The present study evaluated whether the unilateral 6-hydroxydopamine (6-OHDA) model of Parkinson's disease produces autonomic deficits. Autonomic parameters were assessed by implanting a small radiofrequency telemetry device which measured heart rate variability (HRV), diurnal rhythms of heart rate (HR), core body temperature (cBT) and locomotor activity (LA). Rats then received 6-OHDA lesion or sham surgery. 6-OHDA lesioned rats exhibited head and body axis biases, defective sensorimotor function ("disengage" test), and prominent apomorphine rotation (all P < .05 versus controls). Diurnal rhythm of HR was lower for 6-OHDA lesioned rats (n = 8) versus controls (n = 6; P < .05). Whilst HR decreased similarly in both groups during the day, there was a greater decrease in HR for the 6-OHDA lesioned rats at night (by 38 b.p.m. relative to 17 b.p.m. for controls). LA and cBT did not differ between surgery groups. This study indicates the unilateral 6-OHDA model of PD shows subtle signs of cardiovascular autonomic dysfunction.

Although the sympathetic nervous system (SNS) plays a major role in mediating the peripheral stress response, due consideration is not usually given to the effects of prolonged stress on the SNS. The present study examined changes in neurotransmission in the SNS after exposure of mice (BALB/c) to stressful housing conditions. Focal extracellular recording of excitatory junction currents (EJCs) was used as a relative measure of neurotransmitter release from different regions of large surface areas of the mouse vas deferens. Mice were either group housed (control), isolation housed (social deprivation), group housed in a room containing rats (rat odor stress), or isolation housed in a room containing rats (concurrent stress). Social deprivation and concurrent stressors induced an increase of 30 and 335% in EJC amplitude, respectively. The success rate of recording EJCs from sets of varicosities in the concurrent stressor group was greater compared with all other groups. The present study has shown that some common animal housing conditions act as stressors and induce significant changes in sympathetic neurotransmission.

Objective: Rapid ventricular pacing in dogs results in a low output cardiomyopathic state similar to idiopathic dilated cardiomyopathy in man. Cell death by apoptosis may play an important role in the loss of cardiac function. This study investigates the molecular pathways involved in the regulation of apoptosis in dogs with pacing-induced heart failure. Methods: Apoptosis was identified by terminal transferase nick end-labelling (TUNEL) in the ventricles and atria of dog hearts affected by rapid-ventricular pacing. Western blots were used to determine expression of the components involved in the initiation (Fas, Fas-Ligand, FADD), regulation (Bcl-2, Bax) and execution (caspase-2 and caspase-3) of apoptosis. Results: Pacing-induced heart failure resulted in a significant increase in the number of ventricular and atrial myocyte nuclei undergoing apoptosis as measured by TUNEL. Compared to the samples from control hearts (n = 6) the expression of Bcl-2, an inhibitor of apoptosis, was significantly reduced in ventricles from five dogs with pacing-induced heart failure. No change in the expression of the apoptotic inducer Bax was detected. Fas and FADD were significantly elevated in all paced ventricles, and Fas-L was only detected in the paced hearts. Both caspase-2 and caspase-3 were elevated following ventricular pacing. Conclusions: We have identified components of the signalling pathways along which apoptosis proceeds following the induction of heart failure in dogs. Apoptosis was also detected in the atria raising the possibility that, like human dilated cardiomyopathy, the molecular changes are global.

The likelihood of successful defibrillation and resuscitation decreases as the duration of cardiac arrest increases. Prolonged cardiac arrest is also associated with the development of acidosis. These experiments were designed to determine whether administration of sodium bicarbonate and/or adrenaline in combination with a brief period of cardiopulmonary resuscitation (CPR) prior to defibrillation would improve the outcome of prolonged cardiac arrest in dogs. Ventricular fibrillation (VF) was induced by a.c. shock in anaesthetised dogs. After 10 min of VF, animals received either immediate defibrillation (followed by treatment with bicarbonate or control) or immediate treatment with bicarbonate or saline (followed by defibrillation). Treatment with bicarbonate was associated with increased rates of restoration of spontaneous circulation. This was achieved with fewer shocks and in a shorter time. Coronary perfusion pressure was significantly higher in NaHCO3-treated animals than in control animals. There were smaller decreases in venous pH in NaHCO3-treated animals than in controls. The best outcome in this study was achieved when defibrillation was delayed for approximately 2 min, during which time NaHCO3 and adrenaline were administered with CPR. The results of the present study indicate that in prolonged arrests bicarbonate therapy and a period of perfusion prior to defibrillation may increase survival.

