Biomedical subjects

Y Lecarpentier

Publications and source records attributed to Y Lecarpentier.

At least 55 records · Page 3Linked to original sources

PubMed1998

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

BACKGROUND: Halothane potentiates the positive inotropic effects of alpha- and beta-adrenoceptor stimulations but impairs the positive lusitropic effect of beta-adrenoceptor stimulations. However, the interactions of isoflurane and sevoflurane with alpha- and beta-adrenoceptor stimulation have not been entirely defined. METHODS: The effects of 1 minimum alveolar concentration isoflurane and sevoflurane on the inotropic responses induced by phenylephrine (10(-8) to 10(-4) M) or isoproterenol (10(-8 to 10(-4) M) were studied in rat left ventricular papillary muscles in vitro (Krebs-Henseleit solution, 29 degrees C; pH, 7.4; 0.5 mM calcium; stimulation frequency, 12 pulses/min). The positive lusitropic effects of alpha- and beta-adrenoceptor stimulations were studied under isotonic and isometric conditions. Data are mean percentages of baseline +/- SEM. RESULTS: In control groups, phenylephrine (134 +/- 8%; P < 0.05) and isoproterenol (171 +/- 7%; P < 0.05) induced a positive inotropic effect. Isoflurane enhanced the positive inotropic effects of phenylephrine (185 +/- 10%; P < 0.05) and of isoproterenol (203 +/- 11%; P < 0.05). Sevoflurane enhanced the positive inotropic effects of phenylephrine (187 +/- 10%; P < 0.05) and of isoproterenol (228 +/- 11%; P < 0.05). These potentiations were similar to those previously reported with halothane. Isoflurane and sevoflurane did not modify the positive lusitropic effects under low and high loads of isoproterenol. CONCLUSION: Although isoflurane and sevoflurane have moderate negative inotropic effects, they potentiated the positive inotropic effects of alpha- and beta-adrenoceptor stimulations but did not modify the positive lusitropic effects of beta-adrenoceptor stimulation.

Anesthetics, Inhalation↗

PubMed1998

Myocardial effects of desflurane in hamsters with hypertrophic cardiomyopathy.

BACKGROUND: The effects of desflurane on myocardial contraction and relaxation in diseased myocardium have not been completely understood. METHODS: The effects of desflurane (1.8 to 9.4 vol%) in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 degrees C, pH 7.40, Ca2+ 2.5 mM; stimulation frequency, 3/min) under low (isotony) and high (isometry) load. Data are mean percentages of baseline +/- SD. RESULTS: Desflurane induced no significant inotropic effect in healthy muscles (maximum unloaded shortening velocity and isometric active force at 9.4 vol%: 97 +/- 9% and 92 +/- 20%, respectively). In contrast, in cardiomyopathic muscles, desflurane induced a moderate negative inotropic effect (maximum unloaded shortening velocity and active force at 9.4 vol%: 84 +/- 19% and 75 +/- 25%, respectively). The negative inotropic effect was more pronounced than that in healthy muscles under low (P < 0.05) but not high load, and even when concentrations were corrected for minimum alveolar concentrations in each strain. Adrenoceptor blockade or pretreatment with reserpine did not modify the inotropic effect of desflurane, suggesting the absence of intramyocardial catecholamine release. However, tyramine also did not induce any significant catecholamine release in hamster myocardium. In both strains, desflurane induced no significant lusitropic effect under low or high load. CONCLUSIONS: Desflurane had no inotropic effect in healthy muscles and a moderate negative inotropic effect in cardiomyopathic muscles. The absence of desflurane-induced intramyocardial catecholamine release was related to hamster myocardium characteristics.

Adrenergic Uptake Inhibitors↗

PubMed1998

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↗

PubMed1998

Effects of initial length on intrinsic tone in guinea pig tracheal smooth muscle.

