Cardioprotective effects of endotheline receptor antagonist in cyanotic heart

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: OKAYAMA UNIVERSITY
• Principal Investigator: ISHINO Kozo Okayama University Graduate School of Medicine and Dentistry, Assistant Professor, 大学院・医歯学総合研究科, 講師 (90314690)
• Co-Investigator(Kenkyū-buntansha): KAWADA Masaaki Okayama University Hospita, Assistant Professor, 医学部附属病院, 講師 (30177703) ; SANO Shunji Okayama University Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (50235438)
• Project Period (FY): 2000 – 2001
• Keywords: Endothelin receptor antagonist / Cyanosis rat model / Ischemia-reperfusion injury / Echocardiography / hypoxemia

Research Abstract

1. Effects of chronic hypoxia on cardiac function were evaluated by trans-thoracic echocardiography in rats. Eight-week-old male Wistar rats were housed in the hypoxic chambers for 8 weeks. The rats had severe hypoxemia and polycythemia. They demonstrated pulmonary hypertension due to hypoxic pulmonary vasoconstriction and right ventricular (RV) hypertrophy. Left ventricular systolic function was preserved, but its diastolic function was impaired probably due to RV hypertrophy or prolongation of RV ejection time due to pulmonary hypertension.
2. Newborn rats were housed in the hypoxic chambers either for 4 weeks or for 8 weeks. The isolated hearts were perfused on the Langendorff apparatus, subjected to 20 min global warm ischemia, and reperfused for 40 min. Left ventricular functional recovery after ischemia in 4-week-old cyanotic rats was better than 8-week-old cyanotic rats.
3. Efficacy of an endotheline A receptor antagonist for heart transplantation from non-heart-beating donors was evaluated in canine models. The anatagonist was administered before cardiac arrest and added to coronary perfusate in donor animals. Pulmonary artery pressure before cardiac arrest in the study group was lower than control animals. Cardiac function after transplantation in the study group was better than controls.