Pretreatment of donors with endothelin receptor antagonist TAK-044 improves cardiac functional recovery following preservation with University of Wisconsin solution.
OBJECTIVE
Previous studies suggest that endothelin-1 (ET-1) plays a role in myocardial ischemia/reperfusion injury. Although administration of an endothelin receptor antagonist to the recipient has been shown to improve myocardial function after ischemia/reperfusion in a rat heart transplantation model, the effect of administering an endothelin receptor antagonist to the donor has not yet been examined. This study was designed to investigate the effects of pretreating donors with an ET(A)/ET(B) endothelin receptor antagonist (TAK-044) on myocardial function after cold preservation of a rat heart.


METHODS
Male rats were pretreated with normal saline (control group, n = 8), TAK-044 (TAK group, n = 8, 1 mg/kg). Following cardiac arrest using cardioplegia, we washed out the coronary vascular beds with cold University of Wisconsin solution followed by 6-h preservation. After preservation, the hearts were mounted on a Langendorff apparatus to estimate aortic flow (AF), coronary flow (CF), cardiac output (CO), systolic pressure (SP), heart rate (HR), and rate-pressure product (RPP: HR x SP). The concentration of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) within the coronary perfusate during reperfusion was measured.


RESULTS
AF, SP, and CO were significantly greater in the TAK group than in the control group (p = 0.0045, 0.004, and 0.0295, respectively).


CONCLUSIONS
Pretreatment of donors with a nonselective endothelin receptor antagonist (TAK-044) improved cardiac functional recovery following preservation and may be beneficial for prolonged myocardial preservation.
Kaneda
Toshio
T
Department of Cardiovascular Surgery, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. toshio_kaneda@hotmail.com
Zhang
Zhi-Wei
ZW
Ogawa
Tatsuya
T
Otaki
Masaki
M
Saga
Toshihiko
T
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D065128:Endothelin Receptor Antagonists; D005978:Glutathione; D006334:Heart Function Tests; D016027:Heart Transplantation / Q000502:physiology*; D007328:Insulin; D008297:Male; D023421:Models, Animal; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D011887:Raffinose; D051381:Rats; D017208:Rats, Wistar; D014019:Tissue Donors; D019172:Transplantation Conditioning
D065128:Endothelin Receptor Antagonists; D007328:Insulin; D019188:Organ Preservation Solutions; D010456:Peptides, Cyclic; C055206:University of Wisconsin-lactobionate solution; C088196:TAK 044; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose