Biochemical and structural correlates in unloaded and reloaded cat myocardium*

Kent, Robert L.; Uboh, Cornelius E.; Thompson, E. W.; Gordon, Sandra S.; Marino, Thomas A.; Hoober, J. Kenneth; Cooper, George

doi:10.1016/s0022-2828(85)80018-3

Cited by 49 publications

(19 citation statements)

References 31 publications

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“…In a recent study of protein synthesis in isolated hearts, it was found that increased cardiac load had a stimulatory effect on cardiac protein synthesis that could be dissociated from other potential contributors to this process (32). Finally, we have documented very rapid and substantial alterations in cardiac structure and function, which appear to be related almost entirely to changes in cardiac load in vivo (4,5,25,26), and we have attributed these structural and functional changes primarily to changes in cardiac protein biochemistry, with reduced and then augmented cardiac loads being correlated with reduced and increased amounts of contractile proteins (33).…”

Section: Differential Loadingmentioning

confidence: 85%

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

Th¹,

Kent²,

Uboh³

et al. 1985

J. Clin. Invest.

137

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The purpose of this study was to determine whether cardiac hypertrophy in response to hemodynamic overloading is a primary result of the increased load or is instead a secondary result of such other factors as concurrent sympathetic activation. To make this distinction, four experiments were done; the major experimental result, cardiac hypertrophy, was assessed in terms of ventricular mass and cardiocyte cross-sectional area. In the first experiment, the cat right ventricle was loaded differentially by pressure overloading the ventricle, while unloading a constituent papillary muscle; this model was used to ask whether any endogenous or exogenous substance caused uniform hypertrophy, or whether locally appropriate load responses caused ventricular hypertrophy with papillary muscle atrophy. The latter result obtained, both when each aspect of differential loading was simultaneous and when a previously hypertrophied papillary muscle was unloaded in a pressure overloaded right ventricle. In the second experiment, epicardial denervation and then pressure overloading was used to assess the role of local neurogenic catecholamines in the genesis of hypertrophy. The degree of hypertrophy caused by these procedures was the same as that caused by pressure overloading alone. In the third and fourth experiments, fi-adrenoceptor or a-adrenoceptor blockade was produced before and maintained during pressure overloading. The hypertrophic response did not differ in either case from that caused by pressure overloading without adrenoceptor blockade. These experiments demonstrate the following: first, cardiac hypertrophy is a local response to increased load, so that any factor serving as a mediator of this response must be either locally generated or selectively active only in those cardiocytes in which stress and/or strain are increased; second, catecholamines are not that mediator, in that adrenergic activation is neither necessary for nor importantly modifies the cardiac hypertrophic response to an increased hemodynamic load.

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Section: Differential Loadingmentioning

confidence: 85%

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

Th¹,

Kent²,

Uboh³

et al. 1985

J. Clin. Invest.

137

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show abstract

“…In adult cat heart in situ, unloading of the right ventricular papillary muscle resulted in a substantial cellular atrophy and a decrease in protein content, both of which were reversed when the muscle was "reloaded" by repairing the cut. 36 In the absence of contraction, incubation with serum or catecholamines promotes growth of myocytes in culture. demonstrated that «-adrenergic receptor stimulation of cultured myocytes increased cell surface area, increased protein content, and promoted expression of the oncogene c-myc, suggesting that catecholamine stimulation during the hypertrophic phase of cardiac development may promote myocyte enlargement.…”

mentioning

confidence: 99%

Genetic, neurohumoral, and hemodynamic influences on spontaneously hypertensive rat heart development in oculo.

