Normothermic Extracorporeal Perfusion as a Method of Donor Heart Conditioning in Experiment

INTRODUCTION: Extracorporeal perfusion of transplants is a promising area that is actively studied to eliminate the existing shortage of donor organs. However, the optimal parameters and duration of extracorporeal perfusion that would not lead to impairment of the morphofunctional condition of transplants, have not been sufficiently studied.

AIM: To present the results of development and experimental testing of an original device for perfusion preservation of an isolated heart on the biomodel.

MATERIALS AND METHODS: An original perfusion device for preserving donor hearts has been developed and experimentally tested on mature outbred male rats. During 15-hour normothermic extracorporeal perfusion of the heart in the proposed device, its rhythmic and contractile function, temperature, pH of the perfusate, pressure in the aorta, hematocrit, рО₂ and рСО₂ in the perfusate were studied, the content of glucose, lactate, and creatine phosphokinase (CPK) activity in perfusate samples were determined.

RESULTS: During perfusion of isolated hearts, sinus rhythm was observed at a sufficient rate. Perfusate pH stayed within 7.3–7.4. Hearts were perfused at constant pressure in the aorta of 70 mm Hg in normothermic conditions (t=37°С). After stabilization of the heart function, the systolic pressure in the left ventricle was 96.0 [93.7; 98.5] mm Hg and remained without significant changes during 12 hours of perfusion; at 15 hours of perfusion, the parameter decreased by 15.0% to 82.0 [79.5; 84.2] mm Hg, p=0.01208. After stabilization of the heart function, diastolic pressure in the left ventricle was 4.0 [3.0; 5.0] mm Hg and remained without significant changes during 12 hours of perfusion; by 15 hours of perfusion, it increased 1.5 times to 6.0 [5.0; 7.0] mm Hg, p=0.0164. During the experiment, biochemical markers in the perfusate after 30 min of perfusion and stabilization were at the level of physiological values without significant dynamics within 12 hours of perfusion: glucose consumption was 80.5 [70.2; 85.5] μmol/(kg×min×mm Hg); lactate excretion — 35.7 [32.5; 44.2] μmol/(kg×min×mm Hg); CPK leakage — 95.8 [93.7; 111.3] IU/l. After 15 hours of perfusion, the level of glucose consumption by isolated hearts per unit of performed function increased significantly to 136.8 [130.5; 145.7] μmol/(kg×min×mm Hg), p=0.01208; lactate excretion and CPK leakage into the perfusate increased to 58.2 [55.7; 67.4] μmol/(kg×min×mm Hg), p=0.02144, and 229.7 [215.8; 242.4] IU/L respectively, p=0.01208.

CONCLUSION: The study showed that extracorporeal perfusion of the heart in the developed device allows maintaining its viability for 12 hours in conditions maximally close to physiological ones, and also conducting dynamic assessment of the functional and metabolic state of the organ.