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Triple strategy to improve early graft function after heart transplantation
ELSEVIER
Triple Strategy to Improve Early Graft Function After Heart Transplantation P. Herijgers, Y. Nishimura, Y.-i. Kim, and W. Flameng
A
FTER TRANSPLANTATION, a small percentage of hearts exhibit poor function without apparent surgical or immunologic reasons. Early graft function is the result of the quality of the donor heart at harvest, and the duration and efficacy of the ischemic preservation process. These three determinants can be targeted to improve early graft function. The ischemic preservation time can be shortened by the time needed for implantation by starting continuous cold retrograde oxygenated blood cardioplegia as soon as the heart arrives at the recipient center. Brain death (BD) induces histologic and functional myocardial damage.’ Due to this, 20% to 25% of the BD potential organ donors become hemodynamically unstable, requiring high-dose inotropic support, thus rendering the heart unsuitable for transplantation. Also, in hearts accepted for transplantation, histologic damage is observed before any ischemic preservation.’ We studied the pathogenic mechanisms of this phenomenon to find strategies to improve the quality of donor hearts at harvest. The hypothesis-derived from the histologic characteristics-that the damage was caused by coronary vasospasms, was tested. Optimization of the preservation technique is necessary for these already damaged hearts. Illustrative for this is the fact that the safe ischemic preservation time is much shorter in clinical practice than could be expected from experimental studies with non-BD donor animals.3 An experimental study to improve myocardial preservation with a novel Na+/H+ exchange inhibitor was performed with BD animals as organ donors.
METHODS
dogs, weighing 21 to 35 kg, were anesthetized with ketamine hydrochloride, piritramide, sodium pentobarbital, and halothane. BD was induced in half of them by sudden inflation of an intracranial balloon.
40 mmol/L K+, and vasodilation as a proportion
reversal of the
preconstriction. Protocol 2
Forty-five minutes after BD, HOE642 (2 mg/kg IV, n = 5) or placebo (n = 7) was administered. After cardioplegic arrest with NIH-2, the hearts were excised 60 minutes after BD and stored at below 4°C. Four hours later, orthotopic heart transplantation was performed with HOE642 or placebo administered to the recipient dogs 15 minutes before reperfusion. After 60 minutes of reperfusion, pressure-volume loops were constructed, and weaning from extracorporeal circulation was performed without inotropic support. RESULTS Protocol 1
Serotonin caused a severe dose-dependent vasoconstriction in nonpreconstricted coronary segments from brain dead dogs, but had barely an effect on segments from control hearts (lo-‘: 5% vs 35%; lo-? 9% vs 58%; lo-‘: 2% vs 33%; P < .OOl). When preconstricted, coronary segments from brain dead dogs exhibited less vasodilatation on serotonin (lo-‘: 5% vs -14%; lo-‘? 56% vs 11%; lo-‘: 105% vs 91%; P < .OOl). Protocol 2 All dogs treated could be weaned from bypass, whereas two placebo-treated hearts failed. Untreated hearts tended to be slightly more edematous (water content: 79.9% 2 0.2% vs 79.0% ? 0.3%, P = .06), and had stiffer left ventricles (stiffness coefficients: 0.127 2 0.006 vs 0.072 ? 0.016, P = .02).
Mongrel
Protocol 1
One hour after BD (n = 7), or in controls (n = 7), coronary segments were suspended in an organ chamber and connected to an isometric force transducer. Serotonin (lo-’ to 1O-5 moI/L) was administered with or without preconstriction with PGF,,. Vasoconstriction was expressed proportional to the constrictory effect of 0041-1345/97/$17.00
CONCLUSIONS
All intermediary steps in heart procurement, preservation, and transplantation are potential targets for optimization. Brain death induces a propensity for coronary vasospasms, with possible therapeutic implications. Furthermore, myoFrom the Department of Cardiac Surgery, Leuven, Belgium. Address reprint requests to W. Flameng, Cardiac Surgery, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
PII so041 -1345(97)01000-2
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3512
TransplantationProceedings, 29, 3512-3513 (1997)
TRIPLE STRATEGY
cardial protection and preservation can and should be optimized for these already “damaged” hearts, as shown by the beneficial effect of the novel Na’/H’ exchange inhibitor HOE642. A considerable reduction in ischemic preservation time can be realized by starting continuous cold oxygenated retrograde blood cardioplegia as soon as the donor heart arrives at the recipient center.
