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I Medugorac

Publications and source records attributed to I Medugorac.

At least 19 recordsLinked to original sources
PubMed1985

Left ventricular enzyme activities of the energy-supplying metabolism in Goldblatt-II rats.

The hypertrophied left ventricles of renovascular hypertensive Wistar rats were examined for several enzyme activities 4-6 and 8-12 weeks after operation (Goldblatt-II), and compared with controls. The activities of beta-hydroxyacyl-CoA dehydrogenase in hypertrophied myocardial tissue were found to be markedly diminished, as were those of citrate synthase, although to a lesser degree. In both stages of left ventricular hypertrophy hexokinase activity was considerably increased, whereas that of lactate dehydrogenase was only initially slightly elevated. Both enzymes showed an altered isoenzyme composition. The possible reasons and consequences of these changes are discussed.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1983

Characterisation of left ventricular collagen in the rat.

Collagen of the normal and hypertrophied rat left ventricle was successively extracted with neutral salt and dilute acid solutions, and pepsin digestion. The yield of dilute-acid soluble collagen was only 0.3 to 0.6% of total collagen; the solubility with neutral salt was even lower. Limited pepsin digestion permitted extraction of 50 to 65% of total collagen. The distribution of the various types of collagen molecules was analysed in pepsin-solubilised collagen in the presence of 3.6 mol . litre-1 urea with the aid of electrophoresis on polyacrylamide gels. In all samples of nonreduced and reduced left ventricular collagen of the rat, disc patterns of pepsin-soluble collagen revealed the occurrence of dimeric and trimeric components, as well as aggregates of higher molecular weight. Such observations suggest the presence of an extensive interchain and intermolecular cross-linking network. Electrophoretic analysis of nonreduced and reduced pepsin-solubilised collagen also revealed heterogeneity of left ventricular rat collagen due to its occurrence as a mixture of type I and type III collagen. The proportion of type I collagen molecule components was substantially higher than that of type III components in all investigated samples of rat left ventricular connective tissue. Postnatal growth, aging and myocardial hypertrophy may affect the ratio of type I to type III components.

Age Factors↗
PubMed1980

Myocardial collagen in different forms of heart hypertrophy in the rat.

The hydroxyproline concentration, representing collagen content, has been investigated in normal and hypertrophied rat hearts. Enlargement of the heart was produced by four methods: a. Experimental renal hypertension (Goldblatt rats); b. Spontaneous hypertension (SHR); c. Experimental aortic stenosis; d. Swimming training. In spontaneously hypertensive rats the free wall of the right and left ventricles and the septum were analyzed separately. Furthermore, the left ventricular free wall was divided into endomyocardial and epimyocardial slices to permit separate investigation. Otherwise, the hydroxyproline concentration was always analyzed in left ventricular tissue. In swimming rats the absolute enlargement was very slight (15%), whereas the hydroxyproline concentration remained unchanged. The degree of hypertrophy was greater in all other experimental animals and was associated with an increase in hydroxyproline concentration in hypertrophied tissue. There was a positive correlation between the rate of hydroxyproline concentration increase and the degree of hypertrophy. The findings only vary in different experimental groups of Goldblatt rats at an early stage. Four weeks after surgery we found a left ventricular hypertrophy of 34%, whereas hydroxyproline concentration in left ventricular tissue was unchanged in comparison to control values. In spontaneously hypertensive rats the increase in hydroxyproline concentration in endomyocardial areas was considerably greater than in epimyocardial areas. Significant differences in water retention and nitrogen content (microgram/mg dry tissue) of hypertrophied and normal ventricular tissue were not found.

Animals↗
PubMed1980

Collagen content in different areas of normal and hypertrophied rat myocardium.

Hydroxyproline concentration, representing the collagen content, in different areas of hypertrophied hearts from spontaneously hypertensive rats aged 109 and 16 months and in similar areas of hearts from control rats of the same age was investigated. As was expected, the hydroxyproline concentration in the left ventricular free wall from normal rats was lower than in the right ventricle and septum. In different parts of the normal left ventricle (endomyocardial and epimyocardial areas, papillary muscles) the hydroxyproline concentration was approximately the same. In all myocardial parts from the 16-month-old normal rats, the hydroxyproline concentration was greater than in respective tissue from younger (10-month-old) rats. The hydroxyproline concentration was increased in all parts of the hypertrophied myocardium in spontaneously hypertensive rats. The increase was greatest in endomyocardial areas of the left ventricular wall. The difference in increase of hydroxyproline concentration between epimyocardial and endomyocardial areas was greater in 10, than in 16-month-old spontaneously hypertensive rats. In the hypertrophied left ventricular papillary muscles the hydroxyproline concentration was lower than the average hydroxyproline concentration in the hypertrophied left ventricle as a whole. The results of this study demonstrate that pathophysiological changes in the hypertrophied left myocardium of spontaneously hypertensive rats are not the same in all ventricular areas.

Animals↗
PubMed1976

Concentration and adenosinetriphosphatase activity on left ventricular actomyosin in Goldblatt rats during the compensatory stage of hypertrophy.

