Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult

Abstract

Key pointsr The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype r Chronic intermittent workload induced features of adaptive hypertrophy r This was paralleled by protection against acute pressure overload insult r The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. AbstractThe present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg -1 , S.C.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week -1 for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca Abbreviations Akt/mTOR, protein kinase B/mammalian target of rapamycin; BN, blue native; BW, body weight; CO, cardiac output; dP/dt max , peak rate of pressure rise; dP/dt min , peak rate of pressure fall; ESP, end-systolic pressure; EDP, end-diastolic pressure; ESV, end-systolic volume; EDV, end-diastolic volume; E a , arterial elastance; EF, ejection fraction; ESPVR, end-systolic pressure volume relation; E max , maximal elastance; EDPVR, end-diastolic pressure volume relation; Gast/BW, gastrocnemius weight/body weight; Gast, gastrocnemius weight; HR, heart rate; HW, heart weight; HW/BW, heart weight/body weight; LV, left ventricle; LV+S, left ventricle+septum; LV+S/BW, left ventricle+septum/body weight; LVP max , left ventricular peak systolic pressure; MHC, myosin heavy chain; PRSW, preload-recrutable stroke work; P max , peak systolic pressure; SERCA2a, sarcoplasmic reticulum Ca 2+

Regulation of the Adaptive Response of Cardiac Cells to Ischemia: Role of Nanovesicles

“…Physiological hypertrophy occurs in response to a transient increase in cardiac work (i.e. exercise, pregnancy, overweight) [26] and it is distinguished from genetic familial hypertrophic cardiomyopathy mutations [27] in which the stimulus for hypertrophy is intrinsic to the cardiomyocyte. Conversely, reactive hypertrophy, a pathological form of hypertrophy, occurs after an injury that causes cell loss and matrix degradation and would provide compensatory morbidity and mortality worldwide.…”

Pathological vs. physiological cardiac hypertrophy

“…In this issue of The Journal of Physiology, a group of researchers form Portugal performed a study to address the question of whether submitting the heart to intermittent and tolerable amounts of stress, independent of its nature, could induce a cardiac phenotype that would fit within the 'physiological' spectrum (Moreira-Goncalves et al 2015).…”

Nature versus exposure: matched exposure to circulatory stressors of different natures elicits adaptive remodelling

“…Recently, Moreira‐Gonçalves et al . () examined whether the LV hypertrophic response to chronic overload is dependent on the features of the overload (magnitude and duration) rather than the inducing nature. Male Wistar rats were subjected to controlled chronic intermittent exercise training or pharmacological β‐adrenergic stimulation (dobutamine).…”

“…In the present study by Moreira‐Gonçalves et al . (), LV chamber performance following treatment was evaluated at baseline, in response to sustained acute afterload increase, and in terms of isovolumetric LV performance. All groups appeared able to sustain the 35% increase in systolic pressure for 120 min.…”

“…Moreira‐Gonçalves et al . () highlight a currently evolving literature considering the concept of ‘excessive’ exercise training as support for the concept that stimulus quantity (volume) is an important determinant of remodelling pattern (Benito et al . ), potentially more so than quality (type).…”