zoniporide and Ventricular-Fibrillation

The antiarrhythmic properties of the Na+/H(+)-exchanger inhibitor zoniporide have been studied in experiments on rats. On the model of 45-min myocardial ischemia followed by 45-min reperfusion, the drug produced a significant (two-fold) decrease in the intensity of post-reperfusion arrhythmias (p < or = 0.05). On the model of 7-min ischemia followed by 5-min reperfusion, zoniporide prevented the development of ventricular fibrillation in 71.43% of cases as compared to control (p < or = 0.05). The drug also increased the threshold of electrical fibrillation by 69.23% and reduced the time to recovery of the heart rhythm by 37.85%.

Topics: Animals; Animals, Outbred Strains; Anti-Arrhythmia Agents; Guanidines; Injections, Intraperitoneal; Male; Myocardial Reperfusion Injury; Pyrazoles; Rats; Recovery of Function; Ventricular Fibrillation

To investigate whether sodium-hydrogen exchanger isoform-1 (NHE-1) inhibition attenuates myocardial injury during resuscitation from ventricular fibrillation through effects on energy metabolism, using an open-chest pig model in which coronary perfusion was controlled by extracorporeal circulation.. Randomized controlled animal study.. University research laboratory.. Male domestic pigs.. Ventricular fibrillation was electrically induced and left untreated for 8 mins, after which extracorporeal circulation was started and its flow adjusted to maintain a coronary perfusion pressure of 10 mm Hg. After 10 mins of extracorporeal circulation, restoration of spontaneous circulation was attempted by epicardial defibrillation and gradual reduction in extracorporeal flow. Two groups of eight pigs each were randomized to receive the NHE-1 inhibitor zoniporide (3 mg.kg-1) or vehicle control immediately before starting extracorporeal circulation.. Identical extracorporeal flows (approximately = 9% of baseline cardiac index) were required in zoniporide and control groups to attain the target coronary perfusion pressure, resulting in comparable left anterior descending coronary artery blood flow (9 +/- 1 and 10 +/- 1 mL.min-1) and resistance (0.10 +/- 0.01 and 0.10 +/- 0.01 dyne.sec.cm(-5)). Yet zoniporide prevented reductions in left ventricular volume and wall thickening while favoring higher myocardial creatine phosphate to creatine ratios (0.14 +/- 0.03 vs. 0.06 +/- 0.01, p < .05), lower myocardial adenosine (0.7 +/- 0.1 vs. 1.3 +/- 0.2, p < .05), and lower myocardial lactate (80 +/- 9 vs. 125 +/- 6 mmol.kg-1, p < .001). Postresuscitation, zoniporide-treated pigs had higher left ventricular ejection fraction (0.57 +/- 0.07 vs. 0.29 +/- 0.05, p < .05) and higher cardiac index (4.8 +/- 0.4 vs. 3.4 +/- 0.2 L.min-1.m-2, p < .05).. Zoniporide ameliorated myocardial injury during resuscitation from ventricular fibrillation through beneficial effects on energy metabolism without effects on coronary vascular resistance and coronary blood flow.

Topics: Animals; Energy Metabolism; Guanidines; Heart; Male; Myocardium; Pyrazoles; Swine; Ventricular Fibrillation; Ventricular Function, Left