Preload-induced changes in isometric tension and [Ca2+](i) in rat myocardium

Abstract Preload-induced changes of active tension and [Ca2+]i are “dissociated” in mammalian myocardium. This study aimed to describe the distinct effects of preload at low and physiological [Ca2+]o. Rat RV papillary muscles were studied in isometric conditions at 25‡C and 0.33 Hz at 1 mM (hypo-Ca group) and 2.5 mM [Ca2+]o (normal-Ca group). [Ca2+]i was monitored with fura-2/AM. Increase of preload caused a rise of active tension in hypo-Ca and normal-Ca groups whereas peak fluorescence rose significantly only at low [Ca2+]o. End-diastolic tension, end-diastolic level of fluorescence, time-to-peak tension, but not time-to-peak of Ca2+ transient, progressively increased with preload. Mechanical relaxation decelerated with preload while Ca2+ transient decay time decreased in the initial phase and increased in the late phase, resulting in a prominent “bump” configuration. The “bump” was assessed as a ratio of its area to the fluorescence trace area. It was a new finding that the preload-induced rise of this ratio was twice as large in hypo-Ca. Our results indicate that preload-induced changes in active tension and [Ca2+]i are “dissociated” in rat myocardium, with relatively higher expression at low [Ca2+]o. Ca-dependence of Ca-TnC association/dissociation kinetics is thought to be a main contributor to these preload-induced effects.</jats:p

Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless ‘Frank–Starling Gain’ index

This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties

Differences in Effects of Length-Dependent Regulation of Force and Ca2+ Transient in the Myocardial Trabeculae of the Rat Right Atrium and Ventricle

The comparative differences in the fundamental mechanisms of contractility regulation and calcium handling of atrial and ventricular myocardium remain poorly studied. An isometric force&ndash;length protocol was performed for the entire range of preloads in isolated rat right atrial (RA) and ventricular (RV) trabeculae with simultaneous measurements of force (Frank-Starling mechanism) and Ca2+ transients (CaT). Differences were found between length-dependent effects in RA and RV muscles: (a) the RA muscles were stiffer, faster, and presented with weaker active force than the RV muscles throughout the preload range; (b) the active/passive force&mdash;length relationships were almost linear for the RA and RV muscles; (c) the value of the relative length-dependent growth of passive/active mechanical tension did not differ between the RA and RV muscles; (d) the time-to-peak and amplitude of CaT did not differ between the RA and RV muscles; (e) the CaT decay phase was essentially monotonic and almost independent of preload in the RA muscles, but not in the RV muscles. Higher peak tension, prolonged isometric twitch, and CaT in the RV muscle may be the result of higher Ca2+ buffering by myofilaments. The molecular mechanisms that constitute the Frank-Starling mechanism are common in the rat RA and RV myocardium

Contractile Behavior of Right Atrial Myocardium of Healthy Rats and Rats with the Experimental Model of Pulmonary Hypertension

There is a lack of data about the contractile behavior of the right atrial myocardium in chronic pulmonary heart disease. We thoroughly characterized the contractility and Ca transient of isolated right atrial strips of healthy rats (CONT) and rats with the experimental model of monocrotaline-induced pulmonary hypertension (MCT) in steady state at different preloads (isometric force-length), during slow force response to stretch (SFR), and during post-rest potentiation after a period of absence of electrical stimulation (PRP). The preload-dependent changes in the isometric twitch and Ca transient did not differ between CONT and MCT rats while the kinetics of the twitch and Ca transient were noticeably slowed down in the MCT rats. The magnitude of SFR was significantly elevated in the MCT right atrial strips and this was accompanied by the significantly higher elevation of the Ca transient relative amplitude at the end of SFR. The slow changes in the contractility and Ca transient in the PRP protocol did not differ between CONT and MCT. In conclusion, the alterations in the contractility and Ca transient of the right atrial myocardium of monocrotaline-treated rats with pulmonary hypertension mostly concern the elevation in SFR. We hypothesize that this positive inotropic effect in the atrial myocardium may (partly) compensate the systolic deficiency of the right ventricular failing myocardium.</jats:p

Contractile Behavior of Right Atrial Myocardium of Healthy Rats and Rats with the Experimental Model of Pulmonary Hypertension

There is a lack of data about the contractile behavior of the right atrial myocardium in chronic pulmonary heart disease. We thoroughly characterized the contractility and Ca transient of isolated right atrial strips of healthy rats (CONT) and rats with the experimental model of monocrotaline-induced pulmonary hypertension (MCT) in steady state at different preloads (isometric force-length), during slow force response to stretch (SFR), and during post-rest potentiation after a period of absence of electrical stimulation (PRP). The preload-dependent changes in the isometric twitch and Ca transient did not differ between CONT and MCT rats while the kinetics of the twitch and Ca transient were noticeably slowed down in the MCT rats. The magnitude of SFR was significantly elevated in the MCT right atrial strips and this was accompanied by the significantly higher elevation of the Ca transient relative amplitude at the end of SFR. The slow changes in the contractility and Ca transient in the PRP protocol did not differ between CONT and MCT. In conclusion, the alterations in the contractility and Ca transient of the right atrial myocardium of monocrotaline-treated rats with pulmonary hypertension mostly concern the elevation in SFR. We hypothesize that this positive inotropic effect in the atrial myocardium may (partly) compensate the systolic deficiency of the right ventricular failing myocardium