ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Although abnormal vasoconstriction may be involved in the pathogenesis of the acute coronary syndromes, the vasoreactivity of the lesion responsible for unstable angina (culprit lesion) has not been directly investigated. It is also unknown if enhanced vasoreactivity is found downstream to this lesion or extends to uninvolved coronary arteries.Methods and ResultsWe studied seven unstable angina patients whose condition had sufficiently stabilized to allow ergometric bicycle exercise and a cold pressor test to be performed as provocative stimuli during coronary arteriography. We measured the luminal diameter of the culprit lesion, a normal-appearing distal segment, and the segment of an uninvolved coronary artery using quantitative coronary angiography. Seven stable angina patients served as controls. Antianginal medications were tapered and interrupted. The culprit lesion constricted significantly with exercise and the cold pressor test compared with a stable angina control lesion. The culprit lesion measured 1.41±0.07 mm at baseline and diminished to 1.09±0.07 mm with exercise (P= .001). It measured 1.26±0.07 mm before the cold pressor test and diminished to 1.09±0.03 mm with this test (P= .015). In contrast, the profile of the stable lesion in the stable angina control group differed significantly (P= .006). Its luminal diameter measured 1.42±0.17 mm at baseline and 1.48±0.21 mm with exerciseP=NS). It measured 1.57±0.18 mm before and 1.55±0.18 mm with the cold pressor test (P=NS). There were no significant changes to these stimuli in the uninvolved coronary artery segments in unstable angina and in the distal segments in both unstable and stable angina patients.ConclusionsThis study demonstrates increased vasoreactivity of the culprit lesion in unstable angina compared with a control lesion in stable angina. The lack of an effect either in the uninvolved coronary artery or downstream to the culprit lesion suggests that systemic neurohumoral or seeding mechanisms are not operative. This abnormal vasoreactivity might predispose to, or be a marker for, the recurrence of acute ischemia at this site.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Tumor necrosis factor-α (TNFα), which we and others have shown to be elevated in patients with severe congestive heart failure (CHF), is involved in the regulation of nitric oxide metabolism. Whether increased concentrations of TNFα affect nitric oxide-mediated vasodilation in patients with CHF has not been studied previously.Methods and ResultsSerum concentrations of TNFα, interleukin- 1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined in venous blood (pg/mL) from 17 patients with stable New York Heart Association classes II and III CHF (mean age, 58±11 years; mean left ventricular ejection fraction, 19.5±7.3) and 17 age-matched normal subjects with enzyme-linked immunosorbent assays (detection limit of assays, 20 pg/mL). Forearm blood flows were determined with plethysmography (mL/min per 100 mL) in 17 patients and 7 normal subjects in response to brachial artery administration of graded concentrations of acetylcholine (10−6mol/L and 10−5mol/L) and nitroglycerin (10−7mol/L and 10−6mol/L). Serum concentrations of TNFα were above the detection limits of the assay in 10 of 17 patients with CHF (mean serum concentration, 39.4±3.8 pg/mL). Forearm blood flow responses to acetylcholine and nitroglycerin were significantly greater in these 10 patients than in the 7 patients without detectable serum TNFα and were closely correlated with INFα serum concentrations (r. ≥ .81,P< .01 andr≥ .65,P< .05 respectively). In 1 of 17 normal subjects, the serum oncentration of TNFα was just above the detection limit of the assay. Serum concentrations of IL-2 were above the detection limit of the assay in 14 of 17 patients with CHF (mean serum concentration, 112±19 pg/mL). IL-2 was not detected in the serum of normal subjects. Serum concentrations of IL-1 and IL-6 were below the detection limit of the assays in all patients and normal subjects assayed.ConclusionsIncreased TNFα concentrations are closely correlated with forearm blood flow responses to regional administration of acetylcholine and nitroglycerin. The significant correlation between serum concentrations of TNFα and forearm blood flow responses to acetylcholine and nitroglycerin suggests that both the inducible and the constitutive forms of nitric oxide synthase are involved in the regulation of peripheral vasomotor tone in patients with CHF.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The α-adrenergic component of the sympathetic nervous system plays a major role in the pathophysiology, clinical manifestations, and natural history of human congestive heart failure (CHF). However, the functional integrity of vascular α1- and α2-adrenoceptors in CHF remains to be elucidated. The present study was designed to assess the vascular responsiveness of α1- and α2-adrenoceptors in patients with CHF.Methods and ResultsTo evaluate α1- and α2- adrenoceptor responsiveness, we studied the effects of the regional infusion into the brachial artery of increasing doses of phenylephrine (a selective α1- adrenoceptor agonist) and BHT 933 (a selective α2-adrenoceptor agonist) on vascular responses in 12 healthy subjects and in 24 patients with CHF secondary to primary dilated cardiomyopathy or ischemic heart disease. Left ventricular ejection fraction was measured by radionuclide angiography, and forearm blood flow was determined by venous occlusion plethysmography. Phenylephrine reduced forearm blood flow in normal subjects from 5.2±0.9 to 2.5±0.6 mL per 100 mL of tissue/min (P< .05) at the highest dose (−50.8±4.8% versus baseline). A similar vasoconstriction was obtained in patients with CHF (from 3.5±0.5 to 1.5±0.2 mL per 100 mL of tissue/min (P< .05) (−58.7±5.0% versus baseline). The dose-response curves produced by phenylephrine in the two groups were comparable. The highest dose of BHT 933 reduced forearm blood flow in normal subjects from 5.3±0.9 to 2.3±0.6 mL per 100 mL of tissue/min (P< .05) (−59.0±4.9% versus baseline). In patients with CUF, a similar vasoconstriction was obtained (from 4.2±0.8 to 1.5±0.3 mL per 100 mL of tissue/min,P< .05, −62.1±6.5% versus baseline). The dose-response curves produced by BHT 933 also were comparable in the two groups. In patients with CHF, plasma concentrations of norepinephrine were significantly higher than in normal subjects.ConclusionsThe results of the present study demonstrate that α1- and α2-adrenoceptor stimulations produced an equivalent vasoconstriction in patients with CHF and in normal subjects. This indicates that the vascular responsiveness to α-adrenoceptor agonists may be preserved in the limb vessels of patients with CHF.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Cutaneous laser Doppler flowmetry enables monitoring of changes in skin perfusion by quantifying the phase shift of laser light induced by moving red blood cells under a fiberoptic probe. It thus can identify the presence of and response to a vasoconstrictive stimulus. However, aspects of the technique must be defined before it can be used with maximum effectiveness. We evaluated the responses of two different laser Doppler outputs, the concentration of moving blood cells (CMBC) and red cell flux (CMBC times cell velocity), and the responses at two sites of probe application, the finger and forearm, during systemic infusions of phenylephrine.Methods and ResultsEight healthy volunteers were monitored with a brachial blood pressure cuff, ECG, and laser Doppler flowmeter probes applied to the palmar surface of the fourth finger and volar forearm of the arm opposite the pressure cuff. After baseline readings were obtained, the subjects received three 10-minute intravenous infusions of phenylephrine at rates of 0.4, 0.8, and 1.6,μg · kg−1· min−1. The two parameters, flux and CMBC, trended similarly. Flux and CMBC at the finger declined significantly in response to each infusion (P< .05 using repeatedmeasures ANOVA with Duncan's multiple range test). In contrast, flux and CMBC of the forearm had highly variable responses, with an overall increase during each infusion (P< .05 for %Δ of forearm versus %Δ of finger readings during the 0.4μg−1· min−1infusion). Heart rate declined significantly during each infusion, consistent with a baroreceptor-mediated response, even though systolic and diastolic blood pressures each increased by less than 2 mm Hg during the 0.4 μg · kg−1· min−1infusion.ConclusionsAs expected, laser Doppler readings at the finger decreased during infusion of an α1-agonist. Although, like the digital vessels, forearm vessels have the potential to constrict, the increases in forearm readings suggest that these vessels are highly susceptible to homeostatic responses. The increase in CMBC (a parameter that is sensitive primarily to local changes in vascular caliber) suggested vasodilation of the underlying vessels. The forearm vasodilation and the concomitant decline in heart rate most likely represented vagally mediated baroreceptor activity, which was altered even though blood pressure changed minimally during the 0.4,μg · kg−1· min−1infusion. Thus, integrated assessment of skin perfusion at the finger and forearm may provide valuable information about the direct and indirect effects of a vasoactive stimulus. The present application of laser Doppler flowmetry suggests activation of vasodilatory reflexes despite minimal changes in blood pressure.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Smoking is a major risk factor for the development of atherosclerosis. Because endothelial dysfunction may be a marker for future atherosclerosis, we investigated the effects of smoking on endothelium-dependent control of vascular tone.Methods and ResultsThe effects of brachial arterial infusions ofNG-monomethyl-L- arginine (L-NMMA), a nitric oxide synthesis inhibitor; sodium nitroprusside; endothelin-1; and norepinephrine on forearm blood flow (strain-gauge plethysmography) were compared in 29 long- term smokers and 16 nonsmokers. The acute effects of smoking on systemic hemodynamics, plasma catecholamines, and forearm vascular responses to these compounds were investigated in smokers only. Smokers did not differ from nonsmokers (n= 16) regarding the vascular effects of sodium nitroprusside (n= 13) or vasoconstriction due to norepinephrine and endothelin-1 (n= 16). Low- dose endothelin-1-induced vasodilation, believed to reflect endothelial prostacyclin or nitric oxide release, was absent in smokers (n= 16), and their increase of forearm vascular resistance (FVR) after L-NMMA (n=13) was impaired impaired (35.6±27.9% versus 118.8±43.2%,P< .001). Shortterm smoking (n=11) increased blood pressure, heart rate, and plasma epinephrine concentrations (P< .05 or less); enhanced endothelin-1-induced vasoconstriction (ΔFVR, 457±192% versus 254±143%,P< 01); and decreased norepinephrine- induced vasoconstriction (P< .05), but had no effect on the other interventions.ConclusionsLong-term smoking is associated with a diminished nitric oxide-dependent component of basal vascular tone and an impaired endothelium-dependent vasodilator response to low-dose endothelin-1 and short-term smoking enhances endothelin-1-induced vasoconstriction. Impaired endothelial control of vascular tone might reflect impairment of normal antiatherosclerotic endothelial functions in smokers, but the relevance of smoking-induced enhancement of endothelin-1 vasoconstriction remains to be determined.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Endothelial dysfunction is increasingly recognized as an early and important feature of vascular disease. Endothelium-dependent vasodilation is impaired in humans with hypercholesterolemia, although it is unknown whether this defect is selective for some pathways of nitric oxide production or indicates a more generalized abnormality of endothelial function. The aim of this study was to further elucidate the nature of endothelial dysfunction in human hypercholesterolemia by comparing vascular responses of agonists that use different signal transduction pathways to activate production of nitric oxide.Methods and ResultsForearm flow was measured in 12 hypercholesterolemic patients (total cholesterol, 286±35 mg/dL [mean±SD]) aged 50±11 years and in 12 healthy subjects (total cholesterol, 173±27 mg/dL) aged 48±7 years using strain-gauge plethysmography and brachial artery drug infusions. The endothelium-dependent vasodilators used were acetylcholine (7.5, 15, and 30 μg/min), which uses a pertussis toxin-sensitive signal transduction pathway, and bradykinin (100, 200, and 400 ng/min), which uses a pertussis toxininsensitive signal transduction pathway to activate nitric oxide production. Sodium nitroprusside (0.8, 1.6, and 3.2 μg/min) was used to test endothelium-independent vasodilation. The maximum flow in response to acetylcholine was markedly impaired in patients compared with healthy subjects (8.0±5.1 versus 17.5±7.7 mL · min−1· 100 mL−1,P= .002). However, the maximum forearm flow in response to bradykinin was similar in the two groups (13.0±4.5 versus 16.2±5.5 mL · min−1100 mL−1,P= .14), as was the maximum flow in response to sodium nitroprusside (7.0±2.8 versus 8.4±2.2 mL · min−1· 100 mL−1,P= .13).NG-Monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, reduced the maximum forearm vasodilation induced by bradykinin to the same extent in patients and in healthy subjects (-29±8% versus −32±6% reduction in peak flow,P= .80), with similar maximum flows in response to bradykinin (9.2±4.0 versus 10.4±2.6 mL · min−1· 100 mL−1,P= .35).ConclusionsHypercholesterolemic patients are capable of normal nitric oxide bioavailability in response to bradykinin. Impairment of microvascular endothelial vasodilator function in human hypercholesterolemia is selective, and the defect occurs at the level of the acetylcholine receptor or its signal transduction pathway.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The Monitored Atherosclerosis Regression Study, a randomized, double- blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions < 50%S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets.Methods and ResultsTwo hundred seventy subjects, 37 to 67 years old, with plasm/ba total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate ( < 50%S) and severe ( < 50%S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P< .05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the pre-dominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDLassociated apolipoprotein C-Ill (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/ HDL-C was the predominant risk factor.ConclusionsThese results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID