Left-Ventricular Pressure Relaxation and Diastolic Function of Isolated Working Mammalian Hearts at Hypothermia


  • Stefan F. J. Langer




ventricular pressure, myocardial relaxation, diastole, hypothermia, isolated heart


Background: Hypothermia is well known to elevate the time constant (whatever model is used) of the isochoric left-ventricular pressure fall. Due to different critera in use, it remained unclear whether prolonged diastole in hypothermia is sufficient for complete relaxation. Detecting and quantifying incomplete relaxation may become a valuable tool to prevent diastolic heart failure in hypothermia.
Methods: Left-ventricular pressure decays in isolated guinea pig and rat hearts are analysed by 4-parametric regression at different temperatures, at sinus rhythm and electrical stimulation. Residual contraction (F_RC) is introduced and quantified by extrapolating the model's pressure forecast to end-systole, subtracting the asymptote, and normalising.
Resultts: Isochoric pressure decay fits the regression model at all temperatures and heart beat frequencies. Residual contraction is virtually absent at normothermia and remains very small (F_RC<3%) down to 31°C. Lower temperatures or pacing induces higher F_RC. Eventually, the pressure curve becomes considerably elevated and looses its concavity.
Conclusions: Despite slower pressure fall, ventricular relaxation remains fairly complete at hypothermia; and depends on considerable autoregulation of the individual heart. It is concluded (not proved) that individual emergence of negative lusitropy may indicate imminent heart failure. Asymptotic pressure rises are interpreted at higher ventricular tonus, independent from velocity of relaxation. Gradual increasing time constants may be attributed to a general slowing of bioreactions as temperature falls. Remarkable curve shape changes may be caused by aftercontractions due to elevated Ca++ sensitivity at hypothermia and high Ca++ load by pacing.


Kusuoka H, Ikoma Y, Futaki S, Suga H, Kitabatake A, Kamada T, Inoue M: Positive inotropism in hypothermia partially depends on an increase in maximal Ca--activated force. Am. J. Physiol. 1991;261: H1005–H1010 (DOI: 10.1152/ajpheart.1991.261.4.H1005).

Nishimura Y, Naito Y, Nishioka T, Okamura Y: The effects of cardiac cooling under surface--induced hypothermia on the cardiac function in the in situ heart. Interact. Cardiovasc. Thorac. Surg. 2005;4: 101–105 (DOI: 10.1510/icvts.2004.097188).

Schwarzl M, Alogna A, Zirngast B, Steendijk P, Verderber J, Zweiker D, Huber S, Maechler H, Pieske BM, Post H. Mild hypothermia induces incomplete left ventricular relaxation despite spontaneous bradycardia in pigs. Acta Physiol. (Oxf) 2015;213(3): 653--663 (DOI: 10.1111/apha.12439).

Langer SFJ, Schmidt HD: Different left ventricular relaxation parameters in isolated working rat and guinea pig hearts. Influence of preload, afterload, temperature and isoprenaline. Int. J. Card. Imaging 1998;14: 229--240 (DOI: 10.1023/a:1006083306901).

Langer SF. Ransacking the curve of cardiac isovolumic pressure decay by logistic--and--oscillation regression. Jpn. J. Physiol. 2004;54: 347--356 (DOI: 10.2170/jjphysiol.54.347).

Sachs L. Angewandte Statistik [6th ed; engl. ed. as: Applied Statistics, 2nd ed]. Berlin etc: Springer 1984 (DOI: 10.1007/978-3-662-05750-6).

Matsubara H, Araki J, Takaki M, Nakagawa ST, Suga H. Logistic characterization of left ventricular isovolumic pressure-time curve. Jpn. J. Physiol. 1995;45: 535-552 (DOI: 10.2170/jjphysiol.45.535).

Brecher GA, Kissen AT: Relation of negative intraventricular pressure to ventricular volume. Circ. Res. 1957;5,2: 157-162 (DOI 10.1161/01.RES.5.2.157).

Langer SFJ: Regression analysis of the left--ventricular isochoric pressure decay of the heart: Four or five model parameters? International Cardiovascular Forum Journal 2015;4: 53-58 (DOI: 10.17987/icfj.v4i0.168).

Yellin EL, Hori M, Yoran C, Sonnenblick EH, Gabbay S, Frater FW.: Left ventricular relaxation in the filling and nonfilling intact canine heart. Am. J. Physiol. 1986;250,4: H620-H629 (DOI: 10.1152/ajpheart.1986.250.4.H620).

Weisfeldt ML, Frederiksen JW, Yin FCP, Weiss JL: Evidence of incomplete left ventricular relaxation in the dog. Prediction from the time constant for isovolumic pressure fall. J. Clin. Invest. 1978;62,6: 1296-1302 (DOI: 10.1172/JCI109250).

Mirsky I, Pasipoularides A: Clinical assessment of diastolic function. Prog. Cardiovasc. Dis. 1990;32,4: 291-318 (DOI: 10.1016/0033-0620(90)90018-W).

Jewell BR, Wilkie DR: The mechanical properties of relaxing muscle. J. Physiol. 1960;152: 30-47 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1363293/.

Parmley WW, Sonnenblick EH: Relation between mechanics of contraction and relaxation in mammalian cardiac muscle. Am. J. Physiol. 1969;216,5: 1084-1091 (DOI: 10.1152/ajplegacy.1969.216.5.1084).

Langer SF, Schmidt HD. Influence of preload on left ventricular relaxation in isolated ejecting hearts during myocardial depression. Exp. Clin. Cardiol. 2003;8: 83--90 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716204).

Post H, Schmitto JD, Steendijk P, Christoph J, Holland R, Wachter R, Schondube FW, Pieske B: . Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction. Acta Physiol. (Oxf) 2010;199: 43-52 (DOI: 10.1111/j.1748-1716.2010.02083.x).

Luke RA, Gillbe CE, Bonser RS, Paneth M, Somerset D, Thomas J, Gibson DG: Effect of temperature on rate of left ventricular pressure fall in humans. Br. Heart J. 1989;61,5: 426-431 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216695/).

Mizuno J, Matsubara H, Mohri S, Shimizu J, Suzuki S, Mikane T, Araki J, Hanaoka K, Akins R, Morita S,: Half-logistic time constant: a more reliable lusitropic index than monoexponential time constant regardless of temperature in canine left ventricle. Can. J. Physiol. Pharmacol. 2008;86,3: 78-87 (DOI: 10.1139/y08-001).

Meek WJ: The question of cardiac tonus. Physiol. Rev. 1927;7: 259-287.

deTombe PP, Mateja RD, Tachampa K, Ait Mou Y, Farman GP, Irving TC. Myofilament length dependent activation [review]. J. Mol. Cell. Cardiol. 2010;48: 851-858 (DOI: 10.1016/j.yjmcc.2009.12.017).

Egdell RM, MacLeod KT: Calcium extrusion during aftercontractions in cardiac myocytes: the role of the sodium-calcium exchanger in the generation of the transient inward current. J. Mol. Cell. Cardiol. 2000;32,1: 85--93 (DOI: 10.1006/jmcc.1999.1056).

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2 (DOI: 10.17987/icfj.v2i1.4).






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