Onset of relaxation in cardiac muscle segments

1983 ◽  
Vol 245 (4) ◽  
pp. H610-H615
Author(s):  
J. F. Rondinone ◽  
D. A. Martyn ◽  
L. L. Huntsman

The onset of relaxation has been studied in undamaged central segments of isolated ferret papillary muscles at 27 degrees C, 12 beats/min. A technique that provides a signal proportional to the length of a chosen segment was used to assess segment velocity and length. Feedback control was employed to obtain segment isometric contractions. At a variety of times during segment isometric twitches, rapid load clamps were imposed using a range of loads from resting force to greater than half peak developed force. For the purposes of this study, the onset of relaxation was defined as occurring when active segment shortening ceased and elongation began (i.e., Vseg = 0). Early load clamps to low loads resulted in V = 0 at comparatively short segment lengths and early times. Later load clamps caused zero velocity to occur at longer segment lengths and later times. The V = 0 points in fact formed a line in the segment length-time plane. Contractions clamped to higher loads exhibited reduced shortening and a prolonged time course so that the V = 0 points showed the same dependence on length and time. Remarkably, all the variations of load-clamp load, time, and initial length yielded V = 0 points that were intermixed along a single line. Increasing or decreasing extracellular Ca2+ caused the V equal to O points to shift to later times and shorter segment lengths or earlier times and longer segment lengths, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1983 ◽  
Vol 244 (5) ◽  
pp. H701-H707
Author(s):  
L. L. Huntsman ◽  
J. F. Rondinone ◽  
D. A. Martyn

Using a new technique that measures the length of a segment in the central region of isolated papillaries, we have determined the force-segment length relation for ferret papillary muscles at 27 degrees C. The muscles contracted under muscle length isometric (auxotonic) and segment isometric conditions in physiological solutions containing 9.0, 4.5, 2.25, and 1.125 mM Ca2+. Force-segment length relations obtained from auxotonic and segment isometric contractions were identical in a given Ca2+ concentration. Calcium variations, however, changed the position, shape, and segment length intercept of the force-segment length relation. Force, at a given segment length, increased with increasing Ca2+ up to 9.0 mM Ca2+. The force-segment length relation changed shape from linear, in 4.5 mM Ca2+, to concave in 1.125 mM Ca2+. The segment length intercept was found by extrapolation to be 68, 69, and 74% SLmax in 4.5, 2.25, and 1.125 mM Ca2+, respectively. Two passive force corrections were used to calculate the developed force-segment length relations. Assuming passive force to be related primarily to segment length yields curves that change shape with Ca2+ concentration, suggesting length-dependent activation. On the other hand, assuming passive force to be related to muscle length results in curves for different Ca2+ concentrations that are nearly vertically shifted versions of each other, suggesting the influence of internal loads.


1975 ◽  
Vol 229 (3) ◽  
pp. 646-651 ◽  
Author(s):  
JE Strobeck ◽  
AS Bahler ◽  
EH Sonnenblick

The force-velocity-length determinants of isotonic relaxation were studied in 12 cat papillary muscles. Isotonic relaxation velocity (VL) was found to be a function of total load (preload + afterload), with peak VL increasing to a maximum at loads approximately .3 to .4 Po(L') (Po(L') defined as maximum isometric force developed during a twitch at the experimental length) and falling with increasing loads. Initial muscle length (ML) had no effect on the peak VL with constant load. Increasing the initial length at which isotonic relaxation occurred (LL) decreased peak VL but did not alter the unique length-velocity trajectory at constant load. This unique length-velocity trajectory occurred, despite a wide variation in time during the contraction when peak VL was measured. Increasing Ca++ from 2.5 to 7.5 mM increased peak VL (1.73 +/- .16 to 2.32 +/- .20 ML/s) and shifted the entire length-velocity trajectory toward higher velocities of lengthening. The addition of 10 mM caffeine increased peak VL also (1.67 +/- .18 to 2.54 +/- .20 ML/s) and had a similar effect on the length-velocity trajectory during lengthening as Ca++. Both increased Ca++ and caffeine (10 mM) augmented the maximum VL measured on addition of load.


