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 µm 2 /µm 3 ; 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/m 2 ( 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.

Keywords: Cardioplegia; Energy metabolism; Myocardial protection; Ultrastructure.

Figure 1

Left ventricular haemodynamic variables, mean (SE) or median (25%; 75%), at Baseline and after CPB and 60 min of cardiac arrest with polarizing (STH-POL; n = 10) and depolarizing (STH-2; n =10) cardioplegia. CI: cardiac index; LVSP and LVEDP: left ventricular peak systolic- and end-diastolic pressures; dP/dt_max and dP/dt_min:peak positive and peak negative of the first derivative of left ventricular pressure; RM-ANOVA: analysis of variance for repeated measurements; P_w, P_g and P_i:P-values for within subjects, between groups and interaction from two-way RM-ANOVA, respectively; #: significantly different from STH-2 at corresponding time after declamping with Bonferroni tests.

Figure 2

Myocardial tissue levels of creatine phosphate, high energy phosphates and degradation products at Baseline, after 58 min of cardiac arrest with polarizing (STH-POL) and depolarizing (STH-2) cardioplegia, and 20 and 180 min after aortic declamping and reperfusion, n = 10 in both groups. CrP: creatine phosphate; ATP, ADP and AMP: adenosine tri-, di- and monophosphate. P_w, P_g and P_i: P-values for within subjects, between groups and interaction from two-way RM-ANOVA, respectively; *: significantly different from the previous value in the STH-POL group; #: significantly different compared to STH-2 at the corresponding time after declamping with post hoc multiple contrast tests.

Figure 3

Myocyte mitochondrial surface to volume ratio (S_vratio_mit) (A) and surface density (S_Vmit) (B) in 10 animals in the STH-POL group and 9 animals in the STH-2 group. Bars are mean + SEM. P_w, P_g and P_i:P-values for within subjects, between groups and interaction from two-way nested ANOVA, respectively; #: significantly different from STH-2 at 20 min after declamping. One micrograph from each group with morphometric readings close to mean values at 20 min after declamping.