Cardiac ultrastructural abnormalities in Syrian hamsters with spontaneous cardiomyopathy or subjected to cardiac overloads.

Ultrastructural and morphometric abnormalities of Syrian hamster cardiomyopathy were compared to those observed in two different models of cardiac hypertrophy produced by mechanical overload (abdominal aortic stenosis, 60-day duration) or by isoproterenol injection during 15 days in normal Syrian hamsters of the same strain. Aspects of increased protein synthesis were observed in all three groups of animals. This was the only abnormality observed in the aortic stenosis group. Cardiomyopathy was different from the two other types of overload by the existence of large calcium deposits inside of the myocytes, by the presence of thin filaments and amorphous material accumulation suggesting abnormal synthesis and by a significant reduction of myofibrils at the heart-failure phase. Nuclear abnormalities with nuclear constrictions suggesting a division process and an increased number of myocytes with two nuclei were present in both spontaneous cardiomyopathy and isoproterenol-induced cardiopathy. Therefore, Syrian hamster cardiomyopathy appears to be different from cardiopathy induced by hemodynamic overload but, in spite of specific aspects, resembles that induced by isoproterenol injections, strengthening the hypothesis of a pathogenic role of catecholamines in the Syrian hamster cardiomyopathy.

Relationship of myocardial morphometry in aortic valve regurgitation to myocardial function and post-operative results.

In 24 patients with aortic insufficiency undergoing aortic valve replacement, a clinical and hemodynamic study was performed pre-operatively. Left ventricular biopsies were obtained perioperatively for morphometric study. No significant relations were found when morphometric data were compared to functional class, cardiothoracic radio and ECG findings. The percentage of interstitial fibrosis was not correlated with any of the measured hemodynamic parameters. Myocardial cell diameter was weakly correlated with left ventricular systolic function parameters. A decrease in the percentage of contractile material was strongly correlated with an impaired left ventricular function, assessed pre-operatively. During clinical follow-up, patients were divided into two groups: Group A (17 patients) included patients who were in class I or II of NYHA after surgery. Group B (seven patients) included patients who died or were in functional class III or IV. As compared with Group A, Group B patients had a significantly lower ejection fraction; their myocardial cell diameter was larger and the percentage of myofibrils, and the content of contractile material were significantly lower. This suggests that, in aortic regurgitation, left ventricular dysfunction is correlated with contractile material loss and not with interstitial fibrosis, and that morphometric changes are good predictors of follow-up after surgery.

Morphological approach to the mechanism of heart failure.

From the ultrastructural aspects of the myocardial cell in different types of heart overloading, several points concerning the nature of the myofibrillar changes, the changes in volume, number and size of mitochondria, and the dependence of cellular lesions on the severity of the load were discussed.

[Influence of preload on myocardial relaxation in the rat]. / Influence de la précharge sur la relaxation du myocarde de rat.

Preload, which determines the initial muscle length, has proved to be a basic determinant of the muscle relaxation phase. The mechanical properties of the papillary muscle of Wistar rats (n = 20) were studied at different initial lengths (L): Lmax and 98 p. 100, 94 p. 100, 90 p. 100, 86 p. 100 and 82 p. 100 Lmax. In isometry, the relaxation phase was proportionally less sensitive to a reduction of preload than the contraction phase. When L decreased the peaks of maximal force derivative of the contraction phase (+dF.dt-1 max) and relaxation phase (-dF.dt-1 max) were linearly and significantly lowered at L = 94 p. 100 Lmax and L = 90 p. 100 Lmax respectively. Conversely, in isotonia the relaxation phase was much more sensitive to a reduction of preload than the contraction phase. On a muscle preloaded from 82 p. 100 Lmax to Lmax, the highest max Vr value (i.e. maximal speed of isotonic relaxation) was measured at Lmax, which is the apex of the Starling's isometric curve. When L decreased max Vr decreased linearly and significantly at 94 p. 100 Lmax. In contrast, the maximal speed of contraction (max Vc) increased between Lmax and 94 p. 100 Lmax, became maximal, then significantly decreased beyond 82 p. 100 Lmax. Thus, in the physiological range of the myocardium (Lmax - 85 p. 100 Lmax) the rat papillary muscle tended to maintain its maximal isotonic speed of contraction, or even to increase that speed, whereas the isometric contraction, isometric relaxation and isotonic relaxation phases were early and significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between inotropy and relaxation in rat myocardium.

