Effects of vasoactive substances released from ischemic reperfused liver on the isolated rat heart.

BACKGROUND: Cardiovascular dysfunction frequently occurs after major vascular surgery or liver transplantation. OBJECTIVE: To evaluate the effects on myocardial activity of vasoactive agents released from ischemic-reperfused liver. ANIMALS AND METHODS: Isolated rat livers were perfused with Krebs-Henseleit solution (KH), propranolol 10(-5) M, losartan 2x10(-5) M and indomethacin 10(-5) M, then made globally ischemic for 120 min (37 degrees C) and reperfused. Isolated hearts from other rats were stabilized with KH and reperfused for 15 min with the perfusate exiting the livers. Livers were disconnected, and the hearts continued to be recirculated with the accumulated liver and heart effluent for an additional 50 min. Enzyme leakage, different vasoactive substances, left ventricular developed pressure (LVP) and coronary flow were measured during the experimental protocol. RESULTS: Hepatic release of adrenaline, noradrenaline, angiotensin II, prostaglandin E(2) and thromboxane B(2) was significantly increased in the liver effluent following ischemia. When this effluent was directed to the heart, LVP was significantly raised in the first 10 min of reperfusion (137+/-5%) followed by marked decreased (46+/-6%) during the following 65 min of myocardial reperfusion. In the ischemic-reperfused drug-treated groups, the initial positive effect on LVP was milder than in controls (propranolol 112+/-12%, losartan 111+/-11%, indomethacin 113+/-9%) and the final LVP was lower (propranolol 29+/-6%, losartan 27+/-7% [P<0.05 versus ischemic control], indomethacin 46 +/-12%). CONCLUSION: During the initial phase of reperfusion, vasoactive substances released in the hepatic effluent potentiated LVP of the hearts exposed to this effluent. When the three inhibitory drugs were added to KH, this initial augmentation was not sustained. Propranolol and losartan, but not indomethacin, further depressed LVP. Vasoactive substances released from ischemic reperfused livers directly influenced heart function.

Clinical, psychophysiological, and neurological characteristics of volunteers with impaired smooth pursuit eye movements.

Two hundred eighty-five volunteers from a community college were screened on campus for accuracy of their smooth pursuit eye movements (SPEM) by electrooculograph (EOG). Those volunteers with the least and the most accurate SPEM were recalled to the laboratory for a comprehensive evaluation of clinical and demographic characteristics, family history, neurological status, and psychophysiological and biological measures, including SPEM [repeat EOG test and infrared (IR) test], an electroencephalogram, auditory and visual evoked potentials, reaction time (RT), the continuous performance task (CPT), platelet monoamine oxidase (MAO), plasma amine oxidase, and dopamine-beta-hydroxylase (DBH). Low-accuracy SPEM was associated with social isolation, inadequate rapport, eccentricity, and a variety of related schizotypal or schizophrenia-like characteristics, but not with generalized psychopathology or other demographic/medical/clinical history variables. Low-accuracy SPEM also was associated with neurological and psychophysiological abnormalities frequently observed in schizophrenic patients. These results suggest that impaired SPEM may reflect an underlying central nervous system dysfunction that is specifically associated with clinical and biological characteristics related to schizophrenia, even in the absence of overt schizophrenia.

A new scale for the assessment of depressed mood in demented patients.

Twenty-one subjects with clinically diagnosed dementia of the Alzheimer type were rated on the Dementia Mood Assessment Scale, a new instrument intended to measure the severity of depressed mood in cognitively impaired patients. Ratings were based on direct observation and a semistructured interview of the patient. Interrater reliability was established. There were highly significant correlations between patients' scores on the instrument's 17-item depression subscale and their scores on global measures of depression and sadness. The potential usefulness of this new scale in assessing the severity of depression in demented patients longitudinally or under drug treatment conditions is discussed.

Eye-tracking, attention and amphetamine challenge.

Smooth pursuit eye movement (SPEM) performance has been linked to nonvoluntary attentional processes. Amphetamine is a psychotropic drug with documented effects on attentional performance. In order to evaluate the relationship between SPEM performance and amphetamine's attentional effects, SPEM performance was measured prior to and following amphetamine administration in five bipolar patients and eight obsessive-compulsive patients. In these 13 patients, amphetamine did not significantly alter the accuracy of SPEM in the two patient groups. However, significant negative correlations were observed in the obsessive-compulsive patients and in the combined patient groups between baseline SPEM impairment and changes in eye-tracking accuracy following amphetamine, i.e. individuals with poorer SPEM accuracy improved while better SPEM performers deteriorated in tracking accuracy during amphetamine treatment.

Smooth pursuit eye movement disorder and its psychobiologic correlates in unmedicated schizophrenics.

