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.

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 Substrain specific response to cardiac pressure overload in C57BL/6 mice

2013 ◽  
Vol 305 (3) ◽  
pp. H397-H402 ◽  
Author(s):  
Lorena Garcia-Menendez ◽  
Georgios Karamanlidis ◽  
Stephen Kolwicz ◽  
Rong Tian
Keyword(s):  
Cardiac Function ◽  
Pressure Overload ◽  
Data Interpretation ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Heart Weight ◽  
Specific Response ◽  
Aortic Constriction ◽  
Lung Weight ◽  
Left Ventricular Dilatation

The C57BL/6 mouse strain is one of the most commonly used in experimental research. It is known to differ from other strains in baseline cardiovascular phenotypes as well as in response to pressure overload induced by aortic constriction. Since the generation of the C57BL/6 mouse line over a century ago, multiple substrains have been generated from the original. To identify potential substrain specific differences in response to pressure overload, we evaluated the effects of transverse aortic constriction (TAC) on survival, cardiac function, and expression of hypertrophic markers in three commonly used C57BL/6 substrains: C57BL/6J (JL), C57BL/6NCrl (CL), and C57BL/6NTac (TF). Survival and cardiac function were significantly lower in the CL and TF substrains compared with JL mice after TAC. Furthermore, the heart weight and lung weight as well as the expression of the hypertrophic marker Bnp were significantly greater in the CL mice compared with the JL. Histological assessment revealed marked left ventricular dilatation of CL and TF hearts while JL hearts showed increased wall thickness without dilatation. Our data demonstrate that cardiac response to pressure overload is distinct among the three commonly used C57BL/6 substrains of mice, which raises a cautionary note in study design and data interpretation.

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.

scholarly journals 4-Methylumbelliferone Attenuates Macrophage Invasion and Myocardial Remodeling in Pressure-Overloaded Mouse Hearts

Hypertension ◽  
2021 ◽  
Author(s):  
Katarzyna Hackert ◽  
Susanne Homann ◽  
Shakila Mir ◽  
Arne Beran ◽  
Simone Gorreßen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Pressure Overload ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Cardiac Wall

Cardiac wall stress induces local and systemic inflammatory responses that are increasingly recognized as key modulators of extracellular matrix remodeling. Hyaluronic acid interacts with immune cells and mesenchymal cells thereby modulating profibrotic signals. Here we tested the hypothesis that 4-methylumbelliferone (4-MU), an inhibitor of hyaluronic acid synthesis, would attenuate inflammation and extracellular matrix remodeling of pressure-overloaded myocardium in C57BL/6J male mice fed with 4-MU and subjected to TAC (transverse aortic constriction) surgery. Flow cytometry of immune cells showed TAC-induced leukocytosis due to an increase of neutrophils and monocytes. 4-MU strongly attenuated both circulating and cardiac leukocyte numbers 3 days after TAC. In the hearts, 4-MU reduced the number of CCR2 − resident macrophages. At later time points, 4-MU also prevented the infiltration of heart tissue by bone marrow-derived circulating monocytes leading to reduced cardiac macrophage counts even 7 weeks after TAC. The long-term attenuation of macrophage-driven inflammation was associated with less myocardial fibrosis in 4-MU-treated compared with untreated mice. Unexpectedly, 4-MU also reduced the development of left ventricular hypertrophy and increased cardiac output after TAC without affecting blood pressure. The data demonstrate that 4-MU reduces both resident and invading cardiac macrophages and may be a promising agent to alleviate pressure-overload induced myocardial damage.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

Abstract 13469: Drp1 Accumulates in Mitochondria and Plays a Protective Role in the Heart in Response to Pressure Overload

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Akihiro Shirakabe ◽  
Yoshiyuki Ikeda ◽  
Peiyong Zai ◽  
Junichi Sadoshima
Keyword(s):  
Diastolic Pressure ◽  
Pressure Overload ◽  
Protective Role ◽  
Left Ventricular ◽  
Multiple Time ◽  
Lung Weight ◽  
Knock Out ◽  
Multiple Time Points ◽  
Increased Activity ◽  
Adaptive Role

