The Mechanisms of Pain-Induced Pulmonary Vasoconstriction: An Experimental Study in Fetal Lambs

Abstract

Nociceptive stimulation induces pulmonary vasoconstriction in fetuses and newborns. The mechanism of this response is not fully understood. As the systemic hemodynamic response to pain is mainly mediated by sympathetic stimulation, we hypothesized that pain-induced pulmonary vasoconstriction results from the activation of catecholaminergic receptors. To test this hypothesis, we studied the pulmonary vascular response to nociceptive stimuli in fetal lambs before and after alpha-adrenoceptor blockade. Surgery was performed in fetal lambs. Catheters were placed into the ascending aorta, superior vena cava, and main pulmonary artery. An ultrasonic flow transducer was placed around the left pulmonary artery, and subcutaneous catheters were placed in the limb. The hemodynamic responses to (1) subcutaneous injection of formalin (which is used as nociceptive stimulus in experimental studies), (2) prazosin (specific alpha(1)-adrenoceptor antagonist), and (3) formalin during prazosin infusion were evaluated. Plasma cortisol and catecholamine concentrations were measured. Pulmonary vascular resistance (PVR) increased by 50% (P < 0.01) after the formalin test. PVR did not change after the formalin test during prazosin infusion or during prazosin infusion alone. Catecholamine and cortisol levels did not change during any of the protocols. Our results indicate that the fetal pulmonary vasoconstrictive response to pain involves alpha(1)-adrenoceptors activation. As plasma catecholamine concentrations did not change after the formalin test, we speculate that the pulmonary vascular response to nociceptive stimuli could be triggered by a local release of catecholamine induced by sympathetic stimulation.