Resveratrol modifies risk factors for coronary artery disease in swine with metabolic syndrome and myocardial ischemia.

Resveratrol has been purported to modify risk factors for obesity and cardiovascular disease. We sought to examine the effects of resveratrol in a porcine model of metabolic syndrome and chronic myocardial ischemia. Yorkshire swine were fed either a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with supplemental resveratrol (HCD-R; 100mg/kg/day) for 11 weeks.

Effect of thrombin fragment (TP508) on myocardial ischemia reperfusion injury in a model of type 1 diabetes mellitus.

Background: We investigated the efficacy of novel thrombin fragment TP508 on ischemia-reperfusion injury using a porcine model of type 1 diabetes mellitus.

Methods And Results: Alloxan-induced diabetic male Yucatan swine underwent 60 minutes of mid-left anterior descending coronary artery occlusion, followed by 120 minutes of reperfusion. Fifty minutes into ischemia, animals received either placebo (DM; n=8) or TP508 as a bolus of 1 mg/kg followed by infusion at 2.

Effects of cardiopulmonary bypass on endothelin-1-induced contraction and signaling in human skeletal muscle microcirculation.

Background: We investigated the effects of cardiopulmonary bypass (CPB) on the contractile response of human peripheral microvasculature to endothelin-1 (ET-1), examined the role of specific ET receptors and protein kinase C-alpha (PKC-α), and analyzed ET-1-related gene/protein expression in this response.

Methods And Results: Human skeletal muscle arterioles (90 to 180 μm in diameter) were dissected from tissue harvested before and after CPB from 30 patients undergoing cardiac surgery. In vitro contractile response to ET-1 was assessed by videomicroscopy, with and without an endothelin-A (ET-A) receptor antagonist, an endothelin-B (ET-B) antagonist, or a PKC-α inhibitor.

Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia.

Background: Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia.

Methods And Results: Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7).

Temporal and spatial changes in collateral formation and function during chronic myocardial ischemia.

Background: We investigated time dependence and spatial progression of cardiac function and angiogenesis signaling in a porcine model of chronic myocardial ischemia.

Study Design: Yorkshire mini-swine (n = 7/group) were subjected to chronic myocardial ischemia by placing an ameroid constrictor on the left circumflex coronary artery under general anesthesia. Swine were sacrificed after either 4 or 7 weeks of ischemia.

Is hyperglycemia bad for the heart during acute ischemia?

Objective: This study investigates the impact of diabetes on myocardium in the setting of acute ischemia-reperfusion in a porcine model.

Methods: In normoglycemic (ND group) and alloxan-induced diabetic (DM group) male Yucatan pigs, the left anterior descending coronary artery territory was made ischemic and then reperfused. Hemodynamic values and myocardial function were measured.

Endothelin-1-induced contractile responses of human coronary arterioles via endothelin-A receptors and PKC-alpha signaling pathways.

Background: We investigated the contractile function in responses to endothelin-1 (ET-1) in the human coronary microvasculature as well as the roles of endothelin receptors and protein kinase C-alpha (PKC-alpha) in these responses.

Methods: Human atrial tissue was harvested from patients who underwent cardiac surgery pre- and post-cardioplegia (CP)/cardiopulmanory bypass (CPB). Microvascular constriction was assessed in pre- and post-CP/CPB samples in responses to ET-1, in the presence and absence of an endothelin-A (ET-A) receptor antagonist, an endothelin-B (ET-B) receptor antagonist, or a PKC-alpha inhibitor, respectively.

Effect of hydrogen sulfide on myocardial protection in the setting of cardioplegia and cardiopulmonary bypass.

We investigated the impact of hydrogen sulfide (H(2)S) on myocardium in the setting of cold crystalloid cardioplegia and cardiopulmonary bypass (CP/CPB). Eighteen male Yorkshire pigs underwent 1 h CP/CPB followed by 2 h of reperfusion. Pigs received either: placebo (control, n=9), or H(2)S (as NaHS) as a bolus/infusion (bolus/infusion, n=6), or as an infusion (infusion, n=6).

Effect of hypercholesterolemia on myocardial necrosis and apoptosis in the setting of ischemia-reperfusion.

Background: Hypercholesterolemia is prevalent in patients who experience myocardial ischemia-reperfusion injury (IR). We investigate the impact of dietary-induced hypercholesterolemia on the myocardium in the setting of acute IR.

Methods And Results: In normocholesterolemic (NC, n=7) and hypercholesterolemic (HC, n=7) Yucatan male pigs, the left anterior descending coronary artery was occluded for 60 minutes, followed by reperfusion for 120 minutes.

Large conductance calcium-activated potassium channels contribute to the reduced myogenic tone of peripheral microvasculature after cardiopulmonary bypass.

Background: We investigated the role of calcium-activated potassium (K(Ca)) channel activation in myogenic tone in human peripheral microvasculature after heart surgery.

Methods: Human skeletal muscle arterioles (90-180microm diameter) were dissected from tissue harvested pre- and post-cardiopulmonary bypass (CPB) during cardiac surgery. Myogenic reactivity in response to stepwise increases in intraluminal pressure was studied between pressure steps.

Altered coronary microvascular serotonin receptor expression after coronary artery bypass grafting with cardiopulmonary bypass.

Objective: We evaluated roles of serotonin 1B and 2A receptors, thromboxane synthase and receptor, and phospholipases A(2) and C in response to cardiopulmonary bypass.

Methods: Patients' atrial tissues were harvested before and after cardiopulmonary bypass with cardioplegia (n = 13). Coronary microvessels were assessed for vasoactive response to serotonin with and without inhibitors of serotonin 1B and 2A receptors and phospholipases A(2) and C.

Effect of hydrogen sulfide in a porcine model of myocardial ischemia-reperfusion: comparison of different administration regimens and characterization of the cellular mechanisms of protection.

Objective: We investigate the impact of different regimens of parenteral hydrogen sulfide (H2S) administration on myocardium during ischemia-reperfusion (IR) and the molecular pathways involved in its cytoprotective effects.

Methods: Eighteen male Yorkshire pigs underwent 60 minutes of mid-left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. Pigs received either placebo (control, n = 6) or H2S as a bolus (bolus group, n = 6, 0.

Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling.

Nutritional excess and hyperlipidemia increase the heart's susceptibility to ischemic injury. Mammalian target of rapamycin (mTOR) controls the cellular response to nutritional status and may play a role in ischemic injury. To explore the effect of hypercholesterolemia on cardiac mTOR signaling, we assessed mTOR signaling in hypercholesterolemic swine (HC) that are also susceptible to increased cardiac ischemia-reperfusion injury.

Effect of thrombin fragment (TP508) on myocardial ischemia-reperfusion injury in hypercholesterolemic pigs.

Myocardial ischemia-reperfusion (IR) injury occurs frequently in the setting of hypercholesterolemia. We investigated the potential efficacy of a novel thrombin fragment (TP508) on IR injury in a hypercholesterolemic porcine model. Twenty-one hypercholesterolemic male Yucatan pigs underwent 60 min of mid-left anterior descending coronary artery occlusion followed by 120 min of reperfusion.

Thrombin fragment (TP508) decreases myocardial infarction and apoptosis after ischemia reperfusion injury.

Background: Myocardial ischemia-reperfusion injury may lead to cardiac dysfunction or death. This study investigates the potential efficacy of a novel thrombin fragment (TP508) on myocardial ischemia-reperfusion injury.

Methods: Fourteen male Yucatan pigs underwent 60 minutes of mid-left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion.