PubMed Health⌕ Search

Biomedical subjects

D Chemla

Publications and source records attributed to D Chemla.

At least 19 recordsLinked to original sources
PubMed2006

Heart rate responses during the 6-minute walk test in pulmonary arterial hypertension.

Patients with pulmonary arterial hypertension (PAH) exhibit a limited increase in stroke volume on exercise, and the heart rate (HR) increases may reflect the main mechanism that allows cardiac output to increase. The current prospective study documented the contribution of HR to the 6-min walking distance (6MWD) in idiopathic (IPAH) and nonidiopathic PAH. Eighty-three patients (46 IPAH and 37 nonidiopathic PAH) underwent haemodynamic evaluation and a 6MWD test. Chronotropic response (peak walking HR minus resting HR) and peripheral oxygen saturation were monitored. Fifty-seven patients were also assessed after 5+/-2 months of treatment (bosentan n = 38, epoprostenol n = 14, bosentan-epoprostenol n = 3, iloprost n = 2). Before treatment, the 6MWD was related to numerous demographic, haemodynamic and walking test characteristics. Stepwise regression analysis indicated that the only factors significantly associated with the 6MWD were stroke volume and chronotropic response in both IPAH and nonidiopathic PAH patients. Following treatment, changes in 6MWD were significantly related to changes in chronotropic response in both IPAH and nonidiopathic PAH. In conclusion, baseline stroke volume and chronotropic response were independently associated with the 6-min walking distance in pulmonary arterial hypertension. The lack of chronotropic response may reflect the loss in normal physiological reserve in more unwell patients.

Analysis of Variance↗
PubMed2003

Mechanics and crossbridge kinetics of tracheal smooth muscle in two inbred rat strains.

The aim of the study was to determine whether the nonspecific in vivo airway hyperresponsiveness of the inbred Fisher F-344 rat strain was associated with differences in the intrinsic contractile properties of tracheal smooth muscle (TSM) when compared with Lewis rats. Isotonic and isometric contractile properties of isolated TSM from Fisher and Lewis rats (each n=10) were investigated, and myosin crossbridge (CB) number, force and kinetics in both strains were calculated using Huxley's equations adapted to nonsarcomeric muscles. Maximum unloaded shortening velocity and maximum extent of muscle shortening were higher in Fisher than in Lewis rats (approximately 46% and approximately 42%, respectively), whereas peak isometric tension was similar. The curvature of the hyperbolic force/velocity relationship did not differ between strains. Myosin CB number and unitary force were similar in both strains. The duration of CB detachment and attachment was shorter in Fisher than in Lewis rats (approximately -46% and -34%, respectively). In Fisher rats, these results show that inherited, genetically determined factors of airway hyperresponsiveness are associated with changes in crossbridge kinetics, contributing to an increased tracheal smooth muscle shortening capacity and velocity.

Animals↗
PubMed2002

Myosin cross-bridge kinetics in airway smooth muscle: a comparative study of humans, rats, and rabbits.

To analyze the kinetics and unitary force of cross bridges (CBs) in airway smooth muscle (ASM), we proposed a new formalism of Huxley's equations adapted to nonsarcomeric muscles (Huxley AF. Prog Biophys Biophys Chem 7: 255-318, 1957). These equations were applied to ASM from rabbits, rats, and humans (n = 12/group). We tested the hypothesis that species differences in whole ASM mechanics were related to differences in CB mechanics. We calculated the total CB number per square millimeter at peak isometric tension (Psi x10(9)), CB unitary force (Pi), and the rate constants for CB attachment (f(1)) and detachment (g(1) and g(2)). Total tension, Psi, and Pi were significantly higher in rabbits than in humans and rats. Values of Pi were 8.6 +/- 0.1 pN in rabbits, 7.6 +/- 0.3 pN in humans, and 7.7 +/- 0.2 pN in rats. Values of Psi were 4.0 +/- 0.5 in rabbits, 1.2 +/- 0.1 in humans, and 1.9 +/- 0.2 in rats; f(1) was lower in humans than in rabbits and rats; g(2) was higher in rabbits than in rats and in rats than in humans. In conclusion, ASM mechanical behavior of different species was characterized by specific CB kinetics and CB unitary force.

