Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

Janssen, Paul M. L.; Periasamy, Muthu

doi:10.1016/j.yjmcc.2007.08.012

Cited by 89 publications

(97 citation statements)

References 56 publications

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“…Under such unloaded conditions, cross-bridges cycle much faster than loaded crossbridges, and the sequestration rate by the SR may indeed limit cytosolic calcium decline (21). However, under loaded conditions, relaxation of the myocardium may be more closely linked to myofilment properties (21, 22).…”

Section: Discussionmentioning

confidence: 99%

Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo

O’Donnell

Fields²,

Xu³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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O'Donnell JM, Fields A, Xu X, Chowdhury SA, Geenen DL, Bi J. Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo. Am J Physiol Heart Circ Physiol 295: H2483-H2494, 2008. First published October 24, 2008 doi:10.1152/ajpheart.01023.2008.-Adenoviral gene transfer of sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA)2a to the hypertrophic heart in vivo has been consistently reported to lead to enhanced myocardial contractility. It is unknown if the faster skeletal muscle isoform, SERCA1, expressed in the whole heart in early failure, leads to similar improvements and whether metabolic requirements are maintained during an adrenergic challenge. In this study, Ad.cmv.SERCA1 was delivered in vivo to aortic banded and shamoperated Sprague-Dawley rat hearts. The total SERCA content increased 34%. At 48 -72 h posttransfer, echocardiograms were acquired, hearts were excised and retrograded perfused, and hemodynamics were measured parallel to NMR measures of the phosphocreatine (PCr)-to-ATP ratio (PCr/ATP) and energy substrate selection at basal and high workloads (isoproterenol). In the Langendorff mode, the rate-pressure product was enhanced 27% with SERCA1 in hypertrophic hearts and 10% in shams. The adrenergic response to isoproterenol was significantly potentiated in both groups with SERCA1.31 P NMR analysis of PCr/ATP revealed that the ratio remained low in the hypertrophic group with SERCA1 overexpression and was not further compromised with adrenergic challenge.13 C NMR analysis revealed fat and carbohydrate oxidation were unaffected at basal with SERCA1 expression; however, there was a shift from fats to carbohydrates at higher workloads with SERCA1 in both groups. Transport of NADH-reducing equivalents into the mitochondria via the ␣-ketoglutamate-malate transporter was not affected by either SERCA1 overexpression or adrenergic challenge in both groups. Echocardiograms revealed an important distinction between in vivo versus ex vivo data. In contrast to previous SERCA2a studies, the echocardiogram data revealed that SERCA1 expression compromised function (fractional shortening) in the hypertrophic group. Shams were unaffected. While our ex vivo findings support much of the earlier cardiomyocyte and transgenic data, the in vivo data challenge previous reports of improved cardiac function in heart failure models after SERCA intervention. sarco(endo)plasmic reticulum Ca 2ϩ -ATPase; glucose oxidation; fatty acid oxidation; phosphocreatine-to-ATP ratio; myocardial energy potential THE CHANGES in intracellular Ca 2ϩ handling reported for the failing myocardium have been linked to sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA). Calcium uptake into the sarcoplasmic reticulum (SR) by SERCA determines the rate of calcium removal for relaxation, the SR calcium content, and calcium released for contractions (33,45). In the failing heart, it has been proposed that SERCA contributes to reduced contractil...

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Section: Discussionmentioning

confidence: 99%

Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo

O’Donnell

Fields²,

Xu³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…In contrast, the increase is only about 50% for the rat and only 10% for the mouse (16). Similarly, Georgakopoulos and Kass (12) reported only modestly enhanced contraction and relaxation (13-15%) at heart rates between 400 and 500 bpm with a flat force-frequency relation with heart rate above 600 bpm in anesthetized, openchest mice.…”

Section: Mice/rat Comparisonsmentioning

confidence: 93%

“…In a recent review, Janssen and Periasamy (16) reported that the relative increase in isometric force, of small and thin ventricular trabeculae, within the in vivo frequency range for man, dog, and rabbit are similar, nearly doubling between resting and exercise heart rate. In contrast, the increase is only about 50% for the rat and only 10% for the mouse (16).…”

