Timing and magnitude of systolic stretch affect myofilament activation and mechanical work

Dyssynchronous activation of the heart leads to abnormal regional systolic stretch. In vivo studies have suggested that the timing of systolic stretch can affect regional tension and external work development. In the present study, we measured the direct effects of systolic stretch timing on the magnitude of tension and external work development in isolated murine right ventricular papillary muscles. A servomotor was used to impose precisely timed stretches relative to electrical activation while a force transducer measured force output and strain was monitored using a charge-couple device camera and topical markers. Stretches taking place during peak intracellular Ca2+ statistically increased peak tension up to 270%, whereas external work due to stretches in this interval reached values of 500 J/m. An experimental analysis showed that time-varying elastance overestimated peak tension by 100% for stretches occurring after peak isometric tension. The addition of the force-velocity relation explained some effects of stretches occurring before the peak of the Ca2+ transient but had no effect in later stretches. An estimate of transient deactivation was measured by performing quick stretches to dissociate cross-bridges. The timing of transient deactivation explained the remaining differences between the model and experiment. These results suggest that stretch near the start of cardiac tension development substantially increases twitch tension and mechanical work production, whereas late stretches decrease external work. While the increased work can mostly be explained by the time-varying elastance of cardiac muscle, the decreased work in muscles stretched after the peak of the Ca2+ transient is largely due to myofilament deactivation.

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Myocardial mechanics predict hemodynamic performance during normal function and alcohol-induced dysfunction in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.261.6.h1880 ◽

1991 ◽

Vol 261 (6) ◽

pp. H1880-H1888

Author(s):

J. M. Capasso ◽

P. Li ◽

P. Anversa

Keyword(s):

Pressure Rise ◽

Normal Function ◽

Left Ventricular ◽

Isometric Tension ◽

Papillary Muscles ◽

Least Squares Regression ◽

Tension Development ◽

Myocardial Mechanics

To determine whether mechanical evaluation of muscle tissue removed from the myocardium can be employed as a direct indicator of cardiac contractile performance in situ, isometric and isotonic parameters of muscle mechanics in vitro were correlated with in vivo global functional characteristics of the same heart. Twelve-month-old animals maintained on standard food and water were employed as representative of normal cardiac function. Animals of identical age with left ventricular (LV) dysfunction induced by oral alcohol (30%) ingestion from 4 to 12 mo were utilized to represent depressed cardiac performance. Accordingly, 24 h after the establishment of the hemodynamic profile for a control or experimental heart, the LV posterior papillary muscle was removed from the same heart and examined isometrically and isotonically. Least squares regression analysis was employed to establish a correlation coefficient and P values between various in vitro and in vivo parameters. Hemodynamic measurements were performed under chloral hydrate anesthesia and LV pump performance was evaluated with respect to aortic and ventricular pressures and the rates of rise and decay of the LV pressure trace. Papillary muscles were evaluated with respect to timing parameters of the isometric and isotonic twitch, the first derivative of isometric tension development, and the speed of muscle shortening at increasing physiologic loads. LV peak rate of pressure rise and decay were then correlated with the various isometric and isotonic properties. Myocardial mechanics and hemodynamics revealed depressed function in the papillary muscles and hearts from alcoholic rats. Moreover, significant correlations were found between the LV rate of pressure change (peak +dP/dt and -dP/dt) and both isometric and isotonic twitch measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

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Measurement of axial forces during emptying from the human stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.263.2.g230 ◽

1992 ◽

Vol 263 (2) ◽

pp. G230-G239 ◽

Cited By ~ 10

Author(s):

M. J. Vassallo ◽

M. Camilleri ◽

C. M. Prather ◽

R. B. Hanson ◽

G. M. Thomforde

Keyword(s):

Axial Force ◽

Longitudinal Axis ◽

Force Transducer ◽

Human Stomach ◽

In Vitro Studies ◽

In Vivo Studies ◽

Dependent Manner ◽

Axial Forces

Our aim was to measure axial forces in the stomach and to evaluate their relation to circumferential contractions of the gastric walls and the emptying of gastric content. We used a combination of simultaneous radioscintigraphy, gastroduodenal manometry, and an axial force transducer with an inflatable 2-ml balloon fluoroscopically placed in the antrum. In vitro studies demonstrated that the axial force transducer records only antegrade forces along the longitudinal axis of this probe in an intensity-dependent manner. In vivo studies were performed in five healthy subjects for at least 3 h after ingestion of radiolabeled meals. When administered separately, the emptying of liquids or solids from the stomach is associated with generation of antral axial forces and coincident phasic pressure activity; however, almost 20% (average) of gastric axial forces during emptying of liquids or solids are unassociated with proximal or distal antral pressure activity ("isolated" forces). High amplitude antral axial forces and pressures occur during both lag and postlag emptying phases. During emptying of liquids, there is a trend for axial forces to be coincident more often with proximal than with distal antral pressure activity and vice versa for the emptying of solids (P = 0.015). These data suggest that when placed in the antrum, the transducer can semiquantitatively record axial forces during gastric emptying. By combining these observations with the data from in vitro studies, it appears that axial forces predominantly result from traction on the balloon by the longitudinal vector resulting from circumferential gastric contractions. The combination of radioscintigraphy and measurement of antral axial forces is a promising method to evaluate mechanical forces involved in the emptying of the human stomach.

