Calcium overload and strophanthidin-induced mechanical toxicity in cardiac Purkinje fibers

1983 ◽  
Vol 61 (11) ◽  
pp. 1329-1339 ◽  
Author(s):  
Cheng-I Lin ◽  
Mario Vassalle

In cardiac Purkinje fibers, strophanthidin increases and then decreases contractile force. The relationship between the decrease in force and calcium overload was studied by recording the electrical and mechanical activity under conditions known to increase calcium overload or its effects. Inhibitors of oxidative phosphorylation reduced the positive inotropy of strophanthidin and enhanced the decrease in force. These inhibitors also reduced the inotropic effect of high calcium. Increasing intracellular calcium by decreasing extracellular sodium concentration also resulted in a decrease in the strophanthidin inotropy. When arrhythmia was delayed, strophanthidin induced contracture and this was favored by blockers of glycolysis and by enhancing cellular calcium. Some of these effects were also observed in ventricular muscle fibers but at higher strophanthidin concentrations. The results suggest that the decline in contractile force during strophanthidin exposure is related to calcium overload, although it is made clear that in Purkinje fibers contractile force and resting force may be independently affected under suitable conditions.

1983 ◽  
Vol 244 (1) ◽  
pp. C110-C114 ◽  
Author(s):  
C. O. Lee ◽  
M. Vassalle

The actions of norepinephrine and high calcium on the electrical, mechanical, and intracellular sodium ion activities were studied in electrically driven canine cardiac Purkinje fibers under different conditions. It was found that norepinephrine and high calcium decrease intracellular sodium ion activity (aiNa). The exposure to either agent is followed by a transient decline of force that correlates with the lower aiNa. Inhibition of the Na+ -K+ pump by strophanthidin reduces or abolishes the decrease in aiNa by norepinephrine but not that by high calcium. It is concluded that norepinephrine and high calcium both decrease aiNa and thereby the contractile force but (unlike high calcium) norepinephrine acts through the stimulation of the Na+ -K+ pump.


1979 ◽  
Vol 236 (5) ◽  
pp. H689-H697 ◽  
Author(s):  
M. Vassalle ◽  
C. I. Lin

The role of calcium in the electrical and mechanical toxicity induced by strophanthidin (10(-6) M) was studied in canine Purkinje fibers perfused in vitro. Strophanthidin caused an increase in contractile force ("therapeutic effect") followed by a subsequent decrease and by the onset of arrhythmias ("toxic effects"). The onset of arrhythmias occurred sooner in low- and later in high-calcium solutions with respect to the normal calcium. The positive inotropic (therapeutic) effect of strophanthidin was reduced or prevented by caffeine (1 mM) or by high calcium. The late (toxic) decline in force during exposure to strophanthidin was temporarily reversed by decreasing [Ca]o to a low value. Similarly, the contractile force decreased when [Ca]o was increased from 8.1 to 16.2 mM and this decline was transiently reversed when [Ca]o was reduced to a low value. It is concluded that in Purkinje fibers 1) electrical toxicity may occur independently of an intracellular calcium accumulation, and 2) the mechanical toxicity may be due to an excessive accumulation of calcium in the fiber.


1994 ◽  
Vol 80 (6) ◽  
pp. 1360-1368 ◽  
Author(s):  
David F. Stowe ◽  
Juraj Sprung ◽  
Lawrence A. Turner ◽  
John P. Kampine ◽  
Zeljko J. Bosnjak

1997 ◽  
Vol 272 (4) ◽  
pp. H1826-H1832 ◽  
Author(s):  
R. F. Gilmour ◽  
N. F. Otani ◽  
M. A. Watanabe

The contribution of cumulative changes in action potential duration (memory) to complex cellular electrophysiological behavior was investigated in canine cardiac Purkinje fibers. Complex behavior induced during constant pacing was caused by reciprocal interactions between the time to full repolarization (TFR), where TFR = response duration + latency, and the diastolic interval (DI). The relationship between TFR and the preceding DI during complex behavior differed from that obtained using a standard restitution protocol. In particular, higher-order periodicities and chaos were produced in fibers in which the restitution curve lacked the prerequisites for such behavior. To investigate whether shifts in the restitution curve might be expected during rapid pacing, the relationship between TFR of a test response (TFR(n + 1)) and the immediately preceding response (TFR(n)) was determined. For any fixed DI(n), reduction of TFR(n) from 240 to 130 ms was accompanied by a corresponding reduction of TFR(n + 1), whereas as TFR(n) was reduced further to 120 ms, TFR(n + 1) increased. Because of the dependence of TFR(n + 1) on TFR(n) (memory) and on the preceding DI(n) (restitution), the slope of the low-dimensional relationship between TFR(n + 1) and DI(n) at a constant pacing cycle length depended on the slopes of the restitution and memory functions. These results suggest that rapid accumulation and dissipation of memory may contribute importantly to complex electrical behavior in cardiac tissue.


1981 ◽  
Vol 240 (4) ◽  
pp. H561-H570
Author(s):  
M. L. Bhattacharyya ◽  
M. Vassalle

The effects of strophanthidin on electrical and mechanical events in canine cardiac Purkinje fibers were studied in vitro in the absence and presence of tetrodotoxin (TTX), norepinephrine, and high calcium. In Tyrode solution, strophanthidin (1-3 X 10(-7) M), norepinephrine (3-5 X 10(-7) M), and high calcium 8.1 mM) increased the force of contraction, and TTX markedly reduced it. In the presence of TTX, strophanthidin had little or no inotropic effect, whereas that of norepinephrine and high calcium was less than in Tyrode solution. In the presence of TTX, strophanthidin increased force markedly if (and as long as) either norepinephrine or high calcium were also present. A higher dose of strophanthidin (10(-6) M) induced a markedly delayed increase in force in presence of TTX. The results suggest that, in the presence of TTX, in a low concentration strophanthidin has little effect on force, because cellular calcium is low; however, it becomes effective when the calcium is increased by norepinephrine or high calcium. In toxic doses, strophanthidin increases force even in the presence of TTX as the inhibition of the pump should increase intracellular sodium and therefore calcium.


1975 ◽  
Vol 65 (3) ◽  
pp. 345-365 ◽  
Author(s):  
W R Gibbons ◽  
H A Fozzard

The two-microelectrode technique of voltage clamping sheep cardiac Purkinje fibers was used to examine the changes in contraction which occur during trains of voltage clamps. (A "train" is defined as a series of voltage clamps delivered at a particular rate, beginning after a rest long enough that the effects of previous stimulation have died away.) Contractions showed striking staircases, or progressive changes in peak isometric tension, during trains. Short clamps, clamps to voltages more negative than --20 or --30 mV, or holding potentials less negative than the resting potential favored negative staircases, while long clamps, clamps to positive voltages, and holding potentials near the resting potential each favored positive staircases. The staircase behavior appeared to be due to changes in the initial rate of recovery of the ability to contract. The changes in staircase behavior as a function of clamp voltage suggested that the relationship between peak tension and clamp voltage should depend on the experimental design. When the steady-state contraction was plotted as a function of clamp voltage, voltage-tension relations like those recently reported for working ventricle were obtained, with a threshold between --30 and --40 mV and a steep relation between tension and voltage. When the first contraction after a rest was plotted, the threshold voltage was more negative, the curve was flatter, and the peak tensions at inside positive voltages were reduced.


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