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Disproportional Response between Refractory Period and Blood Flow to α1- and β-Adrenoceptor Blockade in Canine Ischemic Myocardium

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Abstract

We investigated the response of refractory periods and blood flow to blockade of α1- and β-adrenoceptors alone, or in combination on endocardium and epicardium, during myocardial ischemia. Dogs were anesthetized with α-chloralose and divided into bunazosin (an α1-blocking agent)-treated (0.1–0.2 mg/kg, IV, n = 14), propranolol-treated (0.2 mg/kg, IV, n = 12), and vehicle-control (n = 10) groups. The diagonal branches of the left anterior descending artery were ligated. The refractory period (ERP) and blood flow (RMBF) were determined by an S1-S2 extrastimulus method and a nonradioactive microsphere technique, respectively. The duration of regional electrograms (DRE) was measured in the endocardial and epicardial sites. Bunazosin alone reversed the ischemia-related shortening of ERPs at both the endocardial and epicardial sites, with a greater effect seen epicardially (P < .05). Subsequent administration of propranolol further prolonged ERPs in both sites, although the effect was greater in the epicardial surface (P < .05). Bunazosin reduced RMBF to a greater degree at the endocardial site than at the epicardial site in the ischemic zone (P < .01 and P < .05, respectively), but the magnitude of the reduction in RMBF and the difference in RMBF between sites were similar to the control group (P < .01). Propranolol alone and subsequent administration of bunazosin prolonged the ERP more at the epicardial site (P < .01) than at the endocardial sites in the ischemic zone. Propranolol produced no significant difference in RMBF between both sites. DREs in animals treated with bunazosin and propranolol alone, or in combination, were similar to those in animals treated with vehicle. These results suggest that differences in ERPs between endocardium and epicardium with blockade of α1- and/or β-adrenoceptor are not due to concomitant alterations in RMBF, but to differences in electrophysiological properties of the endocardial and epicardial cells during the acute phase of myocardial ischemia.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Tokai University, Isehara, Japan

    Kazutane Usui, Teruhisa Tanabe & Shunnosuke Handa

  2. Department of Physiology, School of Medicine, Tokai University, Isehara, Japan

    Yoshiro Shinozaki & Hidezo Mori

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  1. Kazutane Usui
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  2. Teruhisa Tanabe
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  3. Shunnosuke Handa
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  4. Yoshiro Shinozaki
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  5. Hidezo Mori
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Usui, K., Tanabe, T., Handa, S. et al. Disproportional Response between Refractory Period and Blood Flow to α1- and β-Adrenoceptor Blockade in Canine Ischemic Myocardium. Cardiovasc Drugs Ther 12, 561–571 (1998). https://doi.org/10.1023/A:1007739421023

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