Cerebral blood flow response to Pa(CO₂) during hypothermic cardiopulmonary bypass in rabbits

Differences in cerebral blood flow (CBF) between alpha-stat and pH-stat management depend on preserved responsiveness of the cerebral vasculature to changes in arterial carbon dioxide tension (Pa(CO₂)). We tested the hypothesis that hypothermia-induced reductions in CBF would decrease the CBF response to changing Pa(CO₂) (ΔCBF/ΔPa(CO₂)). Anesthetized New Zealand white rabbits were randomly assigned to one of three temperature groups-group 1 (37° C, n = 9); group 2 (31° C, n = 10); or group 3 (25° C, n = 10)-and were cooled using cardiopulmonary bypass. After esophageal temperature equilibration (~ 40 min), oxygenator gas flows were serially varied to achieve Pa(CO₂) values of 20, 40, and 60 mmHg (temperature-corrected). All animals were studied at all three Pa(CO₂) levels in random order. At each level of Pa(CO₂), CBF and masseter blood flow were determined using radiolabeled microspheres. There were no significant differences between groups with respect to mean arterial pressure (~ 80 mmHg), central venous pressure (~ 4 mmHg), or hematocrit (~ 22%). Prior normothermic studies have found ΔCBF/ΔPa(CO₂) to be proportional to CBF. Nevertheless, in this study, with hypothermia-induced reductions in CBF, ΔCBF/ΔPa(CO₂) was not significantly different between temperature groups. Thus, hypothermia either increased the sensitivity of the cerebral vasculature to carbon dioxide and/or increased the effective level of cerebrospinal fluid respiratory acidosis produced by each increment of temperature-corrected Pa(CO₂). This latter possibility is consistent with 'alpha-stat' acid-base theory, wherein such increments of actual (temperature-corrected) Pa(CO₂) would produce increasing degrees of 'respiratory acidosis' (measured at 37° C) with progressive hypothermia. When we compared ΔCBF/ΔPa(CO₂) between temperature groups using Pa(CO₂) values measured at 37° C, we found that ΔCBF/ΔPa(CO₂) did decrease with hypothermia-induced reductions in CBF. Over the Pa(CO₂) range of 40-60 mmHg (measured at 37° C), ΔCBF/ΔPa(CO₂) equalled 0.97 ± 0.60 ml · 100 g^-1 · mmHg^-1 at 37° C versus 0.54 ± 0.23 ml · 100 g^-1 · min^-1 · mmHg^-1 at 25° C, (P = 0.02). These findings suggest that the CBF response to changes in Pa(CO₂) is sensitive to variations around electrochemical neutrality and not to absolute levels of Pa(CO₂). Although hypothermia lead to marked reductions in CBF, extracranial blood flow (in the masseter muscle) was little affected. This alteration of intracranial/extracranial flow distribution could lead to underestimation of CBF with xenon clearance methods used during hypothermic cardiopulmonary bypass, if the detection systems used overlie extracranial muscle.