Animals↗
PubMed2002

Haemodynamic evaluation of pulmonary hypertension.

Pulmonary hypertension is characterised by the chronic elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) leading to right ventricular enlargement and hypertrophy. Pulmonary hypertension may result from respiratory and cardiac diseases, the most severe forms occurring in thromboembolic and primary pulmonary hypertension. Pulmonary hypertension is most often defined as a mean PAP >25 mmHg at rest or >30 mmHg during exercise, the pressure being measured invasively with a pulmonary artery catheter. Doppler echocardiography allows serial, noninvasive follow-up of PAPs and right heart function. When the adaptive mechanisms of right ventricular dilatation and hypertrophy cannot compensate for the haemodynamic burden, right heart failure occurs and is associated with poor prognosis. The haemodynamic profile is the major determinant of prognosis. In both primary and secondary pulmonary hypertension, special attention must be paid to the assessment of pulmonary vascular resistance index (PVRI), right heart function and pulmonary vasodilatory reserve. Recent studies have stressed the prognostic values of exercise capacity (6-min walk test), right atrial pressure, stroke index and vasodilator challenge responses, as well as an interest in new imaging techniques and natriuretic peptide determinations. Overall, careful haemodynamic evaluation may optimise new diagnostic and therapeutic strategies in pulmonary hypertension.

Blood Pressure↗
PubMed2001

Pulmonary artery pulse pressure and wave reflection in chronic pulmonary thromboembolism and primary pulmonary hypertension.

OBJECTIVES: The purpose of this time-domain study was to compare pulmonary artery (PA) pulse pressure and wave reflection in chronic pulmonary thromboembolism (CPTE) and primary pulmonary hypertension (PPH). BACKGROUND: Pulmonary artery pressure waveform analysis provides a simple and accurate estimation of right ventricular afterload in the time-domain. Chronic pulmonary thromboembolism and PPH are both responsible for severe pulmonary hypertension. Chronic pulmonary thromboembolism and PPH predominantly involve proximal and distal arteries, respectively, and may lead to differences in PA pressure waveform. METHODS: High-fidelity PA pressure was recorded in 14 patients (7 men/7 women, 46 +/- 14 years) with CPTE (n = 7) and PPH (n = 7). We measured thermodilution cardiac output, mean PA pressure (MPAP), PA pulse pressure (PAPP = systolic - diastolic PAP) and normalized PAPP (nPAPP = PPAP/MPAP). Wave reflection was quantified by measuring Ti, that is, the time between pressure upstroke and the systolic inflection point (Pi), deltaP, that is, the systolic PAP minus Pi difference, and the augmentation index (deltaP/PPAP). RESULTS: At baseline, CPTE and PPH had similar cardiac index (2.4 +/- 0.4 vs. 2.5 +/- 0.5 l/min/m2), mean PAP (59 +/- 9 vs. 59 +/- 10 mm Hg), PPAP (57 +/- 13 vs. 53 +/- 13 mm Hg) and nPPAP (0.97 +/- 0.16 vs. 0.89 +/- 0.13). Chronic pulmonary thromboembolism had shorter Ti (90 +/- 17 vs. 126 +/- 16 ms, p < 0.01) and higher deltaP/PPAP (0.26 +/- 0.01 vs. 0.09 +/- 0.07, p < 0.01). CONCLUSIONS: Our study indicated that: 1) CPTE and PPH with severe pulmonary hypertension had similar PA pulse pressure, and 2) wave reflection is elevated in both groups, and CPTE had increased and anticipated wave reflection as compared with PPH, thus suggesting differences in the pulsatile component of right ventricular afterload.

Adult↗
PubMed2001

Myosin cross bridges in skeletal muscles: "rower" molecular motors.

Different classes of molecular motors, "rowers" and "porters," have been proposed to describe the chemomechanical transduction of energy. Rowers work in large assemblies and spend a large percentage of time detached from their lattice substrate. Porters behave in the opposite way. We calculated the number of myosin II cross bridges (CB) and the probabilities of attached and detached states in a minimal four-state model in slow (soleus) and fast (diaphragm) mouse skeletal muscles. In both muscles, we found that the probability of CB being detached was approximately 98% and the number of working CB was higher than 10(9)/mm(2). We concluded that muscular myosin II motors were classified in the category of rowers. Moreover, attachment time was higher than time stroke and time for ADP release. The duration of the transition from detached to attached states represented the rate-limiting step of the overall attached time. Thus diaphragm and soleus myosins belong to subtype 1 rowers.

