Minoxidil accelerates heart failure development in rats with ascending aortic constriction

1998 ◽  
Vol 76 (6) ◽  
pp. 613-620 ◽  
Author(s):  
Marian Turcani ◽  
Ruthard Jacob
Keyword(s):  
Heart Failure ◽  
Myocardial Contractility ◽  
Pressure Overload ◽  
Volume Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Aortic Constriction ◽  
Lung Weight ◽  
Eccentric Hypertrophy ◽  
Hemodynamic Overload

To test the ability of the heart to express characteristic geometric features of concentric and eccentric hypertrophy concurrently, constriction of the ascending aorta was performed in 4-week-old rats. Simultaneously, these rats were treated with an arteriolar dilator minoxidil. An examination 6 weeks after induction of the hemodynamic overload revealed no signs of congestion in systemic or pulmonary circulation in rats with aortic constriction or minoxidil-treated sham-operated rats. The magnitude of hemodynamic overload caused by aortic constriction or minoxidil treatment could be considered as equivalent, because the same enlargement of left ventricular pressure-volume area was necessary to compensate for either pressure or volume overload. Myocardial contractility decreased in rats with aortic constriction, and the compensation was achieved wholly by the marked concentric hypertrophy. Volume overload in minoxidil-treated rats was compensated partially by the eccentric hypertrophy and partially by the increased myocardial contractility. In contrast, increased lung weight and pleural effusion were found in all minoxidil-treated rats with aortic constriction. Unfavorable changes in left ventricular mass and geometry, relatively high chamber stiffness, and depressed ventricular and myocardial function were responsible for the massive pulmonary congestion.Key words: cardiac hypertrophy, heart failure, pressure overload, volume overload, minoxidil.

scholarly journals O-ring-induced transverse aortic constriction (OTAC) is a new simple method to develop cardiac hypertrophy and heart failure in mice

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasuhisa Nakao ◽  
Jun Aono ◽  
Mika Hamaguchi ◽  
Kayo Takahashi ◽  
Tomohisa Sakaue ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Experimental Models ◽  
Left Ventricular ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Lung Weight ◽  
Simple Method ◽  
Fractional Shortening

AbstractSuture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure. However, the incidence of heart failure in the conventional TAC depends on the operator’s skill. To optimize and simplify this method, we proposed O-ring-induced transverse aortic constriction (OTAC) in mice. C57BL/6J mice were subjected to OTAC, in which an o-ring was applied to the transverse aorta (between the brachiocephalic artery and the left common carotid artery) and tied with a triple knot. We used different inner diameters of o-rings were 0.50 and 0.45 mm. Pressure overload by OTAC promoted left ventricular (LV) hypertrophy. OTAC also increased lung weight, indicating severe pulmonary congestion. Echocardiographic findings revealed that both OTAC groups developed LV hypertrophy within one week after the procedure and gradually reduced LV fractional shortening. In addition, significant elevations in gene expression related to heart failure, LV hypertrophy, and LV fibrosis were observed in the LV of OTAC mice. We demonstrated the OTAC method, which is a simple and effective cardiac pressure overload method in mice. This method will efficiently help us understand heart failure (HF) mechanisms with reduced LV ejection fraction (HFrEF) and cardiac hypertrophy.

scholarly journals Myocardial work index better reflects contractility than longitudinal strain in rat models of pressure- and volume overload-induced heart failure

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
BK Lakatos ◽  
M Ruppert ◽  
M Tokodi ◽  
A Olah ◽  
S Braun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Longitudinal Strain ◽  
Pressure Overload ◽  
Volume Overload ◽  
Left Ventricular ◽  
Stroke Work ◽  
Loading Conditions ◽  
Rat Models ◽  
Work Index ◽  
Hemodynamic Overload

