Postcardioplegic myocardial recovery: effects of halothane, nifedipine, HOE 694, and quinacrine.
Halothane has been shown to be a powerful myocardial protectant during normothermic cardioplegic arrest and subsequent reperfusion. In view of its multiple effects on cellular Ca2+ movements and the role of this ion in ischemia-reperfusion injury, the questions of whether halothane is capable of maximally protecting the heart or whether combination therapy of halothane with other Ca2+ blocking agents may be more effective arose. Therefore, the effects of combination therapy with halothane and a calcium antagonist (nifedipine), or a Na+/H+ inhibitor (HOE 694), or a Na+/Ca2+ inhibitor (quinacrine) on postcardioplegic functional recovery were evaluated. The isolated perfused rat heart subjected to 45 minutes normothermic cardiac arrest was used as an experimental model. Dose-response curves were performed for each drug. Using the optimal dosage for each drug, the following results were obtained: (1) Nifedipine (10(-7) M; administered retrogradely 10 minutes before and after cardioplegia) and halothane (1.5% administered during cardioplegia), when administered separately, improved functional recovery. Combination therapy did not further improve protection. (2) HOE 694 (10(-7) M) or quinacrine (10(-9) M) improved post-cardioplegic functional recovery when added for 2 minutes at the onset of reperfusion. Simultaneous administration of HOE 694 and 1.5% halothane was the only combination that yielded additive protection. (3) Quinacrine, a phospholipase and Na+/Ca2+ exchanger inhibitor, appeared to be the most powerful drug used. In summary, the results obtained indicate that interventions aimed at preventing intracellular Ca2+ overload improve recovery after cardioplegic arrest. The beneficial effects of halothane could be further improved by HOE 694.
Lochner
A
A
Department of Medical Physiology and Biochemistry, Faculty of Medicine, University of Stellenbosch, Tygerberg, Republic of South Africa. alo@gerge.sun.ac.za
Genade
S
S
Tromp
E
E
Theron
S
S
Trollip
G
G
D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D006221:Halothane / Q000627:therapeutic use; D006324:Heart Arrest, Induced; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009543:Nifedipine / Q000627:therapeutic use; D011796:Quinacrine / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000627:therapeutic use*
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D006146:Guanidines; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine; D011796:Quinacrine; D009543:Nifedipine; D006221:Halothane