).
Only quinapril was associated with significant improvement in FMD, and this response is related to the presence of the insertion allele of the ACE genotype.
Journal of the American College of Cardiology 02/2000; 35(1):60-6. · 14.16 Impact Factor
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ABSTRACT: To examine the outcome of intracoronary stent placement by 'primary intention', guided by angiography alone, and without the use of postprocedural anticoagulation.
Prospective, observational study.
Canadian university teaching hospital.
Patients (n=559) undergoing urgent or elective percutaneous revascularization procedures (n=616) in whom a preprocedural decision to employ coronary stent placement was made. Emergency and bailout stent procedures were excluded.
Stents were delivered at high pressure (1616 to 1818 kPa) on balloons matched to the proximal reference segment diameter. Adequacy of stent deployment was judged by angiographic criteria alone. Postprocedural medication included acetylsalicylic acid and ticlopidine. Quantitative coronary angiographic analysis was independently performed. Acute procedural outcomes were prospectively collected. Patients were followed for one year.
All but one patient had a successful angiographic result. Periprocedural death (0.3%), Q wave myocardial infarction (MI) (0%), non-Q MI (1.6%) and stent thrombosis (0.6%) were uncommon events. At one year, 96% of patients were alive and free of MI, while 12% of patients required repeat target lesion revascularization.
A primary intention strategy of intracoronary stenting, guided by angiography alone, is a safe and effective approach to percutaneous coronary revascularization.
The Canadian journal of cardiology 09/1999; 15(8):873-8. · 3.36 Impact Factor
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C E Buller,
V Dzavik,
R G Carere,
G B Mancini,
G Barbeau,
C Lazzam, T J Anderson,
M L Knudtson,
J F Marquis,
T Suzuki,
E A Cohen,
R S Fox,
K K Teo
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ABSTRACT: Balloon angioplasty (PTCA) of occluded coronary arteries is limited by high rates of restenosis and reocclusion. Although stenting improves results in anatomically simple occlusions, its effect on patency and clinical outcome in a broadly selected population with occluded coronary arteries is unknown.
Eighteen centers randomized 410 patients with nonacute native coronary occlusions to PTCA or primary stenting with the heparin-coated Palmaz-Schatz stent. The primary end point, failure of sustained patency, was determined at 6-month angiography. Repeat target-vessel revascularization, adverse cardiovascular events, and angiographic restenosis (>50% diameter stenosis) constituted secondary end points. Sixty percent of patients had occlusions of >6 weeks' duration, baseline flow was TIMI grade 0 in 64%, and median treated segment length was 30.5 mm. With 95.6% angiographic follow-up, primary stenting resulted in a 44% reduction in failed patency (10.9% versus 19.5%, P=0.024) and a 45% reduction in clinically driven target-vessel revascularization at 6 months (15.4% versus 8.4%, P=0.03). The incidence of adverse cardiovascular events was similar for both strategies (PTCA, 23.6%; stent, 23.3%; P=NS). Stenting resulted in a larger mean 6-month minimum lumen dimension (1.48 versus 1.23 mm, P<0.01) and a reduced binary restenosis rate (55% versus 70%, P<0.01).
Primary stenting of broadly selected nonacute coronary occlusions is superior to PTCA alone, improving late patency and reducing restenosis and target-vessel revascularization.
