Rat model of exercise-induced cardiac hypertrophy: hemodynamic characterization using left ventricular pressure-volume analysis

2013 ◽  
Vol 305 (1) ◽  
pp. H124-H134 ◽  
Author(s):  
Tamás Radovits ◽  
Attila Oláh ◽  
Árpád Lux ◽  
Balázs Tamás Németh ◽  
László Hidi ◽  
...  
Keyword(s):  
Exercise Training ◽  
Cardiac Hypertrophy ◽  
Rat Model ◽  
Left Ventricular ◽  
Heart Weight ◽  
Stroke Work ◽  
Functional Changes ◽  
Exercise Induced

Long-term exercise training is associated with characteristic structural and functional changes of the myocardium, termed athlete's heart. Several research groups investigated exercise training-induced left ventricular (LV) hypertrophy in animal models; however, only sporadic data exist about detailed hemodynamics. We aimed to provide functional characterization of exercise-induced cardiac hypertrophy in a rat model using the in vivo method of LV pressure-volume (P-V) analysis. After inducing LV hypertrophy by swim training, we assessed LV morphometry by echocardiography and performed LV P-V analysis using a pressure-conductance microcatheter to investigate in vivo cardiac function. Echocardiography showed LV hypertrophy (LV mass index: 2.41 ± 0.09 vs. 2.03 ± 0.08 g/kg, P < 0.01), which was confirmed by heart weight data and histomorphometry. Invasive hemodynamic measurements showed unaltered heart rate, arterial pressure, and LV end-diastolic volume along with decreased LV end-systolic volume, thus increased stroke volume and ejection fraction (73.7 ± 0.8 vs. 64.1 ± 1.5%, P < 0.01) in trained versus untrained control rats. The P-V loop-derived sensitive, load-independent contractility indexes, such as slope of end-systolic P-V relationship or preload recruitable stroke work (77.0 ± 6.8 vs. 54.3 ± 4.8 mmHg, P = 0.01) were found to be significantly increased. The observed improvement of ventriculoarterial coupling (0.37 ± 0.02 vs. 0.65 ± 0.08, P < 0.01), along with increased LV stroke work and mechanical efficiency, reflects improved mechanoenergetics of exercise-induced cardiac hypertrophy. Despite the significant hypertrophy, we observed unaltered LV stiffness (slope of end-diastolic P-V relationship: 0.043 ± 0.007 vs. 0.040 ± 0.006 mmHg/μl) and improved LV active relaxation (τ: 10.1 ± 0.6 vs. 11.9 ± 0.2 ms, P < 0.01). According to our knowledge, this is the first study that provides characterization of functional changes and hemodynamic relations in exercise-induced cardiac hypertrophy.

scholarly journals P74Reversible cardiac hypertrophy and left ventricular functional changes after exercise training in a rat model

2014 ◽  
Vol 103 (suppl 1) ◽  
pp. S12.2-S12
Author(s):  
A Olah ◽  
A Lux ◽  
BT Nemeth ◽  
C Matyas ◽  
D Kellermayer ◽  
...  
Keyword(s):  
Exercise Training ◽  
Cardiac Hypertrophy ◽  
Rat Model ◽  
Left Ventricular ◽  
Functional Changes

scholarly journals Hemodynamic characterization of a transgenic rat strain stably expressing the calcium sensor protein GCaMP2

2019 ◽  
Vol 316 (5) ◽  
pp. H1224-H1228 ◽  
Author(s):  
Attila Oláh ◽  
Mihály Ruppert ◽  
Tamás István Orbán ◽  
Ágota Apáti ◽  
Balázs Sarkadi ◽  
...  
Keyword(s):  
Systolic Function ◽  
Left Ventricular ◽  
Heart Weight ◽  
Transgenic Rat ◽  
Calcium Sensor ◽  
Transgenic Rats ◽  
Sensor Protein ◽  
Rat Strain

