| Nitrovasodilators ITF 296 and isosorbide dinitrate exert antiischemic activity by dilating coronary penetrating arteries. | |
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MedLine Citation:
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PMID: 7630161 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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D J Duncker; J Mizrahi; R J Bache |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 25 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1995 May |
Date Detail:
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Created Date: 1995-09-05 Completed Date: 1995-09-05 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 823-32 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University of Minnesota Medical School, Minneapolis 00000, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HL20598/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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