David H. Rosenbaum

Perfusion Preservation versus Static Preservation for Cardiac Transplantation: Effects on Myocardial Function and Metabolism

INTRODUCTION Continuous perfusion of donor hearts for transplantation has received increasing interest, but the effects on cellular metabolism, myocyte necrosis, and myocardial edema are not well defined. METHODS Pig hearts were instrumented with sonomicrometry crystals and left ventricular catheters. Left ventricular function was quantified by the pre-load-recruitable stroke work (PRSW) relationship. Hearts were arrested with Celsior solution with 5.5 mM 13C-glucose added, and removed and stored in cold solution (n = 4) or placed in a device providing continuous perfusion of this solution at 10 ml/100 g/min (n = 4). After 4 hours of storage, left atrial samples were frozen, extracted, and analyzed by magnetic resonance spectroscopy. Hearts were then transplanted into recipient pigs and reperfused for 6 hours, with function measured hourly. At the end of the experiment, left ventricular water content and serum creatine kinase-MB isoenzyme levels were measured. RESULTS Baseline left ventricular function was similar in both groups. During reperfusion, the volume-axis intercept of the PRSW relationship was significantly lower in hearts stored with continuous perfusion (p < 0.05), suggesting reduced contractile impairment. Magnetic resonance spectroscopy revealed a decrease in tissue lactate in hearts that received continuous perfusion. Serum creatine kinase-MB isoenzyme levels were higher hearts that had static storage (30.8 +/- 9.0 vs 13.2 +/- 2.7 ng/ml; p < 0.05). Left ventricular water content was similar in both groups (0.797 +/- 0.012 vs 0.796 +/- 0.014; p = 0.45). CONCLUSIONS Donor hearts sustain less functional impairment after storage with continuous perfusion. This technique reduces tissue lactate accumulation and myocardial necrosis without increasing myocardial edema and appears promising as a method to improve results of cardiac transplantation.

Myocardial perfusion characteristics during machine perfusion for heart transplantation.

BACKGROUND Optimal parameters for machine perfusion preservation of hearts prior to transplantation have not been determined. We sought to define regional myocardial perfusion characteristics of a machine perfusion device over a range of conditions in a large animal model. METHODS Dog hearts were connected to a perfusion device (LifeCradle, Organ Transport Systems, Inc, Frisco, TX) and cold perfused at differing flow rates (1) at initial device startup and (2) over the storage interval. Myocardial perfusion was determined by entrapment of colored microspheres. Myocardial oxygen consumption (MVO(2)) was estimated from inflow and outflow oxygen differences. Intra-myocardial lactate was determined by (1)H magnetic resonance spectroscopy. RESULTS MVO(2) and tissue perfusion increased up to flows of 15 mL/100 g/min, and the ratio of epicardial:endocardial perfusion remained near 1:1. Perfusion at lower flow rates and when low rates were applied during startup resulted in decreased capillary flow and greater non-nutrient flow. Increased tissue perfusion correlated with lower myocardial lactate accumulation but greater edema. CONCLUSIONS Myocardial perfusion is influenced by flow rates during device startup and during the preservation interval. Relative declines in nutrient flow at low flow rates may reflect greater aortic insufficiency. These factors may need to be considered in clinical transplant protocols using machine perfusion.

Effects of Antegrade and Retrograde Machine Perfusion Preservation on Cardiac Function After Transplantation in Canines

INTRODUCTION Most studies investigating machine perfusion preservation for heart transplantation perfuse through the aortic root (antegrade), but the coronary sinus (retrograde) is a potential option. We hypothesized that retrograde machine perfusion provides better functional protection than static storage, while avoiding the potential irregular perfusion seen when aortic insufficiency occurs with antegrade perfusion. MATERIALS AND METHODS Eighteen canine donor hearts were arrested, procured, and stored in modified Celsior solution for 4 hours by using either static storage at 0°C to 4°C (n = 6) or machine perfusion preservation at 5°C via the aortic root (antegrade, n = 6) or coronary sinus (retrograde, n = 6). Lactate and myocardial oxygen consumption were measured in perfused hearts. Hearts were reimplanted and reperfused for 6 hours with hourly function calculated by using the preload recruitable stroke work (PRSW) relation. Myocardial water content was determined at the end of the experiment. RESULTS Storage lactate levels and myocardial oxygen consumption were comparable in both perfused groups. The PRSW was increased immediately after bypass in the antegrade group (120.6 ± 19.1 mm Hg) compared with the retrograde (75.0 ± 11.3 mm Hg) and static (78.1 ± 10.5 mm Hg) storage groups (P < .05). At the end of reperfusion, PRSW was higher in the retrograde group (69.8 ± 7.4 mm Hg) compared with the antegrade (40.1 ± 6.8 mm Hg) and static (39.9 ± 10.9 mm Hg) storage groups (P < .05). Myocardial water content was similar among groups. CONCLUSIONS Both antegrade and retrograde perfusion demonstrated excellent functional preservation, at least equivalent to static storage. Initial function was superior in the antegrade group, but the retrograde hearts displayed better function late after reperfusion. Neither perfused group developed significant edema. Machine perfusion preservation is a promising technique for improving results of cardiac transplantation.