Myocardial mechanics of 56 rat papillary muscles were investigated in various inotropic states, i.e., early postpartum (1st day, 1st mo) and, in adult, by altering external calcium concentration, [Ca2+]0, stimulation frequency (F), and initial muscle length (L). In all these protocols, the decrease of the inotropic level paralleled a progressive diminution in load sensitivity of relaxation. In such protocols modifying cardiac contractility, peak shortening velocity of the twitch with preload only at Lmax (Vcmax) was always less depressed than peak lengthening velocity (Vrmax), and the ratio R1 = Vcmax/Vrmax always increased. This increase of R1 was linearly related with the decrease of the maximum unloaded shortening velocity (Vmax). The ratio R2 (positive over negative peak force derivatives of the isometric twich at Lmax) was significantly lowered in newborn and was lowered in adult for [Ca2+]0 less than or equal to 1 mM and L less than or equal to 94% Lmax. For a given change in Vmax, each of the experimental protocols gave rise to specific changes in contraction-relaxation coupling tested at low load (R1) and at heavy load (R2).

[Absence of ultra-structural histological lesions of the myocardium in cardiac insufficiency of hyperthyroidism]. / Absence de lésions histologiques ultra-structurales du myocarde dans l'insuffisance cardiaque de l'hyperthyroïdie.

Myocardial failure may complicate hyperthyroidism. Some authors consider that preexisting myocardial lesions are necessary for its development. We studied a case of myocardial failure, presenting as a dilated cardiomyopathy, complicating hyperthyroidism in a 57 year old woman. She had a bio-clinical evaluation and a haemodynamic study with endomyocardial biopsy of the left ventricule. No valvular or coronary disease were noted. The light and ultra-microscopic aspects of the myocardium were within normal limits. We conclude that preexisting myocardial lesions are not essential to the development of myocardial failure complicating hyperthyroidism.

Real-time kinetics of sarcomere relaxation by laser diffraction.

Kinetics of sarcomere movement were studied in real-time by laser diffraction. Instantaneous sarcomere shortening was measured during afterloaded twitches simultaneously with instantaneous shortening and tension of the whole trabecula excised from rat right ventricle. Resting sarcomere length at optimal length was 2.20 +/- 0.02 micron (mean +/- SEM). Maximum amplitude of sarcomere shortening was 0.30 +/- 0.01 and 0.16 +/- 0.01 micron, respectively, in twitches loaded with preload only, and in "isometric" twitches. When the isotonic load (expressed as a percentage of maximum isometric force TF) increased, the maximum velocity of sarcomere relaxation max Vr (micron/sec) decreased: max Vr = -4 exp (-2.5 X 10(-2) % TF); r = 0.95. The time course of sarcomere relaxation appeared to be progressively delayed when the total load increased from preload only up to "isometric" load. Sarcomere relaxation occurred in two successive exponential phases, a rapid phase [time constant (msec): tau 1] followed by a slower one (time constant: tau 2). When the total load increased, tau 1 increased and tau 2 decreased according to the linear relations: % TF = 0.2 tau 1 + 4.8 (r = 0.83) and % TF = -0.1 tau 2 + 157 (r = 0.95). The relative predominance of both the time course and the amplitude of these two phases depended upon the level of total load. The rapid process predominated at low load, the slow one at high load. The role of load and/or shortening in the time course of these two phases is discussed.

Myocardial cell nucleus in cardiac overloading in the rat.

The myocardial cell nucleus was studied in the rat during its normal growth and under different types of heart overloading. Under overloading of short duration, a disappearance of condensed chromatin and an increase in the nucleolus and nucleolonema were interpreted as representing cell overactivity. With isoproterenol overloading, a first stage of cell necrosis and of its consequences on chromatin and nucleolus was followed by the process of cell repair and overactivity. With overloading of long duration, several different nuclear aspects were encountered: (a) enlarged and distorted nuclei as possible supports of polyploidy; (b) a partial coupling between two adjacent nuclei, interpreted either as nuclear fusion or amitosis; (c) segregation of different proteins, probably due to cell damage. The number of nuclei per myocyte was high (90%) in the adult. It decreased (80%) two days after isoproterenol overloading, as well as in heart hypertrophy of 6-9-months duration. Nuclear size increased under isoproterenol overdosage of 48-h duration. The amount of nuclear DNA also increased two days after isoproterenol overdosage, particularly in mononucleated cells.