Animals↗
PubMed2001

Angiotensin-converting enzyme inhibitor therapy improves respiratory muscle strength in patients with heart failure.

STUDY OBJECTIVES: Respiratory muscle strength has been shown to be reduced in patients with chronic heart failure. The purpose of this prospective study was to determine whether long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor perindopril improves respiratory muscle strength in patients with chronic heart failure. PATIENTS AND METHODS: Eighteen patients with stable chronic heart failure were administered perindopril, 4 mg/d, in addition to their standard therapy for a period of 6 months. Fourteen patients completed the study. Maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) expressed in percentage of predicted values, left ventricular ejection fraction (LVEF) determined by means of two-dimensional echocardiography, and pulmonary volumes were obtained before and after therapy. MEASUREMENTS AND RESULTS: As compared to baseline, there was a significant increase in both PImax and PEmax after therapy (57 +/- 27% predicted vs 78 +/- 36% predicted and 62 +/- 20% predicted vs 73 +/- 15% predicted, respectively; each p < 0.05). LVEF increased (34 +/- 5% vs 41 +/- 10%; p < 0.05); functional class improved by > or = 1 New York Heart Association (NYHA) class in five patients. There were no changes in pulmonary volumes. No correlation was found between changes in PImax and PEmax and changes in either LVEF or NYHA functional class. CONCLUSIONS: In patients with chronic heart failure, long-term therapy with the ACE inhibitor perindopril improved respiratory muscle strength, as indicated by significant increases in PImax and PEmax.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Isotonic mechanics of a pharyngeal dilator muscle and diaphragm in the rat before and after fatigue.

Pharyngeal and diaphragm muscles contract and relax in synergy, which is why it was decided to compare their mechanical performance throughout the overall load continuum. The effects of fatigue were also studied. The isotonic mechanics of rat sternohyoid (SH; n=10) and diaphragm (D; n=10) were investigated in vitro. Force and length were measured in muscles contracting from zero load up to isometry. Maximum isometric tension (Pmax), peak mechanical work (Wmax), maximum unloaded shortening velocity (vzL) and mechanical efficiency (eff(max)) were recorded. Data were obtained both at baseline and after fatigue. SH muscles had a lower Pmax (96.0+/-13.7 versus 119.5+/-22.7 mN x mm(-2); p<0.05), a lower Wmax (5.5+/-1.2 versus 8.0+/-2.1 mJ x g(-1); p<0.01), a lower eff(max) (56.0+/-6.9 versus 62.6+/-5.8%; p<0.05) and a higher vzL (4.8+/-0.4 versus 3.4+/-0.4 initial length (L0) x s(-1); p<0.001) than D muscles. Wmax occurred at a higher relative load in SH (40% Pmax) than in D (30% Pmax). Fatigue did not modify eff(max) in SH muscles, whereas it significantly improved eff(max) in D muscles. These findings suggest that under control conditions, economy of force generation was less efficient in sternohyoid than in diaphragm muscles. Fatigue in sternohyoid muscles induced unfavourable mechanical behaviour. This may partly explain pharyngeal dilator muscle failure in the presence of increased loads. Whether these findings are relevant to human sleep apnoea syndrome has yet to be determined.

Animals↗
PubMed2000

Restoration of flow-dependent coronary dilation by ACE inhibition improves papaverine-induced maximal coronary blood flow in hypertensive patients: demonstration that large epicardial coronary arteries are more than conductance vessels.

