Preconditioning in humans.

Brief ischemia to the myocardium initiates a cascade of biochemical events in cardiac myocytes that protects the heart muscle during subsequent ischemic insults. This phenomenon is called ischemic preconditioning. If an acute myocardial infarction is preceded by preinfarction angina, it results in smaller infarction size, fewer cardiac arrhythmias, and better-left ventricular function.

Vardenafil: a selective inhibitor of phosphodiesterase-5 for the treatment of erectile dysfunction.

Vardenafil is a selective phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. It was found to be effective in a high percentage of patients and a broad spectrum of underlying conditions. It potentiates the increase in intracellular cGMP in the corpora cavernosa in response to sexual stimuli, resulting in enhanced and prolonged erections.

Cardiac cells implanted within the outer aortic wall of rats generate measurable contractile force.

Purpose: To determine whether neonatal cardiomyocytes grafted into the aortic wall contract, develop pressure, and can be paced.

Methods And Results: Medium only (n = 9) or neonatal cardiomyocytes (n = 12, 5 x 10(6) cells each) were injected into the outer aortic wall in adult female Fischer rats. At 6 weeks after implantation, 11 out of 12 cardiomyocyte-treated aortas showed spontaneous rhythmic beating at the grafted site following excision of the heart.

Role of a paracrine action of mesenchymal stem cells in the improvement of left ventricular function after coronary artery occlusion in rats.

Purpose: We aimed to determine whether soluble factors released by cultured mesenchymal stem cells (MSCs) improved cardiac function in an experimental model of myocardial infarction.

Methods: MSCs were cultured in fresh medium. The conditioned medium, which contained factors secreted by MSCs, was collected after 4 days of culture.

Development of a spontaneously beating vein by cardiomyocyte transplantation in the wall of the inferior vena cava in a rat: a pilot study.

Purpose: This study was conducted to determine whether it is feasible to develop a vein that rhythmically beats by implanting immature cardiomyocytes in its wall.

Methods: Neonatal cardiomyocytes (5 x 10(6) cells each) were transplanted into the wall of the inferior vena cava in six female Fischer rats; in six rats, only the medium was transplanted. At 3 weeks after transplantation, the grafted site of the inferior vena cava was exposed and videotaped, and then processed for histology.

Sexual function in hypertensive patients receiving treatment.

In many forms of erectile dysfunction (ED), cardiovascular risk factors, in particular arterial hypertension, seem to be extremely common. While causes for ED are related to a broad spectrum of diseases, a generalized vascular process seems to be the underlying mechanism in many patients, which in a large portion of clinical cases involves endothelial dysfunction, ie, inadequate vasodilation in response to endothelium-dependent stimuli, both in the systemic vasculature and the penile arteries. Due to this close association of cardiovascular disease and ED, patients with ED should be evaluated as to whether they may suffer from cardiovascular risk factors including hypertension, cardiovascular disease or silent myocardial ischemia.

Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit.

Ranolazine is a selective inhibitor of the late sodium current relative to peak sodium channel current, and via this mechanism, it may decrease sodium-dependent intracellular calcium overload during ischemia and reperfusion. Ranolazine reduces the frequency of angina attacks, but there is little information on its effects on myocardial stunning after short-term ischemia. The objective of this study was to test the effects of ranolazine on left ventricular (LV) function and myocardial stunning after ischemia/reperfusion in rabbits.

The Bolger conference on PDE-5 inhibition and HIV risk: implications for health policy and prevention.

Introduction: Recent reports have linked the use of phosphodiesterase type 5 (PDE-5) inhibitors with increased rates of high-risk sexual behavior and HIV transmission in some individuals.

Aim: A National Institute of Mental Health (NIMH)-funded, multidisciplinary conference was convened to evaluate scientific research, clinical and ethical considerations, and public policy implications of this topic.

Main Outcome Measures: Published and unpublished findings on effects of PDE-5 inhibitors on sexual behavior; published guidelines and management recommendations.

Cardiovascular effects of phosphodiesterase 5 inhibitors.

Phosphodiesterase 5 inhibitors, such as sildenafil, vardenafil and tadalafil, are now approved for the treatment of erectile dysfunction. They inhibit the cGMP-specific isoform 5 of phosphodiesterase, resulting in cGMP accumulation, which, for example in smooth muscle cells, reduces muscular tone. In the cardiovascular system, they slightly reduce arterial systemic blood pressure.

The no-reflow phenomenon: A basic mechanism of myocardial ischemia and reperfusion.

