Myofilament properties comprise the rate-limiting step  for cardiac relaxation at body temperature in the rat

Janssen, Paul M.L.; Stull, Linda B.; Marbán, Eduardo

doi:10.1152/ajpheart.00595.2001

Cited by 131 publications

(212 citation statements)

References 30 publications

Supporting

Mentioning

183

Contrasting

Order By: Relevance

“…It is well known that lowering the temperature causes a slow down of contractile kinetics, and thus the lower end of the kinetic range is more easily assessed at room temperature. Figure 5 shows data from our previous work in which the same muscles were studied at both room temperature as well as body temperature and, in addition, under a variety of lengths and frequencies at both temperatures (23). Figure 5A shows average values for the same analysis on a wide variety of protocols in rat trabeculae.…”

Section: Resultsmentioning

confidence: 99%

“…The majority of data presented in this article are derived from muscle studies published in the past 5 yr by our laboratory with or without the help of collaborating laboratories (18,19,21,23,29,36), with the remaining experiments having been conducted for this study specifically. However, the specific data in this article were collected during those studies but were not analyzed or presented in/for those studies.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

Janssen

2010

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Janssen PM. Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere. Am J Physiol Heart Circ Physiol 299: H1092-H1099, 2010. First published July 23, 2010; doi:10.1152/ajpheart.00417.2010.-The regulation of myocardial contraction and relaxation kinetics is currently incompletely understood. When the amplitude of contraction is increased via the Frank-Starling mechanism, the kinetics of the contraction slow down, but when the amplitude of contraction is increased with either an increase in heart rate or via ␤-adrenergic stimulation, the kinetics speed up. It is also unknown how physiological mechanisms affect the kinetics of contraction versus those of relaxation. We investigated contraction-relaxation coupling in isolated trabeculae from the mouse and rat and stimulated them to contract at various temperatures, frequencies, preloads, and in the absence and presence of ␤-adrenergic stimulation. In each muscle at least 16 different conditions were assessed, and the correlation coefficient of the speed of contraction and relaxation was very close (generally Ͼ0.98). Moreover, in all but one of the analyzed murine strains, the ratio of the minimum rate of the derivative of force development (dF/dt) over maximum dF/dt was not significantly different. Only in trabeculae isolated from myosin-binding protein-C mutant mice was this ratio significantly lower (0.61 Ϯ 0.07 vs. 0.84 Ϯ 0.02 in 11 other strains of mice). Within each strain, this ratio was unaffected by modulation of length, frequency, or ␤-adrenergic stimulation. Rat trabeculae showed identical results; the balance between kinetics of contraction and relaxation was generally constant (0.85 Ϯ 0.04). Because of the great variety in underlying excitation-contraction coupling in the assessed strains, we concluded that contraction-relation coupling is a property residing in the cardiac sarcomere. trabeculae; mouse; rat; calcium handling; exitation-contraction coupling NOT ONLY IS THE FORCEFULNESS of contraction of the myocardium important, but the speed at which the contraction and relaxation takes place is a critical determinant of cardiac performance. When the heart cannot relax sufficiently fast, and as a result cannot adequately fill the ventricles before the next excitation stimulus, cardiac output is compromised. Whether called heart failure with preserved ejection fraction, diastolic dysfunction, or impaired myocardial relaxation, inadequate relaxation kinetics of the heart pose a clinical problem that affects a very large fraction of patients with cardiac pathology (5, 16). To treat, manage, or possibly cure impaired myocardial relaxation kinetics, a better understanding of the cardiac relaxation process at the level of the cardiac muscle is warranted. It has become increasingly clear that myocardial relaxation is not a mere passive process that follows a contraction but a complex systems biology property that is brought about by a multitude of factors (30). These factors include cytosolic Ca 2ϩ ...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

Janssen

2010

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, relaxation of the myocardium under loaded conditions as it occurs in vivo is likely governed in a significantly different manner. Several studies indicate that the myofilament properties play a prominent role in governing the rate of myocardial relaxation [9,47]. Moreover, recent work by us [48], and others [38] argues in favor of a significant involvement of the myofilaments in FDAR.…”

