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.

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.

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.

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.

Detection of the fluorescence of GI vessels in rats using a CCD camera or a near-infrared video endoscope.

BACKGROUND: Choroidal near-infrared fluorescent angiography can detect vessels in the eye with high resolution. Observation of fluorescent gastrointestinal (GI) vessels by endoscopy may be useful in portal hypertension and bleeding ulcer. We here describe a technique for the detection of fluorescent GI vessels with a CCD camera or a near-infrared video endoscope. METHODS: Laparotomy was performed on rats. A tissue target was excited by means of a laser diode. We took pictures of tissue under both white and near-infrared light, both before and after intravenous injection of indocyanine green. Fluorescent light was selected by means of filters placed in front of the lens of a CCD camera or a near-infrared video endoscope. RESULTS: Under near-infrared light and after dye injection, we observed fluorescent vessels in real time and distinguished arterial from venous fluorescence. CONCLUSIONS: This device permits visualization of GI vessels, which could be useful for diagnosis of vascular abnormalities during endoscopy and surgery.

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.

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.

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.

Relaxation is impaired in the diaphragm muscle of the cardiomyopathic Syrian hamster.

Relaxation was examined in diaphragm muscle strips of cardiomyopathic Syrian hamsters and control hamsters. Isotonic lengthening velocity and isometric tension decay were analyzed over the load continuum in response to twitch. For each load level (P), we measured the maximum extent of shortening (deltaL), the peak lengthening velocity (VL), and the peak rate of tension decline (-dP/dtmax). The kinetics of sarcomere length (SL) were simultaneously measured by laser diffraction. In an attempt to account for the influence of shortening and/or load on relaxation, we calculated the slopes of the VL - deltaL and -dP/dtmax - P relationships. In both groups, there was a direct relationship between (1) VL and deltaL and (2) -dP/dtmax and P. In myopathic hamsters, we observed a decrease in the slope of the VL - deltaL relationship (p < 0.05), a decrease in VL at any common value of both muscle and sarcomere extent of shortening, and an increase in the duration of overall lengthening. Isometric tension decay was significantly prolonged in myopathic muscle strips, while the -dP/dtmax - P relationship was not significantly different than in controls. At low-to-medium loads, SLs at the onset of tension decline were greater in myopathy. These data indicate that relaxation of the diaphragm was both slowed and prolonged in myopathic Syrian hamsters.

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.

Sarcomere relaxation in hamster diaphragm muscle.

We characterized instantaneous sarcomere relaxation over the load continuum in isolated hamster diaphragm muscles by means of laser diffraction. In afterloaded twitches, sarcomere relaxation displayed two consecutive phases. The bulk of sarcomere lengthening occurred during the first phase and corresponded in time to muscle lengthening. The second phase of sarcomere relaxation was slower and corresponded in time to tension decay. At initial muscle length, the peak velocity of sarcomere lengthening (SVL) was linearly related to both the maximum extent of sarcomere shortening (delta SL) and sarcomere length at peak shortening (SLmin; each P < 0.01). Varying preload modified the SVL vs. SLmin relationship but not the SVL vs. delta SL relationship. At a given preload, muscle tension decay began at a similar sarcomere length, regardless of the afterload level. In conclusion, our results support the role played by sarcomere length in regulating the diaphragm muscle-lengthening rate but not the rate of tension decline.

M mode and Doppler echocardiographic assessment of left ventricular diastolic function in primary antiphospholipid syndrome.

BACKGROUND: High titres of serum antiphospholipid antibodies are a possible pathogenic factor for cardiac lesions in patients with systemic lupus erythematosus. OBJECTIVE: To test the hypothesis of a causal link between high titres of antiphospholipid antibodies in the serum and myocardial involvement in patients without systemic lupus erythematosus. PATIENTS AND DESIGN: 18 patients with primary antiphospholipid syndrome (recurrent fetal loss, arterial and/or venous thrombosis, high titres of antiphospholipid antibodies, and no criteria for systemic lupus erythematosus) were prospectively studied by cross sectional, M mode, and pulsed Doppler echocardiography, and compared with 18 healthy controls. The pulsed Doppler indices of left ventricular diastolic function included isovolumic relaxation time and four mitral outflow indices: peak velocity of early flow, peak velocity of late flow, early to late peak flow velocity ratio, and rate of deceleration of early flow. Four computerised M mode indices were also measured: peak rate of left ventricular enlargement in diastole, peak rate of posterior wall thinning, peak velocity of lengthening of the posterior wall, and velocity of circumferential chamber lengthening. RESULTS: Compared with controls, patients with primary antiphospholipid syndrome had higher values for isovolumic relaxation time and peak velocity of late mitral outflow and lower values for early to late mitral peak outflow velocity ratio, rate of deceleration of early mitral outflow, peak rate of left ventricular enlargement in diastole, peak rate of posterior wall thinning, peak velocity of lengthening of the posterior wall and velocity of circumferential chamber lengthening. CONCLUSION: This abnormal pattern reflects an impairment of myocardial relaxation and filling dynamics of the left ventricle in patients with primary antiphospholipid syndrome who were free of any clinically detectable heart disease. These data suggest that high serum titres of antiphospholipid antibodies may be associated with subclinical myocardial damage.

