Heart
Heart preservation has employed simple static cold storage. As 85 per cent of the energy consumed by the heart fuels contraction of the myofibrils, cardioplegic arrest has been an essential feature of heart preservation. The development of heart transplantation from open heart surgery had a considerable influence on the strategies applied in heart preservation. Cardioplegic solutions developed for cardiac surgery provided safe preservation of myocardial function for only 5 to 6 h.
For transplantation, the heart is excised after induction of hypothermic cardioplegic arrest by in-situ flush with one of several standard cardioplegic solutions. The graft is then stored cold in the flush-out solution or in EuroCollins solution. Sinus node dysfunction (usually transient) is common after transplantation and is related to the duration of ischaemia. Microvascular injury has been reported in the presence of well-preserved myocytes.
Flushing solutions commonly used for the preservation of other organs are also cardioplegic, but generally contain much higher concentrations of potassium (over 100 mmol/l instead of 20 to 30 mmol/l) and do not contain any calcium. Initial reluctance to apply such solutions to heart preservation stems from earlier studies indicating that potassium-induced contraction band necrosis occurred with potassium concentrations above 40 mmol/l, and that a ‘calcium paradox’ effect in cardiac preservation was important (cardiac muscle incubated in calcium-free medium undergoes severe irreversible damage when reperfused with calcium-containing medium due to a massive influx of calcium). Warm ischaemic damage enhances calcium influx. The occurrence of the calcium paradox during hypothermia is controversial; but removal of calcium from St Thomas's solution has been shown to be detrimental, and the calcium paradox phenomenon has been seen in experimental cardiopulmonary bypass.
Recently, modifications of UW solution have been used clinically in open heart surgery and for transplantation, and in experimental studies. The range of available experimental models include heterotopic transplants to the abdomen or neck in small animals, isolated perfused working heart models, metabolic tissue analysis and histology, nuclear magnetic resonance spectroscopy, and allograft function in larger animals. Specimens of human atrial myocardium can be obtained for study during open heart surgery. Successful orthotopic transplants have been reported after 12 h of preservation with UW solution in primates, and clinical trials with UW solution have given superior donor heart preservation over that obtained by Stanford and other solutions.
Maintenance of high energy phosphate levels (ATP and creatine phosphate) has been another goal, but no linear correlation exists between the concentration of adenine nucleotides in preserved heart and the functional outcome. When the level of these high energy compounds falls below a certain level no functional recovery occurs, but inadequate preservation may occur at normal levels. Addition of ATP or its precursors to preserving solutions can improve cardiac function, but this does not correlate with maintenance of tissue ATP levels and may have been due to the vasodilatory properties of the additives.
Generation of oxygen free radicals has been implicated in ischaemic heart disease and in reperfusion injury. Metabolic inhibitors and free radical scavengers have been used to pretreat the donor and as additions to the preserving solution. Improvements in left ventricular function, lipid peroxidation, and platelet aggregation have been demonstrated. Prostacyclins also dilate coronary vessels, inhibit platelet aggregation, and stabilize lysosomal membranes. A stable prostacyclin analogue added to the cardioplegic solution has been shown to improve ventricular function after clinical cardiac transplantation.
More prolonged myocardial preservation may depend on techniques. Perfusion at low flow rates with oxygenated perfusate improved preservation of rabbit hearts using a modified UW solution incorporating polyethylene glycol (PEG). A colloid is essential in such perfusates; PEG may prove a suitable alternative to hydroxyethyl starch.
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