scholarly journals Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function

2021 ◽  
Vol 153 (8) ◽  
Author(s):  
June-Chiew Han ◽  
Kenneth Tran ◽  
David J. Crossman ◽  
Claire L. Curl ◽  
Parisa Koutsifeli ◽  
...  
Keyword(s):  
Energy Efficiency ◽  
Energy Expenditure ◽  
Cardiac Hypertrophy ◽  
Mechanical Performance ◽  
Force Production ◽  
Premature Mortality ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Heat Output ◽  
Cross Bridge

Increased heart size is a major risk factor for heart failure and premature mortality. Although abnormal heart growth subsequent to hypertension often accompanies disturbances in mechano-energetics and cardiac efficiency, it remains uncertain whether hypertrophy is their primary driver. In this study, we aimed to investigate the direct association between cardiac hypertrophy and cardiac mechano-energetics using isolated left-ventricular trabeculae from a rat model of primary cardiac hypertrophy and its control. We evaluated energy expenditure (heat output) and mechanical performance (force length work production) simultaneously at a range of preloads and afterloads in a microcalorimeter, we determined energy expenditure related to cross-bridge cycling and Ca2+ cycling (activation heat), and we quantified energy efficiency. Rats with cardiac hypertrophy exhibited increased cardiomyocyte length and width. Their trabeculae showed mechanical impairment, evidenced by lower force production, extent and kinetics of shortening, and work output. Lower force was associated with lower energy expenditure related to Ca2+ cycling and to cross-bridge cycling. However, despite these changes, both mechanical and cross-bridge energy efficiency were unchanged. Our results show that cardiac hypertrophy is associated with impaired contractile performance and with preservation of energy efficiency. These findings provide direction for future investigations targeting metabolic and Ca2+ disturbances underlying cardiac mechanical and energetic impairment in primary cardiac hypertrophy.

scholarly journals Energy expenditure by Ba2+contracture in rat ventricular slices derives from cross-bridge cycling

1999 ◽  
Vol 277 (1) ◽  
pp. H74-H79 ◽  
Author(s):  
Hisaharu Kohzuki ◽  
Hiromi Misawa ◽  
Susumu Sakata ◽  
Yoshimi Ohga ◽  
Hiroyuki Suga ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Energy Expenditure ◽  
Cyclopiazonic Acid ◽  
Left Ventricular ◽  
Basal Metabolism ◽  
Dependent Manner ◽  
Tyrode Solution ◽  
Cross Bridge ◽  
Butanedione Monoxime ◽  
Dose Dependent

To clarify the energy-expenditure mechanism during Ba2+ contracture of mechanically unloaded rat left ventricular (LV) slices, we measured myocardial O2 consumption (V˙o 2) of quiescent slices in Ca2+-free Tyrode solution andV˙o 2 during Ba2+ contracture by substituting Ca2+ with Ba2+. We then investigated the effects of cyclopiazonic acid (CPA) and 2,3-butanedione monoxime (BDM) on the Ba2+ contractureV˙o 2. The Ca2+-freeV˙o 2 corresponds to that of basal metabolism (2.32 ± 0.53 ml O2 ⋅ min−1 ⋅ 100 g LV−1). Ba2+ increased theV˙o 2 in a dose-dependent manner (from 0.3 to 3.0 mmol/l) from 110 to 150% of basal metabolic V˙o 2. Blockade of the sarcoplasmic reticulum (SR) Ca2+ pump by CPA (10 μmol/l) did not at all decrease the Ba2+-activatedV˙o 2. BDM (5 mmol/l), which specifically inhibits cross-bridge cycling, reduced the Ba2+activatedV˙o 2 almost to basal metabolic V˙o 2. These energetic results revealed that the Ba2+-activatedV˙o 2 was used for the cross-bridge cycling but not for the Ca2+ handling by the SR Ca2+ pump.

