scholarly journals Length and PKA Dependence of Force Generation and Loaded Shortening in Porcine Cardiac Myocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kerry S. McDonald ◽  
Laurin M. Hanft ◽  
Timothy L. Domeier ◽  
Craig A. Emter

In healthy hearts, ventricular ejection is determined by three myofibrillar properties; force, force development rate, and rate of loaded shortening (i.e., power). The sarcomere length and PKA dependence of these mechanical properties were measured in porcine cardiac myocytes. Permeabilized myocytes were prepared from left ventricular free walls and myocyte preparations were calcium activated to yield ~50% maximal force after which isometric force was measured at varied sarcomere lengths. Porcine myocyte preparations exhibited two populations of length-tension relationships, one being shallower than the other. Moreover, myocytes with shallow length-tension relationships displayed steeper relationships following PKA. Sarcomere length-Ktrrelationships also were measured andKtrremained nearly constant over ~2.30 μm to ~1.90 μm and then increased at lengths below 1.90 μm. Loaded-shortening and peak-normalized power output was similar at ~2.30 μm and ~1.90 μm even during activations with the same [Ca2+], implicating a myofibrillar mechanism that sustains myocyte power at lower preloads. PKA increased myocyte power and yielded greater shortening-induced cooperative deactivation in myocytes, which likely provides a myofibrillar mechanism to assist ventricular relaxation. Overall, the bimodal distribution of myocyte length-tension relationships and the PKA-mediated changes in myocyte length-tension and power are likely important modulators of Frank-Starling relationships in mammalian hearts.

1997 ◽  
Vol 273 (5) ◽  
pp. H2428-H2435 ◽  
Author(s):  
Thomas Wannenburg ◽  
Paul M. L. Janssen ◽  
Dongsheng Fan ◽  
Pieter P. De Tombe

We tested the hypothesis that the Frank-Starling relationship is mediated by changes in the rate of cross-bridge detachment in cardiac muscle. We simultaneously measured isometric force development and the rate of ATP consumption at various levels of Ca2+ activation in skinned rat cardiac trabecular muscles at three sarcomere lengths (2.0, 2.1, and 2.2 μm). The maximum rate of ATP consumption was 1.5 nmol ⋅ s−1 ⋅ μl fiber vol−1, which represents an estimated adenosinetriphosphatase (ATPase) rate of ∼10 s−1 per myosin head at 24°C. The rate of ATP consumption was tightly and linearly coupled to the level of isometric force development, and changes in sarcomere length had no effect on the slope of the force-ATPase relationships. The average slope of the force-ATPase relationships was 15.5 pmol ⋅ mN−1 ⋅ mm−1. These results suggest that the mechanisms that underlie the Frank-Starling relationship in cardiac muscle do not involve changes in the kinetics of the apparent detachment step in the cross-bridge cycle.


1970 ◽  
Vol 117 (538) ◽  
pp. 257-260 ◽  
Author(s):  
R. E. Kendell ◽  
Jane Gourlay

Proof that two clinical syndromes are distinct entities depends on a demonstration that patients with features of both syndromes are less common than those with features only of the one or the other. The intermediate forms, the greys, must be shown to be less numerous than the blacks and the whites, which means in graphical terms that a bimodal distribution of scores must be demonstrated on some chosen dimension. The optimal dimension for this purpose is Fisher's discriminant function (Fisher, 1936; Rao, 1948), and it may be useful before proceeding further to describe how this is derived. From the universe of all patients with syndrome X (psychotic depression) or syndrome Y (neurotic depression) every patient is assigned to one or other category, and the two populations are then rated on a series of N items which comprise the recognized discriminators between the two syndromes. From these data the analysis produces a set of weights for the N items which maximizes the ratio of between group to within group variance. The effect of this is that, when a single weighted score is calculated for each patient by combining the weights of the relevant items, the overlap between the scores of members of the two populations, X and Y, is reduced to a minimum. If the distribution of the scores of X and Y combined is bimodal the validity of the distinction between the two is confirmed.


1994 ◽  
Vol 266 (2) ◽  
pp. H779-H786 ◽  
Author(s):  
P. Li ◽  
E. H. Sonnenblick ◽  
P. Anversa ◽  
J. M. Capasso

To determine whether changes in sarcomere length affect the inotropic response of the heart to angiotensin II (ANG II) differently in dilated and failing myocardium, papillary muscles were removed 2 days after infarction, and the effects of ANG II were studied at various muscle lengths. Myocardial infarction, which averaged 52% of the left ventricle inclusive of the interventricular septum, was characterized hemodynamically by left ventricular failure and right ventricular dysfunction. ANG II administration at 100% the muscle length where force development is maximal (Lmax) produced a 12% depression of developed tension in papillary muscles from noninfarcted ventricles and a 37% decrease in developed tension in the viable myocardium of infarcted rats. In contrast, at 85 and 92.5% Lmax and in the presence of ANG II, control muscles increased active tension by 16 and 1.0%, whereas muscles from coronary occluded hearts augmented developed tension by 13 and 22%, respectively. In conclusion, ANG II exerted a positive inotropic effect on rat myocardium at muscle lengths on the ascending limb of the Starling curve but a negative inotropic action at the muscle length normally associated with maximum force development. This phenomenon emphasizes that hormonal influences on the contractile state of the diseased heart may be modulated by the interaction of end-diastolic pressure, sarcomere length, and ventricular size and shape.