1987 ◽  
Vol 252 (4) ◽  
pp. H760-H770 ◽  
Author(s):  
D. T. Yue

The relation between the rate of rise of tension (dF/dt) and intracellular free Ca2+ concentration ([Ca2+]i) during twitch contraction was investigated in mammalian ventricular myocardium. [Ca2+]i was assessed from luminescence emitted by ferret papillary muscles microinjected with the calcium-regulated photoprotein aequorin. Evidence was found that during the phase of rising tension following maximum positive dF/dt, there was an approximately linear relationship between dF/dt at a given instant and the estimated [Ca2+]i at that same instant. A single such instantaneous relationship held true for physiological contractions of widely varying strength (n = 5 preparations), up to 65.3 +/- 6.0% (means +/- SE) of maximal Ca2+-activated force, as assessed from maximally activated cardiac tetani. Furthermore, the identical relationship determined from physiological contractions also held true for virtually the entire rising phase of tension in contractions with [Ca2+]i transients slowed (approximately 4- to 5-fold) by exposure of muscles to 5 microM ryanodine (n = 5 preparations). That a unique relation applies to contractions of both vastly different strength and time course provides evidence that the correlation between instantaneous dF/dt and [Ca2+]i is not merely fortuitous but indicates a fundamental property of myocardium. Such a property provides considerable insight into many features of physiological contraction and may represent a central clue as to the mechanism of activation in mammalian cardiac muscle.


1988 ◽  
Vol 254 (4) ◽  
pp. R633-R640 ◽  
Author(s):  
A. Morimoto ◽  
T. Nakamori ◽  
T. Watanabe ◽  
T. Ono ◽  
N. Murakami

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.


1994 ◽  
Vol 267 (3) ◽  
pp. H1157-H1166 ◽  
Author(s):  
G. M. Wahler ◽  
S. J. Dollinger ◽  
J. M. Smith ◽  
K. L. Flemal

The rat ventricular action potential shortens after birth. The contribution of increases in the transient outward current (Ito) to postnatal action potential shortening was assessed by measuring Ito in isolated cells and by determining the effect of 2 mM 4-aminopyridine (4-AP) on the action potentials of papillary muscles. 4-AP had no effect on 1-day action potential duration at 25% repolarization (APD25), and 1-day cells had little Ito. In 8- to 10-day muscles, 4-AP caused a small, but significant, increase in APD25. Ito increased slightly between day 1 and days 8-10, but this increase was not significant. Most of the increase in Ito (79%) and in the response to 4-AP (64%) occurred between days 8-10 and adult; however, approximately 75% of the APD25 shortening took place by days 8-10. Thus, while Ito may contribute to repolarization in late neonatal and adult cells, the different time courses of action potential shortening and increases in Ito suggest that changes in Ito are unlikely to be responsible for most of the postnatal action potential shortening.


1991 ◽  
Vol 260 (3) ◽  
pp. H989-H997 ◽  
Author(s):  
C. S. Moravec ◽  
M. Bond

We have used electron-probe microanalysis (EPMA) to address the question of Ca2+ release by junctional sarcoplasmic reticulum (JSR) as well as Ca2+ regulation by mitochondria (MT) during cardiac muscle contraction. Hamster papillary muscles were rapidly frozen during relaxation or at the peak rate of tension rise (+dT/dt). Total Ca2+ content was measured by EPMA in the JSR, within a MT, over the A band, and in the whole cell, in nine cells per animal (five animals per group). JSR Ca2+ content was found to be significantly lower in muscles frozen at the peak of contraction [7.3 +/- 1.3 (mean +/- SE) mmol Ca2+/kg dry wt] than in those frozen during relaxation (12.5 +/- 1.9 mmol Ca2+/kg dry wt; P less than 0.01), suggesting that Ca2+ is released from this storage site during cardiac muscle contraction. In contrast, MT Ca2+ content did not change significantly during contraction (0.4 +/- 0.1 mmol/kg dry wt) compared with relaxation (0.1 +/- 0.2 mmol/kg dry wt). A third group of muscles was frozen during relaxation after pretreatment with 10(-7) M ryanodine. Ca2+ content of the JSR was significantly decreased (P less than 0.01) in this group of muscles, (6.4 +/- 1.8 mmol/kg dry wt) compared with those frozen during relaxation in the absence of the drug. This suggests that the intracellular storage site with a decreased Ca2+ content in muscles frozen at the peak of contraction is the ryanodine-releasable store. These results provide the first direct measurement of the Ca2+ content of both JSR and MT during a normal cardiac muscle contraction and demonstrate that Ca2+ is released from the JSR during muscle contraction.


1999 ◽  
Vol 276 (3) ◽  
pp. H998-H1011 ◽  
Author(s):  
Amir Landesberg ◽  
Samuel Sideman

The well-known linear relationship between oxygen consumption and force-length area or the force-time integral is analyzed here for isometric contractions. The analysis, which is based on a biochemical model that couples calcium kinetics with cross-bridge cycling, indicates that the change in the number of force-generating cross bridges with the change in the sarcomere length depends on the force generated by the cross bridges. This positive-feedback phenomenon is consistent with our reported cooperativity mechanism, whereby the affinity of the troponin for calcium and, hence, cross-bridge recruitment depends on the number of force-generating cross bridges. Moreover, it is demonstrated that a model that does not include a feedback mechanism cannot describe the dependence of energy consumption on the loading conditions. The cooperativity mechanism, which has been shown to determine the force-length relationship and the related Frank-Starling law, is shown here to provide the basis for the regulation of energy consumption in the cardiac muscle.


