pyrimidinones and Cardiomyopathy--Dilated

The potential utility of nifekalant, a new Class III antiarrhythmic drug, to offer long-term protection against ventricular arrhythmia has been investigated in this case report. A 44-year-old male patient with dilated cardiomyopathy complicated with heart failure and persistent ventricular tachycardia was treated with nifekalant. The patient was treated with nifekalant for 31 days, which effectively terminated ventricular tachycardia and maintained sinus rhythm, with no clinical adverse reactions. After heart transplantation, postoperative follow-up showed good cardiac function and no arrhythmia. On the basis of nifekalant's working mechanism, there is a good chance that it can cure ventricular arrhythmia on a long-term basis.

Topics: Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Humans; Male; Pyrimidinones; Tachycardia, Ventricular

The clinical use of HIV protease inhibitors is associated with insulin resistance and other metabolic changes that increase long-term cardiovascular risk. Since the failing heart has increased reliance on glucose, the influence of drug exposure on glucose homeostasis, myocardial glucose uptake, cardiac function, and survival was determined in TG9 mice, an established transgenic model of dilated cardiomyopathy generated by cardiac-specific overexpression of Cre-recombinase, as these animals progressed to overt heart failure. Beginning on day of life 75, TG9 mice and nontransgenic littermate controls were given a daily 10 mg/kg intraperitoneal injection of HIV protease inhibitors (ritonavir, lopinavir/ritonavir 4:1, atazanavir, atazanavir/ritonavir 4:1) or vehicle. Glucose tolerance testing, measurement of in vivo myocardial 2-deoxyglucose uptake, and echocardiography were performed before and 30 min following drug administration. The progression of dilated cardiomyopathy in TG9 animals was accompanied by impaired glucose tolerance, which was acutely exacerbated by exposure to ritonavir. Ritonavir and lopinavir precipitated acute, decompensated heart failure and death from pulmonary edema in TG9 mice. However, atazanavir, which does not inhibit glucose transport, had no effect. These studies demonstrate that, in the presence of dilated cardiomyopathy, HIV protease inhibitors that impair glucose transport induce acute, decompensated heart failure. The potential for HIV protease inhibitors to contribute to or exacerbate cardiomyopathy in human patients warrants further investigation.

Topics: Animals; Atazanavir Sulfate; Blood Glucose; Cardiomyopathy, Dilated; Deoxyglucose; Disease Models, Animal; Echocardiography; Glucose Tolerance Test; Glucose Transporter Type 4; Heart Failure; HIV Protease Inhibitors; Humans; Insulin Resistance; Lopinavir; Mice; Myocardium; Oligopeptides; Pulmonary Edema; Pyridines; Pyrimidinones

Topics: Adult; Cardiomyopathy, Dilated; Crystallization; Echocardiography, Transesophageal; Female; Heart Diseases; Humans; Infusions, Intravenous; Potassium Channel Blockers; Pyrimidinones; Thrombosis