A unique micromechanocalorimeter for simultaneous measurement of heat rate and force production of cardiac trabeculae carneae

2009 ◽  
Vol 107 (3) ◽  
pp. 946-951 ◽  
Author(s):  
June-Chiew Han ◽  
Andrew J. Taberner ◽  
Robert S. Kirton ◽  
Poul M. Nielsen ◽  
Nicholas P. Smith ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Thermal Performance ◽  
Mechanical Performance ◽  
Force Production ◽  
Muscle Length ◽  
Heat Rate ◽  
Force Transducer ◽  
Muscle Energetics ◽  
Flow Through

To study cardiac muscle energetics quantitatively, it is of paramount importance to measure, simultaneously, mechanical and thermal performance. Ideally, this should be achieved under conditions that minimize the risk of tissue anoxia, especially under high rates of energy expenditure. In vitro, this consideration necessitates the use of preparations of small radial dimensions. To that end, we have constructed a unique micromechanocalorimeter, consisting of an open-ended flow-through microcalorimeter, a force transducer, and a pair of muscle-length actuators. The device enables the metabolic and mechanical performance of cardiac trabeculae carneae to be investigated for prolonged periods in a continuously replenished oxygen- and nutrient-rich environment.

Myocardial cross-bridge kinetics in transition to failure in Dahl salt-sensitive rats

2001 ◽  
Vol 281 (3) ◽  
pp. H1390-H1396 ◽  
Author(s):  
Daniel T. McCurdy ◽  
Bradley M. Palmer ◽  
David W. Maughan ◽  
Martin M. LeWinter
Keyword(s):  
Mechanical Performance ◽  
Dynamic Stiffness ◽  
Calcium Sensitivity ◽  
Left Ventricular ◽  
Isometric Tension ◽  
High Salt Diet ◽  
Salt Diet ◽  
Cross Bridge ◽  
Cross Bridges

The role of altered cross-bridge kinetics during the transition from cardiac hypertrophy to failure is poorly defined. We examined this in Dahl salt-sensitive (DS) rats, which develop hypertrophy and failure when fed a high-salt diet (HS). DS rats fed a low-salt diet were controls. Serial echocardiography disclosed compensated hypertrophy at 6 wk of HS, followed by progressive dilatation and impaired function. Mechanical properties of skinned left ventricular papillary muscle strips were analyzed at 6 wk of HS and then during failure (12 wk HS) by applying small amplitude (0.125%) length perturbations over a range of calcium concentrations. No differences in isometric tension-calcium relations or cross-bridge cycling kinetics or mechanical function were found at 6 wk. In contrast, 12 wk HS strips exhibited increased calcium sensitivity of isometric tension, decreased frequency of minimal dynamic stiffness, and a decreased range of frequencies over which cross bridges produce work and power. Thus the transition from hypertrophy to heart failure in DS rats is characterized by major changes in cross-bridge cycling kinetics and mechanical performance.

A Novel Push-pull Central-lever Mechanism Reduces Peak Forces and Energy-cost Compared to Hand-rim Wheelchair Propulsion During a Controlled Lab-based Experiment

2021 ◽  
Author(s):  
Thomas A le Rütte ◽  
Fransisca Trigo ◽  
Luca Bessems ◽  
Lucas HV van der Woude ◽  
Riemer JK Vegter
Keyword(s):  
Energy Expenditure ◽  
Repeated Measures ◽  
Perceived Exertion ◽  
Force Production ◽  
Mechanical Efficiency ◽  
Wheelchair Propulsion ◽  
Physiological Strain ◽  
Wheelchair Users ◽  
Propulsion Mechanism ◽  
Push And Pull

Abstract Background: Hand-rim wheelchair propulsion is straining and mechanically inefficient, often leading to upper limb complaints. Previous push-pull lever propulsion mechanisms have shown to perform better or equal in efficiency and physiological strain. Propulsion biomechanics have not been evaluated thus far. A novel push-pull central-lever propulsion mechanism is compared to conventional hand-rim wheelchair propulsion, using both physiological and biomechanical outcomes under low-intensity steady-state conditions on a motor driven treadmill. Methods: In this 5-day (distributed over a maximum of 21 days) between-group experiment, 30 able-bodied novices performed 60 minutes (5x3x4 min) of practice in either the push-pull central lever wheelchair (n=15) or the hand-rim wheelchair (n=15). At the first and final sessions cardiopulmonary strain, propulsion kinematics and force production were determined in both instrumented propulsion mechanisms. Repeated measures ANOVA evaluated between (propulsion mechanism type), within (over practice) and interaction effects. Results: Over practice, both groups significantly improved on all outcome measures. After practice the peak forces during the push and pull phase of lever propulsion were considerably lower compared to those in the handrim push phase (42±10 & 46±10 vs 63±21 N). Concomitantly, energy expenditure was found to be lower as well (263±45 vs 298±59 W), on the other hand gross mechanical efficiency (6.4±1.5 vs 5.9±1.3 %), heart-rate (97±10 vs 98±10 bpm) and perceived exertion (9±2 vs 10±1) were not significantly different between modes.Conclusion: The current study shows the potential benefits of the newly designed push-pull central-lever propulsion mechanism over regular hand rim wheelchair propulsion. The much lower forces and energy expenditure might help to reduce the strain on the upper extremities and thus prevent the development of overuse injury. This proof of concept in a controlled laboratory experiment warrants continued experimental research in wheelchair-users during daily life.

