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D Chemla

Publications and source records attributed to D Chemla.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cardiotoxicity of colchicine in the rat.

OBJECTIVES: Colchicine poisoning may be lethal and a decrease in cardiac function has been reported in several case reports, but the precise cardiotoxicity of colchicine remains unknown. DESIGN: The experimental in vitro study assessed the intrinsic contractility of left ventricular papillary muscle in rats, 24 h after administration of intraperitoneal colchicine or saline. RESULTS: The administration of colchicine (2 or 4 mg.kg-1) in adult Wistar rats markedly impaired intrinsic myocardial contractility, as shown by a decrease in maximum shortening velocity (-32 and -61%, respectively), active isometric force (-47 and -65%, respectively), and peak power output (-57 and -69%, respectively) of left ventricular papillary muscle. Colchicine impaired isotonic relaxation and load dependence of relaxation, suggesting a decrease in sarcoplasmic reticulum function. Conversely, colchicine significantly accelerated isometric relaxation, suggesting a decrease in calcium myofilament sensitivity. Myothermal economy was markedly impaired only in some rats (3/10 in each group), in which the negative inotropic effect of colchicine appeared to be more particularly pronounced. CONCLUSION: The results indicate that the administration of high doses of colchicine induced intrinsic cardiotoxic effects. Due to its amplitude, such cardiotoxic action may participate in the fatal outcome of acute colchicine poisoning.

Acute Disease↗
PubMed1994

Effects of early and late therapy with perindopril on survival and myocardial inotropic state in experimental dilated cardiomyopathy.

We wished to test (a) whether single-drug therapy with a low dose of the angiotensin-converting enzyme (ACE) inhibitor perindopril has the capacity to improve early survival of the cardiomyopathic Syrian hamster (CSH); (b) whether early treatment with perindopril modifies CSH survival to a greater extent than perindopril treatment initiated later in the course of the disease; and (c) the effects of early and late perindopril therapy on the intrinsic contractility of left ventricular (LV) papillary muscle. We studied CSH from the Bio 53.58 dilated strain (n = 76), in which myocardial necrosis is known to develop from age 30 days, whereas congestive heart failure (CHF) is observed only after age 6 months. Animals were randomly assigned to three groups. In early-treated animals, perindopril (1 mg/kg body weight once daily in distilled water) was administered by force-feeding from age 1 month to 9 months (PE1, n = 21). Animals receiving delayed treatment received distilled water from age 1 month to 6 months, followed by 1 mg/kg body weight from age 6 to 9 months (PE2, n = 34). Controls received distilled water from age 1 month to 9 months (C, n = 21). At endpoint (9 months), mechanical properties of LV papillary muscles and serum ACE activity were studied in a subgroup of 32 CSH (C, n = 8; PE1, n = 10; and PE2, n = 14). Maximum unloaded shortening velocity, maximum extent of systolic shortening in twitch with preload only, and normalized peak of isometric active force were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

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.

Animals↗
PubMed1994

Isometric relaxation of isolated diaphragm muscle: influence of load, length, time, and stimulation.

Determinants of the isometric relaxation rate were investigated in isolated rat diaphragm (n = 30). We tested the hypothesis that these determinants could include loading conditions, namely preload and afterload; abrupt changes in load during the contraction phase; stimulation conditions; and time. Two relaxation sequences were studied. When isometric relaxation occurred at initial muscle length (isotonic-isometric sequence), an increase in total load (P) accelerated the negative peak rate of tension decline (-dP/dtmax). Variations in initial length, stimulation, and onset of relaxation did not modify the -dP/dtmax vs. afterload relationship. When isometric relaxation was analyzed after -dP/dtmax, for a given afterload level the instantaneous rate of tension decline (-dP/dt) was a unique function of instantaneous tension, regardless of previous loading conditions, stimulation mode, or time. When the isometric relaxation occurred at end-shortening muscle length (isometric-isotonic sequence), the -dP/dtmax vs. P relationship was flat. The rate of tension decay, as attested by either -dP/dtmax or instantaneous -dP/dt vs. instantaneous tension phase plane, differed markedly depending on stimulation conditions. Thus the regulation of isometric relaxation rate differed according to the relaxation sequence. In muscle isometrically relaxing at initial muscle length, peak isometric relaxation rate was mainly determined by afterload. Conversely, in muscle isometrically relaxing at end-shortening length, isometric relaxation rate was highly dependent on the level of activation and was independent of preload and afterload.