Influence of dietary polyunsaturated fatty acids on contractility, lusitropy and compliance of isolated rat myocardium.

Two groups of 15 rats were fed for 4 weeks with diets containing 15% by weight of fat varying in polyunsaturated fatty acids (PUFA) content and type. Diet C18:2 (n-6) contained 20% of total fatty acids as linoleic acid and small amount of (n-3) PUFA (0.4% of the total fatty acids). Diet LC (n-3) contained the same amount of 18:2 (n-6) and of long chain (n-3) C20 and C22 PUFA (10% of the total fatty acids). Contents of both saturated fatty acids and amount of total PUFA were kept constant in the two diets. Left ventricular papillary muscle mechanics were studied blind at Lmax and over the entire load-continuum, in terms of inotropy, characteristics of the force-velocity relationship, relaxation and compliance. Inotropy, force-velocity relationships and muscle compliance were similar in both groups. There was a trend towards a lower peak lengthening velocity at preload in the LC (n-3) group (P = 0.10) together with an unchanged peak rate of isometric force decline. This resulted in a significant impairment of the two mechanical indexes testing the load dependence of myocardial relaxation (P = 0.019 and P = 0.002). In conclusion, short-term differences in PUFA regimen were associated with an unchanged myocardial contractility and economy of force generation. The decreased load dependence of relaxation together with unchanged myocardial compliance strongly favored a physiological relevance of the previously reported modifications of sarcoplasmic reticulum phospholipid composition and calcium transport under (n-3) PUFA regimen.

Reactive hyperemia unmasks reduced compliance of cutaneous arteries in essential hypertension.

To evaluate changes in distal cutaneous arteries during hypertension, we used a noninvasive method to assess the compliance and vascular resistance of the hand radial arteries, mainly distributed to the skin, in 10 normotensive and 10 hypertensive (HT) men. Radial artery diameter and blood velocity were measured by means of pulsed Doppler concomitantly with measurements of finger arterial pressure by photoplethysmography. Hand radial vascular resistance was calculated as the ratio of mean arterial pressure to mean radial blood flow. A simple resistive-capacitive model of large and small arteries of the hand allowed us to evaluate arterial compliance from the exponential slope of finger diastolic pressure decay and vascular resistance. Measurements were made at baseline and during reactive hyperemia after 5 min of complete occlusion of the brachial artery with a pneumatic cuff. Except for pressure, there were no baseline differences between the groups. In normotensive and HT subjects, hyperemia increased radial artery diameter and blood velocity (P < 0.001) and compliance (P < 0.01 and P < 0.05, respectively) and decreased mean pressure (P < 0.01 and P < 0.001, respectively) and resistance (P < 0.001). During hyperemia, the only difference between the groups, except for pressure, was lower compliance in HT subjects (P < 0.01). Moreover, compliance during hyperemia negatively correlated with baseline mean pressure (P = 0.001). Thus hyperemia unmasked reduced compliance in the HT patients but did not show abnormal resistance, suggesting that the elastic properties of the hand skin radial arteries might be more sensitive than their resistive properties to high blood pressure.

Left ventricular diastolic function in asymptomatic and symptomatic human immunodeficiency virus carriers: an echocardiographic study.

