10
Regulation of Coronary
Vascular Tone and
Microvascular Physiology
by Basel Ramlawi, Munir Boodhwani and Frank W. Sellke
1. Introduction
There are many cell types that make up the walls of blood vessels. The innermost layer is made of endothelial cells. This intimal endothelial layer is surrounded by a variable number of layers of smooth muscle cells comprising the medial layer. The adventitial layer surrounds the vascular smooth muscle layers. This last layer is responsible for providing structural integrity to the blood vessel, particularly larger arteries. While initially the endothelium was thought mainly to serve as a barrier to the diffusion of macromolecules, much has recently been learned about the pivotal role it plays in vascular function, regulation of vascular tone and control of local blood flow.1 Smooth muscle cells also control vascular tone via humoral vascoactive factors, neural mediators or local paracrine factors (Fig. 1).
The classification of microvessels based on structural characteristics is rather arbitrary and there is lack of uniformity in the definitions
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Fig. 1. Regulation of vascular tone by factors released from the endothelium, activated platelets and leukocytes, neuronally released factors and circulating substances. Ang, angiotensin; 5HT, 5-hydroxytrypamine (serotonin); ET, endothelin; ADP, adenosine diphosphate; EDHF, endothelium-derived hyperpolarizing factor; PGI2, prostaglandin I2; Ach, acetylcholine; NE, norepinephrine. (Adapted from Ref. 71.)
of microvascular segments such as small arteries, arterioles, venules, and so on. The transition between these segments is gradual and there is no clear demarcation between them. In general, “microvessels” are defines as vessels < 300 µm in internal diameter. Capillaries are the smallest blood vessels defined as vessels whose walls are composed of only endothelial tubes. The microvessels through which blood flows toward capillaries are defined as “arterial microvessel” and those that drain from capillaries are defined as “venous microvessel.”2 Arterial microvessels usually have three coats, i.e. a thin tunica intima; a relatively thick tunica media, composed of one to several layers of smooth muscle cells disposed circumferentially; and a tunica adventitia, which
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is made up of fibrous elements and fibroblasts. Venous microvessels collect the blood from capillaries and have thinner vascular walls compared with arterial microvessels. Venules, 50 µm in diameter do not possess smooth muscle cell layers. Smaller venules have only endothelial cells and pericytes, and these venules are the most permeable sites that play an important role in substance exchange.
The various vascular beds within the body possess many similarities and subtle differences. This chapter will particularly focus on the coronary microcirculation. The regulation of myocardial perfusion is dependent on many intrinsic and extrinsic factors that may be affected by atherosclerotic lesions. For this reason, a thorough understanding of coronary flow regulation is critical for optimal care of cardiac patients. It has been shown that vasomotor regulation of coronary vessels, in addition to the actual anatomy, plays an important role in coronary perfusion and operative decision making. Myocardial blood flow is largely also dependent on the resistance generated by the microcirculation. While early coronary vasomotor regulation studies consisted of indirect assessments using measurements of coronary flow and calculations of coronary resistance, more recent investigations yielded much information into the properties of the intact coronary circulation and modern methods of analysis for interpretation of physiological data.3−6
The coronary microcirculation possesses unique features that allow it to respond to the dynamic changes in nutrient requirements as well as interact with surrounding contractile tissue. As in other vascular beds, it is composed of arterioles, capillaries and venules. This chapter will focus on issues relating to coronary physiology and pharmacology as well as myocardial perfusion in relation to the microcirculation.
2. Coronary Resistance
An understanding of vascular resistance is important as it is these resistance vessels that cause pressure losses and are responsible for regulation of myocardial perfusion. Initially it was thought that the precapillary arterioles were responsible for vascular resistance, with little resistance involvement by the vessels larger than 25–50 µm in diameter. Subsequent work revealed that over half of total coronary resistance
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Fig. 2. Intravascular pressures in the coronary microcirculation under basal conditions and during vasodilation with dipyridamole. The distribution of vascular resistance is not static. Rather the size of the vessels regulating vascular tone depends on the tone of the vasculature. (Adapted from Ref. 9.)
is caused by vessels larger than 100 µm and can be observed in vessels larger than 300 µm.7,8 Also, contrary to previous belief, the venous circulation under similar conditions of vasodilation, may account for up to 30% of vascular resistance. Figure 2 shows that under the vasodilatory effects of dipyridamole, larger arteries and veins assume a greater resistance role.8,9 Similarly, ischemia results in a significant redistribution of vascular resistance.9 This reveals that the distribution of vascular resistance is dynamic and is dependent on vascular tone among other factors.
The redistribution of microvascular resistance may change the myogenic tone in each microvascular segment because the luminal pressure in a certain vascular segment is determined by the systemic pressure and the relative distribution of vascular resistance. That is, when resistance is shifted upstream by dilation of small arterioles, for instance, the luminal pressure in the upstream microvessels decreases, resulting in myogenic