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Biomedical subjects

V Paul

Publications and source records attributed to V Paul.

At least 19 recordsLinked to original sources
PubMed1995

Genomic organization of the human cystathionine beta-synthase gene: evidence for various cDNAs.

A CBS cDNA isolated from an adult liver cDNA library was cloned and sequenced. The 5' untranslated region (5'-UTR) contains a sequence which is only partially common (88nt) with that previously published (3). It is expressed as a 2.5kb species mostly in liver and pancreas and faintly in brain, heart, kidney and lung and as a 3.7 kb in pancreas and liver. The human cystathionine beta-synthase gene (CBS) was isolated from a cosmid genomic library and its structure was determined. The CBS gene is at least 23 kb long and is composed of 17 exons. The organization of the human gene is different from that of the rat especially in the 5'-UTR. In the rat gene the ATG is present in exon 1, conversely in the human gene first the ATG is present in exon 3 and second the 5'-UTR contains two different exons 1 (E1a and E1b) linked with exon 2.

Adult↗
PubMed1995

The concept of "direct mechanical ventricular assistance" in the treatment of left-ventricular failure. Part 1: Idea, development and construction of an implantable multi-chamber pump system partially surrounding the heart.

In this paper we present a therapeutic concept for the treatment of heart failure due to muscular inability to pump properly. The basic principle of this concept triggered numerous studies, then with the aim of cardiopulmonary resuscitation, back in the 1970s. In general, it dealt with mechanical systems which led to an increase in stroke volume, systolic blood pressure, and cardiac output through the application of pressure directly to the left ventricle. After a critical appraisal of the relevant literature from technical, physical, and medical viewpoints, and our own preliminary studies on animal hearts within the framework of mock circulation experiments, we have conceived a new functional principle for direct mechanical ventricular assistance based on squeezing the left ventricle only. We have begun development of the system which has the advantages of ease of use, high biocompatibility due to lack of contact between blood and system components, the prevention of infection through complete intrathoracic implantation (long-range goal), and the fact that the patient's own heart can be supported by the system without being removed from the circulatory system (support of the residual myocardial function). Technical as well as medical prerequisites are indicated, and the materials selection and construction principles of the control, pressure generation, pressure transduction, and ventricular compression unit are described. It has proved possible to construct a prototype system to be used in animal experiments, which, through pneumatic inflation of a chamber system partially surrounding the left ventricle, should be able to augment or take over the pumping function of the left ventricle.

Animals↗
PubMed1995

Cyclodiene insecticides-induced changes in the central depressive effect of chlorpromazine in rats.

Spontaneous motor activity (SMA), conditioned avoidance response (CAR), muscle coordination (MC) and pentobarbital sleep were tested in rats treated orally for 90 days with tolerated doses of the cyclodiene insecticides, aldrin (1 mg/kg) and endosulfan (2 mg/kg). The same tests were repeated in similarly treated animals after injecting chlorpromazine (4 mg/kg, i.p.). Both the insecticides shortened pentobarbital sleeping time indicating their microsomal enzyme inducing property. Aldrin suppressed SMA, CAR and MC, whereas endosulfan stimulated SMA, inhibited CAR and unaltered MC. However, their concurrent action with CPZ did not result in change in the central depressive effects of the latter, but its potency during the course of its action was altered. Its potency 15 min after injection was greater and 60-180 min later was lesser in these animals than that observed in control animals. This finding was interpreted to suggest that aldrin and endosulfan has quickened the biotransformation of CPZ and thereby shortened its duration of action. A temporary promotion of its potency was accounted to its active metabolites, since prior to inactivation, CPZ is known to be metabolized by the microsomal enzymes to active compounds.

Aldrin↗
PubMed1994

The neurobehavioural toxicity of endosulfan in rats: a serotonergic involvement in learning impairment.

Oral administration of the insecticide endosulfan (2 mg/kg per day) for 90 days in immature male rats resulted in an inhibition of pole-climbing escape response to electric shock (unconditioned) and avoidance response to buzzer (conditioned). These responses reflect respectively their learning and memory processes. The escape response but not the avoidance response was reinstated significantly by the 5-hydroxytryptamine (5-HT) depletor, p-chlorophenylalanine (PCPA, 100 mg/kg per day for 3 days). Endosulfan increased 5-HT concentrations in the cerebrum and midbrain regions. Protein content and acetylcholinesterase activity were unaltered in the brain. The spontaneous motor activity of these animals was stimulated. Their muscle coordination on rota-rod apparatus was unaffected. These findings were interpreted as an indication that a motivation deficit and not motor impairment was responsible for the inhibitory action of endosulfan on pole-climbing escape and avoidance responses. Thus, endosulfan was suggested to produce learning and memory deficit. A serotonergic involvement was significant in endosulfan-induced learning impairment and it appeared to be negligible in its memory disrupting action.

