Lithium and KB‐R7943 effects on mechanics and energetics of rat heart muscle

Bonazzola, Patricia; Egido, Patricia; Marengo, Fernando D.; Savio‐Galimberti, Eleonora; Ponce-Hornos, J. E.

doi:10.1046/j.1365-201x.2002.01001.x

Cited by 9 publications

(10 citation statements)

References 38 publications

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“…The H r measured in the presence of control perfusate (18.6 Ϯ 2.2 mW/g; n ϭ 11) is in agreement with the values reported in the literature (5,14). As shown in Fig.…”

Section: Discussionsupporting

confidence: 78%

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Mechanical and energetic effects of chronic chagasic patients' antibodies on rat myocardium

Savio‐Galimberti

Costa²,

Carvalho³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Chagasic (Ch) and nonchagasic (NCh) IgG fraction (20 microg/ml) effects on cardiac performance of adult Wistar rat ventricles were studied with a novel approach applying a microcalorimetric technique. Resting heat (Hr) was significantly decreased by Ch antibodies (DeltaHrCh = 4.8 +/- 0.9 mW/g). Although the Hr decrease can be associated with diminished activity of the Na+/K+ pump, the magnitude of the effect (25% of control Hr) indicates that additional processes may also be affected. Ch antibodies induced an initial increase in developed pressure (P), which was associated with a decreased contractile economy. However, after 30 min of Ch antibody perfusion, P reached a significantly lower level (DeltaPCh = 3.8 +/- 1.2 mN/mm2) without changes in active heat per beat (Ha'). Consequently, Ha'/P ratio increased, indicating that the energetic cost per unit of P was higher. In contrast, P and Ha' were both significantly and reversibly decreased by NCh antibodies (DeltaPNCh = 4.4 +/- 1.2 mN/mm2; DeltaHa'NCh = 9.7 +/- 2.2 mJ/g), but Ha'/P remained unaffected. According to these data, normal hearts exposed to Ch antibodies present a biphasic mechanical response: 1) an initial period of increased contractility (and decreased global muscle economy) consistent with antibodies with beta1-adrenergic activity, such as those used in the present study, and 2) a decrease in P at 30 min of Ch antibody perfusion, which suggests that another Ca(2+)-related mechanism is compromised. These data contribute to redefine the role of antibody-mediated responses in the pathophysiology of chronic chagasic cardiomyopathy as agents of myocardial failure.

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“…The H r measured in the presence of control perfusate (18.6 Ϯ 2.2 mW/g; n ϭ 11) is in agreement with the values reported in the literature (5,14). As shown in Fig.…”

Section: Discussionsupporting

confidence: 78%

“…The averaged water content for the present experiments was 80.9 Ϯ 0.9%, and the averaged dried weight of the tissue was 0.1571 Ϯ 0.01 g (n ϭ 11). Both values are in agreement with previously reported values (5,19). All of the energetic results included in this study are expressed per gram of dry weight.…”

Section: Methodssupporting

confidence: 68%

Mechanical and energetic effects of chronic chagasic patients' antibodies on rat myocardium

Savio‐Galimberti

Costa²,

Carvalho³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…The average water content in the present experiments was 82 Ϯ 0.3% (n ϭ 20), which is consistent with values previously published (5,36,50,51).…”

Section: Biological Preparationsupporting

confidence: 89%

“…Lithium was used because it reduces Ca 2ϩ uptake under intracellular Na ϩ -overload conditions (46), and the bigeminic couple is an example of such a condition (16,20,26). In addition, lithium also reduces contractile Ca 2ϩ availability under physiological conditions (5). Lithium was added to the perfusion medium in the presence of Ver (0.2/mol/l) to a final concentration of 45 mmol/l.…”

Section: Extracellular Ca 2ϩ Source: Ca 2ϩ Channels and Ncxmentioning

confidence: 99%

Effects of caffeine, verapamil, lithium, and KB-R7943 on mechanics and energetics of rat myocardial bigeminies

