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D Chemla

Publications and source records attributed to D Chemla.

At least 37 records · Page 2Linked to original sources

Diaphragm strength and cross-bridge properties during chronic growth hormone hypersecretion.

The aim of the study was to determine diaphragm performance and cross-bridge properties in rats bearing a growth hormone (GH)-secreting tumour. The tumour was induced by subcutaneous injection of GH-hypersecreting cells (GC cells) into the flank. Eighteen weeks after GC cell injection, rats developed a GH-secreting tumour (45.4+/-5.1 g) and the GH plasma level reached 5,408+/-648 microg x L(-1) in GH rats versus 7.2+/-2.2 microg x L(-1) in control rats (p<0.001). Diaphragm mechanics and cross-bridge properties were studied by applying the equations of A. Huxley in isolated diaphragm strips (control rats: n=12; GH rats n=20). In comparison to control rats, the total tension and total number of cross-bridges x mm(-2) in GH rats were lower in both twitch and tetanus (p<0.001). A linear relationship was observed between total tension and total cross-bridge number (r=0.94; p<0.001). Conversely, the cross-bridge single force and peak mechanical efficiency did not differ between control and GH rats, in either twitch or tetanus modes. In conclusion, the diaphragm strength was significantly lower in rats bearing growth hormone secreting tumours, and this was essentially determined by the lower cross-bridge number x mm(-2) without change in cross-bridge single force.

Animals↗

Arrhythmogenic right ventricular dysplasia.

Arrhythmogenic right ventricular dysplasia (ARVD) is a new form of cardiomyopathy probably more frequent than commonly reported. It is a rare but important cause of sudden arrhythmic death in young, otherwise healthy persons, as well as a subtle cause of congestive heart failure. It may lead to temporary incapacitation with catastrophic consequences. Proper electrocardiographic criteria, echocardiography, nuclear medicine, or magnetic resonance imaging could identify most of these individuals. With the exception of full-thickness histological examination of the right ventricular free wall, contrast ventriculography remains the most definitive standard for a positive diagnosis. The wide clinical spectrum of arrhythmogenic right ventricular cardiomyopathies/dysplasia appears to be the result of one or possibly two factors: (a) replacement of most of the right ventricular myocardium by fat and (b) genetic susceptibility to environmental agents (myocarditis). Current treatment modalities include drug therapy, catheter or surgical ablative techniques, and modern treatments of congestive heart failure. Heart transplant is exceptional. Implantable defibrillators, used alone or in combination with drug therapy, will probably play an increasing role in ARVD and related cardiomyopathies.

Adipose Tissue↗

Myosin molecular motor dysfunction in dystrophic mouse diaphragm.

Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control (n = 12) and mdx (n = 12) mice. Compared with control, peak tetanic tension fell by 50% in mdx mice (P < 0.001). The total number of cross bridges per square millimeter (x10(9)), the elementary force per cross bridge, and the peak mechanical efficiency were lower in mdx than in control mice (each P < 0.001). The duration of the cycle and the rate constant for cross-bridge detachment were significantly lower in mdx than in control mice. In the overall population, there was a linear relationship between peak tetanic tension and either total number of cross bridges per square millimeter or elementary force per cross bridge (r = 0.996 and r = 0.667, respectively, each P < 0.001). The mdx mice presented a higher proportion of type IIA MHC (P < 0.001) than control mice and a reduction in type IIX MHC (P < 0.001) and slow myosin isoforms (P < 0.01) compared with control mice. We concluded that, in mdx mice, impaired diaphragm strength was associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per cross bridge contributed to diaphragm weakness in mdx mice.

Animals↗

Relaxation of diaphragm muscle.

Relaxation is the process by which, after contraction, the muscle actively returns to its initial conditions of length and load. In rhythmically active muscles such as diaphragm, relaxation is of physiological importance because diaphragm must return to a relatively constant resting position at the end of each contraction-relaxation cycle. Rapid and complete relaxation of the diaphragm is likely to play an important role in adaptation to changes in respiratory load and breathing frequency. Regulation of diaphragm relaxation at the molecular and cellular levels involves Ca(2+) removal from the myofilaments, active Ca(2+) pumping by the sarcoplasmic reticulum (SR), and decrease in the number of working cross bridges. The relative contribution of these mechanisms mainly depends on sarcomere length, muscle tension, and the intrinsic contractile function. Increased capacity of SR to take up Ca(2+) can arise from increased density of active SR pumping sites or in slow-twitch fibers from phosphorylation of phospholamban, whereas impaired coupling between ATP hydrolysis and Ca(2+) transport into the SR or intracellular acidosis reduces SR Ca(2+) pump activity. In experimental conditions of decreased contractile performance, slowed, enhanced, or unchanged relaxation rates have been reported in vitro. In vivo, a slowing in the rate of decline of the respiratory pressure is generally considered an early reliable index of respiratory muscle fatigue. Impaired relaxation rate may, in turn, favor mismatch between blood flow and metabolic demand, especially at high breathing frequencies.