1965 ◽  
Vol 208 (6) ◽  
pp. 1237-1242 ◽  
Author(s):  
Mario Penna ◽  
Francisco Linares ◽  
Laura Cáceres

In isolated guinea pig atria, hypoxia was induced by bubbling nitrogen through Tyrode solution. A significant increase in both the amplitude and frequency of the contractions occurred, followed by a decrease. Average rate in 11 control atria was 138 ± 9.2 contractions/min and increased during hypoxia by an average value of 12.7 ± 2.3 contractions/min ( P < 0.001). Amplitude of shortening increased by an average of 10.5 ± 2.12% ( P <0.001). In 19 preparations pretreatment with reserpine blocked the transient stimulant effect of hypoxia on both amplitude and frequency of contractions. Isometric contractions were recorded from 30 isolated cat papillary muscles. The developed isometric tension increased during hypoxia by an average of 17.3 ± 2.8% ( P < 0.001). Later, a decrease in contractile force was observed. Pretreatment of the animals with guanethidine and chronic cardiac sympathectomy blocked and pretreatment with reserpine decreased the stimulant effect of hypoxia on the cat papillary muscle. The transient stimulant effect of hypoxia was compared to the staircase phenomenon. Both chronic cardiac sympathectomy and pretreatment with reserpine blocked the increase in force induced by a change in rate from 60 to 120.


2012 ◽  
Vol 113 (7) ◽  
pp. 996-1003 ◽  
Author(s):  
J.-C. Han ◽  
A. J. Taberner ◽  
K. Tran ◽  
S. Goo ◽  
D. P. Nickerson ◽  
...  

Two very different sorts of experiments have characterized the field of cardiac energetics over the past three decades. In one of these, Gibbs and colleagues measured the heat production of isolated papillary muscles undergoing isometric contractions and afterloaded isotonic contractions. The former generated roughly linear heat vs. force relationships. The latter generated enthalpy-load relationships, the peak values of which occurred at or near peak isometric force, i.e., at a relative load of unity. Contractile efficiency showed a pronounced dependence on afterload. By contrast, Suga and coworkers measured the oxygen consumption (V̇o2) while recording the pressure-volume-time work loops of blood-perfused isolated dog hearts. From the associated (linear) end-systolic pressure-volume relations they derived a quantity labeled pressure-volume area (PVA), consisting of the sum of pressure-volume work and unspent elastic energy and showed that this was linearly correlated with V̇o2 over a wide range of conditions. This linear dependence imposed isoefficiency: constant contractile efficiency independent of afterload. Neither these data nor those of Gibbs and colleagues are in dispute. Nevertheless, despite numerous attempts over the years, no demonstration of either compatibility or incompatibility of these disparate characterizations of cardiac energetics has been forthcoming. We demonstrate that compatibility between the two formulations is thwarted by the concept of isoefficiency, the thermodynamic basis of which we show to be untenable.


1956 ◽  
Vol 186 (2) ◽  
pp. 317-324 ◽  
Author(s):  
Brian F. Hoffman ◽  
E. E. Suckling

The effects of changes in the extracellular concentrations of Ca, K and Mg on the transmembrane resting and action potentials of single fibers of the auricle, ventricle and specialized conducting system of the dog heart have been studied by means of intracellular microelectrodes. With respect to Ca, the three tissues exhibit quite different sensitivities. Changes in concentration of this ion alter the time course of the action potential recorded from auricle and ventricle but have little effect on the action potential configuration of the Purkinje fiber. In the latter tissue, on the other hand, pacemaker activity is most strongly enhanced by Ca depletion and excitability is lost at Ca concentrations permitting normal propagation in papillary muscle. The effect of K on the resting transmembrane potential is dependent on the simultaneous Ca concentration. The interrelationship is such that the depolarizing effect of high K is decreased by elevated Ca and the depolarization produced by low K is diminished by low levels of Ca. Changes in the concentration of Mg have little effect on the transmembrane potentials of cardiac muscle unless the level of Ca is low. Under this condition a simultaneous decrease in Mg gives rise to a marked prolongation of the action potential duration of both auricle and ventricle. Some evidence for the basic similarity of the processes underlying repolarization in these three tissues is presented and it is thought the normally encountered differences in their action potentials may be related to the sensitivity of each tissue to extracellular Ca.


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