An increase in myocardial beta-adrenoceptors to compensate for postischaemic dysfunction following coronary micro-embolisation in dogs.
This study examined whether beta-adrenoceptors increase in number during recovery from prolonged myocardial stunning and whether they compensate for lack of physiological response to beta-adrenergic stimulation in this abnormality. The left coronary artery was embolished in anaesthetised dogs with non-labelled microspheres (15 +/- 1 micron; 1.2 X 10(6).kg-1 body weight). Haemodynamic studies were performed before (control) and 24 h and 1 week after embolisation, in the conscious state. Myocardial noradrenaline content, plasma catecholamine concentrations and the density of beta-adrenoceptors (Bmax) were also assessed at three study intervals. At 24 h after embolisation, both systolic and diastolic cardiac function was significantly depressed. The inotropic response to isoprenaline was preserved, but the response to forskolin was markedly depressed. One week after embolisation, resting systolic function was restored to control levels and histological examination showed absence of myocardial necrosis. Although plasma noradrenaline concentration had returned to normal, myocardial noradrenaline content had decreased by 36% and the density of beta-adrenoceptors had increased by 48%. Myocardial relaxation was still impaired and the inotropic response to forskolin was also still depressed, whereas the response to isoprenaline was normal. Moreover, the down regulation of the increased beta-adrenoceptors by isoprenaline infusion for 24 h unmasked the latent systolic dysfunction. These results indicate that the density of beta-adrenoceptors increases during the recovery process from prolonged myocardial stunning and that this increase may compensate, at least in part, for impairment of the inotropic mechanism distal to the beta-adrenoceptors.
Hori
M
M
First Department of Medicine, Osaka University Medical School, Japan.
Koretsune
Y
Y
Kagiya
T
T
Watanabe
Y
Y
Iwakura
K
K
Iwai
K
K
Kitabatake
A
A
Yoshida
H
H
Inoue
M
M
Kamada
T
T
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003289:Convalescence; D003327:Coronary Disease / Q000209:etiology / Q000378:metabolism*; D004285:Dogs; D004617:Embolism / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008297:Male; D008863:Microspheres; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D007773:Lactates; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D007545:Isoproterenol; D009638:Norepinephrine