The pulmonary vascular system is a low resistance circuit that may react to stroma-free hemoglobin compounds to cause rises in pulmonary artery pressure (PAP). These compounds are known to inactivate nitric oxide (NO). The endothelial activity and smooth muscle constriction may be mediated by several agents, including NO and constrictor eicosinoids. To clarify dose-response relationships and actions, seventeen anesthetized, open-chested 20-22 kg pigs were monitored with pulmonary and systemic arterial and left ventricular pressure catheters. While measuring PAP and pulmonary vascular resistance, we determined the cumulative dose-response curve to a 10% DCLHb solution in three-fold increments starting at 1 mg/kg and increasing up to 1g/kg. Seven of the animals were given indomethacin (6mg/kg) to block the cycloxygenase pathway. A rise in PAP from 21.8±5.3mmHg to 27.1±7.5mmHg and a small decrease in cardiac output from a baseline of 3.1±0.51/min to 2 . 8±.51/min were observed with DCLHb doses as low as 30 mg/kg. Very small doses of DCLHb constrict pulmonary resistance vessels. At a dose of 1g/kg the PAP rose to 37.7 ± 6.8mmHg. The PAP rises were partially blocked by indomethacin implying that this effect is in part amplified in anesthetized swine by cyclooxygenase products. No other hemodynamic parameters differed significantly.
|State||Published - 1996|