Dynamin-related protein 1 (Drp1) plays an essential role in maintaining the quality control of mitochondria through mitochondrial (Mt) fission and mitophagy. We investigated how Mt function, autophagy and Drp1 are regulated in the heart during pressure overload (PO) and whether endogenous Drp1 plays an important role in regulating cardiac function. Mice were subjected to transverse aortic constriction (TAC) at multiple time points between 6 hours and 30 days. Left ventricular (LV) weight/tibial length (LVW/TL) was significantly elevated at Day 7 (TAC vs sham; 5.92 ± 0.27 vs 4.22 ± 0.12, p<0.05). Ejection fraction (EF) was maintained at Day 7, but gradually decreased thereafter (at 30 days; 65±9 vs 83±9 %, p<0.05). LC3-II was decreased (-45.7%, p<0.05) while p62 accumulated (1.17 fold, p<0.05) significantly at Day 7. Both Mt ATP content (-65.6%, p<0.05) and production (-90.3%, p<0.05) were reduced significantly at Days 7 and 14, respectively, and thereafter. Mt mass, evaluated by electron microscopy, was also reduced (-19.9%, p<0.05) at Day 7. Drp1 accumulated in mitochondria at Day 7, and S616 phosphorylation of Drp1, associated with increased activity, was increased at Day 7. Thus, PO suppresses autophagy and induces Mt dysfunction by Day 7, at which time Drp1 accumulates in mitochondria and Mt mass is decreased. To examine the functional significance of endogenous Drp1 during PO, cardiac-specific heterozygous Drp1 knock out (Drp-hetCKO) mice were subjected to TAC. At Day 7, decreases in EF (61± 2 vs 84 ± 7%, p<0.05) and increases in LVW/TL (7.22 ± 0.26 vs 5.86 ± 0.65, p<0.05) and lung weight/TL (12.01 ± 1.10 vs 6.31 ± 1.19, p<0.05) were exacerbated in Drp-hetCKO compared to in control mice. LV end diastolic pressure was significantly higher (22.0 ± 2.8 vs 5.7 ± 2.9 mmHg, p<0.05) and myocardial fibrosis (14.1 ± 2.5 vs 6.2 ± 4.3 %, p<0.05) was greater in Drp-hetCKO than in control mice. Mt mass was also significantly greater in Drp-hetCKO than in control mice (relative Mt mass, 1.21 ± 0.46 vs 1.00 ± 0.02, p<0.05). These results suggest that PO inhibits autophagy and induces mitochondrial dysfunction by Day7, which coincides with Mt accumulation of Drp1. Drp1 plays an adaptive role in this condition, mediating decreases in Mt mass and protecting the heart from dysfunction.

Altered renal dopamine receptors during development of cardiac hypertrophy

1992 ◽  
Vol 262 (5) ◽  
pp. E569-E573
Author(s):  
P. K. Ganguly ◽  
K. Mukherjee ◽  
Y. Chen
Keyword(s):  
Cardiac Hypertrophy ◽  
Dopamine Receptors ◽  
Pressure Overload ◽  
Total Body Weight ◽  
Left Ventricular ◽  
Kidney Cortex ◽  
Sprague Dawley ◽  
Aortic Constriction ◽  
Compensatory Response ◽  
Abdominal Aortic

The characteristics of dopamine receptors were studied in heart and kidney using the radiolabeled receptor assay of [3H]spiperone during the development of cardiac hypertrophy. Male Sprague-Dawley rats (175-200 g) underwent abdominal aortic constriction above the renal arteries and were studied 3, 14, and 28 days thereafter. Sham-operated animals without aortic constriction were used as control. Although the ratio of left ventricular weight to total body weight was significantly increased 14 and 28 days after aortic constriction in animals, [3H]spiperone binding in left ventricular membrane was increased as early as 3 days after aortic constriction. At 14 days, the binding was still elevated and, by 28 days, it returned to control values. In contrast, membranes obtained from kidney cortex showed an elevation of [3H]spiperone binding only at 28 days after aortic constriction; at 3 days the binding values were decreased. A reciprocal correlation was found between the number of dopamine receptors and the activity of Na(+)-K(+)-ATPase at 28 days of aortic constriction; the enzyme activity, as measured by the release of 32Pi from [gamma-32P]ATP, was decreased in kidney cortex. Autoradiographic data also showed an increased number of dopamine receptors in kidney at 28 days after abdominal aortic constriction. These results suggest that the dopamine receptor is increased very early in heart in response to pressure overload as a result of a compensatory response to maintain an optimal left ventricular output. Kidney dopamine receptors are triggered at a later stage possibly to maintain fluid homeostasis secondary to the cardiac hypertrophic process.