Circulation 08/1999; 100(3):236-42. · 14.74 Impact Factor
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ABSTRACT: In vitro studies indicate that nitric oxide synthase (NOS) inhibitors alter sinus node automaticity. Moreover, whereas the systemic delivery of N(G)-monomethyl-L-arginine (L-NMMA), a NOS inhibitor, results in sinus bradycardia and arterial hypertension, its intracoronary administration has little effect on sinus heart rate. Therefore whether L-NMMA directly alters sinus node function in humans is not known. By using a crossover design, we evaluated the effect of intracoronary L-NMMA (20 micromol/min x 10 min) on corrected sinus node recovery time (CSNRT), heart rate, mean arterial blood pressure, electrocardiographic intervals, and coronary artery blood flow in nine men and 13 women aged 48+/-12 years. All were in sinus rhythm and had normal baseline CSNRTs. Baseline measurements were made during a dextrose infusion, and then L-NMMA was administered, and these parameters remeasured. In 11 patients, the infusions were near the origin of the sinus node artery (Concordant), whereas in the remaining 11, they were into the opposite coronary circulation (Discordant). After L-NMMA, significant prolongations in CSNRT were seen in Concordant (p < 0.001) and Discordant patients (p < 0.05), but were most pronounced in the Concordant group (p < 0.05). Although a significant reduction in coronary artery blood flow and nonsignificant changes in blood pressure and heart rate were observed after L-NMMA, these changes were not related to changes in CSNRT (r2 < or = 0.2; p > or = 0.2). These data support the notion that NO is a modifier of human sinus node automaticity.
Journal of Cardiovascular Pharmacology 07/1999; 34(1):1-6. · 2.29 Impact Factor
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The American Journal of Cardiology 12/1998; 82(10A):34S-36S. · 3.37 Impact Factor
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ABSTRACT: Healthy coronary vascular endothelium releases nitric oxide to modulate resting and dynamic coronary arterial tone. We studied the impact of atherosclerosis and/or its risks on endothelial nitric oxide release in response to metabolic stimuli by evaluating coronary vasomotor responses to atrial pacing before and after the inhibition of nitric oxide production by intracoronary NG-monomethyl-L-arginine (L-NMMA) (20 micromol/min) infusion. The study includes 34 patients (15 with coronary disease, 11 with normal coronary arteries and > or =1 risk factor, and 8 with normal coronary arteries and no risks). Coronary blood flow was derived from Doppler flow velocity (0.018-inch Doppler wire) and coronary diameter. L-NMMA infusion reduced coronary blood flow by 18 +/- 16% and coronary diameter by 10 +/- 9%. Responses were identical in all subgroups. Coronary blood flow responses to pacing were similar in all subgroups and were unaffected by L-NMMA (11 +/- 11 vs 13 +/- 9 ml/min; p = 0.26). Epicardial coronary vasodilation to control pacing occurred in patients with normal coronary arteries with (4.0 +/- 5.2%, p = 0.01) or without (8.0 +/- 5.2%, p = 0.03) risks, but not in patients with coronary disease (2.8 +/- 5.9%). L-NMMA abolished pacing-induced epicardial vasodilation in patients without coronary artery disease, producing a 1.8 +/- 5.1% response, which was similar in all subgroups. We conclude that microvascular responses to rapid atrial pacing are not mediated by nitric oxide. Flow-mediated epicardial coronary arterial responses may be nitric oxide dependent.
The American Journal of Cardiology 12/1998; 82(9):1034-9. · 3.37 Impact Factor
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ABSTRACT: Allograft coronary artery disease (CAD) remains the leading cause of morbidity and mortality affecting the long-term survival of patients after cardiac transplantation. Because there is increasing evidence that imbalances in hemostatic and fibrinolytic pathways are associated with graft failure, we hypothesized that atherothrombotic risk factors may contribute to allograft CAD. This study sought to determine if plasma hemostatic and fibrinolytic parameters are associated with the severity of allograft CAD. The extent of allograft CAD was investigated by angiography and intravascular ultrasound (IVUS) in 16 cardiac transplant recipients. Intimal thickening was quantified using IVUS by measuring the intimal index (li = intimal area/[intimal area + luminal area]) in two to five segments of the left anterior descending (LAD) coronary artery. The maximal li per patient was calculated and index to the time post-transplant (Mxli/Yr). Plasma fibrinogen (FGN), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), lipoprotein(a) (Lp(a)), and net fibrinolytic activity of plasma were assayed 6-24 months after transplant as indicators of the fibrinolytic system and then correlated with the IVUS measurements. The FGN level correlated with the severity of intimal thickening, Mxli/Yr (r2 = 0.41, p = 0.008), and was inversely correlated with angiographic tertiary vessel filling (r2 = 0.25, p = 0.051). In patients with lower plasma fibrinolytic activity (lytic zone less than 100 mm2), Mxli/Yr was increased eightfold (0.218 +/- 0.137 versus 0.025 +/- 0.021, p = 0.001). t-PA (r2 = 0.0004, p = 0.94), PAI-1 (r2 = 0.008, p = 0.75) and Lp(a) levels (r2 = 0.11, p = 0.21) did not predict Mxli/Yr. Thus, we demonstrate that plasma FGN and net fibrinolytic activity correlate with the degree of intimal thickening measured by IVUS after cardiac transplantation. These data suggest that fibrin deposition may play a role in allograft CAD after cardiac transplantation.
