Heart transplantation cardiac donors

Artificial Hearts. Congestive heart failure (CHF) is a common cause of disabiHty and death. It is estimated that three to four million Americans suffer from this condition. Medical therapy in the form of inotropic agents, diuretics (qv), and vasofilators is commonly used to treat this disorder (see Cardiovascularagents). Cardiac transplantation has become the treatment of choice for medically intractable CHF. Although the results of heart transplantation are impressive, the number of patients who might benefit far exceeds the number of potential donors. Long-term circulatory support systems may become an alternative to transplantation (5). 

This concept has enormous implications in the setting of cardiac surgery and heart transplantation [11-13]. Conditions of ischemia and reperfusion are created routinely by the surgeon during open heart procedures, i.e., cardiopulmonary bypass and aortic cross-clamping [11,12], Similar conditions prevail during heart transplantation when the ischemic donor heart is rapidly reoxygenated by the recipient s blood [14]. 

Moreover, cardiac muscle cannot replicate and regenerate by itself after injury [131, 132], Heart transplantation is a treatment option for end-stage heart failure, but it has endured a slow and somewhat troubled evolution to transform itself into a more validated and useful therapy for patients, mainly because of the limited availability of donor organs and potential complications involved in its use [133]. Stem cell therapy and TE might solve the problem of how to treat thousands of patients who survive myocardial infarction and heart failure. 

Treatment strategies for progressive pulmonary venous hypertension should focus on treatment of the underlying disease. For patients with advanced decompensated systolic heart failure and secondary pulmonary hypertension, it is essential to reduce the pulmonary vascular resistance prior to heart transplantation to prevent acute RV failure of the donor heart. The use of continuous milrinone, occasionally nesirit-ide, and earlier intervention with mechanical circulatory device support (19) as a bridge to cardiac transplantation is considered a standard approach for this group of patients. Earlier intervention with valve repair or replacement for patients with mitral valve disease and aortic valve disease with associated pulmonary hypertension is recommended. 

Cardiac transplantation is the ultimate therapeutic option in end-stage CHF. Orthotopic cardiac transplantation is the surgical technique of choice, whereas heterotopic cardiac transplantation is performed primarily when there is high resistance in the pulmonary circulation of the recipient (and a heart-lung transplantation is impossible), the donor heart is too small, or in selected cases with acute but potentially reversible heart failure. In orthotopic transplantation the donor heart is joined to the recipients atria, aorta, and pulmonary artery. In heterotopic transplantation, the donor heart is implanted into the right thoracic cavity and anastomosed with the recipient s heart in a complex maimer in such a way that the donor heart takes over most of left ventricular output, while the recipient s heart continues to ensure right ventricular output. 

While the number of medical centers performing cardiac transplantation continues to grow, the shortage of donor hearts continues to limit the availability of this type of surgery particularly in the US, where only 2000-2700 procedures a year are performed (Massad 2004 Poston and Griffith 2004 Winkel et al. 1999). Worldwide, an estimated 4000 cardiac transplantations are performed annually (Taylor et al. 2004). As of May 2004,66,000 heart transplantations have been reported to the International Society for Heart and Lung Transplantation (Hosenpud et al. 1999 Taylor et al. 2004). 

More specifically in heart transplant recipients, bleeding, leaks, and frank rupture can occur at the anastomosis sites the most critical of which is the aortic anastomosis, particularly if there is a marked difference in diameter between the donor and recipient aorta (Knisely et al. 1999 Reitz et al. 1982) (Fig. 2.2.3). In addition, acute or chronic breakdown at the aortic anastomosis can lead to aortic dehiscence, dissection, and pseudoaneurysm formation (Henry et al. 1989 Knollmann et al. 2000a Knosalla et al. 1996). Pseudoaneurysms can also form at two additional sites in the cardiac transplant patient at the cannulation sites used for cardiopulmonary bypass and at the endomyocardial biopsy sites in the right ventricle, taken to look for rejection (Knisely et al. 1999). Although most of these complications occur in the immediate post-operative period, some can occur months to years later (Knisely et al. 1999). Aortic dissection, when it occurs in the heart transplant patient (l%-2%), usually involves the recipient s native aorta, although rare cases of dissection involving the donor s aorta have been reported (ScHELLEMANS et al. 2004). Dissection can occur in the immediate peri-operative period usually due to mismatches in donor-recipient vessel size or years later when they may he due to infection or accelerated atherosclerosis (Schellemans et al. 2004). 

Potential cardiovascular therapeutic uses for PFC emulsions, other than CPB, include treatment of acute myocardial infarction, cardioplegia, reperfusion, coronary angioplasty and preservation of donor hearts for transplantation. High 02-delivery capacity, small particle sizes, and low viscosity may improve tissue perfusion and oxygenation. Treatment of cardiac arrest is also being explored. 

Elevated pulmonary vascular resistance is a risk factor prior to cardiac transplantation which is manifested by an increased risk of right ventricular failure postoperatively. " Nevertheless, patients with left atrial hypertension may have a reversible component to their pulmonary hypertension if the underlying cause can be relieved. Therefore, assessment of the degree of pulmonary vasoconstriction assumes importance prior to transplantation. The limited number of donor organs dictates that accurate assessment of pulmonary vascular disease be made in order to limit combined heart-lung transplantation and ensure more effective use of scarce resources. 

If there is dear evidence of worsening prompt hospital admission for intensive therapy is necessary. As the availability of a suitable donor heart is not predictable, hemodynamic deterioration is first treated with intravenous inotropic support. When the low-cardiac-output syndrome continues to be refractory, patients are put on a mechanical circulatory device for temporary mechanical support. This bridge to transplantation concept enables patient stabilization, withdrawal of intravenous medication (inotropic agents, catecholamines, calcium sensitizers) and rehabilitation (Antretter et al. 2002a). During chronic mechanical circulatory support a low level of exercise is possible and the patients are able to walk around, to leave hospital and sometimes they are followed up by heart failure specialists in an outpatient clinic. Nearly 25% of the most recent cohort transplanted from 1 January, 2001 to 30 June, 2003 were on some type of mechanical circulatory support (Taylor et al. 2004). 

The upper age limit of donors varies between transplant centers the older the donor the more extensive the evaluation that is needed. Most centers have an upper age limit of 55 years although some centers have extended this to 65 years of age (Kirklin et al. 2002b). In special cases it is important that donor age is not viewed in absolute terms, but considered along with other important variables such as donor cardiac dysfunction, projected ischemia time, and the recipient s clinical condition. The risk of early mortality after HTX from donors older than 40 years is increased nearly threefold and is multifactorial in nature (Lietz et al. 2004). The use of older donor hearts is associated with an increase in the incidence of transplant vasculopathy at 1 year. 

The operative cardiac transplant technique is nearly the same as described above adapted to the underlying congenital disease. In hypoplastic left heart syndrome hypothermic circulatory arrest is necessary to enable the aortic anastomosis and reconstruction of the aortic arch using donor tissue. 

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