Document Detail


Nitrovasodilators ITF 296 and isosorbide dinitrate exert antiischemic activity by dilating coronary penetrating arteries.
MedLine Citation:
PMID:  7630161     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined the effect of the novel nitrovasodilator ITF 296 and isosorbide dinitrate (ISDN) on myocardial blood flow (BF) distal to a coronary artery stenosis. Eleven dogs with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis. On separate days, the effects of ITF 296 in doses of 4 and 20 micrograms/kg/min i.v. or ISDN 20 micrograms/kg/min i.v. were compared. Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of either nitrovasodilator. Neither ITF 296 nor ISDN significantly altered heart rate (HR), arterial blood pressure (BP), or left ventricular end-diastolic pressure (LVEDP). In the presence of a stenosis that decreased distal coronary pressure to 58 +/- 4 mm Hg, mean myocardial BF measured with microspheres was 0.91 +/- 0.08 ml/min/g in the LAD-dependent region and 2.36 +/- 0.11 ml/min/g in the posterior control region, respectively. With no change in distal coronary pressure, ITF 296 increased mean BF in the LAD region to 1.25 +/- 0.05 ml/min/g (4 micrograms/kg/min i.v.) and 1.40 +/- 0.10 ml/min/g (20 micrograms/kg/min i.v.), whereas ISDN (20 micrograms/kg/min i.v.) increased flow to 1.28 +/- 0.18 ml/min/g (each p < 0.05). The increase in BF occurred exclusively in the deeper layers, with no change in subepicardial BF. Consequently, the endocardial/epicardial (endo/epi) BF ratio increased from 0.33 +/- 0.04 during control stenosis to 0.70 +/- 0.10 after ITF 296 (20 micrograms/kg/min), and to 0.56 +/- 0.08 after ISDN (each p < 0.05). Neither ITF 296 nor ISDN had an effect on myocardial BF in the normally perfused control region. Therefore, both ITF 296 and ISDN improved BF to the deeper myocardial layers distal to a coronary artery stenosis. This effect occurred without alterations in stenosis severity or diastolic intraventricular pressure, suggesting that these agents act by dilating the penetrating arteries which deliver BF to the subendocardium.
Authors:
D J Duncker; J Mizrahi; R J Bache
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  25     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1995 May 
Date Detail:
Created Date:  1995-09-05     Completed Date:  1995-09-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  823-32     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Minnesota Medical School, Minneapolis 00000, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Benzoxazines
Blood Pressure / drug effects
Coronary Circulation / drug effects*
Coronary Disease / drug therapy
Coronary Vessels / drug effects,  pathology
Disease Models, Animal
Dogs
Exercise Test
Heart Rate / drug effects
Injections, Intravenous
Isosorbide Dinitrate / administration & dosage,  pharmacology,  therapeutic use*
Laser-Doppler Flowmetry
Myocardial Ischemia / drug therapy*
Myocardium / pathology
Nitrates / administration & dosage,  pharmacology,  therapeutic use*
Oxazines / administration & dosage,  pharmacology,  therapeutic use*
Vasodilation / drug effects*
Grant Support
ID/Acronym/Agency:
HL20598/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Benzoxazines; 0/Nitrates; 0/Oxazines; 143248-63-9/sinitrodil; 87-33-2/Isosorbide Dinitrate

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


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