Prolonged protective effect of the calcium antagonist anipamil on the ischemic reperfused rabbit myocardium: comparison with verapamil.
To assess whether pretreatment with the calcium antagonist anipamil protects the heart against ischemic and reperfusion damage and to establish how long the protection persists after cessation of the therapy, rabbits were injected subcutaneously twice daily for 5 days with 2 mg/kg body weight of this drug. The heart was then isolated 2, 6, or 12 hours after the last injection and was perfused by the Langendorff technique during a control period and 90 minutes of total ischemia (37 degrees C), followed by 30 minutes of reperfusion. Diastolic and developed pressure was monitored; coronary effluent was collected and assayed for creatine phosphokinase (CPK); mitochondria were harvested and assayed for respiratory activity, ATP production, and calcium content; and tissue concentration of adenosine triphosphate (ATP) and creatine phosphate were determined. The data obtained with anipamil were compared with those obtained with verapamil administered to the rabbit at the same dose and following the same procedure. Pretreatment with anipamil induced a negative inotropic effect under normoxic conditions; reduced the rate and extent of depletion of ATP and creatine phosphate during ischemia, with an incomplete restoration of the nucleotides after reperfusion; maintained mitochondrial function and calcium homeostasis during ischemia and reperfusion; reduced the rate of CPK release; and improved the recovery of ventricular function on reperfusion. The protective effects of anipamil persisted for as long as 12 hours after the last administration. In contrast, the protective and negative inotropic effects of verapamil were no longer apparent in heart isolated 6 or 12 hours after the last dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferrari
R
R
Cattedra di Cardiologia e Cattedra di Chimica, Università degli Studi di Brescia, Italy.
Raddino
R
R
Ceconi
C
C
Curello
S
S
Ghielmi
S
S
Visioli
O
O
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D011437:Propylamines / Q000627:therapeutic use*; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D014700:Verapamil / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D011437:Propylamines; D011506:Proteins; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; C045313:anipamil; D014700:Verapamil; D003402:Creatine Kinase