Neurohumoral modulation of the pulmonary vasoconstrictor response in the autoperfused working heart-lung preparation during cardiopulmonary preservation

Uncontrolled pulmonary hypertension during autoperfusion of the heart and lungs for preservation has been described, and it may result in extensive pulmonary injury and occasional early failure of the preparation. In order to investigate the neurohumoral mediators of the vasoconstrictor response in the pulmonary circulation of the autoperfused working heart-lung preparation, heart-lung organ blocks were harvested from calves, placed in a normothermic autoperfusion circuit, and studied. Effects of beta-adrenergic stimulation with isoproterenol, nonspecific vasodilatation with nitroglycerin, alpha-adrenergic blockade with phentolamine, phospholipase A2 inhibition with methylprednisolone, cyclooxygenase inhibition with indomethacin, and white blood cell depletion were independently evaluated. Untreated animals, pre- and postexpiant, served as controls. Multipoint pulmonary vascular pressure-cardiac output plots were constructed for each animal. An index of pulmonary vascular resistance was obtained from the linear relation: mean pulmonary artery pressure minus pulmonary capillary wedge pressure divided by cardiac output. An intense flow-dependent pulmonary vasoconstrictor response was confirmed to exist in the denervated bovine autoperfused working heart-lung preparation. Isoproterenol afforded better protection against this response than the other agents studied. White blood cell depletion reduced postexpiant pulmonary vasoconstriction, implying that circulating polymorphonuclear leukocytes mediate the response in the autoperfused working heart-lung preparation. White blood cell depletion and the administration of selected pharmacologic agents provide modalities for regulating the pulmonary vasoconstrictor response, and thus may enhance lung preservation in the autoperfusion model.