Pyruvate‐enhanced cardioplegia preserves myocardial Hsp 70 and endothelial NOS in a porcine model of cardiopulmonary bypass

Abstract

Background: The use of pyruvate‐fortified cardioplegia to arrest the heart during cardiopulmonary bypass (CPB) enhances post‐surgical recovery of cardiac function, compared with conventional cardioplegia solutions. Pyruvate's energy‐yielding and antioxidant effects wane as pyruvate is cleared from the circulation, yet its functional benefits persist, suggesting a protein‐mediated cardioprotective mechanism.Hypothesis: Pyruvate cardioplegia during CPB prevents subsequent depletion of the cytoprotective proteins eNOS and Hsp‐70. Methods: After sternotomy, swine were subjected to 60 min cardioplegic arrest and 30 min myocardial reperfusion on CPB, then were weaned from bypass. The crystalloid portion of the 4:1 blood:crystalloid cardioplegia contained 24 mM lactate or pyruvate. Left ventricular myocardium was sampled at 4 h post‐CPB for extraction and immunoblot detection of Hsp70 and eNOS; actin served as loading control. Sham pigs underwent the same surgical and analytical procedures, but without CPB.Results: Actin‐normalized myocardial eNOS and Hsp‐70 contents fell by 32 and 68%, respectively, and NOS activity fell from 132 ± 10 to 91 ± 6 nmol/min/g protein in the lactate cardioplegia group, vs. respective sham values (P < 0.05). Pyruvate cardioplegia prevented loss of eNOS and Hsp70, and maintained NOS activity at 134 ± 8 nmol/min/g protein (P < 0.05 vs. lactate group).Conclusions: Cardioplegic arrest on CPB can deplete myocardium of the cytoprotective proteins eNOS and Hsp70. Protection of these proteins by pyruvate‐enriched cardioplegia may support improved post‐CPB cardiac performance.Support: Osteopathic Heritage Foundation 02‐18‐522