scholarly journals Transient Upregulation of Protein Kinase C in Pressure-Overloaded Neonatal Rat Myocardium

2010 ◽  
pp. 25-33 ◽  
Author(s):  
B Hamplová ◽  
F Novák ◽  
F Kolář
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Left Ventricular Myocardium ◽  
Aortic Constriction ◽  
Cardiac Growth ◽  
Kinase C

Protein kinase C (PKC) appears to play a significant role in the signal transduction of cardiac growth and development. The aim of this study was to determine changes in the total PKC activity and the expression of PKC isoforms α, δ and ε in the rat heart that was affected by pressure overload imposed at postnatal day (d) 2. Three groups of Wistar rats were employed for the experiment: rats submitted to the abdominal aortic constriction (AC), sham-operated controls (SO) and intact controls. Animals were sacrificed at d2, d3, d5 and d10. The total PKC activity was measured by the incorporation of 32P into histone IIIS and the expression of PKC was analyzed by immunoblotting in the homogenate of the left ventricular myocardium and in the cytosolic, membrane-enriched (105 × g) and nuclear-cytoskeletalmyofilament-enriched (103 × g) fractions. We observed the significant transient increase in both the total PKC activity and the expression of all isoforms at d5 (the 3rd day after the operation) in the cardiac homogenate of AC rats as compared with SO animals. Aortic constriction did not significantly affect the distribution of activity and isoform abundance among individual cellular fractions except for PKCδ, which increased significantly at d10 in the cytosolic fraction at the expense of the membraneenriched fraction. It is concluded that PKCα, PKCδ and PKCε undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period.

Cardiac changes on MRI and SPECT after definitive radiotherapy in patients with lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17059-17059
Author(s):  
P. A. Lind ◽  
T. Larsson ◽  
A. Lideståhl ◽  
L. Thoren ◽  
A. Ågren-Cronqvist ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Correlation Coefficient ◽  
Myocardial Fibrosis ◽  
Structural Changes ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Repeated Measurements ◽  
Cardiac Damage ◽  
Entire Cohort ◽  
The Mean

17059 Background: To determine if lung cancer irradiation (RT) induces myocardial damage. Methods: Patients undergoing definitive RT with > 10% incidental cardiac RT (>30 Gy) were evaluated pre-RT and at 2 and 6 mos post-RT FUs. They underwent gadolinium enhanced cardiac MRI and rest-SPECT. The mean cardiac (MCD) and left ventricular (MLVD) doses were calculated on the dose planning CT. Data on confounding factors, e.g. diabetes, smoking, and levels of TGF-B, plasma glucose/fats were collected. The MRIs were analyzed for reductions in stroke volume (SV), ejection fraction (EF), left ventricular mass (LVM), and for visual signs of myocardial fibrosis/damage. The severity of SPECT-changes were analyzed with the semiquantitative summed rest score (SRS)-method (16-segments) and the extent was further quantified with the Bull’s-eye-view technique as volume-% (cutoff level for 1.5 SD below the mean). The Wilcoxon Matched Pairs test was used to study changes in repeated measurements. To test variable relation the Pearson’s Correlation Coefficient was calculated. Results: Presently, 13/30 patients are evaluated after their first FU. There was a limited decrease in LVM at first FU compared to pre-RT (median change: −6 g; P = 0.02), but no changes in SV or EF. The correlation coefficient for MCD (range: 2–32 Gy) (MLVD: 1–36 Gy) and MRI-reductions in SV, EF, and LVM at 2 mos were −0.46 (−0.27), −0.22 (−0.1), −0.30 (−0.12), respectively (P-values > 0.05). On rest-SPECT, a clinically significant SRS-increase was evident in one patient (SRS: +13; extent of defect 19%) at 2 mos. A new, extra cardial mass was, however, evident in this patient which would cause attenuation. No myocardial fibrosis/damage was detected on visual inspection of the MRIs. There was no increase in S-troponin levels at the first FU. Conclusions: At this stage of our study, no cardiac changes were evident following lung RT. This contrasts against studies in breast cancer RT were SPECT-defects corresponding to the tangential beams have been reported. RT-induced chest wall damage could in our series explain new SPECT-defects in one patient, who had no structural changes on MRI. Our entire cohort should be evaluated after both planned post-RT FUs before definitive conclusions can be drawn concerning cardiac damage and lung cancer RT. No significant financial relationships to disclose.

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