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1. |
Gap Junctional Channels in Adult Mammalian Sinus Nodal CellsImmunolocalization and Electrophysiology |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 229-239
J. Anumonwo,
H.-Z. Wang,
E. Trabka-Janik,
B. Dunham,
R. Veenstra,
M. Delmar,
J. Jalife,
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摘要:
The subcellular mechanism of cell-to-cell communication in the natural pacemaker region of the mammalian heart was studied using electrophysiological and immunofluorescence techniques in isolated pairs of rabbit sinus nodal cells. By measuring whole-cell currents using a double patch-clamp approach, it was demonstrated that communication in the sinus node is mediated through gap junctional channels similar to those in other types of adult cardiac cell pairs. Macroscopic sinus nodal junctional resistance had a mean value of 387.9±97.1 MΩ (mean ±SEM,n=10) and was greatly increased by superfusion with alkanols. Single-channel junctional conductance could be resolved in three cell pairs. Given their high membrane resistance (1.16±0.32 GΩ,n= 12), the electrical coupling provided by as few as three gap junctional channels between nodal cells will allow for pacemaker synchronization. Further evidence for the presence of the channels was obtained from immunofluorescent double-labeling of desmin and the gap junction protein (connexin43) in sinus nodal tissue as well as in cultured sinus nodal cells. Using antisera against residues 243–257 of the connexin43 protein, a specific staining at the site of cell-to-cell apposition was demonstrated. These data provide direct evidence in favor of electrotonic coupling as the means for achieving pacemaker synchronization in the rabbit sinus node.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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2. |
Persisting Zones of Slow Impulse Conduction in Developing Chicken Hearts |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 240-250
F. de Jong,
T. Opthof,
A. Wilde,
M. Janse,
R. Charles,
W. Lamers,
A. Moorman,
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摘要:
We performed a correlative electrophysiological and immunohistochemical study of embryonic chicken hearts during the septational period (Hamburger and Hamilton stages 13–31 [2–7 days of incubation]). The analyses yield conclusive evidence for slow conduction, up to 7 days of development, in the outflow tract, in the atrioventricular canal, and in the sinoatrial junction. The conduction velocity remains approximately 1 cm/sec in the outflow tract and increases in the ventricle 20-fold to approximately 20 cm/sec between 2 and 7 days of development. Transmembrane potentials of myocytes in the outflow tract and atrioventricular canal slowly rise (<5 V/sec), whereas in the atrium and ventricle, the upstroke velocity is eightfold to 13-fold higher. In the outflow tract, repolarization is completed only after the start of the next cycle. Because of the persistence of slow conduction, the myocardium flanking the developing atria and ventricle is thought to represent segments of persisting “primary” myocardium, whereas the more rapidly conducting “working” myocardium of the ventricle and atria is thought to represent more advanced stages of myocardial differentiation. The persisting primary myocardium was characterized by a continued coexpression of both the atrial and ventricular isoforms of myosin heavy chain. The developing atria and ventricle could be demarcated morphologically from the primary myocardium because the free walls of these segments only express their respective isoforms of myosin heavy chain. The slowly conducting myocardial zones appear to be essential for the function of the embryonic heart because 1) they provide the septating heart with alternating segments of slow and relatively fast conduction necessary for consecutive contraction of the atrial and ventricular segments and 2) their sphincterlike prolonged peristaltic contraction pattern can substitute for the adult type of one-way valves that start to develop at the end of septation.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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3. |
Acidic and Basic Fibroblast Growth Factors in Adult Rat Heart MyocytesLocalization, Regulation in Culture, and Effects on DNA Synthesis |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 251-259
Edith Speir,
Virginia Tanner,
Ana Gonzalez,
James Farris,
Andrew Baird,
Ward Casscells,
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摘要:
Basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor (aFGF) are involved in the induction of embryonic mesoderm, angiogenesis, neuronal differentiation, and proliferation and survival of many cell types. In cardiac myocytes their roles are not well understood. Effects of fibroblast growth factors on reexpression of fetal actin genes have been reported. In freshly isolated adult rat cardiac myocytes, bFGF mRNA was not detectable by in situ hybridization, although the cells contained significant amounts of bFGF and aFGF as quantified by radioimmunoassays, mitogen assays with immunoneutralization, and Western blotting. After culturing, bFGF mRNA was detected (aFGF mRNA was not studied), and the cells contained 2.5-fold more bFGF and 60% more aFGF than freshly isolated cells. The FGFs were not found in conditioned medium. They were localized, especially in cultured cells, to the nucleus. Cultured myocytes bound fourfold more125I-FGF than freshly isolated cells and expressed the fibroblast growth factor R-1 (flg) gene. The addition of bFGF or aFGF in serum-free medium to pure populations of myocytes (after 10 days in culture, at which time they are spread, beating, and multinucleated) led to increased thymidine incorporation. Expression of fibroblast growth factors and fibroblast growth factor receptors by adult cardiac myocytes that survive the shock and “dedifferentia-tion” of culturing may contribute to DNA synthesis and, by analogy, to other cell types, to regulation of ribosomal and actin genes, and to cell survival. These possibilities and their in vivo relevance will require further study.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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4. |
Reflection After Delayed Excitation in a Computer Model of a Single Fiber |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 260-270
Candido Cabo,
Roger Barr,
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摘要:
Reflection (reflected reentry) is a case of reentry in a one-dimensional structure, divided into proximal and distal segments, in which tissue excited by a wave front propagating in a forward direction is reexcited by electrical activity coming backward from the original direction of propagation. Cases of reflection have been demonstrated in Purkinje fibers and in ventricular muscle preparations containing multiple fibers. Several mechanisms possibly responsible for reflected reentry have been proposed. However, the difficulty in the interpretation of the experimental results, as well as the limited number of different conditions in which reflection was obtained, has kept open the question about conditions and mechanisms for reflection. We have developed a computer model in which reflection occurs. The model involves a single fiber and uses the DiFrancesco-Noble equations for the Purkinje fiber to model the ionic currents. The results show that reflection is possible in a single fiber and that diastolic depolarization (automaticity) is not a requirement for reflection. Active membrane responses to a just-above-threshold stimulus were important for achieving the necessary time delay. Systematic simulations showed further that reflection occurred only when the right coupling conditions linked a short or long proximal fiber to a short distal segment.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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5. |
Mechanism of Flecainide's Antiarrhythmic Action in Experimental Atrial Fibrillation |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 271-287
Zhiguo Wang,
Pierre Pagé,
Stanley Nattel,
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摘要:
Class Ic antiarrhythmic drugs are effective in the treatment of atrial fibrillation, but their mechanism of action is unknown. In previous work, we have found that flecainide causes tachycardia-dependent increases in atrial action potential duration (APD) and effective refractory period (ERP) by reducing APD accommodation to heart rate. The present study was designed to evaluate the efficacy and mechanisms of action of flecainide in an experimental model of sustained atrial fibrillation (AF). AF was produced by a brief burst of atrial pacing in the presence of vagal stimulation and persisted spontaneously until vagal stimulation was stopped. The actions of flecainide at two dose levels were compared with those of isotonic glucose placebo in each dog, with a randomized order of blinded drug administration. Flecainide terminated AF in all 16 dogs, while glucose was effective in none (p<0.0001). Flecainide increased atrial ERP and reduced conduction velocity in a tachycardia-dependent manner. Doses of flecainide that converted AF resulted in larger changes in ERP than in conduction velocity, increasing the minimum pathlength capable of supporting reentry (wavelength). In addition, flecainide reduced regional heterogeneity in ERP and wavelength, an action opposite that of vagal stimulation. Atrial epicardial mapping with a 112-electrode atrial array was used to study the mechanism of flecainide action on AF. Under control conditions, multiple small zones of reentry coexisted. Flecainide progressively increased the size of reentry circuits, decreased their number, and slowed the frequency of atrial activation until the arrhythmia finally terminated; all changes were compatible with an increase in wavelength. We conclude that flecainide terminates atrial fibrillation in this experimental model by causing tachycardia-dependent increases in atrial ERP, which increase the wavelength at the rapid rates characteristic of AF to the point that the arrhythmia can no longer sustain itself.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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6. |
αB‐Crystallin in Cardiac Tissue Association With Actin and Desmin Filaments |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 288-294
Federico Bennardini,
Antoni Wrzosek,
Michele Chiesi,
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摘要:
