Perfusion-induced changes in cardiac contractility  depend on capillary perfusion

Dijkman, Marieke A.; Heslinga, J. W.; Sipkema, Pieter; Westerhof, Nico

doi:10.1152/ajpheart.1998.274.2.h405

Cited by 20 publications

(28 citation statements)

References 12 publications

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“…The increase of F dev , which results from a change from low to high P perf (Gregg effect), has been reported several times in literature (1,14,15,17,18,39). Recently, we showed in perfused rat papillary muscle that the Gregg effect, which is accompanied by an increase in muscle diameter (transversal stretch), was initiated by activation of Gd 3ϩ -sensitive SACs (31) -sensitive positive inotropic mechanism is active.…”

Section: Discussionmentioning

confidence: 77%

“…From the literature, it is known that SACs could be located on the sarcolemma or t-tubular system of the cardiomyocytes (45); however, SACs have also been found on the vascular (33) or endocardial (24,27) endothelium. Dijkman et al (16)(17)(18) showed that perfusion-induced changes in contractility were related to Fig. 2.…”

Section: Discussionmentioning

confidence: 98%

“…Schouten et al (39) showed that no hypoxic core is formed at these low flow conditions. The maximal P perf of 80 cmH2O (ϳ65 mmHg) was used because this reflects normal P perf in the septal artery and it is the Pperf at which the increase in Fdev is maximal (18). Furthermore, at this Pperf, the Gregg effect was of comparable magnitude as the Anrep effect for a muscle length increase from 85 to 95% L max.…”

Section: Methodsmentioning

confidence: 99%

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

Lamberts

Rijen

Sipkema

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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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...

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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

Lamberts

Rijen

Sipkema

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…We (9) previously reported that the Gregg effect is associated with increases in PVA-independent V O 2 without changes in the slope of the V O 2 -PVA relation. Dijkman et al (5) have shown that capillary pressure is in fact the main determinant of the Gregg effect. Therefore, to the extent that the higher perfu- sion pressure in HF rats resulted in higher capillary pressure this would have tended to improve contractility and increase PVA-independent V O 2 in HF rats, i.e., it would act as a bias against the results we found.…”

Section: Endogenous Et-1 and Pva-independent V O 2 Contractile Effimentioning

confidence: 99%

Endothelin receptor blockade has an oxygen-saving effect in Dahl salt-sensitive rats with heart failure

Noguchi

Chen

Bell

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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. Endothelin receptor blockade has an oxygen-saving effect in Dahl salt-sensitive rats with heart failure. Am J Physiol Heart Circ Physiol 285: H1428-H1434, 2003. First published June 5, 2003 10.1152/ ajpheart.00731.2002The effects of endothelin (ET) receptor blockade on energy utilization in heart failure (HF) are unknown. We administered ET type A (ET A), ET type B (ET B), and ETA/ETB antagonists to isolated hearts from Dahl salt-sensitive (DS) rats with HF and controls. Contractile efficiency was assessed as slope Ϫ1 of myocardial O2 consumption (V O2)-pressure-volume area relation. In HF, ETA and ETA/ETB but not ETB blockade decreased the contractility index (Emax) (Ϫ15 Ϯ 3% and Ϫ17 Ϯ 2%, P Ͻ 0.05), excitationcontraction (E-C) coupling V O2 (Ϫ39 Ϯ 4% and Ϫ37 Ϯ 5%, P Ͻ 0.01), and efficiency (Ϫ15 Ϯ 4% and Ϫ17 Ϯ 2%, P Ͻ 0.05). Despite decreased efficiency, ETA and ETA/ETB blockade decreased total V O2 (Ϫ24 Ϯ 3% and Ϫ22 Ϯ 2%, P Ͻ 0.05). Na ϩ /H ϩ exchanger inhibition decreased Emax and E-C coupling V O2 similar to ETA and ETA/ETB blockade, but did not alter efficiency. In HF, endogenous ET-1 maintains contractility at expense of increased V O2 through ETA receptor activation, likely mediated by Na ϩ /H ϩ exchange.oxygen consumption ACUTELY ADMINISTERED ENDOTHELIN (ET)-1 has positive inotropic effects in normal myocardium (22,27). In contrast, chronic ET-1 inhibition improves cardiac function and prognosis in animal models of heart failure (HF) (23,29,33). Recently, Takeuchi et al. (35) reported that in addition to positive inotropic effects acutely administered exogenous ET-1 increases left ventricular (LV) chemomechanical energy conversion efficiency through ET type A (ET A ) receptor activation in normal rats. The role of endogenous ET-1 in energy utilization in HF, where chronic activation is present, has not been assessed in vitro. Moreover, there are no reports comparing ET A and ET B receptors in this setting.To clarify these issues, we used the myocardial O 2 consumption (V O 2 )-pressure-volume area (PVA) framework to delineate effects of acute ET-1 blockade on mechanoenergetics in isolated, crystalloid-perfused hearts from Dahl salt-sensitive (DS) rats, which develop pressure and volume overload when fed a highsalt (HS) diet (4). The V O 2 -PVA relationship allows quantification of energy conversion efficiency of the contractile machinery (contractile efficiency) and energy use for excitation-contraction (E-C) coupling and basal metabolism (6, 34). We found that blockade of endogenous ET-1 in HF produces complex effects on V O 2 through ET A receptor inhibition. E-C coupling energy saving effects compensate for the energy-wasting effects on the contractile machinery, resulting in net reduction in energy consumption. METHODS Animal ModelAll protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Vermont.Sixty 6-wk-old male DS rats (Taconic Farms, Germantown, NY) were divided into groups receiving a HS (8% NaCl) or low-salt (LS) diet (0.3% NaCl). Com...