Section: Role Of Myofilaments In Fdarmentioning

confidence: 99%

“…A prime example is that rats and mice are reported to have a negative force-frequency response, but this however has recently been shown to be true mainly, or only, for non-physiological conditions. Under near physiological conditions, and within their respective in vivo heart rate range, the FFR in small rodents is slightly positive or nearly flat, but not negative [2,8,9]. There are two main experimental reasons that have led to the still widely held misconception that the FFR is negative in rats and mice.…”

Section: Role Of Experimental Conditions On the Force Frequency Responsementioning

confidence: 99%

Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

Janssen

Periasamy

2007

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

“…This force-frequency behavior is determined by both calcium handling and myofilament properties (26). It has been shown that the integrated dynamic balance of the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) is the primary cellular mechanism responsible for the force-frequency relation (FFR) and is determined by sarcoplasmic reticulum (SR) Ca 2ϩ load and Ca 2ϩ flux through the sarcolemma via L-type Ca 2ϩ channels and the Na ϩ -Ca 2ϩ exchanger (13).…”

mentioning

confidence: 99%

Levosimendan restores the positive force-frequency relation in heart failure

Masutani

Cheng

Tachibana

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Masutani S, Cheng HJ, Tachibana H, Little WC, Cheng CP. Levosimendan restores the positive force-frequency relation in heart failure. Am J Physiol Heart Circ Physiol 301: H488 -H496, 2011. First published May 13, 2011; doi:10.1152/ajpheart.01116.2010.-Frequency potentiation of contractile function is a major mechanism of the increase in myocardial performance during exercise. In heart failure (HF), this positive force-frequency relation is impaired, and the abnormal left ventricular (LV)-arterial coupling is exacerbated by tachycardia. A myofilament Ca 2ϩ sensitizer, levosimendan, has been shown to improve exercise tolerance in HF. This may be due to its beneficial actions on the force-frequency relation and LV-arterial coupling (end-systolic elastance/arterial elastance, EES/EA). We assessed the effects of therapeutic doses of levosimendan on the forcefrequency relation and EES/EA in nine conscious dogs after pacinginduced HF using pressure-volume analysis. Before HF, pacing tachycardia increased E ES, shortened , and did not impair EES/EA and mechanical efficiency (stroke work/pressure-volume area, SW/PVA). In contrast, after HF, pacing at 140, 160, 180, and 200 beat/min (bpm) produced smaller a increase of EES or less shortening of , whereas EES/EA (from 0.56 at baseline to 0.42 at 200 bpm) and SW/PVA (from 0.52 at baseline to 0.43 at 200 bpm) progressively decreased. With levosimendan, basal E ES increased 27% (6.2 mmHg/ml), decreased 11% (40.8 ms), EES/EA increased 34% (0.75), and SW/PVA improved by 15% (0.60). During tachycardia, E ES further increased by 23%, 37%, 68%, and 89%; decreased by 9%, 12%, 15%, and 17%; and EES/EA was augmented by 11%, 16%, 31%, and 33%, incrementally, with pacing rate. SW/PVA was improved (0.61 to 0.64). In conclusion, in HF, treatment with levosimendan restores the normal positive LV systolic and diastolic force-frequency relation and prevents tachycardia-induced adverse effect on LV-arterial coupling and mechanical efficiency.drugs; contractility; diastole; heart rate UNDER NORMAL CONDITIONS, an increase in heart rate (HR) augments myocardial contractility and the rate of relaxation (15,39,44). This force-frequency behavior is determined by both calcium handling and myofilament properties (26). It has been shown that the integrated dynamic balance of the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) is the primary cellular mechanism responsible for the force-frequency relation (FFR) and is determined by sarcoplasmic reticulum (SR) Ca 2ϩ load and Ca 2ϩ flux through the sarcolemma via L-type Ca 2ϩ channels and the Na ϩ -Ca 2ϩ exchanger (13). The positive FFR and relaxation-frequency relation (RFR) enhance cardiac performance during stress or exercise (7,36,39,44,52). In heart failure (HF), the positive FFR and RFR are impaired (16,24,28,29,44), and the abnormal left ventricular (LV)-arterial coupling is exacerbated by tachycardia. This contributes to exercise intolerance in HF (44, 52). The altered responses of LV contraction and relaxation to HR in HF may at least partially ...

show abstract

Myofilament properties comprise the rate-limiting step for cardiac relaxation at body temperature in the rat

Cited by 131 publications

References 30 publications

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

Levosimendan restores the positive force-frequency relation in heart failure

Contact Info

Product

Resources

About