Fumiko Okazaki

RETRACTED: Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study

BACKGROUND Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease. However, evidence for this effect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease. METHODS We initiated a multicentre, prospective, randomised controlled trial of 3081 Japanese patients, aged 20-79 years, (mean 65 [SD 10] years) who were undergoing conventional treatment for hypertension, coronary heart disease, heart failure, or a combination of these disorders. In addition to conventional treatment, patients were assigned either to valsartan (40-160 mg per day) or to other treatment without angiotensin receptor blockers. Our primary endpoint was a composite of cardiovascular morbidity and mortality. Analysis was by intention to treat. The study was registered at clintrials.gov with the identifier NCT00133328. FINDINGS After a median follow-up of 3.1 years (range 1-3.9) the primary endpoint was recorded in fewer individuals given valsartan than in controls (92 vs 149; absolute risk 21.3 vs 34.5 per 1000 patient years; hazard ratio 0.61, 95% CI 0.47-0.79, p=0.0002). This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack (29 vs 48; 0.60, 0.38-0.95, p=0.028), angina pectoris (19 vs 53; 0.35, 0.20-0.58, p<0.0001), and heart failure (19 vs 36; 0.53, 0.31-0.94, p=0.029) in those given valsartan than in the control group. Mortality or tolerability did not differ between groups. INTERPRETATION The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment. These benefits cannot be entirely explained by a difference in blood pressure control.

Atrial pacing failure following termination of atrial fibrillation by acute administration of disopyramide phosphate.

Atrial pacing failure occurred after termination of atrial fibrillation by acute administration of disopyramide phosphate in a 71-year-old woman implanted with an AAI pacemaker for sick sinus syndrome. The atrial pacing threshold showed an 810% increase; however, the serum concentration of disopyramide corresponded to therapeutic level. Infusion of the same dose of disopyramide phosphate used during the period of atrial pacing rhythm did not increase the atrial pacing threshold. In the present patient, we supposed that atrial pacing failure did not occur by the effect of disopyramide alone, but rather was a reciprocal action in response to atrial fibrillation.

Effects of Ischemic Preconditioning on Na+-Ca2+ Exchanger Activity and Ion Regulation in Isolated Perfused Rat Hearts

We investigated the effects of ischemic preconditioning (IP) on the incidence of reperfusion-induced ventricular fibrillation (VF), intracellular ion regulation, and Na+-Ca2+ exchanger activity using isolated perfused rat hearts. The hearts perfused in a working-heart mode were exposed to sustained global ischemia for 15 minutes and were reperfused for 20 minutes. For preconditioning, the hearts were exposed to two short periods (3 or 5 minutes) of ischemia and repehsion prior to induction of sustained ischemia. The incidence of VF decreased from 90% in the control hearts to 20% in the preconditioned hearts (p < 0.05). Treatment with an Na+-Ca2+ exchanger blocker, Ni2+ (0.5 μM, reduced the antianhythmic effect of IP. Thus, 70% of the preconditioned hearts treated with Ni2+ developed VF on reperfusion. To investigate the effect of IP on changes in intracellular ion levels, rat hearts perfused in Langendorff’s mode were exposed to low-flow ischemia for 15 minutes and were reperfused for 15 minutes. Intracellular pH (pHi) and Ca2+ concentrations ([Ca2+]i) were measured ratiometrically using the fluorescent ion indicators 2′,7′-bis(2-carboxylethyl)-5(6)-carboxyfluorescein (BCECF) or fura-2 with the simultaneous measurement of left ventricular pressure. IP limited the development of intracellular acidosis and prevented the rise in diastolic [Ca2+]i during sustained ischemia. Ni2+ treatment reversed this effect of IP on diastolic [Ca2+]i. During exposure to an Na+ free extracellular medium, which reversed the Na+-Ca2+ exchanger mode, IP significantly suppressed the peak amplitude (65.2% ± 7.8% of control, p < 0.005) and prolonged the time to peak (16.7 ± 0.9 seconds vs. 12.8 ± 1.5 seconds, p < 0.05) of the diastolic [Ca2+]i increase. Results indicated that the Na+-Ca2+ exchanger may be important in ion regulation during IP.