title: Discrepant recovery course of sympathetic neuronal function and beta-adrenoceptors in rat hearts after reperfusion following transient ischemia.
abstract: 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.
authors.affiliation: The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
authors.forename: Bun-ichi
authors.initials: B
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozawa
authors.forename: Norio
authors.initials: N
authors.lastname: Igarashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nonomura
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fujii
authors.forename: Akihiko
authors.initials: A
authors.lastname: Igawa
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Asanoi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamada
authors.forename: Minoru
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: 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
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; D019797:3-Iodobenzylguanidine; D020120:Iodocyanopindolol