摘要:

This study tested the hypothesis that with hypertrophy, the proportion, distribution, and structural alignment of fibrillar collagen are important determinants of myocardial stiffness. Toward this end, the collagen volume fraction (morphometry), the transmural or subendocardial distribution of collagen, and the structural arrangement of fibrillar collagens (picrosirius red) were examined in the hypertrophied ventricle secondary to pressure overload (abdominal aorta banding or perinephritis), isoproterenol, and pressure overload plus isoproterenol. In the same hearts, the slopes of the systolic and diastolic stress-strain relations of the left ventricle, representing its active and passive stiffness, respectively, were obtained. In comparison with controls, we found 1) for a moderate rise in transmural collagen, active and passive stiffness increased with pressure-overload hypertrophy; 2) following isoproterenol alone there was a marked increase in subendocardial collagen, and active and passive stiffness increased; 3) in pressure-overload hypertrophy plus isoproterenol, active stiffness declined. Passive stiffness was increased except when fibrosis and thinning of the interventricular septum occurred, in which case it decreased; and 4) fibrillar collagens involved in remodeling included the formation of either collagen strands and fibers in a greater number of previously collagen-free intermuscular spaces in pressure-overload hypertrophy, or a dense crisscrossing latticework of fibers that encircled muscle fibers after isoproterenol. Thus, an increase in fibrillar collagen in pressure- overload hypertrophy is partially adaptive in that it enhances the tensile strength and three- dimensional delivery of force by the myocardium, but at the expense of reducing distensibility. The appearance of a dense collagen meshwork within the subendocardium after isoproterenol can be considered pathological in that it entraps muscle fibers causing active stiffness to fall while impairing distensibility. Finally, fibrosis may paradoxically reduce passive stiffness if it leads to a thinning of the interventricular septum.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The chronotropic responses of isolated sinoatrial node and ventricular muscle cells to neurotransmitters were compared in vitro with and without selective adrenergic and cholinergic innervation. Explants of either thoracolumbar sympathetic ganglion or sacrococcygeal spinal cord were added to cultures of newborn rat sinus node regions or ventricular apexes harvested before the onset of autonomic innervation in vivo. Catecholamine synthesis was detected by glyoxylic acid histofluorescence. Acetylcholine synthesis was indicated by monoclonal antibody labeling of choline acetyltransferase. After electrical or pharmacological stimulation of neurons, the chronotropic response of individual myocardial cells confirmed the presence of neuroeffector transmission; the nature of the myocyte response identified the stimulated neuron as either adrenergic or cholinergic. Chronotropic responses of all myocardial cells to norepinephrine or acetylcholine were transcribed on a recorder coupled to a video photoconductive cell monitor. Isolated sinoatrial node cells were supersensitive to norepinephrine and acetylcholine; thresholds were 3xl0-16M and 6xlO-15M, respectively. These sinoatrial node cells remained sensitive to both norepinephrine and acetylcholine after the development of innervation in vitro. Ventricular cells also were sensitive with thresholds of 3xlO-11M and 6xl0-14M to noreprinephrine and acetylcholine, respectively. However, following in vitro innervation, ventricular cells were significantly less sensitive to noreprinephrine and acetylcholine (thresholds 3x10-9M and 6x10-11M). These data are the first to demonstrate that neurotrophic modulation is not homogeneous throughout the myocardium and that it may be dependent on the specific myocardial cell innervated.