Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

The cardiovascular electrophysiologic basis for the action of pyridostigmine, an acetylcholinesterase inhibitor, has not been investigated. The objective of the present study was to determine the cardiac electrophysiologic effects of a single dose of pyridostigmine bromide in an open-label, quasi-experimental protocol. Fifteen patients who had been indicated for diagnostic cardiac electrophysiologic study underwent two studies just before and 90-120 min after the oral administration of pyridostigmine (45 mg). Pyridostigmine was well tolerated by all patients. Wenckebach nodal anterograde atrioventricular point and basic cycle were not altered by pyridostigmine. Sinus recovery time (ms) was shorter during a 500-ms cycle stimulation (pre: 326 ± 45 vs post: 235 ± 47; P = 0.003) but not during 400-ms (pre: 275 ± 28 vs post: 248 ± 32; P = 0.490) or 600-ms (pre: 252 ± 42 vs post: 179 ± 26; P = 0.080) cycle stimulation. Pyridostigmine increased the ventricular refractory period (ms) during the 400-ms cycle stimulation (pre: 238 ± 7 vs post: 245 ± 9; P = 0.028) but not during the 500-ms (pre: 248 ± 7 vs post: 253 ± 9; P = 0.150) or 600-ms (pre: 254 ± 8 vs post: 259 ± 8; P = 0.255) cycle stimulation. We conclude that pyridostigmine did not produce conduction disturbances and, indeed, increased the ventricular refractory period at higher heart rates. While the effect explains previous results showing the anti-arrhythmic action of pyridostigmine, the clinical impact on long-term outcomes requires further investigation.

Abnormal response of left ventricular systolic function to submaximal exercise in post-partial left ventriculotomy patients

Patients with heart failure who have undergone partial left ventriculotomy improve resting left ventricular systolic function, but have limited functional capacity. We studied systolic and diastolic left ventricular function at rest and during submaximal exercise in patients with previous partial left ventriculotomy and in patients with heart failure who had not been operated, matched for maximal and submaximal exercise capacity. Nine patients with heart failure previously submitted to partial left ventriculotomy were compared with 9 patients with heart failure who had not been operated. All patients performed a cardiopulmonary exercise test with measurement of peak oxygen uptake and anaerobic threshold. Radionuclide left ventriculography was performed to analyze ejection fraction and peak filling rate at rest and during exercise at the intensity corresponding to the anaerobic threshold. Groups presented similar exercise capacity evaluated by peak oxygen uptake and at anaerobic threshold. Maximal heart rate was lower in the partial ventriculotomy group compared to the heart failure group (119 ± 20 vs 149 ± 21 bpm; P < 0.05). Ejection fraction at rest was higher in the partial ventriculotomy group as compared to the heart failure group (41 ± 12 vs 32 ± 9 percent; P < 0.0125); however, ejection fraction increased from rest to anaerobic threshold only in the heart failure group (partial ventriculotomy = 44 ± 17 percent; P = non-significant vs rest; heart failure = 39 ± 11 percent; P < 0.0125 vs rest; P < 0.0125 vs change in the partial ventriculotomy group). Peak filling rate was similar at rest and increased similarly in both groups at the anaerobic threshold intensity (partial ventriculotomy = 2.28 ± 0.55 EDV/s; heart failure = 2.52 ± 1.07 EDV/s; P < 0.0125; P > 0.05 vs change in partial ventriculotomy group). The abnormal responses demonstrated here may contribute to the limited exercise capacity of patients with partial left ventriculotomy despite...

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61 percent males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (<100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (>280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin

Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 + 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1) - (MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10(-3), STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 + 12.9 to 319,2 + 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 + 1.67 to 19.87 + 2.60 ms, did not change MAP, and reduced P1 from 61.0 + 5.3 to 51.5 + 1.8 arbitrary units (AU), P2 from 41.3 + 0.3 to 29.0 + 1.8 AU, and MN from 171.1. + 30.2 to 77.2 + 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r=-0.76, P=0.03) as well as with the MN index (r=-0.83, P=0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence the results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability.

Atherosclerosis and acute arterial thrombosis in rabbits: a model using ballon desendothelization without dietary intervention

Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1 per cent cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80 per cent) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P<0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches.

Infarto agudo do miocárdio na era trombolítica: elevada mortalidade em pacientes idosos / Acute myocardial infarction in the thrombolytic era: elevated mortality in elderly patients

Pacientes com infarto agudo do miocárdio internados em um hospital geral säo muitos heterogêneros e diferem daqueles relatados em grandes estudos multicêntricos. Objetivo. Analisar a mortalidade intra-hospitalar dos pacientes com infarto agudo do miocárdio (IAM) internados em um hospital geral na era trombilítica, bem como determinar fatores associados com pior prognóstico. Métodos. Foram estudados 113 pacientes com IAM internados consecutivamente no período de um ano no Hospital de Clínicas de Porto Alegre. Foram coletadas diversas variáveis clínicas e laboratoriais relacionadas a um maior risco em pacientes com infarto. Seguindo a rotina do hospital, 47// dos pacientes receberam traombolíticos e seus efeitos e complicaçöes foram estudados. Resultados. A mortalidade intra-hospitalar foi de 19,5//. Na análise univariada, a idade, o sexo e o pico de creatinafosfoquinase se mostraram significativos em predizer o óbito hospitalar. Utilizando o modelo de regressäo logística múltipla, o único fator prognóstico significativo foi a idade, mesmo após ajuste de fatores de pior prognóstico. Em pacientes acima de 70 anos, a mortalidade intra-hospitalr chegou a 41// versus 8,1// nos pacientes com idade inferior a 70 anos. Näo houve diferença significativa na taxa de mortalidade com a presença de outros fatores como: IAM prévio, uso de trombolíticos, insuficiência cardíaca, área infartada, diabétes e hipertensäo arterial. Nos pacientes que receberam trombolíticos, observou-se número elevado de complicaçöes pelo seu uso, das quais em 9,4// foram consideradas graves. Conclusäo. A alta mortalidade intra-hospitalar no IAM, em um hospital geral, está associada à idade avançada dos pacientes. A despeito dos recentes avanços terapêuticos, este grupo de pacientes näo obteve beneficio comparável ao dos pacientes mais jovens

