48Coronary microvascular dysfunction in a porcine model of familial hypercholesterolemia results in perturbations of myocardial oxygen balance at rest and during exercise

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Purpose. Coronary microvascular dysfunction is increasingly recognized as a contributor to myocardial ischemia in patients with coronary artery disease. Here we investigated perturbations in the regulation of coronary resistance vessel tone and myocardial oxygen balance at rest and during treadmill exercise, in a porcine model of familial hypercholesterolemia.

Methods. Swine (7 control; 4 FH) were chronically instrumented for measurement of systemic and coronary hemodynamics as well as arterial and coronary venous blood gases, at rest and during graded treadmill exercise. At sacrifice (1-8 weeks later) intravascular ultrasound (IVUS) was used to determine lumen area and plaque burden in the proximal coronary arteries.

Results. FH swine on a western diet exhibited significantly higher levels of cholesterol than control swine (17.9±3.1 vs. 1.9±0.1 mmol/L), resulting in a uniform plaque burden of 34±5% over the first 3 cm of the left anterior descending coronary artery, but with a preserved lumen area and without focal stenoses. Exercise resulted in an increase in myocardial O2 consumption (MVO2) in both control and FH swine (Figure). At rest and during exercise, MVO2 was met by a slightly lower coronary O2 delivery in FH compared to control swine, necessitating an increase in myocardial O2 extraction, thus leading to a decrease in coronary venous (CV) O2 content (Figure). These findings, which imply elevated coronary resistance vessel tone in FH swine, were accompanied by a widening of the arterio-venous pH difference in FH, but not control swine (Figure); suggesting a shift towards anaerobic metabolism.

Conclusions. FH results in microvascular dysfunction, which hampers myocardial oxygenation particularly during exercise.

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