Left ventricular myocardia of Goldblatt rats with an average increase in arterial blood pressure to about 200 mm Hg showed a progressive reduction of the Ca-activated specific acotmyosin ATPase activity 4 -12 weeks after the coarctation of one renal artery, as compared with controls of the same age. During the same period, a significant increase in the concentration of contractile proteins was noticeable, whereas the content of nonprotein substances and of water corresponded to the control values. The hydroxyproline concentration, as a measure of the collagen tissue content, increased only after 24 weeks. The time course of the specific ATPase activity was closely parallel to the decrease in the unloaded myocardial shortening velocity, as estimated at the same stage by our group. This is in accordance with the assumption of a fundamental relationship between the two values. The reduced rate of energy turnover and of the shortening velocity is regarded as an adaptive mechanism which, however, has a negative effect in advanced hypertrophy when further diminution takes place. The decrease in the specific enzymatic activity of actomysin is not necessarily linked to a large increase in myocardial mass, but is already apparent at moderate degrees of hypertrophy (34%).

Actomyosin↗
PubMed1976

[Maximum velocity of load-free shortening Vmax, myocardial capacity and "contractility indices" in the hypertrophic myocardium].

Based upon literature and our own experimentation on Goldblatt rats, the significance of a decrease of the maximal shortening velocity of the myocardium at zero load (Vmax) in the hypertrophied, chronically pressure-loaded heart is discussed. In the hypertrophied myocardium with varying concentrations of the contractile structures, the developed tension under isometric conditions (sigma) and the maximum rate of tension development (d sigma/dtmax) can indicate significant deviations from the values of controls of the same age, without, however, making it possible to draw from these changes absolute conclusions about the elementary contractile process. With the enhanced concentration of contractile proteins, the mentioned isometric values, as well as the maximum instantaneous power (cross-sectionally related) of the myocardium can be increased during a stage of hypertrophy in which Vmax is already reduced. The decrease of Vmax shows a rough correlation with the reduction of the specific ATPase activity of actomyosin and is already observed at moderate degrees of hypertrophy (30 to 50%). The time course of the change of both parameters in experimental hypertrophy suggests a causal relation between the changes of those two parameters and the failure of the myocardium in later stages of a chronic overload. Under the condition of reliable estimation, Vmax allows for, also with changed actomyosin concentration, an assessment of the elementary contractile process. On the other hand, Vmax does not present a sufficient measure for the cross-sectionally related power capacity of the hypertrophied myocardium. The possible dissociation between the unloaded shortening velocity and the cross-sectionally related power capacity could, in certain cases, explain an unsatisfactory correlation between Vmax and the clinical state of the heart. The so-called empirical indices of contractility, which are not always clearly related to basic physiological characteristics of the myocardium, should be interpreted with particular reserve in relation to the hypertrophied cardiac muscle.

Actomyosin↗
PubMed1975

[Influence of long-term swimming training on the structure and enzyme activity of myosin in the rat myocardium (author's transl)].

Intermittent hemodynamic loading of the rat myocardium due to swimming training for several weeks leads to a significant increase in the specific ATPase activity of myosin. This enzymatic alteration of the myosin molecule is accompanied by changes in the stoichiometry of its light chains which are of great significance for the ATPase activity. The maximum shortening velocity of the unloaded myocardium (Vmax), estimated on the basis of afterloaded contractions, shows a slight increase as a result of the physical training. Since, on the other hand, the increase is not significant using the quick release technique, a close relationship between the specific ATPase activity and the augmented cross-sectional contractile capability cannot be proved in our experiments.

Actomyosin↗
PubMedDate not supplied

Myocardial function in different models of cardiac hypertrophy. An attempt at correlating mechanical, biochemical, and morphological parameters.

Based on mechanical, biochemical and electron microscopic studies performed in the same stage of experimental cardiac hypertrophy, an attempt is made to define the significance of individual factors responsible for the alterations in myocardial function. Using swimming rats, it is demonstrated that a load-induced increase in cardiac mass is not necessarily connected with an impairment of contractile capability on a cellular level. Yet, also, the reduction of specific ATPase activity and unloaded shortening velocity in pressure-induced hypertrophy (goldblatt rats; aortic stenosis) seems to be the expression of adaptation rather than of cellular damage, at least in the earlier stages. Although there are distinct indications of alterations in Ca-dependent activation and deactivation, in the Goldblatt model electromechanical coupling does not seem to be the main cause of altered contraction parameters. The correlation between specific ATPase activity of actomyosin and unloaded shortening velocity as well as the persistance of decrease in shortening velocity, also under optimal electromechanical coupling conditions, point to an inner relationship between the two values. A discrepancy between unloaded shortening velocity on the one hand and developed tension on the other is mainly due to an increased content of contractile structures. In later stages, an increased connective tissue content influences both isometric and isotonic parameters.

Actomyosin↗
PubMedDate not supplied

Characteristics of the hypertrophied left ventricular myocardium in Goldblatt rats.