Vascular Medicine 12/1997; 2(4):306-12. · 1.46 Impact Factor
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ABSTRACT: Coronary risk factors adversely affect coronary resistance vessel dilation to acetylcholine, but little is known about the effect of risk factors on coronary blood flow (CBF) responses to physiologic stimuli. CBF was derived from Doppler flow velocity (0.018-inch Doppler wire) and coronary diameter (quantitative angiography) in response to rapid atrial pacing in 50 patients (mean age 52 +/- 12 years). Patients were prospectively divided into 3 groups based on their angiograms: group 1 (n = 17), normal coronary arteries; group 2 (n = 18), 1-vessel coronary artery disease (CAD) with a smooth study artery; group 3 (n = 15), 1-vessel CAD and an irregular study artery (<20% stenosis). Pacing produced a significant increase in CBF compared with baseline in groups 1 and 2 (34 +/- 40%, 42 +/- 35%, p < 0.0001), respectively, but not in group 3 (21 +/- 33%), but there was no difference in the pacing response among the 3 groups. The increase in CBF to pacing was inversely related to serum cholesterol (p = 0.01) and triglycerides (p = 0.06) and directly related to the increase in heart rate-blood pressure product (p = 0.007). By multivariate analysis, total cholesterol and the increase in double product were the only factors related to the increase in CBF. Increases in CBF to atrial pacing are inversely related to serum total cholesterol and are not related to the angiographic presence of atherosclerosis in patients with mild CAD.
The American Journal of Cardiology 08/1997; 80(1):16-20. · 3.37 Impact Factor
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ABSTRACT: Coronary atherosclerosis is characterized by an early loss of endothelium-dependent vasodilation. However, the methods of assessing coronary endothelial function are invasive and difficult to repeat over time. Recently, a noninvasive ultrasound method has been widely used to measure flow-mediated dilation in the brachial artery as a surrogate test for endothelial function. We seek to further validate this method of measuring vascular function. The brachial artery diameters and blood flow of 20 normal volunteers (10 males and 10 females) were measured using high resolution (7.5 MHz) ultrasound and strain gauge plethysmography. Flow-mediated endothelium-dependent vasodilation was measured in the brachial artery during reactive hyperemia after 5 minutes of cuff occlusion in the upper arm. The brachial artery diameter increased maximally by 9.7 +/- 4.3% from baseline at 1 min after cuff release and blood flow increased by 1002 +/- 376%. Five min of cuff occlusion was sufficient to achieve 97 +/- 6% of maximal brachial artery dilation and degree of dilation was not different whether the cuff was inflated proximally or distally to the image site. The intraobserver variability in measuring brachial diameters was 2.9% and the variability of the hyperemic response was 1.4%. In young, healthy men and women, the baseline brachial artery diameter was the only factor that was predictive of the flow-mediated vasodilation response. The brachial noninvasive technique has been further validated by the determination of flow-mediated dilation. This method of assessing endothelial function may help to determine the importance of vasodilator dysfunction as a risk factor in the development of atherosclerosis.
Vascular Medicine 01/1997; 2(2):87-92. · 1.46 Impact Factor
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ABSTRACT: This study was designed to determine whether enhanced sensitivity to exogenous nitrovasodilators is present in the coronary arteries of patients with impaired endothelium-dependent dilation.