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The O2 cost of the tension-time integral in isolated single myocytes during fatigue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00715.2009 ◽

2010 ◽

Vol 298 (4) ◽

pp. R983-R988 ◽

Cited By ~ 22

Author(s):

Russell T. Hepple ◽

Richard A. Howlett ◽

Casey A. Kindig ◽

Creed M. Stary ◽

Michael C. Hogan

Keyword(s):

Slow Component ◽

Motor Units ◽

Isometric Tension ◽

Aerobic Metabolism ◽

Whole Body ◽

Cellular Respiration ◽

Tension Development ◽

Phosphorescence Quenching ◽

Contraction Frequency ◽

Peak Tension

One proposed explanation for the V̇o2 slow component is that lower-threshold motor units may fatigue and develop little or no tension but continue to use O2, thereby resulting in a dissociation of cellular respiration from force generation. The present study used intact isolated single myocytes with differing fatigue resistance profiles to investigate the relationship between fatigue, tension development, and aerobic metabolism. Single Xenopus skeletal muscle myofibers were allocated to a fast-fatiguing (FF) or a slow-fatiguing (SF) group, based on the contraction frequency required to elicit a fall in tension to 60% of peak. Phosphorescence quenching of a porphyrin compound was used to determine Δ intracellular Po2 (PiO2; a proxy for V̇o2), and developed isometric tension was monitored to allow calculation of the time-integrated tension (TxT). Although peak ΔPiO2 was not different between groups ( P = 0.36), peak tension was lower ( P < 0.05) in SF vs. FF (1.97 ± 0. 17 V vs. 2. 73 ± 0.30 V, respectively) and time to 60% of peak tension was significantly longer in SF vs. FF (242 ± 10 s vs. 203 ± 10 s, respectively). Before fatigue, both ΔPiO2 and TxT rose proportionally with contraction frequency in SF and FF, resulting in ΔPiO2/TxT being identical between groups. At fatigue, TxT fell dramatically in both groups, but ΔPiO2 decreased proportionately only in the FF group, resulting in an increase in ΔPiO2/TxT in the SF group relative to the prefatigue condition. These data show that more fatigue-resistant fibers maintain aerobic metabolism as they fatigue, resulting in an increased O2 cost of contractions that could contribute to the V̇o2 slow component seen in whole body exercise.

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Mechanisms of pHi control and relationships between tension and pHi in human subcutaneous small arteries

AJP Cell Physiology ◽

10.1152/ajpcell.1995.268.3.c580 ◽

1995 ◽

Vol 268 (3) ◽

pp. C580-C589 ◽

Cited By ~ 9

Author(s):

P. Carr ◽

W. McKinnon ◽

L. Poston

Keyword(s):

Isometric Tension ◽

Disulfonic Acid ◽

Physiological Salt Solution ◽

Ang Ii ◽

Tension Development ◽

Small Arteries ◽

Transport Inhibitor ◽

Acid Load ◽

Ethanesulfonic Acid

Intracellular pH (pHi) control and relationships between pHi and tension have been investigated in human subcutaneous small arteries. Isometric tension and pHi (using 2',7'-bis(carboxyethyl)- 5(6)-carboxyfluorescein) were estimated simultaneously. pHi recovery from an acute acid load was dependent on external Na+ and partially inhibited by the absence of HCO3(-) [N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution] or by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In an HCO3(-)-buffered physiological salt solution (PSS), pHi recovery was partially blocked by hexamethylene amiloride (HMA), an inhibitor of Na+/H+ exchange, and completely blocked by DIDS and HMA together. Intracellular Cl- depletion of arteries did not affect the rate of pHi recovery in PSS from an acid load. pHi recovery from acute alkalosis was unaffected by external Na+ removal, reduced in HEPES buffer, and abolished by removal of external Cl-. These data suggest that human small arteries maintain pHi by Na+/H+ exchange and Na(+)-dependent HCO3(-) exchange in response to an acid load, and Na(+)-independent Cl-/HCO3(-) exchange to counteract intracellular alkalosis. Norepinephrine (NE)-, endothelin-1 (ET-1)-, arginine vasopressin (AVP)-, and K(+)-induced tension did not alter pHi in PSS, but there was a small fall with angiotensin II (ANG II). In HEPES, stimulation with K+, NE, ANG II, or AVP led to a fall in pHi, but this did not occur with ET-1. It is therefore unlikely in vivo that an increase in pHi in these arteries would be involved in either tension development or growth induced by these agonists.