In Goldblatt rats (GV) 4-24 weeks after coarctation of one renal artery the following characteristics were registered as compared to controls (CV) of the same age: Arterial blood pressure increased to 190-200 mmHg in comparison to 105-110 mmHg in controls. This pressure overload induced an increase in ventricular weights (34%-54%). Noteworthy differences in myocardial water, total protein, and nonprotein substance contents were found. Hydroxyproline concentration in GV did not increase significantly until 24 weeks after onset of pressure overload. No significant alterations were detected in the relationship of myocardial, sarcoplasmic, and stromal protein fractions. However, greater changes could be registered in the concentration of the myofibrillar protein fraction and its single components. Furthermore, a correlative depression in specific actomyosin ATPase activity and in maximum shortening velocity of the unloaded cardiac muscle (2,3) was observed.

Actomyosin↗
PubMedDate not supplied

Editorial: Subunits of myosin. Relations to ATPase activity and mechanical function of muscle.

Under certain conditions the specific ATPase activity of myosin of a given muscle can be altered. The cause of this alteration can only lie in the myosin molecule itself. To produce an enzymatic activity of myosin, an interaction between their light and heavy chains is necessary. However, the specific activity appears to be determined mainly by light chains. Hence, one ought also to look for a basis of the changed activity in changes of the subunits of myosin. There are strong indications that the alterations in specific activity are accompanied by changes in the relative stoichiometry of the essential light chains of the respective myosin preparation. They differ in their pattern of subunits. The specific activity of a given kind of myosin seems to be determined by the combination of their light chains. Thus, a close correlation exists between these two properties of myosin (ATPase activity and structure of its molecule). There are sufficient indications, that these two properties of myosin correlate also with the mechanical capabiltiy of the corresponding muscle. Particularly the results of cross innervation studies demonstrate a close correlation between these three properties in skeletal muscle. The single subunits of myosin are produced and degraded independently and at heterogenous rates. The synthetis of these subunits is significantly accelerated in response to work overload. Thus, it is quite likely that the individual chains are non-coordinately synthesized, giving rise to variations in the relationship of different molecule types of myosin with different specific ATPase activity. Hence, the control mechanism to synthesize the individual subunits could also be the regulative mechanism to produce a myosin of the specific ATPase activity appropriate to the activity pattern of tissue.

Adenosine Triphosphatases↗
PubMedDate not supplied

Mechanics of the isolated ventricular myocardium of rats conditioned by physical training.

Force-velocity relations from after-loaded contractions, from isometric and isotonic QR experiments, resting-tension curves and biochemical analyses were conducted on sixteen trabecular muscles (SH) from hearts of rats conditioned by eight weeks of swimming training (increase in heart weight 8%), and compared to a control (CH) of eighteen trabecular muscles. (SH) showed increased tension development (p less than 0.01), whereas the diastolic properties remained almost unchanged. Analysis of the amount of hydroxyproline did not prove any variation. Vmax of (SH) was only slightly increase when there was a singificnat rise in actomyosin and myosin ATPase activity, while PO of the force-velocity relations of (SH) on the x axis (tension) shifted clearly to the right (p less than 0.01). Consequently, the maximum instantaneous power of (SH), expressed by the maximum rectangular plane under the force-velocity curve, increased considerably (p less than 0.01) in comparison with (CH). The experiments show that haemodynamic load induced by training does not alter the passive properties of the myocardium, but does bring about an increase in the contractile capabiltiy.

Actomyosin↗
PubMedDate not supplied

Different fractions in the normal and hypertrophied rat ventricular myocardium: an analysis of two models of hypertrophy.

Long-term hemodynamic overload of the heart leads to an increase in myocardial mass. In most cases it is not known to what degree the single components in the myocardium (water, protein, nonprotein substance) increase. As an answer to the overloading of the myocardium, many authors have established an intensification in the synthesis of myocardial proteins. It is, however, little known which proteins are then more intensively created and accumulated. This study examines the dynamics of the protein and nonprotein content as well as of single protein fractions (sarcoplasmic, myofibrillar, and stromal) in both hypertrophied and normal tissue from rat myocardia. The results revealed that in Goldblatt rats, 4-24 weeks after stenosis of one renal artery, no noteworthy differences in the relationships of protein and nonprotein content were caused by hypertrophy (34-54%) due to left ventricular pressure overload. The same is true of the tissue from moderately hypertrophied myocardia (12-17%) of rats exercised for several weeks by swimming training. Determination of hydroxyproline concentration showed that significant differences in the content of the collagen tissue in relation to control animals of the same age occurred only in Goldblatt rats 24 weels after operation. However, greater alterations in the concentrations of various protein fractions could be registered. The increase in the concentration of myofibrillar proteins in hypertrophied myocardial tissue is of particular significance and is to be considered as an adaption of the muscle to the increased mechanical demands. Certain changes regarding the relation of the single components within the myofibrillar fraction (relation of actomyosin concentration to T-fraction; relation of both components to total fraction), whose cause and significance is as yet unclear, could be observed.

Animals↗