In Reply:-Undar et al. point out two differences in cardiopulmonary bypass protocols between our laboratory study [1]and current clinical practice. Arterial pressure during deep hypothermic cardiopulmonary bypass was high in our piglets compared with human neonates. There are several physiologic reasons for this. Normal arterial pressure in newborn pigs is higher than in newborn humans, and the hemodynamic response to deep hypothermic cardiopulmonary bypass in healthy piglets is robust compared with human newborns with cardiac disease. In addition, our cardiopulmonary bypass cooling protocol held flow rate constant, whereas some clinical protocols decrease flow rate. [2]During cardiopulmonary bypass cooling arterial pressure follows flow rate. Thus, the higher flow rates at deep hypothermia yielded higher arterial pressures in our piglets. Bubble oxygenators were used in our study rather than membrane oxygenators. The newborn pig has a small blood volume, necessitating blood in the pump prime. Obtaining allogeneic blood for pigs is problematic (e.g., no blood bank). Bubble oxygenators are advantageous in our model because they require less priming volume and, therefore, less blood prime. Although low-prime membrane oxygenators are commercially available, the cost is prohibitive for laboratory studies.
The bubble-versus-membrane oxygenator raises an important question. Is brain damage associated with neonatal heart surgery related to microemboli? Several lines of evidence indicate the damage is not from emboli (in contrast to adult heart surgery). First, microemboli are uncommon during pediatric heart surgery. [3]Second, the histopathologic features of brain damage in neonates are not consistent with microemboli. [4]Third, pH-stat improves neurologic outcome compared with alpha-stat, [5]even though pH-stat increases cerebral blood flow and embolic load. [1]If not microemboli, what might be the cause of brain damage in neonates? Brain damage appears to result from selective vulnerability of neurons and oligodendrocytes in certain regions to cellular hypoxia. [4]Why these cells are vulnerable remains uncertain, but seems to involve the activation of enzymes and genes associated with cellular suicide (apoptosis). [6]pH-Stat may confer protection, in part, by inhibiting apoptosis.
C. Dean Kurth, M.D.
Associate Professor
Maureen M. O'Rourke, M.D.
Assistant Professor
Irene B. O'Hara, M.D.
Assistant Professor; Brain Research Laboratory; Department of Anesthesiology/Critical Care Medicine; Children's Hospital of Philadelphia; Philadelphia, Pennsylvania; Department of Anesthesia and Pediatrics; University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania
(Accepted for publication November 17, 1998.)
