Reduced oxygen tension during cardiopulmonary bypass limits myocardial damage in acute hypoxic immature piglet hearts

Objectives.

Cardiopulmonary bypass (CPB) is usually instituted in a hyperoxic fashion (oxygen tension (pO₂) 300–500 mmHg), which may expose cyanotic infants to potential reoxygenation damage. Oxygen free radicals play an important role in this injury. The rate of production of this highly reactive toxic oxygen species is dependent on the oxygen level during reoxygenation. This study tested the hypothesis that reduction of the oxygen in the bypass prime and in blood cardioplegia (BCP) to normoxic levels can reduce reoxygenation injury and will result in improved contractility.

Methods.

We operated on 19 Duroc-Yorkshire piglets (2–3 weeks, 3–5 kg). Five underwent 30 min of BCP arrest during 1 h of CPB without hypoxia (control). Fourteen underwent 120 min of hypoxia (arterial pO₂ 20–30 mmHg) on ventilator before reoxygenation on CPB. Reflecting the clinical routine procedure, nine of them were reoxygenated on CPB for 5 min with high pO₂ (350–450 mmHg) followed by 30 min of BCP arrest (high pO₂) and 25 min of reoxygenation/reperfusion on CPB with high pO₂ levels (NoRx). Five others were put on CPB with pO₂ reduced to normoxic levels (pO₂ 100 mmHg) in CPB and BCP (Rx). Functional and biochemical measurements were made before hypoxia, as well as during and after reoxygenation.

Results.

In contrast to controls, NoRx resulted in a 40% decrease in antioxidant reserve capacity (P<0.01) at 4 mM t-butyl hydroperoxide (t-BHP), a 1212% increase in moycardial conjugated diene production during BCP induction (P<0.0003), a 1000% during reperfusion (P<0.002), a 36.1% and a 37.0% increase in coronary sinus blood conjugated dienes at 35 min (P<0.05) and 60 min (P<0.05) of reoxygenation. These biochemical changes were accompanied by a 79% reduction of left ventricular contractility (P<0.0003). Conversely, Rx led to an improvement in antioxidant reserve capacity (939±212 vs 1342±177 nmol/g protein; P<0.003), less conjugated diene production during BCP induction (15.5±6.1 vs 42.1±8.8 A₂₃₃nm/min per 100 g; P<0.003) and reperfusion (1.8±3.9 vs 22.0±5.5 A₂₃₃nm/min per 100 g; P<0.005), and to a significantly improved post bypass LV contractility (58±25 vs 21±5; P<0.0003).

Conclusions.

These data document that hypoxemic/reoxygenation injury occurs in acute hypoxic immature piglet hearts when reoxygenated on CPB with hyperoxic pO₂ (normal clinical practice). By lowering the antioxidant reserve capacity, hypoxemia seems to render the developing heart susceptible to reoxygenation damage, which occurs with the reintroduction of molecular oxygen, and is associated with free radical production, subsequent lipid peroxidation, and depressed post bypass LV function. Reduction of pO₂ during the initial reoxygenation period and during BCP arrest to normoxic levels resulted in a significant reduction of this oxygen-related damage and in much improved myocardial performance.