3513 REFERENCES 1. Shivalkar B, Van Loon J, Wieland W, et al: Circulation
87:230, 1993 2. Novitzlq D, Rhodin J, Cooper DKC, et al: Transplant Int 10:24, 1997 3. MBllhoff T, Sukehiro S, Van Aken H, et al: Circulation 82(suppl IV):IV264, 1990
Triple Strategy to Improve Early Graft Function After Heart Transplantation P. Herijgers, Y. Nishimura, Y.-i. Kim, and W. Flameng
A
FTER TRANSPLANTATION, a small percentage of hearts exhibit poor function without apparent surgical or immunologic reasons. Early graft function is the result of the quality of the donor heart at harvest, and the duration and efficacy of the ischemic preservation process. These three determinants can be targeted to improve early graft function. The ischemic preservation time can be shortened by the time needed for implantation by starting continuous cold retrograde oxygenated blood cardioplegia as soon as the heart arrives at the recipient center. Brain death (BD) induces histologic and functional myocardial damage.’ Due to this, 20% to 25% of the BD potential organ donors become hemodynamically unstable, requiring high-dose inotropic support, thus rendering the heart unsuitable for transplantation. Also, in hearts accepted for transplantation, histologic damage is observed before any ischemic preservation.’ We studied the pathogenic mechanisms of this phenomenon to find strategies to improve the quality of donor hearts at harvest. The hypothesis-derived from the histologic characteristics-that the damage was caused by coronary vasospasms, was tested. Optimization of the preservation technique is necessary for these already damaged hearts. Illustrative for this is the fact that the safe ischemic preservation time is much shorter in clinical practice than could be expected from experimental studies with non-BD donor animals.3 An experimental study to improve myocardial preservation with a novel Na+/H+ exchange inhibitor was performed with BD animals as organ donors.
METHODS
dogs, weighing 21 to 35 kg, were anesthetized with ketamine hydrochloride, piritramide, sodium pentobarbital, and halothane. BD was induced in half of them by sudden inflation of an intracranial balloon.
40 mmol/L K+, and vasodilation as a proportion
reversal of the
preconstriction. Protocol 2
Forty-five minutes after BD, HOE642 (2 mg/kg IV, n = 5) or placebo (n = 7) was administered. After cardioplegic arrest with NIH-2, the hearts were excised 60 minutes after BD and stored at below 4°C. Four hours later, orthotopic heart transplantation was performed with HOE642 or placebo administered to the recipient dogs 15 minutes before reperfusion. After 60 minutes of reperfusion, pressure-volume loops were constructed, and weaning from extracorporeal circulation was performed without inotropic support. RESULTS Protocol 1
Serotonin caused a severe dose-dependent vasoconstriction in nonpreconstricted coronary segments from brain dead dogs, but had barely an effect on segments from control hearts (lo-‘: 5% vs 35%; lo-? 9% vs 58%; lo-‘: 2% vs 33%; P < .OOl). When preconstricted, coronary segments from brain dead dogs exhibited less vasodilatation on serotonin (lo-‘: 5% vs -14%; lo-‘? 56% vs 11%; lo-‘: 105% vs 91%; P < .OOl). Protocol 2 All dogs treated could be weaned from bypass, whereas two placebo-treated hearts failed. Untreated hearts tended to be slightly more edematous (water content: 79.9% 2 0.2% vs 79.0% ? 0.3%, P = .06), and had stiffer left ventricles (stiffness coefficients: 0.127 2 0.006 vs 0.072 ? 0.016, P = .02).
Mongrel
Protocol 1
One hour after BD (n = 7), or in controls (n = 7), coronary segments were suspended in an organ chamber and connected to an isometric force transducer. Serotonin (lo-’ to 1O-5 moI/L) was administered with or without preconstriction with PGF,,. Vasoconstriction was expressed proportional to the constrictory effect of 0041-1345/97/$17.00
CONCLUSIONS
All intermediary steps in heart procurement, preservation, and transplantation are potential targets for optimization. Brain death induces a propensity for coronary vasospasms, with possible therapeutic implications. Furthermore, myoFrom the Department of Cardiac Surgery, Leuven, Belgium. Address reprint requests to W. Flameng, Cardiac Surgery, UZ Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
PII so041 -1345(97)01000-2
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3512
TransplantationProceedings, 29, 3512-3513 (1997)
TRIPLE STRATEGY
cardial protection and preservation can and should be optimized for these already “damaged” hearts, as shown by the beneficial effect of the novel Na’/H’ exchange inhibitor HOE642. A considerable reduction in ischemic preservation time can be realized by starting continuous cold oxygenated retrograde blood cardioplegia as soon as the donor heart arrives at the recipient center.
3513 REFERENCES 1. Shivalkar B, Van Loon J, Wieland W, et al: Circulation
87:230, 1993 2. Novitzlq D, Rhodin J, Cooper DKC, et al: Transplant Int 10:24, 1997 3. MBllhoff T, Sukehiro S, Van Aken H, et al: Circulation 82(suppl IV):IV264, 1990