Section: Mice/rat Comparisonsmentioning

confidence: 99%

Ventricular function during exercise in mice and rats

Lujan

Janbaih

Feng

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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The mouse has many advantages over other experimental models for the molecular investigation of left ventricular (LV) function. Accordingly, there is a keen interest in, as well as an intense need for, a conscious, chronically instrumented, freely moving mouse model for the determination of cardiac function. To address this need, we used a telemetry device for repeated measurements of LV function in conscious mice at rest and during exercise. For reference, we compared the responses in mice to the responses in identically instrumented conscious rats. The transmitter body of the telemetry device (rat PA-C40; mouse PA-C10; Data Sciences International, St. Paul, MN) was placed in the intraperitoneal space through a ventral abdominal approach (rat) or subcutaneously on the left flank (mouse). The pressure sensor, located within the tip of a catheter, was inserted into the left ventricle through an apical stab wound (18 gauge for rat; 21 gauge for mouse) for continuous, nontethered, recordings of pulsatile LV pressure. A minimum of 1 wk was allowed for recovery and for the animals to regain their presurgical weight. During the recovery period, the animals were handled, weighed, and acclimatized to the laboratory, treadmill, and investigators. Subsequently, LV parameters were recorded at rest and during a graded exercise test. The results document, for the first time, serial assessment of ventricular function during exercise in conscious mice and rats. This methodology may be adopted for advancing the concepts and ideas that drive cardiovascular research.gene-manipulated; mouse models; embryonic stem cell technology THE MOUSE HAS SIGNIFICANT advantages over other experimental models for the molecular investigation of cardiac function. For example, with the exception of man, significantly more is known about the genetics of mice than any other mammal (5-9, 25, 29, 32). Furthermore, investigators have identified spontaneous mouse mutants and used embryonic stem cell technology to design mice with mutations in many nonlethal genes to understand cardiac function. Specifically, several gene-manipulated mouse models of cardiac hypertrophy and cardiac failure are now available (10,13,22,28,37,40). Accordingly, gene-manipulated mice are an important model in cardiovascular research (1, 4, 18 -20, 27, 30, 37).These ground-breaking efforts for gene-manipulated mouse models have generated an interest in, as well as a need for, a conscious, chronically instrumented, freely moving mouse model for the determination of cardiac function (36,38). Original work has made it possible to record ventricular pressure (14), as well as ventricular pressure and volume (17) in conscious, restrained mice (the mice were restrained in a soft plastic cone). These pioneering studies overcame the confounding influences of anesthesia and surgical trauma.However, the original, pioneering work recording ventricular function in conscious mice required that the mouse be restrained and/or tethered to the recording system (14, 17, 38). These procedures prev...

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“…7E). This phenomenon has been attributed to an increase in sarco/endoplasmic reticulum Ca 2ϩ -ATPase (SERCA) pump activity and enhanced SR Ca 2ϩ reuptake at high pacing rates (14,15).…”

Section: H885 Myocyte Repolarization and Myocardial Agingmentioning

confidence: 99%

Myocyte repolarization modulates myocardial function in aging dogs

Sorrentino

Signore

Qanud

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions. aging; myocardium; contractile reserve NEW & NOTEWORTHYWe have investigated the effects of aging on the heart using a genetically uniform large animal model, maintained under highly regulated conditions. Our results indicate that the myocyte compartment undergoes physiological alterations with age that negatively interfere with ventricular function.STUDIES OF MYOCARDIAL AGING in humans are complex, as it is difficult to separate the effects of time from genetic, ethnic, lifestyle, and environmental factors, which may modify physiological cardiac aging. Additionally, the incidence of cardiovascular diseases increases with age (24) and intervening pathologies may change the natural temporal evolution of the organ. Therefore, the mechanisms involved in the age-related deterioration of ventricular performance and decreased functional reserve of the old heart (9, 12, 17, 18, 39) remain to be properly defined.The general belief has been that abnormalities in ventricular compliance with age occur as a result of collagen deposition and diffuse interstitial fibrosis, which, together with cardiomyocyte loss, lead to depressed systolic and diastolic function (17,18,26,39). Additionally, myocardial hypertrophy has been proposed as a critical variable of the senescent myopathy (5), in spite of the lack of organ hypertrophy in older humans (25). Current understanding of the pathophysiology of the aging myopathy and the mechanisms involved in the increased incidence of heart failure and ...

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Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

Cited by 89 publications

References 56 publications

Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo

Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo

Ventricular function during exercise in mice and rats

Myocyte repolarization modulates myocardial function in aging dogs

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