Effect of verapamil post-treatment in myocardial reperfusion injury.
Effect of verapamil post-treatment (0.2 mg/kg bolus, followed by 0.01 mg/kg/min infusion) on the functional and metabolic changes of the heart after a brief regional ischemia (20 min) followed by 1 hr of reperfusion was studied in open-chest pentobarbitone anaesthetized dogs. In control dogs 1 hr of reperfusion failed to cause any improvement of depressed myocardial contractility (LVdP/dtmax and LVEDP) caused by 20 min of ischemia, which confirmed the earlier reported phenomenon of 'Stunned Myocardium'. Myocardial ischemia caused a significant loss of high-energy phosphate (HEP) content of the affected myocardium (ATP decreased by 60% and CP decreased by 75% of non-ischemic level). Following 1 hr of reperfusion, myocardial ATP was not replenished, though creatine phosphate became near normal. When verapamil was administered just before reperfusion, it showed a profound beneficial effect on the incidence of fatal reperfusion arrhythmias. At the end of 1 hr of reperfusion in this group, the recovery of the myocardial contractility was incomplete, but a significant replenishment of the myocardial HEP content was observed. Thus verapamil post-treatment can prevent reperfusion-induced myocardial injury but functional recovery may be delayed due to the drug's inherent direct myocardial depressant effect.
Maulik
S K
SK
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi.
Seth
S D
SD
Manchanda
S C
SC
Reddy
K S
KS
Gupta
Y K
YK
Maulik
M G
MG
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D003864:Depression, Chemical; D004285:Dogs; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D014693:Ventricular Fibrillation / Q000517:prevention & control; D014700:Verapamil / Q000494:pharmacology* / Q000633:toxicity
D000255:Adenosine Triphosphate; D014700:Verapamil; D003402:Creatine Kinase