Efficacy of oxygenated University of Wisconsin solution containing endothelin-A receptor antagonist in twenty-four-hour heart preservation.
BACKGROUND
The University of Wisconsin solution has been proven to be effective for prolonged heart preservation. However, 24-hour heart preservation by simple cold immersion in University of Wisconsin solution has been disappointing. We have performed hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution for experimental prolonged heart preservation. However, the high potassium concentration of University of Wisconsin solution combined with prolonged ischemia has detrimental effects on endothelial function, which increases coronary tone during preservation and after reperfusion. The severe vasoconstriction and tissue edema result in damage to the coronary microcirculation. The purpose of this study was to determine whether hypothermic low-pressure continuous coronary perfusion technique with oxygenated University of Wisconsin solution containing a selective endothelin-A receptor antagonist (FR139317) would increase the effectiveness of the perfusion technique and improve postischemic cardiac function, both minimizing tissue edema and suppressing vasoconstriction.


RESULTS
Preischemic and postischemic cardiac function of isolated rabbit hearts was evaluated with a Langendorff apparatus. The hearts were divided into three groups (n = 7 each): group I (hypothermic low-pressure continuous coronary perfusion with University of Wisconsin solution), group II (hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution), and group III (hypothermic low-pressure continuous coronary perfusion with oxygenated University of Wisconsin solution containing 10 mg/L of FR139317). Preservation was performed for 24 hours. The initial perfusion pressure for continuous coronary perfusion was set at 5 mm Hg. Measurement of percentage of tissue water content and ultrastructural examination of the myocardium was then performed. In groups I, II, and III, the perfusion pressures at the end of the 24-hour preservation period increased from 5 mm Hg to 12.2 +/- 2.5, 8.1 +/- 1.3, and 5.4 +/- 0.8 mm Hg (p < 0.05), respectively. Percent recovery rate of cardiac output was 56.6 +/- 2.8, 82.3 +/- 8.2, and 93.3 +/- 6.0 (p < 0.05), respectively. And percent recovery rate of coronary flow was 55.5 +/- 8.1, 80.0 +/- 8.0, and 94.3 +/- 9.4 (p < 0.05), respectively. A significant inverse correlation was found between continuous coronary perfusion pressure at the end of preservation and the recovery rate of cardiac output (r = 0.85, p < 0.05). Tissue water content was significantly higher in group I than in groups II and III. These effects were inhibited by oxygenation of the University of Wisconsin solution (group II) and by the addition of the selective endothelin-A receptor antagonist (FR139317) (group III). Damage to coronary circulation was reduced by oxygenation and the addition of endothelin-A receptor antagonist during prolonged heart preservation.


CONCLUSIONS
We concluded that hypothermic low-pressure continuous coronary perfusion technique with oxygenated UW solution containing endothelin-A receptor antagonist (FR139317) maintained coronary circulation by suppressing tissue edema and vasoconstriction during preservation, which improved postischemic functional recovery.
Okada
K
K
Department of Surgery, Kobe University School of Medicine, Japan.
Yamashita
C
C
Okada
M
M
Okada
M
M
D000241:Adenosine / Q000008:administration & dosage / Q000627:therapeutic use; D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000737:chemistry; D002302:Cardiac Output / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000008:administration & dosage / Q000627:therapeutic use*; D003326:Coronary Circulation; D015925:Cryopreservation; D004487:Edema / Q000517:prevention & control; D065128:Endothelin Receptor Antagonists; D005978:Glutathione / Q000008:administration & dosage / Q000627:therapeutic use; D016027:Heart Transplantation; D007036:Hypothermia, Induced; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007511:Ischemia; D008833:Microcirculation / Q000187:drug effects; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry / Q000648:ultrastructure; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D011887:Raffinose / Q000008:administration & dosage / Q000627:therapeutic use; D015424:Reperfusion; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D001381:Azepines; D002314:Cardioplegic Solutions; D065128:Endothelin Receptor Antagonists; D007211:Indoles; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; C079574:FR 139317; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen