Overview of Cardiac Inotropic Mechanisms

Siegl, P. K. S.

doi:10.1097/00005344-198611001-00001

Cited by 29 publications

(17 citation statements)

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“…These results also demonstrate novel sex-related differences in cardiac reliance on exogenous glucose, Ca 2+ sensitivity and SR function and thus should be considered in future studies. (Siegl, 1986), many of which elevate intracellular Ca 2+ (Ca 2+ i ). Although we identified potential mechanisms and intracellular signals for steroid-induced inotropism and sex differences in hormone responsiveness, key issues remain to be resolved.…”

Section: +mentioning

confidence: 99%

“…However, analysis of the actions of caffeine is complicated because of its multiplicity of actions in cardiac muscle. Although caffeine increases the rate of activator Ca 2+ from the SR and inhibits post-rest stimulation in mammals (Siegl, 1986), studies have also indicated that caffeine can modulate Ca 2+ sensitivity of contractile proteins (Wendt and Stephenson, 1983), increase activator Ca 2+ through inhibition of phosphodiesterase and subsequent increase flux through the sarcolemma (Siegl, 1986), decrease Ca 2+ -ATPase activity (Gupta et al, 1990) and even stimulate the reverse mode of the Na + /Ca 2+ exchanger (Léoty et al, 2001). While the present experiments of caffeine-induced contraction provide further evidence that sex differences exist in Ca 2+ handling by trout cardiac tissue, the exact mechanism remains to be elucidated.…”

Section: +mentioning

confidence: 99%

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Steroid-induced cardiac contractility requires exogenous glucose,glycolysis and the sarcoplasmic reticulum in rainbow trout

Farrar

Battiprolu

Pierson

et al. 2006

Journal of Experimental Biology

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SUMMARY Recent data from our laboratory suggest that sex steroids promote contractile function in cardiac muscle of rainbow trout (Oncorhynchus mykiss Walbaum), and there are sex differences in hormone signaling and cardiac function. The current study investigated whether steroid-induced inotropism in electrically paced (0.5 Hz, 14°C) ventricle strips at 90%Lmax (1) has a metabolic requirement for exogenous glucose and (2) is associated with enhanced intracellular Ca2+ storage and release from the sarcoplasmic reticulum (SR). We also explored whether sex differences exist in extracellular Ca2+(Ca2+o) or cardiac sensitivity to Ca2+o. In the absence or at low concentrations (1 or 2 mmol l-1) of exogenous glucose, resting tension and relaxation time were increased selectively in cardiac tissue from females. Increasing glucose promoted twitch force in a bell-shaped manner, with 5 mmol l-1representing the optimal concentration for both sexes. The positive inotropic effects of physiological concentrations of testosterone (T) and 17β-estradiol (E2) in male and female trout ventricle strips,respectively, developed slowly (10-45 min) and were not apparent in glucose-free medium, in medium containing iodoacetate (IAA), an inhibitor of glycolysis, or medium containing 5 mmol l-1 lactate or pyruvate. Male ventricle strips had increased inotropic responses to glucose and T compared with female strips exposed to glucose and E2. Furthermore, sexually maturing males showed a greater inotropic response than immature males or females. Pretreatment with ryanodine (a specific blocker of SR Ca2+release) also eliminated the inotropic effects of sex steroids and exogenous glucose and reduced the post-rest potentiation of contractile force (a marker of SR Ca2+ storage). By contrast, the inotropic effects of epinephrine (Epi) or elevated Ca2+o were faster(developing within 1-3 min) and were not diminished by the presence or absence of glucose or by pretreatment with IAA or ryanodine. Sex differences were also found in responsiveness to caffeine (males > females) and the relationship between Ca2+ concentration and force development above baseline. The Ca2+50 was lower in female cardiac tissue than males, suggesting greater Ca2+ sensitivity, and although plasma albumin was higher in females, total and ionized plasma Ca2+ did not differ between the sexes. For the first time, our study highlights the importance of extracellular glucose, glycolytic activity and SR Ca2+ storage and release for sex steroid-induced inotropism in the trout ventricle. Conversely, the inotropes Epi and elevated[Ca2+o] do not require the presence or metabolism of exogenous glucose or the SR for signaling their positive effects on contractility. These results also demonstrate novel sex-related differences in cardiac reliance on exogenous glucose, Ca2+ sensitivity and SR function and thus should be considered in future studies.

