Systolic time intervals: assessment by isolated cardiac muscle studies

To document the independent effects of acute changes in preload, afterload and inotropic state on the systolic time intervals, 10 isolated rat left ventricular muscle preparations were studied. Experiments were performed using physiologically sequenced contractions that simulate the loading conditions of the intact left ventricle. The preshortening period was measured from the time of the electrical stimulus to the onset of muscle shortening, and the isotonic contraction time was measured as the duration of shortening. These variables are analogous to the preejection period and the left ventricular ejection time in the intact heart. It was found that an isolated increase in preload shortened the preshortening period and prolonged the isotonic contraction time, whereas an increase in afterload prolonged the former and shortened the latter. Isoproterenol shortened both the preshortening period and the isotonic contraction time, while an increase in calcium shortened the preshortening period and lengthened the isotonic contraction time. All changes were significant (p less than 0.01) by analysis of variance. Thus, the similar dependence of preshortening period, isotonic contraction time and clinical systolic time intervals on changes in preload, afterload and inotropic state supports the derivation of systolic time intervals from fundamental principles of myocardial mechanics. These data provide an improved basis for the rational interpretation of systolic time intervals in patients with and without heart disease.     

Physiologic consequences of vasopeptidase inhibition in humans: effect of sodium intake

The in vivo inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were monitored simultaneously by sequentially measuring the urinary excretion of N-Acetyl-Ser-Asp-Lys-Pro and of the atrial natriuretic factor to compare the magnitude and the duration of action of a vasopeptidase inhibitor, omapatrilat, and an ACE inhibitor, fosinopril. Single oral doses of 40 or 80 mg of omapatrilat or 20 mg of fosinopril were administered to 24 normotensive, sodium-depleted or -replete volunteers in a placebo-controlled crossover study. ACE inhibition persisted longer after treatment with omapatrilat than with fosinopril, and there was no major difference between the effects of 40 and 80 mg of omapatrilat. The duration of NEP inhibition by omapatrilat was shorter than that of ACE inhibition. Although omapatrilat effectively inhibited NEP, it had a mild and transient natriuretic effect and did not increase natriuresis more than fosinopril. Omapatrilat induced a decrease in BP and an increase in plasma renin more rapidly and more effectively than fosinopril. The BP and renin effects of omapatrilat persisted despite high sodium intake, which neutralized the effects of fosinopril. The simultaneous inhibition of ACE and NEP may be more effective in reducing BP than the inhibition of ACE alone and less dependent on sodium balance.     

Neuropsychological effects of hyperbaric oxygen therapy in cerebral palsy

We conducted a double-blind placebo study to investigate the claim that hyperbaric oxygen treatment (HBO2) improves the cognitive status of children with cerebral palsy (CP). Of 111 children diagnosed with CP (aged 4 to 12 years), only 75 were suitable for neuropsychological testing, assessing attention, working memory, processing speed, and psychosocial functioning. The children received 40 sessions of HBO2 or sham treatment over a 2-month period. Children in the active treatment group were exposed for 1 hour to 100% oxygen at 1.75 atmospheres absolute (ATA), whereas those in the sham group received only air at 1.3 ATA. Children in both groups showed better self-control and significant improvements in auditory attention and visual working memory compared with the baseline. However, no statistical difference was found between the two treatments. Furthermore, the sham group improved significantly on eight dimensions of the Conners' Parent Rating Scale, whereas the active treatment group improved only on one dimension. Most of these positive changes persisted for 3 months. No improvements were observed in either group for verbal span, visual attention, or processing speed.     

Metabolic and electrophysiological alterations in subtypes of temporal lobe epilepsy: a combined proton magnetic resonance spectroscopic imaging and depth electrodes study

PURPOSE: This study compared the metabolic regional alterations, characterized by proton magnetic spectroscopic imaging ((1)H-MRSI), with electrophysiological abnormalities recorded by using depth electrodes and with structural lesions, in patients with several subtypes of temporal lobe epilepsy (TLE). METHODS: Twenty-five subjects were investigated, including 15 controls and 10 patients with drug-resistant unilateral TLE, nine of whom had structural abnormalities identified by MRI. All patients underwent noninvasive presurgical evaluation and then stereoelectroencephalography (SEEG). We performed an original metabolic exploration combining two (1)H-MRS imaging acquisitions associated with two single-voxel acquisitions (temporal poles) to map the most informative regions of interest (ROIs) including mesial and neocortical localizations. The N-acetyl aspartate/(choline+creatine) ratio was chosen as a metabolic index. SEEG analysis allowed the classification of each ROI as electrically normal or abnormal (i.e., involved in ictal and/or interictal discharges). Groups were compared by using a nonparametric Mann-Whitney U test. RESULTS: N-Acetyl aspartate/(choline+creatine) was significantly lower in all regions involved in SEEG electrophysiological epileptic abnormalities than in controls (p < 0.05). In contrast, the regions without any electrophysiological abnormalities were not metabolically different from those in controls (p > 0.05) except in one ROI. No differences between the metabolic profiles of epileptogenic and irritative zones were found. The metabolic alterations included, but also extended beyond, the lesions. The presence of metabolic abnormalities in mesial structures was not specific for the mesial subtype and generally extended outside the mesial structures. CONCLUSIONS: These results indicate that metabolic abnormalities are linked to ictal and interictal epileptiform activities rather than to structural alterations in TLE.     

Semiologic and electrophysiologic correlations in temporal lobe seizure subtypes

PURPOSE: The International League Against Epilepsy (ILAE) classification distinguishes medial and neocortical temporal lobe epilepsies. Among other criteria, this classification relies on the identification of two different electroclinical patterns, those of medial (limbic) and lateral (neocortical) temporal lobe seizures, depending on the structure initially involved in the seizure activity. Recent electrophysiologic studies have now identified seizures in which medial and neocortical structures are both involved at seizure onset. The purpose of the study was therefore to study the correlations of ictal semiology with the spatiotemporal pattern of discharge in temporal lobe seizures. METHODS: The 187 stereoelectroencephalography-recorded seizures from 55 patients were analyzed. Patients were classified into three groups according to electrophysiologic findings: medial (M; seizure onset limited to medial structures, n=24), lateral (L; seizure onset limited to lateral structures, n=13), and medial-lateral (ML; seizure onset involving both medial and lateral structures, n=18). Clinical findings were compared between groups. RESULTS: Initial epigastric sensation, initial fear, delayed oroalimentary and elementary upper limb automatisms, delayed loss of contact, long seizure duration, and absent or rare secondary generalizations were associated with M seizures. Initial auditory illusion or hallucination, initial loss of contact, shorter duration of seizures, and more frequent generalizations were associated with L seizures. Initial epigastric sensation, initial loss of contact, early oroalimentary and verbal automatisms, and long duration of seizures were associated with ML seizures. CONCLUSIONS: Although the syndrome of mesial temporal epilepsy is now relatively well defined, our findings support the idea that the organization of temporal lobe seizures may be complex and that different patterns exist. We demonstrate three distinct patterns, characterized by both semiologic and electrophysiologic features. This distinction may help to define better the epileptogenic zone and the subsequent surgical procedure.