PubMed Health⌕ Search

Biomedical subjects

Y Lecarpentier

Publications and source records attributed to Y Lecarpentier.

At least 19 recordsLinked to original sources

Statistical mechanics of myosin molecular motors in skeletal muscles.

Statistical mechanics provides the link between microscopic properties of matter and its bulk properties. The grand canonical ensemble formalism was applied to contracting rat skeletal muscles, the soleus (SOL, n = 30) and the extensor digitalis longus (EDL, n = 30). Huxley's equations were used to calculate force (pi) per single crossbridge (CB), probabilities of six steps of the CB cycle, and peak muscle efficiency (Eff(max)). SOL and EDL were shown to be in near-equilibrium (CB cycle affinity 2.5 kJ/mol) and stationary state (linearity between CB cycle affinity and myosin ATPase rate). The molecular partition function (z) was higher in EDL (1.126+/-0.005) than in SOL (1.050+/-0.003). Both pi and Eff(max) were lower in EDL (8.3+/-0.1 pN and 38.1+/-0.2%, respectively) than in SOL (9.2+/-0.1 pN and 42.3+/-0.2%, respectively). The most populated step of the CB cycle was the last detached state (D3) (probability P(D3): 0.890+/-0.004 in EDL and 0.953+/-0.002 in SOL). In each muscle group, both pi and Eff(max) linearly decreased with z and statistical entropy and increased with P(D3). We concluded that statistical mechanics and Huxley's formalism provided a powerful combination for establishing an analytical link between chemomechanical properties of CBs, molecular partition function and statistical entropy.

Adenosine Triphosphatases↗

Effects of halogenated anaesthetics on diaphragmatic actin-myosin cross-bridge kinetics.

BACKGROUND: The effects of halogenated anaesthetics on cross-bridge (CB) kinetics are unclear. As halogenated anaesthetics do not markedly modify the intracellular calcium transient in the diaphragm, we used an isolated rat diaphragm preparation to assess the effects of halothane and isoflurane on CB kinetics. METHODS: The effects of halothane and isoflurane (1 and 2 minimum alveolar concentration (MAC)) on rat diaphragm muscle strips were studied in vitro (Krebs-Henseleit solution, 29 degrees C, oxygen 95%/carbon dioxide 5%) in tetanus mode (50 Hz). From the force-velocity curve and using A. F. Huxley's equations, we determined the main mechanical and energetic variables and calculated CB kinetics. RESULTS: At 1 and 2 MAC, isoflurane and halothane induced no significant inotropic effects. Whatever the concentrations tested, halothane and isoflurane did not significantly modify the CB number, the elementary force per CB, the attachment and detachment constants, the duration of the CB cycle and mean CB velocity. CONCLUSION: In the rat diaphragm at therapeutic concentrations, halogenated anaesthetics do not significantly modify CB mechanical and kinetic properties.

Actins↗

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↗

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↗

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↗

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↗

Mechanical and electrophysiological effects of thiopental on rat cardiac left ventricular papillary muscle.

Thiopental induces a negative inotropic effect on mammalian heart muscle, where it decreases Ca2+ current and Ca2+ release from the sarcoplasmic reticulum and reduces K+ currents. We analysed the effects of thiopental on the mechanical and electrical activities of rat myocardium, which differ markedly from those of other mammals. The effects of thiopental on mechanical parameters and on the transmembrane resting (RP) and action (AP) potentials of rat left ventricular papillary muscle were investigated. These effects were also studied in the presence of atenolol, a beta-blocking agent, and 4-aminopyridine (4-AP), a blocker of the transient outward K+ current. Thiopental (3.8 x 10(-6), 3.8 x 10(-5) and 1.1 x 10(-4) M) induced a dose-dependent positive inotropic effect. This positive inotropic effect persisted in the presence of atenolol (1 x 10(-6) M) but did not develop in the presence of 1 mM 4-AP; 4-AP had a positive inotropic effect but not in the presence of thiopental. Moreover, thiopental (3.8 x 10(-5) M) lengthened the plateau and the slow repolarizing phase of the AP, while 1 mM 4-AP only prolonged the plateau duration. In rat myocardium, the positive inotropic effect of thiopental in part mimics that of 4-AP, and in part may be explained by the lengthening of the slow repolarizing phase of the AP.

