ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Structural complexities produced by the inhomogeneous distribution of the connections between cells and between muscle bundles have previously been considered to be of minor importance in the propagation of depolarization in cardiac muscle; conduction disturbances usually are attributed to changes in membrane properties along the course of the fibers. However, we observed marked effects of these connections on the velocity and the safety factor of propagation in atrial muscle under normal and abnormal conditions. First, within individual muscle bundles, intermittent connective- tissue septa were associated with localized dissociation of excitation when propagation occurred in the transverse direction, but not when it occurred in the longitudinal direction. Second, at sites where muscle bundles branch or join with other bundles, we observed abrupt slowing of normal action potentials and changes in the shape of the extracellular waveform. We also studied such a junction in a computer simulation of propagation and found that the local delay of propagation and the change in the shape of the extracellular waveform could only be accounted for by an abrupt change in the effective axial resistivity in the direction of propagation. Under normal conditions, enough depolarizing current is coupled across such discontinuities to maintain propagation. However, when the maximum membrane depolarizing current was reduced by increasing the extracellular potassium concentration or by premature stimulation, block occurred at these sites. We observed that most known cardiac conduction disturbances considered to require longer refractory periods in the direction of propagation (e.g., local conduction delay, decremental conduction, block, and reentry) can be produced by the effects on propagation of such discontinuities of effective axial resistivity. The results indicate that models of propagation that ignore the inhomogeneous and multidimensional distribution of cell-to-cell connections produce incomplete, and sometimes incorrect, descriptions of normal and abnormal propagation in cardiac muscle.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

We used numerical integration techniques to simulate action potential propagation along one-dimensional strands of cells coupled with electrical junctions. We considered the standard case to be a series of cardiac cells (20 μm in diameter, 50 μm long) with intercellular coupling such that the effective longitudinal resistance was 200 Ω cm. The membrane properties were represented by the model of Beeler and Reuter (1977) (Sharp and Joyner, 1980). By increasing Ri(and thus decreasing the space constant, L), we showed that effects due to the discrete cell length, ΔX, became apparent when ΔX/L was greater than about 0.2, producing an increased maximal dV/dt but a decrease in peak inward current. We also simulated the effects of a periodic spatial variation in Ri, representing a structure with groups of well-coupled cells but with minimal coupling between the groups. Even with a constant membrane model and cell size, variations in the spatial pattern of interconnection produced significant changes in action potential shape and velocity, with some patterns producing decremental conduction or propagation failure.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Myosin light chains from normal and hypertrophied human hearts were partially sequenced in order to see whether structural modifications of these light subunits could provide a molecular basis for the changes observed in heart properties and in myosin enzymatic activity. Normal light chains were prepared from hearts taken at autopsy, weighing 350 g or less and apparently devoid of myocardial disease. “Hypertrophied cardiac myosin light chains” were prepared from two greatly hypertrophied hearts, weighing 600 and 750 g. No amino acid substitutions, deletions, or additions were observed in the light chains from hypertrophied hearts. The third light chain previously reported in human cardiac myosin and related to hypertrophy was found to be a proteolytic product of LC2. The comparison between human and beef cardiac myosin light chains indicate that the sequences of these subunits of the myosin molecule are highly conserved.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Steady state studies have shown that quinidine is more depressant at low pH. To determine whether changes in pH affect the kinetics of quinidine interaction with the sodium channel, we measured transmembrane potential and dV/dtmaxin guinea pig papillary muscles mounted in a single sucrose gap. pH was changed from 7.4 to 6.9 by changing either the bicarbonate concentration [HC(V] (25–7.5 mm) or the CO2content (5–20%). dV/dtn,., kinetics were studied by stimulating the preparation with 20-second trains having 500- or 1000-msec interstimulus intervals and 20 seconds between the trains. Time constants (TO) for the onset of block were 6.2 pulses and 2.7 pulses at interstimulus intervals of 500 and 1000 msec, respectively (P< 0.05) in fibers treated with 4 mg/liter quinidine. Time constant for the onset of block did not show any pH dependence. Recovery from block was not frequency dependent (4.7 ± 0.8 seconds at an interstimulus interval of 500 and 4.0 ± 1.0 second at an interstimulus interval of 1000 msec,P> 0.1). At an interstimulus interval of 500 msec, the recovery time constant increased from 4.7 ± 0.8 to 7.8 ± 2 seconds (P< 0.05) as the pH was lowered to 6.9 by decreasing [HCO3-]o. This effect was fully reversed when the pH was restored to 7.4 (7.8 ± 2 back to 4 ± 0.4 seconds). Lowering the pH by elevating the CO2content gave similar results. The results at an interstimulus interval of 1000 msec parallel those of 500 msec. Elevating the drug concentration from 4 to 16 mg/liter increased the rate of onset of block (TO5.8 ± 2 pulses to 4.2 ± 1.6 pulses,P< 0.05) but not the rate of recovery from block. These results are consistent with the hypothesis that slowing of the recovery process at low pH is the result of increased protonation of receptor-bound drug and are similar to data previously reported for lidocaine. The data support the view that quinidine and lidocaine interact with the sodium channel in a similar manner, despite suggestions that they have fundamentally different mechanisms of action.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

