The success of organ transplantation is critically dependent on the quality of the donor organ. Donor organ quality, in turn, is determined by a variety of factors including donor age and preexisting disease, the mechanism of brain death, donor management prior to organ procurement, the duration of hypothermic storage, and the circumstances of reperfusion. It has been recognized for some time that both the short- and long-term outcomes after cadaveric organ transplantation are significantly inferior to those obtained when the transplanted organ is obtained from a living donor, regardless of whether the donor is related or unrelated to the recipient. Brain death results in a series of hemodynamic, neurohormonal, and pro-inflammatory perturbations, all of which are thought to contribute to donor organ dysfunction. The process of transplantation exposes the donor organ to an obligatory period of ischemia and reperfusion. Traditionally, hypothermic storage of the donor organ has been used to protect it from ischemic injury, but donor organs differ markedly in their capacity to withstand hypothermic ischemia. Data from the Registry of the International Society for Heart and Lung Transplantation indicate that the risk of primary graft failure and death rises dramatically for both the heart and lung as ischemic time increases. Based on these data, maximum recommended ischemic times for the donor heart and lung are 6 and 8 h, respectively. In this chapter, strategies aimed at minimizing the adverse consequences of brain death and ischemia/reperfusion injury to the donor heart and lung are discussed. These strategies are likely to become increasingly important as the reliance on marginal donors increases to meet the growing demand for organ transplantation.
Sodium-hydrogen exchange inhibitors, such as cariporide, are potent cardioprotective agents, however, safety concerns have been raised about intravenously (i.v.) administered cariporide in humans. The aim of this study was to develop a preservation strategy that maintained cariporide's cardioprotective efficacy during heart transplantation while minimizing recipient exposure. We utilized a porcine model of orthotopic heart transplantation that incorporated donor brain death and 14 h static heart storage. Five groups were studied: control (CON), hearts stored in Celsior; CAR1, hearts stored in Celsior with donors and recipients receiving cariporide (2 mg/kg i.v.) prior to explantation and reperfusion, respectively; CAR2, hearts stored in Celsior supplemented with cariporide (10 lmol/L); GTN, hearts stored in Celsior supplemented with glyceryl trinitrate (GTN) (100 mg/L); and COMB, hearts stored in Celsior supplemented with cariporide (10 lmol/L) plus GTN (100 mg/L). A total of 5/5 CAR1 and 5/6 COMB recipients were weaned from cardiopulmonary bypass compared with 1/5 CON, 1/5 CAR2 and 0/5 GTN animals (p = 0.001). Hearts from the CAR1 and COMB groups demonstrated similar cardiac function and troponin release after transplantation. Supplementation of Celsior with cariporide plus GTN provided superior donor heart preservation to supplementation with either agent alone and equivalent preservation to that observed with systemic administration of cariporide to the donor and recipient.
We compared the effects of hormone resuscitation (HR) with a norepinephrine-based protocol on cardiac function, hemodynamics and need for vasopressor support after brain death in a porcine model. Following brain death induction, animals were treated with norepinephrine and fluids for 3 h. In the following 3 h, they continued on norepinephrine and fluids (control) or received additional HR (triiodothyronine, methylprednisolone, vasopressin, insulin). Data were collected pre-brain death, 3 and 6 h post-brain death. At 6 h, median norepinephrine use was higher in controls (0.563 vs. 0 lg/kg/min; p < 0.005), with 6/8 HR animals weaned off norepinephrine compared with 0/9 controls. Mean arterial pressure was higher in HR animals at 6 h (74 ± 17 vs. 54 ± 14 mmHg; p < 0.05). Cardiac contractility was also significantly higher in HR animals at 6 h (stroke work index 1.777 vs. 1.494). After collection of 6 h data, all animals were placed on the same low dose of norepinephrine. At 6.25 h, HR animals had higher stroke work (3540 ± 1083 vs. 1536 ± 702 mL.mmHg; p < 0.005), stroke volume (37.2 ± 8.2 vs. 21.5 ± 9.8 mL; p < 0.01) and cardiac output (5.8 ± 1.4 vs. 3.2 ± 1.2 L/min; p < 0.005). HR in a porcine model of brain death reduces norepinephrine requirements, and improves hemodynamics and cardiac function. These results support the use of HR in the management of the brain-dead donor.
A floating giant aortic thrombus is a rare finding in the absence of any coagulation disorder. Patients usually remain asymptomatic until the development of embolic complications. Our report highlights cocaine abuse as a potential cause of aortic thrombus and bowel perforation. Clinicians should have a high index of suspicion when treating patients with a history of illicit cocaine use with signs and symptoms of arterial ischemia. The risks of cardiovascular and abdominal complications related to cocaine use should not be underestimated. Prompt diagnosis is required to circumvent potentially life-threatening complications.
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