Intracellular distribution of adrenoceptors in the failing human myocardium.

Although it is increasingly recognized that the density of cardiac membrane-bound beta adrenoceptors declines in heart failure, the mechanisms involved are unclear. Furthermore, it is not known whether cardiac alpha-1 adrenoceptors are similarly affected. Inasmuch as agonist-induced desensitization results in translocation of adrenoceptors from the plasma membrane to an intracellular vesicular fraction, we determined the intracellular distribution of cardiac adrenoceptors in two groups: group 1 (n = 9) consisted of papillary muscles from patients with mild-to-moderate heart failure undergoing valve replacement, and group 2 (n = 8) consisted of severely failing hearts removed during orthotopic cardiac transplantation. The density of cardiac beta adrenoceptors was lower in membranes from group 2 (17.8 +/- 3.3 fmol/mg protein vs 27.8 +/- 3.7 fmol/mg in group 1; (p less than 0.01), and the percentage of beta receptors recovered in the vesicular fraction was higher in group 2 (47.1 +/- 3.3% vs 36.8 +/- 5.0% in group 1; p less than 0.01). In group 1 but not group 2 there was a significant inverse correlation (r = -0.87; p less than 0.001) between the density of membrane-bound beta receptors and the percentage of beta receptors recovered in the vesicular fraction. Alpha-1 adrenoceptors were lower in both membrane and vesicular fraction of group 2 compared to group 1; in group 2 but not group 1 there was a significant negative correlation between the density of membrane-bound alpha-1 adrenoceptors and the percentage of alpha-1 receptors in the vesicular fraction (r = -0.8; p less than 0.01). These results suggest that the regulation of alpha-1 and beta adrenoceptors differs in the failing myocardium. Furthermore, agonist-induced desensitization may play a predominant role only in mild-to-moderate heart failure.

Calcium-antagonist receptors in the atrial tissue of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is characterized by a nondilated, hypertrophied left ventricle in the absence of any overt cause. A possible role of adrenergic innervation or of cellular calcium regulation is suggested by the presence of hyperdynamic left ventricular function and by the clinical and symptomatic improvement seen in patients treated with beta-receptor antagonists or calcium antagonists. Therefore, we measured the density of calcium-antagonist receptors and beta-adrenoceptors in the atrial myocardium of 16 patients with hypertrophic cardiomyopathy and 19 patients with various other cardiac disorders. For comparison, we also measured the number of voltage-sensitive sodium channels. Calcium-antagonist binding sites, measured as the amount of dihydropyridine bound to atrial tissue, were increased by 33 percent in patients with hypertrophic cardiomyopathy (mean [+/- SD], 397 +/- 104 fmol per milligram of protein in patients with hypertrophic cardiomyopathy, as compared with 299 +/- 108 in patients with other cardiac disorders; P less than 0.01). The densities of saxitoxin-binding sites on voltage-sensitive sodium channels and beta-adrenoceptors were the same in the two groups, although the density of beta-adrenoceptors was higher in atrial samples from patients receiving beta-receptor antagonists (165 +/- 86 fmol per milligram of protein [patients receiving beta-blockers] vs. 85 +/- 60 [patients not receiving beta-blockers]; P less than 0.04). The increase in the number of calcium-antagonist receptors in hypertrophic cardiomyopathy suggests that abnormal calcium fluxes through voltage-sensitive calcium channels may play a pathophysiologic part in the disease.

Regional changes in ornithine decarboxylase activity and polyamine levels during thyroxine-induced cardiac hypertrophy.

Ornithine decarboxylase activities (ODC) and polyamine levels were determined in five cardiac regions of the rat heart, following daily administration of 1 mg/kg of thyroxine, in the right and left atria, the right and left ventricles and the septum. The thyroxine stimulated ODC activity in all five regions of the heart. Enzyme activity in the left atrium and the septum peaked a day earlier than in other regions and the decline of ODC activity was slower. Putrescine in control animals was present in all regions except the right atrium, where its content was below detectable levels. Following the administration of thyroxine, the putrescine content of the left atrium, the right ventricle and the septum declined, while spermidine and spermine levels remained unchanged. In direct contrast to the other regions of the heart, thyroxine stimulated an increase in polyamines, as well as in weight which occurred exclusively in the left ventricle. These findings suggest a causal relationship between increased polyamines and hypertrophy.

Atrial septation in the rat. I. A light microscopic and histochemical study.

Light microscopy and histochemistry consisting of alcian blue staining were utilized to study atrial septation in the albino rat heart. Light microscopy shows septum primum to develop from the dorsocranial wall of the primitive atrium by day 12.50. Foramen secundum rapidly develops in the ventrocranial portion of septum primum during day 13.00. A second septum appears to the right of septum primum in the rat as the foramen secundum increases in size. The first evidence of septum secundum can be noted on histologic preparations as a small rounded bulge extending into the right atrium from the ventrocranial wall. This occurs at day 14.50. This septum continues to enlarge but does not fuse with the endocardial cushions as does septum primum. Alcian blue staining shows the presence of glycosaminoglycans (GAGs) concentrated heavily in the leading edge of the 12.50 day septum primum. GAGs are also present during foramen secundum formation in areas where endocardial cells aggregate. As development progresses, GAGs diminish in all areas of septum primum. Of particular interest is an area of intense alcian blue staining in the wall of the right atrium ventral and caudal to septum secundum development. This appears in histologic preparations of 13.50 and 14.50 day rat hearts.