Acquired immunodeficiency syndrome (AIDS) is a systemic illness affecting multiple organs, including the heart. Left ventricular (LV) diastolic dysfunction has been reported as the first echocardiographically detectable abnormality in several cardiovascular disorders. We tested the hypothesis that Human Immunodeficiency Virus (HIV) carriers have LV diastolic impairment when studied early in the clinical course of the infection. Doppler echocardiographic and computerized time-motion parameters of LV diastolic function were obtained in 51 HIV patients and in 25 age- and sex-matched healthy controls. The HIV population consisted of 28 totally asymptomatic subjects and 23 patients with incipient AIDS. As compared to controls, the HIV group had similar heart rate, blood pressure level, LV dimensions and fractional shortening, but increased isovolumetric relaxation time (P = 0.03), early filling duration (P < 0.001) and decreased early mitral flow peak velocity (E) (P = 0.02) and EF slope (P < 0.001). HIV patients also showed lower values for posterior wall thinning (PWT, P < 0.01) and peak lengthening velocity of the posterior wall (PVL, P < 0.05), and a trend to a decreased peak rate of LV enlargement in diastole (D+, P = 0.05). Doppler-derived parameters of diastolic function were significantly altered in the asymptomatic HIV group vs controls. The LV diastolic indices were similar in symptomatic and asymptomatic HIV patients except for PWT, which was lower in the symptomatic HIV group (P = 0.04). Since mild and focal wall motion abnormalities were detected in 11 HIV carriers (22%), comparison of LV diastolic indexes between HIV patients and controls was also performed in two subgroups; these included asymptomatic (n = 26) and symptomatic (n = 14) patients with normal contractile state. The two subgroups had abnormalities of diastolic function similar to those of the HIV group as a whole, but with somewhat lower levels of statistical significance. Our data strongly suggest that there is myocardial involvement at the early stage of HIV infection; however, its impact on the clinical course of the disease remains to be clarified.

Relaxant effects of isoproterenol in isolated cardiac muscle: influence of loading patterns.

The purpose of this study was to test the hypothesis that loading patterns (i.e., loading sequence, total load, and preload) modulate the relaxant effects of isoproterenol. The effects of isoproterenol (10(-6) M) on peak rate of force decline (-dF/dt) were studied in rat left ventricular papillary muscle (n = 24) with respect to two sequences of relaxation: the classical, isotonic-isometric sequence, in which tension fall occurs at initial muscle length, and the physiological, isometric-isotonic sequence, in which tension fall occurs at end-systolic muscle length. The influences of muscle load and initial length were accounted for in the evaluation of relaxation rate by plotting -dF/dt against the entire range of loads both at preload = maximum length (Lmax) and 90% Lmax. The main results are the following: 1) in the classical, isotonic-isometric sequence of relaxation, and whatever the preload, the magnitude of the relaxant effect of isoproterenol increased with load; 2) after reversal into the physiological, isometric-isotonic sequence of relaxation, the relaxant effect of isoproterenol behaved independently of load level in muscle preloaded at Lmax; 3) conversely, in muscle preloaded at 90% Lmax and relaxing according to the physiological sequence, the relaxant effect of isoproterenol increased with load; and 4) the peak relaxant effect of isoproterenol was proportionally higher in the physiological sequence of relaxation than in the classical one and occurred at a similar level of load, whatever the loading sequence and whatever the preload level. Our results indicate that loading patterns finely modulated the relaxant effects of isoproterenol and that muscle length, both before the contraction phase and at the onset of relaxation phase, influenced the effects of isoproterenol on myocardial relaxation rate.

Myocardial effects of early therapy with perindopril during experimental cardiomyopathy.

The effects of chronic angiotensin-converting enzyme (ACE) inhibition on intrinsic myocardial contractility of the failing myocardium have been poorly documented. In the present study, inotropy, lusitropy, and economy of force generation were studied in vitro in papillary muscles from cardiomyopathic Syrian hamster (CSH) under early perindopril therapy, i.e., therapy begun at a stage when experimental heart failure was not yet observed. One-month-old CSH from the dilated strain Bio 53.58 were randomly treated over a 5-month period with either the ACE inhibitor perindopril 1 mg/kg/day (n = 11) or placebo (n = 11), and 7 age-matched controls were given placebo. Compared with control, placebo had a lower maximum shortening velocity (Vmax) (p < 0.01) and normalized total force (p < 0.05), and a lower curvature of the force-velocity relationship (p < 0.01). It has been shown that the higher the value of the curvature, the better the myothermal economy of force generation. Compared with placebo, perindopril had a 68% inhibition of plasma ACE activity and a greater Vmax (p < 0.05), whereas total force/mm2 was similar. This resulted in a lesser decrease of the curvature compared to control (p < 0.05). Placebo had a decreased peak lengthening velocity and rate of force decline. However, compared to control, no intrinsic abnormalities of the relaxation phase were observed in either placebo or perindopril when relaxation parameters were corrected for the lower systolic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

[Protective effects of perindopril in an experimental model of cardiomyopathy]. / Effets cardioprotecteurs du périndopril dans un modèle expérimental de cardiomyopathie dilatée.