Relaxation of mammalian heart muscle during chronic cardiac overload.

Cardiac relaxation was studied in rat papillary muscle during hypertrophy induced by different chronic volume and/or pressure overload (aortic insufficiency, aorto-caval fistula, aortic stenosis, spontaneously hypertensive rat). Maximum velocity of lengthening did not depend upon the degree of cardiac hypertrophy, but rather on the type of chronic overload. Cardiac hypertrophy did not modify the load sensitivity of relaxation, whatever the type and stage of chronic overload, although, during acute hypoxia, the load sensitivity disappeared both in normal and in hypertrophied heart muscle.

Lithium causing a serious sinus-node dysfunction at therapeutic doses.

The cardiovascular effects of lithium have been indexed in literature since 1900, most frequently in cases of intoxication. We recently studied the exceptional case of a patient showing a serious sinus node dysfunction during lithium treatment. The serum lithium levels were always within the therapeutic range. After two endocardial explorations and withdrawal of lithium, we found that the sinus node dysfunction was due to lithium and reversible after withdrawal of it. Some ignored dysfunctions could exist with a regularly controlled treatment.

[Cardiac relaxation in experimental chronic myocardial hypertrophy: role of the sarcoplasmic reticulum]. / La relaxation cardiaque au cours de l'hypertrophie myocardique chronique expérimentale: le rôle du réticulum sarcoplasmique.

The relaxation phase was studied in normal rat hearts submitted to chronic myocardial pressure and/or volume overload (stenosis of the abdominal aorta, aortic regurgitation, aorto-caval fistula) and in spontaneously hypertensive rats, some of which also had aorto-caval fistulae. Four indices were chosen to quantify the relaxation phase: maximal velocity of relaxation during contraction with preload alone, the negative peak of the derivative of isometric tension, and two other indices testing the sensitivity of the relaxation phase to other conditions of load. The first two indices were found to be depressed during chronic myocardial overload, especially with aorto-caval fistulae and mixed overload. On the other hand, the other two indices of the degree of sensitivity to the relaxation load by two different methods showed no significant difference between chronically overloaded and control hearts, though changes were observed after acute hypoxia. These two indices are related to morphological development and to the functional state of the sarcoplasmic reticulum. These results suggest that the rate of calcium uptake by the sarcoplasmic reticulum is reduced during chronic myocardial overload but that the myocardium retains its ability to regulate the relaxation phase with respect to time and the degree of total load. This property disappears temporarily after hypoxia when the heart behaves like frog myocardium which has practically no sarcoplasmic reticulum.

Serious sinus node dysfunction caused by therapeutic doses of lithium.

We studied an exceptional case of a patient showing serious sinus node dysfunction during lithium treatment with levels constantly within the therapeutic range. After two endocardial explorations we found that the sinus node dysfunction was due to lithium and reversible after its withdrawal.

[The use of lasers in the study of cardiac mechanics]. / Apport du laser à l'étude de la mécanique cardiaque.

Cardiac and skeletal muscles exhibit regularly spaced light and dark transverse striations (the I and A bands respectively). Consequently, when they are illuminated by a laser beam, they behave like diffraction gratings. The diffraction line spacing varies inversely with the sarcomere length. Real-time kinetics of sarcomere can be measured with a high accuracy. The analysis of the diffraction pattern indicates a high degree of synchronization of sarcomere movements (contraction and relaxation). This technique represents a powerful method to analyse the mechanical behaviour of heart muscle at subcellular level.

Force-velocity-length relationship during cardiac hypertrophy. Time course of activation.

Basic mechanical properties observed during cardiac hypertrophy were studied in left ventricular rat papillary muscles after exposure to chronic pressure and/or volume overloading. It is always possible, during such overloading conditions, to define the level of contractility in terms of a force-velocity-length (F-V-L) relationship regardless of time and initial length. Thus, during a determined period of the contraction phase and for a given total load, shortening velocity remained an univocal time-invariant function of shortening length, involving a time-independent maximum intensity of activation. The onset of this precise phase was reached relatively soon after stimulus. The time-independent F-V-L relation was observed both in controls and in hypertrophied heart muscles, whatever the degree and the type of induced hypertrophy, and even during the latest phases of congestive heart failure.