Ventricular myocardial catecholamines in primates.

We report myocardial catecholamine levels in primate ventricles assayed by high-pressure liquid chromatography with electrochemical detection. The norepinephrine content of the left ventricles of 11 monkeys (four rhesus and seven cynomolgus) was 1391 +/- 362 ng/gm (+/-SD) with a definite gradient from base (highest) to apex (lowest concentration). Dopamine and epinephrine were present in much lower concentrations (51.8 +/- 24.5 ng/gm and 59.2 +/- 20.0 ng/gm, respectively), but were similarly distributed throughout the left ventricle. There was considerable variation in norepinephrine concentration between animals, but the dopamine/norepinephrine ratio was very consistent within a given animal, averaging 3.7% +/- 1.4%. These values are probably indicative of what normal concentrations of catecholamines are likely to be in humans, and provide a basis for interpretation of results obtained in disease studies.

Myosin light chain compositions of the interatrial and interventricular septa of sheep heart.

The myosin light chain composition of sheep interatrial and interventricular septa were analysed by one- and two-dimensional polyacrylamide gel. The interventricular septum has myosin light chain composition indistinguishable from that of ventricular myosin. Myosin from the interatrial septum contains three light chains, two of which co-migrated with the two atrial light chains (ALC1 and ALC2), while the third co-migrated with ventricular light chain 2 (VLC2). ALC1 are more abundant than ALC2 or VLC2 suggesting a mixed myosin population. Myosin with ALC1 and VLC2 light chain composition may be present, and its possible relationship with cardiac "conducting" cells is discussed.

Somatostatin in the human heart and comparison with guinea pig and rat heart.

Somatostatin has been shown to have negative inotropic and chronotopic effects and to restore sinus rhythm in some cases of cardiac arrhythmia. Using acid extracts, regions of human heart were examined by radioimmunoassay to determine their somatostatin content. Mean (SD) concentrations of 4.1 (0.8) pmol/g and 2.9 (0.8) pmol/g were found in atrioventricular node and right atria respectively and were significantly higher than in other heart regions. Using fresh heart tissue from guinea pigs, somatostatin was localised to cardiac nerves by immunocytochemistry. Nerves containing somatostatin were most abundant in the atria, where the concentrations measured by radioimmunoassay were 7.6 (1.0) and 2.6 (0.4) pmol/g for right and left atria respectively. Somatostatin contained in cardiac nerves may have a physiological role in the cardiac conduction system.

Myosin types and fiber types in cardiac muscle. I. Ventricular myocardium.

Antisera against bovine atrial myosin were raised in rabbits, purified by affinity chromatography, and absorbed with insolubilized ventricular myosin. Specific anti-bovine atrial myosin (anti-bAm) antibodies reacted selectively with atrial myosin heavy chains, as determined by enzyme immunoassay combined with SDS-gel electrophoresis. In direct and indirect immunofluorescence assay, anti-bAm was found to stain all atrial muscle fibers and a minor proportion of ventricular muscle fibers in the right ventricle of the bovine heart. In contrast, almost all muscle fibers in the left ventricle were unreactive. Purkinje fibers showed variable reactivity. In the rabbit heart, all atrial muscle fibers were stained by anti-bAm, whereas ventricular fibers showed a variable response in both the right and left ventricle, with a tendency for reactive fibers to be more numerous in the right ventricle and in subepicardial regions. Diversification of fiber types with respect to anti-bAm reactivity was found to occur during late stages of postnatal development in the rabbit heart and to be influenced by thyroid hormone. All ventricular muscle fibers became strongly reactive after thyroxine treatment, whereas they became unreactive or poorly reactive after propylthiouracil treatment. These findings are consistent with the existence of different ventricular isomyosins whose relative proportions can vary according to the thyroid state. Variations in ventricular isomyosin composition can account for the changes in myosin Ca2+-activated ATPase activity previously observed in cardiac muscle from hyper- and hypothyroid animals and may be responsible for the changes in the velocity of contraction of ventricular myocardium that occur under these conditions. The differential distribution of ventricular isomyosins in the normal heart suggests that fiber types with different contractile properties may coexist in the ventricular myocardium.

[Noradrenaline and adrenaline concentration in the myocardium of persons who have died suddenly or from injuries]. / Soderzhanie noradrenalina i adrenalina v miokarde liudei, pogibshikh ot travmy i vnezapno.

To investigate mechanisms of sudden death the authors determined the content of noradrenaline and adrenaline in the myocardium of different heart sections in deceased persons by the fluorimetric method; similar studies of the myocardium of persons who died of trauma were conducted. Heterotopia in the noradrenaline content between the cardiac chambers proved to be considerably more pronounced in sudden death than in fatal trauma. The differences in the adrenaline and noradrenaline content in the heart chambers of persons who died of trauma and suddenly indicated the death mechanisms to be different in these cases.

