Decrease in Coronary Blood Flow Reserve During Hyperlipidemia Is Secondary to an Increase in Blood Viscosity

Abstract

Background-During maximal hyperemia, capillaries provide the greatest resistance to flow. A major determinant of capillary resistance is viscosity. We, therefore, hypothesized that abnormal coronary blood flow (CBF) reserve observed during hyperlipidemia is secondary to increased blood viscosity and not abnormal coronary vasomotion. Methods and Results-Maximal hyperemia was induced in 9 dogs using adenosine. Serum triglyceride levels were increased by incremental doses of Intralipid. A good correlation was noted between serum triglyceride levels and blood viscosity (rϭ0.82). Neither total coronary blood volume nor myocardial blood volume changed with increasing serum triglyceride levels, indicating lack of vasomotion. Myocardial vascular resistance (MVR) increased with increasing triglyceride levels (rϭ0.84), while hyperemic myocardial blood flow (MBF) decreased (rϭϪ0.64). The decrease in hyperemic MBF was associated with a decrease in blood velocity (rϭϪ0.56). These findings were confirmed with direct intravital microscopic observations in the mice cremaster muscle. Conclusions-Increasing lipid levels in a fully dilated normal coronary bed causes no change in large or small vessel dimensions. Instead, the increase in blood viscosity causes capillary resistance to rise, which attenuates hyperemic CBF. Therefore, the abnormal CBF reserve associated with hyperlipidemia is due to increase blood viscosity and not abnormal vascular function. Key Words: risk factors Ⅲ lipids Ⅲ microcirculation A bnormal coronary blood flow (CBF) reserve has been associated with hyperlipidemia even in the absence of structural changes in coronary arteries. [1][2][3][4] It is generally thought that this phenomenon is secondary to endothelial dysfunction that affects the ability of coronary vessels to dilate. 5,6 At rest, maximal resistance to CBF is offered by the coronary arterioles with only a small portion offered by the capillaries and venules. 7 During hyperemia, however, coronary arterial and venular resistances decrease significantly, but capillary resistance remains unaffected. Consequently, capillaries offer the most resistance to CBF during hyperemia and thus determine the maximal possible increase in hyperemic CBF. 8 According to Hagen-Poiseuille's equation, resistance to flow within a tube depends on the dimensions of the tube and the viscosity of the fluid in it. In large vessels, resistance is determined mainly by the dimensions of the vessels with viscosity playing a negligible role. In vessels with Ͻ30 m diameter, however, an abrupt increase in viscosity is seen with an inverse relation between vessel size and effective viscosity. 9 Increased whole blood and plasma viscosity are observed in patients with hyperlipoproteinemia. 10 -12 A major factor affecting capillary resistance is blood viscosity. Because capillaries play a dominant role in limiting maximal hyperemic CBF, we hypothesized that abnormal CBF reserve observed during hyperlipidemia in the absence of coronary stenosis is secondary to increased blood viscosity ...

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“…These differences in hemodynamic responses may be attributed to the difference in pharmacological action between calcium channel blockers and L-arginine. Blood viscosity is a parameter that defines the blood velocity (45)(46)(47). Therefore, effects on blood viscosity may provide a possible explanation of the difference in pharmacological action between calcium channel blockers and L-arginine.…”

Increased Blood Viscosity in Ischemic Stroke Patients with Small Artery Occlusion Measured by an Electromagnetic Spinning Sphere Viscometer

“…[8][9][10] Furthermore, relationships have been reported between blood viscosity and some cardiovascular risk factors, such as hypertension, dyslipidemia, smoking, and obesity. [11][12][13][14] An increase in blood viscosity has been identified in the acute phase of ischemic stroke, similar to other thrombotic diseases. [15][16][17][18][19] However, actual 4 measurements of blood viscosity have not been performed because of the stereotypical belief that blood viscosity increases equally in all ischemic stroke subtypes, which is within expectations and with less clinical value.…”

Microvasculature in Acute Myocardial Ischemia: Part I

“…12 A number of studies have shown an increase in blood viscosity with hyperlipoproteinemia. [13][14][15][16] A strong positive correlation has been noted between increased blood viscosity and CAD. 17 Several studies have shown abnormal CBF reserve even in patients with CAD risk factors in the absence of CAD on angiography.…”