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Active State in Heart Muscle

The Journal of General Physiology ◽

10.1085/jgp.50.3.661 ◽

1967 ◽

Vol 50 (3) ◽

pp. 661-676 ◽

Cited By ~ 81

Author(s):

Edmund H. Sonnenblick

Keyword(s):

Heart Muscle ◽

Mechanical Response ◽

Electrical Stimulus ◽

Isometric Tension ◽

Maximum Intensity ◽

Active State ◽

Tension Development ◽

Peak Tension ◽

Time To Peak ◽

Time Required

The course of active state in heart muscle has been analyzed using a modified quick release method. The onset of maximum active state was found to be delayed, requiring 110–500 msec from time of stimulation, while the time to peak isometric tension required 250–650 msec. Further, the time from stimulation to peak tension was linearly related to the time required to establish maximum intensity of active state as well as to the duration of maximum active state. The duration of maximum active state was prolonged (90–220 msec), occupying most of the latter half of the rising phase of the isometric contraction. Norepinephrine (10-5 M) shortened the latency from electrical stimulus to mechanical response, accelerated the onset of maximum active state, increased its intensity, decreased its duration, and accelerated its rate of decline. These changes were accompanied by an increase in the rate of tension development and the tension developed while the time from stimulation to peak isometric tension was abbreviated. Similar findings were shown for strophanthidin (1 µg/ml) although lesser decrements in the duration of maximum active state and time to peak tension were found than with norepinephrine for similar increments in the maximum intensity of active state.

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Influence of aldosterone on isometric tension development in the rat heart

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.204.6.1001 ◽

1963 ◽

Vol 204 (6) ◽

pp. 1001-1004 ◽

Cited By ~ 5

Author(s):

William C. Ullrick ◽

Robert L. Hazelwood

Keyword(s):

Heart Muscle ◽

Rat Heart ◽

Isolated Rat Heart ◽

Isometric Tension ◽

Muscle Performance ◽

Tension Development ◽

Tension Time ◽

Isometric Twitch

Isometric twitch curves were recorded from preparations of rat heart trabeculae carneae removed from normal or adrenalectomized animals, or from normal animals injected for 3 days with saline or with 3 µg/day of d-aldosterone. Preparations from normal and from adrenalectomized animals were stimulated for 60 min in aldosterone-free Ringer's solution, or for 30 min in aldosterone-free Ringer's followed by 30 min in Ringer's containing 3 x 10–4 µg/ml of d-aldosterone. For a number of preparations from adrenalectomized animals the concentration of aldosterone was increased to 3 x 10–1 µg/ml. Regardless of treatment, all preparations were stimulated for a total of 1 hr at a rate of approximately 395/min; subsequently the recorded twitch curves were analyzed for peak tension development and for tension-time area. Although adrenalectomy tended to lower these variables of in vitro heart muscle performance, aldosterone, either administered in vivo or added directly to the isolated muscle bath, was without influence. It is concluded that aldosterone in the concentrations used does not alter the isometric tension characteristics of isolated rat heart muscle.

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Endotoxemia-induced myocardial dysfunction is not associated with changes in myofilament Ca2+responsiveness

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.2.h580 ◽

1998 ◽

Vol 274 (2) ◽

pp. H580-H590 ◽

Cited By ~ 7

Author(s):

Sherri L. Rigby ◽

Polly A. Hofmann ◽

Juming Zhong ◽

H. Richard Adams ◽

Leona J. Rubin

Keyword(s):

Ventricular Myocytes ◽

Contractile Function ◽

Myocardial Dysfunction ◽

Isometric Tension ◽

Saline Control ◽

Tension Development ◽

Maximal Tension ◽

Myocardial Contractile ◽

The Relationship

Myocardial contractile function is depressed after onset of endotoxemia and is intrinsic to the ventricular myocyte. We tested the hypothesis that decreased Ca2+ responsiveness of the contractile myofilaments underlies this inotropic depression. Specifically, we evaluated the relationship between Ca2+ and unloaded cell shortening and isometric tension development of skinned guinea pig ventricular myocytes. Myocytes were isolated 4 h after intraperitoneal injection of 4 mg/kg Escherichia colilipopolysaccharide (LPS) or saline (control; Ctl). Myofilament Ca2+ responsiveness assessed by image analysis of shortening of skinned myocytes at pH 7.0 was not different between Ctl [pCa value that resulted in half-maximal shortening (pCa50): 5.78 ± 0.04] and LPS (pCa50: 5.72 ± 0.02). Similarly, myofilament Ca2+ responsiveness measured by isometric tension of skinned myocytes was not different between Ctl (pCa50: 5.73 ± 0.02) and LPS (pCa50: 5.76 ± 0.02). Maximal tension generated by LPS myocytes (2.89 ± 0.23 g/mm2) was significantly less ( P < 0.05) than Ctl (3.75 ± 0.34 g/mm2). However, when myocytes were isolated and skinned in the presence of protease inhibitors, maximal tension generated by LPS myocytes (3.53 ± 0.98 g/mm2) was similar to Ctl (3.01 ± 0.80 g/mm2). We conclude that in vivo administration of LPS resulting in endotoxemia without shock does not alter myofilament Ca2+ responsiveness of ventricular myocytes. Rather, reduced contractility is more likely a result of decreased Ca2+ availability because systolic Ca2+ transients of fura 2-loaded LPS myocytes were significantly decreased ( P < 0.05) compared with Ctl myocytes.

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