Animals↗

Impaired load dependence of diaphragm relaxation during congestive heart failure in the rabbit.

The load dependence (LD) of relaxation was studied in the diaphragm of rabbits with congestive heart failure (CHF). CHF (n = 15) was induced by combined chronic volume and pressure overload. Aortic insufficiency was induced by forcing a catheter through the aortic sigmoid valves, followed 3 wk later by abdominal aortic stenosis. Six weeks after the first intervention, animals developed CHF. Sham-operated animals served as controls (C; n = 12). Diaphragm mechanics were studied in vitro on isolated strips, at 22 degrees C, in isotonic and isometric loading conditions. Contractility was lower in the CHF group, as reflected by lower total tension: 1.11 +/- 0.10 in CHF vs. 2.38 +/- 0.15 N/cm(2) in C in twitch (P < 0.001) and 2.46 +/- 0.22 in CHF vs. 4.90 +/- 0.25 N. cm(-2) in C in tetanus (P < 0.001). The index LD was used to quantify the load dependence of relaxation: LD is <1 in load-dependent muscles and tends toward 1 in load-independent muscles. LD was significantly higher in CHF than in C rabbits, in both twitch (0.99 +/- 0.01 vs. 0.75 +/- 0.03; P < 0. 001) and tetanus (0.95 +/- 0.02 vs. 0.84 +/- 0.02; P < 0.001). In the CHF rabbits' diaphragm, the fall in total tension was linearly related to the fall in load dependence of relaxation. The decrease in load dependence of relaxation in CHF animals suggests sarcoplasmic reticulum abnormalities. Impairment of the sarcoplasmic reticulum may also partly account for the decrease in contractile performance of diaphragm in CHF animals.

Animals↗

Clinical use of respiratory changes in arterial pulse pressure to monitor the hemodynamic effects of PEEP.

In ventilated patients with acute lung injury (ALI) we investigated whether respiratory changes in arterial pulse pressure (DeltaPP) could be related to the effects of PEEP and fluid loading (FL) on cardiac index (CI). Measurements were performed before and after application of a PEEP (10 cm H2O) in 14 patients. When the PEEP-induced decrease in CI was > 10% (six patients), measurements were also performed after FL. Maximal (PPmax) and minimal (PPmin) values of pulse pressure were determined over one respiratory cycle and DeltaPP was calculated: DeltaPP (%) = 100 x ((PPmax - PPmin)/ ([PPmax + PPmin]/2)). PEEP decreased CI from 4.2 +/- 1.1 to 3.8 +/- 1.3 L/min/m2 (p < 0.01) and increased DeltaPP from 9 +/- 7 to 16 +/- 13% (p < 0.01). The PEEP-induced changes in CI correlated with DeltaPP on ZEEP (r = -0.91, p < 0.001) and with the PEEP-induced increase in DeltaPP (r = -0.79, p < 0.001). FL increased CI from 3.5 +/- 1.1 to 4.2 +/- 0.9 L/min/m2 (p < 0.05) and decreased DeltaPP from 27 +/- 13 to 14 +/- 9% (p < 0.05). The FL-induced changes in CI correlated with DeltaPP before FL (r = 0.97, p < 0.01) and with the FL-induced decrease in DeltaPP (r = -0.85, p < 0.05). In ventilated patients with ALI, DeltaPP may be useful in predicting and assessing the hemodynamic effects of PEEP and FL.

Adult↗

The effects of gadolinium, a stretch-sensitive channel blocker, on diaphragm muscle.