Acetylcholinesterase↗
PubMed1994

Postoperative hemodynamic improvement with paced linkage of the donor and recipient hearts following heterotopic cardiac transplantation.

It has been shown that following heterotopic heart transplantation the recipient left ventricle ejects more effectively when it contracts out of phase with the donor left ventricle. However, this is rarely the situation, as the two hearts beat independently of one another and the denervated donor heart tends to beat faster than the recipient. In this study the hemodynamic effects of connecting the two hearts by an external temporary dual-chamber pacemaker were evaluated. The donor right ventricle was sensed and the recipient right atrium paced after a timed delay. The delay was adjusted so that recipient systole coincided with donor diastole. Eleven patients were studied in the first postoperative day. Pacing resulted in an improvement in cardiac output from 5.0 to 5.6 l/min (p = 0.003) and a reduction in pulmonary capillary wedge pressure from 16 to 12 mmHg (p = 0.0035). This was associated with a 35% reduction in inotrope requirements. It is concluded that sequential pacing of the two hearts is a useful adjunct to inotropic support in the postoperative period.

Cardiac Output↗
PubMed1994

A rate responsive pacemaker that physiologically reduces pacing rates at rest.

Current rate responsive pacemakers incorporate sensors such as minute ventilation (MV) for adapting to changing patient conditions during exercise and periods of exertion. However, for sleep and/or rest periods, the only pacemakers currently on the market that slow the pacing rate utilize an internal timer to determine a decrease in pacing rate. It would be advantageous if the pacing rate could be automatically lowered during periods of sleep or rest. This study utilized a rate responsive sensor, MV, to track the patient's sleeping and resting periods and to decrease the pacing rate at such times. A total of eight patients implanted with Sentri 1210 single chamber MV sensor pacemakers were studied. A sleep rate (SR) of 45 beats/min was selected. A sleep rate response function, which indicated the relationship between changes in MV and corresponding heart rate, was initially set at a value of 16 and continually and automatically updated in a 3-month study. Adaptation was based on the premise that 3 hours per day should be spent at the SR. The average decrease in pacing rates from onset to 3 month for the eight patients was 12.4% +/- 5.3%. Correspondingly, the histograms of the lowest datalog histogram (40-59 beats/min) increased from 0% to 15.4% +/- 0.9% of paced beats. Correlation between the patients' 24-hour diary and Holter recordings showed that the pacing rates during sleep were consistently lower than when the patients were awake and active. This was also the case with a patient whose nocturnal and daily routine was intentionally altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Septal short atrioventricular delay pacing: additional hemodynamic improvements in heart failure.

Controversy exists as to whether short AV delay pacing is beneficial in left ventricular dysfunction with the studies performed coming to disparate conclusions. The right ventricular apical pacing previously studied results in asynchronous contraction and relaxation sequences and may limit the potential benefits of short AV delay pacing. In this study the hemodynamic effects of septal (resulting in a more physiological activation sequence) and apical right ventricular activation were compared in 15 patients with heart failure. VDD pacing with AV delays of 50, 100, and 150 msec was evaluated. Apical VDD pacing did not increase the cardiac output significantly, 4.1 +/- 0.75 to 4.45 +/- 0.74 L/min, whereas septal VDD pacing increased the cardiac output to 4.86 +/- 0.79 L/min (P = 0.037). Apical pacing increased the cardiac output in 10 patients and septal pacing in 11 patients. We conclude that selected patients with ventricular dysfunction benefit from short AV delay pacing. Septal ventricular activation confers significant hemodynamic improvements over apical activation.

Atrioventricular Node↗
PubMed1994

Hemodynamic and metabolic effects of paced linkage following heterotopic cardiac transplantation.