Action Potentials↗

Extracellular calcium modulates the effects of protamine on rat myocardium.

UNLABELLED: We studied the effects of protamine (10-300 microg. mL(-1)) as well as its interaction with heparin in rat left ventricular papillary muscles in vitro at calcium concentrations of 0.5 and 1 mM under low (isotony) and high (isometry) loads. Protamine induced a negative inotropic effect that was less pronounced at calcium 0.5 mM (active force at protamine 300 microg/mL, 84 +/- 20 vs 57 +/- 15% of baseline, P: < 0.05); whereas at calcium 1 mM there was a marked contracture of the muscle. For the smallest concentrations of protamine and at calcium 0.5 mM, we observed a moderate positive inotropic effect that was suppressed by nifedipine. Protamine induced a negative lusitropic effect under low load and decreased postrest potentiation, suggesting an impairment in the functions of the sarcoplasmic reticulum. Heparin was able to inhibit and reverse the negative inotropic effect of protamine. The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects. IMPLICATIONS: The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects.

Animals↗

Interaction of protamine with alpha- and beta-adrenoceptor stimulations in rat myocardium.

BACKGROUND: Protamine alters the inotropic responses to beta-adrenoceptor stimulation, but its mechanism of action is not well-understood. Moreover, its interaction with alpha-adrenoceptor stimulation and the lusitropic (relaxation) response to beta-adrenoceptor stimulation remain unknown. METHODS: The effects of protamine (10 or 100 microg/ml) on the responses induced by phenylephrine and isoproterenol were studied in rat left ventricular papillary muscles. Inotropic and lusitropic effects were studied under low and high loads. The authors also studied the interaction of protamine with forskolin (50 microm) and dibutyryl 3',5'-cAMP (0.5 mm). Data are mean percentage of baseline active force +/- SD. RESULTS: In control groups, phenylephrine (135 +/- 17%, P < 0.05) and isoproterenol (185 +/- 44%, P < 0.05) induced a positive inotropic effect. Isoproterenol induced positive lusitropic effects under low and high loads. Protamine abolished the inotropic responses to alpha- (102 +/- 23%, not significant) and beta-adrenoceptor stimulations (99 +/- 17%, not significant) but did not modify the lusitropic responses to isoproterenol. Protamine abolished the inotropic responses to forskolin (89 +/- 6 vs. 154 +/- 20%, P < 0.05) and markedly decreased that of dibutyryl 3',5'-cAMP (132 +/- 31 vs. 167 +/- 30%, P < 0.05) but did not modify their lusitropic responses. CONCLUSIONS: Protamine abolished the inotropic responses to alpha- and beta-adrenoceptor stimulations but preserved the lusitropic responses to beta-adrenoceptor stimulation. Although protamine may act at several sites on the adrenoceptor stimulation cascade, one of its main sites of action is situated downstream from cAMP-mediated phosphorylation.

Adrenergic alpha-Agonists↗

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↗

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↗

Species-dependent changes in mechano-energetics of isolated cardiac muscle during hypoxia.

The present study investigates the mechanical and energetic changes induced by hypoxia in isolated cardiac muscles of different species characterized by different myosin isoforms. Classic mechanical parameters of contraction and energetic parameters derived from the tension-velocity relationship were studied in rat and guinea pig left ventricular papillary muscles and in frog ventricular strips before and after 15 min hypoxia (n = 8 in each group). The isomyosin pattern is predominantly V1 with high ATPase activity in rat and V3 with low ATPase activity in guinea pig and frog heart ventricles. At baseline, cardiac mechanical performance was greater in rat than in guinea pig and frog muscle, but the economy of tension generation did not differ significantly between the three species. Hypoxia significantly decreased myocardial mechanical performance in all three groups. Mechanical impairment was more marked in rat than in the other two species and was intermediate in guinea pig. The energetic consequences of hypoxia differed according to species and in a different manner from the mechanical parameters. Hypoxia decreased the economy of tension generation in rat heart, in contrast to no change in guinea pig and frog muscle. These results suggest that in terms of mechano-energetic properties, cardiac muscles with V1 isomyosin were more sensitive to hypoxia than those containing V3 isomyosin.

Adenosine Triphosphatases↗

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↗

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↗

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↗

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↗

[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↗