Erectile dysfunction and atherosclerosis

Erectile dysfunction (ED) is a common problem in the United States, with estimates that 30 million men suffer with some degree of ED. Although causes include psychogenic, organic, and mixed forms, in middle-aged and older men one of the most common causes is vascular disease. Endothelial dysfunction, even without definitive arterial stenosis, as well as atherosclerosis with definitive stenosis of blood vessels, contributes to the problem. Endothelial dysfunction and atherosclerosis of blood vessels that supply the penis are associated with the same cardiovascular risk factors that affect the coronary arteries: smoking, lipid abnormalities, hypertension, and diabetes.     

Preconditioning and the human heart

Brief episodes of ischemia prior to coronary occlusion protect the heart during sustained coronary ischemia and is known as ischemic preconditioning. During acute myocardial infarction it is associated with smaller infarction size, less cardiac arrhythmias, and better left ventricular function. Brief balloon inflation in the cardiac catheterization laboratory during coronary intervention enables the operator to have further prolonged balloon inflations with lesser degrees of ischemia. Brief ischemia prior to coronary bypass surgery results in smaller perioperative infarctions and lesser degrees of postoperative arrhythmias. Preconditioning mimetic drugs may have a promising future in simulating ischemic preconditioning.     

New cellular and molecular approaches for the treatment of cardiac disease

Similar to the kidney in uremia, end-stage cardiac failure is an outcome common to many disparate disease processes including hypertension, various inflammatory pathologies, as well as ischemic loss of tissue. In regard to the heart, cellular and molecular mechanisms responsible for heart failure have been investigated with renewed intensity over the past several years with newer techniques of molecular genetics, genomic analysis, and cell biology. Although this article reviews some recent advances made in our understanding of molecular and cellular events in the heart leading to heart failure and explores possible new targets for therapeutics, the main point is to stress the importance of investigative interactions between organ physiologists and molecular and cellular biologists. These interactions between organ physiologists and molecular geneticists is stressed and supported as a mechanism for rapid advancement for both understanding the underlying pathophysiology of human disease and the development of therapeutic strategies.     

Stem cell therapy for the heart

Cellular cardiomyoplasty is an expanding field of research that involves numerous types of immature cells administered via several modes of delivery. The purpose of this review is to investigate the benefits of different types of cells used in stem cell research as well as the most efficient mode of delivery. The authors also present data showing that stem cells isolated from bone marrow are present at both 2 weeks and 3 months after engraftment in a myocardial infarction. These cells express muscle markers at both time points, which suggests that they have begun to differentiate into cardiomyocytes. Several questions must be answered, however, before stem cells can be used routinely in the clinic. Once these questions have been addressed, the use of stem cells in clinical practice can be realized.     

Development of abnormal tissue architecture in transplanted neonatal rat myocytes

BACKGROUND: Most myocardial cell transplant studies focus on demonstration of improved function; however, such improvement depends on the development of appropriate tissue structure. Thus, our aim was to assess the architectural changes that occurred after cell transplant into normal and infarcted myocardium. METHODS: Male neonatal cells (1 to 2 days old) were injected into the left ventricular free wall of adult female rats. The tissue was examined 0 to 1 days and 1 to 2, 4 to 6, and 12 weeks later in noninfarcted hearts and 6 months after transplant into infarcts. In histologic sections, we assessed the cells' retardation of polarized light (to measure development of contractile elements), two-dimensional cell orientation, cell nuclear morphology, and collagen content. RESULTS: The transplant cells' retardation of polarized light gradually increased to 81% of that of host cells after 6 months (p < 0.001). The transplant cells were disorganized and although their nuclei increased in size, they always had a rounded appearance. Collagen content in the transplant was 210% to 430% higher than in host tissue (p < 0.01). In addition, scar collagen always separated transplant and host cells. CONCLUSIONS: One architectural feature, the rounded nuclei, provided a distinctive marker to identify transplanted cells. Nevertheless, the transplants' inhibited muscle development together with disorganization, separation from the host muscle, and a substantial increase in collagen resulted in a structure unlikely to play an active role in systolic function.     

Adenosine A1 Agonist at Reperfusion Trial (AART): Results of a Three-Center, Blinded, Randomized, Controlled Experimental Infarct Study

Adenosine A₁ receptor agonists given prior to myocardial ischemia limit ischemic injury in several species. However, the ability of adenosine receptor agonists to limit infarct size when given at reperfusion has proved controversial. We designed a three-center experimental study using a blinded, randomized treatment protocol to test the hypothesis that adenosine A₁ receptor activation during early reperfusion can attenuate lethal reperfusion injury, thereby reducing infarct size. Sixty anesthetized rabbits (20 in each laboratory) underwent 30 minutes coronary artery occlusion followed by 120 minutes reperfusion. The selective adenosine A₁ receptor agonist GR79236 (10.5 g/kg, a dose shown to limit infarction in this model when given before ischemia) or vehicle were administered IV 10 minutes before reperfusion. Infarct size was assessed by tetrazolium staining and, after the randomization code was revealed, data from the three laboratories were pooled for statistical analysis. Infarct size was not modified by administration of GR79236. In the vehicle-treated group, the infarct-to-risk ratio was 28.9 ± 2.7% (n = 24) compared with 31.9 ± 2.6% (n = 26) in the GR79236-treated group (not significant). Risk zone volume was similar in the two groups (1.06 ± 0.05 cm³ vs 1.00 ± 0.05 cm³, respectively). A modest reduction in rate-pressure product was noted following the administration of GR79236, but this effect was transient. The same dose of GR79236 was found to limit infarct size when given prior to coronary artery occlusion. We conclude that A₁ receptor activation does not modify lethal reperfusion injury in myocardium.