Interval dependent inotropic effects in the rat myocardium and the effect of calcium

Forester, George V.; Mainwood, G. W.

doi:10.1007/bf00590484

Cited by 91 publications

(28 citation statements)

References 14 publications

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“…In all groups, an increase in [Ca 2ϩ ] o from 0.5 to 1.5 mM resulted in an increase in baseline contractility; the 2.7-fold increase in LVDP 0 is comparable with the value observed by Gaszner et al (13) and in accordance with the positive correlation between inotropy and [Ca 2ϩ ] o in rats (11). Note that the [Ca 2ϩ ] o of 1.5 mM corresponds to the physiological level of un-ionized Ca 2ϩ in rats (5).…”

Section: Effect Of [Ca 2ϩ ] Osupporting

confidence: 89%

Systems analysis of digoxin kinetics and inotropic response in the rat heart: effects of calcium and KB-R7943

Weiß¹,

Baek²,

Kang³

2004

American Journal of Physiology-Heart and Circulatory Physiology

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To gain more insight into the mechanistic processes controlling the kinetics of inotropic response of digoxin in the perfused whole heart, an integrated kinetic model was developed incorporating digoxin uptake, receptor binding (Na+-K+-ATPase inhibition), and cellular events linking receptor occupation and response. The model was applied to data obtained in the single-pass Langendorff-perfused rat heart for external [Ca2+] of 0.5 and 1.5 mM under control conditions and in the presence of the reverse-mode Na+/Ca2+ exchange inhibitor KB-R7943 (0.1 μM) in perfusate. Outflow concentration and left ventricular developed pressure data measured for three consecutive doses (15, 30, and 45 μg) in each heart were analyzed simultaneously. While disposition kinetics of digoxin was determined by interaction with a heterogeneous receptor population consisting of a high-affinity/low-capacity and a low-affinity/high- capacity binding site, response generation was >80% mediated by binding to the high-affinity receptor. Digoxin sensitivity increased at lower external [Ca2+] due to higher stimulus amplification. Coadministration of KB-R7943 significantly reduced the positive inotropic effect of digoxin at higher doses (30 and 45 μg) and led to a saturated and delayed receptor occupancy-response relationship in the cellular effectuation model. The results provide further evidence for the functional heterogeneity of the Na+-K+-ATPase and suggest that in the presence of KB-R7943 a reduction of the Ca2+ influx rate via the reverse mode Na+/Ca2+ exchanger might become the limiting factor in digoxin response generation.

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Section: Effect Of [Ca 2ϩ ] Osupporting

confidence: 89%

Systems analysis of digoxin kinetics and inotropic response in the rat heart: effects of calcium and KB-R7943

Weiß¹,

Baek²,

Kang³

2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…Potentiation.had no effect on developed tension at an external calcium concentration of 2.5 mM as was found previously (Forester and Mainwood, 1974). The relation between tension and sarcomere length obtained from potentiated contractions at [Ca 2+ ] o = 2.5 mM was identical to the relation at [Ca 2+ ] o = 2.5 mM at a stimulus rate of 0.2 Hz.…”

Section: Frequency Potentiation and Tension Development At Low Calciusupporting

confidence: 83%

“…It has been shown that rat cardiac muscle is more sensitive to the rate of stimulation at low external calcium concentrations (e.g., 0.5 nw) than at high external calcium concentrations (e.g., equal to or higher than 2.5 mM) (Forester and Mainwood, 1974). The difference in response of the trabeculae to frequency potentiation at low (0.5 mM) and high (2.5 HIM) external calcium concentrations was used to study whether the extracellular calcium concentration has a direct influence on the shape of the relation between tension and sarcomere length, or whether [Ca 2+ ] o exerts its influence through the calcium turnover within the cell.…”

Section: Frequency Potentiation and Tension Development At Low Calciumentioning

confidence: 99%

Tension development and sarcomere length in rat cardiac trabeculae. Evidence of length-dependent activation.

