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Neurologic injury as a consequence of cerebral embolism of either air or atherosclerotic debris during cardiac or aortic surgery is still a major cause of postoperative morbidity and mortality. While exploring various means of improving cerebral protection during complex cardiothoracic procedures, we have developed a chronic porcine model to study retrograde cerebral perfusion. We have previously demonstrated that retrograde perfusion results in a small amount of nutritive flow and provides cerebral protection that appears to be superior to simple prolonged hypothermic circulatory arrest. The current study was designed to evaluate the efficacy of retrograde cerebral perfusion in mitigating the effects of particulate cerebral embolism occurring during cardiac surgery. Four groups of pigs (19 to 28 kg) underwent cardiopulmonary bypass with deep hypothermia at an esophageal temperature of 20^oC: an antegrade control group (AC, n = 5), an antegrade embolism group (AE, n = 10), a retrograde control group (RC, n = 5), and a retrograde embolism group (RE, n = 10). In addition, because of extreme heterogeneity in outcome in the initial RE group, an additional group of 10 animals underwent embolism and retrograde perfusion at a later time. Embolization was accomplished by injection of 200 mg of polystyrene microspheres (250 to 750 @mg in diameter) via the aortic cannula into an isolated aortic arch preparation in the AE and RE groups; the control groups received injections of 10 ml of saline solution. After infusion of the microspheres or saline solution, conventional perfusion, with the aortic arch pressure maintained at 50 mm Hg, was continued for a total of 30 minutes in the antegrade groups; in the retrograde groups, retrograde flow was initiated via a cannula positioned in the superior vena cava, and was continued for 25 minutes. Superior vena caval flow was regulated to maintain a sagittal sinus pressure of approximately 30 mm Hg in the retrograde groups, and blood returning to the isolated aortic arch was collected and measured. All animals were allowed to recover and were evaluated daily according to a quantitative behavioral score in which 9 indicates apparently complete normalcy, with lower numbers indicating various degrees of cerebral injury. At the time of planned death on day 6, half of the brain was used for recovery of embolized microspheres after digestion with 10N sodium hydroxide. The other half was submitted for histologic study. Neurologic recovery in both the antegrade and retrograde control groups appeared to be complete, although mild evidence of histologic damage was present in some animals in the retrograde control group. After embolization, unequivocal neurologic injury occurred in both groups, accompanied by significant cerebral histopathologic abnormalities. Although neurologic outcome was not significantly better in the initial RE group as a whole than in the AE group, it was noted that several of the RE animals recovered almost completely after retrograde cerebral perfusion (behavioral scores >7). The animals with good behavioral recovery were noted to have been perfused with markedly lower superior vena caval pressures than those used in animals that sustained severe neurologic injury. An additional 10 animals were therefore subjected to embolization and retrograde perfusion to clarify the impact on outcome of different superior vena caval pressures during retrograde perfusion. When these additional animals are included in the analysis, the behavioral and neuropathologic evidence suggests that use of retrograde cerebral perfusion may attenuate the severity of cerebral injury resulting from particulate emboli when adequate retrograde perfusion can be maintained at low superior vena caval pressures (<40 mm Hg). This observation merits further study. (J THORAC CARDIOVASC SURG 1995;110:1470-85)

Objective: We assessed the impact on histologic and behavioral outcome of an interval of retrograde cerebral perfusion after arterial embolization, comparing retrograde cerebral perfusion with and without inferior vena caval occlusion with continued antegrade perfusion. Methods: Sixty Yorkshire pigs (27 to 30 kg) were randomly assigned to the following groups: antegrade cerebral perfusion control; antegrade cerebral perfusion after embolization; retrograde cerebral perfusion control; retrograde cerebral perfusion after embolization; retrograde cerebral perfusion with inferior vena cava occlusion, retrograde cerebral perfusion with inferior vena cava occlusion control, and retrograde cerebral perfusion with inferior vena cava occlusion after embolization. After cooling to 20^o C, a bolus of 200 mg of polystyrene microspheres 250 to 750 (@mm diameter (or saline solution) was injected into the isolated aortic arch. After 5 minutes of antegrade cerebral perfusion, 25 minutes of antegrade cerebral perfusion, retrograde cerebral perfusion, or retrograde cerebral perfusion with inferior vena cava occlusion was instituted. After the operation, all animals underwent daily assessment of neurologic status until the time of death on day 7. Results: Aortic arch return, cerebral vascular resistance, and oxygen extraction data during retrograde cerebral perfusion showed differences, suggesting that more effective flow occurs during retrograde cerebral perfusion with inferior vena cava occlusion, which also resulted in more pronounced fluid sequestration. Microsphere recovery from the brain revealed significantly fewer emboli after retrograde cerebral perfusion with inferior vena cava occlusion. Behavioral scores showed full recovery in all but one control animal (after retrograde cerebral perfusion with inferior vena cava occlusion) by day 7 but were considerably lower after embolization, with no significant differences between groups. The extent of histopathologic injury was not significantly different among embolized groups. Although no histopathologic lesions were present in either the antegrade cerebral perfusion control group or the retrograde cerebral perfusion control group, mild significant ischemic damage occurred after retrograde cerebral perfusion with inferior vena cava occlusion even in control animals. Conclusions: Although effective washout of particulate emboli from the brain can be achieved with retrograde cerebral perfusion with inferior vena cava occlusion, no advantage of retrograde cerebral perfusion with inferior vena cava occlusion after embolization is seen from behavioral scores, electro- encephalographic recovery, or histopathologic examination; retrograde cerebral perfusion with inferior vena cava occlusion results in greater fluid sequestration and mild histopathologic injury even in control animals. Retrograde cerebral perfusion with inferior vena cava occlusion shows clear promise in the management of embolization, but further refinements must be sought to address its still worrisome potential for harm.(J Thorac Cardiovasc Surg 1998;115:1142-59) J Thorac Cardiovasc Surg 1998;115:1142-59