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Studies of meclofenamic acid and two metabolites in horses--pharmacokinetics and effects on exercise tolerance.

The pharmacokinetics and the effects on treadmill exercise of the anti-inflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two-compartment open model. The average elimination half-life was 1.4 h, the apparent volume of distribution 0.14 l/kg and the plasma clearance 0.12 l/h kg. Absorption was the rate-limiting step after oral administration. Non-compartmental analysis showed a mean absorption time of 4.3 h. The pharmacokinetics of two metabolites of meclofenamic acid were also studied in two of the horses. The elimination half-lives of the two metabolites were virtually the same in each horse (3.0 h and 3.4 h). The blood lactate response to exercise was significantly decreased after treatment with meclofenamic acid, indicating a lower utilization of the glycolytic ('anaerobic') energy contribution during exercise. Circulatory capacity was apparently unaffected with an unchanged heart rate response to exercise.

Absorption↗

[Maximal respiratory pressures and exercise tolerance in patients with COPD].

UNLABELLED: Many authors reported respiratory muscle function impairment in patients with chronic obstructive pulmonary disease (COPD). Impaired respiratory muscle function may contribute exercise intolerance which is frequently observed in this disease. AIM OF THE STUDY: was to determine the influence of respiratory muscle function on exercise capacity in patients with COPD. METHODS: 23 patients with stable COPD aged 62.7 +/- 9.3 years (6F, 17M; mean post-bronchodilator FEV1 = 47.9 +/-12.4% value predicted) participated in the study. Exercise capacity was assessed by the six-minute walk test and the incremental cardiopulmonary exercise test (CPET) on a treadmill. Maximal respiratory pressures (PImax, PEmax) were evaluated before and directly after CPET. RESULTS: The mean peak oxygen uptake (VO max) was 27.2 +/- 6.1 mlO2/min/kg and the mean distance walked during the 6MWT was 569.4 +/- 101.7 m. Both PIMax and PE max decreased significantly after maximal exercise (71.4 +/-23.0 vs 63.6 +/- 22.2 cmH2O, p = 0.001 and 124.9 +/- 46.5 vs 112.3 +/- 46.6 cm H2O, p = 0.02 respectively). No correlation between VO2max and the 6-minute walk distance and the maximal respiratory pressures was found. We observed a negative correlation between the 6-minute walk distance and the difference between the pre- and post CPET maximal inspiratory pressure. CONCLUSIONS: respiratory muscle function is impaired in patients with COPD but this does not affect exercise performance. Exercise causes a decrease of the respiratory muscle strength.

Aged↗

Prediction of postoperative exercise tolerance after aortic valve replacement.

Valve size selection for aortic valve replacement is still a controversial matter, particularly in patients with small aortic annuli. To assess optimal valve size, exercise capacity, as measured by peak oxygen consumption levels, was determined in 39 patients (age range, 18 to 77 years; mean, 56 years) who underwent isolated aortic valve replacement with a St. Jude Medical valve. This assessment was carried out at a mean of 2.2 years post-operatively using ergometer exercise testing. These levels were evaluated as a measure of the percentage of predicted. At rest, there was no significant correlation between the predicted peak oxygen consumption and the pressure gradients across the prostheses, as measured by Doppler ultrasound. In 18 patients with aortic regurgitation, the preoperative dimensions of the left ventricle in end-diastole and end-systole correlated inversely (p < 0.05) with the percentage of predicted peak oxygen consumption. In 21 patients with aortic stenosis, the linear regression line (p < 0.01) was derived from the correlation between the percentage of predicted peak oxygen consumption and the valve area index (geometric valve orifice area/body surface area). We conclude that the preoperative end-systolic and end-diastolic dimensions should be less than 50 mm and 70 mm, respectively, in the setting of aortic regurgitation, and a valve area index, though it proved to be weakly correlated with the percentage of the peak oxygen uptake, should probably be more than 1.5 cm2/m2 in the setting of aortic stenosis to achieve good exercise capacity postoperatively (> 80% of predicted peak oxygen consumption).

