Document Detail

Pharmacologic heart rate reduction: effect of a novel, specific bradycardic agent on the heart.
MedLine Citation:
PMID:  9618805     Owner:  NLM     Status:  MEDLINE    
Because heart rate (HR) is a major determinant of myocardial oxygen consumption (MVO2) a decrease in HR could prevent ischemia or reduce its consequences. We examined the effects of a novel bradycardic agent of the benzazepinone type, DK-AH 269 (DK), on ventricular function and perfusion in 12 isolated, blood-perfused rabbit hearts. HR was significantly reduced by 1mumol/L DK (160 +/- 28 vs. 124 +/- 23 min-1); diastole lengthened from 235 +/- 69 to 334 +/- 85 ms. Aortic flow tended to fall after DK (50.0 +/- 29.6 vs. 35.6 +/- 21.5 ml/min), but stroke volume remained unchanged (0.29 +/- 0.16 vs. 0.28 +/- 0.17 ml) following DK. Peak left-ventricular pressure (LVPmax) (106 +/- 29 vs. 92 +/- 35 mmHg) and dp/dtmax (1482 +/- 582 vs. 1247 +/- 644 mmHg/s) were decreased. dp/dtmin, as a measure of early relaxation, was also decreased (-1361 +/- 362 vs, -1125 +/- 488 mmHg/s), whereas the end-diastolic pressure (LVPed) was increased (20 +/- 12 vs. 25 +/- 17 mmHg). Coronary blood flow (CBF) per beat was not affected by DK: 0.07 +/- 0.02 vs. 0.07 +/- 0.02 ml. However, the coronary resistance increased with DK from 0.76 +/- 0.29 to 1.13 +/- 0.66 mmHg/(ml/min/100 g). The MVO2 was decreased (6.8 +/- 3.4 vs. 5.9 +/- 2.8 ml/min/100 g). The relation between subendocardial and subepicardial flow (colored microspheres) was unchanged after DK (1.12 +/- 0.22 vs. 1.13 +/- 0.16). Using electrical pacing to restore the control HR, dp/dtmax, LVPed, and MVO2 were nearly restored to predrug levels. In contrast, stroke volume, LVPmax, dp/dtmin and CBF per beat were less than control. In summary: DK effectively reduces heart rate and increases diastole. In parallel with the moderately reduced contractile function, MVO2 is reduced whereas CBF per beat is preserved. These results suggest that this novel bradycardic agent could be useful in treating unwanted tachycardia in the experimental setting, postoperative tachycardia in patients with heart disease or be useful even in treating coronary heart disease.
A Granetzny; U Schwanke; C Schmitz; G Arnold; D Schäfer; H D Schulte; E Gams; J D Schipke
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Thoracic and cardiovascular surgeon     Volume:  46     ISSN:  0171-6425     ISO Abbreviation:  Thorac Cardiovasc Surg     Publication Date:  1998 Apr 
Date Detail:
Created Date:  1998-08-24     Completed Date:  1998-08-24     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7903387     Medline TA:  Thorac Cardiovasc Surg     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  63-9     Citation Subset:  IM    
Clinic of Thoracic and Cardiovascular Surgery, Düsseldorf, Germany.
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MeSH Terms
Anti-Arrhythmia Agents / pharmacology*
Benzazepines / pharmacology*
Coronary Circulation / drug effects
Heart / drug effects
Heart Rate / drug effects*
Myocardial Contraction / drug effects
Myocardium / metabolism*
Oxygen Consumption / drug effects*
Ventricular Function, Left / drug effects
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Benzazepines

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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