Animals↗
PubMed1994

[Positive inotropic and lusitropic effect of RP 62719, a new class III antiarrhythmia agent].

Antiarrhythmic drugs, especially the Class I family, exert a negative inotropic effect on the myocardium which is particularly undesirable in patients with depressed left ventricular function. Therefore, research has been directed to the development of new, more specific molecules of the Class III family. The authors studies the mechanical effects of RP 62719 on guinea pig left ventricular papillary muscle. This new molecule is a pure Class III antiarrhythmic, known to lengthen the duration of the cardiac action potential by selectively blocking the potassium current iK1 (inward rectifier K+ current). The mechanical parameters were determined during the phases of contraction and relaxation under isotonic and isometric conditions. At 0.2 and 2 microM concentrations, RP 62719 improved cardiac contraction under both isotonic and isometric conditions with an increase of about 30% of Vmax (p < 0.001), the maximum unloaded shortening velocity delta 1 (p < 0.001), the peak isometric active force normalized per cross-sectional area [AF/S (p < 0.001)]. At these two concentrations, a positive lusitropic effect (improved relaxation) was demonstrated by an increase in negative peak of derivative per mm2-dF/s and maximum lengthening velocity VR max (p < 0.01). At higher concentrations (20 microM), the inotropic and lusitropic effects were less marked with a bell-shaped form of the dose-effect curve. This study indicates that RP 62719 has moderate but significant positive inotropic and lusitropic effects. These actions could provide significant therapeutic advantages especially in patients cardiac failure.

Animals↗
PubMed1993

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)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Intrinsic alterations of diaphragm muscle in experimental cardiomyopathy.

Diaphragmatic function was investigated in the cardiomyopathic Syrian hamster (CSH) from the dilated Bio 53:58 strain, after long-term therapy with the angiotensin-converting enzyme inhibitor perindopril. Twenty-two 1-month old CSHs were treated during a 5-month period by either oral gavage with perindopril (1 mg/kg/day) (n = 11) or placebo (n = 11). Control hamsters from the F1B strain received placebo (n = 7). Mechanical properties were studied in isolated diaphragm strips electrically stimulated in both twitch and tetanic conditions. Compared with F1B control hamsters, peak active tension and positive (+dP/dtmax) and negative (-dP/dtmax) peaks of isometric tension derivative were significantly depressed in placebo treated CSHs. Compared with placebo-treated CSHs, peak active tension was significantly higher in perindopril-treated CSHs in both twitch (25 +/- 4 vs 16 +/- 1 mN/mm2; p < 0.01) and tetanus modes (56 +/- 4 vs 38 +/- 2 mN/mm2; p < 0.01). Moreover, +dP/dtmax and -dP/dtmax were improved significantly in twitch (p < 0.01 and p < 0.01, respectively) and tetanus modes (p < 0.05 and p < 0.01, respectively). We conclude that, in the CSH, long-term therapy with the angiotensin-converting enzyme inhibitor perindopril helped to preserve the diaphragmatic function.

Acetylcholinesterase↗
PubMed1993

A comparison of cyclopiazonic acid and ryanodine effects on cardiac muscle relaxation.