Restoration of flow-dependent coronary artery dilation by angiotensin-converting enzyme inhibition (ACEI) has been demonstrated in patients with hypertension. The aim of the present study was to evaluate whether dilation of conductance coronary arteries may alter maximal coronary blood flow (CBFmax) and minimal coronary resistance (CRmin) in hypertensive patients with reversible impairment of flow-dependent coronary artery dilation. Thirteen hypertensive patients with angiographically normal coronary arteries and no other risk factors were studied. Cross-sectional areas (CSAs) of proximal and distal left anterior descending (LAD) coronary arteries were determined by quantitative angiography. Coronary flow velocity was recorded in the distal LAD with an intracoronary Doppler catheter. Estimates of coronary blood flow and resistance were calculated at rest and during maximal increase in blood flow induced by papaverine injected in the midportion of the LAD, both before and after ACEI. Flow-dependent dilation of the proximal LAD, abolished before ACEI, was restored after (26.7 +/- 11.2%; p < 0.001). The increase in CSA of the distal LAD exposed to papaverine was significantly higher after ACEI than before (from 33.4 +/- 20.5% to 51.5 +/- 23.4%; p < 0.001). After restoration of proximal LAD flow-dependent dilation, CBFmax was increased by +21.0 +/- 10.3% (p < 0.001), and CRmin was reduced by 19.3 +/- 9.5% (p < 0.001). Thus, dilation of epicardial coronary arteries participates substantially in the coronary resistance in hypertensive patients. Restoration of flow-dependent coronary artery dilation by ACEI may improve the ability of coronary circulation to deliver its maximal myocardial blood flow in hypertensive patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Short-term variability of pulse pressure and systolic and diastolic time in heart transplant recipients.

In heart transplant recipients (HTR), short-term systolic blood pressure variability is preserved, whereas heart rate variability is almost abolished. Heart period is the sum of left ventricular ejection time (LVET) and diastolic time (DT). In the present time-domain prospective study, we tested the hypothesis that short-term fluctuations in aortic pulse pressure (PP) in HTR were related to fluctuations in LVET. Seventeen male HTR (age 48 +/- 6 yr) were studied 16 +/- 11 mo after transplantation. Aortic root pressure was obtained over a 15-s period using a micromanometer both at rest (n = 17) and following the cold pressor test (CPT, n = 14). There was a strong positive linear relationship between beat-to-beat LVET and beat-to-beat PP in all patients at rest and in 13 of 14 patients following CPT (each P < 0.01). The slope of this relationship showed little scatter both at rest (0.34 +/- 0.07 mmHg/ms) and following CPT (0.35 +/- 0.09 mmHg/ms, P = not significant). Given the essentially fixed heart period, DT varied inversely with LVET. As a result, in 13 of 17 HTR at rest and in 12 of 14 HTR following CPT, there was a negative linear relationship between beat-to-beat PP and DT. In conclusion, our short-term time-domain study demonstrated a strong positive linear relationship between LVET and blood pressure variability in male HTR. We also identified a subgroup of HTR in whom there was a mismatch between PP and DT.

Adult↗
PubMed2000

Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure.

In mechanically ventilated patients with acute circulatory failure related to sepsis, we investigated whether the respiratory changes in arterial pressure could be related to the effects of volume expansion (VE) on cardiac index (CI). Forty patients instrumented with indwelling systemic and pulmonary artery catheters were studied before and after VE. Maximal and minimal values of pulse pressure (Pp(max) and Pp(min)) and systolic pressure (Ps(max) and Ps(min)) were determined over one respiratory cycle. The respiratory changes in pulse pressure (DeltaPp) were calculated as the difference between Pp(max) and Pp(min) divided by the mean of the two values and were expressed as a percentage. The respiratory changes in systolic pressure (DeltaPs) were calculated using a similar formula. The VE-induced increase in CI was >/= 15% in 16 patients (responders) and < 15% in 24 patients (nonresponders). Before VE, DeltaPp (24 +/- 9 versus 7 +/- 3%, p < 0.001) and DeltaPs (15 +/- 5 versus 6 +/- 3%, p < 0.001) were higher in responders than in nonresponders. Receiver operating characteristic (ROC) curves analysis showed that DeltaPp was a more accurate indicator of fluid responsiveness than DeltaPs. Before VE, a DeltaPp value of 13% allowed discrimination between responders and nonresponders with a sensitivity of 94% and a specificity of 96%. VE-induced changes in CI closely correlated with DeltaPp before volume expansion (r(2) = 0. 85, p < 0.001). VE decreased DeltaPp from 14 +/- 10 to 7 +/- 5% (p < 0.001) and VE-induced changes in DeltaPp correlated with VE-induced changes in CI (r(2) = 0.72, p < 0.001). It was concluded that in mechanically ventilated patients with acute circulatory failure related to sepsis, analysis of DeltaPp is a simple method for predicting and assessing the hemodynamic effects of VE, and that DeltaPp is a more reliable indicator of fluid responsiveness than DeltaPs.

