Jean Jobin

Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease.

PURPOSE AND METHODS In this study, we examined the fiber-type proportions, cross-sectional areas (CSA), and capillarization from needle biopsies of the vastus lateralis muscle in 20 patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 37 +/- 11% predicted, peak VO2 = 13 +/- 4 mL.min-1.kg-1) and nine age-matched normal subjects (peak VO2 = 33 +/- 7 mL.min-1.kg-1). The effects of endurance training on these parameters were also evaluated in 11 of the 20 patients with COPD. RESULTS The proportion of Type I fiber was smaller in COPD than normals (34 +/- 14% vs 58 +/- 16 in normals, P < 0.0005) with a corresponding increase in Type IIb fiber (P = 0.015). The CSA of Type I, IIa, and IIab fibers was also smaller in COPD. The capillary to fiber ratio tended to be reduced in patients, but this difference did not reach statistical significance (P = 0.15). The number of capillary contact for Type I, IIa, and IIab fibers was significantly reduced in COPD compared with normal subjects (P < 0.05). When corrected for the CSA, this parameter was similar for both groups. After training, peak VO2 increased by 11% (P < 0.05), the fiber-type proportion remained unchanged, and the CSA of Type I and IIa fibers increased by 31 and 21%, respectively (P < 0.05). Although the number of capillary contact for each fiber types increased with training, the capillary to fiber ratio and the number of capillary contact for the different fiber types relative to their CSA remain unchanged. CONCLUSIONS We conclude that in COPD, 1) the vastus lateralis muscle is characterized by a marked decrease in Type I fiber proportion, an increase in Type IIb fiber proportion, a decrease in Type I, IIa, and IIab fiber CSA and by a relatively preserved capillarization; and 2) a 12-wk training program induces a significant increase in Type I and IIa CSA.

Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD

BACKGROUND Enzymatic and histochemical abnormalities of the peripheral muscle may play a role in exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to measure the mitochondrial enzyme activity of the vastus lateralis muscle in patients with COPD and to evaluate the relationship between enzyme activities and functional status. METHODS Fifty seven patients with COPD of mean (SD) age 66 (7) years with forced expiratory volume in one second (FEV1) 39 (15)% predicted and peak oxygen uptake (V˙o 2) of 14 (4) ml/min/kg and 15 normal subjects of similar age were included in the study. Each subject performed a stepwise exercise test up to maximal capacity during which five-breath averages of V˙o 2were measured. Muscle specimens were obtained by percutaneous needle biopsy of the vastus lateralis muscle and the activity of two mitochondrial enzymes (citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH)) was measured. The functional status of the patients was classified according to peakV˙o 2. RESULTS CS and HADH activities were markedly reduced in patients with COPD compared with normal subjects (22.3 (2.7) versus 29.5 (7.3) μmol/min/g muscle (p<0.0001) and 5.1 (2.0) versus 6.7 (1.9) μmol/min/g muscle (p<0.005), respectively). The activity of CS decreased progressively with the deterioration in the functional status while that of HADH was not related to functional status. Using a stepwise regression analysis, percentage predicted functional residual capacity (FRC), the activity of CS, oxygen desaturation during exercise, age, and inspiratory capacity (% pred) were found to be significant determinants of peakV˙o 2. The regression model explained 59% of the variance in peak V˙o 2 (p<0.0001). CONCLUSIONS The oxidative capacity of the vastus lateralis muscle is reduced in patients with moderate to severe COPD compared with normal subjects of similar age. In these individuals the activity of CS correlated significantly with peak exercise capacity and independently of lung function impairment.