Animal studies have demonstrated that the dilator response to exogenous nitrovasodilators is exaggerated in the setting of endothelial dysfunction (diminished nitric oxide activity). Whether such relative hyperresponsiveness to exogenous nitrates occurs and is important in humans is unknown.
We assessed coronary vasomotion in 110 patients (mean [+/- SD] age 56 +/- 10 years) by serial intracoronary infusions of acetylcholine (10(-8) to 10(-6) mol/liter) to test endogenous nitric oxide and nitroglycerin (40 micrograms) to test responses to exogenous nitrovasodilators.
The vasomotor response to 10(-6) mol/liter of acetylcholine differed between patients with (n = 95) and those without (n = 15) normal endothelial dysfunction (-21 +/- 14% vs. 12 +/- 8%, respectively, p < 0.001). However, neither the dilator response to nitroglycerin (21 +/- 14% vs. 18 +/- 13%) nor the baseline diameter differed between those with endothelial dysfunction and normal function, respectively. There was no correlation between the magnitude of the dilator response to nitroglycerin and acetylcholine. The response to nitroglycerin was decreased with increasing age (r = -0.21, p = 0.03) but was not related to any other demographic factors or to the angiographic appearance of the vessel.
The coronary vasodilator response to nitroglycerin is not significantly enhanced in patients with impaired endothelium-dependent dilation but decreases with increasing age. This finding provides indirect evidence that basal coronary tone is not increased in patients with endothelial dysfunction and that supersensitivity to exogenous nitrates is not clinically important in humans.
Journal of the American College of Cardiology 10/1996; 28(3):580-4. · 14.16 Impact Factor
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ABSTRACT: Annual coronary angiography is routinely performed to evaluate cardiac allografts. Recently, magnetic resonance coronary angiography has been used to imagine native coronary arteries, but its use in transplant recipients, with rapid heart rates, metallic sternal sutures, and altered cardiac orientation, has not been described. Our goal was to describe the feasibility of noninvasive magnetic resonance coronary angiography in cardiac allograft recipients, detect flow-limiting focal stenoses, and quantify the altered coronary artery orientation.
We performed magnetic resonance coronary angiography is 18 adult heart transplant recipients (15 men and 3 women) with use of a breath-hold ECG-gated segmented k-space technique. Multiple transverse and oblique images were obtained in each subject. A control population of 16 adult patients without transplant and without angiographic evidence of coronary disease provided a reference for the coronary artery length visualized by magnetic resonance coronary angiography. This technique identified the left main coronary artery in 15 of 15 transplant recipients with normal coronary anatomy. Magnetic resonance coronary angiography demonstrated a +25-degree anterior (clockwise) right coronary artery ostial rotation in transplant recipients (p = 0.0001 versus control group) with corresponding realignment of the left main ostium. By magnetic resonance coronary angiography, the mean contiguous length of coronary artery visualized in the transplant recipients was similar to that in the control subjects for all major vessels (p = not significant). Five transplant recipients had nine discrete stenoses (50% or greater luminal diameter) identified by contrast angiography, of which seven stenoses were identified as signal voids by magnetic resonance coronary angiography. coronary stenoses not seen by this technique were located in the distal one third of the artery.
These data confirm and for the first time quantify the previously observed anterior rotation of the coronary ostia, which may be used to guide coronary engagement for subsequent interventions. In addition, these data demonstrate the potential of magnetic resonance coronary angiography to image noninvasively the coronary arteries and identify focal stenoses in cardiac allograft recipients.
The Journal of Heart and Lung Transplantation 07/1996; 15(6):580-6. · 4.33 Impact Factor
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ABSTRACT: Oxidatively modified LDL has been shown to markedly impair endothelium-dependent dilation in experimental studies. The aim of the present study was to determine the relationship between the coronary vasomotor response to the endothelium-dependent agonist acetylcholine and the in vitro susceptibility of LDL to oxidation in patients.
