441 ISSN 0006-3509, Biophysics, 2018, Vol. 63, No. 3, pp. 441–448. © Pleiades Publishing, Inc., 2018. Original Russian Text © O.N. Lookin, Yu.L. Protsenko, 2018, published in Biofizika, 2018, Vol. 63, No. 3, pp. 573–581. Deficiency of Length-Dependent Activation of Contraction in the Cardiac Muscle of Rats with Heart Failure: Assessment of the Muscle Strip and Single Cell Levels O. N. Lookin a, b, * and Yu. L. Protsenko a a Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences, Yekaterinburg, 620049 Russia b Yeltsin Ural Federal University, Yekaterinburg, 620002 Russia *e-mail: o.lookin@iip.uran.ru Received March 13, 2018 Abstract⎯This paper reports on a comparison of the extent of length-dependent activation of contraction in the right ventricle myocardium in healthy rats and rats with monocrotaline-induced heart failure on two lev- els of heart-tissue organization, that is, muscle stripes and isolated cardiomyocytes, within the framework of a single study. It has been shown that a deficiency in the length-dependent increase in the contractile force produced by failing myocardium when expressed in quantitative terms is similar at both levels of organization of myocardial tissue. These findings indicate that the mechanisms of length-dependent regulation of myocar- dial contractility in the failing heart are suppressed mainly at the cellular level. In muscle strips, the deficiency of the length–tension relationship appears to be more pronounced, most likely because the spatial organiza- tion of myocytes affects the integral contractile response of the muscle. Keywords: muscle, cardiomyocyte, length–tension relationship, heart failure, monocrotaline DOI: 10.1134/S0006350918030132 INTRODUCTION In the adaptation of the heart pump function to exercise, a key role is played by the mechanisms of myocardial contractility regulation, which depend on the actual length of sarcomeres in cardiomyocytes [1– 3]. The length-dependent mechanisms that regulate the contractile force of the cardiac muscle manifest themselves in the form of the Frank–Starling law, according to which the maximum pressure in the car- diac chamber is proportional to its end-diastolic vol- ume (in the case of muscle strips, this phenomenon is referred to as the length–tension relationship). In fail- ing myocardium, only a limited increase in the myo- cardial contractility following the change in the sarco- mere length has been demonstrated [4–6], with some authors even reporting almost complete disappear- ance of this phenomenon, for instance, in a patient with terminal stage left-ventricle failure [7]. According to other works, the Frank–Starling mechanism remains partially functional in the heart of patients with pulmonary heart disease, as well as in dog and rat cardiomyocytes [8–10]. Finally, some data indicate that cardiomyocytes in the right ventricle of dogs with the severe whole ventricle failure retain their normal contractile function [11]. The significantly varying data on the degree of manifestation of the Frank–Starling phenomenon in failing myocardium may be accounted for by the dif- ferences in the level at which the study is carried out, as well as in the disease model that is used. Different experimental models of pulmonary heart disease in rats exist, including pulmonary artery ligation, use of animal lines with renal dysfunction, use of compounds that compromise normal renin–angiotensin–aldoste- rone system function with subsequent expression of endothelin and angiotensin. In our work we used a noninvasive experimental model involving the admin- istration of a single dose of the monocrotaline (MCT) alkaloid, which induces the constriction of the pulmo- nary trunk with subsequent development of concen- tric hypertrophy of the right ventricle and pulmonary hypertension and heart failure. The quantitative data on the extent of the deficit in the length-dependent tension increase were collected either using multicellular objects, or isolated cardio- myocytes, but no works exist that report an assessment performed simultaneously at the cellular and tissue levels. We have quantitatively assessed the extent of length-dependent activation of contraction in both muscle strips and isolated cardiomyocytes in rats with pulmonary heart disease and compared the results with the corresponding data obtained for rats with normal right ventricle myocardial function. This Abbreviations: MCT, monocrotaline, L max , the muscle length at which the maximum tension is produced. COMPLEX SYSTEMS BIOPHYSICS