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Binding of cardiac glycosides to the Na+,K+-dependent ATPase has been shown to occur at both high- and low-affinity sites. However, recent reports suggest that glycoside-induced inhibition of electrogenic Na-K pump current occurs with simple first-order binding kinetics at relatively low-affinity sites. This implies that high-affinity binding sites have little to do with Na-K pump inhibition during exposure to cardiac glycosides. To better understand the role of the high-affinity site, we investigated the concentration dependence of Ipumpinhibition by dihydroouabain (DHO) hi guinea pig ventricular myocytes through use of wide-pore patch pipettes to "fix" internal Na+activity at ˜30 mM and to voltage clamp at -40 mV (T=34± C). DHO was found to have no effect on membrane conductance at a holding potential of -40 mV. Holding current was monitored and the difference between steady-state holding current before and during external exposure to nine concentrations (range, 0.01-1,000 ±M) of DHO was measured and normalized to cellular membrane capacitance. The concentration dependence of the inhibition of Na-K pump current was biphasic and well fitted to a two-binding site model with inhibitory KDvalues of 0.05 ±M and 64.5 ±M. This is consistent with previously reported3H-ouabain binding studies in guinea pig myocardium. These findings indicate that the electrogenic properties of the Na-K pump can be inhibited by glycoside binding to both high- and low-affinity sites.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Experiments were performed to determine the effect of ouabain on the release of relaxing factor(s) from cultured endothelial cells, and its action on the effect of the relaxing factor(s) on arterial smooth muscle. A column of porcine aortic endothelial cells grown on microcarrier beads in suspension culture was perfused with modified Krebs-Ringer bicarbonate solution. The release of relaxing factor(s) by the endothelial cells was detected under bioassay conditions by measuring the relaxing activity of the perfusate overflowing a ring of canine coronary artery (without endothelium) contracted with prostaglandin F2α. Incubation of the endothelial cells with ouabain did not affect the relaxation of the bioassay ring under basal conditions or upon stimulation of the endothelial cells with ADP but impaired the relaxation Induced by bradykinin or the calcium ionophore A23187. Incubation of the bioassay ring with ouabain reduced the relaxation under basal conditions as well as the relaxation induced by ADP but did not affect the relaxation observed upon stimulation with bradykinin and A23187 and the endothelium- independent relaxations induced by nitric oxide. These experiments suggest that cultured porcine aortic endothelial cells release two endothelium-derived relaxing factors; one is released under basal conditions and upon stimulation with adenosine diphosphate and the other (which presumably is nitric oxide) upon stimulation with bradykinin and the calcium ionophore A23187.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Previous studies from this laboratory have demonstrated rapid and reversible changes in cardiac structure, composition, and function in response to load alterations in vivo. The purpose of the present in vitro study was to examine directly in the isolated, quiescent adult cardiocyte the potential growth-regulating effects of load changes through the use of an extremely simple and well-defined cell culture preparation. Freshly isolated cardiocytes were plated onto a deformable, laminin-coated substrate and maintained in serum-free culture medium for 3 days. On the third day in culture, the resting length of these quiescent cardiocytes, and thus their external load, was increased by linear deformation of the substrate to which these cells were firmly adhered. Cardiocyte loading resulted in increases of ˜10percent; in cell length, ˜8percent; in cell surface area, and ˜7percent; in sarcomere length. Three markers of increased synthetic activity were then examined: 1) [3H]uridine incorporation into nuclear RNA, 2) [3H]phenylalanine incorporation into cytoplasmic protein, and 3) [3H]thymidine incorporation into DNA. Cardiocyte loading resulted in mean increases of 186percent; in nuclear RNA labeling and 89percent; in cytoplasmic protein labeling. The finding that the increase in [3H]phenylalanine incorporation could be blocked readily by cycloheximide showed that the Increase hi cytoplasmic labeling in response to cardiocyte loading was not simply the result of increased amino acid transport but instead resulted from the incorporation of label into newly synthesized protein. An absence of [3H]thymidine nuclear incorporation in the loaded cardiocytes indicated that DNA synthesis was not activated in these cells. These data constitute the initial demonstration that an increase in load is at least a sufficient stimulus for the induction of increased RNA and protein synthetic activity in the adult mammalian cardiocyte. This evidence for the role of load as an independent regulator of cardiac growth in the adult suggests that hemodynamic changes may lead directly to appropriate alterations in cardiac structure and composition through the transduction of this physical stimulus into one or more biochemical signals that modulate gene expression.