Endothelium-dependent coronary vasomotion in response to acetylcholine (10(-8) to 10(-6) mol/L) was assessed in 23 patients with hypercholesterolemia (mean age, 56 +/- 9 years) after 1 year of therapy with either an American Heart Association Step 1 diet (seven patients), lovastatin and cholestyramine (seven patients), or lovastatin and probucol (nine patients). The susceptibility of LDL to oxidation was determined by measuring the lag phase of conjugated diene formation induced by Cu2+. Patients treated with lovastatin and probucol had prolongation of the lag phase (263 +/- 64 minutes) compared with diet- (91 +/- 22 minutes) or lovastatin and cholestyramine-(118 +/- 57 minutes) treated patients (P<.0001). By univariate analysis, the coronary vasomotor response to acetylcholine was significantly related to the lag phase of conjugated diene formation (P=.002), cholesterol-lowering therapy (P=.002), and serum cholesterol (P=.02). By multivariate analysis, the lag phase remained a significant predictor of the acetylcholine vasomotor response, independent of the effect of cholesterol-lowering treatment.
In patients treated with lipid-lowering agents, the vasodilator response to acetylcholine is related to the susceptibility of LDL to oxidation. These findings suggest that oxidative stress is an important determinant of the coronary endothelial dysfunction observed in patients with atherosclerosis and hypercholesterolemia.
Circulation 05/1996; 93(9):1647-50. · 14.74 Impact Factor
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ABSTRACT: Although endothelium-derived nitric oxide contributes to basal vascular tone, little is known about its role in regulating blood flow during changes in metabolic supply and demand. We examined the contribution of endothelium-derived nitric oxide to reactive hyperemia in the forearm of 20 normal subjects (12 women, 8 men) aged 27 +/- 4 yr (means +/- SD), using the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). Forearm ischemia was induced by suprasystolic blood pressure cuff inflation for 5 min, and the subsequent hyperemic flow was recorded for 5 min using venous occlusion strain-gauge plethysmography. The efficacy of nitric oxide blockade was tested by comparing the dose-response relationship to the endothelium-dependent agonist, acetylcholine (3, 10, and 30 mg/min), before and after intra-arterial infusion of up to 2,000 mg/min of L-NMMA. L-NMMA produced a significant downward and rightward shift in the dose-response relationship to acetylcholine and a 39% reduction in response to the maximum dose (P < 0.001). In the presence of L-NMMA, peak hyperemic flow was reduced 16% (26.5 +/- 2.1 to 22.3 +/- 1.5 ml.min-1.100 ml of forearm-1, P < 0.03), and the minimum forearm vascular resistance was increased 22.8% (3.5 +/- 0.3 to 4.3 +/- 0.4 mmHg.ml-1.min.100 ml, P < 0.02). Total hyperemia, calculated from the area under the flow vs. time curve, at 1 and 5 min after cuff release was 17 and 23% less, respectively (13.6 +/- 1.2 vs. 11.3 +/- 1.1 and 31.8 +/- 2.7 vs. 24.6 +/- 1.8 ml/100 ml, P < 0.002), following L-NMMA. These data suggest that endothelium-derived nitric oxide plays a role in both reactive hyperemia and in the maintenance of the hyperemic response following ischemia in the forearm.
The American journal of physiology 04/1996; 270(4 Pt 2):H1435-40.
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ABSTRACT: Accelerated coronary arteriosclerosis is the major obstacle to long-term survival after cardiac transplantation. Endothelial dysfunction is common early posttransplant. The relationship between early endothelial dysfunction and the development of allograft arteriosclerosis has not been analyzed serially with intravascular ultrasound in the same patients. We hypothesized that an early constrictor response to acetylcholine, indicative of endothelial dysfunction, may predict the development of transplant coronary arteriosclerosis.