Stretch-activated channels (SAC) have been identified in many cell types including striated muscles. In diaphragm muscle, the influence of SAC on the length-active tension relationship remains unknown. Patch clamp experiments were performed on single fibres (n = 10). In isolated diaphragm muscle from adult hamsters, the effects of gadolinium (Gd3+), the most potent inhibitor of SAC blocker, on tension response to stretch at baseline were studied (n = 10), after pretreatment of the muscle with 1 nmol isoproterenol (n = 10), 0.5 micromol forskolin (n = 6), or 0.1 mmol dibutyryl cyclic adenosine monophosphate (cAMP) (n = 10). Results were compared to those obtained in low [Na+]e (n = 10), Ca2+-free medium (n = 6) or after 5 micromol nifedipine (n = 8). Gd3+ reduced active tension measured over a range of initial muscle lengths in a concentration-dependent manner (10 and 50 micromol). In isolated fibres, mechanical stretch generated a membrane current that was sensitive to Gd3+. In muscles, lowering [Na+]e mimicked the effects of Gd3+, while no change in the length-tension relationship was observed in Ca2+-free medium or after nifedipine. Drugs which increase cAMP prevented the effects of Gd3+ on active tension. In the diaphragm, gadolinium-sensitive channels are activated during physiological changes in length and influence tension development. Moreover, cyclic adenosine monophosphate content modulates the effects of gadolinium on stretch-activated channels.

Action Potentials↗

Impaired skeletal muscle performance in the early stage of cardiac pressure overload in rabbits: beneficial effects of angiotensin-converting enzyme inhibition.

Abnormalities of skeletal muscles are frequently observed in patients with congestive heart failure. In these patients, angiotensin-converting enzyme (ACE) inhibitors improve exercise performance. The present study was designed to assess whether skeletal muscle dysfunction develops in the early stage of cardiac overload and if so, whether such functional alterations can be prevented by ACE inhibition. Mechanical performance, cross-bridge (CB) properties, and myosin heavy chain composition were investigated in respiratory and limb skeletal muscles of rabbits with moderate cardiac hypertrophy, and after single therapy with the ACE inhibitor perindopril (PE). After constriction of the aorta, the rabbits were treated during a 10-week period with either PE (1 mg/kg/day; n = 9) or a placebo (PL; n = 15). A third group of sham-operated animals received PL (n = 10). Analyses were performed on isolated diaphragm and soleus strips. Compared with sham-operated animals (shams), peak tetanic tension in PL fell by 40% in diaphragm and 34% in soleus. There were no significant differences in peak tetanic tension and the maximum shortening velocity between PE and shams. In both muscles, the total number of CBs was significantly lower in PL than in shams, but did not differ between shams and PE. The elementary force per CB did not differ between groups. In both muscles, the myosin heavy chain composition did not differ between groups. The study demonstrated that intrinsic performance of diaphragm and soleus muscles was affected early in the development of chronic pressure overload. Single therapy with PE tended to preserve muscle strength, essentially by limiting the loss of CBs.

Angiotensin-Converting Enzyme Inhibitors↗

Relation between dicrotic notch and mean pulmonary artery pressure studied by using a Swan-Ganz catheter in critically ill patients.

OBJECTIVE: It has been recently shown that there is a match between dicrotic notch and mean pulmonary artery (PA) pressures in spontaneously breathing patients studied by means of high-fidelity pressure catheters. The aim of the study was to analyze the relation between mean PA pressure and PA pressure at the incisura by using a Swan-Ganz catheter in critically ill, mechanically ventilated patients. MEASUREMENTS AND RESULTS: Fluid-filled PA pressures were obtained over four ventilatory cycles in 32 consecutive, mechanically ventilated patients in the intensive care unit. We measured mean PA pressure and dicrotic notch pressure. We also calculated the widely used approximation of mean PA pressure (mean PAPapprox = diastolic + 1/3 pulse pressure). Cardiac output was measured in triplicate by using the thermodilution technique. Dicrotic notch was clearly identified in 30 of 32 patients. Mean PA pressure (32.1 +/- 10.2 mm Hg) and PA dicrotic notch pressure (31.8 +/- 10.4 mm Hg) were linearly related (r = 0.989, p < 0.001). Agreement between dicrotic notch and mean PA pressures was suggested (mean difference +/- SD = -0.3 +/- 1.5 mm Hg). Similar agreement was found between mean PAPapprox and mean PA pressure (mean difference +/- SD = -0.7 +/- 0.8 mm Hg; p = 0.20). CONCLUSION: By using a Swan-Ganz catheter we found that dicrotic notch pressure equalled mean PA pressure in the critically ill, mechanically ventilated patients studied. This indicated that right-sided ejection was completed at a PA pressure equal to mean PA pressure in these patients.