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The pathophysiological effects of congestive heart failure and physiological effects of exercise training on skeletal muscle may be mediated in part by modulation of β-adrenergic receptor density. To shed light on the physiological role of skeletal muscle β-receptors, their density and distribution were characterized in muscle fibers and resistance arterioles of whole tissue slices of three rat inndquarter muscles differing markedly in fiber type composition and capacities for oxidative metabolism and vasodilatation. Binding isotherms and quantitative light microscopic autoradiograpinc localization of receptors were performed by incubating tissue slices in selected concentrations of [125I]cyanopindolol with and without 10-5M T-propranolol. Muscle fiber types were delineated in adjacent sections by histochemical staining of myofibrillar ATPase activity at pH 4.5-4.55. The total tissue content of receptors (Bmaxwas nearly threefold greater in the soleus, a muscle consisting almost entirely of slow-twitch (type I) fibers than in superficial white vastus lateralis, a muscle composed of >95percent; fast-twitch (type IIb) fibers. Bmaxwas intermediate in gastrocnemius, a mixed fiber muscle (all differences p<0.01). Receptor affinity for radioligand was higher in the white vastus than in the mixed fiber and slow-twitch muscles (Kd= 3.5±0.4 pM for white vastus versus 6.8±0.8 and 6.4±1.1 pM in gastrocnemius and soleus, respectively; both p<0.01 versus white vastus). Disparities in Bmaxamong muscles were due entirely to differences in receptor densities of skeletal muscle cells as shown autoradiographically. Furthermore, variations in Bmaxof the three skeletal muscles were directly related to percentage of type I fibers (r=0.99; p<0.001), winch had a β-receptor density that was approximately 4.5-fold greater than in superficially located type IIb fibers, 3.2-fold greater than in intermediate depth type IIb fibers, and 2.0-fold greater than in type IIa fibers. In contrast, grain densities of resistance arterioles were similar regardless of surrounding skeletal muscle fiber type composition. However, resistance arterioles were 2.5- and 6.1-fold more numerous in the slow-twitch soleus than in the gastrocnemius and superficial white vastus, respectively (all differences p<0.01). We conclude that β-receptor density of rat hindquarter skeletal muscles is directly proportional to percentage of slow-twitch fibers, while receptor affinity for antagonist is ingher in fast-twitch than in slow-twitch or mixed fiber muscles, β-receptor density of resistance arterioles is similar among types of muscles but these vessels are far more numerous in the slow-twitch soleus. Such differences reflect the diverse metabolic and physiological characteristics of the rat hindquarter musculature.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Little is known about the hemodynamic properties of the rapidly expanding arterial bed during embryonic development. Using a servo-null pressure system and 20-MH<sc>z</sc> pulsed Doppler velocity meter, we recorded simultaneous dorsal aortic pressure and velocity waveforms. The waveforms were digitized at 3-msec intervals and subjected to Fourier analysis. We calculated hydraulic energy and the impedance spectrum to 10 H<sc>z</sc>. From stages 18 to 29, heart rate (148±3 to 193±9 beats/min), systolic pressure (1.14±0.12 to 3.04±0.10 mm Hg), and mean dorsal aortic blood flow (21 ±2 to 214±19 mm3/min) increased. Peripheral vascular resistance (Z0: 30.4±4.8 to 6.4±0.7 dyneXsec/mm5), and the impedance moduli (Z1: 6.5±1.0 to 1.7±0.2 dyneYsec/mm5; Z2:6.1±1.2 to 1.7±0.1 dyneXsec/mm5; Z3: 7.3±1.1 to 1.7±0.2 dyneXsec/mm5) decreased. Total hydraulic power increased from 48±7 to 2,606±96 nW, while the proportion of oscillatory energy increased from 29±2percent; to 65±4percent;. With development hydraulic load decreases, total external work increases and the dorsal aorta and embryonic vascular bed becomes more compliant. A greater proportion of total energy is expanded in pulsatile blood flow, suggesting that ventricular-arterial coupling is less efficient later in development.