The effect of chronic administration of beta-guanidinopropionic acid (GPA) on the protein profiling, energy metabolism and right ventricular (RV) function was studied in the rat heart during the weaning and adolescence period. GPA was given in tap water (1-1.5%) using pair drink controls. The feeding of animals with GPA solution for a six week period resulted in elevation of heart to body weight ratio due to body growth retardation. GPA accumulated in the myocardium up to 67.37 +/- 5.3 mumoles.g dry weight and the tissue content of total creatine, phosphocreatine and ATP was significantly decreased to 15%, 9% and 65% of control values respectively. Total activity of creatine kinase (CK) was not changed, but the proportion of mitochondrial (Mi) CK isoenzyme was decreased; the percentage of MB isoenzyme of CK was significantly higher. GPA treatment resulted in an elevation of the content of cardiac collagenous proteins and decrease of non-collagenous proteins in the heart; in parallel, a decrease of the collagen I to collagen III ratio was detected. The function of the RV was assessed using an isolated perfused heart with RV performing pressure-volume work. As compared to pair-drink controls, RV function was significantly impaired the GPA group: at any given right atrial filling pressure, the RV systolic pressure and the rate of pressure development were decreased by almost a factor of two. Elevation of the RV diastolic pressure with increasing pulmonary artery diastolic pressure was also significantly steeper in the GPA group which also showed decrease of cardiac output, especially at high outflow resistance. It may be assumed that chronic administration of GPA deeply influenced metabolic parameters, protein profiles and contractile function of the developing heart. On the other hand, concentrations of glucose, total lipids and triglycerides in blood plasma were not affected. All these data confirm the concept that the CK system is of central importance both for heart function and for the regulation of normal growth of cardiac myocytes.

Animals↗

PubMedDate not supplied

Myocardial fibrosis and right ventricular function of heterotopically transplanted hearts in rats treated with cyclosporin.

The aim was to determine whether treatment of rats with cyclosporin A (CsA) leads to deleterious side effects on heterotopically iso- or allotransplanted hearts when compared with recipient native in situ hearts. Four experimental groups were employed: inbred (Lewis) rats receiving either no immunosuppression or CsA at a dose of 15 mg.kg-1 per day for 7 days after surgery, and outbred (Wistar) rats receiving CsA at the same daily dose for either 7 or 21 days. One month following surgery, the mass of all transplanted hearts decreased and resulting atrophy was associated with relative myocardial fibrosis. Treatment with CsA significantly increased the concentration and content of collagen in the right and left ventricles of all transplanted and recipient hearts. No appreciable difference was observed between corresponding hearts of inbred and outbred groups receiving the identical dose of CsA, and between hearts in outbred groups treated for either 7 or 21 days. No signs of right ventricular mechanical dysfunction, as assessed on the isolated perfused "working' preparation, were observed after CsA treatment in both transplanted and recipient hearts. The maximal steady state developed pressure (RVDevP) and the rate of its development [(+dP/dt)max] were slightly higher in transplants than in the corresponding recipients, and in CsA-treated versus untreated hearts, while the index of contractile state [(+dP/dt)/P] was similar in all groups. The data suggest that treatment of rats with CsA can induce a similar degree of fibrosis both in heterotopic cardiac transplants and in recipient native hearts without impairment of their contractile performance.

Animals↗

PubMedDate not supplied

Differences between atrial and ventricular protein profiling in children with congenital heart disease.

The purpose of the present study was to compare protein profiling of atria and ventricles in children operated for congenital heart disease. Tissue samples were obtained during surgery from patients with normoxemic (ventricular and atrial septal defects) and hypoxemic (tetralogy of Fallot) diseases. Protein fractions were isolated by stepwise extraction from both right ventricular and atrial musculature. The concentration of total atrial protein in the normoxemic patients exceeded the ventricular value (110 +/- 2.1 vs 99.9 +/- 4.0 mg.g-1 wet weight, respectively); in the hypoxemic group this atrio-ventricular difference disappeared. The concentration of contractile proteins in all cardiac samples was significantly higher in the ventricles as compared with atria, while the concentration of collagenous proteins was significantly higher in the atria (due to a higher amount of the insoluble collagenous fraction). The concentration of sarcoplasmic proteins (containing predominantly enzyme systems for aerobic and anaerobic substrate utilization), however did not differ between ventricles and atria. Furthermore, ventricular contractile fractions obtained from both normoxemic and hypoxemic patients were contaminated with the myosin light chain of atrial origin. Soluble collagenous fractions (containing newly synthesized collagenous proteins, predominantly collagen I and III), derived from all ventricular samples, were contaminated by low molecular weight fragments (mol. weight 29-35 kDa). The proportion of the soluble collagenous fraction was significantly higher in atrial but not in ventricular myocardium of hypoxemic children as compared with the normoxemic group. It seems, therefore, that lower oxygen saturation affects the synthesis of collagen preferentially in atrial tissue.