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Section: +mentioning

confidence: 99%

Section: +mentioning

confidence: 99%

Steroid-induced cardiac contractility requires exogenous glucose,glycolysis and the sarcoplasmic reticulum in rainbow trout

Farrar

Battiprolu

Pierson

et al. 2006

Journal of Experimental Biology

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“…Bipyridine deriva tives have been shown to inhibit the cardiac phosphodiesterase (PDE), Fill fraction (cyclic AMP specific PDE with low Km, inhibited by cyclic GMP) and accumulate cyclic AMP in myocardial tissues (5)(6)(7)(8)(9). Therefore, the in hibition of the Fill fraction by bipyridine derivatives has been implicated to be an es sential mechanism of the PIE of these com pounds (10,11). However, a closer inspection of the relation between the time course or concentration-dependence of PDE inhibition or accumulation of cyclic AMP and those of the increase in force of contraction during induction of the PIE by bipyridine derivatives revealed a definite apparent discrepancy in a number of experimental preparations (7,9,11).…”

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confidence: 99%

Effects of a new cardiotonic agent 1,2-dihydro-6-methyl-2-oxo-5-(imidazo(1,2-a)pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate (E-1020) on contractile force and cyclic AMP metabolism in canine ventricular muscle.

Satoh

Endoh

1990

Jpn.J.Pharmacol

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Abstract-E-1 020, a newly synthesized imidazopyridinylpyridine or imidazopyridine derivative (structurally closely related to the bipyridine derivative milrinone) in creased the force of contraction and cyclic AMP levels in a concentration-dependent manner in the isolated canine ventricular trabeculae electrically driven at 0.5 Hz at 37°C. The concentration-response curve for the increase in force of contraction by E-1020 was biphasic. The maximal positive inotropic effect (PIE) of E-1020 is comparable to that of milrinone, and its potency is 3-fold less than that of milrinone, but 10-fold higher than that of amrinone. The time course of increases in force of contraction induced by E-1020 was coincident with that of cyclic AMP accumulation. The concentration-response curve for the PIE of E-1020 was superimposable to that of cyclic AMP accumulation. A Q-adrenoceptor antagonist, (±)-bupranolol (3x10-7 mol/I), did not affect the PIE of E-1020. The increase in the force of contraction and accumulation of cyclic AMP produced by E-1020 were inhibited by a muscarinic receptor agonist, carbachol. The relationship between the force of contraction and cyclic AMP levels in the presence of E-1020 was not modified by addition of carbachoi or isoproterenol. E-1020 shifted the concentration-response curve for isoproterenol to the left. E-1020 shortened the total duration of contraction and relaxation time of isometric contractions. These findings indicate that cyclic AMP is essentially involved in the PIE of E-1020 on the canine ventricular muscle, although the possible involvement of a cyclic AMP independent mechanism can not be excluded.

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“…As cardiac contraction is regulated by various mechanisms, one can increase cardiac contractility by the intervention of some of the mechanisms (16,17 (24); and gingerol, a recently found cardiotonic agent, exerts its action by a mechanism involving direct stimulation of the Ca2+ pumping activity of SR (22,25). Therefore, we investigated the effects of MCI-154 on Ca2+ pumping activity of the isolated SR and on Ca2+ release from the SR. MCI-154 somewhat stimulated the Ca2+ pumping activity, which is probably due to the enhancement of SR Ca2+-ATPase activity as demonstrated in the present experiment.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that the Ca2+-sensitivity increasing effect may be the main mechanism for the positive inotropic action of MCI-154. To clarify this, we have to examine other possible me chanisms because myocardial contraction is regulated by various mechanisms and many interventions can be theoretically cardiotonic (16,17).…”

mentioning

confidence: 99%

In vitro characterization of the effects of MCI-154, anovel cardiotonic agent, on cardiac tissues.

Narimatsu¹,

Kitada²,

Satoh³

et al. 1989

Jpn.J.Pharmacol

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Abstract-In vitro cardiac effects of a cardiotonic drug, MCI-154, for which the main action mechanism was proposed to be the enhancement of Ca2+ sensitivity of cardiac contractile proteins, were investigated.MCI-154 (3X10-8-3X10-4 M) increased the developed tension in isolated ventricular muscles from cats, dogs, guinea pigs and rats and increased that of isolated left atrial muscles of guinea pigs and rats. However, species differences were observed in the responses to MCI 154. The positive inotropic potency of MCI-154 was stronger than those of amrinone and milrinone.In the isolated right atria from guinea pigs and rats, properties of the chronotropic effect of MCI-154 were different from those of amrinone and milrinone.The positive inotropic action of MCI-154 was not affected by phentolamine, propranolol, cimetidine and tetrodotoxin.

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Overview of Cardiac Inotropic Mechanisms

Cited by 29 publications

References 0 publications

Steroid-induced cardiac contractility requires exogenous glucose,glycolysis and the sarcoplasmic reticulum in rainbow trout

Steroid-induced cardiac contractility requires exogenous glucose,glycolysis and the sarcoplasmic reticulum in rainbow trout

Effects of a new cardiotonic agent 1,2-dihydro-6-methyl-2-oxo-5-(imidazo(1,2-a)pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate (E-1020) on contractile force and cyclic AMP metabolism in canine ventricular muscle.

In vitro characterization of the effects of MCI-154, anovel cardiotonic agent, on cardiac tissues.

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