Cardiac dysfunction and mesenteric ischemia are significant factors in morbidity and mortality after cardiopulmonary bypass (CPB), and there are evidence to suggest vascular dysfunction as an important mechanism. HMG CoA reductase inhibitors may improve post-operative outcomes by way of beneficial effects on coronary and mesenteric vascular function. To investigate the response of coronary and mesenteric arteries to HMG CoA reductase inhibitors, the study uses a pig model of CBP. Pigs are fed a high cholesterol diet and treated with an HMG CoA reductase inhibitor regimen for six weeks while a control group receives a placebo. The animals are placed on CPB or are part of the non-CPB group and receive only anesthesia. During the animal experiment, cardiac hemodynamics and parameters of gut function including mucosal blood flow, pH, and permeability are measured. In addition, intestinal and cardiac tissue will be obtained to determine the amount of tissue edema, nitric oxide synthase protein content and gene expression, and using a microvessel protocol, evaluate relaxation and contraction responses of coronary and mesenteric vessels. The hypothesis of the study is that treatment with HMG CoA reductase inhibitors will enhance coronary and mesenteric vascular function as well as myocardial and gut performance. The results are expected to ultimately contribute to the perioperative management of patients who undergo CPB resulting in improved clinical outcomes.
