Acute myocardial rescue with endogenous endothelial progenitor cell therapy.

Purpose: Post-myocardial infarction heart failure is a major health concern with limited therapy. Molecular revascularisation utilising granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated.

Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function.

Objective: A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood.

Myocardial regeneration therapy for ischemic cardiomyopathy with cyclin A2.

Objective: Heart failure therapies ranging from revascularization to remodeling to replacement are variably effective. Theoretically, endogenous repair via myocardial regeneration would be an ideal therapy. This study examined the ability to initiate regeneration by adenoviral-mediated expression of the cell cycle regulator cyclin A2.

Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression.

Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood.

Off-pump revascularization for significant left ventricular dysfunction.

Left ventricular dysfunction is a predictor of perioperative morbidity and mortality in on-pump coronary artery bypass grafting. Obligatory global myocardial ischemia and injury induced during crossclamping as well as adverse systemic effects of cardiopulmonary bypass may induce a disproportionately greater overall physiologic insult in patients with poor ventricular function. All patients undergoing nonemergency off-pump coronary artery bypass by a single surgeon during an 18-month period were retrospectively analyzed.

Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure.

Background: Heart failure is a global health concern. As a novel therapeutic strategy, the induction of endogenous myocardial regeneration was investigated by initiating cardiomyocyte mitosis by expressing the cell cycle regulator cyclin A2.

Methods And Results: Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 (n =32) or empty adeno-null (n =32).

Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy.

Background: Ischemic cardiomyopathy is a global health concern with limited therapy. We recently described endogenous revascularization utilizing granulocyte-macrophage colony stimulating factor (GMCSF) to induce endothelial progenitor cell (EPC) production and intramyocardial stromal cell-derived factor-1alpha (SDF) as a specific EPC chemokine. The EPC-mediated neovascularization and enhancement of myocardial function was observed.

Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction.

Background: Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia.