Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue

Narolska, N.A.; Loon, Ramon B. van; Boontje, Nicky M.; Zaremba, R.; Penas, Sonia Eiras; Russell, J.; Spiegelenberg, Stefan R.; Huybregts, M. A. J. M.; Visser, Frans C.; Jong, Jan Willem de; Velden, Jolanda van der; Stienen, G. J. M.

doi:10.1016/j.cardiores.2004.09.029

Cited by 69 publications

(66 citation statements)

References 30 publications

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“…We have previously shown a linear relationship between tension-cost and the ␣/␤-myosin ratio in both rat and mouse myocardium (25,36); a similar result was also reported in guinea-pig myocardium, albeit over a smaller range of ␣/␤-myosin ratio (43). Likewise, human ventricular myocardium displays a lower tension cost than human atrial myocardium that is largely explained by the difference in myosin composition (29). It should be noted that the tension-cost parameter is measured during an isometric contraction, that is, under conditions in which the cross-bridges are under high strain and developing force.…”

Section: Discussionsupporting

confidence: 75%

Development of contractile dysfunction in rat heart failure: hierarchy of cellular events

Daniëls

Naya²,

Rundell³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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The cellular mechanisms underlying the development of congestive heart failure (HF) are not well understood. Accordingly, we studied myocardial function in isolated right ventricular trabeculae from rats in which HF was induced by left ventricular myocardial infarction (MI). Both early-stage (12 wk post-MI; E-pMI) and late, end-stage HF (28 wk post-Mi; L-pMI) were studied. HF was associated with decreased sarcoplasmic reticulum Ca2+ ATPase protein levels (28% E-pMI; 52% L-pMI). HF affected neither sodium/calcium exchange, ryanodine receptor, nor phospholamban protein levels. Twitch force at saturating extracellular [Ca2+] was depressed in HF (30% E-pMI; 38% L-pMI), concomitant with a marked increase in sensitivity of twitch force toward extracellular [Ca2+] (26% E-pMI; 68% L-pMI). Ca2+-saturated myofilament force development in skinned trabeculae was unchanged in E-pMI but significantly depressed in L-pMI (45%). Tension-dependent ATP hydrolysis rate was depressed in L-pMI (49%), but not in E-pMI. Our results suggest a hierarchy of cellular events during the development of HF, starting with altered calcium homeostasis during the early phase followed by myofilament dysfunction at end-stage HF.

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Section: Discussionsupporting

confidence: 75%

Development of contractile dysfunction in rat heart failure: hierarchy of cellular events

Daniëls

Naya²,

Rundell³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…While these observations are suggestive of an important role of ␣-MHC expression in the human myocardium, such an extension of the present results to humans is premature since the ATP turnover rates for both ␣-MHC and ␤-MHC are slower in humans and not known for certain. However, recent evidence has suggested that the rate of ATP utilization by ␤-MHC is nearly fivefold slower in the human myocardium than in the rodent (36). In light of this observation, our model would predict that expression of ␣-MHC on the order of 10% would dramatically increase the rate of force development and thus enhance dP/dt max .…”

Section: Implications Of Altered Mhc Expression On the Rate Of Rise Omentioning

confidence: 84%

Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics

Locher¹,

Razumova²,

Stelzer³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Locher MR, Razumova MV, Stelzer JE, Norman HS, Patel JR, Moss RL. Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics. Am J Physiol Heart Circ Physiol 297: H247-H256, 2009. First published April 24, 2009 doi:10.1152/ajpheart.00922.2008The ventricles of small mammals express mostly ␣-myosin heavy chain (␣-MHC), a fast isoform, whereas the ventricles of large mammals, including humans, express ϳ10% ␣-MHC on a predominately ␤-MHC (slow isoform) background. In failing human ventricles, the amount of ␣-MHC is dramatically reduced, leading to the hypothesis that even small amounts of ␣-MHC on a predominately ␤-MHC background confer significantly higher rates of force development in healthy ventricles. To test this hypothesis, it is necessary to determine the fundamental rate constants of cross-bridge attachment (fapp) and detachment (gapp) for myosins composed of 100% ␣-MHC or ␤-MHC, which can then be used to calculate twitch time courses for muscles expressing variable ratios of MHC isoforms. In the present study, rat skinned trabeculae expressing either 100% ␣-MHC or 100% ␤-MHC were used to measure ATPase activity, isometric force, and the rate constant of force redevelopment (ktr) in solutions of varying Ca 2ϩ concentrations. The rate of ATP utilization was ϳ2.5-fold higher in preparations expressing 100% ␣-MHC compared with those expressing only ␤-MHC, whereas ktr was 2-fold faster in the ␣-MHC myocardium. From these variables, we calculated fapp to be approximately threefold higher for ␣-MHC than ␤-MHC and gapp to be twofold higher in ␣-MHC. Mathematical modeling of isometric twitches predicted that small increases in ␣-MHC significantly increased the rate of force development. These results suggest that low-level expression of ␣-MHC has significant effects on contraction kinetics.␣-myosin heavy chain; rate constants of cross-bridge attachment and detachment; rate of rise of force THE MYOSIN MOLECULE, a hexamer composed of two heavy chains (ϳ220 kDa) and four light chains (16 -25 kDa), is the principal component of the thick filament and is responsible for the generation of force in mammalian striated muscle. The rod-shaped COOH-terminal domain of the myosin molecule (light meromyosin) forms the backbone of the thick filament, whereas the globular NH 2 -terminus (subfragment 1) contains the actin-binding and catalytic domains (13). Thus, S1 is an important determinant of contractile speed and power developed in the mammalian myocardium.Two isoforms of myosin heavy chain (MHC), ␣ and ␤, have been identified in cardiac muscle (23). These MHC isoforms share 93% amino acid sequence homology (32), and yet they confer distinct functional properties to the myocardium: ␣-MHC has been shown to have markedly higher ATPase activity, faster shortening velocity (V max ), and faster rates of force development (42), whereas ␤-MHC exhibits a lower tension cost and is thus more efficient (1,24,40).Expression levels of the ventricular MHC isoforms are sp...

