Non Working Beating Heart ” : novo método de proteção miocárdica no transplante cardíaco Non Working Beating Heart : a new strategy of myocardial protection during heart transplant

1. Full Professor at the University of São Paulo Medical School (USP), Head Physician of the Medical Section of Transplantation at Dante Pazzanese Cardiology Institute (IDPC / SP), São Paulo, Brazil. 2. Doctor of Medicine, Cardiovascular Sur geon at the IDPC / SP , Sao Paulo, Brazil. 3. Doctor of Medicine, Cardiologist at the IDPC / SP , Sao Paulo, Brazil. 4. Graduate Student, Cardiologist at the IDPC / SP , Sao Paulo, Brazil. 5. Doctor of Medicine, Immunologist at the IDPC / SP , Sao Paulo, Brazil. 6. PhD in Medicine, Cardiologist at the IDPC / SP , Sao Paulo, Brazil. Jarbas Jakson Dinkhuysen , Carlos Contreras , Reginaldo Cipullo, Marco Aurélio Finger, João Rossi , Ricardo Manrique , Hélio M. Magalhães , Paulo Chaccur 2 Rev Bras Cir Cardiovasc 2011;26(4):630-4 ORIGINAL ARTICLE


INTRODUCTION
The effective myocardial protection is a commitment that lies between two opposite strategies, reducing the metabolic needs by cardiac arrest at low temperatures, and increasing the myocardial temperature during the arrest, to increase the chances of immediate recovery of cardiac function. The crystalloid cardioplegia at 4°C obviously reduces the metabolic needs; however, it is not enough to provide adequate protection [1] and warm reperfusion that provides immediate recovery of cardiac function which reverses protection induced by cold crystalloid cardioplegia [2].
Despite advances in heart transplantation, the lack of donors is still a reality, and, whenever possible, the ideal situation is to capture the graft preferably without long ischemic times. The various protocols of donor organ preservation using hypothermic arrest induced by various crystalloid cardioplegic solutions, however, it is the suboptimal state associated with long ischemic times.
The ischemic damage contributes to the risk of primary graft dysfunction and limits from 4 to 6 hours the safe period between stopping the beating heart donor and recovering the beating already implanted in the receiver. Several studies have been developed to improve results and, in 1991, Lichtenstein et al. [3] introduced the normothermia with a beating heart and other authors [4,5] followed the technique. On the other hand, blood cardioplegia has been suggested as the most appropriate method to preserve the donor heart [6] and continuous infusion with a beating heart extends the time and helps the recovery of the contractile function [7,8].
The hypothesis on this study is that, the earlier coronary reperfusion is performed at normothermia with the recovery of heart rate without the presence of pre-or post-load during the heart transplant, the better the results will be.

METHODS
In the Medical Section of Transplant at IDPC/SP, 288 cardiac transplants were performed in the period from November 1991 to February 2011. In 10 (3.4%) of these transplants, the new methodology was applied in the preservation of the donated organ, called "Non Working Beating Heart", which is to reperfuse the coronary arteries of the graft, restoring and maintaining the beat at normothermia without its pre-and afterload during implantation.
The process of capturing and removal of the donor organ did not change, and after visual examination and palpation of possible modificatoin (atherosclerotic plaques in coronary arteries, palpable thrill, anatomical changes, etc.) cardiectomia is performed after the application of 1000 ml of 4°C crystalloid cardioplegic solution (Celsior ®) in the aortic root, obtaining complete myocardial relaxation. The body is then placed in sterile conditions at 4 ° C for air or ground transportation.
Meanwhile, the compatible receiver is placed in the operating room, monitored and then, the native heart is exposed under general anesthesia with mechanical ventilation using transsternal median thoracotomy. At the time the donor organ arrives in the operating room, extracorporal circulation is installed into the receiver (EC) by aortic and both venae cavae cannulation. After initiation of EC and stabilization through anoxic arrest, the organ is removed, remaining stumps of right and left pulmonary veins, inferior and superior vena cava, pulmonary artery and aorta [9], maintaining the esophageal temperature around 35 ° C. Immediately before anastomosis were started, a new application of 500 ml 4°C Celsior ® solution was made in the ascending aortic graft.
The first suture to be made is the medial half of the left pulmonary vein, followed by aortic anastomosis and, after its completion, the aortic clamping is stopped, reperfusing the coronary arteries of the graft, which spontaneously or after electrical defibrillation, resumes the beats in sinus rhythm, narrow QRS and positive T-wave. Under these conditions, the anastomosis of the pulmonary veins, inferior and superior venae cavae, and, finally, pulmonary artery are concluded, assuming, by the application of a low dose of inotropic drugs, the debt and systemic/pulmonary flow of the receiver.
With stable hemodynamic and metabolic parameters, the EC is interrupted and, after review of hemostasis and mediastinal drainage, the chest is closed in layers and the patient is referred to ICU, using breathing apparatus. In addition to routine monitoring, it is common in our service the installation of the pulmonary artery catheter for continuous control of systolic pressure (PASP), to diagnose and treat right ventricular failure possibly determined by several factors in the postoperative period.
There were no immediate deaths and all patients, both in the operating room and ICU, showed good hemodynamic, metabolic, and electrocardiographic conditions, therefore, the use of inotropic drugs was limited. The ischemia time ranged from 58 to 100 min (mean 68 ± 14 min) and EC was 90 to 140 min (mean 116 ± 19 min). The length of stay in ICU in nine patients ranged from 2 to 5 days (mean 3.4 ± 1.3 days), except one case with neurological damage, which lasted 30 days. The length of stay in the ward ranged from 7 to 36 days (mean 16 ± 10 days), and in two cases (neurological and mediastinitis), were 30 to 36 days. All patients were discharged in good clinical condition.
The late evolution ranged from 20 days to 10 months, with one death occurring 4 months after the transplant due to sepsis.