Endothelium-dependent vasomotion was assessed early posttransplant in 20 patients by serial intracoronary acetylcholine infusion, and the percent change in diameter was measured by quantitative angiography. The development of arteriosclerosis was studied by use of intravascular ultrasound in the same 20 patients by quantifying the changes in intimal index (delta Ii) and maximal intimal thickness [delta Mt] of 46 matched coronary segments between initial and 1-year follow-up studies. Coronary segments with endothelial dysfunction (constriction > or = 5%; n = 23) demonstrated a significantly greater increase in mean Ii and Mt by 1 year posttransplant compared with segments with normal endothelial function (n = 23) (delta Ii = 7 +/- 2% versus 2 +/- 1% [P < .05] and delta Mt = 140 +/- 40 versus 50 +/- 20 microns [P < .05]). No other parameters examined predicted the development of allograft arteriosclerosis in the initial year posttransplant.
Paired studies that used intravascular ultrasound showed that early endothelial dysfunction predicts the development of allograft arteriosclerosis during the initial year posttransplant. This early pathophysiological feature is likely an important marker that could be useful in therapeutic trials.
Circulation 02/1996; 93(3):457-62. · 14.74 Impact Factor
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ABSTRACT: Endothelium-derived nitric oxide (NO) may be an important mediator of vascular resistance in the pulmonary circulation. We tested the hypotheses that in conscious adults the endothelium, through NO production, is important in maintaining basal pulmonary vascular resistance and that it can increase NO production further in response to receptor-mediated stimulation, leading to further vasodilation.
Pulmonary arterial resistance vessel function was studied within the distribution of a segmental lower lobe pulmonary artery in eight conscious adults 37 to 76 years old who were undergoing cardiac catheterization. Segmental blood flow was determined with use of a Doppler-tip guide wire and quantitative angiography. Drugs were administered locally within the segmental artery through an infusion catheter. NG-Monomethyl-L-arginine (L-NMMA) was used as a specific inhibitor of NO production, whereas acetylcholine (ACh) was used to test receptor-mediated vasodilation. To demonstrate that vasodilation to ACh was NO dependent, ACh response was tested alone, in the presence of L-NMMA, and in the presence of a control constrictor phenylephrine. Basal pulmonary vascular resistance was NO dependent because L-NMMA infusion resulted in a dose-dependent decrease in local flow velocity (P < .005), with flow decreasing 33% at the highest dose of L-NMMA. ACh infusion resulted in a dose-dependent increase in flow velocity (P = .001). The ACh response was at least in part NO dependent because it was diminished by the presence of L-NMMA (P < .05). The effect of L-NMMA on the ACh response was not due to nonspecific preconstriction because L-NMMA diminished the ACh response significantly more than did the endothelium-independent constrictor phenylephrine (P < .05) despite comparable preconstriction.
In healthy conscious adults, (1) normal basal pulmonary resistance is maintained in part by continuous local production of NO and (2) the local NO production is responsive to receptor-mediated stimulation, leading to further vasodilation, and can be tested with ACh.
Circulation 02/1996; 93(2):266-71. · 14.74 Impact Factor
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ABSTRACT: The relation between endothelium-dependent vasodilator function in the brachial and coronary arteries was determined in the same subjects.
Coronary artery endothelial dysfunction precedes the development of overt atherosclerosis and is important in its pathogenesis. A noninvasive assessment of endothelial function in a peripheral conduit vessel, the brachial artery, was recently described, but the relation between brachial artery function and coronary artery vasodilator function has not been explored.
In 50 patients referred to the catheterization laboratory for the evaluation of coronary artery disease (mean age +/- SD 56 +/- 10 years), the coronary vasomotor response to serial intracoronary infusions of the endothelium-dependent agonist acetylcholine (10(-8) to 10(-6) mol/liter), was studied. Endothelium-dependent vasodilation was also assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia.
Patients with coronary artery endothelial dysfunction manifested as vasoconstriction in response to acetylcholine had significantly impaired flow-mediated vasodilation in the brachial artery compared with that of patients with normal coronary endothelial function (4.8 +/- 5.5% vs. 10.8 +/- 7.6%, p < 0.01). Patients with coronary artery disease also had an attenuated brachial artery vasodilator response compared with that of patients with angiographically smooth coronary arteries (4.5 +/- 4.6% vs. 9.7 +/- 8.1%, p < 0.02). By multivariate analysis, the strongest predictors of reduced brachial dilator responses to flow were baseline brachial artery diameter (p < 0.001), coronary endothelial dysfunction (p = 0.003), the presence of coronary artery disease (p = 0.007) and cigarette smoking (p = 0.016). The brachial artery vasodilator response to sublingual nitroglycerin was independent of coronary endothelial responses or the presence of coronary artery disease. The positive predictive value of abnormal brachial dilation ( < 3%) in predicting coronary endothelial dysfunction is 95%.