Aged↗

Decreased regional blood flow in patients with acromegaly.

BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS: Twelve patients with active acromegaly (five females, seven males; mean (+/- SD) age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects served as controls. METHODS: Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two-dimensional pulsed Doppler system (double transducer probe and range-gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio. RESULTS: Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/- 1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 +/- 61 vs. 83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.

Acromegaly↗

Mechanics, energetics, and crossbridge kinetics of rabbit diaphragm during congestive heart failure.

Crossbridge (CB) properties were investigated in isolated diaphragm of rabbits during congestive heart failure (CHF, n=9) induced by chronic volume and pressure overload. This model induced cardiac hypertrophy and heart failure. Controls (C) were prepared (n=14). Compared to C, peak tension in CHF fell by 57% in twitch and by 40% in tetanus; Vmax declined by 47% in twitch and by 48% in tetanus. Our study provided an analytical means of calculating from A. F. Huxley's equations the rate constants for CB attachment and detachment, CB single force (II), CB number per mm3 (m'), peak mechanical efficiency (Effmax), and turnover rate of myosin ATPase (kcat); m', II, and Effmax were lower in CHF than in C in both twitch and tetanus. The marked decline in m' and II accounted for the fall in diaphragm strength. In the overall population of C and CHF, Effmax was linearly related to II. Conversely, there was no relationship between Vmax and kcat. Dissociation between Vmax and kcat might be explained by the crucial role attributed to two apparently nonconserved surface 'loops' on the motor domain of myosin head.

Animals↗

Total arterial compliance estimated by stroke volume-to-aortic pulse pressure ratio in humans.

On the basis of the windkessel model, the stroke volume-to-aortic pulse pressure ratio (SV/PP) has been proposed as an estimate of total arterial compliance, but recent studies have questioned this approximation. Aortic pressure was obtained at rest in 31 adults undergoing cardiac catheterization (47 +/- 14 yr): controls (n = 7), patients with dilated cardiomyopathy (n = 10), and patients with other cardiac diseases (n = 14). We calculated PP, mean aortic pressure (MAoP), heart period (T), SV (thermodilution cardiac output/heart rate), total peripheral resistance (R), total arterial compliance estimated by area method (Carea), and the time constant of aortic pressure decay in diastole (RCarea). In the overall population (n = 31), there was no significant difference between SV/PP and Carea. SV/PP was linearly related to Carea (SV/PP = 0.99Carea + 0.05; r = 0.98; P < 0.001); the slope and intercept did not differ from unity and zero, respectively. Similar results were obtained in the three subgroups. These results implied that PP/MAoP and T/RCarea were proportionally related (T/RCarea = 1.18PP/MAoP - 0.07; r = 0.96; P < 0.001). We conclude that for humans at rest 1) SV/PP gave a reliable estimate of Carea, and 2) T normalized by the time constant of aortic pressure decay in diastole was proportionally related to PP/MAoP. This last relationship could be considered an aspect of the coupling between the left ventricle and its load.

Adult↗

Pulse pressure response to the strain of the valsalva maneuver in humans with preserved systolic function.

Arterial pulse pressure response during the strain phase of the Valsalva maneuver has been proposed as a clinical tool for the diagnosis of left heart failure, whereas responses of subjects with preserved systolic function have been poorly documented. We studied the relationship between the aortic pulse amplitude ratio (i.e., minimum/maximum pulse pressure) during the strain phase of the Valsalva maneuver and cardiac hemodynamics at baseline in 20 adults (42 +/- 14 yr) undergoing routine right and left heart catheterization. They were normal subjects (n = 5) and patients with various forms of cardiac diseases (n = 15), and all had a left ventricular ejection fraction >/=40%. High-fidelity pressures were recorded in the right atrium and the left ventricle at baseline and at the aortic root throughout the Valsalva maneuver. Aortic pulse amplitude ratio 1) did not correlate with baseline left ventricular end-diastolic pressure, cardiac index (thermodilution), or left ventricular ejection fraction (cineangiography) and 2) was positively related to total arterial compliance (area method) (r = 0.59) and to basal mean right atrial pressure (r = 0.57) (each P < 0.01). Aortic pulse pressure responses to the strain were not related to heart rate responses during the maneuver. In subjects with preserved systolic function, the aortic pulse amplitude ratio during the strain phase of the Valsalva maneuver relates to baseline total arterial compliance and right heart filling pressures but not to left ventricular function.