The accuracy of smooth pursuit eye movements (SPEMs) was evaluated electrooculographically in 14 medication-free schizophrenics. Concentrations of monoamine metabolites and gamma-amino-butyric acid (GABA) were measured in their cerebrospinal fluid (CSF). Ventricular-brain ratios (VBR) were determined by computed axial tomography (CT scan). Premorbid adjustment was evaluated by the Phillips Scale. The SPEMs of eight of the patients were reevaluated after 2 weeks of treatment with either prazosin or pimozide. No consistent significant correlations were found between SPEM accuracy and CSF metabolite concentrations, VBR, or premorbid adjustment. SPEM accuracy was not correlated with number of days off medication and was significantly correlated when measured before and during medication.

Obsessive-compulsive disorder and serotonin: is there a connection?

Reports of the antiobsessional efficacy of clomipramine have led to a "serotonin hypothesis" of obsessive-compulsive disorder (OCD). To test this hypothesis, 16 outpatients with DSM-III OCD were studied using several measures of serotonergic function. Platelet 3H-imipramine binding and serotonin uptake were not significantly different between the OCD patients and a normal, age-matched control group. The level of the metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) was significantly higher in a small cohort of obsessionals compared with healthy volunteers, possibly reflecting increased brain serotonin turnover. In a direct test of the role of serotonin uptake in clomipramine's antiobsessional effects, the serotonin uptake inhibitor zimelidine was compared with the noradrenergic uptake inhibitor desipramine in a double-blind, controlled study. Zimelidine reduced CSF 5-HIAA, but was clinically ineffective in this group. Desipramine had weak but significant clinical effects. Nonresponders to zimelidine or desipramine improved significantly during a subsequent double blind trial of clomipramine. These findings demonstrate that pharmacological blockade of serotonin reuptake alone is not sufficient for an antiobsessional response.

Impaired smooth pursuit eye movement: vulnerability marker for schizotypal personality disorder in a normal volunteer population.

Impaired smooth pursuit eye movement has been proposed as a possible biologic marker for schizophrenia. Preliminary studies have suggested that this impairment may be associated with social introversion and related psychopathology in a nonpsychiatric population. To evaluate the relationship between dysfunctional smooth pursuit eye movement and schizophrenia-related psychopathology, the authors screened a new, volunteer sample of 284 male college students for eye tracking accuracy. Volunteers identified as low-accuracy trackers were significantly more likely to be diagnosed (blindly) as having a schizotypal personality disorder by DSM-III criteria than those identified as high-accuracy trackers. The authors suggest that disordered smooth pursuit eye movement may reflect a vulnerability marker for schizotypal personality disorder.

Neurological and neuropsychological studies of patients with obsessive-compulsive disorder.

We studied 18 DSM-III diagnosed obsessive-compulsive disorder patients with the Halstead-Reitan Battery (HRB), EEGs, and CT scans. Results for the group as a whole were within the normal range; however two patients had abnormal EEGs and four showed average impairment ratings on the HRB high enough to suggest organic deficits. More than half of the subjects were impaired on the tactual performance test from the HRB suggesting a possible deficit in spatial perception. These data, however, do not define a single neuropsychological deficit nor do they replicate an earlier report of left frontal lobe dysfunction in obsessive-compulsive disorder. Cerebral CT scans in ten patients, including all those with EEG and average impairment rating abnormalities, showed VBR, asymmetry, and sulcal prominence measures indistinguishable from a matched group of nonpsychiatric control subjects.

Obsessive-compulsive disorder. A double-blind trial of clomipramine and clorgyline.

Patients with obsessive-compulsive disorder who met DSM-III criteria and who had been ill for at least one year were studied in a double-blind, randomized, crossover comparison of the tricyclic antidepressant clomipramine hydrochloride and the monoamine oxidase inhibitor clorgyline hydrochloride. No significant improvement was evident after four weeks of treatment with placebo prior to the crossover study. Treatment with clomipramine was associated with significant improvement after both four and six weeks in measures of obsessions, anxiety, and depression. Antiobsessional responses to clomipramine did not depend on presence of depression. Improvement was correlated with plasma concentrations of clomipramine, but not with the plasma concentrations of any of its metabolites. No significant improvement was evident for the entire group with clorgyline treatment, although the conditions of individual patients did respond to the drug.

Lithium and mood change in affective disorder patients.

The authors evaluated whether the dysphoric effects reported by normals given lithium in several recent studies might also be found in depressed patients if detailed self-ratings were used in a double-blind study design. Nine depressed patients were studied at the end of lithium and placebo treatment trials. No overall adverse effects of lithium were found for the entire group, but individuals showed significant inverse correlations between pretreatment dysphoria and depression and the development of these symptoms with lithium, i.e., the less dysphoric and depressed patients (the more "normal" individuals) did report more adverse symptoms while the patients with higher initial symptom scores rated themselves as improved.