2007 ◽  
Vol 293 (1) ◽  
pp. R20-R29 ◽  
Author(s):  
István Ferenc Édes ◽  
Dániel Czuriga ◽  
Gábor Csányi ◽  
Stefan Chłopicki ◽  
Fabio A. Recchia ◽  
...  

The increase in Ca2+ sensitivity of isometric force development along with sarcomere length (SL) is considered as the basis of the Frank-Starling law of the heart, possibly involving the regulation of cross-bridge turnover kinetics. Therefore, the Ca2+ dependencies of isometric force production and of the cross-bridge-sensitive rate constant of force redevelopment ( ktr) were determined at different SLs (1.9 and 2.3 μm) in isolated human, murine, and porcine permeabilized cardiomyocytes. ktr was also determined in the presence of 10 mM inorganic phosphate (Pi), which interfered with the force-generating cross-bridge transitions. The increases in Ca2+ sensitivities of force with SL were very similar in human, murine, and porcine cardiomyocytes (ΔpCa50: ∼0.11). ktr was higher ( P < 0.05) in mice than in humans or pigs at all Ca2+ concentrations ([Ca2+]) [maximum ktr ( ktr,max) at a SL of 1.9 μm and pCa 4.75: 1.33 ± 0.11, 7.44 ± 0.15, and 1.02 ± 0.05 s−1, in humans, mice, and pigs, respectively] but ktr did not depend on SL in any species. Moreover, when the ktr values for each species were expressed relative to their respective maxima, similar Ca2+ dependencies were obtained. Ten millimolar Pi decreased force to ∼60–65% and left ΔpCa50 unaltered in all three species. Pi increased ktr,max by a factor of ∼1.6 in humans and pigs and by a factor of ∼3 in mice, independent of SL. In conclusion, species differences exert a major influence on ktr, but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts.


Author(s):  
Halima Dziri ◽  
Mohamed Ali Cherni ◽  
Dorra Ben Sellem

Background: In this paper, we propose a new efficient method of radionuclide ventriculography image segmentation to estimate the left ventricular ejection fraction. This parameter is an important prognostic factor for diagnosing abnormal cardiac function. Methods: The proposed method combines the Chan-Vese and the mathematical morphology algorithms. It was applied to diastolic and systolic images obtained from the Nuclear Medicine Department of Salah AZAIEZ Institute.In order to validate our proposed method, we compare the obtained results to those of two methods of the literature. The first one is based on mathematical morphology, while the second one uses the basic Chan-Vese algorithm. To evaluate the quality of segmentation, we compute accuracy, positive predictive value and area under the ROC curve. We also compare the left ventricle ejection fraction estimated by our method to that of the reference given by the software of the gamma-camera and validated by the expert, using Pearson’s correlation coefficient, ANOVA test and linear regression. Results and conclusion: Static results show that the proposed method is very efficient in the detection of the left ventricle. The accuracy was 98.60%, higher than that of the other two methods (95.52% and 98.50%). Likewise, the positive predictive value was the highest (86.40% vs. 83.63% 71.82%). The area under the ROC curve was also the most important (0.998% vs. 0.926% 0.919%). On the other hand, Pearson's correlation coefficient was the highest (99% vs. 98% 37%). The correlation was significantly positive (p<0.001).


1986 ◽  
Vol 250 (4) ◽  
pp. H612-H619 ◽  
Author(s):  
R. S. Moreland ◽  
T. C. Major ◽  
R. C. Webb

This study characterizes isometric force development in response to ouabain and K+-free solution in isolated aortic strips from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR aortas were more sensitive to ouabain than those from WKY (threshold: SHR, 3.1 X 10(-5) M; WKY, 25.6 X 10(-5) M), and force development in response to 10(-3) M ouabain was greater in SHR (SHR, 586 +/- 51 mg; WKY, 245 +/- 24 mg). Monensin, a Na+ ionophore, potentiated contractile responses to ouabain, whereas amiloride, a Na+ channel blocker, and low Na+ solutions depressed contractile responses to ouabain. Contractile responses of SHR aortic strips to K+-free solution were faster than those of WKY aortic strips [time to half-maximal response (t1/2): SHR, 24 +/- 5 min; WKY, 47 +/- 4 min]. Maximal force development by aortic strips from SHR in response to K+-free solution was not different from that of WKY aortic strips (SHR, 808 +/- 34 mg; WKY, 750 +/- 37 mg). Monensin (10(-5) M) increased the rate of force development to K+-free solution to a greater extent in WKY aortic strips than in those from SHR (t1/2: SHR, 3 +/- 1 min; WKY, 4 +/- 2 min). Amiloride and low Na+ solution depressed contractile responses to K+-free solution in both SHR and WKY aortic strips. These observations demonstrate that SHR aortas are more responsive to ouabain and K+-free solution compared with WKY aortas. Contractile responses to ouabain and K+-free solution were sensitive to experimental interventions that alter transmembrane Na+ movements.(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
Casandra L. Niebel ◽  
Kelley C. Stewart ◽  
Takahiro Ohara ◽  
John J. Charonko ◽  
Pavlos P. Vlachos ◽  
...  

Left ventricular diastolic dysfunction (LVDD) is any abnormality in the filling of the left ventricle and is conventionally evaluated by analysis of the relaxation driven phase, or early diastole. LVDD has been shown to be a precursor to heart failure and the diagnosis and treatment for diastolic failure is less understood than for systolic failure. Diastole consists of two filling waves, early and late and is primarily dependent on ventricular relaxation and wall stiffness.


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