Adult↗

Increased compliance in diaphragm muscle of the cardiomyopathic Syrian hamster.

We investigated the hypothesis that diaphragm compliance was abnormal in cardiomyopathic Syrian hamsters (CSH), an experimental model of myopathy. The passive elastic properties of isolated diaphragm muscles were analyzed at both the muscle and sarcomere levels. We used the following passive exponential relationship between stress (sigma) and strain (epsilon): sigma = (Eo/beta) (ebetaepsilon - 1), where Eo is the initial elastic modulus and beta is the stiffness constant. Immunocytochemistry procedures were used to analyze the distribution of two key elastic components of muscle, extracellular collagen and intracellular titin elastic components, as well as the extracellular matrix glycoprotein laminin. Muscle and sarcomere values of beta were nearly twofold lower in CSH (8.7 +/- 1.9 and 8.3 +/- 1.4, respectively) than in control animals (19.7 +/- 1.7 and 16.8 +/- 2.1, respectively) (P < 0.01 for each). Compared with controls, Eo was higher in CSH. Sarcomere slack length was significantly longer in CSH than in control animals (2.1 +/- 0.1 vs. 1.9 +/- 0.1 micrometer, P < 0.05). The surface area of collagen I was significantly larger in CSH (17.4 +/- 1.8%) than in control animals (12.4 +/- 0.7%, P < 0.05). There was no change in the distribution of titin or laminin labelings between the groups. These results demonstrate increased diaphragm compliance in cardiomyopathic hamsters. The increase in CSH diaphragm compliance was observed despite an increase in the surface area of collagen and was not associated with an abnormal distribution of titin or laminin.

Animals↗

A comparison between systolic aortic root pressure and finger blood pressure.

BACKGROUND: Digital photoplethysmography is used to assess hemodynamic variability and baroreflex sensitivity. Numerous studies have critically evaluated the accuracy of the photoplethysmographic device against peripheral pressure. The aim of our study was to compare finger blood and aortic root pressure. METHODS: We prospectively compared simultaneous recordings of systolic pressure at the aortic root and finger level over three consecutive respiratory cycles in 15 patients (56+/-11 years) undergoing routine cardiac catheterization. Data were obtained at baseline, during deep breathing maneuver (0.1 Hz), and after left ventricular cineangiography. RESULTS: At baseline, systolic finger pressure overestimated systolic aortic pressure (145.2+/-22.5 vs 115.0+/-20.1 mm Hg; p<0.001). The pressure difference (30.2+/-17.0 mm Hg) was not influenced by systolic aortic pressure. There was no relationship between pressure difference and the main determinants of the pulse wave amplification phenomenon. There was a beat-to-beat relationship between finger and aortic pressure in 14 of 15 subjects (slope ranging from 0.37 to 1.70; ordinate: from -56 to +98 mm Hg). During the deep breathing maneuver and after left ventricular cineangiography, finger pressure still overestimated aortic pressure by 32.3+/-15.0 mm Hg and 38.3 13.9 mm Hg, respectively (each p<0.001). There was a beat-to-beat relationship between systolic aortic root pressure (IAoBP) and systolic finger (FBP) in 13 of 15 patients, with major scattering of both slopes and ordinates. Throughout the study, there was no predictable relationship between the level of IAoBP and pressure bias. CONCLUSIONS: As expected, FBP was almost always higher than IAoBP. Importantly, the differences in systolic pressure did not correlate with known determinants of the pulse wave amplification phenomenon. The device must be used cautiously if one wants to noninvasively track spontaneous or induced changes in IAoBP.

Aorta↗

In vitro negative inotropic effect of plasma collected at the time of reperfusion in humans undergoing liver transplantation.

