A new role for cardioplegic buffering: should acidosis or calcium accumulation be counteracted to salvage jeopardized hearts?
OBJECTIVE
Thirty minutes of unprotected ischemia produced a jeopardized heart that was treated with a blood cardioplegic solution containing the natural erythrocyte and protein buffers. Cardioplegic pH was changed to 7.7 (buffered) or 7.2 (nonbuffered), and this was tested alone and after pretreatment with Na(+)-H(+) exchange blockade (cariporide) to define their protective effects.


METHODS
Twenty-four Yorkshire-Duroc pigs (27-34.5 kg) underwent 30 minutes of normothermic global ischemia, followed by 30 minutes of aortic clamping during protection with buffered (n = 12) or nonbuffered (n = 12) glutamate-aspartate-enriched blood cardioplegic solution. Twelve hearts (6 buffered and 6 nonbuffered) were pretreated with intravenous cariporide (5 mg/kg) 15 minutes before ischemia.


RESULTS
Severe and comparable left ventricle dysfunction followed buffered or nonbuffered cardioplegia: Preload recruitable stroke work recovered to 56% +/- 21% and 45% +/- 20% of baseline levels; creatine kinase MB, conjugated dienes, and myeloperoxidase activity markedly increased; moderate myocardial edema occurred; and endothelin-1 increased 2-fold more than baseline values. Cariporide pretreatment caused a similar return of preload recruitable stroke work to 86% +/- 9% and 90% +/- 6% after buffered or nonbuffered cardioplegia (P <.05 vs nonpretreated groups), allowed only minor creatine kinase MB and conjugated diene changes, and reduced endothelin-1 release 3-fold compared with hearts without sodium-hydrogen exchange blockage.


CONCLUSIONS
The severe ischemia-reperfusion injury of 30 minutes of normothermic ischemia is not altered by an acidic or alkalotic pH cardioplegic solution. Correction of damage is achieved by adding Na(+)-H(+) exchange blocker therapy before treatment with buffered and nonbuffered solutions; thus, sodium-hydrogen exchange inhibition plays a more vital role in recovery than pH management.
Castellá
Manuel
M
Department of Surgery, Division of Cardiothoracic Surgery, University of California, Los Angeles, School of Medicine, USA.
Buckberg
Gerald D
GD
Saleh
Saleh
S
Tan
Zhongtuo
Z
Ignarro
Louis J
LJ
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004195:Disease Models, Animal; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D006863:Hydrogen-Ion Concentration; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D007527:Isoenzymes / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology
D002021:Buffers; D002314:Cardioplegic Solutions; D006146:Guanidines; D007527:Isoenzymes; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D002118:Calcium