Abstract
Background: Orthotopic heart transplantation following ischemic times beyond four hours is associated
with increased risk of early graft failure. The use of modern myocardial preservation
strategies could enable safe transplantation after long-term conservation. In this
study, we tested a new myocardial protection regime in an experimental model of 24
h storage. Methods: Orthotopic heart transplantations (n = 15) were performed in a pig model. Donor hearts
were flushed with Bretschneider solution, excised, and stored for 24 hours at 4 °C.
During implantation, controlled reperfusions with substrate-enriched leukocyte-depleted
blood cardioplegia were performed after each anastomosis. Blood cardioplegia contained
1 mmol/l of the Na+-H+-exchange inhibitor HOE 642 and 100 mg/l of adenosine. Controlled reperfusion was
continued with leukocyte-depleted blood for 20 min. A microaxial pump was inserted
after heart transplantation and circulatory assistance was maintained for five hours
to prevent right heart failure. Results: No initial graft failure could be observed. Thirteen hearts could be weaned from
extracorporeal circulation. Due to bleeding problems, kidney and lung failure only
five hearts could be included in the final analysis. Hemodynamics of these hearts
remained stable with epinephrine at 0.1 µg/kg/min. Myocardial oxygen consumption 20
min after start of reperfusion (5.3 ± 2.0 ml/100 g/min) did not differ significantly
versus baseline (6.8 ± 2.0 ml/100 g/min). Oxygen extraction six hours after heart
transplantation was also well preserved compared to baseline (58.0 ± 10.2 versus 49.2
± 8.8 %). Histological examination six hours after transplantation using luxol fast
blue staining revealed that only 1.0 % of the myocytes were irreversibly damaged.
Conclusions: The data indicate full viability of the myocardium after 24 h conservation. The preservation
technique described could contribute to the extension of conservation times in heart
transplantation and enable transplantation of marginal donor hearts.
Key words
Heart transplantation - myocardial protection - blood cardioplegia - organ conservation
References
- 1
Reichenspurner H, Russ C, Überfuhr P, Nollert G, Schluter A, Reichart B, Klövekorn W P,
Schüler S, Hetzer R, Brett W.
Myocardial preservation using HTK solution for heart transplantation. A multicenter
study.
Eur J Cardiothorac Surg.
1993;
7
414-419
- 2
Briganti E M, Bergin P J, Rosenfeldt F L, Esmore D S, Rabinov M.
Successful long-term outcome with prolonged ischemic time cardiac allografts.
J Heart Lung Transplant.
1995;
14
840-845
- 3
Obadia J F, Girard C, Frerrara R, Chuzel M, Chassignolle J F, Dureau G.
Long conservation organs in heart transplantation: postoperative results and long-term
follow-up in fourteen patients.
J Heart Lung Transplant.
1997;
16
256-259
- 4
Tsai F, Marelli D, Laks H, Houston E, Sykes A, Bresson J, Friend L, Vellaca A, Burch C,
Kobashigawa J.
Cardiac allografts with ischemic time over 300 minutes.
J Heart Lung Transplant.
2001;
20
182
- 5
Pearl J M, Drinkwater D C, Laks H, Capouya E R, Gates R N.
Leukocyte-depleted reperfusion of transplanted human hearts: A randomized, double-blind
clinical trial.
J Heart Lung Transplant.
1992;
11
1082-1092
- 6
Burt J M, Copeland J G.
Myocardial function after preservation for 24 hours.
J Thorac Cardiovasc Surg.
1986;
92
238-246
- 7
Wicomb W N, Hill D J, Collins G M.
Twenty-four h ice storage of rabbit hearts.
J Heart Lung Transplant.
1994;
13
891-894
- 8
Martin J, Sarai K, Yoshitake M, Haberstroh J, Takahashi N, Lutter G, Beyersdorf F.
Orthotopic transplantation of pig hearts harvested after 30 min of normothermic ischemia:
controlled reperfusion with blood cardioplegia containing the Na+-H+-exchange inhibitor HOE 642.
Eur J Cardiothorac Surg.
1998;
14
607-614
- 9 Martin J, Lutter G, Ihling C, Siepe M, Wagner S, Hilberath J, Kemper M, Sarai K,
Beyersdorf F. Myocardial viability 24 hours after orthotopic heart transplantation
from non-heart-beating donors. J Thorac Cardiovasc Surg 2003 (in press)
- 10
Martin J, Sarai K, Yoshitake M, Haberstroh J, Takahashi N, Lutter G, Beyersdorf F.
Successful orthotopic pig heart transplantation from non-heart-beating donors.
J Heart Lung Transplant.
1999;
18
597-606
- 11 Swindle M.
Porcine models in surgical research: an overview. In: Tumbleson ME, editor Swine in biomedical research. New York, London; Plenum Press
1986: 135-142
- 12
Buckberg G D.
Editorial: endothelial and myocardial stunning.
J Thorac Cardiovasc Surg.
2000;
120
640-641
- 13
Hottenrott C, Maloney J, Buckberg G.
Studies of the effects of ventricular fibrillation on the adequacy of regional myocardial
flow.
J Thorac Cardiovasc Surg.
1974;
68
615-625
- 14
Hohlfeld T, Meyer-Kirchrath J, Vogel Y C, Schror K.
Reduction of infarct size by selective stimulation of prostaglandin EP(3) receptors
in the reperfused ischemic pig heart.
J Mol Cell Cardiol.
2000;
32
285-296
- 15
Rosenkranz E R, Okamoto F, Buckberg G D, Vinten-Johansen J, Robertson J M, Bugyi H.
Safety of prolonged aortic clamping with blood cardioplegia.
J Thorac Cardiovasc Surg.
1984;
88
402-410
- 16
Luciani G B, Faggian G, Montalbano G, Casali G, Forni A, Chiominto B, Mazzucco A.
Blood versus crystalloid cardioplegia for myocardial protection of donor hearts during
transplantation: a prospective, randomized clinical trial.
J Thorac Cardiovasc Surg.
1999;
118
787-795
- 17
Duilio C, Ambrosio G, Kuppusamy P, Dipaula A, Becker L C, Zweiser J L.
Neutrophils are primary source of O2 radicals during reperfusion after prolonged myocardial ischemia.
Am J Physiol Heart Circ Physiol.
2001;
280
H2649-H2657
- 18
Vinten-Johansen J, Thourani V H, Ronson R S, Jordan J E, Zhao Z Y, Nakamura M, Velez D,
Guyton R A.
Broad-spectrum cardioprotection with adenosine.
Ann Thorac Surg.
1999;
68
1942-1948
- 19
Hendrikx M, Mubagwa K, Verdonck F, Overloop K, Hecke P van, Vanstapel F, Lommel A
van, Verbeken E, Lauweryns J, Flameng W.
New Na+-H+ exchange inhibitor HOE 642 improves postischemic function and high-energy phosphate
resynthesis and reduces Ca2+-overload in isolated perfused rabbit heart.
Circulation.
1994;
89
2787-2798
- 20
Theroux P, Chaitman B R, Danchin N, Erhardt L, Meinertz T, Schroeder J S, Gognoni G,
White H D, Willerson J T, Jessel A.
Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial
infarction in high-risk ischemic situations. Main results of the GUARDIAN trial.
Circulation.
2000;
102
3032-3038
Jürgen MartinMD
Department of Cardiovascular Surgery, Albert Ludwigs University
Hugstetter Straße 55
79106 Freiburg
Germany
Phone: +49/761/270-2818
Fax: +49/761/270-2550
Email: Martin@ch11.ukl.uni-freiburg.de