title: pH strategies and cerebral energetics before and after circulatory arrest.
abstract: The pH-stat strategy compared with the alpha-stat strategy provides more rapid recovery of brain high-energy phosphate stores and intracellular pH after 1 hour of hypothermic circulatory arrest in pigs. Possible mechanisms for this difference are (1) improved oxygen delivery and homogeneity of brain cooling before deep hypothermic circulatory arrest and (2) greater cerebral blood flow and reduced reperfusion injury owing to extracellular acidosis during the rewarming phase. To identify which of these mechanisms is predominant, we studied 49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest. Four groups were defined according to cooling/rewarming strategy: alpha/alpha, alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate levels and intracellular pH were measured by magnetic resonance spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25 animals cerebral blood flow was measured by labeled microspheres, cerebral metabolic rate by oxygen and glucose extraction, and the redox state of cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6). Cerebral blood flow was greater with pH-stat than alpha-stat during cooling (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p < 0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the initial 45 minutes of reperfusion was more rapid in group pH/pH compared with that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in the initial 30 minutes was faster in group pH/pH compared with that in group alpha/alpha (p = 0.026). Intracellular pH became more acidic during early reperfusion only in group alpha/alpha, whereas it showed continuous recovery in the other groups. This study suggests that there are mechanisms in effect during both the cooling and rewarming phases before and after deep hypothermic circulatory arrest that could contribute to an improved cerebral outcome with pH-stat relative to more alkaline strategies.
authors.affiliation: Department of Cardiovascular Surgery, Children's Hospital, Boston, MA 02115, USA.
authors.forename: T
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: T
authors.initials: T
authors.lastname: Miura
authors.forename: J M
authors.initials: JM
authors.lastname: Forbess
authors.forename: A
authors.initials: A
authors.lastname: Du Plessis
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: F
authors.initials: F
authors.lastname: Nomura
authors.forename: D
authors.initials: D
authors.lastname: Holtzman
authors.forename: R A
authors.initials: RA
authors.lastname: Jonas
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D006324:Heart Arrest, Induced; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature
chemical_list: D010710:Phosphates; D000255:Adenosine Triphosphate; D010100:Oxygen