In animals, acetylcholine dilates normal arteries and produces vasoconstriction in the presence of hypercholesterolemia, hypertension, or atherosclerosis, reflecting endothelial cell dysfunc- (Circulation 1990;81:491-497) In animals, acetylcholine produces endotheliumdependent dilation of normal arteries and vasoconstriction in pathologic states such as hypersee p 697 cholesterolemia, hypertension, or atherosclerosis.1-9 Clinical studies have shown that intracoronary acetylcholine infusion constricts atherosclerotic coronary arteries.9-11 Smooth segments may also constrict in patients with coronary artery disease evident in

In patients with hypertension, a pattern of left ventricular hypertrophy on the electrocardiogram is associated with a risk of sudden death in excess of the risk attributable to hypertension alone. We therefore investigated the frequency of complex ventricular arrhythmias by means of 48-hour ambulatory electrocardiographic monitoring in 100 treated hypertensive patients, of whom 50 had electrocardiographic evidence of left ventricular hypertrophy and 50 did not, and in 50 normotensive controls. The groups were matched for age, sex, and smoking habits, and the two hypertensive groups were matched for blood-pressure levels before and after antihypertensive therapy. Nonsustained ventricular tachycardia, defined as greater than or equal to 3 complexes at a rate greater than or equal to 120 beats per minute, occurred in 14 (28 percent) of the 50 patients with an electrocardiographic pattern of left ventricular hypertrophy, in 4 (8 percent) of the 50 patients without hypertrophy (P less than 0.05), and in 1 (2 percent) of the control subjects. Eight of the 50 patients (16 percent) with hypertrophy had episodes of nonsustained ventricular tachycardia longer than 5 complexes, whereas no patients without hypertrophy and no controls had such episodes. The group with nonsustained ventricular tachycardia was characterized by a high left ventricular mass on echocardiography and a high prevalence of ST-T abnormalities on electrocardiography. Ventricular tachycardia was not closely related to blood-pressure levels, nor was it associated with diuretic therapy or hypokalemia. The clinical importance of these arrhythmias is uncertain. Nevertheless, our data suggest that complex ventricular arrhythmias occur commonly in hypertensive patients with left ventricular hypertrophy and may contribute to the higher incidence of sudden death in these patients.

Objective-To evaluate the role of haemostatic and haemodynamic variables in left atrial thrombosis in non-rheumatic atrial fibrillation. Design-Case-control study. Subjects-One hundred and nine patients with non-rheumatic atrial fibrillation. Interventions-Peak blood velocity measured at three sites in the left atrium. Venous blood sampled for coagulant proteins and markers of haemostatic activation. Conclusions-Haemostatic and haemodynamic abnormalities are associated with left atrial thrombus in nonrheumatic atrial fibrillation, and may help stratify thromboembolic risk.

No abstract

This study investigated the vasodilator function of endothelium that regenerated after balloon angioplasty and the relation of this function to the extent of vascular injury and to subsequent intimal proliferation. Balloon angioplasty was performed in the left iliac artery of 47 New Zealand White rabbits. Vascular responses were examined in vitro 2 and 4 weeks after a "severe" injury (3.0-mm balloon) or a "moderate" injuiry (2.5-mm balloon). Both degrees of balloon injury caused complete endothelial denudation. Endothelial regrowth 2 weeks after either injury was confirmed histologically. Although the regenerated cells had irregular sizes and polygonal shapes and lacked the typical alignment in the direction of blood flow, immunocytochemical staining for factor VILI-related antigen identified these cells as endothelium. To study the vasodilator function of regenerated endothelium, rings of balloon-injured and control (contralateral) iliac arteries were suspended in organ chambers for recording of isometric force. Endothelium-dependent relaxation of balloon-injured vessels to acetylcholine and to the calcium ionophore A23187 were reduced at 2 and at 4 weeks after severe injury. After moderate injury, endothelium-dependent relaxations to these agents were reduced at 2 weeks but had normalized by 4 weeks. Endothelium-independent relaxation to sodium nitroprusside, however, was preserved in all study groups. Morphometric analysis revealed an inverse correlation between the degree of intimal thickening and maximal relaxation to acetylcholine (r=0.45,p<0.01). Thus, there is a persistent attenuation ofreceptor-and nonreceptor-mediated endothelium-dependent relaxations after arterial injury. The regenerated cells have an altered morphological appearance, but staining for factor VIII-related antigen confirms their endothelial origin. The degree and duration of endothelial dysfunction depends on the severity of the initial injury and is related to the extent of intimal thickness. (Circulation 1990;81:1667-1679 Normal endothelial function includes the formation of a semipermeable barrier that actively regulates coagulation, cell growth, and vasoreactivity.-4 Endothelium-derived relaxing

Patient education should include focused discussions addressing the 'mismatches' that may occur between their expectations and reality. In this way, a more coherent understanding can be promoted, with greater awareness of heart disease as a long-term condition requiring ongoing self-management.

Intracoronary acetylcholine produces endothelium-dependent dilation of normal coronary arteries and paradoxical constriction of atherosclerotic vessels. Regional differences in endothelium-dependent vasomotion, however, have not been studied in relation to the nonuniform development of atherosclerosis. We compared the vasomotor response to increasing doses of acetylcholine of angiographically smooth coronary artery segments prone to atherosclerosis (coronary branch points) with segments remote from branch points (straight segments). In patients with entirely smooth coronary arteries and a dilator response to acetylcholine (group 1, n=7), branch points and straight segments demonstrated equal and significant dosedependent dilation to acetylcholine (14.7±8.9%o and 12.3±12.7%, respectively; p_NS). In patients with early atherosclerosis as manifest by luminal coronary irregularities, the lowest dose of acetylcholine (10-8 M) produced constriction at branch points and slight dilation at straight segments (-6.3 ±7.4% vs. +2.2+7.3%, p <0.05). At higher doses of acetylcholine, both branch point and straight segments constricted, but constriction remained more pronounced at branch points. Both branch point and straight segments, however, retained the ability to dilate to the non-endothelium-dependent agent, nitroglycerin. In a third group of patients with angiographically entirely smooth coronary arteries but without dilation to acetylcholine, constriction to acetylcholine again occurred first at branch points. Thus, coronary branch points demonstrate increased sensitivity to acetylcholine-induced constriction in patients with angiographic evidence of early coronary atherosclerosis and in middle-aged patients with smooth coronary arteries. These segments, however, retain the ability to dilate to nitroglycerin.Whether this early evidence of defective endothelium-dependent vasodilation predicts the later development of occlusive atherosclerosis is not yet known. (Circulation 1990;82:1169-1173 C oronary atherosclerosis has a long asymptomatic phase of development,1'2 and only the later phases, particularly segmental narrowing and stenosis, can be assessed by coronary arteriography. Furthermore, atherosclerosis is a focal disease with specific sites of predilection that include branch points and other regions of disturbed flow.3 Experimental studies suggest that alterations in local arterial wall shear stress produce morphological changes in the vascular endothelium that may play a central role in atherogenesis.4-6

Endothelium-dependent vasodilation in response to both acetylcholine and increased blood flow may be lost early in the course of developing atherosclerosis before the appearance of stenosing and occlusive disease.