title: Effects of cerebroplegic solutions during hypothermic circulatory arrest and short-term recovery.
abstract: Previous studies have suggested that a simple crystalloid "cerebroplegic" solution may prolong the safe duration of hypothermic circulatory arrest. We tested the hypothesis that pharmacologic modification of the cerebroplegic solution would further enhance cerebral protection. Forty-six 4-week-old miniature piglets underwent core cooling to 15 degrees C nasopharyngeal temperature and 2 hours of hypothermic circulatory arrest. Twelve animals had a 50 ml/kg dose of saline infused into the carotid artery system at the onset of hypothermic circulatory arrest and repeat doses of 10 ml/kg every 30 minutes during arrest. Eleven animals received the same initial and repeat doses of University of Wisconsin organ preservation solution and 10 received University of Wisconsin solution with 7.5 mg/L of MK-801, an excitatory neurotransmitter antagonist. In 13 control animals blood was partially drained from the piglet before 2 hours of circulatory arrest at 15 degrees C and no cerebroplegic solution was infused. All solutions were delivered at 4 degrees C. Brain temperature (n = 24) at the onset of hypothermic circulatory arrest was 15.0 degrees +/- 0.1 degrees C (mean +/- standard error). Brain temperature after cerebroplegic infusion dropped to 13.0 degrees +/- 0.3 degrees C and stayed lower than brain temperature in the control group throughout the hypothermic circulatory arrest period. Recovery of cerebral adenosine triphosphate and intracellular pH determined by phosphorus 31 magnetic resonance spectroscopy (n = 22) was significantly improved by saline infusion and was further improved with University of Wisconsin solution and University of Wisconsin solution plus MK-801 (p < 0.001). Recovery of cerebral blood flow measured by microspheres (n = 24) also was augmented by University of Wisconsin solution (p < 0.001) but not in the presence of MK-801. The vascular resistance response to acetylcholine and nitroglycerin suggested that MK-801 has a direct vasoconstrictive effect. Recovery of cerebral oxygen consumption (n = 24) was increased by University of Wisconsin solution and University of Wisconsin solution with MK-801 (p = 0.002). Brain water content (n = 46) was significantly lower in all cerebroplegia-treated groups than in controls (p < 0.001).
  
  
  CONCLUSIONS
  Cerebroplegia improves short-term recovery after 2 hours of circulatory arrest in hypothermic piglets. Pharmacologic modification with University of Wisconsin solution further improves the recovery of cerebral blood flow and metabolism. MK-801 does not augment the protective effects of University of Wisconsin solution and reduces the recovery of cerebral blood flow by a direct vascular action. Modified cerebroplegia may provide a novel approach to improved cerebral protection when prolonged hypothermic circulatory arrest is necessary.
authors.affiliation: Department of Cardiac Surgery, Children's Hospital, Boston, MA 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
authors.initials: D
authors.lastname: Holtzman
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D006324:Heart Arrest, Induced; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced; D007328:Insulin / Q000494:pharmacology; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000378:metabolism; D011887:Raffinose / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen