Effect of ventricular stretch on contractile strength, calcium transient, and cAMP in intact canine hearts

Abstract

Isovolumic contractions were imposed by intraventricular balloon in 39 isolated, blood-perfused canine hearts to investigate the effects of myocardial stretch on contractile force. After stabilization at 37°C, left ventricular volume was increased so that end-diastolic pressure increased from 0 to 5 mmHg. After the immediate increase in developed pressure [DP; from 37 ± 14 to 82 ± 22 mmHg (means ± SD)], there was a slow secondary rise in DP (97 ± 27 mmHg) that peaked at 3 min. However, DP subsequently decreased over the next 7 min back to the initial value (84 ± 25 mmHg). Light emission from macroinjected aequorin ( n = 10 hearts) showed that changes in intracellular calcium [3 min: 124 ± 15% ( P < 0.01); 10 min: 99 ± 18% of baseline] paralleled DP changes. Increases in myocardial adenosine 3′,5′-cyclic monophosphate (cAMP) content ( n = 12) accompanied the secondary rise in DP. In contrast, the gradual elevation of DP after the stretch was not exerted during continuous β-adrenergic stimulation by isoproterenol. Thus, in contrast to isolated muscle, stretch only transiently increases intracellular calcium and contractile strength in intact hearts. The findings of changes in cAMP and abolition of the phenomena by β-stimulation suggest that a primary stretch-mediated influence on cAMP metabolism may underlie these phenomena.

The slow force response to stretch in atrial and ventricular myocardium from human heart: Functional relevance and subcellular mechanisms

“…Since then, this finding has been confirmed in other ventricular preparations (Alvarez et al, 1999;Calaghan and White, 2004;Hongo et al, 1996;Kentish and Wrzosek, 1998;Luers et al, 2005;Todaka et al, 1998 (von Lewinski et al, 2004). In line with this finding, caffeine (which releases Ca 2+ from the SR through ryanodine receptors) was found to reduce the SFR in cat ventricle by an SR-dependent mechanism (Chuck and Parmley, 1980).…”

“…The SFD is not unprecedented. A study in dog heart has noted this phenomenon before (Todaka et al, 1998). So far, the cellular mechanisms underlying this stretch-induced negative inotropic response are not known.…”

“…The SFR was originally characterised in cat papillary muscles (Parmley and Chuck, 1973). Since then, it has been observed in a variety of cardiac preparations ranging from whole hearts to single myocytes in various species including cat (Parmley and Chuck, 1973;Perez et al, 2001), dog (Todaka et al, 1998), ferret (Calaghan and White, 2001), guineapig (White et al, 1995), rabbit (von Lewinski et al, 2003), rat (Alvarez et al, 1999;Hongo et al, 1996;Kentish and Wrzosek, 1998), and human (von Lewinski et al, 2004). This implicates that the SFR is a general phenomenon of physiological relevance and that the underlying mechanisms of the SFR, just like the FSM, are intrinsic to the cardiac myocyte.…”

“…Based on experimental and modelling studies various signalling pathways and mechanisms have been proposed to contribute to the SFR. The list of channels, transporters, and signalling molecules possibly involved in the SFR includes angiotensin II (Alvarez et al, 1999;Perez et al, 2001), endothelins (Alvarez et al, 1999;Calaghan and White, 2001;Ennis et al, 2005;Perez et al, 2001), stretch-activated non-selective cation channels (SACs) (Calaghan and White, 2004;Niederer and Smith, 2007), the Na + /H + exchanger (NHE) (Alvarez et al, 1999;Calaghan and White, 2004;Luers et al, 2005;Perez et al, 2001;von Lewinski et al, 2003), the Na + /Ca 2+ exchanger (NCX) (Luers et al, 2005;Perez et al, 2001;von Lewinski et al, 2003), the Na + / K + pump (Bluhm et al, 1998), cAMP (Calaghan et al, 1999;Todaka et al, 1998), phosphatidyinositol-3 kinase (PI3K) (Vila Petroff et al, 2001), and nitric oxide (NO) (Vila Petroff et al, 2001), and is likely to be extended further. The significance of each mechanism may vary depending on experimental conditions (e.g.…”

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

“…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.…”