Savio‐Galimberti¹,

Ponce-Hornos²

2006

American Journal of Physiology-Heart and Circulatory Physiology

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We examined the effects of pharmacological alteration of Ca2+ sources on mechanical and energetic properties of paired-pulse ("bigeminic") contractions. The fraction of heat release that is related to pressure development and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricles. The heat released by regular and bigeminic contractions showed two brief pressure-independent components (H1 and H2) and a pressure-dependent component (H3). We used the ratio of active heat (Ha') to pressure-time integral (PtI) and the ratio of H3 to PtI to estimate the energetic cost of muscle contraction (overall economy) and pressure maintenance (contractile economy), respectively. Neither of these ratios was affected by stimulation pattern. Caffeine (an inhibitor of sarcoplasmic reticulum function) significantly decreased mechanical responses and increased the energetic cost of contraction (delta = 101 +/- 12.6%). Verapamil (an L-type Ca2+ channel blocker) decreased pressure maintenance of extrasystolic (delta = 43.4 +/- 3.7%) and postextrasystolic (delta = 37.5 +/- 3.5%) contractions without affecting postextrasystolic potentiation, suggesting that a verapamil-insensitive fraction is responsible for potentiation. The verapamil-insensitive fraction was further studied in the presence of lithium (45 mM) and KB-R7943 (5 microM), inhibitors of the Na+/Ca2+ exchanger. Both agents decreased all mechanical responses, including postextrasystolic potentiation (delta = 67.3 +/- 3.3%), without altering overall or contractile economies, suggesting an association of the verapamil-insensitive Ca2+ fraction to the sarcolemmal Na+/Ca2+ exchanger. The effect of the inhibitors of the Na+/Ca2+ exchanger on potentiation suggests an increased participation of extracellular Ca2+ (and, thus, a redistribution of the relative participation of the Ca2+ pools) during bigeminic contractions in rat myocardium.

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“…The technique immediately produced a flurry of publications (18, 114 -116, 120). It was later extended to accommodate the perfused rat whole heart, as well as either its isolated left ventricle or right atrium (125), complete with indwelling left ventricular balloon to alter mechanical energy demand (17,26,103,104,125) and, subsequently, the mouse heart (118), culminating in a demonstration of measuring the heat production of aliquots of isolated cardiac myocytes (117). Interestingly, the technique has not been adopted by other groups in the interim.…”

Section: Cardiac Muscle Myometrymentioning

confidence: 99%

Muscle heat: a window into the thermodynamics of a molecular machine

Loiselle

Johnston

Han

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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contraction of muscle is characterized by the development of force and movement (mechanics) together with the generation of heat (metabolism). Heat represents that component of the enthalpy of ATP hydrolysis that is not captured by the microscopic machinery of the cell for the performance of work. It arises from two conceptually and temporally distinct sources: initial metabolism and recovery metabolism. Initial metabolism comprises the hydrolysis of ATP and its rapid regeneration by hydrolysis of phosphocreatine (PCr) in the processes underlying excitation-contraction coupling and subsequent cross-bridge cycling and sliding of the contractile filaments. Recovery metabolism describes those process, both aerobic (mitochondrial) and anaerobic (cytoplasmic), that produce ATP, thereby allowing the regeneration of PCr from its hydrolysis products. An equivalent partitioning of muscle heat production is often invoked by muscle physiologists. In this formulation, total enthalpy expenditure is separated into external mechanical work (W) and heat (Q). Heat is again partitioned into three conceptually distinct components: basal, activation, and force dependent. In the following mini-review, we trace the development of these ideas in parallel with the development of measurement techniques for separating the various thermal components.Microcalorimetry; muscle heat production; myothermy; thermopiles MUSCLE IS A MOLECULAR machine. It operates isothermally, isobarically, and isovolumetrically. At the microscopic level, it directly converts the Free Energy component of the enthalpy of ATP hydrolysis into cyclic attachment and detachment of actomyosin cross bridges, together with transportation of ions up their electrochemical potential gradients. At the macroscopic level, two consequences result: the generation of force and the evolution of heat. Of these two entities, heat is by far the more difficult to quantify and to interpret. In this brief review, we trace the development of techniques to measure muscle heat production from the mid-19th century to the present, providing parallel commentary on the progressive understanding of muscle function. We give particular consideration to the development of techniques of separating the metabolic cost of cross-bridge cycling from the purely "overhead" cost of its activation.

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Lithium and KB‐R7943 effects on mechanics and energetics of rat heart muscle

Cited by 9 publications

References 38 publications

Mechanical and energetic effects of chronic chagasic patients' antibodies on rat myocardium

Mechanical and energetic effects of chronic chagasic patients' antibodies on rat myocardium

Effects of caffeine, verapamil, lithium, and KB-R7943 on mechanics and energetics of rat myocardial bigeminies

Muscle heat: a window into the thermodynamics of a molecular machine

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