Supplementation of University of Wisconsin solution with Nitroglycerin and Nicorandil in long-term myocardial preservation: effects on the oxidative state, endothelial function and morphology.
The purpose of this study was to assess the effects of the addition of Nitroglycerin or Nicorandil to University of Wisconsin solution in long-term myocardial preservation. In a model of heterotopic heart transplantation in pigs, the donor heart was preserved for 24 hours by means of continuous perfusion in this solution, in the presence or absence of these drugs. During this period, the oxygenation and pH of the solution were measured, as were lactate concentrations and enzyme release. At regular intervals following reperfusion we measured the concentrations of enzymes, antioxidants, glutathione peroxidase, glutathione reductase, malondialdehyde, endothelin and nitrite, and, two hours later, samples of both ventricles were taken for a morphological study. In the treated groups there was a higher lactate production during preservation and, during reperfusion, the signs of contracture and the elevation of enzyme levels were more marked than in the untreated groups. In contrast, the glutathione reductase concentrations did not decrease during the first phase of reperfusion and were directly correlated with those of antioxidants, endothelin levels increased less than in the untreated groups and, in the case of nitroglycerin, the nitrite concentration was significantly greater than in the remaining groups. We conclude that nitroglycerin and nicorandil improved the oxidative state and endothelial function and did not produce substantial morphological changes, but increased cell necrosis and contracture, possibly due to the duration of ischemia.
Department of Experimental Surgery, Puerta de Hierro Majadahonda University Hospital, Majadahonda, Madrid, Spain. lalvarez.hpth@salud.madrid.org
L
L
Alvarez-Ayuso
S
S
García Gómez-Heras
E
E
Jorge
J M
JM
Guardiola
A
A
Torralba
I
I
Millán
J R
JR
Roda
P
P
Calero
E
E
García-Poblete
H
H
Fernández-García
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000032:analysis; D002245:Carbon Dioxide / Q000032:analysis; D003402:Creatine Kinase / Q000032:analysis; D019332:Endothelin-1 / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects* / Q000502:physiology; D019084:Fluorescent Antibody Technique, Indirect; D005947:Glucose / Q000032:analysis; D005978:Glutathione; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D016027:Heart Transplantation / Q000379:methods; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007328:Insulin; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D019344:Lactic Acid / Q000032:analysis; D008315:Malondialdehyde / Q000032:analysis; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D020108:Nicorandil / Q000494:pharmacology*; D009573:Nitrites / Q000032:analysis; D005996:Nitroglycerin / Q000494:pharmacology*; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000032:analysis; D019999:Pharmaceutical Solutions / Q000494:pharmacology; D011887:Raffinose; D011897:Random Allocation; D013552:Swine; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D000975:Antioxidants; D019332:Endothelin-1; D007328:Insulin; D009573:Nitrites; D019188:Organ Preservation Solutions; D019999:Pharmaceutical Solutions; C055206:University of Wisconsin-lactobionate solution; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D020108:Nicorandil; D019344:Lactic Acid; D008315:Malondialdehyde; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D003402:Creatine Kinase; D005996:Nitroglycerin; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen; D002118:Calcium