Alterations in the beta-adrenergic receptor system after hypothermic ischemia in hearts with preischemic beta-receptor desensitization.
Although hypothermic cardioplegic arrest is a basic method of myocardial protection in cardiac surgery, the beta-adrenergic receptor (BAR) system has been little investigated in the heart subjected to hypothermic ischemia. Additionally, although the hypothermic arrest is often induced in hearts with preischemic desensitization of the BAR system by preceding congestive heart failure, the functional state of the BAR system after ischemia has not been studied in these hearts. We investigated alterations in the BAR system after hypothermic ischemia in normal rat hearts and in those with preischemic desensitization of the BAR system produced with isoproterenol (ISP: 400 micrograms/kg/hr for 24 hr). Both normal and BAR-desensitized hearts were isolated and subjected either to 40 min of hypothermic (10 degrees C) global ischemia followed by 40 min of reperfusion or subjected to time-matched aerobic perfusion with modified Krebs-Henseleit solution. At the end of perfusion (1) BAR binding properties with [3H]CGP-12177 and adenylate cyclase activity were measured in crude membrane fraction and (2) the inotropic response to ISP (delta LV + dP/dtmax) was evaluated in an isovolumetric contracting heart preparation. Following reperfusion, normal hearts without desensitized BAR showed a higher Bmax value than those of nonischemic time-matched hearts (41.8 +/- 3.1 vs 35.4 +/- 2.4 fmole/mg protein, P less than 0.05), whereas the Kd value was in a similar range in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
1st Department of Surgery, Osaka University Medical School, Japan.
N
N
Sakagoshi
H
H
Matsuda
Y
Y
Watanabe
M
M
Kaneko
Y
Y
Sawa
H
H
Yoshida
Y
Y
Kawashima
D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006352:Heart Ventricles; D007035:Hypothermia; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011412:Propanolamines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D000255:Adenosine Triphosphate; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C033394:CGP 12177