The Condition of the Rat Myocardium and Isolated Sheep Heart after Prolonged 24-Hour Hypothermic Preservation in a Press
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LEX SYSTEMS BIOPHYSICS
The Condition of the Rat Myocardium and Isolated Sheep Heart after Prolonged 24-Hour Hypothermic Preservation in a Pressurized Carbon Monoxide–Oxygen Gas Mixture E. E. Fesenko, Jr.a, *, E. L. Gagarinskya, A. S. Averina, N. V. Grudininb, A. E. Gurina, N. V. Shishovaa, N. E. Shvirsta, M. V. Goltyaeva, and A. L. Kovtunc aInstitute
of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290 Russia Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow, 123182 Russia c Foundation for Advanced Research, Moscow, 121059 Russia *e-mail: [email protected]
b
Received May 8, 2020; revised May 8, 2020; accepted May 15, 2020
Abstract—High organoprotective properties of a carbon monoxide (CO)–oxygen (O2) gas mixture were confirmed after prolonged (24-h) preservation of the papillary muscle and an isolated rat heart at 4°C. Hypothermic preservation in the high-pressure gas mixture (6 atm) provided efficient restoration of the contractile activity of the isolated rat heart after 24-h storage at 4°C. The isolated retrograde-perfused Langendorff heart performed physically relevant mechanical work, which was similar in duration to that of an intact control heart. Staining with triphenyltetrazolium chloride did not detect infarcted regions in the myocardium. After preservation, the heart tissue was highly capable of performing its function in a test for electrically stimulated contractile activity of papillary muscles. In the test group, The frequency–intensity relationship, the potentiation effect induced by a pause, and the response to stimulation with isoproterenol of test hearts generally corresponded to the parameters of a normal rat myocardium. A sheep heart, which is comparable in size and weight to a human heart, was for the first time successfully preserved using the gas mixture. Normal heartbeat was spontaneously restored after the start of perfusion in all experiments. Histology did not detect a significant difference between test and control sheep hearts. The normal tissue structure of the myocardium was preserved in the test hearts. The 24-h preservation achieved in the study was four times longer than the maximum allowable preservation time of standard static cold storage. The results obtained with the large laboratory animal heart model showed that the hypothermic preservation protocol is promising for prolonged storage of human hearts. Keywords: carbon monoxide, oxygen, gas, organ, transplantation, storage, heart, rat, sheep, preservation, hypothermia DOI: 10.1134/S0006350920040065
INTRODUCTION In spite of the achievements in drug therapy of various diseases, transplantation of organs (the kidney, liver, heart, lung, and pancreas) is still the only treatment that may substantially improve life quality and increase lifespan in certain patients. Approximately 140 000 transplantations are annually performed in the global population [1], including 2200 transplantations in Russia [2]. The number of patients waiting for surgery is four to five times
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