Biomedical subjects

F Marcoux

Publications and source records attributed to F Marcoux.

15 recordsLinked to original sources

PubMed1998

Prevention of vasospasm after subarachnoid hemorrhage in dogs by continuous intravenous infusion of PD156707.

This randomized, blinded study tested the prophylactic effect of PD156707, a nonpeptide competitive antagonist of endothelin A receptors, against vasospasm after subarachnoid hemorrhage in dogs. Twenty-two dogs were allocated on day 0 to undergo cerebral angiography followed by injection of arterial blood (0.5 ml/kg) into the cisterna magna. Dogs had central venous catheters implanted for continuous infusion of drug vehicle (n = 10) or PD156707 (n = 12). Cisternal blood injection was repeated on day 2. Drug levels were measured in plasma on days 2, 4, 6, and 7 and in cerebrospinal fluid (CSF) on days 2 and 7. Angiography was repeated on day 7 to assess vasospasm. After angiography on day 7, acute effects of infusion of PD156707, 100 mg, or drug vehicle on established vasospasm were assessed. Analysis of physiological variables within (analysis of variance) groups across time and between (unpaired t-test) groups at each time showed that drug-treated animals had significantly increased heart rate on day 7 compared to day 0 (p < 0.005). Comparison of basilar artery diameters at day 7 showed that PD156707 significantly decreased the degree of basilar artery vasospasm (placebo: -47 +/- 5% reduction [mean +/- SE] versus PD156707: -28 +/- 7%, p < 0.05, unpaired t-test). There was, however, significant vasospasm when comparing within groups (paired t-test, placebo: p < 0.0001, PD156707: p < 0.005). Mean plasma PD156707 levels (322 +/- 123 ng/ml) were adequate to block responses of endothelin-1 on endothelin A receptors in vitro although CSF levels (11 +/- 7 ng/ml) were substantially lower. Infusion of PD156707 into the basilar artery on day 7 caused a small but significant 10 +/- 3% (paired t-test, p < 0.01) increase in diameter compared to placebo (3 +/- 3% increase, p = 0.32). This infusion also was associated with a substantial increase in CSF drug levels to 19 +/- 9 mg/ml. These results suggest that endothelin A receptors mediate some of the vasospasm that occurs after SAH in dogs and that blockade of these receptors may be a beneficial treatment for vasospasm.

Animals↗

PubMed1995

The effect of hypothermia on induction of heat shock protein (HSP)-72 in ischemic brain.

Intra-ischemic hypothermia has been demonstrated to be protective against ischemic neuronal injury. The present study examined the effect of moderate hypothermia on the expression of heat shock protein (HSP)-72 following transient forebrain ischemia in gerbils by immunohistochemistry. Global forebrain ischemia with concurrent moderate hypothermia (30 degrees C) was induced in gerbils by 10-minute bilateral carotid artery occlusion followed by recirculation periods of 1 hour (h), 6h, 24h, and 48h. Normothermic forebrain ischemic animals with similar recirculation periods were utilized for comparison of the HSP expression. Sham-operated normothermic and hypothermic animals were also included. 72-kDa heat shock protein immunoreactivity was demonstrated in the hippocampus and neocortex of the normothermic ischemic animals following 24h and 48h recirculation similar to that reported previously. However, the immunoreactivity was absent in the brains of the animals subjected to hypothermic ischemia or sham-operation. Only the ependymal cells were immunopositive in all hypothermic brains as was the case with all normothermic brains. The hypothermic ischemic brains showed no significant necrosis in the hippocampus. These findings suggest that the protection of ischemic neuronal necrosis conferred by intra-ischemic hypothermia is not associated with induction of HSP-72 protein and that mechanisms other then HSP-72 protein induction are likely to be responsible for this neuroprotective effect.

Animals↗

PubMed1991

Comparison of vascular perfusion in ischemia-sensitive and ischemia-resistant regions of gerbil brain by an automated laser cytometric device: a preliminary study.

Reduced blood supply in the hippocampus has been considered to be a factor contributory to this region's selective susceptibility to ischemia. To determine if there are differences in vascularization of vulnerable and resistant regions of the brain, a quantitative morphometric assessment of vascular filling was performed in the gerbil brain by using a relatively new and highly sensitive automated laser cytometric device, ACAS (Adherent Cell Analysis and Sorting). Evan's blue, an intravital vascular tracer, was injected intracardiac in 5 Mongolian gerbils to identify perfused blood vessels in the cortex and CA1 region of hippocampus. Exactly 3 min later, the animal was decapitated, the brain removed and sections prepared for fluorescent quantitative morphometric analysis of blood vessels. The perfused vessels appeared as fluorescent structures due to the autofluorescent property of Evan's blue. Several fields in each of the two specified regions were studied and integrated numbers of blood vessels/mm2 obtained for statistical comparisons. Control brains perfused with normal saline (vehicle for Evan's blue) were used to determine the background fluorescence. The number of perfused blood vessels of all sizes was found to be lower in the CA1 sector of hippocampus than that in the cerebral cortex. The number of capillary size vessels was also lower in the CA1 region but the difference was not significant. Since it is the capillaries that are of prime importance in the diffusion system, and we found no significant regional difference in the density of capillary size vessels, it appears unlikely that the peculiarities of patterns of vascularization contribute significantly to vulnerability to ischemia.

Animals↗

PubMed1980