1 The effects of stress in rats were evaluated by measuring changes in body weight and in responsiveness to noradrenaline (NA) in the isolated vas deferens and atria after the animals had been exposed to restraint or restraint and isolation.2 Animals which were subjected to restraint alone (1 h day(-1) for 3, 7 or 28 days) had a significantly reduced rate of body weight gain. This effect was not potentiated by the additional stress of isolation.3 Restraint alone did not produce significant changes in the responsiveness of the vas deferens to NA. However, adding isolation to restraint, as an additional stress, produced a further leftward shift of the NA dose-response curve for the vas deferens, so that there was a significant increase in sensitivity compared with control.4 There was a significant rightward shift in the NA dose-response curves or reduction in sensitivity in the atria from animals which had been restrained for 7 or 28 days. Isolation did not produce a further rightward shift in the NA dose-response curve.5 The results from this study indicate that the stress associated with repeated restraint reduces the rate of weight gain and reduces the responsiveness of the atria to NA. The responsiveness of the vas deferens to NA was increased by stress, but the combined effect of isolation and restraint was required to produce a significant effect. The differences in the effects of stress on these tissues could be associated with differences in presynaptic receptor populations.

Over the past three decades, developments in technology have enabled the measurement and recording of physiological variables in completely unrestrained animals. Parameters which can be measured by telemetry include biopotentials (electrocardiogram, electromyogram, electroencephalogram), pressures (blood pressure, intracranial pressure, intraocular pressure), temperature, movement, pH and glucose levels. These techniques can be used in laboratory situations, on farms and in studies on free-roaming wild animals. Transmitter implantation usually requires surgery under general anaesthesia, followed by an appropriate recovery period. Telemetry then facilitates the acquisition of data From animals that are not further stressed by handling, insertion of cannulae or probes, anaesthesia or other procedures. In addition to the potential reduction of stress for the animals, data obtained from such studies are likely to be more reliable, because the animals are in a stable physiological state and confounding effects of stress have been reduced or removed. The claim that telemetry is an effective way of achieving refinement is based on the assumption that the transmitters have no negative effects on the animals in which they are implanted. To ensure that this is the case, the impact of the implantation procedure and the transmitter must be evaluated. Telemetry transmitters used in this laboratory in a recent study in mice were found to have a significant effect on noradrenaline dose-response curves obtained in vasa deferentia taken post mortem, 28 days after transmitter implantation. The factors that might have contributed to the observed changes include anaesthesia, surgery and the mass and volume of the implant located in the peritoneal cavity for 28 days.

Canine rapid ventricular pacing produces a low output cardiomyopathic state which is similar to dilated cardiomyopathy. In this study dogs were paced at 245 beats per minute (bpm) for 3-4 weeks until signs of heart failure were apparent. Unpaced dogs were used as controls. A previous study identified myocardial protein changes in the pH region 4-7 following ventricular pacing by using two-dimensional electrophoresis (2-DE) (Heinke et al., Electrophoresis 1998 19, 2021-2030). Many of these proteins were associated with mitochondria, energy metabolism within the cardiomyocyte, the cytoskeleton and calcium cycling. The present study aimed to examine the proteins migrating in the more basic region of the 2-DE pattern using immobilised pH gradient 3-10 strips to separate myocardial proteins. The expression of 31 proteins was altered in the paced myocardium: 21 were decreased and 10 increased. Following the identification of 23 of these spots by either amino acid compositional analysis or peptide mass fingerprinting or a combination of both, we confirm that many of the proteins whose expression is altered following ventricular pacing are associated with the mitochondria and energy production within the cardiomyocyte, including creatine kinase M, triosephosphate isomerase, phosphoglycerate mutase, cytochrome c oxidase, cytochrome b5, hydroxymethyl glutaryl CoA synthase, myoglobin, and 3,2-trans-enoyl-CoA transferase. Additionally, the cytoskeletal protein actin was increased in the paced hearts. These results strongly support the notion that energy production is impaired and mitochondrial dysfunction is involved in the development of heart failure in the paced dog.

