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Pyruvate-fortified cardioplegia protects myocardium and hastens postsurgical recovery of patients undergoing cardiopulmonary bypass (CPB). Pyruvate reportedly suppresses degradation of the alpha-subunit of hypoxia-inducible factor-1 (HIF-1), an activator of the gene encoding the cardioprotective cytokine erythropoietin (EPO). This study tested the hypothesis that pyruvate-enriched cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in myocardium. Hearts of pigs maintained on CPB were arrested for 60 min with 4:1 blood-crystalloid cardioplegia. The crystalloid component contained 188 mM glucose + or - 24 mM pyruvate. After 30-min cardiac reperfusion with cardioplegia-free blood, the pigs were weaned from CPB. Left ventricular myocardium was sampled 4 h after CPB for immunoblot assessment of HIF-1alpha, EPO and its receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide synthase (eNOS), an effector of EPO signaling. Pyruvate-fortified cardioplegia stabilized arterial pressure post-CPB, induced myocardial EPO mRNA expression, and increased HIF-1alpha, EPO, and EPO-R protein contents by 60, 58, and 123%, respectively, vs. control cardioplegia (P < 0.05). Pyruvate cardioplegia also increased ERK phosphorylation by 61 and 118%, respectively, vs. control cardioplegia-treated and non-CPB sham myocardium (P < 0.01), but did not alter Akt phosphorylation. Nitric oxide synthase (NOS) activity and eNOS content fell 32% following control CPB vs. sham, but pyruvate cardioplegia prevented these declines, yielding 49 and 80% greater NOS activity and eNOS content vs. respective control values (P < 0.01). Pyruvate-fortified cardioplegia induced myocardial EPO expression and mobilized the EPO-ERK-eNOS mechanism. By stabilizing HIF-1alpha, pyruvate-fortified cardioplegia may evoke sustained activation of EPO's cardioprotective signaling cascade in myocardium.

Background and Aim of the Study: Simultaneous antegrade/retrograde cardioplegia (SARC) has been employed frequently during cardiac surgery to preserve the jeopardized myocardium. However, retrograde perfusion of SARC may interfere with myocardial drainage and disrupt myocardial fluid homeostasis, which may affect the myocardial energy metabolism and contractile function. The study was, therefore, designed to assess the effects of SARC on myocardial fluid homeostasis, cellular volumes, and energy metabolism., Methods: Eight isolated pig hearts were subjected to a protocol consisting of a 20-minute control perfusion, 120-minute SARC, and 20-minute reperfusion. The myocardial water content was monitored using near-infrared spectroscopy. Phosphorus-31 magnetic resonance ((31)P MR) spectroscopy was used to monitor the volumes of both intracellular and extracellular compartments and assess myocardial energy metabolism., Results: The near-infrared spectra showed that the 120-min SARC resulted in a 60 +/- 12% increase in the myocardial water content. (31)P MR spectra showed a 36 +/- 4% increase in the intracellular compartment and a 54 +/- 8% increase in the extracellular compartment during SARC relative to their initial volumes measured during control perfusion (100%). However, the myocardial energy metabolites (adenosine triphosphate [ATP] and phosphocreatine [PCr]) remained unchanged during the 120-minute SARC. Moreover, during reperfusion, the hearts showed an almost complete recovery in the left ventricular-developed pressure., Conclusions: A prolonged SARC resulted in water accumulation in both extracellular and intracellular compartments in the normal myocardium. Although its detrimental effect on tissue fluid homeostasis did not jeopardize the myocardial energy metabolism, a prolonged use of SARC should be avoided, particularly in the diseased hearts.

Background: As an alternative to cardioplegic arrest, cardiac surgical conditions have been produced using beta-blocker-induced minimal myocardial contraction (MMC) during cardiopulmonary bypass. The technique of MMC involves the use of high-dose intravenous esmolol to suppress myocardial chronotropy and inotropy sufficiently to produce cardiac surgical conditions. The purpose of this study was to compare conventional crystalloid cardioplegic arrest with MMC in terms of ischemia avoidance, myocardial edema formation, and cardiac function., Methods: Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to crystalloid cardioplegic arrest for 2 hours. Surgical conditions were produced in the other 6 dogs for 2 hours using intravenous esmolol without aortic clamping or cardioplegia. Arterial and coronary sinus lactate concentrations were determined as a gauge of myocardial ischemia. Myocardial water content was determined using microgravimetry and preload recruitable stroke work was determined using sonomicrometry and micromanometry., Results: Significant lactate washout was demonstrated after cardioplegic arrest but not after MMC. Myocardial water content was significantly less during and after MMC compared with cardioplegic arrest (p < 0.05). Preload recruitable stroke work was decreased compared with baseline values in both groups (p < 0.05)., Conclusions: In contrast to a previous study that involved 1 hour of MMC, in this study, ventricular function was decreased to the same extent as with cardioplegic arrest after 2 hours of MMC. This was attributed to the accumulation of ASL-8123, the primary metabolite of esmolol, which possesses beta-antagonist properties. Although postbypass ventricular function is similar in both groups, MMC appears to be superior in terms of ischemia avoidance and myocardial edema formation.

The effects of 1 and 2 hours of hypothermic anoxic arrest and cardioplegia induced by Mg-lidocaine, K-Mg, or K on left ventricular mitochondrial respiratory function, blood flow, and edema were studied in 41 mongrel dogs. Mitochondrial respiration was assessed by the indices of oxidative phosphorylation. Myocardial temperature recorded in ventricular septum was kept at 20 degrees C during ischemic arrest and 10 minutes of reperfusion. Cardioplegic solutions did not influence noncoronary blood flow during cross-clamping of the aorta. Mitochondrial respiratory function remained at control levels after 1 hour of ischemia induced by hypothermic anoxic arrest or by Mg-lidocaine or K-Mg hypothermic cardioplegia. Mitochondrial state 3 respiration after 2 hours of anoxic arrest was significantly higher in Mg-lidocaine cardioplegia than in anoxic arrest (p less than 0.05), but myocardial edema was equivalent in both groups. Mg in the cardioplegic solution suppressed mitochondrial nonphosphorylating oxygen consumption. These data suggest that mitochondrial function after 1 hour of ischemic arrest at 20 degrees C and 10 minutes of reperfusion is not significantly depressed, but at 2 hours of ischemic arrest, mitochondrial respiration is significantly impaired. However, hypothermic Mg-lidocaine cardioplegia appears to be more effective in sustaining myocardial respiration than does simple hypothermic anoxic arrest when the anoxic period is extended to 2 hours.