Interaction of GYKI 52466, a selective non-competitive antagonist of AMPA/kainate receptors, with conventional antiepileptic drugs in amygdala-kindled seizures in rats.

GYKI 52466 [1,4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine], a non-competitive AMPA/kainate receptor antagonist, administered i.p. at the dose of 5 mg/kg, exerted a significant anticonvulsant effect, as it decreased seizure and afterdischarge durations, being ineffective at 2 mg/kg. Subsequently, GYKI 52466 (2 mg/kg) was combined with antiepileptic drugs at doses ineffective in fully kindled rats. Co-administration of GYKI 52466 with clonazepam (0.003 mg/kg i.p.) resulted in a significant reduction of seizure severity (by 20%), seizure duration (by 31%) and afterdischarge duration (by 24%). Co-injection of GYKI 52466 with valproate (75 mg/kg i.p.) also resulted in the respective 8%, 16%, and 17% reductions of the three studied seizure parameters. No protection was observed when GYKI 52466 was co-administered with carbamazepine (20 mg/kg i.p.), phenobarbital (20 mg/kg i.p.), or diphenylhydantoin (40 mg/kg i.p.). Combinations of GYKI 524662 with antiepileptic drugs did not cause any significant motor (rotarod test) or long-term memory deficits (passive avoidance task). Only GYKI 52466 administered alone at 5 mg/kg, caused a significant impairment of retention in amygdala-kindled rats. The interaction at a pharmacokinetic level, at least in case of the combination of GYKI 52466 with valproate, can be excluded because GYKI 52466 did not interfere with the free plasma level of valproate. These results give further support to the idea of a potential clinical benefits of the combined treatment of AMPA/kainate receptor antagonists with some antiepileptic drugs.

Successful repair of blunt cardiac rupture involving both ventricles.

Blunt cardiac rupture occurs infrequently and is usually lethal. Successful repairs of isolated atrial or ventricular ruptures have been reported when the diagnosis is made early. Our patient sustained blunt cardiac rupture of both ventricles in a motor vehicle accident. The diagnosis was made during emergency exploratory laparotomy when her vital signs deteriorated without obvious cause. A large Satinsky clamp was placed across the apices of the right and left ventricle to control hemorrhage while the repair was done without cardiopulmonary bypass. She survived and was discharged to home with a normal echocardiogram.

Does routine use of aortic ultrasonography decrease the stroke rate in coronary artery bypass surgery?

PURPOSE: The purpose of this study is to determine whether the routine use of intraoperative surface aortic ultrasonography decreases the stroke rate in coronary artery bypass graft surgery (CABG). METHODS: One hundred ninety-five consecutive patients undergoing CABG between July 1, 1992, and June 30, 1993 (study group), were evaluated by intraoperative surface aortic ultrasonography. Based on information obtained, changes in the operative technique were made in an effort to decrease the incidence of embolic stroke from unsuspected atherosclerotic disease of the ascending aorta. The outcome of these patients was compared with that of 164 consecutive patients who underwent CABG between July 1, 1991, and June 30, 1992 (control group), in whom the ascending aorta was assessed by inspection and palpation only. RESULTS: Significant disease was detected in three (2.0%) of 164 patients in the control group. Modifications in their operative technique consisted of hypothermic fibrillatory arrest with no cross-clamping of the aorta and left ventricular venting in two patients and single cross-clamping in one patient. There were five strokes overall in this group (3.0%), and six patients died (3.6%), one in whom the stroke contributed directly to the cause of death. In the study group the ultrasonic findings were normal to mild in 168 patients, moderate in 20 patients, and severe in seven patients. These results led to a modification of the technique in 19 patients, (10%): hypothermic fibrillatory arrest with no cross-clamping of the aorta and left ventricular venting in 14 patients, modification in the aortic cannulation site or single cross-clamping in three patients, and modification in placement of proximal anastomoses or all arterial grafts in two patients. No strokes occurred in this group (p < 0.02, Fisher's exact test). Five patients died, for an operative mortality rate of 2.6%. CONCLUSION: These data indicate that intraoperative ultrasonography of the ascending aorta with simple modifications in operative technique reduces the stroke rate in CABG.

Idiopathic hypertrophic subaortic stenosis and coronary atherosclerosis. Results of coronary artery bypass alone and myectomy combined with coronary artery bypass.

Twenty-one patients with combined coronary artery disease and idiopathic hypertrophic subaortic stenosis (IHSS) have had coronary artery bypass grafting alone (Group I, n = 7) or in combination with left ventricular septal myectomy (Group II, n = 14). Patients ranged in age from 46 to 73 years (mean 59 years). There were no operative deaths, but one Group I patient died 16 months after operation. Patients in Group I have had continuing symptoms after the operation, whereas Group II patients have had consistent relief of symptoms. Patients with documented IHSS and coronary atherosclerosis should undergo combined coronary bypass and septal myectomy if symptoms recur with medical management.