Activation of the sympathetic nervous system is an important component of the response to stress, but the effects of prolonged stress on sympathetic neurotransmission have not been assessed. In the present study we have examined the effect of 3 to 10 days exposure to stress induced by frequent handling and sham injections on neurotransmitter release from sympathetic varicosities of the mouse vas deferens. DiOC2(5)-fluorescence was used to visualise the sympathetic varicosities so that extracellular electrodes could be placed over known numbers of varicosities to monitor transmitter release using electrophysiological techniques. The frequency of excitatory junction currents (EJCs) increased with increasing duration of exposure to stress. The mean and maximum EJC amplitude significantly increased by 107% and 43%, respectively after 10 days of exposure to stress. The density of sympathetic varicosities innervating smooth muscle of the mouse vas deferens was not changed throughout the duration of the exposure to stress. The findings from this study demonstrate that the efficacy of transmitter release from the sympathetic varicosities is altered by repeated exposure of mice to stressful stimuli, such as handling and sham injections. Since such procedures are routine in many pharmacological experiments, it is important that investigators are aware of these changes so that due consideration is given when interpreting the data obtained from animals treated in this way.

Ventricular defibrillation studies normally use dogs rather than other large species. To investigate the suitability of sheep, which are often cheaper and more readily available, we compared ventricular fibrillation and defibrillation thresholds (VFT, DFT) in sheep and dogs. A total of 12 sheep (31±5 kg) and six dogs (19±1 kg) were anesthetised with halothane. Fibrillation was induced via epicardial pacing leads, using a 1 s 50 Hz pulse. Biphasic defibrillation shocks were delivered across epicardial patches. Voltage–response curves for both fibrillation and defibrillation were generated. Logistic regression analysis was used to determine 50 and 90% probability of success for fibrillation induction and defibrillation. VFT was similar in sheep and dogs. DFT at 50% probability of success was significantly higher in sheep (369±14 V) than in dogs (299±31 V, P<0.04) but within each species there was no correlation between heart weight and DFT. After defibrillation sheep took longer to return to sinus rhythm than dogs and electro-mechanical dissociation was observed in sheep, but not in dogs. Thus, sheep may not be an ideal model for ventricular defibrillation research but further studies of the intrinsic differences between sheep and dogs may provide insights into basic mechanisms of defibrillation.

The Animal Experimentation Ethics Committee of the University of Sydney is aware of the special educational needs of veterinary science students and others who plan a career in research. Thus, where the defined educational objectives justify the use of animals, the committee approves such use. Undergraduate students in science, medicine and veterinary science participate in animal-based practical classes. Numbers of students in medicine and veterinary science have been fairly constant for 20 years, while numbers in biological and biomedical sciences have greatly increased (for example, the Department of pharmacology which has always used animals in teaching, taught 15-20 science students in 1970/1. In 1995, this number was 350. Despite this increase, the total number of animals used in practical teaching in 1995 was approximately 5% of the number in 1970. For the most commonly used species, the numbers were: mice 55,000 in 1970, 400 in 1995; rats 16,400 in 1970, 3,400 in 1995; rabbits 1,470 in 1970, 60 in 1995 and dogs 2,200 in 1970, and 790 in 1995. Factors which have contributed to these reductions include availability of high quality videotapes and computer-based alternatives, and more careful consideration of the educational objectives and the best way to address these. All animals used in practical classes are registered on a database, which allows researchers access to tissues not required by the class experiment. This facility has been well used and has greatly increased the real reduction in animal use within the university. Students who enrol in an honours year or in graduate, research-based programs attend a 2-day introductory course on animal experimentation. The course promotes the Three Rs by raising awareness in the students of the important ethical and practical issues associated with their work on animals.

The present pilot study evaluated the effect of botulinum toxin A on primarily non-dystonic tremors using accelerometry in a single-blind, placebo-controlled design. Resting, postural, intention, or head tremor were assessed before and approximately 1 month after intramuscular saline and botulinum toxin A (25-50 U) respectively. Half of the patients showed > or = 30% placebo effect. Tremor in 10 of 17 patients (60%) studied improved further after botulinum toxin A (range 30-95%), exceeding the placebo effect by > or = 30%. Nine patients demonstrated clinically significant focal weakness in the extensor muscles after botulinum toxin A which interfered with fine movements. Patients were subdivided into PD-like and ET-like tremor(s). Both groups experienced large placebo effects for resting tremor, with little or no further improvement after botulinum toxin A. The improvement in postural tremor after botulinum toxin A, of 40% in the PD-like and 57% in the ET-like groups, however, was approximately twice that of placebo. In conclusion, botulinum toxin A exerts a modest tremorlytic effect, however the dose, and its distribution over the sites injected, need to be optimised to minimise focal weakness.