Actins↗

PubMedDate not supplied

Structural and biochemical remodelling in catecholamine-induced cardiomyopathy: comparative and ontogenetic aspects.

Excessive release or administration of beta-mimetic catecholamines may induce cardiomegaly, necrotic lesions and accumulation of connective tissue in the heart of adult homoiotherms. It was examined here whether similar changes can also be observed at different stages of evolution of the cardiovascular system, i.e. in poikilotherms and in homoiotherms during embryonic life. Sensitivity of the poikilothermic hearts (carp, frog, turtle) to isoproterenol (IPRO) was significantly lower than in the homoiotherms. Necrotic lesions, if present, were localized in the inner spongious musculature which has no vascular supply but which exhibits higher activities of enzymes connected with aerobic oxidation. Moreover, the IPRO-induced decrease of the phospholipid content was also significantly more expressed in the spongious layer. IPRO treatment did not influence the total weight of the fish heart but the proportion of the outer compact layer was significantly higher. These changes were accompanied by an increase of collagen, higher water content and an increase of isomyosin with a lower ATPase activity. The response of the poikilothermic heart to IPRO-induced overload thus differs significantly from that in the homoiotherms. The administration of IPRO during embryonic life of homoiotherms (chick) induces serious cardiovascular disturbances, including cardiomegaly and cellular oedema. Necroses of myofibrils, characteristic of IPRO-induced lesions of adults, were, however, rather exceptional. IPRO did not elevate the concentration of 85Sr (as a calcium homologue) in the immature myocardium; it seems, therefore, that IPRO-induced changes of the embryonic heart are not necessarily due to an intracellular calcium overload. It may be concluded that the character of catecholamine-induced cardiomyopathy is not uniform and depends strictly on the stage of cardiac development.

Adrenergic beta-Agonists↗

PubMedDate not supplied

The effect of beta adrenergic blockade on pulmonary hypertension, right ventricular hypertrophy and polycythaemia, induced in rats by intermittent high altitude hypoxia.

Adult male rats were used to study the effect of a beta blocking agent on pulmonary hypertension and right ventricular hypertrophy induced by intermittent high altitude (IHA) hypoxia (8 hr daily, 5 days a week, stepwise up to the simulated altitude of 7000 m). Trimepranol was injected subcutaneously in a single dose of 10 mg/kg/b.w. one hour before each IHA exposure. Administration of the beta blocking drug caused significant changes of haematocrit values even in animals kept under normoxic conditions. The initial deep decrease was followed by a slow return to control values; prolongation of treatment led to a further significant decrease of the haematocrit curve. The polycythaemic response of IHA-exposed and Trimepranol-treated animals was, therefore, significantly less pronounced as compared with the hypoxic non-treated group. Administration of Trimepranol to IHA-exposed rats significantly decreased the values of right ventricular systolic and mean pressure, right ventricular hypertrophy as well as the degree of muscularization of pulmonary arteries. It may be assumed that the protective effect of Trimepranol is due to a) changes in pulmonary vascularization, b) reduction of polycythaemia, and c) lower cardiac output, induced by the negative inotropic and chronotropic effect of this drug.

Altitude Sickness↗

PubMedDate not supplied

Myocardial function in chronic pulmonary diseases. The effect of intermittent altitude hypoxia on the myocardium in rats. Preliminary communication.

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Animals↗

PubMedDate not supplied

Analysis of the cardiotoxic effect of isoproterenol in chick embryo.

Intraamnial administration of isoproterenol (IPRO) to chick embryo induces different types of pathological changes of the myocardial and liver tissue: their character depends upon the developmental period during which the drug was administered. Analysis of the embryotoxic effect of IPRO has revealed that the time-course of in vivo uptake of [3H]IPRO by the developing heart appears to present the same pattern as the embryonic liver tissue; both peak values (10 min and 6 h after injection) were, however, significantly higher in the liver as compared with the myocardium. IPRO is rapidly metabolized to 3-o-methyl-IPRO; the proportion of this fraction in both organs represents approximately 40% of total radioactivity as early as 5 min after administration. Intraamnial administration of IPRO significantly increases the cAMP content in the myocardium; dibutyryl cAMP-induced myocardial lesions occurred, however, only occasionally and in comparison with IPRO they were significantly less pronounced. The cardiotoxic effect of IPRO can be significantly reduced by beta-blockade; calcium antagonist, verapamil, was found to have no protective effect. Our results suggest that the following factors may participate in the IPRO-induced embryotoxicity: (1) IPRO, (2) its toxic metabolites, (3) cAMP.

Absorption↗