Auckland Bioengineering Institute


Work-loop calorimeter

See caption.
Section view of the calorimeter. The coloured arrow indicates the path and temperature increase of the fluid.

The ABI Bioinstrumentation Laboratory has developed the world’s only flow-through calorimeter for measuring simultaneously the mechanical (force, length) and energetic (heat production, mechanical work) properties of realistically-contracting individual heart muscles. Our device combines sensitive temperature sensors with a sophisticated laser-interferometer based force-length control system. Oxygen- and nutrient-rich solution flows over the muscle; in this way we can precisely expose the muscle to a wide variety of drugs.

We electrically stimulate the muscle, causing it to contract and create a force-length “work-loop” realistically modelled on the pressure-volume behaviour of the whole heart. With this device, we can programmatically vary the work done by a living heart muscle while measuring its energy consumption.

We measure the rate at which heat is produced by the muscle to 100 nW resolution while controlling muscle length to 2 nm resolution and force to 1 μN resolution. Experiments are conducted at a controlled temperature of up to 40 °C.

Research

Using this unique instrument our “experimental cardiac energetics” team have made some recent discoveries:

  • Pulmonary arterial hypertension reduces the efficiency of muscles from the right ventricle but does not affect those of the left ventricle.
  • Heart muscle samples from the right ventricle shorten faster yet are just as efficient as those from the left ventricle.
  • “Shortening heat” does indeed appear to arise in cardiac muscle.
  • “Activation heat” is independent of muscle length and can be estimated by the y-intercept of the heat-stress relation.
  • Salt-induced hypertension changes the shortening behaviour of the left ventricle but has no effect on peak work output or peak mechanical efficiency.
  • Despite others’ claims to the contrary, we find no evidence of dietary fish-oil improving cardiac efficiency.

The device is being used in several major ongoing studies:

  • Amy Garrett is developing methods for measuring energetic efficiency during time-varying afterloads.
  • Toan Pham is studying the underlying causes of cardiac dysfunction associated with cardiac hypertrophy.
  • Dr June-Chiew Han is using this instrument to compare the energetic performance of the muscle with that of the whole heart.
  • Dr Kenneth Tran is collecting data on the effect of Type 2 diabetes on cardiac efficiency for a Marsden and NHF study.

 

See caption.
Current members of the Experimental Team. Left to right: June-Chiew Han, Toan Pham, Kenneth Tran, Emily Lam Po Tang, Jarrah Dowrick

Researchers and graduate students


Engineering Team

Experimental Team

Collaborators

  • University of Melbourne (the hypertrophic heart rat study)
  • University of Kentucky (the failing human heart tissue study)
  • University of Michigan (the high-salt diet study)
  • University of Stuttgart (the cardiac-titin study)
  • A/Prof Nari Kim (Inje, Korea) has developed multi-scale mathematical models of heart tissue using data measured from this instrument.
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Funding partners

Publications


  1. Pham, T., L. Nisbet, A. Taberner, D. Loiselle, and J.-C. Han, Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae. The Journal of Physiology, 2018. (In press) https://doi.org/10.1113/JP275578 
  2. Tran, K., J.-C. Han, E.J. Crampin, A.J. Taberner, and D.S. Loiselle, Experimental and modelling evidence of shortening heat in cardiac muscle. The Journal of Physiology, 2017. 595(19): p. 6313-6326. DOI: 10.1113/JP274680
  3. Taberner, A.J., C.M. Johnston, T. Pham, J.-C. Han, R. Uddin, D.S. Loiselle, B.P. Ruddy, and P.M.F. Nielsen, A flow-through infusion calorimeter for measuring muscle energetics: design and performance. IEEE Transactions on Instrumentation and measurement, 2017. (In press)DOI: 10.1109/TIM.2018.2800838
  4. Pham, T., K. Tran, K.M. Mellor, A. Hickey, A. Power, M.L. Ward, A. Taberner, J.C. Han, and D. Loiselle, Does the intercept of the heat–stress relation provide an accurate estimate of cardiac activation heat? The Journal of Physiology, 2017. 595(14): p. 4725-4733. DOI: 10.1113/JP274174
  5. Han, J.-C., S.-J. Guild, T. Pham, L. Nisbet, K. Tran, A. Taberner, and D. Loiselle, Left-ventricular energetics in pulmonary arterial hypertension-induced right-ventricular hypertrophic failure. Frontiers in Physiology, 2017DOI: doi: 10.3389/fphys.2017.01115
  6. Tran, K., J.C. Han, A.J. Taberner, C.J. Barrett, E.J. Crampin, and D.S. Loiselle, Myocardial energetics is not compromised during compensated hypertrophy in the Dahl salt-sensitive rat model of hypertension. Am J Physiol Heart Circ Physiol, 2016. 311(3): p. H563-71. DOI: 10.1152/ajpheart.00396.2016
  7. Loiselle, D.S., C.M. Johnston, J.C. Han, P.M. Nielsen, and A.J. Taberner, Muscle heat: a window into the thermodynamics of a molecular machine. Am J Physiol Heart Circ Physiol, 2016. 310(3): p. H311-25. DOI: 10.1152/ajpheart.00569.2015
  8. Loiselle, D.S., J.-C. Han, E. Goo, B. Chapman, C.J. Barclay, A.J.R. Hickey, and A.J. Taberner, Thermodynamic analysis questions claims of improved cardiac efficiency by dietary fish oil. The Journal of general physiology, 2016. 148(3): p. 183-193. DOI: 10.1085/jgp.201611620
  9. Johnston, C.M., J.-C. Han, D.S. Loiselle, P.M.F. Nielsen, and A.J. Taberner, Cardiac activation heat remains inversely dependent on temperature over the range 27–37°C. American Journal of Physiology - Heart and Circulatory Physiology, 2016. 310(11): p. H1512-H1519. DOI: 10.1152/ajpheart.00903.2015
  10. Johnston, C.M., J.C. Han, B.P. Ruddy, P.M. Nielsen, and A.J. Taberner, A high-resolution thermoelectric module-based calorimeter for measuring the energetics of isolated ventricular trabeculae at body temperature. Am J Physiol Heart Circ Physiol, 2015. 309(2): p. H318-24. DOI: 10.1152/ajpheart.00194.2015
  11. Han, J.C., C.J. Barrett, A.J. Taberner, and D.S. Loiselle, Does reduced myocardial efficiency in systemic hypertensive-hypertrophy correlate with increased left-ventricular wall thickness? Hypertens Res, 2015. 38(8): p. 530-8. DOI: 10.1038/hr.2015.37
  12. Loiselle, D.S., J.C. Han, K. Mellor, K. Tran, T.K. Pham, S. Goo, A.J. Taberner, and A. Hickey, Assessing the Efficiency of the Diabetic Heart: a Biophysical Approach. Journal of General Practice, 2014. 2(4)DOI: 10.4172/2329-9126.1000168
  13. Han, J.C., K. Tran, P.M. Nielsen, A.J. Taberner, and D.S. Loiselle, Streptozotocin-induced diabetes prolongs twitch duration without affecting the energetics of isolated ventricular trabeculae. Cardiovasc Diabetol, 2014. 13(1): p. 79. DOI: 10.1186/1475-2840-13-79
  14. Han, J.C., S. Goo, C.J. Barrett, K.M. Mellor, A.J. Taberner, and D.S. Loiselle, The afterload-dependent peak efficiency of the isolated working rat heart is unaffected by streptozotocin-induced diabetes. Cardiovasc Diabetol, 2014. 13(4)DOI: 10.1186/1475-2840-13-4
  15. Han, J.-C., K. Tran, C.J. Johnston, P.M.F. Nielsen, C.J. Barrett, A.J. Taberner, and D.S. Loiselle, Reduced Mechanical Efficiency in Left Ventricular Trabeculae of the Spontaneously Hypertensive Rat. Physiological Reports, 2014. 2(e12211)DOI: 10.14814/phy2.12211
  16. Goo, S., J.C. Han, L.A. Nisbet, I.J. LeGrice, A.J. Taberner, and D.S. Loiselle, Dietary supplementation with either saturated or unsaturated fatty acids does not affect the mechanoenergetics of the isolated rat heart. Physiological Reports, 2014. 2(3)DOI: doi: 10.1002/phy2.272
  17. Han, J.-C., A.J. Taberner, P.M.F. Nielsen, and D.S. Loiselle, Interventricular comparison of the energetics of contraction of trabeculae carneae isolated from the rat heart. The Journal of Physiology, 2013. 591(3): p. 701-717. DOI: 10.1113/jphysiol.2012.242719
  18. Goo, S., T. Pham, J.C. Han, P. Nielsen, A. Taberner, A. Hickey, and D. Loiselle, Multiscale measurement of cardiac energetics. Clin Exp Pharmacol Physiol, 2013. 40(9): p. 671-81. DOI: 10.1111/1440-1681.12139
  19. Han, J.C., A.J. Taberner, K. Tran, S. Goo, D.P. Nickerson, M.P. Nash, P.M. Nielsen, E.J. Crampin, and D.S. Loiselle, Comparison of the Gibbs and Suga formulations of cardiac energetics: the demise of "isoefficiency". J Appl Physiol, 2012. 113(7): p. 996-1003. DOI: 10.1152/japplphysiol.00693.2011
  20. Han, J.-C., K. Tran, A.J. Taberner, D.P. Nickerson, R.S. Kirton, P.M.F. Nielsen, M.-L. Ward, M.P. Nash, E.J. Crampin, and D.S. Loiselle, Myocardial twitch duration and the dependence of oxygen consumption on pressure–volume area: experiments and modelling. The Journal of Physiology, 2012. 590(18): p. 4603-4622. DOI: 10.1113/jphysiol.2012.228965
  21. Han, J.-C., A.J. Taberner, K. Tran, D.P. Nickerson, M.P. Nash, P.M.F. Nielsen, E.J. Crampin, and D.S. Loiselle, Relating components of pressure-volume area in Suga's formulation of cardiac energetics to components of the stress-time integral. Journal of Applied Physiology, 2012. 113(7): p. 988-995. DOI: 10.1152/japplphysiol.00438.2012
  22. Taberner, A.J., J.C. Han, D.S. Loiselle, and P.M. Nielsen, An innovative work-loop calorimeter for in vitro measurement of the mechanics and energetics of working cardiac trabeculae. J Appl Physiol, 2011. 111(6): p. 1798-1803. DOI: 10.1152/japplphysiol.00752.2011
  23. Han, J.C., A.J. Taberner, R.S. Kirton, P.F. Nielsen, R. Archer, N. Kim, and D.S. Loiselle, Radius-dependent Decline of Performance in Isolated Cardiac Muscle Does Not Reflect Inadequacy of Diffusive Oxygen Supply. American Journal of Physiology - Heart and Circulatory Physiology, 2011. 300: p. H1222-H1236. DOI: 10.1152/ajpheart.01157.2010
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