Journal of Autonomic PharmacologyVolume 16, Issue 5 p. 269-280 Changes in cardiovascular responsiveness to dopexamine and β1- and β2-adrenoceptor function after the chronic treatment of β-adrenoceptor antagonists and agonists in anaesthetized dogs D. H. -T. Chang, D. H. -T. Chang Department of Pharmacology, The University of Sydney, N. S. W. 2006, AustraliaSearch for more papers by this authorR. Einstein, Corresponding Author R. Einstein Department of Pharmacology, The University of Sydney, N. S. W. 2006, AustraliaProf R. EinsteinSearch for more papers by this author D. H. -T. Chang, D. H. -T. Chang Department of Pharmacology, The University of Sydney, N. S. W. 2006, AustraliaSearch for more papers by this authorR. Einstein, Corresponding Author R. Einstein Department of Pharmacology, The University of Sydney, N. S. W. 2006, AustraliaProf R. EinsteinSearch for more papers by this author First published: October 1996 https://doi.org/10.1111/j.1474-8673.1996.tb00361.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References BASS, A. S., KOHLI, J. D., LUBBERS, N. and GOLDBERG, L. L. (1987). Mechanisms mediating the positive inotropic and chronotropic changes induced by dopexamine in the anesthetized dog. J. Pharmacol. Exp. Ther., 242, 940–944. BLAKE, D. W., WAY, D., TRIGG, L. and MCGRATH, B. P. (1994). 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A device for measuring myocardial contractility. Med. Biol. Engng., 10, 483–495. HALL, J. A., KAUMANN, A. J., WELLS, F. C. and BROWN, M. J. (1988). Beta adrenoreceptor subtypes in human atrium: Selective regulation of β2-adrenoreceptors by atenolol (abstract). Br. J. Pharmacol., 93, 116P. HALL, J. A., KAUMANN, A. J. and BROWN, M. J. (1990). Selective β1-adrenoreceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through β2-adrenoreceptors in human atrial myocardium. Circ. Res., 66, 1610–1623. HALL, J. A., PETCH, M. C. and BROWN, M. J. (1991). In vivo demonstration of cardiac β2-acitenoreceptor sensitization by β1-antagonist treatment. Circ. Res., 69, 959–964. MARTIN, S. W. and BROADLEY, K. J. (1994). Effects of chronic intravenous infusions of dopexamine and isoprenaline to rats on D1-, β1- and β2-receptor-mediated responses. Br. J. Pharmacol., 112, 595–603. MICHEL, M. C., PINGSMANN, A., BECKERINGH, J. J., ZERKOWSKI, H. -R., DOETSCH, N. and BRODDE, O. -E. (1988). Selective regulation of β1 and β2 adrenoreceptors in the human heart by chronic β-adrenoreceptor antagonist treatment. Br. J. Pharmacol., 94, 685–692. MOLENAAR, P., SMOLICH, J. J., RUSSELL, F. D., MCMARTIN, L. R. and SUMMERS, R. J. (1990). Differential regulation of beta-1 and beta-2 adrenoceptors in guinea pig atrioventricular conducting system after chronic (-)-isoproterenol infusion. J. Pharmacol. Exp. Ther., 255, 393–400. MOTOMURA, S., DEIGHTON, N. M., ZERKOWSKI, H. -R., DOETSCH, N., MICHEL, M. C. and BRODDE, O. -E. (1990). Chronic β1-antagonist treatment sensitizes β2-adrenoceptors, but desensitizes M2-muscarinic receptors in the human right atrium. Br. J. Phamacol., 101, 363–369. NANOFF, C., FREISSMUTH, M., TUISL, E. and SCHUTZ, W. (1989). A different desensitization pattern of cardiac β-adrenoceptor subtypes by prolonged in vivo infusion of isoprenaline. J. Cardiovasc. Pharmacol., 13, 198–203. PANFILOV, V., WAHLQVIST, I. and OLSSON, G. (1995). Use of beta-adrenoceptor blockers in patients with congestive heart failure. Cardiovasc. Drugs Ther., 9, 273–287. ROSS, P. J., LEWIS, M. J., SHERIDAN, D. J. and HENDERSON, A. H. (1981). Adrenergic hypersensitivity after beta-blocker withdrawal. Br. Heart J., 45, 637–642. SARSERO, D. and MOLENAAR, P. (1995). Effects of chronic infusion of (-)-isoprenaline on rat cardiac muscarinic (M2)- cholinoceptors and β1- and β2-adrenoceptors. J. Auton. Pharmacol. 15, 239–255. SMITH, G. W., HALL, J. C., FARMER, J. B. and SIMPSON, W. T. (1987). Cardiovascular actions of dopexamine hydrochloride, an agonist at dopamine receptors and β2-adrenoceptors in the dog. J. Pharm. Pharmacol., 39, 636–641. SUMMERS, R. J., MOLENAAR, P., RUSSELL, F., ELNATAN, J., JONES, C. R., BUXTON, B. F., CHANG, V. and HAMBLEY, J. (1989). Coexistence and localization of β1- and β2-adrenoceptors in the human heart. Eur. Heart J., 10(Suppl. B), 11–22. UEMURA, N., NEJIMA, J., HINTZE, T. H., VATNER, D. E., GRAHAM, R. M., HOMCY, C. J. and VATNER, S. F. (1988). Desensitization to norepinephrine and isoproterenol in conscious dogs. Physiologist, 31, A113. VAN VELDHUISEN, D. J., GIRBES, A. R. J., DE GRAEFF, P. A., and LIE, K. I. (1992). Effects of dopaminergic agents on cardiac and renal function in normal man and in patients with congestive heart failure. Int. J. Cardiol., 37, 292–300. WEBB, J. G., NEWMAN, W. H., WALLS, T. and DANIELL, H. B. (1981). Myocardial sensitivity to isoproterenol following abrupt propranolol withdrawal in conscious dogs. J. Cardiovasc. Pharmacol., 3, 622–635. Citing Literature Volume16, Issue5October 1996Pages 269-280 ReferencesRelatedInformation

1. The studies were designed to investigate the changes in responsiveness to beta-adrenoceptor agonists induced by chronic administration of beta-adrenoceptor antagonists and agonists. 2. Dose-response curves for dopexamine, isoprenaline, noradrenaline and impromidine on heart rate, blood pressure and myocardial contractility (dP/dt:integrated isometric tension) were obtained in untreated dogs and compared to those measured in dogs which had been pretreated with propranolol (8 mg kg-1 day-1), atenolol (6 mg kg-1 day-1), isoprenaline (0.5 microgram kg-1 min-1) or noradrenaline (0.5 microgram kg-1 min-1) for 14 days. 3. Propranolol pretreatment significantly enhanced the inotropic and chronotropic responses to isoprenaline. There were noticeable, but non-significant increases in inotropic sensitivity to noradrenaline and dopexamine, especially at higher dose levels. In the atenolol treatment group, there were significant increases in inotropic responses to dopexamine and isoprenaline and in depressor responses to isoprenaline. 4. Thus, chronic administration of propranolol increased responses mediated by both beta 1- and beta 2-adrenoceptors, whereas, atenolol selectively enhanced the inotropic responsiveness to dopexamine, which is mediated mainly by beta 2-adrenoceptors. 5. Isoprenaline pretreatment caused a significant decrease in inotropic sensitivity to dopexamine, isoprenaline and noradrenaline and a significant reduction in chronotropic responses to dopexamine. The tendency to reduced depressor responses to isoprenaline and dopexamine failed to reach significance. Pretreatment with noradrenaline decreased only the inotropic response to noradrenaline. 6. Thus, chronic isoprenaline treatment reduced the responsiveness of both beta 1- and beta 2-adrenoceptors, while chronic noradrenaline infusion only reduced beta 1-adrenoceptor-mediated responses. 7. There was no significant change in any of the dose-response curves to impromidine after any beta-adrenoceptor antagonist or agonist treatment. This indicates that there was no non-specific alteration in responsiveness and that the observed changes were likely to be associated with specific alterations in beta-adrenoceptor number or function.