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Myosin ATPase activity is usually considered to reflect the contractile capacity of a given muscle since it correlates with the maximum initial speed of shortening of the unloaded muscle (Vmax). There are several exceptions to this scheme, and it was the goal of this study to determine if the Mg2+-ATPase activity of the covalently bound actomyosin SI is a more physiological index of contractility. On polyacrylamide gels, the complex obtained after condensation of fast skeletal myosin SI to skeletal actin is identical to that obtained with myosin SI from the ventricles of different species, including rat, guinea pig, and human, cross-linked to cardiac or skeletal actin. In every condition, the ATPase activity of the complex is 700-fold higher than that of myosin SI. It correlates linearly with the Vmaxboth in phylogeny and in conditions in which an isomyosin shift has been reported, such as hypothyroidism and chronic cardiac overload. Such a relation indicates that, in species that already have a low Vmax, a small change in myosin ATPase may induce dramatic consequences in the shortening velocity. Cardiac hypertrophy in humans, where the drop in Vmaxis not associated with a myosin change, does not fit into this scheme. The enzymatic activity of the complex is also unmodified in this condition, whichshows that, in humans, the myosin ATPase is not a determinant of Vmaxand suggests that other mechanisms may be involved. Measurement of this type of ATPase activity provides a new tool to explore contractility biochemically, which is more reproducible and, from a technical point of view, easier to perform than a kinetic assay. It also correlates better with mechanical data obtained with skinned fibers than with those measured on fresh papillary muscles.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Determination of the effect of Inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonlschernic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5±1 μg/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n=8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114±7 mm Hg to 62±2 mm Hg caused a decrease in percent systolic wall tinckening (percent;WTh) from 34.6±8.1percent; to 25.4±5.8percent; (p<0.005). In the second group of animals (n=8), CAP was decreased to 46±5 mm Hg (control: 115±8 mm Hg) and percent;WTh decreased from 34.1±16.4percent; to 10.4±6.9percent; (p<0.001). Subendocardial blood flow was reduced from 1.41 ±0.38 ml/min/g to 0.65±0.13 ml/min/g (group 1, p<0.001) and from 1.08±0.22 ml/min/g to 0.24±0.08 ml/min/g (group 2, p<0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall tinckening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by percent;WTh remained unchanged (26.2±5.8percent;, p=NS) in group 1 and decreased significantly to 1.6±5.1percent; (p<0.041) in group 2. Subendocardial blood flow decreased to 0.44±0.15 ml/min/g in group 1 (p<0.005) and to 0.15±0.07 ml/min/g in group 2 (p<0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work index was developed in which the sum of the instantaneous left ventricular pressure-wall tinckness product was calculated for estimation of regional myocardial work. Increases in this work Index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16percent; (p<0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Fetal cardiac changes due to ductal constriction by maternal ingestion of nonsteroidal anti-inflammatory drugs were studied morphologically in near-term rats as an animal model, and results were compared with values of control 1 (Cl, twenty-first day) and control 2 (C2, twenty-second day). The fetal ductus was constricted (–-70percent;) (p<0.05) by maternal administration of 10 mg/kg indomethacin. Dilatation of the right ventricle and evidence of congestive heart failure including increased pericardial effusion (+200percent;) (p<0.05) and an increase in water content in the abdominal wall were present at 1,4, and 8 hours after drug administration. At 24 hours after drug administration, concentric right ventricular hypertrophy was shown by a diminished right ventricular cavity (–-36percent; vs. C2) (p<0.05), increased right ventricular wall thickness (+70percent; vs. C2) (p<0.05), and increased right ventricular mass (+31percent; vs. Cl) (p<0.05). Left ventricular dilatation was indicated by an increased cavity volume (+87percent; vs. C2) (p<0.05) and increased muscle mass (+29percent; vs. Cl [p<0.05] or +9percent; vs. C2 [p>0.05]). Both the wet and dry weights of the ventricles were increased. In conclusion, fetal ductal constriction caused right ventricular hypertrophy, diminished right ventricular cavity, and left ventricular dilatation and hypertrophy at 24 hours after drug administration in rats after initial congestive failure.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID