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Biomedical subjects

P Ganz

Publications and source records attributed to P Ganz.

At least 73 records · Page 4Linked to original sources
PubMed1997

Noninvasive assessment of endothelium-dependent flow-mediated dilation of the brachial artery.

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.

Adult↗
PubMed1997

Hemostatic/fibrinolytic predictors of allograft coronary artery disease after cardiac transplantation.

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.

Adult↗
PubMed1996

Flow-induced vasodilation of the human brachial artery is impaired in patients <40 years of age with coronary artery disease.

The objective of this study was to determine whether abnormal flow-induced endothelium-dependent vasodilation in the brachial artery identifies young patients with coronary artery disease (CAD). High-resolution ultrasonography was used to measure vascular reactivity in a peripheral conduit vessel, the brachial artery, in 14 young men with CAD and in 11 age-matched, healthy, male volunteers. Endothelium-dependent vasodilation was determined by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. Endothelium-independent vasodilation was assessed by administration of sublingual nitroglycerin. To ascertain whether flow-mediated vasodilation in humans is mediated by endothelium-derived nitric oxide, brachial artery diameter was measured during reactive hyperemia, before and during administration of the nitric oxide synthase antagonist NG-monomethyl-L-arginine (L-NMMA). Brachial artery diameter was also measured during intraarterial infusion of acetylcholine and nitroprusside before and after administration of L-NMMA. Flow-induced vasodilation was less in patients with CAD than in healthy volunteers (1.3 +/- 1.1% vs 6.2 +/- 0.7%, p <0.05). Nitroglycerin increased brachial artery diameter similarly in each subject group (11.3 +/- 1.0% vs 15.8 +/- 1.2%, p =0.05). L-NMMA inhibited flow-mediated vasodilation and the vasodilative response to acetylcholine, but did not affect the response to nitroprusside. It is concluded that abnormal flow-induced endothelium-dependent vasodilation occurs in the brachial artery of young patients with CAD.

Acetylcholine↗
PubMed1996

Pathogenic mechanisms of atherosclerosis: effect of lipid lowering on the biology of atherosclerosis.

Numerous trials have demonstrated that cholesterol-lowering therapy leads to marked reductions in cardiovascular and overall mortality and in the need for coronary revascularization. Angiographic regression trials have shown that cholesterol lowering can reduce progression and, in some instances, achieve regression of coronary atherosclerotic lesions. However, recent studies have contradicted the traditional view that the clinical course of coronary artery disease is closely linked to the severity of coronary artery stenosis. It is now apparent that stenoses responsible for myocardial infarction or unstable angina are typically mild rather than severe. These observations suggest that regression may not be the principal mechanism by which cholesterol lowering affects cardiovascular risk. Two mechanisms---plaque stabilization and improved endothelial function-have been examined in this regard. Basic studies suggest that cholesterol lowering favorably alters those features of atherosclerosis that promote plaque stability. Recent clinical studies have clearly established that aggressive lipid-lowering therapy improves endothelial function and reduces myocardial ischemia in patients with hypercholesterolemia.

Acetylcholine↗
PubMed1996

Endothelium-dependent coronary vasomotion relates to the susceptibility of LDL to oxidation in humans.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Acetylcholine↗
PubMed1996

Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year posttransplant.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Acetylcholine↗
PubMed1996

Role of nitric oxide in the local regulation of pulmonary vascular resistance in humans.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Acetylcholine↗
PubMed1996

Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus.

Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus. Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals contributes to abnormal vascular reactivity in experimental models of diabetes. To determine whether this observation is relevant to humans, we tested the hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent vasodilation in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus. We studied 10 diabetic subjects and 10 age-matched, nondiabetic control subjects. Forearm blood flow was determined by venous occlusion plethysmography. Endothelium-dependent vasodilation was assessed by intraarterial infusion of methacholine (0.3-10 micrograms/min). Endothelium-independent vasodilation was measured by intraarterial infusion of nitroprusside (0.3-10 micrograms/min) and verapamil (10-300 micrograms/min). Forearm blood flow dose-response curves were determined for each drug before and during concomitant intraarterial administration of vitamin C (24 mg/min). In diabetic subjects, endothelium-dependent vasodilation to methacholine was augmented by simultaneous infusion of vitamin C (P = 0.002); in contrast, endothelium-independent vasodilation to nitroprusside and to verapamil were not affected by concomitant infusion of vitamin C (P = 0.9 and P = 0.4, respectively). In nondiabetic subjects, vitamin C administration did not alter endothelium-dependent vasodilation (P = 0.8). We conclude that endothelial dysfunction in forearm resistance vessels of patients with non-insulin-dependent diabetes mellitus can be improved by administration of the antioxidant, vitamin C. These findings support the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.

Adult↗
PubMed1996

Nitroglycerin-induced coronary vasodilation is not enhanced in patients with impaired endothelium-dependent dilation.

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Acetylcholine↗
PubMed1996

Atherosclerosis: risk factors and the vascular endothelium.

The endothelium can respond to a local environment by releasing a variety of substances that regulate the level of vascular tone. One of the most important of these vasoregulatory substances is EDRF. The function of the endothelium is altered in a variety of pathologic and physiologic conditions. This review focused on the role of risk factors for atherosclerosis as it relates to EDRF. Atherosclerotic blood vessels respond abnormally on exposure to stimuli that release EDRF. It is now also apparent that this abnormal vascular response may precede the development of significant atherosclerosis and that normalization of the EDRF response with treatment is possible. Thus abnormal endothelium-dependent relaxation has been demonstrated in hypercholesterolemic patients with little or no evidence of coronary angiographic disease and in patients with hypertension before the development of atherosclerosis. The interaction between risk factors and the function of the vascular endothelium with development of atherosclerosis may become a useful focus for therapies that benefit patient outcomes.