A novel transgenic rat strain has recently been generated that stably expresses the genetically engineered calcium sensor protein GCaMP2 in different cell types, including cardiomyocytes, to investigate calcium homeostasis. To investigate whether the expression of the GCaMP2 protein itself affects cardiac function, in the present work we aimed at characterizing in vivo hemodynamics in the GCaMP2 transgenic rat strain. GCaMP2 transgenic rats and age-matched Sprague-Dawley control animals were investigated. In vivo hemodynamic characterization was performed by left ventricular (LV) pressure-volume analysis. Postmortem heart weight data showed cardiac hypertrophy in the GCaMP2 group (heart-weight-to-tibial-length ratio: 0.26 ± 0.01 GCaMP2 vs. 0.23 ± 0.01 g/cm Co, P < 0.05). We detected elevated mean arterial pressure and increased total peripheral resistance in transgenic rats. GCaMP2 transgenesis was associated with prolonged contraction and relaxation. LV systolic function was not altered in transgenic rats, as indicated by conventional parameters and load-independent, sensitive indices. We found a marked deterioration of LV active relaxation in GCaMP2 animals (τ: 16.8 ± 0.7 GCaMP2 vs. 12.2 ± 0.3 ms Co, P < 0.001). Our data indicated myocardial hypertrophy, arterial hypertension, and impaired LV active relaxation along with unchanged systolic performance in the heart of transgenic rats expressing the GCaMP2 fluorescent calcium sensor protein. Special caution should be taken when using transgenic models in cardiovascular studies. NEW & NOTEWORTHY Genetically encoded Ca2+-sensors, like GCaMP2, are important tools to reveal molecular mechanisms for Ca2+-sensing. We provided left ventricular hemodynamic characterization of GCaMP2 transgenic rats and found increased afterload, cardiac hypertrophy, and prolonged left ventricular relaxation, along with unaltered systolic function and contractility. Special caution should be taken when using this rodent model in cardiovascular pharmacological and toxicological studies.

Angiotensin II type 2 receptor gene transfer elicits cardioprotective effects in an angiotensin II infusion rat model of hypertension

2004 ◽  
Vol 19 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Beverly L. Falcón ◽  
Jillian M. Stewart ◽  
Erick Bourassa ◽  
Michael J. Katovich ◽  
Glenn Walter ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Gene Transfer ◽  
Cardiac Hypertrophy ◽  
Rat Model ◽  
Lentiviral Vector ◽  
Receptor Gene ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley

The role of the angiotensin II type 2 receptor (AT2R) in cardiovascular physiology remains elusive. We have developed an in vivo lentiviral vector-mediated gene transfer system to study the physiological functions of the AT2R. Our objectives in this study were to determine whether the AT2R influences cardiac hypertrophy and myocardial and perivascular fibrosis in a nongenetic rat model of hypertension. Lentiviral vector containing the AT2R or saline was injected intracardially in 5-day-old Sprague-Dawley rats. This resulted in a persistent overexpression of the AT2R in cardiac tissues. At 15 wk of age, animals were infused with either 200 ng·kg−1·min−1 of angiotensin II or saline by implantation of a 4-wk osmotic minipump. This resulted in an increase in blood pressure (BP) that reached maximal by 2 wk of treatment and was associated with a 123% increase in left ventricular wall thickness (LVWT) and a 129% increase in heart weight to body weight ratios (HW/BW). In addition, the increase in cardiac hypertrophy was associated with a 300% and 158% increase in myocardial and perivascular fibrosis, respectively. Cardiac transduction of the AT2R resulted in an 85% attenuation of LVWT, 91% attenuation of HW/BW, and a 43% decrease in myocardial fibrosis induced by angiotensin infusion. These improvements in cardiac pathology were observed in the absence of attenuation of high BP. Thus our observations indicate that long-term expression of the AT2R in the heart attenuates cardiac hypertrophy and fibrosis in a nongenetic rat model of hypertension.

scholarly journals Inhibition of Cardiac Hypertrophy Effects in D-Galactose-Induced Senescent Hearts byAlpinate Oxyphyllae FructusTreatment

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yung-Ming Chang ◽  
Hen-Hong Chang ◽  
Hung-Jen Lin ◽  
Chin-Chuan Tsai ◽  
Chuan-Te Tsai ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Rat Model ◽  
Cerebrovascular Disorders ◽  
Treated Group ◽  
Left Ventricular ◽  
Heart Weight ◽  
Dependent Manner ◽  
Signaling Mechanism ◽  
Aging Rat ◽  
Whole Heart