DISCUSSION
The graft preservation with the purpose of transplantation is a fundamental process due to scientific and technological advances, allowing full evaluation of the organ and its availability and various alternatives for their preservation during ischemia after removal of the donor and implantation in the receiver.
It is clear that invariably tissue damage will occur to a greater or lesser degree in the process of searching, preservation and implantation of the organ [10,11], such that the pathophysiological effects of brain death, hypoxia at the time of removal and transportation, as well as lesions due to ischemia / reperfusion are deleterious factors in the process of heart transplantation.
Taking into account the current preservation techniques, it is considered as a safe ischemia time a period between 4 to 6 hours [9.12] and longer periods are related to primary graft failure, especially if there is association with an inadequate preservation procedure.
The organic viability maintenance during graft preservation is an important prerequisite for good results and, considering the current practice of accepting organs from older, and possibly adjacent donors, the preservation techniques have become more relevant. Many teams use the hypothermic arrest, however, this method was developed when there was ample supply of younger donors and quality of the graft, and currently, with the need to extend the selection criteria, limitations to this methodology can be questioned. Maathuis et al. [13], in an elegant article, draw attention to this scenario with suggestions for new techniques of myocardial protection.
Heart surgery on a beating heart has gained ground in recent times, however, there are few studies to verify its effectiveness. Mo et al. [14] reported good results, expanding this concept little used in the past.
Osaki et al. [15] draw attention to the use of continuous myocardial perfusion for resuscitation of donor hearts, initially with blood cardioplegia at 20 ° C, and after, oxygenated blood at a temperature ranging from 20 ° to 37° C, which somehow is applied to the method described in this study. On the other hand, keeping the heart beating during the graft preservation showed better results when compared to preservation with hypothermia and cardioplegic solution at the University of Wisconsin, extending the preservation time safely and giving surgeons better means of assessing the applicability of this organ and facilitating long distance transport [8].
Within this line of reasoning and assumption of maintaining continuous perfusion of donor heart to keep their beats, a portable apparatus was developed to preserve it and to be used during transport [7], which are monitored contractility, metabolism and vasomotor functions, extending the time preservation and avoiding injury caused by time-dependent ischemia. The potential benefits are many [16,17], since the continuous supply of oxygen and energy substrates facilitate aerobic metabolism, making the application of important hypothermia not viable. Continuous washing of toxic metabolisms occurs, which increases the graft time preservation safely, facilitating logistics, that often seems to be difficult and complex [18,19].
In 1986, we had the opportunity to publish experimental methodology for thoracic organs preservation at normothermia and in physiological conditions called heartlung preparation [20], which included the removal all cardiopulmonary block from the donor, and was kept for up to 11 hours and then transplanted to another animal experimentation, presenting good results. This embodies the concept of keeping the beat at normothermia, and the organ preservation seems to be more consistent than the application of cardioplegic solutions and hypothermia. Brockmann et al. [21] claimed that the organ preservation by normothermic perfusion maintains the physiological pressure-flow parameters, providing more time and success in transplantation, with the possibility of increasing the number of organs donated for transplant.
In experimental research designs, there are several publications [22][23][24][25][26], in which heterotopic heart implant was applied taken from experimental animals and implanted in the abdomen or neck after the suture occlusion of the functions of superior and inferior venae cavae with right atrium and right and left pulmonary veins with the left atrium, in which the aortic graft is end-to-side anastomosed or with the common carotid artery, and the pulmonary artery with the abdominal portion of the inferior vena cava or the jugular, establishing a situation where the beats of the graft are maintained due to coronary perfusion and coronary sinus return directed to the venous system ( Figure 1).
The beats are kept under these conditions, however, without pre or after-load, a process called "non working beating heart", which one of the methods of myocardial protection that is closest related to the normal physiology.
The methodology presented in this work is actually a hybrid process of preservation using hypothermic cardioplegic solution during the removal of the donor organ and transport, and also coronary reperfusion at normothermia with a beating heart without pre-or afterload while the graft implant is being performed into the receiver. The aortic anastomosis is the first one to be made and then the coronary arteries are immediately reperfused at normothermia, recovering its beating early and, these conditions are maintained throughout this procedure, allowing the graft to the possibility of an earlier recovery of contractile function, toxic metabolic elimination and positive interaction with the host, without the need for maintaining the flow and cardiac output, since the EC performs this function.
The results that draw attention for their performance was noted in this small sample (10 cases) by taking full cardiac function with good contractility and demonstrating very satisfactory postoperative parameters, with no evidence of death, low output or other clinical events.