Aging↗
PubMed1996

Biological mechanisms for the clinical success of lipid-lowering in coronary artery disease and the use of surrogate end-points.

The small changes in luminal narrowing observed with lowering total cholesterol are unlikely to be the principal mechanism by which lipid-lowering achieves a reduction in clinical events and revascularization rates. Endothelium dependent vasomotor function, and the cellular characteristics of plaques that seem to be intimately related to rupture and thrombosis, are factors that may explain the clinical success from correcting the dyslipidemias. Dyslipidemias cause endothelial dysfunction that predisposes to vasoconstriction of the epicardial coronary arteries and the resistance vessels relative to metabolic demand. Dysfunctional endothelium also promotes the recruitment of inflammatory cells into the vessel wall which contributes to the activation of vascular smooth muscle cells and sets up an environment within the plaque that predisposes to rupture and a prothrombotic state. Aggressive lowering of total cholesterol, and especially LDL and oxidized LDL, improves coronary endothelial function both of the epicardial and resistance vessels, and leads to a reduction in myocardial ischemia. Lipid-lowering may promote plaque stability in part by reducing the recruitment of inflammatory cells, and possibly by changing the size or consistency of the lipid-rich core of plaques. A thicker fibrous cap and stiffer plaque that is less likely to rupture may result, and in the event that rupture does occur, cholesterol lowering may reduce the formation of overlying thrombus. Testing coronary or peripheral artery endothelial vasomotor dysfunction may be a surrogate measure for assessing the effectiveness of interventions to prevent coronary heart disease. These tests are likely to be used increasingly to identify interventions that deserve greater attention in larger clinical trials, as well as providing mechanisms for any observed clinical benefits.

Animals↗
PubMed1996

Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide.

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.

Acetylcholine↗
PubMed1996

Activation of ATP-sensitive potassium channels contributes to reactive hyperemia in humans.

Activation of ATP-sensitive potassium (KATP) channels present on vascular smooth muscle cells causes membrane hyperpolarization and vasodilation. The purpose of this study was to determine whether KATP channels contribute to reactive hyperemia in humans. Accordingly, we studied the effect of tolbutamide, a KATP channel inhibitor, on reactive hyperemic forearm blood flow. Forearm blood flow was measured by venous occlusion plethysmography. Forearm ischemia was produced by inflating a sphygmomanometric cuff on the arm to suprasystolic pressures for 5 min. After cuff release, forearm blood flow was measured during the reactive hyperemic phase for 5 min. Tolbutamide (1 mM blood concentration, n = 6) did not affect basal (2.4 +/- 0.2 to 2.2 +/- 0.1 ml.100 ml-1.min-1) or peak reactive hyperemic forearm blood flow (21.9 +/- 3.8 to 22.6 +/- 2.9 ml.100 ml-1.min-1, each P = NS), but it significantly attenuated total hyperemic volume (12.6 +/- 1.7 vs. 9.2 +/- 1.8 ml/100 ml, P < 0.02). Vehicle (n = 6) did not affect basal flow, peak reactive hyperemic flow, or total hyperemia. To determine whether adenosine or endothelium-derived nitric oxide contribute to reactive hyperemia via KATP channels, adenosine (1.5-500 micro grams/min, n = 6) and acetylcholine (30 micrograms/min, n = 6) were infused before and during tolbutamide coinfusion. Tolbutamide did not significantly alter the forearm blood flow response to either adenosine or acetylcholine. In conclusion, KATP channels contribute to vasodilation during reactive hyperemia in humans.

Acetylcholine↗
PubMed1995

Identification of anomalous coronary arteries and their anatomic course by magnetic resonance coronary angiography.

BACKGROUND: Anomalous coronary arteries are a rare but recognized cause of myocardial ischemia and sudden death. Identification currently requires x-ray angiography, which may have difficulty defining the three-dimensional course of the anomalous vessel. Magnetic resonance coronary angiography (MRCA) has been shown to image coronary artery anatomy noninvasively. We hypothesize that MRCA may be useful in the identification of anomalous coronary arteries and their anatomic course. METHODS AND RESULTS: Sixteen patients (9 men, 7 women, age 44 to 81 years) with anomalous aortic origins of the coronary arteries by conventional x-ray angiography underwent MRCA. Multiple images of the major epicardial coronary arteries were obtained by use of a breathhold, fat-suppressed, segmented-k space, gradient-echo technique by investigators blinded to all patient data. Anomalous coronary artery pathology, by x-ray angiography, included right-sided left main coronary artery (n = 3), right-sided left circumflex artery (n = 6), separate left-sided left anterior descending and left circumflex arteries (n = 2), left-sided right coronary artery (n = 4), and an anteriorly displaced right coronary artery (n = 1). MRCA correctly identified the anomalous coronary vessel(s) in 14 of 15 patients. In 1 patient, the anomalous vessel was incorrectly identified, and in 2 patients the course of the anomalous vessel was not clearly seen; one of these was a nondominant, anomalous right coronary artery. CONCLUSIONS: MRCA is a useful technique for the noninvasive identification of anomalous coronary arteries and their anatomic course.

Adult↗
PubMed1995

Close relation of endothelial function in the human coronary and peripheral circulations.

OBJECTIVES: The relation between endothelium-dependent vasodilator function in the brachial and coronary arteries was determined in the same subjects. BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Acetylcholine↗
PubMed1995

Systemic nature of endothelial dysfunction in atherosclerosis.

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.

Arteriosclerosis↗