G. J. Kontos

Donor core-cooling provides improved static preservation for heart-lung transplantation.

Twenty-three dairy calves underwent heart-lung allotransplantation after donor organs were procured using either donor core-cooling through cardiopulmonary bypass (CPB) or pulmonary artery flush (PAF) to assess which method provides optimal graft preservation. In Groups 1 (control) and 2, donors were cooled to 15 degrees C on CPB and organs were either immediately transplanted (Group 1) or stored in saline solution (4 degrees C) for 4 hours (Group 2) prior to transplantation. In Group 3, donors were pretreated with prostaglandin E1 prior to PAF with modified Euro-Collins solution. Organs were stored in saline solution (4 degrees C) for 4 hours and were then transplanted. Acute cardiopulmonary function following transplantation was assessed by the ratio of end-systolic pressure to end-systolic dimension, extravascular lung water (EVLW), lung compliance, arterial oxygenation, and lung biopsy. Cardiac function after the transplantation procedure was similar in all groups, but EVLW values and lung biopsy scores were worse after PAF. Arterial O2 tension appeared lower after PAF, but not significantly so. Core-cooling provides superior static preservation and thus improved graft function in the acute bovine model.

Effects of cyclosporine on cerebral blood flow and metabolism in dogs.

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000–22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Neurohumoral modulation of the pulmonary vasoconstrictor response in the autoperfused working heart-lung preparation during cardiopulmonary preservation.

Uncontrolled pulmonary hypertension during auto-perfusion of the heart and lungs for preservation has been described, and it may result in extensive pulmonary injury and occasional early failure of the preparation. In order to investigate the neurohumoral mediators of the vasoconstrictor response in the pulmonary circulation of the autoperfused working heart-lung preparation, heart-lung organ blocks were harvested from calves, placed in a normothermic autoperfusion circuit, and studied. Effects of beta-adrenergic stimulation with isoproterenol, nonspecific vasodilatation with nitroglycerin, alpha-adrenergic blockade with phentolamine, phospholipase A2 inhibition with methylprednisolone, cyclooxygenase inhibition with indomethacin, and white blood cell depletion were independently evaluated. Untreated animals, pre-and postexplant, served as controls. Multipoint pulmonary vascular pressure-cardiac output plots were constructed for each animal. An index of pulmonary vascular resistance was obtained from the linear relation: mean pulmonary artery pressure minus pulmonary capillary wedge pressure divided by cardiac output. An intense flow-dependent pulmonary vasoconstrictor response was confirmed to exist in the denervated bovine auto-perfused working heart-lung preparation. Isoproterenol afforded better protection against this response than the other agents studied. White blood cell depletion reduced postexplant pulmonary vasoconstriction, implying that circulating polymorphonuclear leukocytes mediate the response in the autoperfused working heart-lung preparation. White blood cell depletion and the administration of selected pharmacologic agents provide modalities for regulating the pulmonary vasoconstrictor response, and thus may enhance lung preservation in the autoperfusion model.