In the guinea pig, tracheal smooth muscle (TSM) exhibits intrinsic tone (IT). The active nature of IT suggests that it could be influenced by muscle length and load. In the guinea pig, IT is entirely suppressed by the cyclooxygenase inhibitor indomethacin. IT could be measured as the difference between resting tone before and after indomethacin addition. We examined, in electrically stimulated TSM strips (n = 9), the influence of initial muscle length (Li) on IT, the relationship between IT and the maximum extent of relaxation (DeltaF1), and the influence of indomethacin on active isometric force. When Li decreased from 100 to 75% of optimal Li, there was a significant decrease in IT (from 12.0 +/- 0.2 to 5.3 +/- 0.1 mN; P < 0.001). Over the range of Li studied, DeltaF1 underestimated the amount of IT, but there was a close linear relationship between DeltaF1 and IT (r = 0.9). Compared with the basal state, indomethacin increased active isometric force (from 9.5 +/- 1.0 to 19.7 +/- 2.0 mN at optimal Li; P < 0.001) and induced its length dependency. In guinea pig TSM, Li was an important determinant of IT.

Animals↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1997

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

BACKGROUND: Halothane induces negative inotropic and lusitropic effects in myocardium. It has been suggested that halothane potentiates beta-adrenoceptor stimulation. However, its effects on the inotropic response to alpha-adrenoceptor stimulation and its effects on the lusitropic effects of alpha- and beta-adrenoceptor stimulation are unknown. METHODS: The effects of halothane (0.5 and 1 minimum alveolar concentration [MAC]) on the inotropic responses induced by phenylephrine (10(-8) to 10(-4) M) and isoproterenol (10(-8) to 10(-4) M) were studied in rat left ventricular papillary muscles in vitro (in Krebs-Henseleit solution at 29 degrees C, pH 7.40, with 0.5 mM calcium and stimulation frequency at 12 pulses/min). The lusitropic effects were studied in isotonic (R1) and isometric (R2) conditions. RESULTS: One MAC halothane induced a negative inotropic effect (54 +/- 3%, P < 0.05), increased R1 (109 +/- 3%, P < 0.05), and decreased R2 (88 +/- 2%, P < 0.05). In control groups, phenylephrine (137 +/- 7%, P > 0.05) and isoproterenol (162 +/- 6%, P < 0.05) induced a positive inotropic effect. Halothane did not significantly modify the positive inotropic effect of calcium, suggesting that it did not modify the inotropic reserve of papillary muscles. In contrast, 1 MAC halothane enhanced the positive inotropic effects of phenylephrine (237 +/- 19%, P < 0.05) and isoproterenol (205 +/- 11%, P < 0.05). Halothane did not modify the lusitropic effect of phenylephrine under high or low load. In contrast, 1 MAC halothane impaired the positive lusitropic effect of isoproterenol under low load (P < 0.05), whereas it did not modify the positive lusitropic effect of isoproterenol under high load. CONCLUSIONS: At clinically relevant concentrations, halothane potentiated the positive inotropic effects of both alpha- and beta-adrenoceptor stimulation. Furthermore, halothane alters the positive lusitropic-effect of beta-adrenoceptor stimulation under low load.

Anesthetics, Inhalation↗

PubMed1997

In vitro effects of dantrolene on rat myocardium.

BACKGROUND: Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on myocardial contraction and relaxation remain debatable. METHODS: The effects of dantrolene (10(-5)-10(-3) M) on the contractility of rat left ventricular papillary muscles were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, 2.5 and 0.5 mM Ca2+, stimulation frequency 12 pulses/min). The authors studied contraction, relaxation, contraction-relaxation coupling under high and low load, energetics, and postrest potentiation. The effects of dantrolene after depletion of catecholamine stores with reserpine also were studied. RESULTS: Dantrolene induced a moderate concentration-dependent negative inotropic effect at a low calcium concentration (active force at 10(-4) M: 86 +/- 14% of control values, P < 0.05), but not at a high calcium concentration. Dantrolene did not significantly modify the curvature of the force-velocity relation, suggesting that it did not modify myocardial energetics. Dantrolene induced no significant lusitropic effect under low load, suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum. Dantrolene did not significantly modify postrest potentiation and postrest potentiation recovery, suggesting that it did not modify maximum capacity of calcium release by the sarcoplasmic reticulum nor its postrest resetting capacity. Reserpine did not modify the myocardial effects of dantrolene. CONCLUSIONS: In rat myocardium, dantrolene did not modify any of the sarcoplasmic reticulum functions tested (uptake, release, postrest recovery). Dantrolene induced a moderate negative inotropic effect, probably mediated by a decrease in transarcolemmal calcium entry, and this negative inotropic effect was blunted by an increase in calcium concentration.

