The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model.
1. We measured the ability of glucagon and amrinone, used alone and in combination, to improve the myocardial function in a rat isolated heart model of calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol consistently decreased heart rate and cardiac contractile force in our Langendorff rat isolated heart preparations. Glucagon increased the heart rate in a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(-1) mol concentration, and had no significant effect on cardiac contractility. 3. A positive linear correlation was found between the glucagon concentration and the percent recovery of baseline contractile force. 4. Although complete reversal of verapamil-induced myocardial depression occurred at glucagon concentrations of > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were administered together, there was no additional increase over glucagon alone in the increase in contractile force. 6. Glucagon, and not amrinone, is an appropriate agent, capable of reversing verapamil-induced myocardial toxicity in this rat isolated heart model. In vivo studies should be performed to assess whether this may be a reliable therapy in clinical cases.
Tuncok
Y
Y
Department of Pharmacology, Dokuz Eylul University, Balcova, Izmir, Turkey.
Apaydin
S
S
Gidener
S
S
Guven
H
H
Oto
O
O
Ates
M
M
Gure
A
A
D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000633:toxicity*; D003864:Depression, Chemical; D005934:Glucagon / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000633:toxicity*
D002121:Calcium Channel Blockers; D010726:Phosphodiesterase Inhibitors; D005934:Glucagon; D014700:Verapamil; D000676:Amrinone