Chronic Obstructive Pulmonary Disease: Capillarity and Fiber-Type Characteristics of Skeletal Muscle

BACKGROUND The purpose of this investigation was to compare capillarity and fiber type proportions of the vastus lateralis muscle between patients with chronic obstructive pulmonary disease (COPD) and healthy subjects. METHODS Fifteen male subjects were included in the study (8 COPD: 61.0 +/- 1.8 years [mean +/- SEM]; forced expiratory volume in 1 second 42.0 +/- 2.1% predicted; 7 N: age 54.0 +/- 1.1). Subjects were submitted to a symptom-limited maximal exercise test on ergocycle. After a transcutaneous biopsy of the vastus lateralis muscle, sections were cut 8 to 10 microns thick and stained with the Andersen method for capillarity and Stevens method for fiber typing. RESULTS Patients with COPD had a decrease in peak oxygen consumption compared with healthy subjects (1.2 +/- 0.1 versus 3.0 +/- 0.2 L/min). Number of capillaries per square millimeter was lower in patients with COPD versus healthy subjects (92.6 +/- 16.1 and 213.3 +/- 33.5, P < 0.001); percentages of fiber types were 43.5 +/- 5.5% type I, 56.5 +/- 5.5% type II in COPD, and 56.7 +/- 3.4% type I, 43.2 +/- 3.4% type II in healthy subjects (P < 0.05). In addition, capillaries/fiber ratio was 0.83 +/- 0.05 in COPD, and 1.56 +/- 0.10 in healthy subjects (P < 0.001). CONCLUSION As expected, patients with COPD showed a decrease in exercise capacity. The muscle analysis results indicate that patients with COPD have a greater proportion of type II fibers and a much lower capillaries/fiber ratio than normal subjects. We conclude that COPD adversely affects fiber type and capillarization of the lower limbs. This could be partly caused by deconditioning in these patients.

Peripheral muscle endurance and the oxidative profile of the quadriceps in patients with COPD

Background: Based on previously reported changes in muscle metabolism that could increase susceptibility to fatigue, we speculated that patients with chronic obstructive pulmonary disease (COPD) have reduced quadriceps endurance and that this will be correlated with the proportion of type I muscle fibres and with the activity of oxidative enzymes. Methods: The endurance of the quadriceps was evaluated during an isometric contraction in 29 patients with COPD (mean (SE) age 65 (1) years; forced expiratory volume in 1 second 37 (3)% predicted) and 18 healthy subjects of similar age. The electrical activity of the quadriceps was recorded during muscle contraction as an objective index of fatigue. The time at which the isometric contraction at 60% of maximal voluntary capacity could no longer be sustained was used to define time to fatigue (Tf). Needle biopsies of the quadriceps were performed in 16 subjects in both groups to evaluate possible relationships between Tf and markers of muscle oxidative metabolism (type I fibre proportion and citrate synthase activity). Results: Tf was lower in patients with COPD than in controls (42 (3) v 80 (7) seconds; mean difference 38 seconds (95% CI 25 to 50), p<0.001). Subjects in both groups had evidence of electrical muscle fatigue at the end of the endurance test. In both groups significant correlations were found between Tf and the proportion of type I fibres and citrate synthase activity. Conclusion: Isometric endurance of the quadriceps muscle is reduced in patients with COPD and the muscle oxidative profile is significantly correlated with muscle endurance.

The metabolic syndrome in patients with chronic obstructive pulmonary disease.

PURPOSE This study was undertaken to evaluate the presence of the metabolic syndrome in COPD patients who participated in a cardiopulmonary rehabilitation program. The metabolic syndrome is characterized by the presence of abdominal obesity, atherogenic dyslipidemia, raised blood pressure, presence of insulin resistance, and prothrombotic and inflammatory states that predispose to cardiovascular diseases. METHODS Thirty-eight COPD patients (age: 66 +/- 7 years, [mean +/- SD], FEV1: 43 +/- 16% predicted) and 34 control participants matched for age and gender are included in this study. The criteria for the identification of the metabolic syndrome include 3 or more of the following features: abdominal obesity (waist circumference: > 102 cm in men, > 88 cm in women), triglycerides levels (>or= 1.69 mmol/L), high-density lipoprotein cholesterol levels (< 1.0 mmol/L in men, < 1.3 mmol/L in women), blood pressure (>or= 130/ >or= 85 mm Hg), and fasting glucose levels (>or= 6.1 mmol/L). RESULTS Forty-seven percent of COPD patients and 21% of control participants presented 3 or more determinants of the metabolic syndrome. CONCLUSIONS The presence of metabolic syndrome is frequent in patients with COPD who participated in a cardiopulmonary program. Hence, this population should be considered for screening for the metabolic syndrome.

