Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model†

Abstract

OBJECTIVES: This study investigated whether the novel St. Thomas’ Hospital polarizing cardioplegic solution (STH-POL) with esmolol/adenosine/magnesium offers improved myocardial protection by reducing demands for high-energy phosphates during cardiac arrest compared to the depolarizing St. Thomas’ Hospital cardioplegic solution No 2 (STH-2). METHODS: Twenty anaesthetised pigs on tepid cardiopulmonary bypass were randomized to cardiac arrest for 60 min with antegrade freshly mixed, repeated, cold, oxygenated STH-POL or STH-2 blood cardioplegia every 20 min. Haemodynamic variables were continuously recorded. Left ventricular biopsies, snap-frozen in liquid nitrogen or fixed in glutaraldehyde, were obtained at Baseline, 58 min after cross-clamp and 20 and 180 min after weaning from bypass. Adenine nucleotides were evaluated by high-performance liquid chromatography, myocardial ultrastructure with morphometry. RESULTS: With STH-POL myocardial creatine phosphate was increased compared to STH-2 at 58 min of cross-clamp [59.9 ± 6.4 (SEM) vs 44.5 ± 7.4 nmol/mg protein; P < 0.025], and at 20 min after reperfusion (61.0 ± 6.7 vs 49.0 ± 5.5 nmol/mg protein; P < 0.05), ATP levels were increased at 20 min of reperfusion with STH-POL (35.4 ± 1.1 vs 32.4 ± 1.2 nmol/mg protein; P < 0.05). Mitochondrial surface-to-volume ratio was decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion (6.74 ± 0.14 vs 7.46 ± 0.13 µm2/µm3; P = 0.047). None of these differences were present at 180 min of reperfusion. From 150 min of reperfusion and onwards, cardiac index was increased with STH-POL; 4.8 ± 0.2 compared to 4.0 ± 0.2 l/min/m2 (P = 0.011) for STH-2 at 180 min. CONCLUSIONS: Polarizing STH-POL cardioplegia improved energy status compared to standard STH-2 depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion.

Left ventricular dysfunction after two hours of polarizing or depolarizing cardioplegic arrest in a porcine model

“…35 Temporary high levels of hypoxanthine are to be expected in the STH-POL group due to degradation of the adenosine component. 12 However, no difference in tissue levels of MDA was found, demonstrating that degradation of hypoxanthine to uric acid by xanthine oxidase did not cause an extra myocardial oxidative stress in the present study. 36…”

“…In a previous study, creatine phosphate and adenosine triphosphate (ATP) levels were temporary increased just before and 20 min after declamping following 60 min of cardioplegic arrest with STH-POL compared to STH-2 cardioplegia. 12 Creatine phosphate exerts both anti-oxidant and anti-apoptotic effects. 26 One could speculate if these factors might contribute to the improved mechanical efficiency (Figure 4) also seen after 120 min of cardioplegic arrest.…”

“…11 Furthermore, STH-POL blood cardioplegia improves myocardial energy status compared to STH-2 blood cardioplegia just before and early after aortic declamping following 60 min of cardioplegic arrest. 12 The aim of the present study was to compare STH-POL and STH-2 oxygenated blood cardioplegia in an experimental setting with prolonged (120 min) myocyte membrane polarization or depolarization, with clear differences in total potassium load. In this clinically relevant animal study, left ventricular function was evaluated and compared up to 4 hours after 120 min of cardioplegic arrest.…”

Relevance and Recommendations for the Application of Cardioplegic Solutions in Cardiopulmonary Bypass Surgery in Pigs

“…Therefore, direct comparisons of different cardioplegic solutions were performed. Comparisons between St. Thomas I and II cardioplegic solutions have shown enhanced functional recovery, better contractile efficiency, and improved energy status with St. Thomas I cardioplegia [ 21 , 22 , 23 , 24 ]. The novel HTK-N solution stabilizes hemoglobin and blood calcium levels, which can potentially increase kidney function [ 25 ].…”

St Thomas' Hospital polarizing blood cardioplegia improves hemodynamic recovery in a porcine model of cardiopulmonary bypass

“…5 The arrest characteristics of esmolol act via Ca 2þ -channel and Na þ -channel blockade. 6 Recently, Aass and colleagues 7 demonstrated the efficacy of this new blood-based St Thomas' Hospital polarized cardioplegia (STH-Pol-B) in a cardiopulmonary bypass (CPB) model in pigs. They pointed out the benefits of polarized arrest on the energy status and cardiac index during late ischemia and the early phase of reperfusion.…”