An upward shift of the left ventricular (LV) diastolic pressure-volume relation has been observed during angina in humans and has recently been induced by pacing tachycardia in dogs with coronary stenoses. To assess the mechanism of this phenomenon, we studied the effects of caffeine (an agent known to prolong intracellular calcium availability) on the upward shift of the LV diastolic pressure-volume relation induced by pacing tachycardia in dogs with coronary stenoses. Severe (90%) coronary artery stenoses were produced on both the left anterior descending and circumflex coronary arteries in 14 chloralose-anesthetized, β-blocked dogs with chest and pericardium open. In six dogs, two pairs of ultrasonic crystals were implanted subendocardially in the ischemic areas. The left atrium was paced at a rate of 1.5 times the resting heart rate for 3 minutes. In the immediate post-pacing period there was a rise of the left ventricular end-diastolic pressure (LVEDP) from 9 ± 1 to 15 ± 1 mm Hg (P< 0.005) at comparable peak-systolic pressures and slightly increased end-diastolic segment lengths (16.8 ± 0.9 mm to 17.5 ± 0.9 mm) (P< 0.005). After the return of LV hemodynamics to baseline values, atrial pacing was repeated at a rate and blood pressure comparable to the first pacing run but with the administration of caffeine (20 ± 4 mg/kg, intravenously) in the last 30 seconds of pacing. In the post-pacing period, the LVEDP rose from 9 ± 1 to 27 ± 2 mm Hg (P< 0.005) at comparable peak systolic pressures and slightly increased end-diastolic segment lengths (16.8 ± 0.9 mm to 17.3 ± 1.0 mm) (P< 0.05). The increased LV filling pressure persisted three times longer than in the control pacing run and was associated with a marked upward shift of the LV diastolic pressure-segment length and pressure-volume relation. The same dose of caffeine, when given in the non-ischemic (control) setting, produced a transient (<1 minute) fall in LV peak systolic pressure (112 ± 6 to 97 ± 3 mm Hg,P< 0.005), LVEDP (9 ± 1 to 7 ± 1 mm Hg,P< 0.01) and end-systolic segment length (14.8 ± 0.9 to 14.3 ± 0.9 mm,P< 0.005) consistent with a peripheral vasodilatory effect of caffeine. It is concluded that caffeine potentiates the ischemia-induced changes in LV diastolic stiffness. These findings could be explained by sustained intracellular calcium availability with persistent contractile element interaction in diastole.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

To assess the importance of the glycocalyx in cardiac cells, isolated preparations of sinus node (SN), atrial working muscle (AM), false tendon (FT), and ventricular working muscle (VM) were studied electrophysiologically with intracellular electrodes and then structurally with the electron microscope. Twenty isolated canine right atria with attached ventricular tissue were arterially perfused (SN artery, FT's were superfused) and at the close of each experiment, ruthenium (Ru) red in a glutaraldehyde fixative solution was substituted for the normal perfusate; this step arrested all cardiac cell activity. The Ru red was found aggregated in a thick (>500 A) layer outside the external leaflet of the cell membrane in SN, AM, FT, and VM cells; this layer corresponded to the location of the glycocalyx. Similar deposits of Ru red were found inside caveolae, transverse tubules, and intercellular junctions. In the SN, the glycocalyx demarcated by Ru red was different, in that it surrounded the peripheries of P cell clusters rather than individual P cells. Neither the junction between two P cells nor that between P and transitional cells was invaded. Fifteen complete sets of cardiac tissues were treated with neuraminidase (1.0 U/ml) for 1 hour or more before the addition of Ru red. In nine different preparations, the Ru red-positive layer became virtually absent after this treatment in SN, AM, and VM cells, but the glycocalyx in FT cells remained normal in appearance. Intracellular electrodes in each tissue sample recorded the electrophysiological changes during neuraminidase treatment. Functional importance of the glycocalyx in AM and VM cells was demonstrated by their inability to conduct impulses after neuraminidase treatment. The same treatment in SN cells ultimately abolished their automaticity, whereas, in quiescent FT cells, it evoked spontaneous firing. Thus, the glycocalyx (or sialic acid removed by neuraminidase) may play a different role in each of the two types of automatic cells. These electrophysiological and ultrastructural results support an important role for the glycocalyx in the canine heart. Removal of part or all of it by neuraminidase promotes aberrant electrical activity in each different type of canine cardiac cell studied.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

