Changes of endothelin-1 and big endothelin-1 levels and action potential duration during myocardial ischemia-reperfusion in dogs with and without ventricular fibrillation.
Myocardial ischemia-reperfusion is associated with increased production of endothelin-1 (ET-1). Moreover, exogenous ET-1 has arrhythmogenic properties. Our aim was to investigate the correlation between endogenous ET-1, big ET-1 levels and epicardial monophasic action potential duration during myocardial ischemia-reperfusion in anesthetized dogs. Thirty-minute myocardial ischemia was followed by a 90-minute reperfusion period in 18 mongrel dogs. The total incidence of ventricular fibrillation (VF) during ischemia and reperfusion was 11.1% and 33.3%, respectively. During ischemia, the monophasic action potential duration at 90% repolarization (MAPD90) decreased significantly (control versus ischemia, 30 minutes, 224.7 +/- 7.1 ms versus 173.8 +/- 7.6 ms; P < 0.05), while during reperfusion a significant prolongation of MAPD90 was observed (ischemia, 30 minutes versus reperfusion, 30 minutes, 173.8 +/- 7.6 ms versus 249.7 +/- 9.9 ms, P < 0.05). During reperfusion ET-1 and big ET-1 levels increased significantly in the coronary sinus and femoral artery (control versus reperfusion, 90 minutes: coronary sinus ET-1, 15.1 +/- 1.4 fmol/mL versus 22.3 +/- 1.1 fmol/mL; big ET-1, 14.7 +/- 1.9 fmol/mL versus 27.4 +/- 2.3 fmol/mL; P < 0.05). The ET-1 concentration increased to a higher level during ischemia in dogs with VF compared with dogs surviving ischemia-reperfusion (non-VF versus VF: control, 15.1 +/- 1.3 versus 15.2 +/- 1.3; ischemia, 30 minutes, 17.6 +/- 1.2 fmol/mL versus 22 +/- 1.6 fmol/mL; P < 0.05), demonstrating a trend of correlation between endothelin levels and development of VF (P = 0.07). ET-1 and big ET-1 levels increased during reperfusion and in the VF group during ischemia; however, there was no correlation between endothelin levels and MAPD90.
Vágó
Hajnalka
H
Department of Cardiovascular Surgery, Semmelweis University Budapest, Hungary. vagoh@freemail.hu
Soós
Pál
P
Zima
Endre
E
Gellér
László
L
Keltai
Katalin
K
Róka
Attila
A
Kékesi
Violetta
V
Juhász-Nagy
Alexander
A
Merkely
Béla
B
D000200:Action Potentials; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D010496:Pericardium / Q000378:metabolism* / Q000503:physiopathology; D011498:Protein Precursors / Q000097:blood*; D013997:Time Factors; D015854:Up-Regulation; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology
D019332:Endothelin-1; D011498:Protein Precursors