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Aspirin delays hyperthermia-induced platelet aggregation in pial microvessels of the mouse
P1-45 ASPIRIN DELAYS HYPERTHERMIA-INDUCED PLATELET AGGREGATION IN PIAL MICROVESSELS OF THE MOUSE F. E1-Sabban 1, M. Fahim 1, M. Hasan2, S. Singh 1 Departments of Physiology 1 and Pharmacology2, Faculty of Medicine and Health Sciences, U.A.E. University, P.O. Box 17666, AI Ain, United Arab Emirates Spontaneous platelet aggregation developed in pial microvessels of the mouse when brain surface reached a setpoint of 43; 1°C [E1-Sabban et al., 1994, FASEB J. 8(5): A1039]. Influence of aspirin on such thrombo-embolic events in response to a 45-minute local cerebral hyperthermic exposure at 44°C was studied. Two groups of adult male mice, 14 per group, were subjected to the same protocol except for the injected solution; given 60 minutes prior to hyperthermia. One group received aspirin (pH 7.3, 100 mg/kg, i.p.) and the control group received a vehicle solution, pH 7.3. Intubation of the trachea and craniotomy were performed on anesthetized animals (urethane, 1-2 mg/g, i.p.). Only untraumatized preparations and microvessels of 30-50 microns in diameter were used. A glass well was affixed on the head, through which irrigating artificial cerebrospinal fluid (ACSF) was delivered and drained from. A temperature-controlled perfusion system was used for raising ACSF temperature first to 37oc for a 30-minute stabilization period, then to 44°C. Animal core body temperature was kept at 37°C throughout the entire experiment. An intravital videomicroscopy was utilized for observations and for their recording on tapes for further viewing and analysis. No thrombo-embolic activity was observed when ACSF temperature was at 37oc. In both groups, passing emboli were observed first when ACSF was heated, followed by thrombi a few minutes later, and arteriolar constriction was evident. Compared to control, aspirin delayed the appearance of passing emboli in arterioles (18.6__+4.2 vs 11.5_+4.5 minutes from heating ACSF above 37oc, P<0.05) and reduced arteriolar constriction (5 vs 24%, P<0.01) at that time.
P1-46 HYPERTHERMIA ALTERS CHEMICALLY AND ELECTRICALLY ELICITED CONVULSION IN RATS Mohamed A. Fahim 1, M. Y. Hassan2, F. E1-Sabban 1 Departments of Physiology1 and Pharmacology2, Faculty of Medicine and Health Sciences, U.A.E. University, A1 Ain, United Arab Emirates There is a strong association between hyperthermia and neurological disorders including stroke arid epilepsy. Although heat stress may be implicated in the predisposition of epilepsy, it is not clear which type will eventually develop. Therefore, the effect of acute heat exposure on seizure induction in rats were studied. Two epileptic seizure models were utilized, electric shock and pentylenetetrazol. Acute heat load of 50°C of ambient temperature for five minutes were applied to each rat. Effect of heat stress on various parameters in electric shock-induced convulsion (occurrence of clonic, tonic-clonic convulsion and death) at different current levels and in pentylenetetrazol-induced convulsion (onset of clonic, onset of tonic, clonic incidence and death) at various doses was recorded. Results indicated that hyperthermia modified convulsive states at various, post-exposure levels. In electric shock-induced convulsion, hyperthermia lowered the current threshold to clonic and tonic-clonic seizure development from 61.8 _+4.3 to 50.3 ± 3.9 mA (P<0.01). Death rates were modified at specific current threshold level, as compared to control. In pentylenetetrazol-induced convulsion, heat stress did not modify the onset of first clonic or tonic-clonic seizures; however, the incidence of clonic and myoclonic seizures was increased from 6.2 ± 0.7 to 7.5 ± 0.9 (P<0.01). It is noted that electrically-induced seizures are more susceptible to heat stress and the modifications are most apparent at low threshold levels. Although pentylenetetrazol-induced seizures were less affected by hyperthermia, death rate was increased. In conclusion, it seems that hyperthermia precipitates partial seizure rather than generalized seizures. Since stressful events change the excitatory/inhibitory balance of the central nervous system, such mechanisms might be of relevance. It is also possible that hyperthermia originates free radicals which modulate cell membrane conductivity and facilitate precipitation of epilepsy.
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P1-46 HYPERTHERMIA ALTERS CHEMICALLY AND ELECTRICALLY ELICITED CONVULSION IN RATS Mohamed A. Fahim 1, M. Y. Hassan2, F. E1-Sabban 1 Departments of Physiology1 and Pharmacology2, Faculty of Medicine and Health Sciences, U.A.E. University, A1 Ain, United Arab Emirates There is a strong association between hyperthermia and neurological disorders including stroke arid epilepsy. Although heat stress may be implicated in the predisposition of epilepsy, it is not clear which type will eventually develop. Therefore, the effect of acute heat exposure on seizure induction in rats were studied. Two epileptic seizure models were utilized, electric shock and pentylenetetrazol. Acute heat load of 50°C of ambient temperature for five minutes were applied to each rat. Effect of heat stress on various parameters in electric shock-induced convulsion (occurrence of clonic, tonic-clonic convulsion and death) at different current levels and in pentylenetetrazol-induced convulsion (onset of clonic, onset of tonic, clonic incidence and death) at various doses was recorded. Results indicated that hyperthermia modified convulsive states at various, post-exposure levels. In electric shock-induced convulsion, hyperthermia lowered the current threshold to clonic and tonic-clonic seizure development from 61.8 _+4.3 to 50.3 ± 3.9 mA (P<0.01). Death rates were modified at specific current threshold level, as compared to control. In pentylenetetrazol-induced convulsion, heat stress did not modify the onset of first clonic or tonic-clonic seizures; however, the incidence of clonic and myoclonic seizures was increased from 6.2 ± 0.7 to 7.5 ± 0.9 (P<0.01). It is noted that electrically-induced seizures are more susceptible to heat stress and the modifications are most apparent at low threshold levels. Although pentylenetetrazol-induced seizures were less affected by hyperthermia, death rate was increased. In conclusion, it seems that hyperthermia precipitates partial seizure rather than generalized seizures. Since stressful events change the excitatory/inhibitory balance of the central nervous system, such mechanisms might be of relevance. It is also possible that hyperthermia originates free radicals which modulate cell membrane conductivity and facilitate precipitation of epilepsy.
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