Both animal models of experimental myocardial infarction and clinical studies on reperfusion therapy for acute myocardial infarction have provided evidence of impaired tissue perfusion at the microvascular level after initiation of reperfusion despite adequate restoration of epicardial vessel patency. Characteristics of this "no-reflow" phenomenon found in basic science investigations, such as distinct perfusion defects, progressive decrease of resting myocardial flow with ongoing reperfusion and functional vascular alterations are paralleled by clinical observations demonstrating similar features during the course of reperfusion. In experimental animal investigations of coronary occlusion and reperfusion, this no-reflow phenomenon could be characterized as a fundamental mechanism of myocardial ischemia and reperfusion.

Ischemic preconditioning for the clinician.

Ischemic preconditioning is a physiologic phenomenon that occurs in the cardiac muscle in which brief episodes of ischemia protect the heart when exposed to a sustained ischemia. Clinical counterparts include potential benefits of preinfarction angina and less ischemia after a second, compared to a first, coronary angioplasty balloon inflation. This article will discuss how preconditioning might be applied to the clinical setting during acute myocardial infarction, coronary interventions, and cardiac surgery.

The phosphodiesterase-5 inhibitor tadalafil reduces myocardial infarct size.

The aim of this study was to determine, in an animal model, the effects of tadalafil on myocardial infarct size (IS), hemodynamics and regional myocardial blood flow after myocardial ischemia and reperfusion. Patients with erectile dysfunction (ED) often have risk factors for coronary artery disease. Tadalafil, a long-acting inhibitor of the enzyme phosphodiesterase-5 (PDE5), is used for the treatment of ED; there are no previous data regarding tadalafil in the setting of coronary artery occlusion (CAO).

In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias.

Exposure to ultrafine particles (UFPs) by inhalation increases the number and severity of cardiac events. The specific mechanism(s) of action are unknown. This study was designed to examine whether UFPs could exert a direct effect on the cardiovascular system without dependence upon lung-mediated responses.

Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial.

Aims: The purpose of this analysis was to determine whether the efficacy of adenosine vs. placebo was dependent on the timing of reperfusion therapy in the second Acute Myocardial Infarction Study of Adenosine (AMISTAD-II).

Methods And Results: Patients presenting with ST-segment elevation anterior AMI were randomized to receive placebo vs.

Cardiovascular safety update of Tadalafil: retrospective analysis of data from placebo-controlled and open-label clinical trials of Tadalafil with as needed, three times-per-week or once-a-day dosing.

Because most men with erectile dysfunction have underlying vascular disease, it is important to update the cardiovascular safety profile of medications used in the treatment of erectile dysfunction. This retrospective analysis evaluated serious cardiovascular treatment-emergent adverse events (CVTEAEs) reported in 36 clinical trials of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. A serious CVTEAE was defined as myocardial infarction, cardiovascular death, or cerebrovascular death.

Myocardial regeneration by embryonic stem cell transplantation: present and future trends.

Embryonic stem cells are a promising source for myocardial regeneration due to their pluripotency and plasticity. In theory, embryonic stem cells are capable of self-renewal in an unlimited fashion, and can differentiate into any cell type required for cell-based therapy, including cardiac myocytes. In recent years, embryonic stem cells have been transplanted for cardiac regeneration in animal models, and the results are encouraging.

Postconditioning markedly attenuates ventricular arrhythmias after ischemia-reperfusion.

Background: Brief periods of reocclusion (postconditioning) during early reperfusion reduce myocardial infarct size. Whether postconditioning has an effect on lethal ventricular arrhythmias independent of infarction in an in-vivo regional ischemia model is unknown. The purpose of this study was to determine if postconditioning limited reperfusion arrhythmias in a necrosis-free model.

Molecular aspects of ischemic heart disease: ischemia/reperfusion-induced genetic changes and potential applications of gene and RNA interference therapy.

Molecular biologic techniques have a variety of applications in the study of ischemic heart disease, including roles in elucidating cardiac genetic changes resulting from ischemia as well as in developing therapeutic interventions to treat ischemic heart disease. This review describes recent studies documenting genetic changes associated with myocardial ischemia and infarction as well as those investigating the safety and effectiveness of gene therapy for stimulating angiogenesis, protecting the heart against reperfusion injury, and treating heart failure. Also discussed are future research directions, including the potential use of RNA interference and combined stem cell therapy and gene therapy for the treatment of cardiovascular disease.

Mildronate, a novel fatty acid oxidation inhibitor and antianginal agent, reduces myocardial infarct size without affecting hemodynamics.

Mildronate is a fatty acid oxidation inhibitor approved as an antianginal drug in parts of Europe. We carried out the first study to determine whether a 10-day course of mildronate could reduce myocardial infarct size (IS) during acute myocardial ischemia. Sprague Dawley rats received 200 mg/kg/d of mildronate (treated group, n = 16) or sterile water (control group, n = 14) subcutaneously for 10 days before ischemia-reperfusion.