Sites Of Atherosclerotic Lesions Research Articles

Platelet Activation in Carotid Sinuses Triggers Reflex Sympathoinhibition and Hypotension

The carotid sinuses, one of the major sites of baroreceptor innervation, are also a common site of atherosclerotic lesions and platelet aggregation. The goal of the present study was to determine whether platelet activation in carotid sinuses causes reflex-mediated changes in renal sympathetic nerve activity and arterial pressure. Rabbit platelets were isolated, resuspended in Krebs' buffer, and activated by thrombin. Injection of activated platelets (3 x 10(8) platelets/mL) into the vascularly isolated carotid sinuses of anesthetized rabbits essentially eliminated sympathetic nerve activity and acutely decreased mean arterial pressure from 126 +/- 5 to 53 +/- 4 mm Hg (n=16; P < .05). Sympathetic activity and arterial pressure returned to control levels over a period of minutes despite sustained exposure to activated platelets. Injection of U-46619, a thromboxane analogue and vasoconstrictor, into carotid sinuses did not alter sympathetic activity or arterial pressure. However, serotonin (5-hydroxytryptamine [5-HT]), which is known to be released from activated platelets, and the 5-HT3 receptor agonist phenylbiguanide mimicked the effect of platelets. Furthermore, the platelet-induced reflex inhibition of sympathetic activity and hypotension were not altered by the cyclooxygenase inhibitor indomethacin but were attenuated significantly by 5-HT receptor antagonists. Platelet activation inhibited sympathetic activity to 5 +/- 2% of control in the absence of antagonists but to only 35 +/- 11 and 76 +/- 4% of control after selective blockade of 5-HT2 and 5-HT3 receptors with ketanserin and MDL-72222, respectively. The results indicate that (1) platelet activation in carotid sinuses triggers reflex inhibition of sympathetic nerve activity and hypotension; (2) the reflex is not caused by carotid vasoconstriction and is not mediated by prostanoids; and (3) the reflex is mediated by 5-HT acting primarily on 5-HT3 and to a lesser extent on 5-HT2 receptors. We speculate that this reflex may contribute to arterial pressure lability and susceptibility to stroke in patients with carotid atherosclerotic disease.

Finite element analysis of two dimensional steady flow in model arterial bifurcation

The purpose of the investigation reported in this paper is to determine theoretically the fluid dynamic field in models of common iliac arterial bifurcation and to identify the flow features which might influence the predominant occurence of atherosclerotic lesions at such sites. This has been accomplished by numerically simulating fluid flow through 90° symmetric bifurcations with branch-to-trunk area ratios of 0.8–1.414 and for Reynolds numbers ranging from 100 to 400. The analysis predicts flow reversal along the outer wall in models with area ratios over unity for high Reynolds number range, while no flow reversal occured in models with area ratio below unity; a low shear zone along the outer wall and high shear stresses at the divider lip. Adverse pressure gradients are observed along the outer wall downstream of the corner point, the magnitudes increased with Reynolds number for a given branch to area ratio. Biological implication of the results is discussed with specific reference to the sites of atherosclerotic lesions found in man for these geometries.

Clinical studies of patients with coronary spasm

Coronary artery spasm may cause myocardial ischemia in patients without severe coronary atherosclerotic obstruction. Spontaneous rest angina, particularly at night, is the predominant symptom; most patients are smokers. Ergonovine tests have high sensitivity and specificity for the diagnosis of coronary spasm, but should be used when vasospasm is suspected but no electrocardiogram was recorded during spontaneous angina. Arterial constriction measured during ergonovine testing suggests that the arterial hypersensitivity to vasoconstrictors at sites of atherosclerotic lesions is independent of the severity of the lesion. Coronary vasospasm may also be provoked by exercise, possibly through an alpha-adrenergic mechanism. Both spontaneous and exercise-induced attacks of vasospasm are prevented by calcium-antagonist drugs that remain effective during longer-term treatment. The cyclic nature of the condition is demonstrated when successful therapy is discontinued without recurrence of symptoms and may be due to alteration of arterial hypersensitivity.

Dynamic vascular factors in the genesis of myocardial ischemia

While fixed atherosclerotic and thrombotic lesions have long been known to cause myocardial ischemia and cardiac pain, the various transient or dynamic events that may also cause ischemia and pain have become better understood in the past 15 years. These can be classified into two broad categories: those that cause a dynamic reduction in the caliber of the coronary arteries and those that reduce the coronary vasodilatory reserve capacity. In the first group are myocardial compression or "bridging" of an artery; coronary vasoconstriction due to frank spasm or generalized arterial hypertonus, particularly at the site of atherosclerotic lesions; reduced arterial distending pressure and platelet aggregation which may transiently occlude a diseased arterial segment. The causes of inadequate coronary vascular reserve flow capacity can be either anatomic or functional. Among the former, the increased muscle mass to blood vessel ratio occurring in myocardial hypertrophy is most important. The functional causes of limited coronary vascular reserve include diastolic transmural compression and coronary "steal," both of hemodynamic origin. In addition, arteriolar "unresponsiveness" or dysregulation caused by smoking, drugs or other unknown conditions may adversely affect coronary vascular reserve. Hence, myocardial ischemia may result from conditions that limit potential for increase in flow or from conditions that reduce flow from a preexisting level. These conditions, which are transient and dynamic in nature, may modify the threshold for ischemia, particularly in patients with fixed coronary obstructive disease.

The mode of calcification in atherosclerotic lesions.

In serveral arterial provinces, atherosclerosis and atherosclerotic calcifications are preceded by primary calcifications which develop in a seemingly unchanged arterial wall and often show regular gross patterns. In contrast, secondary calcifications which appear in the atherosclerotic lesions are irregularly distributed along the thickened atherosclerotic intima. At the predilection sites of atherosclerotic lesions, pronounced primary calcifications often precede the fatty streaking representing an independent pathological process. The deformation of the arterial wall resulting from calcific plaques may favor the activation of intimal mesenchyme and contribute to increased accumulation of lipid above and around calcific deposits. The exact nature of structural and biochemical changes which precede and result in primary and secondary arterial calcification still remains obscure.

Cerebral atherosclerosis in Japanese. 3. Predilection site of atherosclerotic lesions.

Four hundred twenty-three intracranial cerebral arteries (males and females) were obtained from the medicolegal autopsy cases. Special attention was given to the three sites and the circumferential distribution of lesions in order to investigate the effects of hydrodynamics on the development of cerebral atherosclerosis. The severest lesions were primarily found at the inner curvature at the terminal portion of the internal carotid artery, the medial portion at the origin of the anterior cerebral artery, and the posterior portion at the origin of the posterior cerebral artery. The present results obviously demonstrated the relationship between the predilection sites of atherosclerotic lesions and the shape of the cerebral arterial tree.