Coronary Physiology and Atherosclerosis

Published on 07/02/2015 by admin

Filed under Anesthesiology

Last modified 07/02/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 948 times

Chapter 4 Coronary Physiology and Atherosclerosis

When caring for patients with coronary artery disease (CAD), the anesthesiologist must prevent or minimize myocardial ischemia by maintaining optimal conditions for perfusion of the heart. This goal can be achieved only with an understanding of the many factors that determine myocardial blood flow in both health and disease.


The coronary vasculature has been traditionally divided into three functional groups: large conductance vessels visible on coronary angiography, which offer little resistance to blood flow; small resistance vessels ranging in size from about 250 to 10 μm in diameter; and veins. Although it has been taught that arterioles (precapillary vessels < 50 μm) account for most of the coronary resistance, studies indicate that, under resting conditions, 45% to 50% of total coronary vascular resistance resides in vessels larger than 100 μm in diameter. This may be due, in part, to the relatively great length of the small arteries.


Although the vascular endothelium was once thought of as an inert lining for blood vessels, it is more accurately characterized as a very active, distributed organ with many biologic functions. It has synthetic and metabolic capabilities and contains receptors for a variety of vasoactive substances.

Endothelium-Derived Relaxing Factors

The first vasoactive endothelial substance to be discovered was prostacyclin (PGI2), a product of the cyclooxygenase pathway of arachidonic acid metabolism (Box 4-1). The production of PGI2 is activated by shear stress, pulsatility of flow, hypoxia, and a variety of vasoactive mediators. Upon production it leaves the endothelial cell and acts in the local environment to cause relaxation of the underlying smooth muscle or to inhibit platelet aggregation. Both actions are mediated by the stimulation of adenylyl cyclase in the target cell to produce cyclic adenosine monophosphate (cAMP).

It has been shown that many physiologic stimuli cause vasodilation by stimulating the release of a labile, diffusible, nonprostanoid molecule termed endothelium-derived relaxing factor (EDRF), now known to be nitric oxide (NO). NO is the basis of a widespread paracrine signal transduction mechanism whereby one cell type can modulate the behavior of adjacent cells of a different type.1,2 NO is a very small lipophilic molecule that can readily diffuse across biologic membranes and into the cytosol of nearby cells. The half-life of the molecule is less than 5 seconds so that only the local environment can be affected. NO is synthesized from the amino acid L-arginine by NO synthase (NOS). When NO diffuses into the cytosol of the target cell, it binds with the heme group of soluble guanylate cyclase, resulting in a 50- to 200-fold increase in production of cyclic guanosine monophosphate (cGMP), its second messenger. If the target cells are vascular smooth muscle cells, vasodilation occurs; if the target cells are platelets, adhesion and aggregation are inhibited.

It is likely that NO is the final common effector molecule of nitrovasodilators (including sodium nitroprusside and organic nitrates such as nitroglycerin). The cardiovascular system is in a constant state of active vasodilation that is dependent on the generation of NO. The molecule is more important in controlling vascular tone in veins and arteries compared with arterioles. Abnormalities in the ability of the endothelium to produce NO likely play a role in diseases such as diabetes, atherosclerosis, and hypertension. The venous circulation of humans seems to have a lower basal release of NO and an increased sensitivity to nitrovasodilators compared with the arterial side of the circulation.3


Under normal conditions, there are four major determinants of coronary blood flow: perfusion pressure, myocardial extravascular compression, myocardial metabolism, and neurohumoral control.