Adolescent↗

Effect of propranolol on respiratory function and exercise tolerance in patients with chronic obstructive lung disease.

Ten patients with chronic obstructive lung disease (COLD) (group 1) and five patients with combined COLD and cardiac disease (group 2) were studied at rest and during exercise after an intravenous (IV) slaine control followed by IV propranolol (0.2 mg/kg). During rest propranolol did not alter significantly measurements of lung volume in groups 1 or 2. Following propranolol the mean airway resistance (AR) in group 1 increased from 4.49 to 5.2 cm H2O/L/sec (P smaller than 0.02) and airway conductance (Gaw) decreased from 0.28 to 0.24 L/sec-1 cm. H2O1 (P smaller than 0.02). In group 2 following propranolol, the mean AR increased from 3.60 to 4.67 cm H2O1 (P smaller than 0.05), and Gaw decreased from 0.30 to 0.23 L/sec-1/cm H2O1 (P smaller than 0.05). During exercise, from control to propranolol, the heart rate (HR), blood pressure (BP), and heart rate blood pressure (HR x BP) decreased significantly for both groups 1 and 2 except for the systolic pressure in group 2. The duration of exercise and exercising PO2 were not significantly altered from control to propranolol in groups 1 and 2, indicating that the small but statistically significant changes in AR and Gaw did not interfere with symptom tolerated maximal exercise in these patients and were therefore not clinically important.

Airway Resistance↗

Skeletal muscle function and its relation to exercise tolerance in chronic heart failure.

OBJECTIVES: This study sought to define the relation between muscle function and bulk in chronic heart failure (HF) and to explore the association between muscle function and bulk and exercise capacity. BACKGROUND: Skeletal muscle abnormalities have been postulated as determinants of exercise capacity in chronic HF. Previously, muscle function in chronic HF has been evaluated in relatively small numbers of patients and with variable results, with little account being taken of the effects of muscle wasting. METHODS: One hundred male patients with chronic HF and 31 healthy male control subjects were studied. They were matched for age (59.0 +/- 1.0 vs. 58.7 +/- 1.7 years [mean +/- SEM]) and body mass index (26.6 +/- 0.4 vs. 26.3 +/- 0.7 kg/m2). We assessed maximal treadmill oxygen consumption (VO2), quadriceps maximal isometric strength, fatigue (20-min protocol, expressed in baseline maximal strength) and computed tomographic cross-sectional area (CSA) at midthigh. RESULTS: Peak VO2 was lower in patients (18.0 +/- 0.6 vs. 33.3 +/- 1.4 ml/min per kg, p < 0.0001), although both groups achieved a similar respiratory exchange ratio at peak exercise (1.15 +/- 0.01 vs. 1.19 +/- 0.03, p = 0.13). Quadriceps (582 vs. 652 cm2, p < 0.05) and total leg muscle CSA (1,153 vs. 1,304 cm2, p < 0.005) were lower in patients with chronic HF. Patients were weaker than control subjects (357 +/- 12 vs. 434 +/- 18 N, p < 0.005) and also exhibited greater fatigue at 20 min (79.1% vs. 92.1% of baseline value, p < 0.0001). After correcting strength for quadriceps CSA, significant differences persisted (5.9 +/- 0.2 vs. 7.0 +/- 0.3 N/cm2, p < 0.005), indicating reduced strength per unit muscle. In patients, but not control subjects, muscle CSA significantly correlated with peak absolute VO2 (R = 0.66, p < 0.0001) and is an independent predictor of peak absolute VO2. CONCLUSIONS: Patients with chronic HF have reduced quadriceps maximal isometric strength. This weakness occurs as a result of both quantitative and qualitative abnormalities of the muscle. With increasing exercise limitation there is increasing muscle weakness. This progressive weakness occurs predominantly as a result of loss of quadriceps bulk. In patients, this muscular atrophy becomes a major determinant of exercise capacity.

Case-Control Studies↗