Abstract Funding Acknowledgements Type of funding sources: None. Speckle-tracking echocardiography (STE)-derived global longitudinal strain (GLS) is considered to be a sensitive marker of left ventricular (LV) function in a wide variety of cardiovascular diseases. Still, evidence suggests that GLS is significantly influenced by loading conditions. Myocardial work index (MWI) evaluates myocardial deformation in the context of afterload through the interpretation of strain in relation to instantaneous LV pressure. MWI may potentially overcome the limitations of mere strain calculation, and may better reflect cardiac contractility in hemodynamic overload states. Accordingly, our aim was to examine the relationship of GLS and MWI with load-independent markers of LV contractility in rat models of pressure- and volume overload-induced heart failure. Male Wistar rats underwent transverse aortic constriction (TAC; n = 12) to generate LV pressure overload, or aortocaval fistula (ACF; n = 12) was established to induce severe LV volume overload. In case of the control groups, sham procedures were performed (n = 12/12). Echocardiography loops were obtained to determine STE-derived GLS and global MWI. Pressure-volume analysis with transient occlusion of the inferior vena cava was carried out to calculate preload recruitable stroke work (PRSW), as a load-independent „gold-standard" parameter of LV contractility. GLS was mildly reduced in the ACF group (-13.2 ± 2.4 vs. -15.4 ± 2.0%, p < 0.05), while it was significantly lower in TAC group compared to controls (-7.0 ± 2.8 vs. -14.5 ± 2.5%; p < 0.001). In contrast with these findings, PRSW and also MWI were significantly reduced in ACF (58 ± 14 vs. 111 ± 40 mmHg; 1328 ± 411 vs. 1934 ± 308 mmHg%, both p < 0.01), however, they were comparable between TAC and the corresponding sham group (110 ± 26 vs. 116 ± 68 mmHg; 1687 ± 275 Hgmm% vs. 1537 ± 662 Hgmm%; both p = NS). In the pooled population, GLS did not show relationship with PRSW (r=-0.23; p = 0.12), while MWI showed significant correlation with it (r = 0.70; p < 0.001). GLS is significantly influenced by loading conditions, therefore, in case of severe pressure- or volume overload it may not be a reliable marker of LV contractility. In our rat model of pressure overload induced heart failure, contractility was maintained despite decreased GLS, while in the model of volume overload induced heart failure, GLS was maintained despite decreased contractility. MWI reflects contractility in hemodynamic overload states, therefore, it may be a more suitable marker of systolic function. Abstract Figure. Pressure-strain loops of the groups

Longitudinal strain reflects the interaction of myocardial contractility to afterload in rat models of hemodynamic overload-induced heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Ruppert ◽  
B.K Lakatos ◽  
M Tokodi ◽  
C Karime ◽  
I Hizoh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Strong Correlation ◽  
Longitudinal Strain ◽  
Pressure Overload ◽  
Volume Overload ◽  
Left Ventricular ◽  
Funding Source ◽  
Entire Study ◽  
Rat Models ◽  
Hemodynamic Overload

Abstract Background Two-dimensional (2D) speckle tracking echocardiography (STE)-derived myocardial strain parameters are sensitive markers of left ventricular (LV) systolic function. Novel findings suggest that the contractile state of the myocardium, afterload and preload are major determinants of STE measurements. However, the hypothesis that longitudinal strain expresses the interaction between contractility and loading conditions rather than contractility alone in hemodynamic overload-induced heart failure (HF) has not been tested. Purpose This study aimed to explore the connection between longitudinal strain and contractility, afterload and preload in rat models of pressure overload (PO)- and volume overload (VO)-induced heart failure (HF). Methods Pressure overload (PO)-induced HF was evoked by transverse aortic constriction ([TAC], n=14). Volume overload (VO)-induced HF was established by an aortocaval fistula ([ACF], n=12). Age-matched sham operated animals served as controls. Pressure-volume analysis was carried out to compute cardiac contractility (slope of end-systolic pressure-volume relationship [ESPVR]), afterload (arterial elastance [Ea]) and ventriculo-arterial coupling ([VAC] = Ea/ESPVR). Preload was evaluated by meridional end-diastolic wall stress (σend-diastolic). STE was performed to assess global longitudinal strain (GLS). Results GLS was impaired in both PO-induced HF (−5.9±0.6 vs. −12.9±0.5%, TAC vs Sham, P<0.001) and VO-evoked HF (−11.7±0.7 vs. −13.5±0.4%, ACF vs Sham, P=0.048). Hemodynamic measurements indicated that the TAC group presented with maintained ESPVR, increased Ea and enhanced σend-diastolic. In contrast, the ACF group was characterized by reduced ESPVR, decreased Ea and enhanced σend-diastolic. Ordinary least squares non-linear regression revealed that GLS was predominantly determined by afterload (Ea) in the TAC model and by contractility (ESPVR) in the ACF model. In accordance, GLS showed a strong correlation with Ea in case of PO-induced HF (R= 0.848, P<0.001) and with ESPVR in case of VO-evoked HF (R=−0.526; P=0.008), respectively. Furthermore, GLS also demonstrated strong correlation with VAC in both the TAC and the ACF models. Of particular interest, a robust correlation between VAC and GLS could also be detected in the entire study population (R= 0.654, P<0.001). Conclusion Both afterload and contractility define GLS. Hence, under conditions when both factors become altered, GLS reflects VAC. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017

