Endothelial Cell Function and Cardiopulmonary Bypass

Immediately following cardiopulmonary bypass an elevation in pulmonary vascular resistance is poorly tolerated. The pulmonary vasculature of such children is prone to intense vasoconstriction in response to stress that may result in pulmonary hypertensive crises. This may necessitate therapeutic maneuvers, including continued paralysis and anesthesia, to blunt the stress response and hyperventilation and alkalosis to promote pulmonary vasodilation. The realization that inhaled nitric oxide could act as a selective pulmonary vasodilator holds great promise for this patient population, and a number of studies have attested to its efficacy both in the preoperative evaluation during cardiac catheterization and postoperatively in the intensive care unit . 

In our initial studies we used inhaled nitric oxide as a probe to test the effect of cardiopulmonary bypass on pulmonary endothelial function. Cardiopulmonary bypass may result in damage to the pulmonary endothelium, and the degree of pulmonary hypertension is correlated with the extent of such damage. Acetylcholine-induced vasodilation is attenuated in a number of vascular diseases that impair endothelial function,and preconstricted pulmonary artery rings from explanted lungs of patients with 

We challenged 12 patients with congenital heart disease and pulmonary hypertension preoperatively in the cardiac catheterization laboratory and nine postoperative patients (after cardiopulmonary bypass) with a 2-min infusion of 10 M acetylcholine into the pulmonary artery. The nine postoperative patients received a 15-min trial of inhaled nitric oxide following the infusion of acetylcholine. The results are shown in Figs. 4 and 5. The decrease in pulmonary artery pressure and resistance in the preoperative patients in response to acetylcholine was markedly attenuated postoperatively. The percentage reductions in pulmonary artery pressure preoperatively were 27% 4% and 9% 2% P 0.003) postoperatively. Similarly, pulmonary vascular resistance decreased by 46% 5% compared to 11% 4% P 0.002). However, the response to inhaled nitric oxide in the postoperative patients was marked vasodilation contrasted with the blunted effect of acetylcholine. Mean pulmonary artery pressure (34.4 2.6 versus 

4 mm Hg P 0.0001) and pulmonary vascular resistance (6.8 1.2 versus 4.5 0.8 U m P 0.005) after nitric oxide were significantly lower with nitric oxide than with acetylcholine, despite similar baseline values. 

As yet, it has not been possible to pinpoint the exact site of injury to the L-arginine nitric oxide pathway. The defect may lie with the surface receptors, signal transduction, L-arginine deficiency, nitric oxide synthase, tolerance of smooth muscle, physical obstruction to the diffusion of nitric oxide by a thickened intima, or impaired guanylate cyclase activation. However, endogenous guanylate cyclase can be activated by exogenously administered nitric oxide to relax smooth muscle, even when unresponsive to acetyl- 

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