Calpain inhibition decreases myocardial fibrosis in chronically ischemic hypercholesterolemic swine.

Objectives: Calpain activation during ischemia is known to play critical roles in myocardial remodeling. We hypothesize that calpain inhibition (CI) may serve to reverse and/or prevent fibrosis in chronically ischemic myocardium.

Methods: Yorkshire swine were fed a high-cholesterol diet for 4 weeks followed by placement of an ameroid constrictor on the left circumflex artery to induce myocardial ischemia.

Increased coronary arteriolar contraction to serotonin in juvenile pigs with metabolic syndrome.

Metabolic syndrome (MetS) is associated with alterations in coronary vascular smooth muscle and endothelial function. The current study examined the contractile response of the isolated coronary arterioles to serotonin in pigs with and without MetS and investigated the signaling pathways responsible for serotonin-induced vasomotor tone. The MetS pigs (8-weeks old) were fed with a hyper-caloric, fat/cholesterol diet and the control animals (lean) were fed with a regular diet for 12 weeks (n = 6/group).

Impaired coronary contraction to phenylephrine after cardioplegic arrest in diabetic patients.

Background: We have previously found that hyperkalemic cardioplegic arrest in the setting of cardiopulmonary bypass (CP/CPB) is associated with impairment of the coronary arteriolar response to phenylephrine in nondiabetic (ND) patients. We hypothesized that diabetes may alter coronary arteriolar response to alpha-1 adrenergic agonist in the setting of CP/CPB. In this study, we further investigated the effects of diabetes on the altered coronary arteriolar response to phenylephrine in patients undergoing cardiac surgery.

Enhanced coronary arteriolar contraction to vasopressin in patients with diabetes after cardiac surgery.

Objective: Cardioplegic arrest (CP) and cardiopulmonary bypass (CPB) are associated with vasomotor dysfunction of coronary arterioles in patients with diabetes (DM) undergoing cardiac surgery. We hypothesized that DM may up-regulate vasopressin receptor expression and alter the contractile response of coronary arterioles to vasopressin in the setting of CP/CPB.

Methods: Right atrial tissue samples of patients with DM and without (ND) (n = 8 in each group) undergoing cardiac surgery were harvested before and after CP/CPB.

Decreased coronary arteriolar response to K channel opener after cardioplegic arrest in diabetic patients.

We have recently found that diabetes is associated with the inactivation of the calcium-activated potassium channels (K) in endothelial cells, which may contribute to endothelial dysfunction in diabetic patients at baseline. In the current study, we further investigated the effects of diabetes on coronary arteriolar responses to the small (SK) and intermediate (IK) K opener NS309 in diabetic and non-diabetic patients and correlated that data with the changes in the SK/IK protein expression/distribution in the setting of cardioplegic ischemia and reperfusion (CP) and cardiopulmonary bypass (CPB). Coronary arterioles from the harvested right atrial tissue samples from diabetic and non-diabetic patients (n = 8/group) undergoing cardiac surgery were dissected pre- and post-CP/CPB.

Alcohol modulates autophagy and apoptosis in pig liver tissue.

Background: Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury but excessive autophagy can also be detrimental leading to apoptosis. Our laboratory has previously shown that moderate alcohol consumption alters expression of proteins in the insulin signaling pathway and worsens glucose metabolism in the liver in a swine model of metabolic syndrome. We examined the effect of alcohol consumption on apoptosis and autophagy signaling in the liver in our clinically relevant animal model of chronic hypercholesterolemia.