We investigated cardiac muscle behavior after inhibition of either sarcoplasmic reticulum (SR) Ca2+ release or SR Ca2+ uptake. Mechanics of 35 rat papillary muscles were studied after either ryanodine 10(-7) M (n = 11) or cyclopiazonic acid (CPA) 10(-5) M (n = 14) and compared with a control group containing the solvent alone (n = 10). We measured the maximum extent of shortening (delta L) of the preloaded twitch (delta Lp), and the normalized total force (TF) of the full isometric twitch (TFi). The peak lengthening velocity (Vl) of the preloaded twitch (Vlp) and the normalized negative peak force derivative of the fully isometric twitch (-DFi) tested the lusitropic state. With the influence of shortening and/or load on relaxation taken into account, analysis of relaxation was performed using 1) Vlp-to-delta Lp and magnitude of -DFi-to-TFi ratios and 2) slopes of the Vl-delta L and magnitude of -DF-TF relationships over the entire continuum of load. Ca(2+)-release inhibition with ryanodine induced a negative inotropic effect and a decrease in Vlp from 2.7 +/- 0.2 to 1.4 +/- 0.2 Lmax/S, where Lmax is the initial length at the peak of the length-active tension curve (P < 0.001). The Vlp-to-delta Lp ratio and the slope of the Vl-delta L relationship were preserved, indicating that ryanodine was devoid of intrinsic relaxant effect under isotonic conditions. Ca(2+)-uptake inhibition with CPA had no inotropic effect but decreased Vlp from 2.9 +/- 0.1 to 2.2 +/- 0.1 Lmax/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of isoproterenol on myocardial relaxation rate: influence of the level of load.

The present work was undertaken to test the hypothesis that the level of the load faced by the myocardium influences the effects of isoproterenol on relaxation rate. Responses to cumulative doses of isoproterenol (from 10(-10) to 10(-6) M) were studied in rat left ventricular papillary muscle stimulated 12 beats/min at 29 degrees C in 0.5 mM extracellular calcium and preloaded at initial muscle length corresponding to apex of length-active tension curve (Lmax; group 1, n = 20) or at 95% of Lmax (group 2, n = 9). A control group (group 3, n = 8) was studied every 15 min for 75 min. We measured maximum unloaded shortening velocity (Vmax), normalized positive and negative peak force derivatives (+dF and -dF, respectively) of the fully isometric twitch, and peak lengthening velocity of the isotonic twitch with preload only (Vlmax). In group 1, Vmax and +dF increased under 10(-10) and 10(-9) M isoproterenol, respectively, and -dF increased under 10(-9) M isoproterenol (115 +/- 13 vs. 96 +/- 12 mN.s-1.mm-2, P = 0.01). Conversely, Vlmax increased under 10(-7) M isoproterenol only (2.34 +/- 0.19 vs. 1.45 +/- 0.18 Lmax/s, P < 0.001). In group 2, both -dF and Vlmax increased under 10(-7) M isoproterenol only (P = 0.015 and 0.011, respectively). In group 3, -dF and Vlmax did not vary in time. Our results suggest a load-revealed (or length-revealed) difference in the dose dependence of the various biochemical processes involved in the effects of isoproterenol during myocardial relaxation.

Animals↗
PubMed1993

Mechanical determinants of isotonic relaxation in isolated diaphragm muscle.

Determinants of lengthening velocity have not been investigated in the diaphragm muscle. This study was undertaken to define the mechanical determinants of isotonic relaxation rate over the entire load continuum in isolated rat diaphragm (n = 30). We tested the hypothesis that the determinants of lengthening could include loading conditions, namely, preload and afterload; abrupt changes of load during the contraction phase; end-shortening muscle length (ESL); extent of shortening (delta L); time; stimulation mode; and stimulation frequency. In afterloaded contractions preloaded at optimal initial length and stimulated in tetanus at 30 Hz, peak lengthening velocity (+dL/dtmax) was linearly related to delta L, ESL, and/or total load. Varying initial muscle length, ESL, afterload, or the load imposed on the muscle during the isotonic lengthening process did not modify +dL/dtmax vs. delta L relationship, whereas +dL/dtmax vs. load and +dL/dtmax vs. ESL relationships were modified by these procedures. For a given delta L, +dL/dtmax could be modified when lengthening was delayed by reversing the relaxation sequence and when twitch and tetanus modes were compared. In conclusion, our results demonstrate that in isolated diaphragm muscle, delta L is the main determinant of +dL/dtmax over a wide range of loads and under various experimental conditions, independent of ESL and initial muscle length and independent of the load imposed on the muscle during the lengthening process. Time and stimulation mode were also shown to modulate the lengthening rate in diaphragm muscle.