scholarly journals Inhibition of the canonical Wnt signaling pathway by a β-catenin/CBP inhibitor prevents heart failure by ameliorating cardiac hypertrophy and fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thanachai Methatham ◽  
Shota Tomida ◽  
Natsuka Kimura ◽  
Yasushi Imai ◽  
Kenichi Aizawa
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Left Ventricular ◽  
Cardiac Wall ◽  
Macrophage Marker ◽  
Glycolysis Pathway ◽  
Canonical Wnt ◽  
Macrophage Accumulation

AbstractIn heart failure (HF) caused by hypertension, the myocyte size increases, and the cardiac wall thickens. A low-molecular-weight compound called ICG001 impedes β-catenin-mediated gene transcription, thereby protecting both the heart and kidney. However, the HF-preventive mechanisms of ICG001 remain unclear. Hence, we investigated how ICG001 can prevent cardiac hypertrophy and fibrosis induced by transverse aortic constriction (TAC). Four weeks after TAC, ICG001 attenuated cardiac hypertrophy and fibrosis in the left ventricular wall. The TAC mice treated with ICG001 showed a decrease in the following: mRNA expression of brain natriuretic peptide (Bnp), Klf5, fibronectin, β-MHC, and β-catenin, number of cells expressing the macrophage marker CD68 shown in immunohistochemistry, and macrophage accumulation shown in flow cytometry. Moreover, ICG001 may mediate the substrates in the glycolysis pathway and the distinct alteration of oxidative stress during cardiac hypertrophy and HF. In conclusion, ICG001 is a potential drug that may prevent cardiac hypertrophy and fibrosis by regulating KLF5, immune activation, and the Wnt/β-catenin signaling pathway and inhibiting the inflammatory response involving macrophages.

Heat production of rat anococcygeus muscle during isometric contraction

1988 ◽  
Vol 255 (4) ◽  
pp. C536-C542 ◽  
Author(s):  
J. S. Walker ◽  
I. R. Wendt ◽  
C. L. Gibbs
Keyword(s):  
Energy Expenditure ◽  
Heat Production ◽  
Progressive Increase ◽  
Isometric Contractions ◽  
Shortening Velocity ◽  
Anococcygeus Muscle ◽  
Cross Bridge ◽  
Time Integral ◽  
Rat Anococcygeus Muscle ◽  
Cross Bridges

Heat production, unloaded shortening velocity (Vus), and load-bearing capacity (LBC) were studied in the isolated rat anococcygeus muscle during isometric contractions at 27 degrees C. The relation between the total suprabasal heat produced and the stress-time integral for isometric contractions of various durations was curvilinear, demonstrating a decreasing slope as contractile duration increased. The rate of heat production at 600 s was approximately 68% of the peak value of 6.55 mW/g that occurred at 10 s. At the same time, force rose from a mean of 92 mN/mm2 at 10 s to a value of 140 mN/mm2 at 600 s. This produced a nearly threefold increase in the economy of force maintenance. The decline in the rate of heat production was accompanied by a decline in Vus from 0.56 Lo/s at 10 s to 0.28 Lo/s at 600 s, where Lo is the length for optimal force development. This suggests the fall in the rate of heat production was caused, at least in part, by a slowing of cross-bridge kinetics. The ratio of LBC to developed tension at 10 s was not significantly different from the ratio at 600 s, suggesting that the increase in tension was due to an increased number of attached cross bridges. The decline in heat production, therefore, appears contradictory, since an increased number of attached cross bridges would predict an increased rate of energy expenditure. The observations can be reconciled if either 1) the increase in force is caused by a progressive increase in the attachment time of a constant number of cross bridges that cycle at a lower frequency or 2) the decline in energy expenditure caused by the slowing of cross-bridge cycling is sufficient to mask the increase caused by the recruitment of additional cross bridges.

