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CLORICROMENE REDUCES INFARCT SIZE AND ALTERS POSTISCHAEMIC BLOOD FLOW DEFECTS IN DOG MYOCARDIUM
Author(s) -
Groban Leanne,
Zvara David A.,
Deal Dwight D.,
Ver Jason C.,
Flye Christopher W.,
Ma XinLiang,
VintenJohansen Jakob
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02225.x
Subject(s) - medicine , blood flow , hyperaemia , hemodynamics , ischemia , myocardial infarction , saline , cardiology , fissipedia , myeloperoxidase , anesthesia , inflammation
SUMMARY 1. The aim of the present investigation was to evaluate the effect of cloricromene on myocardial infarct size, regional myocardial blood flow and neutrophil accumulation in a canine model of ischaemia‐reperfusion. 2. Dogs were instrumented to measure blood pressure, left anterior descending (LAD) coronary flow (flow probe) and regional myocardial blood flow (coloured microspheres). Two groups were studied: (i) CLO ( n = 8) received an infusion of cloricromene (15 μg/kg per min); and (ii) VEH ( n = 8) received saline. Infusions began at the onset of ischaemia (60 min) and continued through reperfusion (180 min). 3. Haemodynamic responses were not different between groups. Cloricromene reduced the area of necrosis expressed as a percentage of the area at risk from 35 ± 3% in the VEH group to 23 ± 4% in the CLO group ( P <0.05). Regional myocardial blood flow in the ischaemic region was different between groups; VEH dogs showed an early reperfusion hyperaemia followed by a progressive reduction in flow, while CLO dogs exhibited a gradual increase in reflow in the absence of an early hyperaemie response ( P <0.05). Left anterior descending flow was enhanced during the reperfusion period in the CLO group compared with VEH ( P <0.05). Cloricromene reduced polymorphonuclear neutrophil (PMN) infiltration (myeloperoxidase activity) in all myocardial regions when compared with VEH (non‐ischaemic zone, 0.34 ± 0.54 vs 0.05 ± 0.01 IU/l00 mg; ischaemic zone, 2.03 ± 0.80 vs 0.24 ± 0.08 IU/100 mg; and necrotic zone, 0.56 ± 0.04 vs 3.59 ± 1.09 IU/100 mg for VEH vs CLO groups, respectively; P<0.01). In a separate in vitro preparation, cloricromene reduced adherence of platelet‐activating factor (PAF)‐stimulated PMN to canine coronary endothelium. Stimulation of PMN by 100 nmol/L PAF resulted in adherence of 176 ± 36 compared with 48 ± 12 cells/mm 2 in PAF‐stimulated PMN treated with 100 p. mol cloricromene ( P< 0.001). 4. These data indicate that cloricromene reduces myocardial infarct size in a canine model of ischaemia‐reperfusion injury. Postischaemic blood flow patterns are significantly different in cloricromene‐treated dogs. Cloricromene‐mediated reductions in infarct size, neutrophil accumulation and adherence may play a role in this effect.