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Biomedical subjects

K Dickstein

Publications and source records attributed to K Dickstein.

At least 19 recordsLinked to original sources
PubMed1992

Effect of timolol on cardiopulmonary exercise performance in men after myocardial infarction.

The effect of the nonselective beta blocker timolol on maximal cardiopulmonary exercise performance was evaluated in 28 men with previous myocardial infarction without effort angina (mean age 63 +/- 8 years). Patients were randomized to placebo or timolol (10 mg twice daily) for 4 weeks and then crossed over to the alternative therapy in a double-blind manner. At the completion of each treatment period, patients underwent symptom-limited maximal cardiopulmonary exercise on a cycle ergometer. Exercise time, heart rate, oxygen consumption (VO2), oxygen (O2) pulse and respiratory exchange ratio were measured at peak exercise and at a submaximal exercise level defined at a respiratory exchange ratio of 1.00. Timolol treatment reduced peak heart rate from 153 +/- 11 to 102 +/- 14 beats/min (-33%, p less than 0.001). Exercise time decreased from 680 +/- 91 to 633 +/- 78 seconds (-7%, p less than 0.001). Peak VO2 decreased from 25.3 +/- 4.7 to 21.4 +/- 3.5 ml/min/kg (-15%, p less than 0.001). O2 pulse increased from 12.9 +/- 1.9 to 16.7 +/- 2.3 ml/beat (+29%, p less than 0.001). Peak respiratory exchange ratio did not change significantly, indicating comparable effort. At submaximal exercise, defined at a respiratory exchange ratio of 1.00, there was no difference in exercise time between placebo and timolol. Heart rate decreased with timolol compared with placebo, from 126 +/- 16 beats/min by 31% (p less than 0.001), VO2 decreased from 18.5 +/- 4.3 ml/min/kg by 10% (p less than 0.001), O2 pulse increased from 11.5 +/- 2.0 ml/beat by 30% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Digitalis therapy in patients with heart failure and sinus rhythm].

The role of digitalis therapy in patients with sinus rhythm and mild to moderate heart failure has been a subject of controversy. This review critically examines the relevant literature and specifically evaluates trials in this patient population. The pharmacokinetics and the pharmacodynamics of the most commonly prescribed agents are briefly discussed. The available evidence supports the use of this agent in patients with sinus rhythm and clinical signs of systolic dysfunction. Digitalis is not recommended as a routine when the primary cause of heart failure is diastolic dysfunction. The use of digitalis therapy in combination with diuretics and vasodilator therapy deserves further attention.

Arrhythmia, Sinus↗
PubMed1991

Effect of long-term enalapril therapy on cardiopulmonary exercise performance in men with mild heart failure and previous myocardial infarction.

Forty-one men with documented myocardial infarction greater than 6 months previously were randomized to long-term (48 weeks) therapy with placebo or enalapril on a double-blind basis. All patients were receiving concurrent therapy with digitalis and a diuretic drug for symptomatic heart failure (functional class II or III). The mean age was 64 +/- 7.3 years and no patient suffered from exertional chest pain. Patients underwent maximal cardiopulmonary exertional chest pain. Patients underwent maximal cardiopulmonary exercise testing to exhaustion on an ergometer cycle nine times over the course of 48 weeks. Gas exchange data were collected on a breath by breath basis with use of a continuous ramp protocol. In the placebo group (n = 21), the mean (+/- SD) peak oxygen consumption (VO2) at baseline was 18.8 +/- 5.2 versus 18.5 +/- 5.5 ml/kg per min at 48 weeks (-1.4%, p = NS). In the enalapril group (n = 20), the corresponding values were 18.1 +/- 3.1 versus 18.3 +/- 2.6 ml/kg per min (+2.8%, p = NS). The mean VO2 at the anaerobic threshold for the placebo group at baseline study was 13.1 +/- 3.5 versus 12.8 +/- 2.1 ml/kg per min at 48 weeks (-2.2%, p = NS). The corresponding values for the enalapril group were 11.8 +/- 2.3 versus 11.8 +/- 2.4 ml/kg per min (+1.4%, p = NS). The mean total exercise duration in the placebo group at baseline study was 589 +/- 153 versus 620 +/- 181 s at 48 weeks (+5.4%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold↗
PubMed1991

Effects of long-term enalapril therapy on cardiopulmonary exercise performance after myocardial infarction.

