PHENOMENON OF DEMIKHOV. At N.V. Sklifosovsky Institute (1960–1986). Grishka the dog lived with a second, additional heart and transplanted lung without immunosuppression for 142 days (1962)

S. Glyantsev, E. S. Maksimov, M. Gordeeva
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Abstract

On June 20, 1962, at the N.V. Sklifosovsky Research Institute for Emergency Medicine in Moscow, V.P. Demikhov, a biologist, physiologist, and experimental surgeon transplanted a second, additional heart together with the lung through the left thoracotomy access in the fourth intercostal space into the place of the removed two upper lobes of the left lung into the chest to the dog named Grishka. The second heart was implanted in such a way that arterial blood circulated in it and in the transplanted lung. The donor and recipient were selected according to the blood group match. The immediate postoperative period was uneventful. On day 4, the dog became active. On day 12, the sutures were removed from the skin wound. On day 15, antibiotics (penicillin and streptomycin) were discontinued. During the daily examination, general condition and physical activity were noted, rectal temperature, respiratory rate and contractions of one's own and transplanted heart were measured; electrocardiograms were taken from both hearts. On day 13, Grishka gnawed through the electrode, which helped taking the electrocardiograms from the transplanted heart during the first 2 weeks. As a result, in place of the electrode remaining in the chest, the animal developed a fistula with purulent discharge. For this reason, as well as for coughing and wheezing in the lungs on the left, Grishka was periodically administered antibiotics. After the operation and before the withdrawal from the experiment, the dog was injected with heparin. No other pharmaceuticals were given. The dog led an active lifestyle, ate well, and displayed interest in female dogs. The second heart ceased beating 142 days after the operation, on November 8, 1962. Resuscitation measures were unsuccessful. At autopsy, in the right atrial auricle of the transplanted heart, diffuse transmural hemorrhage and a thrombus from the endocardium were revealed, which blocked the blood flow to the heart. The lower lobe of Grishka's lung was in a state of hepatization. Signs of edema and inflammation were observed in the transplanted lung. There were no blood clots at the sites of vascular anastomoses. There were no visual signs of rejection. The results of histological studies are not known. This article for the first time introduced into scientific circulation an operation protocol, a diary of postoperative management and an autopsy protocol for an animal that had lived with a second, additional heart and a transplanted lung without immunosuppression for 142 days, which has been a unique observation in world transplantology. Despite the long-term survival of the animal, nursing the recipient dog in the postoperative period did not meet the complexity of the operation performed, which allows us to conclude that it was impossible at that time to implement the results obtained in the experiment into clinical heart transplantation in humans.
德米霍夫现象。在N.V. Sklifosovsky研究所(1960-1986)。狗狗Grishka在没有免疫抑制的情况下,带着第二颗心脏和移植的肺生活了142天(1962)。
1962年6月20日,在莫斯科的N.V. Sklifosovsky急救医学研究所,生物学家、生理学家和实验外科医生V.P. Demikhov通过第四肋间隙的左开胸通道,将第二颗额外的心脏和肺一起移植到左肺两个上叶切除的地方,并将其移植到名为Grishka的狗的胸部。第二颗心脏的植入方式是动脉血在它和移植的肺中循环。根据血型匹配选择供体和受体。术后即刻无大碍。第四天,狗变得活跃起来。第12天,从皮肤伤口上取下缝合线。第15天停用抗生素(青霉素和链霉素)。在日常检查中,记录一般情况和身体活动,测量自身和移植心脏的直肠温度、呼吸频率和收缩;取了两颗心脏的心电图。第13天,Grishka啃断电极,这有助于获取移植心脏前两周的心电图。结果,在电极留在胸部的地方,动物出现了一个带脓性分泌物的瘘管。由于这个原因,加上左肺咳嗽和喘息,格里什卡定期服用抗生素。手术后和退出实验前,给狗注射肝素。没有其他药物。这只狗过着积极的生活方式,吃得很好,并对雌性狗表现出兴趣。第二颗心脏在手术142天后,1962年11月8日停止了跳动。复苏措施未成功。尸检时,移植心脏右心房发现弥漫性经壁出血和心内膜血栓,阻断了血液流向心脏。格里什卡的肺下叶呈肝化状态。移植肺有水肿、炎症征象。血管吻合处未见血凝块。没有明显的排斥迹象。组织学研究的结果尚不清楚。本文首次在科学循环中介绍了一种动物的手术方案、术后管理日记和解剖方案,该动物在没有免疫抑制的情况下生活了142天的第二颗心脏和移植的肺,这在世界移植学界是独一无二的。尽管动物长期存活,但术后对受体犬的护理并不符合手术的复杂性,这使得我们得出结论,当时不可能将实验所得的结果应用于临床人类心脏移植。
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