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Biomedical subjects

T M Sundt

Publications and source records attributed to T M Sundt.

At least 271 records · Page 15Linked to original sources

Suppression of pentylenetetrazole seizures by oral administration of a dihydropyridine Ca2+ antagonist.

We previously demonstrated that the dihydropyridine calcium channel blocker, nimodipine, is an effective anticonvulsant in experimental seizures when administered parentally. Reported now are the results for the oral administration of nimodipine in pentylenetetrazole (PTZ)-induced seizures in the rabbit. Twenty rabbits were randomly assigned into 10 controls and 10 treated with nimodipine 5 mg/kg/day orally for 5 days. All animals received increasing doses of the convulsant PTZ intravenously (i.v). The epileptogenecity of this agent was assessed in all animals (mg/kg) by four electrocorticographic criteria: first seizure greater than 5 s, two seizures within 5 min, epileptiform activity for 1 h, and status epilepticus. In all four categories, nimodipine increased the seizure threshold by 50-60%. The dose of PTZ required to produce the first seizure was 27.0 +/- 5.4 mg/kg in controls and 49.6 +/- 9.9 mg/kg in treated animals (p less than 0.001). Similar values were obtained for the other three electrocorticographic categories. There were no observable adverse side effects. The results confirm our previous findings that calcium influx is critical for seizure induction, and that selective central nervous system (CNS) calcium channel blockers may emerge as a new class of anticonvulsants.

Administration, Oral↗

Anticonvulsant effects of dihydropyridine Ca2+ antagonists in electrocortical shock seizures.

The dihydropyridine calcium antagonists nimodipine (NMD), PN200-110, and nicardipine were compared with phenytoin (PHT) as potential anticonvulsants in electrocortical shock (ECS)-induced seizures in the white New Zealand rabbit. Before treatment, seizure duration ranged from 43.8 +/- 5.1 to 49.6 +/- 5.2 s with an ECS stimulus of 10-V, 100-Hz, 0.1-ms pulses for 5 s. Each drug was administered into the right internal intracarotid artery 2 min before the ECS. A cumulative nimodipine dose of 440 micrograms/kg decreased seizure discharge to 6.6 +/- 5.0 s (p less than 0.001), whereas a total dose of 1.0 mg/kg PN200-110 was required to achieve a similar effect. Nicardipine was ineffective. A cumulative dose of 7 mg/kg phenytoin was required to suppress seizure discharge. These results indicate that Ca2+ channels modulated by dihydropyridines play a facilitating role in ECS-induced seizures. We propose that the anticonvulsant effects of nimodipine and PN200-110 are due to inhibition of neuronal calcium L-channels. Dihydropyridine Ca2+ antagonists that penetrate the blood-brain barrier (BBB) and bind to neuronal tissue may emerge as a novel class of anticonvulsants.

Animals↗

The effect of combined aspirin and dipyridamole therapy on thrombus formation in an arterial thrombogenic lesion in the dog.

We investigated the potential of aspirin and dipyridamole in combination to inhibit thrombus formation by comparing endarterectomized segments of 20 dog carotid arteries in animals treated with pre- and post-operative aspirin and dipyridamole to 20 arteries from untreated animals and 20 arteries from animals receiving intra-operative heparin. The temporal profile of thrombus formation was assessed by means of angiography, light microscopy, and scanning electron microscopy at time intervals ranging from 30 minutes to three months from the time of surgery. All of the aspirin-dipyridamole vessels remained patent and only one had significant gross thrombus formation. This contrasted to six occlusions and six significant gross thrombi in the control group and one occlusion and six significant gross thrombi in the heparin group. The combination of oral aspirin and dipyridamole minimizes thrombus formation in the highly thrombogenic lesion created by carotid endarterectomy in the dog.

Animals↗

5-hydroxytryptamine: source of activator calcium in human basilar arteries.

We performed experiments in human cerebral arteries to determine the source of activator calcium during contractions induced by 5-hydroxytryptamine. Rings of human basilar artery obtained at autopsy were mounted for isometric tension recording in organ baths filled with a physiological salt solution. Contractile responses to 5-hydroxytryptamine were virtually abolished in Ca++-free solution, and inhibited significantly by nimodipine. In both cases, the depression of the response to 5-hydroxytryptamine was comparable to that seen when KCl was used to contract the vessels. These experiments demonstrate that 5-hydroxytryptamine mediates contraction of the smooth muscle in human basilar artery by increasing membrane permeability to extracellular calcium.

Adult↗

Multicenter retrospective review of results and complications of carotid endarterectomy in 1981.

A multicenter retrospective audit of carotid endarterectomies performed during 1981 was completed with 46 institutions contributing 3,328 cases. Overall, there was a 2.5% risk of transient neurological dysfunction following surgery and a 6% risk of stroke or death. The intra-institutional combined major morbidity and mortality varied from 21% to 0. Those institutions with greater than 700 beds had a statistically lower incidence of stroke or death than did other institutions. The incidence of stroke or death postoperatively was significantly lower for patients who were operated on for amaurosis fugax or for unspecified reasons. Those patients who were operated on for a progressing stroke had a higher incidence of stroke but this group was at greatest risk for stroke without surgery. The incidence of postoperative stroke or death was related to the type of arterial repair; vein patch grafting was statistically better than both fabric patch grafting and primary closure. When all patients who were not monitored during surgery were compared to all patients who had electroencephalographic (EEG) monitoring, there was found to be a significant statistical difference in favor of the EEG group. Endarterectomy combined with coronary artery bypass or simultaneous bilateral endarterectomies had a statistically significant higher incidence of stroke or death than did unilateral carotid endarterectomy.

Canada↗