EFFECTS OF APROTININ ON ACUTE RECOVERY OF CEREBRAL METABOLISM IN PIGLETS AFTER HYPOTHERMIC CIRCULATORY ARREST

Brain protection during cardiopulmonary bypass and hypothermic circula tory arrest is incomplete. Activation of blood protease cascades may c ontribute to cellular injury under these conditions. To test this hypo thesis, effects of the protease inhibitor aprotinin on recovery of bra in energy metabolism after hypothermic circulatory arrest were studied in the piglet. Twenty-four 4-week-old piglets (10 aprotinin-treated a nd 14 control) underwent core cooling, 1 hour of circulatory arrest at 15 degrees C, reperfusion and rewarming (45 minutes), and normothermi c perfusion (3 hours) on cardiopulmonary bypass. Cerebral high-energy phosphate concentration and intracellular pH were studied by phosphoru s-dl magnetic resonance spectroscopy in 12 animals. In the remaining a nimals cerebral and regional blood flow were measured with radioactive microspheres and carotid artery blood how was measured with an electr omagnetic flowmeter. Cerebral oxygen and glucose extraction were measu red, and vascular resistance responses to endothelium-dependent (acety lcholine) and -independent (nitroglycerin) vasodilators were calculate d. Recovery of cerebral adenosine triphosphate (p = 0.02) and intracel lular pH (p = 0.04) in the initial 30 minutes of reperfusion was accel erated in the aprotinin-treated piglets. These piglets showed a greate r in vivo cerebral and systemic endothelium-mediated vasodilation (ace tylcholine response: cerebral p < 0.01, systemic p = 0.04) after reper fusion. The response to endothelium-independent vasodilation (nitrogly cerin) was the same in both groups. Carotid blood how tended to be gre ater at 20 minutes of reperfusion and less during 45 to 80 minutes aft er reperfusion in the aprotinin-treated animals. Brain water content p ostoperatively was 0.8077 in the aprotinin group and 0.8122 in control animals (p = 0.06). Water content in the lungs, heart, kidneys, jejun um, and lower limb muscle was less in the aprotinin group (p < 0.05). Aprotinin enhances recovery of cerebral energy metabolism from the del eterious effects of deep hypothermic circulatory arrest in the immatur e animal, possibly through mechanisms involving preservation of vascul ar integrity.