Comparative regional and subcellular distributions of histamine and norepinephrine in the hearts of rats, mice, guinea pigs, rabbits, and dogs.

The patterns of distribution of histamine and norepinephrine among the 4 chambers of the heart of rats, guinea pigs, and rabbits and among 15 portions of the dog heart were quite similar, except for the coronary ring of the dog, which was disproportionately high in histamine. In whole mouse hearts the separate chambers were not assayed; in the whole heart, the contents of the 2 amines did not correlate. The subcellular distribution of histamine in the rat and guinea pig heart was different from that of norepinephrine. Histamine was mostly associated with mast cell-like granules. Toluidine blue-staining granules of 2 widely different densities were found.

[Content of basic lipid fractions in the myocardium of different regions of the heart in healthy people]. / O soderzhanii osnovnykh lipidnykh fraktsii v miokarde razlichnykh otdelov serdtsa zdorovykh liudei.

Content of lipids was studied in five parts of myocardium of healthy people by means of thin-layer chromatography on silica gel. The higher content of triglycerides and total lipids was found in dexter parts of heart as compared with sinister parts and septum interventriculare. The same distribution was not shown for free and esterified cholesterol.

Isolation and characterization of myosin from subjects with asymmetric septal hypertrophy.

Human cardiac myosin isolated from operatively obtained samples of ventricular septum and left ventricular free wall of subjects with asymmetric septal hypertrophy (ASH) was compared, with respect to structural and enzymatic properties, to myosin isolated from hearts of subjects without heart disease. The following parameters were studied: (1) activation of myosin ATPase activity by K+-EDTA and Ca2+, (2) molecular weight of the heavy and light chains of myosin as determined by electrophoretic migration in polyacrylamide-sodium dodecyl sulfate (SDS) gels and (3) ability to form bipolar aggregates at low ionic strength, as examined by electron microscopy. No difference was present in any of these parameters between human cardiac myosin from subjects with ASH and from subjects without heart disease. Thus, the genetic defect present in subjects with ASH is not expressed in the particular structural and functional characteristics of myosin evaluated in this study.

Effect of nitroglycerin with and without systemic hypotension on canine regional myocardial tritiated water deposition.

A marked alteration in the transmural distribution of left ventricular blood flow, with a relative increase in subendocardial and mid-wall flows, but with no change in the distribution of the relative blood flow to the two ventricles occurred when nitroglycerin was administered and the systemic arterial blood pressure in the upper body maintained near control levels in anaesthetized, open-chested dogs. The relative increase in subendocardial and mid-wall flows may have resulted from a direct action of nitroglycerin on the coronary vasculature. On the other hand, the intravenous administration of nitroglycerin, when followed by the hypotension which it produces, did not alter the transmural distribution of blood flow in the left ventricle of the dog. Blood flow to the right ventricle relative to flow to the left ventricle increased in this situation.

[Comparative morphology of the trabecula septomarginalis in terrestrial mammals]. / Morphologie comparee de la trabecula septo-marginalis chez les mammiferes terrestres

The authors studied macroscopic morphology and histologic structure of the moderator band - trabecula septomarginalis - in 100 earthly mammals. A real trabecula septomarginalis was never found in carnivora (dog and fox) because the "anterior" papillary muscle of the right ventricle is located on the lower part of the septum ventriculorum or at times bridge-shaped above the anteiror interventricular groove and attached on both septum and anterior wall of the right ventricle. On the opposite, in ungulates, a well-known band runs across the right ventricular chamber from the septum close to the musculus papillaris coni arteriosi up to the anterior wall close to the anterior papillary muscle. In fact the attachments lie more or less approximate to the pillars; in suidae, the trabecula usually ends on a vertical trabecula carnea just under Luschka's muscle. Three types of trabecula septomarginalis were encountered as previously described by Bortolami in ox: - Mostly (66%), the trabecula septomarginalis is a short and thick fleshy column. The ratio Length mm Thickness mm amounts to about 4 to 7 and can be regarded as reasonably constant within each variety. Moreover the quotients Length mm Height of septum MM. and Thickness of the trabecula mm Highest thickness of the anterior wall mm (measured just beneath the tricuspid attachment) keep constant in each group; thus it may be concluded that size and shape of the trabecula depend on the volume of the heart and the age of the animal. - Rarely, the trabecula looks like a tendinous cord. Such a fibrous string is nearly constant in suidae, especially in wild boar, but seldom in bovidae and cervidae. In all cases, the trabecula septomarginalis supports the right branch of the atrioventricular bundle and a thin artery which originates from the left coronary artery and branches into the right coronary vessels within the anterior papillary muscle. Some venous capillaries were also observed but only in the muscular trabeculae; they are not constant and mouth into the right ventricular chamber or run towards the septal veins around the atrioventricular node. Therefore whatever is the size, the trabecula septomarginalis must be regarded as the shortest pathway from the septum to the anteiror wall of the right ventricle and is a mere band bearing the "right nodal pedicle".