The effects of an angiotensin converting enzyme (ACE) inhibitor on the intrinsic contractility of the myocardium in cardiac failure have not been studied intensively. The authors studied inotropism, lusitropism and economy of contraction in vitro on left ventricular papillary muscle preparations of cardiomyopathic Syrian hamsters (CSH) treated preventively with perindropil, i.e. before overt signs of cardiac failure. The CSH of the dilated Bio 53.58 strain aged 1 month were treated with perindropil 1 mg/Kg/day for 5 months (PE, N = 11) or with placebo (PL, N = 11) and control hamsters of the F1B strain received placebo (C, N = 7). Compared with C, PL had a significant reduction of the maximal velocity of contraction Vmax (p < 0.01) and of total isometric tension (TF/mm2), p < 0.05, and a reduction of the G curve of the hyperbolic Hill Force-Velocity relationship (p < 0.01). The G value is usually greater in models with improved economy of contraction. When compared with PL, PE showed a 68% inhibition of the plasma activity of ACE, a better Vmax (p < 0.05) but an unchanged TF/mm2. The G value was less depressed than that of C (p < 0.05). The velocity of isotonic relaxation (maxVL) and the negative peak of the derivative of the isometric force (-dF/dt max) were significantly lower in the PL than in the C group but these lusitropic abnormalities remained coordinated with those of the contraction phase, indicating the absence of an intrinsic effect on relaxation in cardiomyopathy. Perindopril prevented the reduction of maxVL but not that of -dF/dt max.(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in the diastolic left ventricular function in primary antiphospholipid antibody syndrome]. / Altération de la fonction ventriculaire gauche diastolique au cours du syndrome primitif des anticorps antiphospholipides.

Previous studies have shown that left ventricular (LV) diastolic function is frequently impaired in patients with systemic lupus erythematosus. We prospectively studied echo-Doppler indices of LV diastolic function in 18 patients with primary antiphospholipid syndrome (PAPS), who where compared to a group of 18 healthy controls. Heretofore undescribed LV relaxation abnormalities were found in the PAPS group: this finding suggests the existence of a causal link.

Effects of perindopril on myocardial inotropy, lusitropy and economy, and on diaphragmatic contractility in the cardiomyopathic Syrian hamster.

Over a 5-month period, 22 1-month-old cardiomyopathic Syrian hamsters were randomly treated with either angiotensin-converting enzyme inhibitor (perindopril 1 mg/kg/day) (PE, n = 11) or placebo (PL, n = 11), and 7 age-matched controls (C) were given placebo. Compared to C, mechanics of left ventricular papillary muscles from PL exhibited a lower maximum unloaded shortening velocity (Vmax) (P less than .01) and normalized peak active force (P less than .05), and a significantly less curved shape of the force-velocity (F-V) relationship (P less than .01). The curvature of the F-V relationship has been proposed as a reflection of the efficiency of muscle contraction. Compared to PL, PE had a 68% inhibition of plasma ACE activity and a greater Vmax (P less than .05), whereas active force (AF) was similar. This resulted in a lesser decrease of the curvature of the F-V relationship compared to that of C (P less than .05). Muscle strips from the ventral costal diaphragm were dissected from the muscle in situ. In both twitch and tetanus modes, intrinsic mechanical performance of diaphragm muscle was markedly decreased in PL compared to C as regards normalized positive (+dF/dtmax/mm2) and negative (-dF/dtmax/mm2) peak rate of force, and normalized peak active force (AF/mm2) (P less than .01 each). In both twitch and tetanus modes, PE had an increased +dF/dtmax/mm2 (P less than .05), -dF/dtmax/mm2 and AF/mm2 (P less than .01 each), compared to PL. These results indicate 1) that the low inotropic state observed in cardiomyopathic Syrian hamsters was associated with decreased myothermal economy of cardiac contraction and with a major impairment of diaphragm intrinsic contractility, and 2) that early therapy with angiotensin-converting enzyme inhibitor helped to preserve myocardial contractility and economy, and diaphragm contractility.