Animals↗
PubMed1993

[Role of sarcoplasmic reticulum in the regulation of myocardial relaxation].

In order to investigate cardiac muscle behavior after inhibition of either sarcoplasmic reticulum (SR) Ca2+ release or SR Ca2+ uptake, 35 papillary muscles of adult Wistar rats were studied after a 60 minutes exposure to ryanodine 10(-7) M (n = 11) or to cyclopiazonic acid (CPA) 10(-5) M (n = 14) and compared with a control group containing the solvent alone (n = 10). We measured the maximum extent of muscle shortening of the preloaded twitch (DLp) and the normalized total force of the fully isometric twitch (FTi). The peak lengthening velocity of the preloaded twitch (VRp) and the normalized negative peak force derivative of the fully isometric twitch (-DFi) tested the lusitropic state. Intrinsic changes in the relaxation phase, independent of the contractile state, i.e., the relaxant effects, were analysed using 1) two ratios; the VRp/DLp ratio of the preloaded twitch and the -DFi/FTi ratio of the fully isometric twitch and 2) the slopes of the VR versus DL and of the -DF versus FT relationship over the whole continuum of load. Ryanodine induced a marked negative inotropic effect associated with a decrease in VRp from 2.7 +/- 0.2 to 1.4 +/- 0.2 Lmax/s (p < 0.001). The VRp/DLp ratio and the slope of the VR versus DL relationship remained unchanged, indicating that ryanodine was devoid of intrinsic relaxant effect under isotonic conditions. At a 10/min stimulation frequency, inhibition of Ca(2+)-uptake function of the SR with CPA had no inotropic effect but decreased VRp from 2.9 +/- 0.1 to 2.2 +/- 0.1 Lmax/s (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Physiopathology of myocardial dysfunction in septic shock].

Left ventricular dysfunction is rarely a prominent feature of septic shock. Initially, it is masked by circulatory changes and adaptive phenomena which increase the cardiac output. Evaluation of intrinsic myocardial function is therefore difficult in this pathology. The different experimental models used (cell culture, isolated muscle, isolated perfused heart and whole animal) and recent clinical studies using angiographic, catheter and echocardiographic data, have confirmed that this condition exists. Its physiopathology is not yet fully understood and involves several mediators. The direct effect of bacterial endotoxins has not been formally established. However, therapy with anti-endotoxin antibodies does give encouraging results. The cytokines, such as interleukin-1, tumour necrosis factor, and platelet activating factor play a key role between the infectious factors and cellular mediators. Their effects on the myocardium are subject of much on-going research. Current date, in particular with respect to the tumour necrosis factor, suggest that they may have a direct cardiodepressor factor. The presence of a circulating negative inotropic substance has been suspected for many years. Recent studies tend to confirm this hypothesis though the substance itself has not yet been isolated. The theory of reduced coronary flow causing myocardial dysfunction in septic shock has fallen out of favour. Some experimental evidence supports the clinical impression of reduced vascular and cardiac reactivity to catecholaminergic stimulation. The actions of different membrane structures involved have not been determined. At cellular level, changes in calcium metabolism, which regulates muscle contraction and relaxation, probably play an important role in septic shock. In addition to the symptomatic therapeutic advances that have been made in septic shock, specific myocardial treatment could be beneficial.

Animals↗
PubMed1993

[Protective effects of perindopril in an experimental model of cardiomyopathy].

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)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Myocardial contractility, lusitropy and calcium responsiveness in young (50 days) and hypertrophied (180 days) cardiomyopathic hamsters.