BACKGROUND AND PURPOSE: Heterotopic cardiac transplantation is a valuable surgical technique that maximizes the use of donor organs. However, recipient heart function may decline steadily postoperatively with resulting clinical deterioration. Paced linkage has the potential of reducing afterload and enhancing coronary flow of both hearts, thereby improving recipient- and donor-heart function. This may have long-term as well as short-term benefits. METHODS AND RESULTS: The study was performed on 11 heterotopic transplant recipients. The two hearts were linked with a pacemaker (paced linkage) to produce recipient heart systole during different periods of donor-heart diastole. The recipient ventricular contraction was timed to occur during early, mid, and late diastole of the donor heart. Hemodynamic baseline measurements were compared with the optimal counterpulsated data. Paced linkage produced significant improvements in total cardiac output, 5.0 +/- 0.9 compared with baseline 4.5 +/- 0.8 L/min (P = .021); recipient coronary sinus flow, 278 +/- 145 versus 186 +/- 108 mL/min (P = .022); and aortic systolic pressure, 135 +/- 27 versus 123 +/- 27 mm Hg (P = .005). There was an overall improvement in systolic ventricular performance in the recipient heart when pace linked, as evidenced by a significant increase in left ventricular systolic pressure of 118 +/- 36 compared with the baseline value of 108 +/- 33 mm Hg (P = .016), an increase in ejection period from 174 +/- 30 versus 203 +/- 48 (P = .046), and a decrease in the pre-ejection period of 147 +/- 37 when paced versus 181 +/- 39 milliseconds (P = .013). The metabolic studies showed a significant decrease in hypoxanthine release from a baseline level of 0.4 mumol/L to a paced value of -0.06 mumol/L (P = .002); these very low values would suggest that there is no evidence of ischemia. Hemodynamic changes in the donor heart included a significant reduction in the left ventricular end-diastolic pressure from 6.8 +/- 4.4 versus baseline of 10.5 +/- 5.8 mm Hg (P = .029) and in maximum -dP/dT from 3.2 +/- 1.7 versus baseline of 2.1 +/- 1.1. CONCLUSIONS: Paced linkage after heterotopic cardiac transplant produces significant functional improvements in both hearts. Permanent pacemaker implantation may sustain these acute benefits and prevent the premature deterioration of the recipient heart.

Adult↗
PubMed1994

A technique for quantitative measurement of clonic convulsions in rats.

A capacitance sensor which detects vibrations caused by the movements of animals can be used for measuring automatically the clonic convulsions induced by chemical convulsants. This knowledge has been utilized to devise an instrument which has satisfactorily measured the clonic convulsions induced by picrotoxin in rats.

Animals↗
PubMed1993

Effects of procainamide on the signal-averaged electrocardiogram in relation to the results of programmed ventricular stimulation in patients with sustained monomorphic ventricular tachycardia.

OBJECTIVES: The aim of this study was to assess the ability of the signal-averaged electrocardiogram (ECG) to predict the efficacy of procainamide. BACKGROUND: The main role of the signal-averaged ECG has been the identification of postinfarction patients at risk of sudden death. Prediction of the efficacy of antiarrhythmic drugs represents another potential clinical application of this technique. METHODS: The study examined the effects of procainamide on the time domain and spectral temporal analysis of the signal-averaged ECG in relation to the results of programmed ventricular stimulation studies in 31 patients with inducible sustained monomorphic ventricular tachycardia. RESULTS: Procainamide significantly prolonged the total and the initial QRS complex and low amplitude signal durations (mean +/- SD 135 +/- 30 vs. 161 +/- 46 ms, p < 0.0001; 87 +/- 16 vs. 98 +/- 20 ms, p < 0.0001, and 48 +/- 23 vs. 63 +/- 36 ms, p < 0.001, respectively) whereas the root-mean-square voltage of the total QRS complex and of the last 40 ms of the QRS complex was significantly reduced (mean +/- SD 112 +/- 36 vs. 87 +/- 36 microV, p < 0.0001; 21 +/- 19 vs. 13 +/- 12 microV, p < 0.002, respectively). The results of spectral temporal mapping of the signal-averaged ECG were similar before and after procainamide administration. Procainamide prevented the inducibility of sustained ventricular tachycardia or prolonged the cycle length of ventricular tachycardia by > or = 100 ms in 16 patients (52%) (responders). The fractional prolongation of the total QRS duration was significantly greater in responders (26 +/- 15%) than in nonresponders (10 +/- 10%) (p < 0.002) and, when this prolongation was > or = 15%, identified responders with a sensitivity of 94%, a specificity of 87% and an overall predictive accuracy of 90%. CONCLUSIONS: The effects of procainamide on inducibility of ventricular tachycardia during programmed ventricular stimulation can be predicted by the degree of drug-induced prolongation of the signal-averaged QRS complex.

Aged↗
PubMed1993

Behavioural and biochemical changes produced by repeated oral administration of the insecticide endosulfan in immature rats.

In order to study the response of rats to repeated administration of the insecticide, endosulfan during the period of growth to maturity, food intake, body weight gain, Spontaneous Motor Activity (SMA) and Muscle Coordination (MC) were determined at regular intervals in male immature Wistar rats treated with a tolerated dose of (2 mg/kg/day) orally for 90 days. Twenty-four h after the termination of the treatment, organ weight and protein concentrations were determined. The convulsive action of picrotoxin (4 mg/kg, ip) was tested in another endosulfan-treated group. Food consumption and body weight gain decreased parallely. No changes occurred in the body tissues but for liver which was enlarged and its protein, glutamic oxaloacetic transminase and glutamic pyruvic transaminase concentrations increased. The MC was unaffected. A stimulation of SMA occurred several days (75-90) after commencing treatment and these animals responded greatly than control animals to the convulsive action of picrotoxin. These findings indicated that although endosulfan produced anorexia, there were no signs of undernourishment and motor impairment in these animals. Its toxic action were confined chiefly to the liver and central nervous system.