Keurs¹,

Rijnsburger²,

Heuningen³

et al. 1980

Circulation Research

328

100

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SUMMARY We studied the influence of inotropic factors on the shape of the relation between tension and sarcomere length. Tension measurements were performed on thin trabeculae dissected from the right ventricle of the rat heart. Sarcomere length was measured by laser diffraction techniques and controlled by a servomotor system. The relations between tension and sarcomere length were derived from contractions at various extracellular calcium concentrations [Ca 2+ ] o . The time course of tension development was dependent on both sarcomere length and [Ca 2+ ] o . At all [Ca 2+ ] o , the tension attained during contraction was zero at sarcomere lengths of 1.55-1.60 pm and maximal at a sarcomere length of 2.35 /im. Neither a summit nor a descending limb was found in the sarcomere length-tension relation. At [Ca 2+ ] o = 0.5 mM, tension increased linearly with sarcomere length, whereas at [Ca 2+ ] o = 2.5 mM, it approached maximal tension exponentially with sarcomere length. The relations between tension and sarcomere length derived from isometric contractions of the muscle and of sarcomeres were identical, and this suggests that shortening of sarcomeres does not contribute significantly to the effect of [Ca 2+ ] o . The relations between tension and sarcomere length obtained at [Ca 2+ ] o = 0.5 mM from contractions 30 seconds after a potentiating burst of stimuli (4 seconds at 4 Hz) were identical to the relation between tension and sarcomere length at [Ca 2+ ] o = 2.5 mm. Our results are consistent with the hypothesis that cardiac muscle length affects contractile performance by its influence on excitation contraction coupling. CircRes 46: [703][704][705][706][707][708][709][710][711][712][713][714] 1980 THE shape of the relation between tension and sarcomere length in cardiac papillary muscle suggests length-dependent activation of the contractile system (Jewell, 1977). However, there are no data on the effect of inotropic interventions on this curve. Only muscle length-tension curves are available, and these give conflicting results (Jewell, 1977;Huntsman and Stewart, 1977;Sonnenblick, 1962;Bodem et al., 1976). It is known that during isometric contractions there is considerable shortening of sarcomeres in the central region of papillary muscle. This happens at the expense of stretch of damaged regions near the clamps holding the ends of the specimen (Krueger and Pollack, 1975;Pollack and Krueger, 1976;Julian et al., 1976;Julian and Sollins, 1975). The damaged regions as well as the normal region may be influenced by inotropic factors. The interpretation of results of isometric contractions of the muscle is therefore ambiguous. The purpose of the present study was to examine the effect of different calcium concentrations on the relations Supported by Grants 74022 and 77086 from the Netherlands Heart Foundation.Dr. ter Keurs is an Established Investigator of the Netherlands Heart Foundation.Address for reprints: Henk E.D.J. ter Keurs, Department of Cardiology, Medical Faculty, State Un...

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“…Although the regulation of intramyocardial cell Ca2+ is an unsolved problem, there are indications that the Ca2+ taken up in vitro by the mitochondria, in absence of complexing anions, is easily released by a variety of treatments (Carafoli, 1975). It is relevant in this context to remember that the myocardium is dependent on the external calcium levels (Forester & Mainwood, 1974). Furthermore, the Ca2+ binding to the mitochondria is particularly important for the work performance, contractility and tension developed by the heart (Sulakhe & Dhalla, 1971).…”

Section: Resultsmentioning

confidence: 99%

Coronary Reactions to Cardiac Hyperactivity and to Hypoxia in Isolated Perfused Heart of Rat

Sen

Sunahara

Talesnik

et al. 1977

British J Pharmacology

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I Continuous recording of cardiac force of contraction, heart rate and coronary flow from isolated perfused hearts of rats was used to study coronary reactions: (a) to cardiostimulation with noradrenaline, CaCl2, or electrically induced tachycardia; (b) to short duration stoppage of coronary inflow (hypoxia). 2 The heart rate was controlled by electrical pacing. Coronary vasodilatation resulted from cardiostimulation or hypoxia. This coronary response was greater at higher heart rates. 3 In parallel experiments administration of noradrenaline to hearts paced at different frequencies resulted in a rate-dependent elevation of adenosine-3',5'-cyclic monophosphate (cyclic AMP). 4 Duration of hypoxia leading to different degrees of reactive hyperaemia did not change the cardiac cyclic AMP levels. SCoronary vasodilatation due to increased cardiac metabolism produced by noradrenaline, Ca2+ or tachycardia was enhanced by the phosphodiesterase inhibitors diazoxide and papaverine while it was inhibited during the administration of prostaglandin E2. 6 Reactive hyperaemia was unaffected by diazoxide, papaverine or prostaglandin E2. 7 Catecholamine depletion by reserpine did not influence metabolic coronary dilatation nor the reactive hyperaemic responses. 8 We postulate that there are at least two types of coronary reactions: one in response to hypoxia, 'reactive hyperaemia', and another resulting from cardiac hyperactivity, 'metabolic coronary dilatation'. The latter, blocked by prostaglandin E2 and enhanced by diazoxide or papaverine, would be triggered by cyclic AMP while reactive hyperaemia would result from other mechanisms.

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Interval dependent inotropic effects in the rat myocardium and the effect of calcium

Cited by 91 publications

References 14 publications

Systems analysis of digoxin kinetics and inotropic response in the rat heart: effects of calcium and KB-R7943

Systems analysis of digoxin kinetics and inotropic response in the rat heart: effects of calcium and KB-R7943

Tension development and sarcomere length in rat cardiac trabeculae. Evidence of length-dependent activation.

Coronary Reactions to Cardiac Hyperactivity and to Hypoxia in Isolated Perfused Heart of Rat

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