No abstract

Coronary heart disease (CHD) is the leading cause of mortality in the United States. Hypertension, diabetes mellitus, hypercholesterolemia, and smoking have all been directly related to CHD. Obesity is on the rise in the United States and has also been associated with CHD. This review clearly establishes obesity as an independent risk factor for CHD as demonstrated by the Framingham Heart Study, Nurses' Health Study, Buffalo Health Study, and the Cancer Prevention Study II. Morbid obesity was found to correlate with a significant risk of mortality from CHD, especially in young men. Prevention of obesity, and therefore reduction in risk from cardiovascular disease, is paramount in the management of obesity. New approaches to behavioral, medical, and surgical management of obesity are reviewed, including thalidomide, an antiangiogenic agent. A primary and secondary prevention model details a multidisciplinary approach to reducing risk in obesity. (Prev Cardiol. 2003;6:42-47)

Myocardial infarction (MI) is complicated by ventricular fibrosis and associated diastolic and systolic failure. Emerging studies implicate Wnt1 signaling in the formation of new blood vessels. Epoxyeicosatrienoic acids (EETs)-mediated up-regulation of heme oxygenase-1 (HO-1) protects against the detrimental consequences of MI in several animal models, however, the mechanism(s) by which this occurs remains unclear. The aim of this study was to examine these mechanisms in the LAD ligation animal model of post infarcted heart failure. Specifically, we sought to clarify the mechanistic basis of the interactions of the Wnt1 canonical pathway, HO-1 and associated angiogenesis. Human microvascular endothelial cells (HMECs) were exposed to anoxia and treated with the EET agonist, NUDSA, in the presence and absence of tin mesoporphyrin (SnMP). Increased capillary density, and Wnt1 and HO-1 expression occurred in cells treated with NUDSA. Anoxic HMECs treated with NUDSA and Wnt1 siRNA, exhibited decreased in the expression of β-catenin and the Wnt1 target gene, PPARδ (p<0.05 vs. NUDSA). Furthermore, blocking the Wnt 1 antagonist, Dickkopf 1, by siRNA increased β-catenin and PPARδ expression, and this effect was further enhanced by the concurrent administration of NUDSA. In in vivo experiments, C57B16 mice were divided into 4 groups: sham, mice with MI via LAD ligation and mice with MI treated with NUDSA, with and without SnMP. Increased fractional area change (FAC) and myocardial angiogenesis were observed in mice treated with NUDSA (p<0.05 vs. MI). Increased expression of HO-1, Wnt1, β-catenin, adiponectin, and phospho-endothelial nitric oxide synthetase (p-eNOS), and a decrease in the glycosylated subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gp91(phox) expression occurred in cardiac tissue of mice treated with NUDSA (p<0.05 vs. MI). SnMP reversed these effects. This novel study demonstrates that increasing the canonical Wnt1 signaling cascade with the subsequent increase in HO-1, adiponectin and angiogenesis ameliorates fibrosis and cardiac dysfunction in a mouse model of MI and support the hypothesis that HO-1 is an integral component of the EETs-adiponectin axis and are central for the control of resistance to fibrosis and vascular dysfunction and in part determine how they influence the cellular/vascular homeostasis and provide insight into the mechanisms involved in vascular dysfunction as well as potential targets for the treatment of CVD.

We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they provide the only controlled data regarding the effect of oral milrinone on exercise capacity in patients receiving converting enzyme inhibitors. Of the 254 patients randomized, 140 completed one of the trials or reached an end point and are the basis of this report. In both trials, there was a clear trend for an increase in exercise capacity in the milrinone-treated patients (+26 +/- 8% vs. +5 +/- 7% in MIL-1077 and +11 +/- 5% vs. +2 +/- 4% in MIL-1078). Symptoms of congestive heart failure were decreased in one trial but not the other. Quality of life, as assessed by a questionnaire, was not effected in either trial. There was an increased incidence of adverse events in milrinone-treated patients. Adverse events related primarily to hypotension and vasodilation led to discontinuation of drug in 18 milrinone-treated patients vs. 1 placebo-treated patient. Milrinone had little or no proarrhythmic effect and cardiovascular deaths were distributed equally between the milrinone and placebo groups. These data suggest that when used in combination with a converting enzyme inhibitor, oral milrinone improves exercise capacity but is associated with a high incidence of adverse events that appear to be related to excessive vasodilation.