αB-Crystallin is a 20-kd peptide highly homologous to the small heat-shock proteins. This protein forms soluble homomultimeric complexes (Mr, 300–700 kd) and is very abundant in cardiac muscle cells. In vitro experiments (affinity column chromatography and binding studies with isolated proteins) have shown that αB-crystallin interacts directly with actin and, in particular, with desmin filaments. The immunocyto-chemical localization of αB-crystallin within the cardiomyocytes showed that the protein is distributed exclusively in the central region of the I bands (Z lines), where desmin is localized. In vitro studies have further shown that the binding affinity of αB-crystallin to actin and desmin filaments increases considerably at slightly acidic pH (6.5) or after a heat treatment (45°C). Moreover, αB-crystallin was found to prevent effectively the tendency of actin filaments to form aggregates (i.e., paracrystals) at acidic pH. These in vitro data suggest a protective role of αB-crystallin during stress conditions such as ischemia of the heart. Crystallin could prevent the aggregation of filaments, which might occur during the acidification of the cytosol and lead eventually to irreversible structural damage. (Circulation Research1992;71:288–294)
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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7. |
Hydrogen Peroxide‐Induced Cardiovascular ReflexesRole of Hydroxyl Radicals |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 295-302
Gregory Stahl,
Barry Halliwell,
John Longhurst,
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摘要:
Mesenteric ischemia reflexly activates the cardiovascular system. In addition, mesenteric ischemia and reperfusion generate reactive oxygen species. However, the ability of these short-lived reactive oxygen species to generate cardiovascular reflexes is unknown. We therefore investigated cardiovascular reflexes induced by serosal application of hydrogen peroxide (H2O2) to the gallbladder, stomach, or duodenum in anesthetized cats. Serosal application of hydrogen peroxide (44 μmol) to the gallbladder (n=14) significantly (p<0.05) increased mean arterial blood pressure (MAP) by 37±6 mm Hg, left ventricular dP/dt by 1,893±416 mm Hg/sec, heart rate by 6±1 beats per minute, and systemic vascular resistance from 0.34±0.01 to 0.42±0.04 peripheral resistance units. The cardiovascular effects were dose-dependent over a range of 0.4 pmol to 132 μmol H2O2. Celiac and superior mesenteric ganglionectomy abolished H2O2-induced cardiovascular effects. Dimethylthiourea (10 mg/kg), a reactive oxygen species scavenger, significantly (p<0.05) attenuated 44 μmol H2O2-induced increases in MAP from 36±3 to 2±2 mm Hg. Deferoxamine (10 mg/kg) also significantly attenuated 44 μmol H2O2-induced increases in MAP from 40±7 to 19±10 mm Hg, but iron-loaded deferoxamine did not. Aspirin (50 mg/kg) did not attenuate H2O2-induced excitation of the cardiovascular system. These data suggest that H2O2activates abdominal visceral afferents to reflexly stimulate the cardiovascular system by a mechanism involving hydroxyl radicals. Thus, reactive oxygen species could modulate systemic vascular tone by stimulating abdominal visceral afferents during mesenteric ischemia and reperfusion.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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8. |
Effects of Complement Activation in the Isolated HeartRole of the Terminal Complement Components |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 303-319
Jonathon Homeister,
Paul Satoh,
Benedict Lucchesi,
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摘要:
The mechanisms of the complement-mediated myocardial injury associated with ischemia and reperfu-sion have not been elucidated fully. Complement activation may directly mediate injury through actions of the anaphylatoxins C3a and C5a or generation of the membrane attack complex C5b-9. A model was developed to examine the direct effects of complement activation on heart function, assess myocardial tissue damage, and determine which complement components mediate tissue injury. Isolated rabbit hearts were perfused with Krebs-Henseleit buffer by using a modified Langendorff apparatus. Human plasma was added to the perfusate as a source of complement. Rabbit tissue activates human complement. Treatment with 6% normal plasma resulted in complement activation as assessed by the generation of Bb, C3a, C5a, and SC5b-9. Functional changes in cardiac performance became apparent 7–15 minutes after plasma addition and developed fully over the next 20–30 minutes. The effects were dependent on the complement titer and included 1) an increase in the end-diastolic pressure, 2) a decrease in the developed pressure, 3) an increase in the coronary perfusion pressure, and 4) an increase in lymphatic fluid formation. These effects were not elicited when an inhibitor of complement activation (FUT-175) was present or when heat-inactivated plasma was used. The effects of complement activation on myocardial function could not be reproduced by treatment with recombinant human C5a, zymosan-activated plasma, or plasma selectively depleted of C8. Myocardial tissue accumulated sodium and calcium and lost potassium as a result of complement activation. Activation caused the release of creatine kinase from myocytes and an increase in the radiolabeled albumin space of the hearts. The data demonstrate that complement activation caused decrements in myocardial function and increased the coronary perfusion pressure and lymphatic fluid flow rate. The effects were not mediated by the anaphylatoxins but were dependent on the distal complement component C8, suggesting that C5b-9 was responsible for the physiological changes. Complement activation directly mediated tissue injury in a manner consistent with plasmalemmal disruption as a result of C5b-9 formation. The data suggest that the C5b-9 complex, which is known to form under conditions of ischemia, may contribute directly to myocardial cell injury.