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“…On the other hand, local regulation of cardiac contractility by capillary endothelial cells has been hypothesized to account for the Gregg effect (30). Increased coronary flow rate stimulates capillary endothelium (4), and a role for endothelial cells in the regulation of cardiac function has been demonstrated (38). Furthermore, a recent study with the papillary muscle preparation showed a role for stretch-activated ion channels in the Gregg effect (17).…”

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Dual role of endothelin-1 via ET_A and ET_B receptors in regulation of cardiac contractile function in mice

Piuhola

Mäkinen

Szokodi³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Piuhola, Jarkko, Markus Mä kinen, Istvá n Szokodi, and Heikki Ruskoaho. Dual role of endothelin-1 via ET A and ETB receptors in regulation of cardiac contractile function in mice. Am J Physiol Heart Circ Physiol 285: H112-H118, 2003. First published February 27, 2003 10.1152/ajpheart.00480.2002.-An increase in coronary perfusion pressure leads to increased cardiac contractility, a phenomenon known as the Gregg effect. Exogenous endothelin (ET)-1 exerts a positive inotropic effect; however, the role of endogenous ET-1 in the contractile response to elevated load is unknown. We characterized here the role of ET A and ET B receptors in regulation of contractility in isolated, perfused mouse hearts subjected to increased coronary flow. Elevation of coronary flow from 2 to 5 ml/min resulted in 80 Ϯ 10% increase in contractile force (P Ͻ 0.001). BQ-788 (ET B receptor antagonist) augmented the load-induced contractile response by 35% (P Ͻ 0.05), whereas bosentan (ET A/B receptor antagonist) and BQ-123 (ET A receptor antagonist) attenuated it by 34% and 56%, respectively (P Ͻ 0.05). CV-11974 (ANG II type 1 receptor antagonist) did not modify the increase in contractility. These results show that endogenous ET-1 is a key mediator of the Gregg effect in mouse hearts. Moreover, ET-1 has a dual role in the regulation of cardiac contractility: ET A receptor-mediated increase in contractile force is suppressed by ET B receptors. angiotensin II; coronary pressure; Gregg effect INCREASED CORONARY FLOW RATE results in an increase in cardiac oxygen consumption and contractility, a phenomenon known as the Gregg effect (6, 8). The molecular and cellular mechanisms of the Gregg effect are not completely understood. It has been suggested that changes in cardiac muscle length occur because of the increased capacity of coronary vasculature (garden hose effect), thereby leading to increased force production according to the Frank-Starling law of the heart (1). However, in a more recent study (30), it was reported that in the papillary muscle preparation the magnitude of the Gregg effect is greater than that of the Frank-Starling response. On the other hand, local regulation of cardiac contractility by capillary endothelial cells has been hypothesized to account for the Gregg effect (30). Increased coronary flow rate stimulates capillary endothelium (4), and a role for endothelial cells in the regulation of cardiac function has been demonstrated (38). Furthermore, a recent study with the papillary muscle preparation showed a role for stretch-activated ion channels in the Gregg effect (17).Elevated coronary flow has been suggested to stimulate the production and release of various vasoactive factors including nitric oxide (NO) and endothelin (ET)-1 (22, 36). Previously, the role of NO in the Gregg effect was excluded (17). ET-1 exerts a direct positive inotropic effect in guinea pig, rat, and human myocardium (12, 23). ET A receptors are considered to mediate the positive inotropic effect (15). ET B receptors also exist on cardiac myocyt...

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Perfusion-induced changes in cardiac contractility depend on capillary perfusion

Cited by 20 publications

References 12 publications

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

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

Endothelin receptor blockade has an oxygen-saving effect in Dahl salt-sensitive rats with heart failure

Dual role of endothelin-1 via ET_A and ET_B receptors in regulation of cardiac contractile function in mice

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Perfusion-induced changes in cardiac contractility depend on capillary perfusion

Cited by 20 publications

References 12 publications

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

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

Endothelin receptor blockade has an oxygen-saving effect in Dahl salt-sensitive rats with heart failure

Dual role of endothelin-1 via ETA and ETB receptors in regulation of cardiac contractile function in mice

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Dual role of endothelin-1 via ET_A and ET_B receptors in regulation of cardiac contractile function in mice