Nonsympathetic increased inotropic state early after aortic insufficiency.

The very early left ventricular response to chronic volume overload induced by aortic insufficiency (AI) was examined in conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring internal diameter, segmental length, and parietal wall thickness. Acute volume loading with dextran (AVL) was compared with that 24 and 48 h after AI induced by a perforation of the aortic valve. beta-Blockade was also produced before and after AI. For a similar increase in preload in AVL and after AI, the percent change in systolic shortening of diameters and segments (% delta L) increased from 30.4 to 34.1% after AI (P less than 0.01). For matched calculated wall stress during AVL and AI, % delta L and peak velocity of shortening were significantly increased after AI, and the same results were reproduced after beta-blockade. We conclude that, at the early phase of chronic volume overload before hypertrophy appears, left ventricular hyperfunction is mainly due to a nonsympathetic increased contractility and that, in the conscious dog, the inotropic state appears to be modified by a sustained increased preload.

Load dependence of mammalian heart relaxation during cardiac hypertrophy and heart failure.

Mechanical properties of relaxation were studied in left ventricular rat papillary muscle during cardiac hypertrophy induced by chronic pressure and/or volume overload. Maximum velocity of isotonic lengthening was linearly related to total extent of isotonic shortening and to maximum velocity of isotonic contraction and depended on the type of chronic overloading without correlation with the degree of cardiac hypertrophy. Time to peak shortening was significantly increased in each group of hypertrophied heart muscles as compared to controls. The sensitivity of cardiac relaxation to the loading conditions was determined by the time course of relaxation. To quantify the degree of load sensitivity, we measured the ratio of isotonic area to isometric area, which was the area limited by the afterloaded force vs. time at 50% of the isometric peak tension divided by the area of the force vs. time trace in the isometric twitch below the same level of load. The value of this ratio was about 0.81 in normal rat and did not show any significant differences in hypertrophied heart muscles even at the terminal stage of congestive heart failure. During acute hypoxia the load sensitivity of relaxation disappeared both in normal and in hypertrophied hearts. Thus inadequacy in oxygen supply has more drastic effects, as compared with those induced by chronic overload, probably by affecting the sarcoplasmic reticulum uptake of activating calcium.

[Comparative study of light and electron microscopic aspects of myocardial lesions induced in the rat by oils with several amounts of gamma-linolenic acid (author's transl)]. / Etude comparative au microscope optique et électronique des lésions myocardiques induites chez le rat après administration d'huiles a différentes teneurs en acide gamma-linolénique.

Four different oils : onager oil, mixture of onager oil (20 p. cent) and middle class triglyceride, sunflower oil and soybean oil were given to the rat during three different periods of time : 1) during 3 months after weaning ; 2) during 6 months after weaning ; 3) from the 9th to 15th months. Three types of myocardial lesions were found : interstitial inflammatory reaction, foci of cellular necrosis and fibrosis. The semi-quantitative study of these lesions did not find important differences from one oil to the other, as well as with the controls. However, subgroups onager are among the least altered, particularly as far as necrotic lesions are concerned. Morphometry of mitochondria, despite evident alterations under electron microscope, gave similar results in every groups.

[Senile cardiac amyloidosis: study of possible relationship between amyloid and atheromatous processes in 923 cases (author's transl)]. / Amylose cardiaque sénile. Amyloïde et processus athéromateux. Une série de 923 vérifications.

Amyloid diseases include a widely dispersed group of conditions. A part from secondary, primary, and familial amyloid diseases, and those due to endocrine tumours of the APUD system, there is a tendency to isolate a group of senile amyloid diseases affecting mainly the heart. A study in a series of 923 elderly subjects demonstrated a negative correlation between amyloid disease and atheromatosis. As certain secondary amyloid diseases, particularly those secondary to myeloma, are, inversely, sometimes associated with rapidly developing atherosclerosis, this suggests the need for further studies to define the relationship between the two processes.