Influence of Caffeine and Other Inotropic Interventions on the Onset of Unloaded Shortening Velocity in Mammalian Heart Muscle

Henderson, A R; Claes, Victor; Brutsaert, Dirk L.

doi:10.1161/01.res.33.3.291

Cited by 17 publications

(6 citation statements)

References 29 publications

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“…Caffeine, however, markedly increases calcium release and decreases the stores of calcium by increasing the calcium permeability of the SR (Blayney et al, 1978). The mechanical effects of caffeine are a delayed onset of activation (Henderson et al, 1973), increased time-to-peak force and slowed relaxation (Henderson et al, 1974). In the presence of these major effects of caffeine, lengthening the muscle might not further increase SR calcium release.…”

Section: Reversal Of Length-dependent Contractile State/chuck and Parmentioning

confidence: 99%

Caffeine reversal of length-dependent changes in myocardial contractile state in the cat.

Chuck¹,

Parmley²

1980

Circulation Research

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SUMMARY The present study evaluated potential mechanisms for the slow length-dependent change in myocardial contractile state. Using 40 isolated right ventricular cat papillary muscles, we found that 10 mM caffeine reversed the subsequent slow change in myocardial performance following a change in muscle length. Since caffeine acts both at the sarcolemma and the sarcoplasmic reticulum, we attenuated the sarcolemmal influx of calcium with verapamil, manganese, and low external calcium concentration. None of these interventions altered the caffeine reversal of the length-dependent effect. It thus appears that the length-dependent alteration of contractile state is of intracellular origin, and probably related to altered calcium handling by the sarcoplasmic reticulum. Circ Res 47: 592-598, 1980 THE relationship between muscle length and cardiac performance has been described by the FrankStarling relationship. After an increase in end-diastolic fiber length along the ascending limb of this relationship, there is an increase in cardiac performance. At any given length, positive inotropic agents can further increase cardiac performance. Thus, the traditional view was that these two mechanisms for altering cardiac performance were independent of each other. The Frank-Starling relationship was explained by a variation in the number of crossbridges formed between the contractile proteins (Gordon et al., 1966). The positive inotropic response was explained by an increase in the rate of interaction of these cross-bridges (Katz, 1970).Contrary to the traditional belief that these two mechanisms for altering cardiac performance were separate from one another, we reported a slow length-dependent change in myocardial contractile state (Parmley and Chuck, 1973). In isolated cat papillary muscles, the immediate response to an increase of muscle length was followed by a slow additional increase in performance. Thus, in addition to the instantaneous length, the length history becomes an important determinant of the "FrankStarling" response. Subsequent studies have suggested that the immediate increase in force along the ascending limb is due not so much to myofilament and cross-bridge overlap, but to a lengthdependent alteration in the amount of calcium activating these cross-bridges (Allen et al., 1974;Jewell, 1977;Lakatta and Jewell, 1977;Fabiato and Fabiato, 1975 Received June 4, 1979; accepted for publication May 27,1980. tions the traditional separation between alterations in performance due to length and contractility. In our early attempts to identify a mechanism for the slow time-dependent coupling between muscle length and contractile state, we ruled out crosssectional area, release of stored catecholamines, temperature effects (24°-37°C), or series viscous elements as mechanisms for this observation (Parmley and Chuck, 1973). We did find, however, that varying the external calcium concentration changed the magnitude of the slow response, suggesting a calcium-mediated mechanism. In this paper, we report additional s...

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Section: Reversal Of Length-dependent Contractile State/chuck and Parmentioning

confidence: 99%

Caffeine reversal of length-dependent changes in myocardial contractile state in the cat.

Chuck¹,

Parmley²

1980

Circulation Research

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“…The transient augmentation of the velocity-length relationship demonstrable for twitch contractions following an abrupt reduction in load under certain circumstances 10 ' "• 13 appears to be analogous to the first phase of the isotonic oscillatory response we have studied, when analyzed in terms of its velocity-length relations (Fig. 9).…”

Section: Transient Response To An Abrupt Decrease In Load During Actimentioning

confidence: 73%

“…Transient augmentation of the velocity-length relationship after an abrupt reduction in load, which is shown to be analogous to the first phase of the isotonic oscillatory response, is not seen in normal Ca-mediated contractions of mammalian heart muscle but occurs under three conditions: Sr-mediated contractions of cat muscle, 13 Ca-mediated contractions of cat muscles exposed to caffeine, 10 and contractions of frog muscles (Ca-or Sr-mediated)." These three conditions have in common an implicit inability to sequester Ca or Sr rapidly.…”

Section: Figure 9 Abrupt Reduction In Load During Normal Ca-mediated mentioning

confidence: 93%

Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle.

Henderson¹,

Cattell²

1976

Circulation Research

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SUMMARY The plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude <5% Z. ma> ) was obtained. Isotonic oscillations were less damped than their isometric counterparts, implying positive feedback and thus a causal role of the perturbation in length. Oscillation frequency was 2-3 Hz at 29°C (

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“…Isolated papillary muscle preparations of cat and rat hearts were mounted and their mechanical performance studied as previously described (Henderson, Brutsaert, Parmley & Sonnenblick, 1969;Henderson, Claes & Brutsaert, 1973b). Rats (male Wistar, 400-450 g) were killed by stunning, and cats were anaesthetized with sodium pentobarbitone (40 mg/kg intraperitoneal injection).…”

Section: Methodsmentioning

confidence: 99%

“…The characteristics of isometric contractions and maximum unloaded shortening velocity (V,,.x) were measured, each under stable loading conditions (Henderson et al, 1973a). Vmax was measured directly by abruptly reducing load to zero at the beginning of contraction as previously described (Brutsaert, Claes & Sonnenblick, 1971;Henderson et al, 1973b). The steady state isometric force-frequency relationship (over the range 0.3 to 24/min) and maximum post extrasystolic potentiation (using the shortest effective coupling interval) were measured in cat muscles.…”

Section: Methodsmentioning

confidence: 99%

Effects of Δ‐trans‐tetrahydrocannabinol on Mechanical Performance of Isolated Heart Muscle Preparations

Graham¹,

Grey²,

Henderson³

et al. 1978

British J Pharmacology

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1 The effects of four concentrations of A'-trans-tetrahydrocannabinol (A1-THC) (0.1, 1, 5 and 20 gg/ml) were compared to that of the vehicle (ethanol, 0.5 Ml/ml) on the mechanical performance of isolated cardiac muscle of the cat and rat. 2 In rat isolated papillary muscles, A1-THC (20 ig/ml) caused a decline in mechanical performance (-8% in developed tension and -11% in V,',x) in contrast to the apparent lack of effect of ethanol.3 All other parameters of mechanical performance studied in both rat and cat papillary muscles were unaffected by A'-THC when compared with ethanol. 4 It was concluded that A'-THC in concentrations up to 20 ug/ml had negligible effect on contractile performance, the time course of contraction or muscle elasticity in rat and cat isolated papillary muscle preparations under the conditions studied.

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Influence of Caffeine and Other Inotropic Interventions on the Onset of Unloaded Shortening Velocity in Mammalian Heart Muscle

Cited by 17 publications

References 29 publications

Caffeine reversal of length-dependent changes in myocardial contractile state in the cat.

Caffeine reversal of length-dependent changes in myocardial contractile state in the cat.

Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle.

Effects of Δ‐trans‐tetrahydrocannabinol on Mechanical Performance of Isolated Heart Muscle Preparations

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