Contractility, lusitropy and responsiveness to the increase of external Ca2+ concentration were studied in left ventricular papillary muscles of normal and cardiomyopathic Syrian hamsters (SCH) from the UM-X 7.1 strain, both at the onset of myolysis (50-day-old animals) and at the cardiac hypertrophy stage (180-day-old animals) in the absence of congestive heart failure. A marked decrease in all indices of systolic performance was observed in 180-day-old myopathic hamsters as compared to age-matched controls. This was associated with (1) an impairment of the relaxation phase, (2) a loss of the load sensitivity of relaxation, and (3) a decrease in the inotropic and lusitropic responsiveness to Ca2+. On the other hand, when some indices of contraction and the inotropic response to Ca2+ were impaired in 50-day-old myopathic hamsters as compared to age-matched controls, relaxation phase and the lusitropic response to Ca2+ did not alter. This study shows that, in the UM-X 7.1 myopathic hamsters at the earlier stage of the disease, alterations in calcium homeostasis and contraction seem to be the first determinant factors of the development of heart failure when relaxation is not impaired. Conversely, when cardiac hypertrophy has developed, impaired relaxation may worsen heart failure.

Age Factors↗
PubMed1992

Positive inotropic effects of RP 62719, a new pure class III antiarrhythmic agent, on guinea pig myocardium.

The mechanical effects of RP 62719 [(-)1-[-2-(3,4-dihydro-2H-1- benzopyran-4-yl)ethyl]-4-(3,4-dimethoxyphenyl)-piperidine] were tested in vitro on guinea pig left ventricular papillary muscle. RP 62719 is a novel pure class III antiarrhythmic agent known to prolong the cardiac action potential duration by selectively blocking the inward rectifying K+ current. Mechanical parameters were determined from contraction and relaxation phases under isotonic and isometric conditions. At a concentration of 0.02 microM, RP 62719 did not produce significant effects on inotropy or lusitropy. At 0.2 and 2 microM, the drug improved contraction under both heavy and low loading conditions, as evidenced by a 30% increase in maximum unloaded shortening velocity (Vmax, P < .001), peak amplitude of shortening (delta L, P < .001), peak isometric active force normalized per cross-sectional area (AF/s, P < .001) and positive peak of the force derivative per mm2 (+dF/s, P < .001). At the same concentrations, positive lusitropic effects were evidenced by an increase in maximum lengthening velocity (maxVr) and negative peak of force derivative per mm2 (-dF/s, P < .001). At a higher concentration (20 microM), effects of RP 62719 on inotropy and lusitropy were less marked, thus accounting for the bell-shaped form of the dose-response curve. An increase in the extracellular Ca++ concentration from 2.5 to 3.75 mM improved inotropy to a similar extent (+30-50%) as did 2 microM RP 62719. However, lusitropy and mechanical coupling between contraction and relaxation were not modified in the same proportion under RP 62719 and under 3.75 mM Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Cardiomyopathy in the Syrian hamster. Physiological and therapeutic aspects].

The primary hereditary cardiomyopathy of the Syrian hamster is a particularly interesting model of experimental cardiomyopathy 1) because of its slow progression to cardiac failure unlike acute experimental volume and pressure overloading; 2) because of the reproducibility and predictable nature of the mechanical, biochemical and electrophysiological abnormalities observed at each stage of the disease; 3) because of involvement of other muscle groups, and particularly, skeletal muscle. The physiopathology is not fully understood but a disturbance of intracellular calcium homeostasis appears to play a major role. From the therapeutic point of view, a number of calcium antagonists have been shown to be effective in restoring myocardial function, but they have no effect on skeletal muscular lesions. Recently, early prophylactic intervention with therapeutic doses of perindopril has been shown to prevent the decrease of certain parameters of myocardial contractility in vitro in the dilated group, before the appearance of any signs of cardiac failure. This study also showed that angiotensin converting enzyme inhibitors had no intrinsic negative inotropic effects.

Angiotensin-Converting Enzyme Inhibitors↗