Calcium antagonists and myocardial protection: a comparative study of the functional, metabolic and electrical consequences of verapamil and nifedipine as additives to the St. Thomas' cardioplegic solution.
Using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest, a comparative study has been undertaken in order to characterize the functional, metabolic and electrophysiological consequences resulting from the addition of dl-verapamil or nifedipine to the St. Thomas' Hospital cardioplegic solution. Hearts (n = 6 in each group) were subjected to cardioplegic infusion with the St. Thomas' solution with or without added verapamil (1.1 micromoles/liter) or nifedipine (0.075 micromoles/liter). After 35 minutes of normothermic (37 degrees C) ischemic arrest, reperfusion was initiated and functional recovery was measured and expressed as a percent of its pre-ischemic control value. Inclusion of nifedipine in the cardioplegic solution improved the post-ischemic recovery of cardiac output from its control value of 59.8 +/- 3.0% to 80.0 +/- 2.5%. The temporal characteristics for the post-ischemic recovery of electrical activity and contractile performance were uncomplicated and similar to control hearts. Inclusion of verapamil also improved the protective properties of the St. Thomas' solution with cardiac output recovering to 76.8% +/- 2.8%. However, in contrast to the control and nifedipine groups, the profile for functional recovery was complex. After an early initial recovery, pressure development declined for 0.5 to 6.0 minutes. This occurred despite the recovery of electrical activity. Hearts then exhibited a second phase of recovery where pressure development returned to normal and this was sustained for the duration of the experiment. Analysis of electrocardiographic characteristics revealed a significant prolongation of the P-P and P-Q interval during the first 10 minutes of reperfusion in the verapamil group.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamamoto
F
F
Manning
A S
AS
Crome
R
R
Braimbridge
M V
MV
Hearse
D J
DJ
D000818:Animals; D001145:Arrhythmias, Cardiac; D002118:Calcium / Q000037:antagonists & inhibitors*; D002302:Cardiac Output / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D004562:Electrocardiography; D006324:Heart Arrest, Induced; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology*
D014700:Verapamil; D009543:Nifedipine; D002118:Calcium