A rabbit model of the brain and cardiopulmonary bypass: the bunny that just keeps going and going and going...

Abstract

Accepted for publication November 19, 1997.Associate Professor, Head, Section on Cardiothoracic Anesthesia, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157–1009.atrogers@bgsm.eduIN this issue of Anesthesiology, Hindman et al. [1]present the latest in their series of experiments that use a rabbit model of cardiopulmonary bypass (CPB). Beginning in 1990, [2]this group meticulously defined relationships among such CPB variables as cerebral blood flow, acid-base management, arterial blood pressure, systemic temperature, and brain cooling. They posed questions that are difficult or impossible to address clinically, clarifying the cerebrovascular physiology of CPB. Subsequently, they developed a robust experimental model of cerebral arterial air embolism (CAAE), [3]using somatosensory-evoked potential (SSEP) measurements as the dependent variable. The extent of SSEP suppression after CAAE is dose-dependent, a finding supported by clinical studies in which neuropsychologic function was the primary measure. [4]A mere 50 micro liter/kg of air injected into the internal carotid artery of a rabbit is followed by abolition of SSEP signals. In a 70-kg adult, this translates into just 3.5 ml of air, emphasizing the potential for catastrophe after a paradoxical embolism.The next chapter in this tale required a 24-h survival study, an arduous undertaking. Dr. Hindman's team showed that SSEP recovery after CAAE correlated with neurologic findings in postoperative animals, i.e., poor SSEP recovery predicted significant impairment. [5]Thus, SSEP measurements are an appropriate surrogate measure of neurologic outcomes. More recently, this group reported that heparin pretreatment has a protective effect in rabbits studied with normal circulation, improving SSEP recovery after CAAE compared with nonheparinized animals. [6]This may be a result of an anti-inflammatory property of heparin that inhibits neutrophil adhesion to injured vascular endothelium. Clearly, the next question was whether this neuroprotective action extended to CPB conditions.In the current study, [1]the authors asked whether CPB with heparinization increased or decreased brain injury from CAAE as compared with the normal circulation. This question is important because bubbles are present in the systemic circulation of nearly all children [7]and adults [8]undergoing CPB. Of course, examining CPB animals without administering heparin is not an option because we lack alternative drugs with comparable anticoagulant efficacy.Several aspects of this study design yielded information worth noting. For example, in sham animals receiving saline injection rather than CAAE, 90 min of CPB conducted with scrupulous avoidance of intravascular air was associated with complete stability of SSEP signals. This suggests that CPB, per se, is not an insult to the brain. In the experimental groups, at 30 and 60 min after CAAE, SSEP recovery was much worse in heparinized CPB animals than in nonheparinized non-CPB animals, i.e., those with normal circulation. Ninety minutes after CAAE, SSEP recovery between CPB and non-CPB groups was not significantly different (24 +/- 19% vs. 39 +/- 24%, respectively; P = 0.146). The authors conclude that, overall, CPB had an adverse impact on SSEP recovery after CAAE, even though CPB animals were heparinized. Thus, although (1) stable CPB is not detrimental to SSEP signals and (2) heparin provides brain protection after CAAE with normal circulation, heparin did not modify CAAE-induced injury during CPB.At first glance, these results are disappointing, yet not really surprising. Those of us who have labored to solve the mysteries of CPB-related brain injury know that nothing is so straightforward. This report represents just one step in a sequence that will ultimately make CPB a safer experience for our cardiac surgical patients. Dr. Hindman and his research group have contributed greatly to this endeavor by developing a valid small-animal model of brain injury with an appropriately tested outcome measure and hopefully will continue with this work.Anne T. Rogers, M.B.Ch.B., F.R.C.P.C.Associate Professor; Head, Section on Cardiothoracic Anesthesia; Department of Anesthesiology; Wake Forest University School of Medicine; Medical Center Boulevard; Winston-Salem, North Carolina 27157–1009atrogers@bgsm.edu