title: Effects of aprotinin on acute recovery of cerebral metabolism in piglets after hypothermic circulatory arrest.
abstract: Brain protection during cardiopulmonary bypass and hypothermic circulatory arrest is incomplete. Activation of blood protease cascades may contribute to cellular injury under these conditions. To test this hypothesis, effects of the protease inhibitor aprotinin on recovery of brain energy metabolism after hypothermic circulatory arrest were studied in the piglet. Twenty-four 4-week-old piglets (10 aprotinin-treated and 14 control) underwent core cooling, 1 hour of circulatory arrest at 15 degrees C, reperfusion and rewarming (45 minutes), and normothermic perfusion (3 hours) on cardiopulmonary bypass. Cerebral high-energy phosphate concentration and intracellular pH were studied by phosphorus-31 magnetic resonance spectroscopy in 12 animals. In the remaining animals cerebral and regional blood flow were measured with radioactive microspheres and carotid artery blood flow was measured with an electromagnetic flowmeter. Cerebral oxygen and glucose extraction were measured, and vascular resistance responses to endothelium-dependent (acetylcholine) and -independent (nitroglycerin) vasodilators were calculated. Recovery of cerebral adenosine triphosphate (p = 0.02) and intracellular pH (p = 0.04) in the initial 30 minutes of reperfusion was accelerated in the aprotinin-treated piglets. These piglets showed a greater in vivo cerebral and systemic endothelium-mediated vasodilation (acetylcholine response: cerebral p < 0.01, systemic p = 0.04) after reperfusion. The response to endothelium-independent vasodilation (nitroglycerin) was the same in both groups. Carotid blood flow tended to be greater at 20 minutes of reperfusion and less during 45 to 80 minutes after reperfusion in the aprotinin-treated animals. Brain water content postoperatively was 0.8077 in the aprotinin group and 0.8122 in control animals (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Cardiovascular Surgery, Children's Hospital, Boston, Massachusetts 02115.
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: R A
authors.initials: RA
authors.lastname: Jonas
authors.forename: F
authors.initials: F
authors.lastname: Nomura
authors.forename: M E
authors.initials: ME
authors.lastname: Stromski
authors.forename: M K
authors.initials: MK
authors.lastname: Tsuji
authors.forename: P R
authors.initials: PR
authors.lastname: Hickey
authors.forename: D H
authors.initials: DH
authors.lastname: Holtzman
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects; D006324:Heart Arrest, Induced; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced; D009682:Magnetic Resonance Spectroscopy; D010101:Oxygen Consumption / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature
chemical_list: D007611:Aprotinin