Dose-Dependent Reduction of Myocardial Infarct Mass in Rabbits by the NHE-1 Inhibitor Cariporide (HOE 642)

The aim of this study was to investigate the dose-dependent effect of pretreatment with the selective sodium-hydrogen exchange NHE-subtype 1 inhibitor cariporide on myocardial infarct mass in a rabbit model of coronary ligation and reperfusion. Furthermore, in a second part of the study, we tested t...

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Bibliographic Details
Published in:Clinical and experimental hypertension (1993) 1998, Vol.20 (7), p.733-749
Main Authors: Linz, W., Albus, U., Crause, P., Jung, W., Weichert, A., Schölkens, B. A., Scholz, W.
Format: Article
Language:English
Subjects:
Animals
Antianginal agents. Coronary vasodilator agents
Biological and medical sciences
Cardiovascular system
Cariporide
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Female
Guanidines - administration & dosage
Guanidines - blood
Guanidines - therapeutic use
HOE 642
Ischemia
Male
Medical sciences
Myocardial Infarction
Myocardial Infarction - blood
Myocardial Infarction - drug therapy
Myocardial Infarction - pathology
Myocardial Reperfusion
NHE-inhibition
Pharmacology. Drug treatments
Rabbits
Reperfusion
Sodium-Hydrogen Exchangers - antagonists & inhibitors
Sulfones - administration & dosage
Sulfones - blood
Sulfones - therapeutic use
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Summary:The aim of this study was to investigate the dose-dependent effect of pretreatment with the selective sodium-hydrogen exchange NHE-subtype 1 inhibitor cariporide on myocardial infarct mass in a rabbit model of coronary ligation and reperfusion. Furthermore, in a second part of the study, we tested the effect of cariporide in the rabbits when given prior to reperfusion. Rabbits (n=49) were randomized in 7 groups: saline vehicle, cariporide: 0.01, 0.03, 0.1 and 0.3 mg/kg, and subjected to a 30 min occlusion of a branch of the left coronary artery followed by 2 h reperfusion. Cariporide was given as a bolus intravenously 10 min before occlusion or 5 min before reperfusion. After reperfusion, myocardial infarct mass was determined by triphenyl tetrazolium chloride staining and expressed as a percent of area at risk. Cariporide given intravenously 10 min before occlusion in doses of 0.01, 0.03, 0.1, 0.3 mg/kg, led to a dose-dependent reduction in infarct mass from 58 ± 6% in controls to 48 ± 4% (-17 %, NS), 36 ± 5% (-38 %, p
ISSN:1064-1963
1525-6006
DOI:10.3109/10641969809052116