Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms

Abstract

Westerhof. Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms. Am J Physiol Heart Circ Physiol 283: H1515-H1522, 2002. First published May 23, 2002 10.1152/ajpheart. 00113.2002.-An increase in coronary perfusion, transversal stretch of the myocardium, increases developed force (Fdev) (Gregg effect) through activation of stretch-activated ion channels (SACs). Lengthening of the muscle, longitudinal stretch of the myocardium, causes an immediate increase in Fdev followed by a slow Fdev increase (Anrep effect). In isometrically contracting perfused papillary muscles of Wistar rats, we investigated whether both effects were based on similar stretch-induced mechanisms by measuring Fdev and intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) after a muscle length increase from 85% to 95% Lmax (length at which maximal isometric force develops) at low and high coronary perfusion before and after inhibition of SACs with gadolinium (10 mol/l Gd 3ϩ ). The increase of F dev and peak [Ca 2ϩ ]i by the Gregg effect was of similar magnitude as the Anrep effect (from 3.5 Ϯ 0.8 to 3.9 Ϯ 1.2 mN/mm 2 and from 3.0 Ϯ 0.7% to 3.8 Ϯ 0.9% normalized [Ca 2ϩ ]i, means Ϯ SE). SAC blockade completely blunted the increase of Fdev and peak [Ca 2ϩ ]i by the Gregg effect; however, it did not affect the Anrep effect. The slow force response, but not the calcium response, was augmented by an increase in coronary perfusion. Therefore, increased coronary perfusion, transversal stretch of the myocardium, and muscle lengthening, longitudinal stretch of the myocardium, increase myocardial contraction in the rat through different stretch-triggered mechanisms. myocardial stretch; papillary muscles; gadolinium; streptomycin; stretch-activated ion channels INCREASED CORONARY PERFUSION induces a slow increase of myocardial contraction, which is known as the Gregg effect (1,7,14,15,17,19,22,39). Recently, we showed in perfused rat papillary muscle that the increase in coronary perfusion, which is accompanied by an increase in muscle diameter, was initiated by activation of Gd 3ϩ -sensitive stretch-activated ion channels (SACs) (31), suggesting that transversal stretch (deformation) of the myocardium is fundamental for the Gregg effect.Increased diastolic filling of the heart results via the Frank-Starling mechanism in an immediate increase in myocardial contraction to elevate cardiac output and eventually match venous return (38). Subsequently, myocardial contraction increases slowly, which is known as the Anrep effect (44). In vitro, this biphasic response to longitudinal stretch of the myocardium was first shown by Parmley and Chuck (34). The first, rapid increase in force is related to an increase of responsiveness of the myofilaments for internal calcium (2). The second, slower force response has been attributed to a slow rise of intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) (3). In rat and cat papillary muscles, the Anrep effect was triggered by stretch-sensitive but endothelium-independ...

Preload-induced changes in isometric tension and [Ca2+]i in rat myocardium

“…Similar findings were made in numerous studies on warm-blooded animal and human myocardium [9,[16][17][18][19][20][21][22][23][24]. The preload-induced interplay between cytosolic calcium and force development is thought to be indirect and most likely involves cooperative effects of association/dissociation of Ca-TnC [2,4,6,7,30,31].…”

“…The higher preload the larger amplitude of Ca 2+ transient has been observed in mouse [9], cat [18], rat [16,17,19] and rabbit [20,21] [18]. In contrast, no preload-dependent changes in Ca 2+ transient amplitude have been shown in ferret [22], rat [18,23] and human myocardium [24] while marked increase of peak isometric force was observed in all the cases.…”

“…The "dissociation" between preloaddependent changes in mechanics and calcium handling has been observed in numerous studies carried out on mammalian and human myocardium [11,12,21,24,[32][33][34][35]. It has been shown in cat [18], rat [16,17,19], mouse [9] and rabbit [20,21] that muscle stretch is not accompanied by increase of Ca 2+ transient amplitude immediately after the stretch but does produce a slow increase. Peak active force, however, increased immediately after stretch and then rose additionally during several minutes.…”

Upregulation of TRPC1 Contributes to Contractile Function in Isoproterenol-induced Hypertrophic Myocardium of Rat

“…in the extracellular solution containing the L-type Ca 2+ channel inhibitor, verapamil (Ver 0.1 μmol/L); (ii). in the extracellular solution containing the SACs blocker, gadolinium chloride (Gd 3+ 10 μmol/L) [17]; (iii). in the extracellular solution containing the NCX inhibitor, nickel chloride (Ni 2+ 5.0 mmol/L) [18].…”

Functional Relevance of the Stretch-Dependent Slow Force Response in Failing Human Myocardium

“…This conclusion is in accordance with previous reports on rat papillary muscle. 27 To elucidate whether the initial or delayed inotropic response to stretch might be mediated by L-type Ca 2ϩ currents, 28 further experiments were performed in the presence of diltiazem. Diltiazem did not affect the relative increase in force during the initial or delayed inotropic response after stretch.…”