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“…Shifts in the relative expression of isoforms are common, and confer critical changes in the contractile strength and speed of the chamber contraction (Narolska et al, 2005a;Narolska et al, 2005b). Atrophy typically induces isoform transitions (Klein et al., 1992; Geenen et al, 1994;Tang et al, 2005), and cardiomyopathy generally leads to a loss of MyHC-α (Buttrick et al, 1991;Takahashi et al, 1992;Miyata et al, 2000;Reiser et al, 2001), at least in non-hibernators.…”

Section: Cardiac Myosin Isoform Expression In Ground Squirrelsmentioning

confidence: 99%

“…MyHC-α isoforms may contract 2-3 times faster, with generally lower force, but species-specific differences are apparent; average force can be similar between MyHC-α and MyHC-β (Sugiura et al, 1998;Alpert et al, 2002;Galler et al, 2002;Malmqvist et al, 2004;Narolska et al, 2005a;Narolska et al, 2005b). The expression of the isoforms varies by heart chamber, and by sex, age and mass of the individual (Cummins and Lambert, 1986;O'Neill et al, 1991;Reiser and Kline, 1998;Barrows et al, 2011).…”

Section: Cardiac Myosin Isoform Expression In Ground Squirrelsmentioning

confidence: 99%

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

Nelson

Rourke

2013

Journal of Experimental Biology

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SUMMARYDeep hibernators such as golden-mantled ground squirrels (Callospermophilus lateralis) have multiple challenges to cardiac function during low temperature torpor and subsequent arousals. As heart rates fall from over 300 beats min -1 to less than 10, chamber dilation and reduced cardiac output could lead to congestive myopathy. We performed echocardiography on a cohort of individuals prior to and after several months of hibernation. The left ventricular chamber exhibited eccentric and concentric hypertrophy during hibernation and thus calculated ventricular mass was ~30% greater. Ventricular ejection fraction was mildly reduced during hibernation but stroke volumes were greater due to the eccentric hypertrophy and dramatically increased diastolic filling volumes. Globally, the systolic phase in hibernation was ~9.5 times longer, and the diastolic phase was 28× longer. Left atrial ejection generally was not observed during hibernation. Atrial ejection returned weakly during early arousal. Strain echocardiography assessed the velocity and total movement distance of contraction and relaxation for regional ventricular segments in active and early arousal states. Myocardial systolic strain during early arousal was significantly greater than the active state, indicating greater total contractile movement. This mirrored the increased ventricular ejection fraction noted with early arousal. However, strain rates were slower during early arousal than during the active period, particularly systolic strain, which was 33% of active, compared with the rate of diastolic strain, which was 67% of active. As heart rate rose during the arousal period, myocardial velocities and strain rates also increased; this was matched closely by cardiac output. Curiously, though heart rates were only 26% of active heart rates during early arousal, the cardiac output was nearly 40% of the active state, suggesting an efficient pumping system. We further analyzed proportions of cardiac myosin heavy-chain (MyHC) isoforms in a separate cohort of squirrels over 5 months, including time points before hibernation, during hibernation and just prior to emergence. Hibernating individuals were maintained in both a 4°C cold room and a 20°C warm room. Measured by SDS-PAGE, relative percentages of cardiac MyHC alpha were increased during hibernation, at both hibernacula temperatures. A potential increase in contractile speed, and power, from more abundant MyHC alpha may aid force generation at low temperature and at low heart rates. Unlike many models of cardiomyopathies where the alpha isoform is replaced by the beta isoform in order to reduce oxygen consumption, ground squirrels demonstrate a potential cardioprotective mechanism to maintain cardiac output during torpor. Received 25 March 2013; Accepted 4 September 2013Key words: hibernation, MyHC, echocardiogram, atrial contraction, cardiac function. Echocardiogram and myosin of hibernatorsThe myosin heavy-chain isoforms (MyHC) are crucial determinants of contractile performance in cardiac muscle t...

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Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue

Abstract: These results clearly indicate that even a minor shift in MHC isoform expression has considerable impact on cardiac performance in human tissue.

Cited by 69 publications

References 30 publications

Development of contractile dysfunction in rat heart failure: hierarchy of cellular events

Development of contractile dysfunction in rat heart failure: hierarchy of cellular events

Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

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