Preponderance of β- over α-adrenoceptors in mediating the positive inotropic effect of phenylephrine in the ferret ventricular myocardium

Summary [³H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (K _d = 0.25 nmol/l and B _max = 27 fmol/mg protein in the right ventricle). [³H]CGP-12177, a -adrenoceptor ligand, bound to the membrane fraction with a _{K d} value of 0.29 nmol/l and a B _max of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37°C, phenylephrine elicited a concentration-dependent positive intropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 ol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 gmol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both - and -adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, -adrenoceptors predominate over -adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of -adrenoceptors is not especially high when compared with other species. Send offprint requests to M. Endoh at the above address     

Pathomorphological characteristics of cardiac remodeling after myocardial infarction

Dilatational, hypertrophic, aneurysmal, and endocardial variants of remodeling were revealed in the postinfarction heart. The most prevalent dilatational remodeling is characterized by uniform or nonuniform elongation of ventricular cavities and increase in ventricular volume. Characteristic features of the hypertrophic type are hypertrophied interventricular septa and left ventricular wall and reduced or unchanged left ventricular volume. Pronounced changes in the configuration of the left ventricle due to the formation of single or multiple aneurysms were typical of aneurysmal remodeling. Endocardial remodeling was characterized by cicatricial changes and smoothed relief of the parietal endocardium. These variants and forms of remodeling determine disturbances in intracardial hemodynamic and thanatogenesis in the postinfarction period.     

Initiation of stress protein synthesis in the myocardium of coronary patients

We studied myocardial biopsy specimens from the right atrium of cardiological patients with different degree of cardiac ischemia obtained during surgery. No inducible HSP70 stress proteins were detected in atrial cardiomyocytes of patients with the WPW syndrome without signs of ischemic injuries of the heart. These proteins were detected in the myocardium of coronary patients. Their expression was more intense in patients with coronary disease paralleled by the development of myocardial dyskinesia. Two-dimensional electrophoresis showed only acid HSP70 but no alkaline isoforms in coronary patients even with pronounced dyskinesia. Presumably, alkaline HSP70 isoforms are present in the myocardium directly involved in the dyskinesia zone.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 10, pp. 412–415, October, 2004     

Ultrastructure of Nuclear Compartment in Cardiomyocytes during Regenerative and Plastic Insufficiency of the Myocardium

We studied ultrastructure of nuclear compartment in cardiomyocytes during regenerative and plastic insufficiency of the myocardium induced by anthracycline antibiotic daunomycin. A peculiarity of ultrastructural organization of cardiomyocyte nuclei under these conditions is almost complete disappearance of the heterochromatin lumps. The earliest changes in nucleoli under conditions of disturbed DNA-dependent RNA synthesis are segregation of the granular and fibrillar nucleolonema components. Deep alterations in the nucleoli manifested by fragmentation and annulation correlate with pronounced changes in cardiomyocytes ultrastructure, intensive lysis of the myofilaments, reduction of the organelles, and enhanced autophagocytosis.     

Reversal of toxic and non-toxic effects of digoxin by digoxin-specific fab fragments in isolated human ventricular myocardium

Summary The time course of the reversal of toxic and nontoxic effects of digoxin by digoxin-specific antibody fragments (Fab) was measured in isolated human ventricular myocardium. A concentration of 2×10^–6 mol/l digoxin was used to produce positive inotropy followed by mechanical signs of toxicity. After addition of a 1.5-fold higher molar concentration of digoxin-specific Fab, signs of toxicity disappeared within 30 min and digoxin-induced force of contraction decayed with a monoexponential time course with a half-life of 52 min. This rate of decay was almost identical to that observed for the dissociation of the digoxin-(Na⁺+K⁺)-ATPase complex in human heart cell membranes. It is concluded that (a) digoxin-specific Fab are capable of completely removing digoxin from its binding sites, (b) the maximal rate of removal of digitalis glycosides from the (Na⁺+K⁺)-ATPase is limited by the dissociation rate constant, and (c) there is a close correlation between the degree of binding of digitalis glycosides to the (Na⁺+K⁺)-ATPase and the increase in force of contraction.Abbreviation Fab Fragment antibody binding (digitalis antidote)     

Relationship between frequency and amplitude of myocardial contractions in rats adapted to heat

After preliminary adaptation of rats to heat (for 3 h daily at 35°C for 1 month) the amplitude of contractions of the isolated papillary muscles from the left ventricle at 28°C at high frequency was higher than in control animals. This difference persisted at 36°C and disappeared at 25°C. It is postulated that adaptation to heat leaves a definite structural imprint in heart muscle cells.Laboratory of Pathophysiology of the Heart, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Institute of Physiology and Experimental Pathology of the Arid Zone, Academy of Sciences of the Turkmenian USSR, Ashkhabad. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 10, pp. 1168–1170, October, 1976.     

Activation of μ-opiate receptors as a factor of regulation of heart resistance to ischemia-reperfusion and oxidative stress

Intravenous injection of the selective μ-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages.In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusionin vitro. Furthermore, stimulation of μ-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe²⁺ and ascorbic acid. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 163–167, August, 2000     

Mechanism of action of baclofen on myocardial and vascular contractility

Department of Anatomy and Physiology of Man and Animals, A. I. Gertsen Leningrad Pedagogic Institute. Department of Pharmacology, Academician I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 10, pp. 436–438, October, 1988.