BACKGROUND: The Enalapril Postinfarction Exercise (EPIE) trial was designed to study the effect of enalapril treatment on peak and submaximal cardiopulmonary exercise performance over the course of 1 year in men after myocardial infarction with mild exercise intolerance. METHODS AND RESULTS: One hundred sixty men with a peak VO2 less than 25 ml/kg/min and without effort angina were randomized to receive enalapril 20 mg qd or placebo on a double-blind basis. The mean age was 60.3 +/- 7.6 years. All patients received concurrent beta-blocker therapy for secondary prophylaxis. Treatment began at 21 days (group 1, n = 100) or more than 6 months after infarction (group 2, n = 60). Patients underwent exercise with real-time gas-exchange analysis nine times over the course of 48 weeks. In group 1, improvement in exercise performance occurred during the course of the trial in both groups of patients receiving placebo or enalapril. The mean peak VO2 for the placebo-treated patients in group 1 increased from 18.3 +/- 3.4 ml/kg/min by 4.9% at 48 weeks (p less than 0.05). The corresponding values for enalapril-treated patients were 18.9 +/- 3.8 ml/kg/min with a 3.7% increase (p = 0.07). Total exercise time increased in the placebo-treated patients from 645 +/- 96 seconds by 7.3% (p less than 0.01). Corresponding values for enalapril-treated patients were 674 +/- 103 seconds with a 5.4% increase (p less than 0.01). In group 2, the mean peak VO2 at baseline for the placebo-treated patients of 20.3 +/- 3.8 ml/kg/min increased by 4.4% at 48 weeks (p = NS). The corresponding values for enalapril-treated patients were 19.2 +/- 3.6 ml/kg/min with a 2.6% increase (p = NS). Total exercise time increased in the placebo-treated patients from 677 +/- 114 seconds by 0.7% (p = NS). Corresponding values for enalapril-treated patients were 659 +/- 99 seconds with a 1.1% increase (p = NS). There were no significant differences between the placebo and enalapril subgroups at any time with regard to peak VO2, exercise duration, or the VO2 at the anaerobic threshold. CONCLUSIONS: This trial demonstrates that long-term converting enzyme inhibition with enalapril had no significant effect on the peak or submaximal cardiopulmonary exercise performance over the course of 1 year in men after myocardial infarction with only mildly reduced exercise capacity.

Aged↗
PubMed1990

Validation of a computerized technique for detection of the gas exchange anaerobic threshold in cardiac disease.

Respiratory gas exchange data were collected from 77 men greater than 6 months after acute myocardial infarction. Maximal exercise was performed on an ergometer cycle programmed for a ramp protocol of 15 W/min. The gas exchange anaerobic threshold (ATge) was determined by analysis of the carbon dioxide elimination (VCO2) vs oxygen consumption (VO2) curve below a respiratory exchange ratio of 1.00 using a computerized algorithm. This value was estimated at the inflection of VCO2 from a line with a slope of 1 which intersects the VCO2 vs VO2 curve. The relation of the ATge to the lactate acidosis threshold was studied in 29 patients. The reproducibility of the ATge method was studied in 77 patients. Mean (+/- standard deviation) VO2 for the ATge was 905 +/- 220 vs 866 +/- 299 ml/min for the lactate acidosis threshold (r = 0.86, p less than 0.001). Mean VO2 at the ATge for test 1 was 968 +/- 225 vs 952 +/- 217 ml/min for test 2 (r = 0.71, p less than 0.001). Mean peak VO2 was 1,392 +/- 379 vs 912 +/- 202 ml/min at the ATge (r = 0.76, p less than 0.001). Results demonstrate that this ATge method correlates well with the lactate acidosis threshold, is reproducible, and should be useful as an objective measure of submaximal exercise performance.