Animals↗

PubMed1997

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↗

PubMed1997

Effects of desflurane in rat myocardium: comparison with isoflurane and halothane.

BACKGROUND: The cardiovascular effects of desflurane have been investigated in several in vivo animal and human studies. To determine the possible contributions of myocardial depression, the effects of desflurane on various contractile parameters in isolated cardiac papillary muscles were compared with those of isoflurane and halothane. METHODS: The effects of desflurane, isoflurane, and halothane (0.5-2.5 minimum alveolar concentration [MAC]) were studied in rat left ventricular papillary muscles (29 degrees C; pH 7.40; stimulation frequency, 12 pulses/min). The inotropic effects were compared under low (isotony) and high (isometry) loads, using the maximum unloaded shortening velocity (Vmax) and maximum isometric active force (AF). The lusitropic effects were compared in isotonic and isometric conditions. RESULTS: Desflurane has no significant inotropic effect (AF at 2.5 MAC: 95 +/- 11% of control values; NS) in contrast with halothane and isoflurane (AF at 2.5 MAC: 37 +/- 14 vs. 65 +/- 10%, respectively; P < 0.05). After alpha- and beta-adrenoceptor blockade or pretreatment with reserpine, desflurane induced a negative inotropic effect (AF at 2.5 MAC: 83 +/- 11 vs. 89 +/- 8%, respectively) that was not significantly different from that of isoflurane (AF at 2.5 MAC: 80 +/- 12%). Halothane induced a negative lusitropic effect under low load, which was significantly greater than those of isoflurane and desflurane. In contrast to halothane, isoflurane and desflurane induced no significant lusitropic effect under high load and did not modify postrest potentiation. These results suggest that desflurane did not impair sarcoplasmic reticulum function. CONCLUSIONS: When compared with isoflurane, desflurane induced a moderate positive inotropic effect related to intramyocardial catecholamine release. After adrenoceptor blockade, desflurane induced a negative inotropic effect comparable with that induced by isoflurane.

Anesthetics, Inhalation↗

PubMed1997

Myocardial effects of halothane and isoflurane in hamsters with hypertrophic cardiomyopathy.

BACKGROUND: The effects of halothane and isoflurane on myocardial contraction and relaxation in diseased myocardium are not completely understood. METHODS: The effects of equianesthetic concentrations of halothane and isoflurane on inotropy and lusitropy in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 degrees C; pH 7.40; Ca2+ 2.5 mM; stimulation frequency, 3/min) in isotonic and isometric conditions. RESULTS: Halothane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (1.5 vol%, active isometric force (AF): 19 +/- 8% vs. 28 +/- 11% of control values; P < 0.05). Isoflurane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (2.0 vol%, AF: 64 +/- 13% vs. 75 +/- 11% of control values; P < 0.01). However, the negative inotropic effects of halothane and isoflurane were not different for cardiomyopathic or healthy hamsters when their concentrations were corrected for minimum alveolar concentration (MAC) values in each strain. Halothane induced a negative lusitropic effect under low load, which was more important in cardiomyopathic hamsters, suggesting a greater impairment in calcium uptake by the sarcoplasmic reticulum. In contrast, isoflurane induced a moderate positive lusitropic effect under low load in healthy but not in cardiomyopathic hamsters. Halothane and isoflurane induced no significant lusitropic effect under high load. CONCLUSIONS: Halothane and isoflurane had greater negative inotropic effects in cardiomyopathic than in healthy hamsters. Nevertheless, no significant differences in their inotropic effects were noted when concentrations were correlated as a multiple of MAC in each strain.