The effect of short-term exposure to homocysteine (Hcy) on the contractile characteristics of rat aortic tissue was assessed both in vitro and in vivo. The contractile response of Hcy-treated aortic rings in culture for 1 or 4 days was unchanged from control responses. By comparison, aortic rings from animals injected with Hcy showed marked attenuation of response compared with controls injected with saline, cysteine or methionine. The contractile response to K+ was decreased within 24 hours of Hcy injection, whereas the response to both K+ (-27%) and noradrenaline (-56%) was significantly decreased by 4 days. In contrast, the contractile response to phorbol-12,13-dibutyrate was not different between Hcy and control groups. Intimal rubbing completely restored the responsiveness of Hcy-treated tissue to K+ and noradrenaline. By comparison, L-NAME only partially restored contractile responsiveness, while the cyclooxygenase inhibitor indomethacin had no effect on contractile attenuation induced by Hcy. Western blot analysis showed a 2-fold increase of endothelial nitric oxide synthase (eNOS) and a 3-fold increase in inducible nitric oxide synthase (iNOS) protein expression in the aortic endothelial cells from Hcy-injected rats. The results indicate an early detectable effect of Hcy on the in vivo contractile properties of vascular smooth muscle. The effect is endothelium-mediated and may vary depending on the agonist studied. The mechanism is uncertain but appears to involve increased nitric oxide (NO) production. Finally, the data suggest that attenuation of contraction may not be due to a direct effect of Hcy but that the compound is modified or acts indirectly in vivo.

Two-dimensional echocardiography has had a significant impact on and is considered the technique of choice for the diagnosis and management of infective endocarditis. Over a thirty-six month period, 106 patients were evaluated by echocardiography for the possibility of endocarditis. The diagnosis of endocarditis was determined by strict clinical and laboratory criteria. All clinical histories, blood cultures, echocardiograms, and autopsy results were reviewed. Five echocardiograms were technically inadequate, resulting in a study population of 101 patients. The age of the patients ranged from forty-five days to eighty-eight years (mean fifty-seven years). The clinical manifestations of endocarditis included fever (83%), chills (60%), congestive heart failure (25%), and splenomegaly (18%). Twelve patients had preexisting valvular or congenital heart disease. Gram-positive cocci were the most common microorganisms. Complications included mitral regurgitation, subarachnoid hemorrhage, renal infarction, stroke, and a pulmonary embolus. The patients were divided into two groups: Group I consisted of 36 patients with definite vegetations by echocardiography, and Group II had 65 patients with no vegetations. In Group I, acute infective endocarditis was present in 35 patients, whereas only 4 patients had endocarditis in Group II. The sensitivity of two-dimensional echocardiography for detecting endocarditis was 90%. The specificity was 98%. The predictive accuracy for a positive test was 97%, and the predictive accuracy for a negative test was 94%. Thus, two-dimensional echocardiography appears to have a high sensitivity, specificity, and predictive value in the evaluation of patients with suspected endocarditis.

No abstract

Abnormal blood rheology is a known characteristics of coronary artery disease. The authors evaluated the effects of pentoxifylline on the exercise capacity ejection fraction and symptoms of 9 patients with ischemic cardiomyopathy. All patients had signs and symptoms of left ventricular dysfunction. All had at least two major vessels obstructed as determined by coronary angiography. Pentoxifylline 400 mg three times daily was administered for twelve weeks. Seven of 9 patients responded with increases in ejection fraction and exercise tolerance. Exercise tolerance correlated with improvement or lack of improvement in ejection fraction. For all patients at twelve weeks post-therapy mean ejection fraction increased 9.8% over baseline (p = .07), total treadmill time increased 15% (p = .27), and mean double product increased 13% (p = .03). Anginal symptoms were significantly improved over baseline at twelve weeks of therapy (p greater than .001), as well as dyspnea on exertion (p = .03). Pentoxifylline was well tolerated. Pentoxifylline may benefit ischemic cardiomyopathy by improving coronary perfusion owing to favorable alterations in hemorheologic properties.