Aged↗
PubMed1990

Plasma atrial natriuretic factor concentration during maximal cardiopulmonary exercise in men with mild heart failure.

The response in terms of production of atrial natriuretic factor to maximal cardiopulmonary exercise was investigated in 13 patients with mild heart failure (New York Heart Association function class II) secondary to previous myocardial infarction. Exercise induced a rapid and gradually increasing production of atrial natriuretic factor. The concentration at the termination of the test was statistically higher than at rest (64.5 +/- 9.7 versus 119.4 +/- 18.3 pmol/l. P = 0.001). Resting levels of the natriuretic factor correlated well to levels at peak exercise (r = 0.797, P = 0.001). The increase in concentration from rest to peak exercise (atrial natriuretic factor delta) was inversely correlated to the peak consumption of oxygen (r = -0.584, P = 0.036), indicating that the response to exercise is not attenuated in the patients with most marked functional impairment. The relationship between resting levels of atrial natriuretic factor and peak consumption of oxygen did not reach statistical significance (r = -0.421, P = 0.152), but a significant inverse relationship was observed between concentration at peak exercise and peak consumption of oxygen (r = -0.671, P = 0.012). Levels of atrial natriuretic factor during peak exercise are related to functional impairment in mild heart failure and may discriminate between the functional capacity of patients belonging in the same class of clinical function.

Aged↗
PubMed1990

A comparison of methodologies in detection of the anaerobic threshold.

Peak cardiopulmonary exercise performance is readily evaluated. The most appropriate methodology for assessment of submaximal exercise performance, however, is a subject of controversy. Therefore, we assessed the difference between conventional methodologies using standard criteria to estimate the onset of anaerobiosis and compared them with known gas exchange and blood lactate [( La]) concentrations. Oxygen uptake (VO2) was determined at both the gas exchange anaerobic threshold (ATge) and the lactate threshold (LaT) using the following three types of commonly used methodologies in a blinded fashion: 1) conventional techniques based on manual inspection of plots of gas exchange indexes and [La] versus time, 2) computerized linear regression analysis of two-segment model plots for VCO2 versus VO2 and log [La] versus log VO2, and 3) fixed values determining the VO2 at a respiratory exchange ratio (VCO2/VO2) of 1.00 and at an [La] of 2 mmol/l. Respiratory exchange data were collected on a breath-by-breath basis in 30 men with documented myocardial infarction. Simultaneously, arterial blood was sampled for [La] every 20 seconds during maximal exercise on an upright bicycle ergometer programmed for a continuous ramp protocol of 15 W/min. The mean (+/- SD) peak VO2 was 1,463 (+/- 312) ml/min. The mean (+/- SD) VO2 values for each method were as follows: (table; see text) These results indicate that a good positive correlation exists between the gas exchange and lactate data by all three approaches. The chosen fixed values yield the highest threshold detection for both ATge and LaT. Detection was lowest using regression analysis for LaT.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

The pharmacokinetics of lisinopril in hospitalized patients with congestive heart failure.

1. The pharmacokinetics of the angiotensin converting enzyme inhibitor, lisinopril, were studied in an open, randomized, balanced, two-period, crossover design in 12 in-patients with stable, chronic congestive heart failure (CHF). 2. To evaluate the pharmacokinetics of lisinopril in CHF, lisinopril was administered orally (10 mg) and intravenously (5 mg) in each patient. Each dose was followed by a 72 h period with frequent blood sampling and fractional urine collections for radioimmunoassay of lisinopril. 3. Mean urinary recovery of lisinopril was 15 and 88% following oral and intravenous administration, respectively; absorption/bioavailability of lisinopril based on urinary recovery ratios was 16%, less than that found in normal subjects. 4. Serum concentrations of lisinopril following intravenous administration were higher in this study than those previously observed in normal subjects. 5. The results of this study suggest a reduced absorption of lisinopril in CHF and altered disposition, possibly associated with age as well as the disease state.

Administration, Oral↗
PubMed1988

Reproducibility of cardiopulmonary exercise testing in men following myocardial infarction.