Aging is a complex physiological phenomenon accelerated by ROS accumulation, with multisystem decline and increasing vulnerability to degenerative diseases and death. Cardiac hypertrophy is a key pathophysiological component that accompanies the aging process. Alpinate Oxyphyllae Fructus (Alpinia oxyphyllaMIQ, AOF) is a traditional Chinese medicine, which provides cardioprotective activity against aging, hypertension, and cerebrovascular disorders. In this study, we found the protective effect of AOF against cardiac hypertrophy in D-galactose-induced aging rat model. The results showed that treating rats with D-galactose resulted in pathological hypertrophy as evident from the morphology change, increased left ventricular weight/whole heart weight, and expression of hypertrophy-related markers (MYH7 and BNP). Both concentric and eccentric cardiac hypertrophy signaling proteins were upregulated in aging rat model. However, these pathological changes were significantly improved in AOF treated group (AM and AH) in a dose-dependent manner. AOF negatively modulated D-galactose-induced cardiac hypertrophy signaling mechanism to attenuate ventricular hypertrophy. These enhanced cardioprotective activities following oral administration of AOF reflect the potential use of AOF for antiaging treatments.

Physiological and pathological left ventricular hypertrophy of comparable degree is associated with characteristic differences of in vivo hemodynamics

2016 ◽  
Vol 310 (5) ◽  
pp. H587-H597 ◽  
Author(s):  
Attila Oláh ◽  
Balázs Tamás Németh ◽  
Csaba Mátyás ◽  
László Hidi ◽  
Árpád Lux ◽  
...  
Keyword(s):  
Stroke Volume ◽  
Systolic Pressure ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Heart Weight ◽  
Similar Degree ◽  
Active Relaxation ◽  
Myocardial Gene Expression

Left ventricular (LV) hypertrophy is a physiological or pathological response of LV myocardium to increased cardiac load. We aimed at investigating and comparing hemodynamic alterations in well-established rat models of physiological hypertrophy (PhyH) and pathological hypertrophy (PaH) by using LV pressure-volume (P-V) analysis. PhyH and PaH were induced in rats by swim training and by abdominal aortic banding, respectively. Morphology of the heart was investigated by echocardiography. Characterization of cardiac function was completed by LV P-V analysis. In addition, histological and molecular biological measurements were performed. Echocardiography revealed myocardial hypertrophy of similar degree in both models, which was confirmed by post-mortem heart weight data. In aortic-banded rats we detected subendocardial fibrosis. Reactivation of fetal gene program could be observed only in the PaH model. PhyH was associated with increased stroke volume, whereas unaltered stroke volume was detected in PaH along with markedly elevated end-systolic pressure values. Sensitive indexes of LV contractility were increased in both models, in parallel with the degree of hypertrophy. Active relaxation was ameliorated in athlete's heart, whereas it showed marked impairment in PaH. Mechanical efficiency and ventriculo-arterial coupling were improved in PhyH, whereas they remained unchanged in PaH. Myocardial gene expression of mitochondrial regulators showed marked differences between PaH and PhyH. We provided the first comparative hemodynamic characterization of PhyH and PaH in relevant rodent models. Increased LV contractility could be observed in both types of LV hypertrophy; characteristic distinction was detected in diastolic function (active relaxation) and mechanoenergetics (mechanical efficiency), which might be explained by mitochondrial differences.

scholarly journals Comparison of changes in electrical activity, in isolated and in vivo hearts, induced by voluntary exercise in female rats

2020 ◽  
Author(s):  
Rachel Stones ◽  
Mark Drinkhill ◽  
Ed White
Keyword(s):  
Exercise Training ◽  
Electrical Activity ◽  
Wheel Running ◽  
Left Ventricular ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Heart Weight ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