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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9. |
Isolated Pulmonary Resistance Vessels From Fetal Lambs Contractile Behavior and Responses to Indomethacin and Endothelin‐1 |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 320-330
Yang Wang,
Flavio Coceani,
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摘要:
A method was developed for recording isometric tension from isolated small arteries (mean internal diameter, 169 μm) and veins (mean internal diameter, 273 μm) of the term fetal lung and was then applied to the study of the mechanisms controlling perinatal pulmonary hemodynamics. The specific purpose was to determine whether the activity of the prostaglandin synthetic system in vessels is conditioned by the oxygen tension and the mode of action of endothelin-1. Both preparations appeared structurally intact and, after normalizing their lumen diameter to either the transmural pressure in vivo (artery) or the contractile capacity of the vessel in vitro (vein), generated force to the activating solution (5 mM Ca2+in K+Krebs' solution) in excess of the expected performance under physiological conditions. Treatment with indomethacin (2.8 μM) had no effect on arteries preequilibrated at low Po2(21±1 mm Hg); however, the same treatment contracted (≈45% of the response to activating solution) arteries at either an intermediate (40±0.8 mm Hg) or high (70±0.9 mm Hg) Po2. Endothelin-1 contracted both arteries and veins in a concentration-dependent manner, the threshold being lower with veins (1–10 versus 10–100 pM). Endothelin-1 constriction was also seen in arteries whose tone had been raised with a thromboxane A2analogue, whereas in thromboxane-treated veins constriction was preceded by a modest relaxation over the range of 1–1,000 pM. The findings with indomethacin lead us to infer that small pulmonary arteries are endowed with a prostaglandin-relaxing mechanism that becomes functional on raising the PO2from fetal to neonatal levels. Endothelin-1 is a constrictor regardless of the level of intrinsic tone, suggesting a possible role of the peptide in maintaining elevated pulmonary vascular tone in the fetus.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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10. |
Balloon Injury and Interleukin‐1 β Induce Nitric Oxide Synthase Activit in Rat Carotid Arteries |
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Circulation Research,
Volume 71,
Issue 2,
1992,
Page 331-338
Ghislaine Joly,
Valérie Schini,
Paul Vanhoutte,
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摘要:
Experiments were performed to investigate whether balloon injury induces nitric oxide synthase activity in the blood vessel wall. Contractions to phenylephrine were compared in left carotid arteries of the rat, previously injured by balloon catheterization and excised either immediately (t=0), 6, or 24 hours after the procedure, with those in control right carotid arteries (with and without endothelium). Phenylephrine evoked comparable concentration-dependent contractions in balloon-injured (t=0) and control carotid arteries without endothelium, whereas those in control arteries with endothelium were depressed. In the balloon-injured carotid arteries (6 and 24 hours), the concentration-contraction curves to phenylephrine were shifted to the right compared with those observed in balloon-injured arteries (t=0). In balloon-injured carotid arteries (6 hours), the hyporeactivity to phenylephrine was enhanced by superoxide dismutase. In balloon-injured carotid arteries (24 hours), nitro-l-arginine and methylene blue restored full contractions, whereas superoxide dismutase potentiated the hyporesponsiveness to phenylephrine. The depressed contractions were associated with a concomitant increase in the basal level of cGMP; this production was abolished by nitro-l-arginine. The depression of the concentration-contraction curves to phenylephrine and the increase of the tissue level of cGMP induced by interleukin-1 β (4 hours) were more pronounced in balloon-injured arteries (24 hours) than in control arteries without endothelium. The effects of interleukin-1 β were inhibited by nitro-l-arginine. These observations indicate that in vivo endothelial injury of the rat carotid arteries induces the production of nitric oxide from l-arginine in the blood vessel wall, an effect which is potentiated by interleukin-1 β.
ISSN:0009-7330
出版商:OVID
年代:1992
数据来源: OVID
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