Alanine Transaminase↗
PubMed1992

Effect of intravenous adenosine on human atrial and ventricular repolarisation.

OBJECTIVE: The aim was to assess the effects of therapeutic doses of intravenous adenosine on human atrial and ventricular repolarisation. METHODS: The effects of 6 mg and 12 mg bolus doses of adenosine on the atrial and ventricular monophasic action potentials were studied using the contact catheter technique in 19 patients undergoing routine diagnostic electrophysiology studies. The effect on atrial repolarisation was studied before and after beta blockade in a subgroup of patients. RESULTS: The duration of the monophasic action potential to 90% repolarisation (MAPD90) was measured in all cases. After 6 mg of adenosine the atrial MAPD90 shortened from 227(SD 29) ms to 188(25) ms (p < 0.005); after 12 mg it shortened from 221(31) ms to 168(32) ms (p < 0.001). The maximum shortening was unaltered by propranolol 0.15 mg.kg-1. The ventricular MAPD90 showed no significant change after 12 mg, at 240(32) ms v 234(33) ms. CONCLUSIONS: Therapeutic doses of adenosine shorten the atrial but not the ventricular monophasic action potential duration. The effect is dose dependent and not abolished by beta blockade.

Action Potentials↗
PubMed1992

Prediction of antiarrhythmic efficacy of class I and III agents in patients with ventricular tachycardia by signal-averaged ECG analysis.

The effects of procainamide and dofetilide (pure Class III antiarrhythmic agent) on the signal-averaged ECG (SAECG) were examined in relation to the results of programmed ventricular stimulation studies in 25 patients with inducible sustained monomorphic ventricular tachycardia. Procainamide prolonged significantly the total QRS and low amplitude signal durations (140 +/- 31 msec vs 166 +/- 48 msec, P < 0.0001; 50 +/- 25 msec vs 65 +/- 38 msec, P < 0.002, respectively) whereas the root mean square voltage of the last 40 msec of the QRS complex was significantly reduced (22 +/- 21 microV vs 13 +/- 12 microV, P < 0.006). Procainamide was effective (prevention of the inducibility of sustained ventricular tachycardia or prolongation of the cycle length of ventricular tachycardia by > 100 msec) in 15 of 27 drug trials. Of the procainamide induced SAECG changes, the fractional prolongation of the total QRS duration was the best parameter that identified effectively treated patients (24% +/- 16% in responders vs 10% +/- 11% in nonresponders, P < 0.014). A fractional prolongation of the total QRS duration by > 15% identified effectively treated patients with a sensitivity of 87%, specificity of 81%, and an overall predictive accuracy of 84%. Dofetilide did not change the SAECG, and no SAECG parameter predicted the results of programmed ventricular stimulation. The effects of both drugs on the spectral analysis (area ratios) and on the spectral temporal mapping (the values of normality factor) of the SAECG were not consistent. In conclusion, antiarrhythmic efficacy of procainamide can be predicted by the degree of drug induced prolongation of the signal-averaged QRS complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1992

Evidence for a hazardous interaction between ethanol and the insecticide endosulfan in rats.

Protein supplemented diet was protective against the deleterious action of endosulfan on body growth and liver. Hepatomegaly and a reduction of body weight produced concurrently by endosulfan and ethanol were greater in male rats, suggesting that males are more susceptible than female rats to the metabolic stress caused by their interaction. Chronic endosulfan exposure resulted in a prolongation of ethanol sleeping time in female and not in male rats. This finding suggests failure of female rats to metabolize ethanol readily on account of their greater susceptibility than male rats to the hepatotoxic action of endosulfan.

Animals↗
PubMed1992

Effects of endosulfan and aldrin on muscle coordination and conditioned avoidance response in rats.

The deteriorative effects after chronic endosulfan exposure on muscle coordination, learning and memory of rats were compared with that produced by aldrin which has been reported to have similar effects in experimental animals. A rota-rod apparatus was used to study the muscle coordination and learning and memory were tested by recording the response to unconditioned and conditioned stimuli using a pole-climbing apparatus. Aldrin but not endosulfan inhibited motor coordination in both sexes. A greater motor deterioration occurred in male group. This finding, together with the previous data which shows inhibition by its metabolite of motor activity, suggests that its metabolic product is responsible for this action. Like aldrin, endosulfan inhibited both learning ability and conditioned avoidance response. A change in the activities of brain monoamines or inhibition of perception and reflexes or both were proposed for these behavioural effects, since the former was reported to be produced by both compounds and the latter was found to occur in aldrin treated rats.

Aldrin↗