The heart, similar to every other transplanted solid organ, undergoes a series of nonphysiologic steps during the arrest-procurement-preservation, ischemic-storage-transport, and reimplantation-reperfusion phases of transplantation. The functional recovery of grafted hearts, therefore, depends upon critical attention and manipulation of all of the above three phases of transplantation.
The functional assessment of the transplanted heart has been reported in terms of myocardial adenine nucleotide content (adenylate charge, or high energy phosphate content), myocardial functional measures (ejection fraction, inotrope dependence, compliance, elastance, preload recruitable stroke work, cardiac output, rate-pressure product, oxygen consumption), and histological evidence of cellular and subcellular injury (especially mitochondrial ultrastructure). A curious observation by Belzer et al25 is that the ATP supply of the hypothermic UW preserved liver, pancreas and kidney is completely exhausted by only 4 hours of hypothermic storage, whereas, the heart retains 80% of its ATP level at 18 hours. However, the time limits to human transplantation with UW hypothermic flush-storage techniques are 18-24 hours for kidneys and livers, and only 4-6 hours for hearts. The heart must regain nearly 90% of its function almost immediately upon reperfusion to be life-sustaining, but other organs have several hours or days to regain life-sustaining function. Adenine nucleotide content measured by myocardial biopsy of hypothermic preserved hearts does not reliably predict postoperative graft function at clinically relevant cold ischemic times,26 but does reliably predict the onset of ischemic contracture after prolonged (12-24 hour) hypother-mic storage.25
The heart, unlike the liver or kidney, has a much greater energy demand immediately upon establishment of reperfusion. This energy demand may be damaging to an already energy-depleted myocardium. ATP levels may be depleted sufficiently to cause dysfunctional actin and myosin interaction and ischemic contracture of the myocardium, and yet the level is insufficient to result in cell-membrane dysfunction and death. Ischemic contracture onset coincides with the loss of myocardial ATP stores, such that as ATP drops to less than 80% (between 12-18 hours in hypothermic UW stored rabbit hearts) the onset of contracture occurs.
Single Flush, Intermittent or Continuous Coronary Perfusion As in pulmonary preservation, a single asanguinous perfusate flush followed by static hypothermic storage is an effective, unencumbered method of procuring and preserving the heart in an ischemic, anaerobic, metabolically arrested state. This technique of hypothermic nonperfused storage allows for a maximum safe limit of 4-6 hours of preservation under current clinical practice. Aerobic preservation by continuous perfusion of oxygenated preservative solution27 or blood (autoperfusion)28 easily meets the low, residual oxygen demands of the hypother-mic heart. This can increase the preservation period up to 48 hours but increases the complexity of procurement and risk of infection by many orders of magnitude. Continuous coronary perfusion (or "microperfusion") has been advocated as a method of extending the preservation and storage phases of transplantation from the current limitations of 4-6 hours. The detrimental effects of cellular swelling and interstitial edema from a disturbance in Starling's forces consequent to a continuous perfusion technique tend to offset its beneficial effects.29,30
Intracellular edema occurs from a failure of the ATP-dependent Na+-K+ pump in the sarcolemmal membrane during the anoxic-ischemic interval. The addition of the trisaccharide impermeant raffinose and lactobionate, and the oncotic agent pentafraction to the University of Wisconsin solution add the ability to suppress cellular and interstitial edema during preservation. Unfortunately, hypothermia induces capillary permeability even to high molecular weight colloids. To counteract this, a low perfusion pressure strategy (10-20 mm Hg) low flow strategy of continuous perfusion has been employed.31-33
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