Protective effects of calcium antagonists on energy and substrate metabolism during ischemia and reperfusion in hypertensive myocardial hypertrophy.
The aim of the present study was to define the protective effects of verapamil and nifedipine on mechanical performance and energy and substrate metabolism of the postischemically reperfused myocardium in a chronic pressure overload cardiac hypertrophy model. The isolated beating rat heart preparation was used and left ventricular pressures and high-energy phosphates were continuously monitored during 30 min of global ischemia and reperfusion, respectively. Recovery of mechanical performance and high-energy phosphate and sugar monophosphate metabolism was significantly impaired in untreated hypertrophied hearts compared with normal control hearts and hypertrophied hearts treated with calcium antagonists. In hypertrophied hearts with chronic verapamil treatment, recovery was significantly improved compared to acute verapamil treatment, nifedipine treatment, and normal control hearts. Thus, verapamil and nifedipine exerted a protective effect on the postischemic recovery of the hypertrophied myocardium that was most prominent following long-term pretreatment with verapamil. Prolonged maintenance of adequate plasma levels and tissue distribution of calcium antagonists before an ischemic event may improve the postischemic prognosis in the presence of pressure-induced myocardial hypertrophy.
Buser
P T
PT
Department of Internal Medicine, University Hospitals, Basel, Switzerland.
Wagner
S
S
Wu
S
S
Higgins
C B
CB
Wikman-Coffelt
J
J
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D006332:Cardiomegaly / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D006973:Hypertension / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D014700:Verapamil; D009543:Nifedipine