Adolescent↗
PubMed2000

Severe mechanical dysfunction in pharyngeal muscle from adult mdx mice.

The mdx mouse is a widely used animal model of human muscular dystrophy. Although diaphragm muscle exhibits severe muscle weakness throughout the life of the animal, the limb muscle function of mdx mice spontaneously recovers by 6 mo of age. Pharyngeal dilator muscles such as sternohyoid (SH) contribute to upper airway patency during breathing. We hypothesized that SH muscle function was impaired in 6-mo-old mdx mice. Mechanical properties and myosin heavy chain (MHC) composition were investigated in isolated SH from 6-mo-old control (C, n = 10) and mdx (n = 10) mice. As compared with C, peak tetanic tension (Pmax) and maximum shortening velocity were 50% and 16% lower in mdx mice (p < 0.001 and p < 0.05, respectively). Peak mechanical power was lower in mdx than in C (19.0 +/- 3.2 versus 57.4 +/- 5.1 mW g(-)(1), p < 0.001). Both C and mdx SH were composed exclusively of fast myosin isoforms. As compared with C, mdx SH presented a higher proportion of IIX-MHC and a reduction in IIB-MHC (each p < 0.001). In conclusion, our results demonstrated severe SH muscle dysfunction in 6-mo-old mdx mice, that is, at a time when limb muscle function has recovered. Thus, SH muscle of the mdx mouse may be an excellent muscle for studying Duchenne muscular dystrophy.

Age Factors↗
PubMed2000

[Biomechanics and bio-energetics of smooth muscle contraction. Relation to bronchial hyperreactivity].

Mechanical studies of isolated muscle and analysis of molecular actomyosin interactions have improved our understanding of the pathophysiology of airway smooth muscle. Mechanical properties of airway smooth muscle are similar to those of other smooth muscles. Airway smooth muscle exhibits spontaneous intrinsic tone and its maximum shortening velocity (Vmax) is 10-30 fold lower than in striated muscle. Smooth muscle myosin generates step size and elementary force per crossbridge interaction approximately similar to those of skeletal muscle myosin. Special slow cycling crossbridges, termed latch-bridges, have been attributed to myosin light chain dephosphorylation. From a mechanical point of view, it has been shown that airway hyperresponsiveness is characterized by an increased Vmax and an increased shortening capacity, with no significant change in the force-generating capacity.

Biomechanical Phenomena↗
PubMed1999

Cross-bridge kinetics in fatigued mouse diaphragm.

The aim of this study was to determine cross-bridge number and kinetics in the diaphragm during fatigue and early recovery. Experiments were conducted in isolated mouse diaphragm (n=10). The force of a single cross-bridge (pi), the number of cross-bridges (m x 10(9) x mm2), the time cycle (tc) and the rate constants for cross-bridge attachment (f1) and detachment (g2) were calculated from the equations of A.F. Huxley. Following the fatigue protocol, peak isometric tension (Po) and maximum unloaded shortening velocity fell by 40+/-1% and 17+/-2%, respectively. In fatigued diaphragm, m fell by approximately 40% and returned to baseline after 10 min. When compared to baseline, g2 fell in fatigued diaphragm and remained significantly lower during the 15-min recovery period. In contrast, fatigue did not significantly modify pi, f1, or tc. There was a strong linear relationship between Po and m (p<0.001, r=0.988). No relationship was observed between tc and g2. These results indicate that changes in tension during fatigue and recovery run parallel to changes in the number of active cross-bridges, with no change in the force generated per cross-bridge. It is conceivable that fatigue durably impairs adenosine diphosphate release from the actomyosin complex without modifying the total duration of the cross-bridge cycle.

Actomyosin↗