By means of transillumination (microtransilluminator and light pipe), comparative analyses were carried out on geometry, topography, and morphometry of microcirculation in the cerebral cortex, left atrial muscle, and mesentery of the cat using computer analysis. In addition, specific types of capillary distribution (concurrent, countercurrent, and asymmetric distribution) in these three organs were ascertained from images visualized on films. These parameters were related to their role in tissue oxygen supply. It was found that mean capillary diameter, mean intercapillary distance, total capillary length, and total capillary surface area differed significantly among the three organs. Differences in mean capillary tortuosity between cerebral cortex and left atrial muscle and between left atrial muscle and mesentery also were significant. Mean capillary tortuosity in mesentery and cerebral cortex was of equal magnitude. In the cerebral cortex, a high degree of tortuosity and asymmetric capillary distribution favor tissue oxygenation. A similar situation exists in left atrial muscle, although some concurrent and countercurrent distribution could be detected. In the mesentery, the combination of high capillary tortuosity and concurrent capillary arrangement is unfavorable for tissue oxygenation.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Because ethanol abusers are susceptible to pancreatitis in animal models, and interruption of the pancreatic circulatory supply may also cause pancreatitis, we studied the effect of ethanol infusion on pancreatic blood flow. We administered ethanol 0.5 g/kg and 1.5 g/kg iv, to 35 conscious dogs (ethanol blood levels, 117 ± 10 (SD) and 297 ± 67 mg/100 ml, respectively). Measurements were made of aortic pressure and regional blood flow by the radioactive microsphere method in the pancreas, stomach, spleen, intestines, adrenal glands, and kidneys. Pancreatic flows were 172 ml/min per 100 g control, 156 ml/min per 100 g after 0.5 g/kg ethanol and 108 ml/min per 100 g after 1.5 g/kg ethanol. After the higher dose, the decrease in pancreatic flow of 64 ml/min per 100 g or 37% was statistically significant (P< 0.01); pancreatic vascular resistance rose by 113% (P< 0.001). There were no significant changes in flow or resistance in the other organs studied. Similar changes in pancreatic flow and resistance occurred after 1.5 g/kg ethanol in groups of dogs pretreated with phenoxybenzamine, an α-adrenergic antagonist; propranolol. a β-adrenergic antagonist; cimetidine, a histamine H2 receptor antagonist; and meclofenamate, a prostaglandin synthetase inhibitor. The changes in pancreatic blood flow and resistance were substantially reversed by 25% mannitol, 3 ml/kg, iv, after infusion of ethanol. We conclude that ethanol, in high doses relevant clinically, selectively elevates pancreatic vascular resistance, probably by inducing perivascular cellular swelling.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The ionic mechanism underlying the shortening of the action potential and the reduction in pacemaker activity by lidocaine, quinidine, and procainamide in sheep cardiac Purkinje fibers was investigated using the two-microelectrode voltage clamp technique. In the presence of lidocaine (1.85 to 3.7 × 10−5M), steady state currents were shifted outward over a broad range of potentials. In contrast, instantaneous currents (holding potential −40 mV) and steady state currents in 20 mM Cs-Tyrode were not affected at potentials negative to −60 mV, the outward shift being restricted to potentials positive to this level. This outward shift of the current at the plateau level by lidocaine was not observed in the presence of a maximal dose of tetrodotoxin (TTX); in Na-free medium, the effect of lidocaine was totally suppressed. On the pacemaker current, the major effect of lidocaine was to reduce the magnitude of the activation curve with no change in time constants or in the shape of the fully activated current-voltage relation. Quinidine and procainamide exerted similar effects on instantaneous currents. Quinidine affected the pacemaker in the same way as lidocaine, whereas procainamide had no effect on this current. The results indicate that local anesthetics do not increase the K inward rectifier current and have no effect on inward background current at potentials negative to −60 mV; the shift in steady state currents at these levels is due to a change in pacemaker current. Because the lidocaine-sensitive pacemaker current does not reverse at the presumed equilibrium potential for K ions, aiid the effect of lidocaine in the presence of 1 mM Ba is similar to that in normal Tyrode, it is concluded that the drug inhibits a pacemaker current which is activated on hyperpolarization and mainly carried by Na ions. The results with TTX and in Na-free medium demonstrate that lidocaine inhibits a Na current, sensitive to TTX. The shortening of the action potential in sheep cardiac Purkinje fibers by local anesthetics is not due to an increase in outward current but can be explained by a block of an inward current, through the TTX-sensitive channel.

ISSN:0009-7330    

出版商:OVID    

年代:1982

数据来源: OVID