1. Animals for the study of congestive heart failure (HF) should have chronic, stable disease produced by methods which allow controllable damage and hence predictable disease severity.2. Pressure and volume loading have commonly been used in the past but these methods are limited by the difficulty of controlling the disease severity.3. HF induced by cardiotoxic agents, particularly doxorubicin, has been widely used for experimental purposes, but again, control of the degree of damage may be difficult.4. Coronary artery ligation or occlusion produces heart failure in experimental animals, with clear clinical relevance. Disadvantages of such techniques include fatal arrhythmias and collateral vessel growth that prevents or slows the onset of HF.5. A minimally invasive model of HF which is relatively controllable can be produced by repeated or single DC shocks across the left ventricle.6. Chronic rapid ventricular pacing produces a technically simple, predictable, stable and controllable preparation of HF with neurohumoral and haemodynamic changes which mimic the clinical pattern, These changes are reversible in the short term but after pacing for 1 year or longer complete recovery does not occur after cessation of pacing.7. It has recently been suggested that a single DC shock, three to seven times the threshold defibrillating current, administered to the left ventricle, might provide the basis for the development of a model of heart failure which is technically simple and controllable (Geddes et al. 1994).

1. Animals for the study of congestive heart failure (HF) should have chronic, stable disease produced by methods which allow controllable damage and hence predictable disease severity. 2. Pressure and volume loading have commonly been used in the past but these methods are limited by the difficulty of controlling the disease severity. 3. HF induced by cardiotoxic agents, particularly doxorubicin, has been widely used for experimental purposes, but again, control of the degree of damage may be difficult. 4. Coronary artery ligation or occlusion produces heart failure in experimental animals, with clear clinical relevance. Disadvantages of such techniques include fatal arrhythmias and collateral vessel growth that prevents or slows the onset of HF. 5. A minimally invasive model of HF which is relatively controllable can be produced by repeated or single DC shocks across the left ventricle. 6. Chronic rapid ventricular pacing produces a technically simple, predictable, stable and controllable preparation of HF with neurohumoral and haemodynamic changes which mimic the clinical pattern. These changes are reversible in the short term but after pacing for 1 year or longer complete recovery does not occur after cessation of pacing. 7. It has recently been suggested that a single DC shock, three to seven times the threshold defibrillating current, administered to the left ventricle, might provide the basis for the development of a model of heart failure which is technically simple and controllable (Ceddes et al . 1994).

A repeated-measures study was conducted on 5 dogs to clinically, radiographically, and echocardiographically characterize the actions of the angiotensin-converting enzyme inhibitor, enalapril, before and after development of experimentally induced heart failure. Heart failure was artificially induced, using a surgically implanted programmable ventricular pacemaker, which stimulated the heart at a rate of 245 beats/min until a low-output cardiomyopathic state developed. This condition was then stabilized by decreasing the pacing rate to 190 beats/min. Pacing-induced heart failure was successfully induced in a mean +/- SD 4.2 +/- 1.95 weeks. The condition closely resembled the clinical, radiographic, and echocardiographic features of naturally acquired idiopathic dilated cardiomyopathy in dogs. Enalapril was well tolerated by dogs, and clinical adverse reactions did not develop. Results of echocardiographic studies indicated that enalapril treatment during the control period resulted in a significant (P < 0.05) increase in velocity of circumferential fiber shortening and a significant (P < 0.05) decrease in left ventricular ejection time. Therapeutic responses to enalapril were evident after development of heart failure. These included reduced severity of clinical signs of disease, evidence of decreased radiographically determined cardiac size (2 of 5 dogs), radiographic evidence of a reduction in pulmonary edema and congestion (4 of 5 dogs), significant (P < 0.05) reductions in left atrial and ventricular chamber dimensions (left atrial dimension, diastolic left ventricular internal dimension as determined echocardiographically), and improvement in some echocardiographic indices of left ventricular performance (velocity of circumferential fiber shortening and left ventricular ejection time).

The tremor present in a small number of patients who present with features of both Parkinson's disease (PD) and essential tremor (ET) is ill-defined. We therefore studied 8 such patients with 'atypical' tremor and compared them clinically to 11 PD and 10 ET patients in a double-blind, cross-over, placebo-controlled trial. Tremor was assessed via accelerometry and surface EMG. Tremor frequency and the acute tremorlytic response to propranolol were not useful in discriminating between groups. Over 80% of atypical and PD patients showed alternating EMG, whereas 90% of ET patients had synchronous EMG activity. Tremor amplitude improved by > 90% in 38% of atypical, 27% of PD and none of the ET patients after single-dose L-dopa/benserazide (300/75 mg), a response which was significantly different between the ET and PD groups. Failure to differentiate electrophysiologically and pharmacologically between the atypical and other groups probably relates to clinical heterogeneity in the atypical group.