Anesthetics, Inhalation↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

Effects of angiotensin converting enzyme inhibition on crossbridge properties of diaphragm in cardiomyopathic hamsters of the dilated bio 53-58 strain.

Crossbridge properties of cardiomyopathic Syrian hamster (CSH) diaphragm from the dilated Bio 53-58 strain were analyzed after 5-mo of treatment with the angiotensin converting enzyme (ACE) inhibitor perindopril (1 mg/kg/d by oral gavage). Three groups were studied: control F1B hamsters (C; n = 14); CSH given placebo (PL; n = 11 ); and perindopril-treated CSH (PE; n = 11). Peak isometric tension was lower in PL than in C, in both twitch (21.4 +/- 1.5 versus 46.9 +/- 1.5 mN/mm2; p < 0.001) and tetanus (41.0 +/- 2.7 versus 90.5 +/- 3.3 mN/mm2; p < 0.001). In PE, peak isometric tension was intermediate between C and PL, and was significantly lower than in C and higher than in PL. The single force of one crossbridge (pi), the number (m) of crossbridges, the turnover rate of myosin adenosine triphosphatase (ATPase) (kcat), and peak mechanical efficiency (Effmax) were calculated from A.F. Huxley's equations; m was lower in PL than in C, in both twitch (3.4 +/- 0.2 versus 4.9 +/- 0.2 10(9)/mm2; p < 0.001) and tetanus (4.0 +/- 0.3 versus 8.9 +/- 0.7 10(9)/mm2; p < 0.001); m was higher in PE than in PL, in both twitch 4.3 +/- 0.5 versus 3.4 +/- 0.2 10(9)/mm2; NS) and tetanus (6.2 +/- 0.4 versus 4.0 +/- 0.3 10(9)/mm2; p < 0.01), with no change in pi. In the three groups, Effmax correlated linearly with kcat (r = 0.93; p = 0.001) and showed a negative linear correlation with pi (r = 0.996; p = 0.001). In conclusion, our results show that in experimental cardiomyopathy, ACE inhibitor mainly helps to prevent a decrease in the number of diaphragm muscle crossbridges, resulting in preserved peak isometric tension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

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.

Animals↗

PubMed1997

Developmental changes in crossbridge properties and myosin isoforms in hamster diaphragm.

The aim of this study was to determine the effects of maturation on crossbridge properties and myosin isoform composition in hamster diaphragm muscle. Diaphragm strips were obtained at postnatal Days 1 and 8 and in adults (10 to 12 wk). Peak isometric tension and maximum unloaded shortening velocity (Vmax) increased with age (p < 0.001). The single crossbridge force (pi), the total number of crossbridges normalized per cross-sectional area (m x 10(9)/mm2), the turnover rate of myosin ATPase (kcat), and peak mechanical efficiency (Effmax) were calculated from Huxley's equations. The value of m increased significantly from birth to adulthood (p < 0.001), with no changes in pi or Effmax; kcat increased significantly only after the first week postpartum. There was a strong linear relationship between peak isometric tension and m (p < 0.001). Conversely, changes in Vmax were not related to kcat. Myosin electrophoresis showed that neonatal bands and slow myosin isoforms (S) were present at birth. The number of fast adult myosin isoforms increased progressively from birth to adulthood, whereas S increased during the first week postpartum. In conclusion, development changes in diaphragm muscle force and myosin isoform composition were associated with changes in crossbridge number and kinetics, with no changes in the average force per crossbridge or in mechanical efficiency.

Age Factors↗

PubMed1996

Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles.

BACKGROUND: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles. METHODS: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect. RESULTS: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group). CONCLUSION: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.

Analysis of Variance↗