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Effect of a bradycardic agent on the isolated blood-perfused canine heart

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Summary

Bradycardic agents could limit the consequences of myocardial ischemia via two mechanisms: by decreasing myocardial oxygen demand (MVO2) and by increasing diastolic coronary blood flow (CBF). We investigated whether the benzazepinon UL-FS 49 affects only sinus node cells or also smooth muscle and/or myocardial cells. To avoid confounding interactions with the periphery, we performed experiments on 11 isolated, blood-perfused canine hearts. Injection of UL-FS 49 (1 mg/kg i.c.) significantly reduced heart rate (HR) from 104 ± 7 to 93 ± 7 min−1 (mean ± SEM) and increased stroke volume (n = 6: 9.8 ± 1.1 vs. 13.2 ± 1.6 ml), so that cardiac output remained unchanged (n = 6: 1.1 ± 0.1 vs. 1.2 ± 0.1 1/min). The contractile state, assessed by isovolumic peak systolic pressure, was unaltered by UL-FS 49 (n = 5: 72 ± 6 vs. 72 ± 6 mmHg). At a constant coronary arterial pressure (CAP) of 80 mmHg, mean CBF was slightly decreased (102 ± 11 vs. 97 ± 10 ml/tmin · 100 g]) by UL-FS 49, such that mean coronary resistance remained unchanged (0.9 ± 0.1 vs 1.0 ±0.1 mmHg · min · 100 g/ml). The slight decreases in arteriovenous oxygen content difference (n = 6: 6.6 ± 0.7 vs. 6.5 ± 0.7 ml/100 ml) and in CBF lead to a calculated, significant decrease in MVO2 (n = 6: 6.9 ± 0.5 vs. 6.0 ± 0.4 ml · 100 g/min). In conclusion, UL-FS 49 at the dose used decreases MVO2 by reducing HR in isolated canine hearts. In the absence of negative inotropic and vasodilating effects, cardiac output is maintained via increased stroke volume, and CAP will likely be preserved in situ. Thus, this specific bradycardic agent could be useful in treating ischemic myocardial disease.

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Authors and Affiliations

  1. Dept. of Experimental Surgery, Universität Düsseldorf, Universitätsstraβe 1, D-4000, Düsseldorf, FRG

    Jochen D. Schipke

  2. Dept. of Biomedical Engineering, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA

    Yasuhiko Harasawa, Seiryo Sugiura, Joe Alexander & Daniel Burkhoff

Authors
  1. Jochen D. Schipke
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  2. Yasuhiko Harasawa
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  3. Seiryo Sugiura
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  4. Joe Alexander
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  5. Daniel Burkhoff
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Schipke, J.D., Harasawa, Y., Sugiura, S. et al. Effect of a bradycardic agent on the isolated blood-perfused canine heart. Cardiovasc Drug Ther 5, 481–488 (1991). https://doi.org/10.1007/BF03029773

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