Acute increase in exercise capacity with milrinone: lack of correlation with resting hemodynamic responses

1-The acute administration of milrinone, a positive inotropic vasodilator agent, improves resting hemodynamic function and maximal and submaximal metabolic rsponses to exercice in patients with severe congestive heart failure. 2. to determine whether the improvement in exerecise capacity induced by milrinone administration can be predicted by its acute positive inotropic and/or vasodilator effects at rest, milrinone was adminstered intravenously (progressive doses of 1.5 to 75 microng/Kg) to 15 patients with heart failure (functional classes III and IV, New York Heart Association) at rest, and during maximal upright exercise testing on a cycke ergometer. Serum drug levels were matched for the resting and exercise tests. Drug administration for exercise tests was placebo-controlled and double-blind. 3. At rest, milrinone administration caused substantial decreases in right atrial pressure (-53%), left ventricular end-diastolic pressure (-30%), and systemic vascular resistance (-35%); and increases in cardiac index (+59%), peak positive dP/dt (+20%) and stroke work index (+51%). Administration of milrinone during exercise resulted in a 15% increase in peak oxygen uptake and a 16% increase in anaerobic threshold. However, none of the changes in resting hemodynamic function correlated significantly in magnitude with the changes in peak oxygen uptake and anaerobic threshold. 4. Thus, the acute improvement in exercise capacity that occus with milrinone is not predicted by the positive inotropic or vasodilator effects of the drug at rest

The use of a new non-verbal test in the evaluation of recent memory

A test for recent memory was developed using non-verbal material. The present report describes a series of experiments conducted to evaluate its reproducibility and the influences of changes in the interval between acquisition and tetrieval, and age and level of instruction, and its sensitivity to the integrity of memory function. A total of 114 subjects participated in 5 experiments. The test of recent memory is reproducible over a period of at least 5 months and can be used with training-testing intervals of 24 to 48h. The performance of the test is affected by age and level of instruction. Moreover, thre memory test is sensitive to differences in the integrity of memory function. Thus, the memory test developed in this study may be used to evaluate the effects of behavioral and/or pharmacological manipulations on recent memory in homogeneous groups of subjects

Lack of association between thyroid function and mitral valve prolapse in Graves' disease

To determine whether the association between mitral valve prolapse and Graves' disease is related to thyroid function, three groups of individuals were studied: 16 patients with Graves' disease and hyperthyroidism (hyperthyroid: T4 > 11.5 microng/100 ml), 16 patients with Graves' disease without hyperthyroidism (euthyroid: T4 < 11.5 microng/100 ml), and 40 healthy individuals. The three groups were similar in age, sex distribution, and anthropometrical characteristics. All apatients were evaluated clinically and by M-mode and two-dimensional echocardiopgraphy to determine the presence of mitral valve prolapse. The frequency of mitral valve prolapse was similar in the hyperthyroid (31%) and euthyroid patients (25%), but was higher than in the normal individuals (5%). The frequency of systolic murmur was in the hyperthyroid patients (75%) than the euthyroid patients (19%) or the normal subjects (0%); however, the presence of a murmur was not associated with mitral valve prolapse. Although patients with Graves' disease have a higher frequency of mitral valve prolapse, this is not associated with thyroid function. The presence of a click but not the presence of a systolic murmur may be a clinical indicator of mitral valve prolapse in Graves' disease

Improvement in wall motion after pindolol: a mechanism for the preservation of left ventricular function in coronary artery disease

In order to evaluate the mechanism by which beta blockers with intrinsic sympathomimetic activity preserve left ventricular systolic function at rest, 46 patients with coronary artery disease were studied by right and left heart catheterization and left ventriculography. Patients were studied using a double-blind, randomized protocol before and after a single intravenous dose of 3 mg propanolol (N = 22) or 0.5 mg pindolol (N = 24). Mean right atrial pressure increased similarly after both drugs. Mean pulmonary artery pressure, left ventricular end-diastolic pressure, mean aortic pressure, and peripheral vascular resistance did not change significantly after either drug. Cardiac index (before: 3.0 + or - 0.7(mean + or - SEM); after: 2.8 + or - 0.2 1 min **-1 m**-2) and heart rate (before: 78 + or - 15; after: 72 + or - 12 bpm) deveased only after propranolol administration. Ejection fraction decreased only after propranolol (48 + or - 16 to 41 + or - 15%). Improvement in segmental wall motion abnormalities was noted (23 of 47 segments) only after pindolo. The total left ventricular wall motion score improved after pindolol and worsened after propranolol (P<0.5). In patients with impaired left ventricular function, pindolol administration resulted in improved resting ejection fraction. Thus, the acute hemodynamic consequences of pindolol administration differ from those of propranolol owing to the preservation of left ventricular systolic function which seem to be related to the...