Discrepant recovery course of sympathetic neuronal function and beta-adrenoceptors in rat hearts after reperfusion following transient ischemia.
Cardiac sympathetic neuronal function is closely coupled with beta-adrenoceptors and adrenergic signaling. However, the recovery process of sympathetic neuronal function and beta-adrenoceptors after reperfusion following transient ischemia is not fully understood. Accordingly, this study was performed to investigate serial changes in sympathetic neuronal function and beta-adrenoceptors after transient myocardial ischemia.


METHODS
The left coronary artery of male Wister rats was ligated for 15 min followed by reperfusion. A dual-tracer method of (131)I-metaiodobenzylguanidine ((131)I-MIBG) and (125)I-iodocyanopindolol ((125)I-ICYP) was used to assess cardiac sympathetic neuronal function and beta-adrenoceptor density on days 1, 3, 7, 14, and 28 after reperfusion. Myocardial norepinephrine (NE) content in ischemic regions (IR) and in remote regions (RR) and hemodynamic indices were determined. Using a membrane preparation of the rat heart after reperfusion, the maximum specific binding (B(max)) of beta-adrenoceptors was compared with (125)I-ICYP accumulation.


RESULTS
The maximum value of the rate of change in left ventricular (LV) pressure (dP/dt(max)) tended to decrease on day 1 after reperfusion but recovered thereafter. Myocardial NE content was significantly reduced in IR compared with RR on day 1 (272 +/- 49 vs. 487 +/- 93 ng/g, P < 0.01), and the decrease became more severe on day 14 (36 +/- 19 vs. 489 +/- 132 ng/g, P < 0.01) and day 28 (37 +/- 14 vs. 455 +/- 216 ng/g, P < 0.01). Decrease in the IR-to-RR uptake ratio of (131)I-MIBG was modest on day 1 (0.64 +/- 0.12) and became more severe on days 7 and 14 (0.38 +/- 0.12 and 0.35 +/- 0.13, respectively). This reduction was partially restored on day 28 (0.50 +/- 0.18). In contrast, the IR-to-RR uptake ratio of (125)I-ICYP was severely decreased until day 3 (0.60 +/- 0.13 on day 1 and 0.54 +/- 0.19 on day 3) and recovered thereafter. On day 3, B(max) was significantly lower in IR than in RR (83 +/- 17 vs. 100 +/- 12 fmol/mg, P < 0.05), but the dissociation constant did not differ between the 2 regions.


CONCLUSIONS
The recovery course of cardiac (131)I-MIBG uptake after reperfusion following transient ischemia is quite different from that of (125)I-ICYP. Simultaneous scintigraphic portrayal of beta-adrenoceptors together with (131)I-MIBG would provide useful information regarding adrenergic system signaling in patients with coronary artery disease.
Kato
Bun-ichi
B
The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Nozawa
Takashi
T
Igarashi
Norio
N
Nonomura
Makoto
M
Fujii
Nozomu
N
Igawa
Akihiko
A
Asanoi
Hidetsugu
H
Yamada
Yoshihisa
Y
Inoue
Minoru
M
Inoue
Hiroshi
H
D019797:3-Iodobenzylguanidine; D000222:Adaptation, Physiological; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D008297:Male; D008657:Metabolic Clearance Rate; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000378:metabolism*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; D019797:3-Iodobenzylguanidine; D020120:Iodocyanopindolol