The George Fahr Lecture

Burch, George E.; Ray, Cynthia; Cronvich, J. A.

doi:10.1161/01.cir.5.4.504

Cited by 168 publications

(12 citation statements)

References 5 publications

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“…[Concentric hypertrophy is marked by increases in wall thickness with relatively little change in ventricular volume; eccentric hypertrophy is marked by increases in both wall thickness and ventricular cavity size.] According to Grossman’s pioneering stress-adaptation hypothesis, these increases in wall thickness are an adaptive response 10 ; based on Laplace’s law, ventricular wall stress is proportional to both ventricular pressure and cavity radius and inversely proportional to ventricular wall thickness 11 . Thus, increases in wall thickness tend to lessen wall stress and thereby diminish oxygen demand.…”

Section: Cardiomyocyte Hypertrophy: Comprehensive Reprogramming Of Thmentioning

confidence: 99%

Inhibition of Hypertrophy Is a Good Therapeutic Strategy in Ventricular Pressure Overload

2015

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Section: Cardiomyocyte Hypertrophy: Comprehensive Reprogramming Of Thmentioning

confidence: 99%

Inhibition of Hypertrophy Is a Good Therapeutic Strategy in Ventricular Pressure Overload

2015

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“…According to Laplace's law, wall stress is directly proportional to pressure and chamber size and inversely proportional to ventricular wall thickness (7). In response to high blood pressure, left ventricular wall thickness increases, normalizing wall stress.…”

Section: Mechanisms Of Remodeling In Hypertensive Heart Diseasementioning

confidence: 99%

Autophagy in Hypertensive Heart Disease

Wang

Rothermel

Hill

2010

Journal of Biological Chemistry

103

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In response to hypertension, the heart manifests robust hypertrophic growth, which offsets load-induced elevations in wall stress. If sustained, this hypertrophic response is a major risk factor for systolic dysfunction and heart failure. Extensive research efforts have focused on the progression from hypertrophy to failure; however, precise understanding of underlying mechanisms remains elusive. Recently, autophagy, a process of cellular cannibalization, has been implicated. Autophagy is activated during ventricular hypertrophy, serving to maintain cellular homeostasis. Excessive autophagy eliminates, however, essential cellular elements and possibly provokes cell death, which together contribute to hypertension-related heart disease.Hypertension is a leading risk factor for mortality worldwide (1). Astonishingly, in 2000, Ͼ25% of the world's adult population was hypertensive (2). The hypertensive population is projected to reach 1.56 billion in 2025, a 60% increase over 25 years. Based on data from the latest National Health and Nutrition Examination Survey, 27% of American adults have hypertension as defined by a systolic blood pressure of 140 mm Hg or higher and/or a diastolic blood pressure of 90 mm Hg or higher (3). Moreover, recent studies highlight an important association between cardiovascular event rates and pre-hypertension, a state affecting Ͼ30% of the American population and defined as a systolic blood pressure between 120 and 139 mm Hg and/or a diastolic blood pressure between 80 and 89 mm Hg (3, 4). Because of the fact that hypertension provokes no symptoms, it is often neglected; it is estimated that one-third of hypertensive patients are not aware of their condition. Incomplete awareness plus barriers to treatment on both the patient and the care provider sides of the healthcare equation together add up to a disease with extraordinarily high prevalence and rising incidence. Indeed, it is difficult to conceive of an illness (hypertension plus pre-hypertension) that afflicts Ͼ60% of adults in the United States.Mounting epidemiological evidence demonstrates a linear and independent relationship between hypertension and CVD, 2 the leading cause of death worldwide (5). Ischemic heart disease and cerebrovascular disease account for more than one-fifth of mortality in both developing and developed countries (5). In the United States, one in three adults has one or more types of CVD, and a death results every 37 s (6). In 2008, the direct and indirect costs of CVD were estimated at $450 billion, an enormous burden to our economic and public health systems. Mechanisms of Remodeling in Hypertensive Heart DiseaseIncreased afterload precipitates increases in systolic wall stress within the pumping left ventricle. According to Laplace's law, wall stress is directly proportional to pressure and chamber size and inversely proportional to ventricular wall thickness (7). In response to high blood pressure, left ventricular wall thickness increases, normalizing wall stress. As post-mitotic cells, cardiomyocytes...

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“…The finding that the cardiac ventricle does not normally function with extended sarcomeres, a condition where increasing fiber length decreases active tension by reducing the number of sites for interaction between actin and myosin (2), may reflect the geometrical constraints upon the performance of the intact heart (3,4). Because the heart is a hollow muscular pump in which impaired contractile performance will increase the residual volume at the end of systole, a stable equilibrium can be achieved only when dilatation improves the ability to eject.…”

mentioning

confidence: 99%

Regulation of Cardiac Muscle Contractility

Katz

1967

The Journal of General Physiology

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The heart's physiological performance, unlike that of skeletal muscle, is regulated primarily by variations in the contractile force developed by the individual myocardial fibers. In an attempt to identify the basis for the characteristic properties of myocardial contraction, the individual cardiac contractile proteins and their behavior in contractile models in vitro have been examined. The low shortening velocity of heart muscle appears to reflect the weak ATPase activity of cardiac myosin, but this enzymatic activity probably does not determine active state intensity. Quantification of the effects of Ca ++ upon cardiac actomyosin supports the view that myocardial contractility can be modified by changes in the amount of calcium released during excitationcontraction coupling. Exchange of intracellular K + with Na + derived from the extracellular space also could enhance myocardial contractility directly, as highly purified cardiac actomyosin is stimulated when K + is replaced by an equimolar amount of Na +. On the other hand, cardiac glycosides and catecholamines, agents which greatly increase the contractility of the intact heart, were found to be without significant actions upon highly purified reconstituted cardiac actomyosin.Regulation of contraction in mammalian cardiac and skeletal muscle, which have many common biochemical and morphological features, is achieved by different physiological mechanisms. Rapid trains of stimuli delivered to a skeletal muscle fiber through its motor nerve enhance tension development by causing the summation of individual contractile responses or, in its fully developed form, a powerful tetanic contraction. In the heart, on the other hand, fusion of contractile responses does not occur because the refractory period persists almost to the end of the active state. Recruitment of increasing numbers of active motor units plays a major role in augmenting the tension developed by a skeletal muscle, whereas all fibers of the heart, which is a functional syncytium, are normally activated during each cardiac systole.The tension generated by both cardiac and skeletal muscle fibers is influenced by initial fiber length (the length-tension relationship of skeletal muscle, and Starling's law of the heart), but the relatively less compliant myocardial fiber appears to operate with shorter sarcomeres than does that x85

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The George Fahr Lecture

Cited by 168 publications

References 5 publications

Inhibition of Hypertrophy Is a Good Therapeutic Strategy in Ventricular Pressure Overload

Inhibition of Hypertrophy Is a Good Therapeutic Strategy in Ventricular Pressure Overload

Autophagy in Hypertensive Heart Disease

Regulation of Cardiac Muscle Contractility

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