Induced moderate hypothermia markedly exacerbates pulmonary hypertension and dysoxia in a neonatal piglet model of elevated pulmonary vascular resistance

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Objective

To assess the cardiopulmonary effects of induced mild to moderate hypothermia in a neonatal animal model of pulmonary hypertension.

Background

Induced hypothermia has been proposed for neuroprotection following perinatal asphyxia. This latter condition is often associated with other pathophysiological derangements such as pulmonary hypertension, depressed cardiac function and decreased mesenteric blood flow. In those instances, hypothermia may become detrimental because of its potential to further increase pulmonary vascular resistance.

Design/methods

Anesthetized piglets (7± 1 days old, n=27) were randomized to receive a thromboxane A₂ mimetic (U46,619, 0.09± .07 μg/kg/min)(TX) or nothing (CONT). One hour later, both groups were subjected to mild (34-36°C) or moderate (32-34°C) whole body hypothermia. Rewarming was started one hour later. At all times mechanical ventilation was modified to preserve normocapnea, pH >7.30 and Pa0₂ >100 torr. The following parameters were measured every 30 min: arterial, pulmonary and superior sagittal sinus blood gases; mean systemic (BP) and pulmonary artery pressures (PAP); cardiac output (thermodilution)(CO); internal carotid (CBF) and superior mesenteric (MBF) blood flow (ultrasonic flow transducers); lung mechanics and blood lactate concentration. Pulmonary (PVR) and systemic vascular resistance (SVR), alveolar-arterial oxygen gradient (A-aDO₂), shunt fraction, oxygen index (mPaw xFiO₂/PaO₂)(OI) and oxygen extraction and O₂ consumption (VO₂) were derived from those parameters.

Results

Administration of TX increased (P<0.01) baseline PVR by 137± 7%, while CO, MBF and CBF decreased by 23± 4%, 33± 1% and 29± 7% respectively. The table shows the mean ± s.e.m % changes from their respective prehypothermia levels for each group at the end of the one hour hypothermic period.

Hypothermia caused a decrease in CBF (CONT: 25± 8%,TX:44± 9%), cerebral (VO₂) (23± 17% vs 34± 11%) and MBF (23± 7 vs 29± 16%). CONT and TX were not statistically different. The physiological responses to mild or moderate hypothermia were similar. No excessive lactate production was observed.

Conclusions

Induced therapeutic hypothermia may exacerbate the adverse pulmonary hemodynamic effect associated with newborn pulmonary hypertension and lead to consequent hypoxemia.

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