The development of a clinically relevant canine model of postperfusion syndrome.

Investigation into the complex etiology of the postperfusion syndrome (PPS) has been limited by access to only retrospective human case studies, and performance of animal studies that examine biochemical predictors of injury rather than the PPS itself. To determine whether a reproducible canine model of the clinical syndrome was possible, seven dogs underwent cardiopulmonary bypass (CPB) with a bubble oxygenator for 0 (n = 1, sham), 2 (n = 1), 4 (n = 1), and 6 (n = 4) hours. Arterial oxygenation, chest radiographs, serum creatinine, and total leukocyte and platelet counts continued to change through the second postoperative day, illustrating the need for prolonged follow-up (48 hours) to accurately detect postperfusion organ dysfunction. The dogs that did not undergo CPB for 6 hours (n = 3) did not develop important pulmonary dysfunction postoperatively, but three of the four dogs undergoing 6 hours of CPB developed profound, persistent, arterial hypoxemia associated with radiographic, histologic, and hemodynamic evidence of severe PPS. Early evidence of renal dysfunction was also apparent within 84 hours of 6 hour CPB. It is concluded that the canine long duration (6 hour) CPB model, with prolonged (48 hour) postoperative monitoring, generates a reproducible, clinically relevant model of human PPS.

Extended clinical support with an implantable left ventricular assist device.

Clinical evaluations are under way of an intracorporeal (abdominally positioned) pulsatile left ventricular assist device (LVAD) that is capable of providing support for extended periods (greater than 30 days) in patients awaiting heart transplantation. The LVAD, developed by Thermo Cardiosystems Inc. (Woburn, MA), has uniquely textured blood contacting surfaces and requires only minimal antithrombotic therapy. It has been used at the Texas Heart Institute as a bridge to transplantation in 11 patients, including 2 who are currently receiving support. Four patients required extended LVAD support (35-132 days); of those, three are doing well at 1.5, 8.5, and 13 months, respectively, after transplantation, and one died of liver failure 49 days after transplantation. The LVAD was operated in a fixed-rate mode to maintain pump flows at 4-8 L/min, resulting in stabilization of hemodynamic and secondary organ function in all patients. Blood chemistry and hematologic values returned to normal during LVAD support in three of four patients. Postoperative anticoagulation was gradually reduced over the course of the trials. The two most recent patients (35 and 132 days) received only oral dipyridamole (75 mg X 3/day) and aspirin (80 mg/day) after the early recovery period (four-six days), resulting in normal prothrombin and partial thromboplastin times. Plasma hemoglobin levels remained within acceptable limits, and there was no evidence of thromboembolism. Blood contacting surfaces were coated with a thin, adherent, biologically derived lining. The initial results indicate that the intracorporeal LVAD, with textured blood contacting surfaces, can effectively support the failing heart for extended periods (greater than 30 days) with minimal antithrombotic therapy.