Inhaled prostacyclin seems to be a safe and effective pulmonary vasodilator for cardiothoracic surgical patients with pulmonary hypertension, refractory hypoxemia, or right heart dysfunction. Overall, inhaled prostacyclin significantly decreases mean pulmonary artery pressures without altering the mean arterial pressure. Compared with nitric oxide, there is no special equipment required for administration or toxicity monitoring, and the cost savings are substantial.
The aim of this study was to characterize the mechanisms underlying pulmonary vascular dysfunction after cardiopulmonary bypass (CPB) by examining responses of isolated pulmonary arteries to selective endothelium-dependent and -independent activators in control and post-CPB dogs. Adult male mongrel dogs were placed on closed-chest, hypothermic CPB for 2.5 h, and then allowed to recover. Anatomically matched pulmonary arterial rings were isolated and suspended for isometric tension recording. Contractile responses to the alpha1-adrenergic agonist phenylephrine were similar in endothelium-containing arteries from control and CPB animals. Endothelium denudation increased contractions to phenylephrine to a similar extent in both groups. Endothelium-dependent relaxation to acetylcholine was decreased 4 days after CPB compared with controls. In contrast to acetylcholine, endothelium-dependent relaxation to bradykinin or to A23187 were not impaired 4 days after CPB. Inhibition of nitric oxide synthase (NOS) with L-NAME depressed the response to acetylcholine in control vessels, confirming that a component of the response to acetylcholine was nitric oxide (NO) dependent. At lower concentrations of acetylcholine, this component of the response was abolished after CPB. The residual relaxation evoked by acetylcholine in the presence of L-NAME also was impaired in CPB compared with control arteries. This suggests that the CPB-induced impairment of acetylcholine-evoked relaxation may not involve both an NO-mediated and an NO-independent component. L-NAME depressed the response to bradykinin to a similar degree in control and CPB arteries. Vascular smooth-muscle dilatation to the NO donor, SIN-1, or to the K+ATP-channel opener, cromakalim, were similar in endothelium-denuded arteries from CPB and control animals. These results suggest that CPB causes a selective impairment in endothelial dilator function without changing the vascular smooth-muscle response to vasodilator or vasoconstrictor stimuli.
It has previously been demonstrated that cardiopulmonary bypass (CPB) causes prolonged pulmonary vascular hyperreactivity (D.P. Nyhan, J.M. Redmond, A.M. Gillinov, K. Nishiwaki, and P.A. Murray. J. Appl. Physiol. 77: 1584-1590, 1994). This study investigated the effects of CPB on endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (sodium nitroprusside) pulmonary vasodilation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q) plots were generated in conscious dogs before CPB and again in the same animals 3-4 days post-CPB. The dose of U-46619 used to acutely preconstrict the pulmonary circulation to similar levels pre- and post-CPB was decreased (0.13 +/- 0.01 vs. 0.10 +/- 0.01 mg.kg-1.min-1, P < 0.01) after CPB. Acetylcholine, bradykinin, and sodium nitroprusside all caused dose-dependent pulmonary vasodilation pre-CPB. The pulmonary vasodilator response to acetylcholine was completely abolished post-CPB. For example, at left pulmonary blood flow of 80 ml.kg-1.min-1 acetylcholine (10 micrograms.kg-1.min-1) resulted in 72 +/- 15% reversal (P < 0.01) of U-46619 preconstriction pre-CPB but caused no change post-CPB. However, the responses to bradykinin and sodium nitroprusside were unchanged post-CPB. The impaired pulmonary vasodilator response to acetylcholine, but not to bradykinin, suggests a selective endothelial defect post-CPB. The normal response to sodium nitroprusside indicates that cGMP-mediated vasodilation is unchanged post-CPB.
Ontogénie changes of protein kinase C in the rat liver, heart and cerebrum were
examined from 17-day gestation until adult. Cerebral protein kinase C activity was 19 times
less at 17-day fetal as compared to 15-day postnatum or older rats. The enzyme activity in
the heart was generally higher in the neonatal period than the adult, but was not correlated
with the previously reported α(1)-adrenergic and cholinergic receptor ontogeny. Likewise in
the liver, the enzyme activity was not correlated with previously reported α(1)-adrenergic and
vasopressin receptor ontogeny. No correlation between protein kinase C and cyclic AMPdependent
protein kinase activities was found among these tissues. The enzyme distribution
expressed by a cytosol/particulate ratio of 0.72, 2.41 and 0.64 in the liver, heart and brain,
respectively, in 20-day fetus was similar to adult values. We conclude that there is a discrete
ontogénie pattern of protein kinase C in each organ and it does not sem to be correlated with
the ontogénie pattern of hormone receptors which relate to phosphatidylinositol breakdown.
The precise role of protein kinase C in relationship to growth and differentiation needs to be
further investigated.
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