This study demonstrated a close relation between coronary artery endothelium-dependent vasomotor responses to acetylcholine and flow-mediated vasodilation in the brachial artery. This noninvasive method may become a useful surrogate in assessing the predisposition to atherosclerosis in patients with cardiac risk factors.
Journal of the American College of Cardiology 12/1995; 26(5):1235-41. · 14.16 Impact Factor
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ABSTRACT: Vascular endothelium plays a pivotal role in the maintenance of vasodilation and the inhibition of platelet aggregation and smooth muscle cell proliferation through the release of nitric oxide and other factors. Extensive data have demonstrated abnormalities in coronary endothelial function in the epicardial coronary arteries in patients with atherosclerosis or risk factors for atherosclerosis. This dysfunction leads to abnormal vasoconstriction and platelet aggregation, which likely play a role in producing ischemia in patients with coronary artery disease. Invasive techniques have been available to assess endothelium-dependent vasodilator responses in the coronary arteries. However, until recently little has been known about endothelial responses in the peripheral vasculature, as methods to assess this have not been readily available. The hypothesis that endothelial dysfunction is a systemic process is explored, and new noninvasive methods of assessing endothelial function are discussed.
The American Journal of Cardiology 03/1995; 75(6):71B-74B. · 3.37 Impact Factor
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ABSTRACT: Patients with coronary artery disease and abnormalities of serum lipids often have endothelial vasodilator dysfunction, which may contribute to ischemic cardiac events. Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilation is unknown.
We randomly assigned 49 patients (mean serum cholesterol level, 209 +/- 33 mg per deciliter [5.40 +/- 0.85 mmol per liter]) to receive one of three treatments: an American Heart Association Step 1 diet (the diet group, 11 patients); lovastatin and cholestyramine (the low-density lipoprotein [LDL]-lowering group, 21 patients); or lovastatin and probucol (the LDL-lowering-antioxidant group, 17 patients). Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine (10(-8) to 10(-6) M) was assessed at base line and after one year of therapy. Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal.
Treatment resulted in significant reductions in LDL cholesterol levels of 41 +/- 22 percent in the LDL-lowering-antioxidant group and 38 +/- 20 percent in the LDL-lowering group (P < 0.001 vs. the diet group). The maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent, respectively, in the LDL-lowering-antioxidant group, -15 and -6 percent in the LDL-lowering group, and -14 and -19 percent in the diet group (P < 0.01 for the LDL-lowering-antioxidant group vs. the diet group; P = 0.08 for the LDL-lowering group vs. the diet group). (The negative numbers indicate vasoconstriction). Thus, the greatest improvement in the vasoconstrictor response was seen in the LDL-lowering-antioxidant group.
The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implications for the activity of myocardial ischemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy.
New England Journal of Medicine 02/1995; 332(8):488-93. · 53.30 Impact Factor
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ABSTRACT: Many similarities exist between the exogenous nitrates and endothelium-derived relaxing factor, which is nitric oxide or a thiol derivative. Both act by way of guanylate cyclase, which increases intracellular concentrations of cyclic guanosine monophosphate, resulting in smooth muscle cell relaxation and antiplatelet effects. Thiols may be important in the biotransformation of exogenous nitrates and other intracellular processes involving nitric oxide. As such, important interactions might be expected between nitrates and endothelium-dependent processes that involve nitric oxide. This review explores the mechanisms of action, biologic effects and potential interactions between nitrates and endothelium-derived relaxing factor.
Journal of the American College of Cardiology 09/1994; 24(2):555-66. · 14.16 Impact Factor
