| Background and ObjectiveOrgan transplantation technology is one of the most important inventions in the 20 th century. On the patients with end-stage heart disease, heart transplantation has been performed world-widely for more than fifty years. With the improvement of surgical technique, postoperative care, cardiac assistive technology and the application of new immunosuppressive drugs, postoperative survival rate was significantly increased in the past half century. Heart transplantation is the most effective treatment for end stage heart disease and has been widely accepted and applied throughout the world. Around 4500 heart transplantations was performed each year world widely. Patients after heart transplantation lived for 11 years on average according to the data provide by the International Society for Heart and Lung Transplantation. But at the same time, the serious shortage of donor heart has become the biggest challenge for clinical heart transplantation. Patients are dying on the waiting list before they get matched heart.Currently, almost all the hearts donors are brain death young patients. It is called donation of after brain death(DBD). To expand the donation, the concept of Donation after circulatory death( DCD) was established in the 1960 s. In fact, the first successful human-to-human heart transplantation was performed in December 3 1967 by Dr. Christiaan Barnard at the Groote Schuur Hospital in Cape Town, South Africa was from a DCD donor. The patient died 18 days after surgery. A year later, Dr. Barnard performed his second heart transplantation. The patient survived for one year after surgery. Donation after cardiac death has been used since 1970 s. Tissue donation has always been possible for non-heart beating donors, and many centers now have established programs for kidney transplants from such donors. A few centers have also moved into DCD liver and lung transplants. But only a few heart transplantations have been done with a heart from a DCD donor so far. A large number of animal experiments confirmed that DCD could provide additional sources to ease the imbalance between supply and demand. But use of DCD heart is still in controversy, because of the physiological characteristics of cardiac metabolism and hypoxia tolerance and unavoidable injury during DCD. But the effect of DCD on the coronary endothelium is still unclear. The integrity of the structure and function of the vascular endothelium of coronary artery is one of the key factors that influence the long-term curative effect of the patients underwent heart transplantation. If the coronary artery blood vessel endothelium is damaged, it may lead to the increase of capillary permeability, myocardial edema, microcirculation perfusion, and even the phenomenon of no reflow phenomenon, increasing coronary resistance, decreasing blood flow and the occurrence of early cardiac dysfunction. Cardiac dysfunction will be occurred in the early stage after operation and heart graft vascular damage in longterm. This study was to investigate the effect on the muscular and endothelial function of the heart coronary artery endothelial cells in 20 minutes of heart ischemia induced by hypoxia, and to provide the relevant evidence for the clinical practice of DCD. Materials and Methods18 healthy Swedish domesticate pigs were randomized into 3 groups, control group, DCD group and DCD followed with cold preservation group(6 pigs in each group). Lidocaine was given intravenously to prevent arrthythmia. The heart was exposed with sternotomy. Heparin(300IU/kg) was given intravenously. The heart was inspected for visual abnormalities. For the animals of DCD group and DCD followed with cold preservation group, muscle relaxation drug rocuronium was given intravenously to stop spontaneous breath. Ventilation was ceased and the endotracheal tube was clamped. At the same time, timer was started to control circulatory arrest time. The lungs were inspected to confirm the absence of spontaneous breathing. The heart was left untouched for strict predetermined periods of warm ischemia irrespective of circulatory cessation times. 20 minutes after ventilation off, the left anterior descending coronary artery of DCD group heart was dissected and transferred into organ bath immediately. For the heart of DCD followed with cold preservation group, Y shape cardiolpegic pin was inserted into the aortic root. St. Thomas solution was used to flush the heart with a pressure of 40 mm Hg. The heart was deflated by cutting off superior vena cava, inferior vena cava and pulmonary veins. The heart was dissected and stored within cold St. Thomas solution for 4 hours. Then the left anterior descending coronary artery was dissected and transferred into organ bath immediately. For the control group, ventricular fibrillation was induced with a 9 volts alkaline battery. Left anterior descending coronary artery was dissected and investigated in organ bath immediately. U-46619 and substance P were used to evaluate the contraction of coronary smooth muscle and endothelium dependent relaxation. ResultsThe maximum coronary endothelium-dependent relaxation(EDRmax) were(91.48±4.04) % in fresh group,(91.12±9.39) % in DCD group,(86.51±8.31) % in DCD+4 hours static storage group(P>0.05). The minus logarithmic of substance concentration induced 50%maximal relaxation(p EC50)were 6.22±0.12、6.13±0.15、6.20±0.11(P>0.05) separately. EDRmax and p EC50 had no significant difference among three groups. When the segements achieved base line,its diameter which is(1.29 ± 0.08)mm、( 1.26 ± 0.09) mm 和(1.27 ± 0.10)mm(P>0.05), The diameter has no significant difference among three groups. ConclusionEDRmax and p EC50 had no significant difference among three groups. 20 minutes warm ischemia with/without 4 hours cold static storage will not significantly impair coronary artery endothelium function. |
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