Hemodynamic and physical performance during maximal exercise in patients with an aortic bioprosthetic valve: comparison of stentless versus stented bioprostheses.

OBJECTIVES The objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to their hemodynamic behavior during exercise. BACKGROUND Stentless aortic bioprostheses have better hemodynamic performances at rest than stented bioprostheses, but very few comparisons were performed during exercise. METHODS Thirty-eight patients with normally functioning stentless (n = 19) or stented (n = 19) bioprostheses were submitted to a maximal ramp upright bicycle exercise test. Valve effective orifice area and mean transvalvular pressure gradient at rest and during peak exercise were successfully measured using Doppler echocardiography in 30 of the 38 patients. RESULTS At peak exercise, the mean gradient increased significantly less in stentless than in stented bioprostheses (+5 +/- 3 vs. +12 +/- 8 mm Hg; p = 0.002) despite similar increases in mean flow rates (+137 +/- 58 vs. +125 +/- 65 ml/s; p = 0.58); valve area also increased but with no significant difference between groups. Despite this hemodynamic difference, exercise capacity was not significantly different, but left ventricular (LV) mass and function were closer to normal in stentless bioprostheses. Overall, there was a strong inverse relation between the mean gradient during peak exercise and the indexed valve area at rest (r = 0.90). CONCLUSIONS Hemodynamics during exercise are better in stentless than stented bioprostheses due to the larger resting indexed valve area of stentless bioprostheses. This is associated with beneficial effects with regard to LV mass and function. The relation found between the resting indexed valve area and the gradient during exercise can be used to project the hemodynamic behavior of these bioprostheses at the time of operation. It should thus be useful to select the optimal prosthesis given the patients body surface area and level of physical activity.

Impact of left ventricular diastolic dysfunction on maximal treadmill performance in normotensive subjects with well-controlled type 2 diabetes mellitus.

Patients with type 2 diabetes often have impaired exercise capacity compared with nondiabetic subjects. Left ventricular (LV) diastolic dysfunction has been shown to limit exercise performance in nondiabetic subjects. Men with well-controlled type 2 diabetes were divided into 2 groups: normal LV diastolic function (group 1, n = 9) or LV diastolic dysfunction (group 2, n = 10) based on standard echocardiographic criteria using pulmonary veins and transmitral flow recordings. They were matched for age and had no evidence of systemic hypertension, macroalbuminuria, coronary artery disease, congestive heart failure, clinical diabetic complications, and thyroid disease. Good metabolic control was demonstrated by glycated hemoglobin levels of 6.7+/-1.6% and 6.6+/-2.5% (means +/- SD) in patients with LV diastolic dysfunction and in controls, respectively. Each subject performed a symptom-limited modified Bruce protocol treadmill exercise test. Maximal treadmill performance was higher in subjects with normal diastolic function compared with subjects with LV diastolic dysfunction when expressed in time (803+/-29 vs. 662+/-44 seconds, respectively, p<0.02) or in METs (11.4+/-1.2 vs. 9.5+/-1.9 METs, respectively, p<0.02). Moreover, there was a correlation between E/A ratio and exercise duration (r = 0.64, p = 0.004) or E/A ratio and METs (r = 0.658, p = 0.003). There were no significant differences in maximal heart rate, maximal systolic and diastolic blood pressure, or maximal rate-pressure product attained during the exercise test. In conclusion, this study demonstrated that LV diastolic dysfunction influences maximal treadmill performance and could explain lower maximal performance observed in patients with type 2 diabetes.

Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity

The prototype “classic” over‐the‐counter antihistamine diphenhydramine was shown to interact with the polymorphic P450 enzyme CYP2D6. This project was undertaken to investigate (1) whether diphenhydramine inhibits the biotransformation of the clinically relevant CYP2D6 substrate metoprolol in vitro and (2) whether this in vitro interaction results in a clinically significant pharmacokinetic and pharmacodynamic drug interaction in vivo. In vitro incubations were carried out with microsomes obtained from lymphoblastic cells transfected with CYP2D6 complementary deoxyribonucleic acid to determine the type and extent of inhibition. We then randomized 16 subjects with genetically determined high (extensive metabolizers) or low (poor metabolizers) CYP2D6 activity to receive metoprolol (100 mg) in the presence of steady‐state concentrations of diphenhydramine or placebo. In vitro, diphenhydramine was a potent competitive inhibitor of metoprolol α‐hydroxylation, exhibiting an inhibitory constant of 2 μmol/L and increasing the Michaelis‐Menten constant of metoprolol sixfold. In vivo, diphenhydramine decreased metoprolol oral and nonrenal clearances twofold and metoprolol→α‐hydroxymetoprolol partial metabolic clearance 2.5‐fold in extensive metabolizers (all P < .05) but not in poor metabolizers (P > .2). Although the hemodynamic response to metoprolol was unaltered by diphenhydramine in poor metabolizers (P > .05), metoprolol‐related effects on heart rate, systolic blood pressure, and Doppler‐derived aortic blood flow peak velocity were more pronounced and lasted significantly longer in extensive metabolizers receiving diphenhydramine compared with poor metabolizers and extensive metabolizers receiving placebo. We conclude that diphenhydramine inhibits the metabolism of metoprolol in extensive metabolizers, thereby prolonging the negative chronotropic and inotropic effects of the drug. Clinically relevant drug interactions may occur between diphenhydramine and many CYP2D6 substrates, particularly those with a narrow therapeutic index.

Differences in Perceived Barriers to Exercise Between High and Low Intenders: Observations Among Different Populations

Purpose. The goal of this study was to describe the salient perceived barriers to exercise in three different groups and to examine the perceived barriers characterizing individuals with a high or a low intention to exercise in the context of the theory of planned behavior. Design. Cross-sectional studies relating perceived barriers and intention to exercise were utilized. Subjects. Three independent samples were used: general population (n=349), individuals who have suffered from coronary heart disease (n=162), and pregnant women (n=139). Measures. Firstly, standard elicitation procedures were applied to identify the particular perceived barriers characterizing each population. Then, three self-administered questionnaires, one per sample, were used to measure perceived barriers and intention to exercise. Results. MANOVA analyses contrasting high and low intenders indicated a significant difference in perceived barriers to exercise in two of the three samples: general population (F5,343=6.37, p<.001) and individuals suffering from coronary heart disease (F9,152=2.28, p<.05). Conclusion. The results indicate not only that each population has specific salient perceived barriers to exercise, but also that within each group high and low intenders differ on a number of these perceived barriers. Therefore, it is recommended that the study of perceived barriers to exercise in any population should be based upon a standardized method of measuring these barriers such as the method adopted in the present study.

Prediction of intention to exercise of individuals who have suffered from coronary heart disease

The aim of the study was to understand the intention to exercise of individuals who suffer from CHD. A group of 161 cardiac patients completed a questionnaire that investigated intentions, attitudes, subjective norms, perceived barriers, habits, perceived difficulties, and personal normative beliefs with respect to exercising, as well as perceived severity of and perceived vulnerability to re-infarction. Regression of intention yielded an R2 of .41 (p less than .0001), with perceived barriers, habits, and perceived difficulties as the significant predictors. MANOVA indicated that high and low intenders differed (p less than .01) according to their perception of three barriers: difficulties in time management, difficulties in psychological adaptation, and laziness. These results suggest that new guidelines should be adopted for the development of cardiac rehabilitation exercise programs.