Abstract 17583: Autophagy Protects the Heart Against Pressure Overload Induced Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Akihiro Shirakabe ◽  
Yoshiyuki Ikeda ◽  
Peiyong Zai ◽  
Toshiro Saito ◽  
Junichi Sadoshima
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Sham Group ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Autophagic Flux ◽  
Aortic Constriction ◽  
Double Positive ◽  
Lung Weight ◽  
Transient Activation

Autophagy is an important mechanism for the degradation of cytosolic proteins and organelles. We investigated how autophagy is regulated in the heart in response to pressure overload (PO). Mice were subjected to transverse aortic constriction (TAC) for multiple durations ranging from 1 hour to 30 days. Left ventricular (LV) weight/tibial length (TL) was significantly elevated at Day 5 (6.21 ± 0.10 vs 4.59 ± 0.10, p<0.05) and thereafter. Ejection fraction (EF) was maintained at Day 7 (82.1±3.4 vs 78.4±3.2%), but gradually decreased thereafter (at Day 30, 51.0±4.5, p<0.05). The level of LC3II increased rapidly, peaking at 3 hours (2.4 fold, p<0.05), returned to normal by 24 hours, and then was significantly decreased at Day 5 (-40.0%, p<0.05) and thereafter. Autophagic flux was evaluated with tandem fluorescent LC3. At 6 hours, both GFP/RFP double positive (yellow) dots and RFP dots were significantly increased in the TAC group compared to the sham group, with or without chloroquine (CQ) (yellow 12±2 vs 4±0 CQ(-), 23±3 vs 9±1 CQ(+); RFP 13±2 vs 5±1 CQ(-), 19±1 vs 13±1 CQ(+)). However, both yellow and RFP dots were significantly decreased at Day 7 and thereafter in the TAC group compared to the sham group, with or without CQ. These data suggest that autophagic flux is activated only transiently after TAC, but is inactivated after Day 5. To examine the functional significance of autophagy during PO, beclin1 heterozygous knockout (beclin1-hetKO) mice, atg7 cardiac-specific knockout (Atg7-CKO) mice, and cardiac-specific U6-shRNA beclin1 (U6shRNAbeclin1) mice were subjected to TAC. At Day 7 and 14 of TAC, decreases in EF (60.7 ± 4.8%, 53.8 ± 2.1% and 46.7 ± 5.9%, p<0.05) and increases in lung weight/TL (8.43 ± 0.87, 11.04 ± 4.16 and 18.76 ± 3.77, p<0.05) were exacerbated in beclin1-hetKO, atg7-CKO and U6shRNAbeclin1 mice compared to in control mice. These results suggest that, after transient activation during the initial 24 hours, PO inhibits autophagy below control levels after Day 5, which coincides with the development of cardiac dysfunction. Since heart failure is exacerbated by further suppression of autophagy, autophagy during PO protects the heart from cardiac dysfunction and PO-induced downregulation of autophagy exacerbates heart failure.