BACKGROUND: During orthotopic liver transplantation (OLT), acute depression of myocardial contractility has been suspected at the time of the graft reperfusion. METHODS: The authors tested the hypothesis that plasma collected at the time of reperfusion in OLT patients exerted a negative inotropic effect on isolated rat myocardium. Plasma from 13 OLT patients was collected either before surgical incision (group 1, n = 8) or 3-5 min after vena cava and portal vein unclamping (group 2, n = 9). Six patients had their pre- and postincision plasma analyzed. A postreperfusion syndrome was observed in 3 of 13 patients. Left ventricular rat papillary muscles were studied at baseline (T0), 30 min after the addition of plasma (T30), and 60 min after the addition of plasma (T60). The authors recorded contraction parameters (maximum unloaded shortening velocity [Vmax], peak extent of systolic shortening at preload [deltaL], maximum active isometric tension [AFi], positive peak tension derivative [+dFi/dt], time-to-peak shortening [TPS], and time-to-peak force [TPF]) and relaxation parameters (maximum lengthening velocity at preload [VI], negative peak tension derivative [-dFi/dt], index of load sensitivity of relaxation [tRi]). RESULTS: In group 1, contraction parameters remained unchanged, with the exception of a decreased Vmax at T30 and AFi at T60 (each P < 0.05). In group 2, all contraction parameters were significantly decreased at T30 and at T60, with the exception of AFi at T60. Both types of plasma decreased V1 and altered tRi at T30 and T60, whereas only reperfusion plasma decreased -dFi/dt at T30 and T60. At T30, deltaL, -dFi/dt, and tRi were significantly more impaired in group 2 than in group 1. There was no relationship between inotropic changes and mean arterial pressure decrease at the time of reperfusion. CONCLUSION: Plasma collected at the time of graft reperfusion in OLT patients exerted negative effects on contraction and relaxation performance in isolated rat left ventricular papillary muscle.

Adult↗

Instantaneous force-velocity-length relationship in diaphragmatic sarcomere.

The simultaneous analysis of muscle force, length, velocity, and time has been shown to precisely characterize the mechanical performance of isolated striated muscle. We tested the hypothesis that the three-dimensional force-velocity-length relationship reflects mechanical properties of sarcomeres. In hamster diaphragm strips, instantaneous sarcomere length (SL) and muscle length were simultaneously measured during afterloaded twitches. SL was measured by means of laser diffraction. We also studied the influence of initial SL, abrupt changes in total load, and 2 x 10-7 M dantrolene. Baseline resting SL at the apex of the length-active tension curve was 2.2 +/- 0.1 microns, whereas SL at peak shortening was 1.6 +/- 0.1 microns in the preloaded twitch and 2.1 +/- 0.1 microns in the "isometric" twitch. Over the whole load continuum and at any given level of isotonic load, there was a unique relationship between instantaneous sarcomere velocity and instantaneous SL. Part of this relationship was time independent and initial SL independent and was markedly downshifted after dantrolene. When five different muscle regions were considered, there were no significant variations of SL and sarcomere kinetics along the muscle. These results indicate that the time- and initial length-independent part of the instantaneous force-velocity-length relationship previously described in muscle strips reflects intrinsic sarcomere mechanical properties.

Animals↗

Hemodynamic correlates of effective arterial elastance in mitral stenosis before and after balloon valvotomy.

This study had the purpose of documenting the hemodynamic correlates of effective arterial elastance (Ea; i.e., an accurate estimate of hydraulic load) in mitral stenosis (MS) patients. The main hypothesis tested was that Ea relates to the total vascular resistance (R)-to-pulse interval duration (T) ratio (R/T) in MS patients both before and after successful balloon mitral valvotomy (BMV). High-fidelity aortic pressure recordings were obtained in 10 patients (40 +/- 12 yr) before and 15 min after BMV. Ea value was calculated as the ratio of the steady-state end-systolic aortic pressure (ESAP) to stroke volume (thermodilution). Ea increased after BMV (from 1.55 +/- 0.63 to 1.83 +/- 0.71 mmHg/ml; P < 0.05). Throughout the procedure, there was a strong linear relationship between Ea and R/T: Ea = 1.09R/T - 0.01 mmHg/ml, r = 0.99, P = 0.0001. This ultimately depended on the powerful link between ESAP and mean aortic pressure [MAP; r = 0.99, 95% confidence interval for the difference (MAP - ESAP) from -18.5 to +4.5 mmHg]. Ea was also related to total arterial compliance (area method) and to wave reflections (augmentation index), although to a lesser extent. After BMV, enhanced and anticipated wave reflections were observed, and this was likely to be explained by decreased arterial compliance. The present study indicated that Ea depended mainly on the steady component of hydraulic load (i.e., R) and on heart period (i.e., T) in MS patients.

Adult↗