Peak oxygen consumption during progressive exercise is of clinical relevance in the functional evaluation of the cardiac patient. The use of cardiopulmonary exercise testing for the evaluation of the efficacy of therapeutic intervention requires that the methods used yield reproducible results. This study compared the results of two consecutive, symptom-limited, maximal exercise tests in 170 men following confirmed myocardial infarction. On-line, real-time respiratory gas exchange was measured on a breath-by-breath basis. The data were processed by the system using a 9 s moving average filter and the peak values were determined as averaged over a representative 20-s interval during the final 1 min of the test. The mean (+/- SD) total exercise times for the two tests were 635 (+/- 109) vs. 652 (+/- 112) (r = 0.946). The mean (+/- SD) peak VO2 values were 1480 (+/- 337) vs. 1495 (+/- 350) ml min-1 (r = 0.923). Performance could not be predicted by routine assessment of infarct type or size. This study demonstrates that maximal cardiopulmonary exercise testing in men following myocardial infarction yields highly reproducible results.

Adult↗
PubMed1988

Comparison of topical timolol vs betaxolol on cardiopulmonary exercise performance in healthy volunteers.

The effects of topical timolol vs betaxolol on cardiopulmonary exercise performance were studied in a randomised double-masked fashion in 12 healthy male volunteers. Cardiopulmonary parameters were evaluated at the anaerobic threshold and at peak exercise. Intraocular pressure was determined before and after treatment by applanation tonometry. No differences were found in aerobic or peak exercise capacity. Maximal heart rate was slightly lower (P less than 0.05) following treatment with timolol compared with betaxolol. However, a correspondingly higher oxygen pulse (oxygen uptake/heart rate) compensated for this reduction and resulted in no difference in peak performance. At physiological work levels, it was not possible to demonstrate any influence of topical, selective or non-selective, beta-adrenergic blockade on cardiopulmonary exercise performance in these healthy volunteers.

Adrenergic beta-Antagonists↗
PubMed1988

Clinical pharmacokinetics in heart failure. An updated review.

Pharmacokinetics is the study of the effect that the body has on drug absorption, distribution, metabolism and excretion. The pharmacokinetics of a specific drug are assessed by the volume of distribution, bioavailability, clearance and elimination half-life. Elimination half-life is directly related to the volume of distribution and inversely related to clearance. Any 1 or more of these parameters may be altered by physiological changes such as ageing, or disease states such as congestive heart failure. Congestive heart failure is associated with hypoperfusion to various organs including the sites of drug clearance, i.e. the liver and kidneys. It also leads to organ congestion as seen in the liver and gut. The main changes in drug pharmacokinetics seen in congestive heart failure are a reduction in the volume of distribution and impairment of clearance. The change in elimination half-life consequently depends on whether both clearance and the apparent volume of distribution change, and the extent of that change. Pharmacokinetic changes are not always predictable in congestive heart failure, but it seems that the net effect of reduction in the volume of distribution and impairment of clearance is that plasma concentrations of drugs are usually higher in patients with congestive heart failure than in healthy subjects. The changes in pharmacokinetics assume importance only in the case of drugs with a narrow therapeutic ratio (e.g. digoxin) and some of the antiarrhythmics such as lignocaine (lidocaine), procainamide and disopyramide. This necessitates reduction in both the loading and maintenance doses. Prolongation of the elimination half-life leads to delay in reaching steady-state, and therefore dose increments must be made more gradually. Plasma concentration measurements of the drugs concerned are a good guide to therapy and help to avoid toxicity. Pharmacokinetic changes are of less importance in the case of drugs with immediate clinical response, e.g. diuretics and intravenous vasodilators such as nitrates and phosphodiesterase inhibitors. The dose in the latter group can be titrated to the desired effect. Not all adverse reactions to drugs that may occur in heart failure are the result of alterations in pharmacokinetics; rather, some may be due to important drug interactions. An interaction may occur directly e.g. reduction of renal clearance of digoxin by captopril and quinidine; or indirectly, e.g. through diuretic-induced hypokalaemia, which exacerbate arrhythmias associated with digoxin and antiarrhythmics such as quinidine and procainamide.

Animals↗