Role of sympathetic nerves during developing cardiac hypertrophy in Grollman hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H818-H825
Author(s):  
R. J. Tomanek ◽  
D. W. Carlson ◽  
P. J. Palmer ◽  
R. K. Bhatnagar
Keyword(s):  
Cardiac Hypertrophy ◽  
Renovascular Hypertension ◽  
Volume Expansion ◽  
Peripheral Resistance ◽  
Sympathetic Nerves ◽  
Left Ventricular ◽  
Lv Function ◽  
Hypertensive Rats ◽  
Anterior Portion ◽  
Mitochondrial Volume

Peak left ventricular (LV) function, during rapid volume expansion, and cardiocyte structure were studied in rats with developing cardiac hypertrophy in response to Grollman hypertension (1 kidney, 1 figure 8) after chemical sympathectomy with 6-hydroxydopamine. This form of renovascular hypertension led to the same magnitude of hypertrophy in rats with or without sympathectomy. Indices of peak LV function, measured during acute volume expansion, tended to be normal or slightly higher in hypertensive rats than in controls. Sympathectomy in rats with hypertension significantly improved cardiac and stroke indices while decreasing total peripheral resistance at peak cardiac output. Despite similar magnitudes of LV hypertrophy (LVH) in the two hypertensive groups, cardiocytes in sympathectomized rats had higher mitochondrial volume densities and slightly lower myofibrillar volume densities. After regional sympathectomy of the anterior portion of the LV with phenol, mitochondrial volume density increased by 21% in hypertensive rats with LVH. These data indicate that, during the development of LVH in response to renovascular hypertension, sympathetic nerves do not contribute to the magnitude of LVH but may limit improvement in peak LV performance in response to increased preload. However, sympathetic nerves do play a role in the regulation of mitochondrial and myofibril growth.

The origin of passive force enhancement in skeletal muscle

2008 ◽  
Vol 294 (1) ◽  
pp. C74-C78 ◽  
Author(s):  
V. Joumaa ◽  
D. E. Rassier ◽  
T. R. Leonard ◽  
W. Herzog
Keyword(s):  
Calcium Concentration ◽  
Force Production ◽  
Primary Source ◽  
Passive Force ◽  
Active Force ◽  
Force Enhancement ◽  
Bridge Formation ◽  
Calcium Dependent ◽  
Cross Bridge ◽  
High Calcium

The aim of the present study was to test whether titin is a calcium-dependent spring and whether it is the source of the passive force enhancement observed in muscle and single fiber preparations. We measured passive force enhancement in troponin C (TnC)-depleted myofibrils in which active force production was completely eliminated. The TnC-depleted construct allowed for the investigation of the effect of calcium concentration on passive force, without the confounding effects of actin-myosin cross-bridge formation and active force production. Passive forces in TnC-depleted myofibrils ( n = 6) were 35.0 ± 2.9 nN/ μm2 when stretched to an average sarcomere length of 3.4 μm in a solution with low calcium concentration (pCa 8.0). Passive forces in the same myofibrils increased by 25% to 30% when stretches were performed in a solution with high calcium concentration (pCa 3.5). Since it is well accepted that titin is the primary source for passive force in rabbit psoas myofibrils and since the increase in passive force in TnC-depleted myofibrils was abolished after trypsin treatment, our results suggest that increasing calcium concentration is associated with increased titin stiffness. However, this calcium-induced titin stiffness accounted for only ∼25% of the passive force enhancement observed in intact myofibrils. Therefore, ∼75% of the normally occurring passive force enhancement remains unexplained. The findings of the present study suggest that passive force enhancement is partly caused by a calcium-induced increase in titin stiffness but also requires cross-bridge formation and/or active force production for full manifestation.

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