Abstract 14952: Hemodynamic Comparison of Left Ventricular Function in Pressure Overload- versus Volume Overload-Induced Heart Failure Models by Invasive Pressure-Volume Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mihály Ruppert ◽  
Christian Karime ◽  
Alex A Sayour ◽  
Attila Oláh ◽  
Dávid Nagy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Function ◽  
Pressure Overload ◽  
Volume Overload ◽  
Detailed Comparison ◽  
Left Ventricular ◽  
Lv Function ◽  
Arterial Elastance ◽  
Lv Remodeling ◽  
Av Shunt

Introduction: Both sustained left ventricular (LV) pressure overload (PO) and volume overload (VO) induces LV remodeling and eventually development of heart failure (HF). Using rat models, the present study aimed to provide a detailed comparison of distinct aspects of LV function in PO- and VO-induced HF. Methods: PO and VO was induced by transverse aortic constriction (TAC, n=12) and aortocaval shunt (AV-shunt, n=12) creation respectively. Controls underwent corresponding sham operations (n=11). LV remodeling was characterized by echocardiography, histology, qRT PCR, and western blot. LV function was assessed by invasive pressure-volume (P-V) analysis. Results: Both sustained PO and VO resulted in the development of HF, as evidenced by increased LV BNP mRNA expression, pulmonary edema, and characteristic symptoms. While the extent of LV hypertrophy was comparable between the HF models, PO induced concentric while VO evoked eccentric LV remodeling. P-V analysis revealed impaired systolic function in both HF models. Accordingly, decreased ejection fraction and impaired ventriculo-arterial coupling (calculated as the ratio of arterial elastance/LV contractility [VAC]: 0.38±0.05 vs. 1.30±0.13, ShamTAC vs. TAC and 0.52±0.08 vs. 1.17±0.13, ShamAV-Shunt vs. AV-shunt; p<0.05) was detected in both HF models. However, in case of VO the severely reduced LV contractility (slope of end-systolic P-V relationship: 1.79±0.19 vs. 0.52±0.06, ShamAV-Shunt vs. AV-shunt, p<0.05 and 2.14±0.28 vs. 2.03±0.21, ShamTAC vs. TAC p>0.05) underpinned the contractility-afterload mismatch, while in case of PO the increased afterload (arterial elastance: 0.77±0.07 vs. 2.64±0.28, ShamTAC vs. TAC and 0.80±0.07 vs. 0.54±0.05, ShamAV-Shunt vs. AV-shunt; p<0.05) was the main determinant. Furthermore, prolongation of active relaxation occurred to a greater extent in case of PO. In addition, increased myocardial stiffness was only observed in PO-induced HF. Conclusion: Systolic function was reduced in both HF models. However, different factors underpinned the impaired VAC in case of VO (reduced LV contractility) and PO (increased arterial elastance). Furthermore, although diastolic function deteriorated in both models, it occurred to a greater extent in case of PO.

scholarly journals Cytosolic H2O2 mediates hypertrophy, apoptosis, and decreased SERCA activity in mice with chronic hemodynamic overload

2014 ◽  
Vol 306 (10) ◽  
pp. H1453-H1463 ◽  
Author(s):  
Fuzhong Qin ◽  
Deborah A. Siwik ◽  
David R. Pimentel ◽  
Robert J. Morgan ◽  
Andreia Biolo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Myocyte ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Transgenic Expression ◽  
Myocardial Oxidative Stress ◽  
Plasmic Reticulum ◽  
Oxidative Modifications ◽  
Hemodynamic Overload

Oxidative stress in the myocardium plays an important role in the pathophysiology of hemodynamic overload. The mechanism by which reactive oxygen species (ROS) in the cardiac myocyte mediate myocardial failure in hemodynamic overload is not known. Accordingly, our goals were to test whether myocyte-specific overexpression of peroxisomal catalase (pCAT) that localizes in the sarcoplasm protects mice from hemodynamic overload-induced failure and prevents oxidation and inhibition of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), an important sarcoplasmic protein. Chronic hemodynamic overload was caused by ascending aortic constriction (AAC) for 12 wk in mice with myocyte-specific transgenic expression of pCAT. AAC caused left ventricular hypertrophy and failure associated with a generalized increase in myocardial oxidative stress and specific oxidative modifications of SERCA at cysteine 674 and tyrosine 294/5. pCAT overexpression ameliorated myocardial hypertrophy and apoptosis, decreased pathological remodeling, and prevented the progression to heart failure. Likewise, pCAT prevented oxidative modifications of SERCA and increased SERCA activity without changing SERCA expression. Thus cardiac myocyte-restricted expression of pCAT effectively ameliorated the structural and functional consequences of chronic hemodynamic overload and increased SERCA activity via a post-translational mechanism, most likely by decreasing inhibitory oxidative modifications. In pressure overload-induced heart failure cardiac myocyte cytosolic ROS play a pivotal role in mediating key pathophysiologic events including hypertrophy, apoptosis, and decreased SERCA activity.

Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal- and background-dependent development of concentric left ventricular hypertrophy

2007 ◽  
Vol 292 (5) ◽  
pp. H2119-H2130 ◽  
Author(s):  
Cordelia J. Barrick ◽  
Mauricio Rojas ◽  
Robert Schoonhoven ◽  
Susan S. Smyth ◽  
David W. Threadgill
Keyword(s):  
Heart Failure ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Dependent Manner ◽  
Geometric Patterns ◽  
Concentric Hypertrophy ◽  
Eccentric Hypertrophy

Left ventricular hypertrophy (LVH), a risk factor for cardiovascular morbidity and mortality, is commonly caused by essential hypertension. Three geometric patterns of LVH can be induced by hypertension: concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Clinical studies suggest that different underlying etiologies, genetic modifiers, and risk of mortality are associated with LVH geometric patterns. Since pressure overload-induced LVH can be modeled experimentally using transverse aortic constriction (TAC) and since C57BL/6J (B6) and 129S1/SvImJ (129S1) strains, which have different baseline cardiovascular phenotypes, are commonly used, we conducted serial echocardiographic studies to assess cardiac function up to 8 wk of post-TAC in male B6, 129S1, and B6129F1 (F1) mice. B6 mice had an earlier onset and more pronounced impairment in contractile function, with corresponding left and right ventricular dilatation, fibrosis, change in expression of hypertrophy marker, and increased liver weights at 5 wk of post-TAC. These observations suggest that B6 mice had eccentric hypertrophy with systolic dysfunction and right-sided heart failure. In contrast, we found that 129S1 and F1 mice delayed transition to decompensated heart failure, with 129S1 mice exhibiting preserved systolic function until 8 wk of post-TAC and relatively mild alterations in histology and markers of hypertrophy at 5 wk post-TAC. Consistent with concentric hypertrophy, our results show that these strains manifest different cardiac responses to pressure overload in a time-dependent manner and that genetic susceptibility to initial concentric hypertrophy is dominant to eccentric hypertrophy. These results also imply that genetic background differences can complicate interpretation of TAC studies when using mixed genetic backgrounds.

Effects of plasma norepinephrine elevation on the heart's adaptation to chronic aortic constriction in rats

1986 ◽  
Vol 64 (7) ◽  
pp. 934-939 ◽  
Author(s):  
Francis M. Siri ◽  
Richard M. Smith
Keyword(s):  
Infusion Rate ◽  
Structural Changes ◽  
Pressure Overload ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Plasma Norepinephrine ◽  
Aortic Constriction ◽  
Lung Weight ◽  
Hydroxyproline Concentration ◽  
Norepinephrine Infusion

Chronically elevated plasma norepinephrine has the potential for supporting function of diseased hearts, yet may also initiate harmful biochemical and (or) structural changes in the myocardium. The present study investigated the dosage-related effects of chronic norepinephrine infusion on markers of myocardial damage and then tested the influence of a relatively low norepinephrine infusion rate (0.05 μg∙kg−1∙min−1) on the heart's adaptation to pressure overload in aortic constricted rats. Norepinephrine infusion at 0.50 μg∙kg−1∙min−1 led to significantly increased myocardial hydroxyproline concentration and significant mortality. A rate of 0.25 μg∙kg−1∙min−1 increased myocardial hydroxyproline concentration and mortality in aortic constricted rats but had no such effects on sham-operated rats. The lowest rate tested (0.05 μg∙kg−1∙min−1) significantly increased mean arterial pressure and lung weight of aortic constricted rats, without affecting the degree of left ventricular hypertrophy. This infusion rate and aortic constriction each increased plasma norepinephrine and impaired cardiac performance during rapid preloading, although their combination did not cause further impairment. Thus, it appears that even modest plasma norepinephrine elevation has a negative effect on the heart's adaptation to sustained pressure overload.

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