AbstractRegular mild exercise is recommended to the general population as beneficial to health. Regular exercise typically leads to structural and electrical remodelling of the heart but in human studies it is difficult to relate the extrinsic and intrinsic influences on intact hearts to changes seen at the single cell level. In this study we wished to test whether changes in electrical activity in intact hearts, in response to voluntary wheel running exercise training, were consistent with our previous observations in single cardiac myocytes and whether these changes resulted in altered susceptibility to arrhythmic stimuli.Female rats performed 5 weeks of voluntary wheel running. Implanted telemetry transmitters were used to measure electrocardiograms (ECGs) and determine heart rate variability (HRV) in conscious, unrestrained, trained (TRN) and sedentary (SED) animals. In isolated hearts, left ventricular epicardial monophasic action potentials (MAPs) were recorded and the responses to potentially arrhythmic interventions were assessed.Exercise training caused cardiac hypertrophy, as indexed by a significantly greater heart weight to body weight ratio. Consistent with previous measurements of action potential duration in single myocytes, MAPs were significantly longer at 50%, 75% and 90% repolarization. Arrhythmic susceptibility was not different between SED and TRN hearts. Trained animals displayed significantly altered HRV by week 5, in a manner consistent with reduced sympathetic tone, however resting ECG parameters, including those most associated with repolarisation duration, were unaltered. We conclude that intrinsic changes to cellular cardiac electrophysiology, induced by mild voluntary exercise, are not attenuated by the electronic loading that occurs in intact hearts. However, in vivo, extrinsic neuro-hormonal control of the heart may minimize the effects of intrinsic alterations in electrical activity.

FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K

2021 ◽  
Author(s):  
Kate L. Weeks ◽  
Yow Keat Tham ◽  
Suzan G. Yildiz ◽  
Yonali Alexander ◽  
Daniel G. Donner ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Interstitial Fibrosis ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Physiological Cardiac Hypertrophy ◽  
Exercise Induced ◽  
Physiological Hypertrophy ◽  
Constitutively Active

The insulin-like growth factor 1 receptor (IGF1R) and phosphoinositide 3-kinase p110a (PI3K) are critical regulators of exercise-induced physiological cardiac hypertrophy, and provide protection in experimental models of pathological remodeling and heart failure. Forkhead box class O1 (FoxO1) is a transcription factor which regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K activation in vitro, but its role in physiological hypertrophy in vivo was unknown. We generated cardiomyocyte-specific FoxO1 knockout (cKO) mice and assessed the phenotype under basal conditions and settings of physiological hypertrophy induced by 1) swim training, or 2) cardiac-specific transgenic expression of constitutively active PI3K (caPI3KTg+). Under basal conditions, male and female cKO mice displayed mild interstitial fibrosis compared with control (CON) littermates, but no other signs of cardiac pathology were present. In response to exercise training, female CON mice displayed an increase (~21%) in heart weight normalized to tibia length vs untrained mice. Exercise-induced hypertrophy was blunted in cKO mice. Exercise increased cardiac Akt phosphorylation and IGF1R expression, but was comparable between genotypes. However, differences in Foxo3a, Hsp70 and autophagy markers were identified in hearts of exercised cKO mice. Deletion of FoxO1 did not reduce cardiac hypertrophy in male or female caPI3KTg+ mice. Cardiac Akt and FoxO1 protein expression were significantly reduced in hearts of caPI3KTg+ mice, which may represent a negative feedback mechanism from chronic caPI3K, and negate any further effect of reducing FoxO1 in the cKO. In summary, FoxO1 contributes to exercise-induced hypertrophy. This has important implications when considering FoxO1 as a target for treating the diseased heart.

Abstract 153: Inhibition of the 5-a-reductase Reduces Cardiac Hypertrophy and Improves Cardiac Function

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Carolin Zwadlo ◽  
Natali Froese ◽  
Johann Bauersachs ◽  
Joerg Heineke
Keyword(s):  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Capillary Density ◽  
Left Ventricular ◽  
Heart Weight ◽  
Rat Cardiomyocytes ◽  
Male And Female ◽  
Female Mice

Objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for increased cardiovascular mortality and a precursor of heart failure. Gender-specific differences point to a pivotal role of androgens in the development of pathological LVH. Dihydrotestosterone (DHT) is metabolized from testosterone via the enzyme 5-α-reductase. The 5-α-reductase is upregulated in the hypertrophied myocardium, leading to our assumption that DHT rather than testosterone is the crucial component in the development of LVH and might therefore constitute a potential therapeutic target. Methods: One week after transverse aortic constriction (TAC) or sham surgery male wild-type mice were treated for 2 weeks via an oralgastric tube with the 5-α-reductase inhibitor finasteride (daily dose 25mg/kg BW) or were left untreated (controls). Male and female transgenic Gαq (TG, a model of dilative cardiomyopathy) or non-transgenic mice were treated with finasteride for 6 weeks. Results: Cardiac hypertrophy after TAC was dramatically reduced by finasteride in male mice (heart weight/ body weight ratio, HW/BW in mg/g: control 6.65±0.35 versus finasteride treated 5.23±0.3; p<0.01). The reduced hypertrophy in these mice was accompanied by a reduction in cardiomyocyte diameter, ANP expression and fibrosis, but increased capillary density and Serca2a expression. Accordingly, finasteride also markedly reduced hypertrophy in isolated primary rat cardiomyocytes in vitro . Amelioration of hypertrophy by finasteride was associated with blunted activation of the prohypertrophic kinase mTOR in vitro and in vivo . Left ventricular dilation in male Gαq TG mice was markedly reduced by treatment with finasteride, which also led to an improvement in left ventricular function (determined as fractional area change in % by echocardiography: finasteride 44.72±1.71 vs. control 32.8±3.84, p<0.05) and a similar trend was observed in female mice. Interestingly, finasteride reduced pulmonary congestion in male and female mice alike. Conclusion: Finasteride treatment reduces hypertrophy and eccentric cardiac remodelling in mice, indicating a possible involvement of DHT in these processes as well as a potential benefit of 5-α-reductase inhibition in cardiac disease.

Abstract 289: Retinoblastoma Gene Deletion Promotes Cardiac Dysfunction, Fibrosis and Apoptosis in Response to Pressure Overload

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Paul B Ammann ◽  
Takanobu Yamamoto ◽  
Peiyong Zhai ◽  
Junichi Sadoshima
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Dysfunction ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Heart Weight ◽  
Tunel Staining ◽  
Pressure Gradients ◽  
Lung Weight ◽  
Rb Protein

The retinoblastoma (Rb) protein is a universal cell cycle regulator in mammals. When the Rb protein is phosphorylated by Cyclins/Cdks, it dissociates from E2F, and Rb-dependent E2F repression is subsequently inactivated. Furthermore, the Rb protein has also been implicated in the regulation of cardiac hypertrophy and apoptosis in cardiomyocytes (CMs). To elucidate the role of Rb in response to mechanical stress, we conducted transverse aortic constriction (TAC) in cardiac-specific Rb knockout mice (cRb-KO) in vivo (C57BL/6J). Cardiac-specific deletion of Rb was achieved by crossing Rb flox/flox mice with αMHC-Cre mice. Under basal conditions, 3- to 5-month-old cRb-KO mice showed increased heart weight (HW) (left ventricular weight/ tibial length (TL): 5.93 ± 029 vs. 4.76 ± 0.14, p< 0.01), increased apoptosis as determined by TUNEL staining (0.12% vs. 0.02%, p< 0.05) and a trend towards cardiac dysfunction (-dP/dt: 4320 ± 388 vs. 5933 ± 489 mmHg/sec, p < 0.05) compared to control mice (Rb flox/flox) Following 2 weeks of TAC, cRb-KO mice showed increased heart weight (HW/TL: 8.58 ± 0.35 vs. 7.50 ± 0.24, p < 0.05), cardiac dysfunction (ejection fraction (EF): 51.1% ± 4.0 vs. 74.3% ± 0.9, p < 0.01) , increased apoptosis as determined by TUNEL staining (0.48% vs. 0.05%, p < 0.01) and increased fibrosis as determined by Masson’s Trichrome staining (1.84% vs. 1.03%, p < 0.05) compared to Rb flox/flox mice after TAC. In response to 4 weeks of TAC, cRb-KO mice showed increased heart weight (HW/TL: 12.93 ± 085 vs. 9.32 ± 0.34, p < 0.01), lung weight (LW) (LW/TL: 18.35 ± 2.66 vs. 10.21 ± 1.93, p < 0.01), cardiac dysfunction (EF: 34.5% ± 8.3 vs. 64.3% ± 8.9, p < 0.01), increased apoptosis as determined by TUNEL staining (0,42% vs. 0,18%, p < 0.05) and increased fibrosis as determined by Masson’s Trichrome staining (4.2 % vs. 1.1 %, p < 0.05) compared to Rb flox/flox mice after TAC. Pressure gradients were similar between the cRb-KO mice submitted to 2 and 4 weeks of TAC and their respective controls. In conclusion, our results suggest that endogenous Rb plays an important role in mediating cell survival in CMs and negatively regulates cardiac hypertrophy at baseline. Furthermore, we showed that the Rb protein is important for the maintenance of cardiac function in response to pressure overload.

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