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

Abstract

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...

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). On the other hand, inhibition of SR function did not diminish the SFR in rat (Calaghan and White, 2004;Kentish and Wrzosek, 1998) and rabbit ventricle (Bluhm and Lew, 1995).…”

The effects of muscle length on intracellular calcium transients in mammalian cardiac muscle.

“…This suggestion is consistent with the finding (Allen, 1977) that action potential duration increases with muscle length. Chuck & Parmley (1980) The slow changes in tension lead to changes in the steepness of the tension-length relation as pointed out by Parmley & Chuck (1973) and Lakatta & Jewell (1977) and demonstrated in Fig. 6.…”

Length dependence of activation studied in the isovolumic blood-perfused dog heart.

“…As a consequence, a new concept has emerged: that muscle length influences inotropic state, and, therefore, a change of muscle length must be regarded as an inotropic intervention. In this respect, the results of previous studies (Parmley and Chuck, 1973;Gulch and Jacob, 1975;Allen, 1977;Lakatta and Jewell, 1977;Chuck and Parmley, 1980;Allen and Kurihara, 1982), which have analyzed changes in active tension when isolated muscle preparations were suddenly stretched, are of particular relevance to the present investigation. Muscle performance is altered in two phases after a sudden stretch: there is an instantaneous increase in developed tension, followed by a relatively slow, time-• dependent increase in tension.…”

“…Muscle performance is altered in two phases after a sudden stretch: there is an instantaneous increase in developed tension, followed by a relatively slow, time-• dependent increase in tension. It also has been shown (Parmley and Chuck, 1973;Lakatta and Jewell, 1977;Chuck and Parmley, 1980;Allen and Kurihara, 1982) that inotropic interventions alter the magnitude of both the sudden elevation and the time-dependent increase in developed tension, as well as the time-course of the myocardial response to stretch. These findings are not in agreement with the concept that simple physical factors alone determine myocardial length-tension relations (Jewell, 1977).…”