Vascular and contractile function and tissue metabolites after prolonged hypothermic ischaemia and reperfusion: Comparison of single- versus multi-dose infusions with two cardioplegic solutions in blood-perfused neonatal pig hearts

Abstract

The effects of single- and multi-dose cardioplegia on post-ischaemic vascular function and contractile activity were compared in 69 blood-perfused neonatal pig hearts, as were the protective properties of two different cardioplegic solutions. Hearts ( n = 6 or 9 per group) from neonatal (3–5 days old) pigs were excised, arrested with a 2 min infusion (at 15°C) of St Thomas' Hospital cardioplegic solution number 1 (STH1) or number 2 (STH2), and then maintained in a state of hypothermic (15°C) ischaemia for 6 or 8 h. Hearts in the multi-dose groups received cardioplegia every hour (2 min at 15°C). At the end of ischaemia all hearts were reperfused (60 ± 2 mmHg perfusion pressure) for 40 min with blood from a support pig. Systolic and diastolic functions were assessed with an intraventricular balloon, and endothelial and smooth muscle functions by measuring the response to infusions of defined concentrations of acetylcholine (8, 16 and 32 μg/min) and glyceryl trinitrate (40, 80 and 160 μg/min). Hearts ( n = 9) not subjected to ischaemia were perfused for the same duration to act as aerobic controls. At the end of the perfusion period, hearts were frozen and taken for metabolite analysis. After 8 h ischaemia, the recovery of left ventricular developed pressure was greatest in the multi-dose STH1 and single-dose STH2 groups (113 ± 6 and 117 ± 6 mmHg, respectively, v 128 ± 9 mmHg in aerobic controls, at an end-diastolic pressure of between 3 and 9 mmHg; P = N.S.) and the poorest in the single-dose STH1 group (92 ± 5 mmHg; P < 0.05 v controls). The recovery of diastolic function was greatest in the multi-dose STH2 group and again poorest in the single-dose STH1 group (left ventricular enddiastolic pressure 1 ± 2 and 30 ± 10 mmHg, at a ventricular volume of 3.0 ml, ν-1 ± 1 mmHg in aerobic controls). Vascular responses to acetylcholine and glyceryl trinitrate and the myocardial high-energy phosphates content were better preserved in multi-dose groups and with STH2. Inter-group differences were less when the duration of ischaemia was reduced to 6 h. In conclusion, the neonatal pig heart was best preserved with multi-dose cardioplegia and STH2 was more efficacious than STH1. However, not all indices were optimally protected by multi-dose STH2. Thus the best protection of systolic function was obtained with multidose STH1and this was followed by single dose STH2. Diastolic was best preserved with multi-dose STH2 as were vascular function and high-energy phosphates.