Tucker

1990

Hypertension

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To distinguish among genetic, neurohumoral, and hemodynamic explanations for structural and functional differences in the hearts of young spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) control rats, embryonic SHR and WKY rat heart tissue was cultured in the anterior eye chamber of adult SHR and WKY rats. In study 1, atria from E-L2 WKY rat embryos grafted into anterior eye chambers of either SHR or WKY host rats achieved a larger size than did SHR grafts by 8 weeks in oculo (2.98 ±0. 75 ; WKY rat hearts, 1.75±0J9 vs. 2 J 9 ± 0 J 2 mm 1 ). Ventricle grafts from SHR embryos into SHR host rats beat more rapidly (165 ±19 beats/min) during weekly measurements than either WKY rat ventricles (92±9 beats/min in SHR hosts and 99±9 beats/min in WKY host rats) or SHR ventricles grafted into WKY host rats (109±7 beats/min, p<0Ml).In study 3, atria from E-13 SHR and WKY rat embryos were grafted into sympathectomized and intact eye chambers of SHR or WKY host rats. Sympathectomy of the eye chamber compromised growth of grafts into WKY host rats (1.54±0.24 vs. 0.90±0.14 mm 2 ) but not SHR hosts (1.54±0.25 vs. 1.73±0.24 mm 2 ). Grafts into sympathectomized eye chambers of WKY host rats beat more slowly than grafts into eye chambers with sympathetic innervatlon intact (282±14 vs. 202±14 beats/min); sympathectomy did not alter beating rate of grafts in SHR hosts (266±14 vs. 255±18 beats/min). These results suggest that the growth and beating rate of SHR atrial grafts may be less sensitive to sympathetic innervation than WKY rat atrial grafts. In these studies, SHR grafts did not grow larger than WKY heart grafts and did not show an increased intrinsic beating rate, suggesting that the cardiac hypertrophy and increased intrinsic beating rate observed in intact SHR are unlikely to result from direct genetic programming. (Hypertension 1990;15:247-256) T he predisposition to development of hypertension is manifested very early in rats of the spontaneously hypertensive rat (SHR) strain. Structural alterations in the heart and vasculature observed in young SHR may contribute to or may result from the increase in blood pressure. Blood pressure in SHR has been measured as early as 20 days of gestation and found to be elevated compared Because of technical difficulties, it is not known how early blood pressure in the SHR fetus becomes elevated relative to WKY rat controls. EcclestonJoyner and Gray 7 found both structural alterations in the vasculature and evidence of increased ventricular mass relative to body weight at 17 days of gestation in SHR compared with WKY rats. Possible explanations of these early structural alterations in the heart and vasculature include: 1) adaptation to the increased blood pressure of SHR, 2) altered development in response to neural or humoral signals, and 3) genetically programmed hypertrophy. 8 In hypertensive animals, hypertrophy of the heart and vascular walls results from increased pressure 9 and from non-pressure-related mechanisms.

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“…This adaptability to the environment may allow immature cardiomyocytes to remodel in response to reduced mechanical load differently from the loss of structural and functional integrity observed in unloaded adult heart. 42 Although LAL initially reduced LV loading, the subsequent increase in passive stiffness after LAL more closely resembled the changes in passive stiffness that occur in adult myocardium in response to increased mechanical load. We therefore investigated the role of microtubules in our LAL model because increased microtubule content has been associated with increased viscous damping in hypertrophied adult myocardium.…”

Section: Discussionmentioning

confidence: 72%

“…This increase in passive stiffness of embryonic myocardium in response to reduced mechanical load is in contrast to the response of the adult myocardium to unloading. 42,43 Rothen-Rutishauser et al 44 observed distinct differences in neonatal rat cardiomyocytes and adult rat cardiomyocytes in their requirement for intact microtubules in culture. They showed that adult cardiomyocytes lose a certain degree of flexibility due to their longer adaptation to specific situations in the heart, whereas neonatal cardiomyocytes can maintain and reassemble myofibrils even after microtubules are destroyed.…”

Section: Discussionmentioning

confidence: 99%

Microtubule Involvement in the Adaptation to Altered Mechanical Load in Developing Chick Myocardium

Schroder

Tobita

Tinney

et al. 2002

Circulation Research

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Abstract-Mechanical load regulates ventricular growth, function, and structure from the earliest stages of cardiac morphogenesis through senescence. Dramatic changes in cardiac form and function have been defined for developing cardiovascular systems, and changes in mechanical loading conditions can produce structural malformations such as left heart hypoplasia. To date, relatively little is known regarding the interactions between changes in mechanical load, morphogenesis, and the material properties of the embryonic heart. We tested the hypothesis that passive material properties in the embryonic heart change in response to altered mechanical load and that microtubules play an important role in this adaptive response. We measured biaxial passive stress-strain relations in left ventricular (LV) myocardial strips in chick embryos at Hamburger-Hamilton stage 27 following left atrial ligation (LAL) at stage 21 to reduce LV volume load and create left heart hypoplasia. Following LAL, myocardial stresses at given strains and circumferential stiffness increased versus control strips. Western blot analysis of LAL embryos showed an increase in both total and polymerized ␤-tubulin and confocal microscopy confirmed an increase in microtubule density in the LV compact layer versus control. Following colchicine treatment, LV stresses and stiffness normalized in LAL specimens and microtubule density following colchicine was similar in LAL to control. In contrast, Taxol treatment increased myocardial stresses and stiffness in control strips to levels beyond LAL specimens. Thus, the material properties of the developing myocardium are regulated by mechanical load and microtubules play a role in this adaptive response during cardiac morphogenesis.

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Biochemical and structural correlates in unloaded and reloaded cat myocardium*

Cited by 49 publications

References 31 publications

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

Genetic, neurohumoral, and hemodynamic influences on spontaneously hypertensive rat heart development in oculo.

Microtubule Involvement in the Adaptation to Altered Mechanical Load in Developing Chick Myocardium

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