Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium

2011 ◽  
Vol 301 (2) ◽  
pp. H548-H554 ◽  
Author(s):  
Mitsuo Sobajima ◽  
Takashi Nozawa ◽  
Takuya Shida ◽  
Takashi Ohori ◽  
Takayuki Suzuki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Smooth Muscle Actin ◽  
Left Ventricular ◽  
Vascular Density ◽  
Peripheral Blood Flow ◽  
Mrna Levels ◽  
Cross Sectional

Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

Severe myocardial dysfunction induced by ventricular remodeling in aging rat hearts

1990 ◽  
Vol 259 (4) ◽  
pp. H1086-H1096 ◽  
Author(s):  
J. M. Capasso ◽  
T. Palackal ◽  
G. Olivetti ◽  
P. Anversa
Keyword(s):  
Ventricular Remodeling ◽  
Volume Fraction ◽  
Diastolic Pressure ◽  
Structural Characteristics ◽  
Myocardial Dysfunction ◽  
Pressure Rise ◽  
Wall Stress ◽  
Left Ventricular ◽  
Cross Sectional

To determine if aging engenders alterations in the functional properties of the myocardium and ventricular remodeling, the hemodynamic performance and structural characteristics of the left ventricle of male Fischer 344 rats at 4, 12, 20, and 29 mo of age were studied by quantitative physiology and morphology. In vivo assessment of cardiac pump function showed no change up to 20 mo, whereas left ventricular end-diastolic pressure was increased at 29 mo. Moreover, peak rates of pressure rise and decay, stroke volume, ejection fraction, and cardiac output were depressed at the later age interval, demonstrating the presence of ventricular failure at this time. The measurements of chamber size and wall thickness showed that ventricular end-diastolic and end-systolic volumes progressively increased with age with the greatest change occurring at 20-29 mo. Aging was also accompanied by a marked augmentation in the volume fraction of fibrotic areas in the ventricular myocardium that was due to an increase in their number and cross-sectional area with time. These architectural rearrangements, in combination with the abnormalities in ventricular function, resulted in an elevation in the volume of wall stress throughout the cardiac cycle. Wall stress increased by 64, 44, and 50% from 4 to 12, 12 to 20, and 20 to 29 mo of age. In conclusion, aging leads to a continuous rise in wall stress that is not normalized by ventricular remodeling. These two independent processes appear to be responsible for the onset of heart failure in the senescent rat.

Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction

2009 ◽  
Vol 296 (2) ◽  
pp. H462-H469 ◽  
Author(s):  
Hiroharu Takenaka ◽  
Mitsuru Horiba ◽  
Hisaaki Ishiguro ◽  
Arihiro Sumida ◽  
Mayumi Hojo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Umbilical Vein ◽  
Left Ventricular ◽  
Wild Type ◽  
Long Term Effects ◽  
Term Survival ◽  
Deficient Mice

Cardiac remodeling is thought to be the major cause of chronic heart dysfunction after myocardial infarction (MI). However, molecules involved in this process have not been thoroughly elucidated. In this study we investigated the long-term effects of the growth factor midkine (MK) in cardiac remodeling after MI. MI was produced by ligation of the left coronary artery. MK expression was progressively increased after MI in wild-type mice, and MK-deficient mice showed a higher mortality. Exogenous MK improved survival and ameliorated left ventricular dysfunction and fibrosis not only of MK-deficient mice but also of wild-type mice. Angiogenesis in the peri-infarct zone was also enhanced. These in vivo changes induced by exogenous MK were associated with the activation of phosphatidylinositol 3-kinase (PI3K)/Akt and MAPKs (ERK, p38) and the expression of syndecans in the left ventricular tissue. In vitro experiments using human umbilical vein endothelial cells confirmed the potent angiogenic action of MK via the PI3K/Akt pathway. These results suggest that MK prevents the cardiac remodeling after MI and improves the survival most likely through an enhancement of angiogenesis. MK application could be a new therapeutic strategy for the treatment of ischemic heart failure.

scholarly journals Clofibrate Treatment Decreases Inflammation and Reverses Myocardial Infarction-Induced Remodelation in a Rodent Experimental Model

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 270 ◽  
Author(s):  
Luz Ibarra-Lara ◽  
María Sánchez-Aguilar ◽  
Elizabeth Soria-Castro ◽  
Jesús Vargas-Barrón ◽  
Francisco Roldán ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Cardiac Damage ◽  
Artery Ligation ◽  
Apoptotic Proteins

Myocardial infarction (MI) initiates an inflammatory response that promotes both beneficial and deleterious effects. The early response helps the myocardium to remove damaged tissue; however, a prolonged later response brings cardiac remodeling characterized by functional, metabolic, and structural pathological changes. Current pharmacological treatments have failed to reverse ischemic-induced cardiac damage. Therefore, our aim was to study if clofibrate treatment was capable of decreasing inflammation and apoptosis, and reverse ventricular remodeling and MI-induced functional damage. Male Wistar rats were assigned to (1) Sham coronary artery ligation (Sham) or (2) Coronary artery ligation (MI). Seven days post-MI, animals were further divided to receive vehicle (V) or clofibrate (100 mg/kg, C) for 7 days. The expression of IL-6, TNF-α, and inflammatory related molecules ICAM-1, VCAM-1, MMP-2 and -9, nuclear NF-kB, and iNOS, were elevated in MI-V. These inflammatory biomarkers decreased in MI-C. Also, apoptotic proteins (Bax and pBad) were elevated in MI-V, while clofibrate augmented anti-apoptotic proteins (Bcl-2 and 14-3-3ε). Clofibrate also protected MI-induced changes in ultra-structure. The ex vivo evaluation of myocardial functioning showed that left ventricular pressure and mechanical work decreased in infarcted rats; clofibrate treatment raised those parameters to control values. Echocardiogram showed that clofibrate partially reduced LV dilation. In conclusion, clofibrate decreases cardiac remodeling, decreases inflammatory molecules, and partly preserves myocardial diameters.

scholarly journals A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone

2011 ◽  
Vol 301 (6) ◽  
pp. H2372-H2382 ◽  
Author(s):  
Natalia López-Andrés ◽  
Beatriz Martin-Fernandez ◽  
Patrick Rossignol ◽  
Faiez Zannad ◽  
Vicente Lahera ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Remodeling ◽  
Diastolic Pressure ◽  
Experimental Models ◽  
Left Ventricular ◽  
Histopathological Analysis ◽  
Myocardial Remodeling ◽  
Wild Type ◽  
Rt Pcr ◽  
Cross Sectional

Hyperaldosteronim is associated with left ventricular (LV) hypertrophy (LVH) and fibrosis. Cardiotrophin (CT)-1 is a cytokine that induces myocardial remodeling. We investigated whether CT-1 mediates aldosterone (Aldo)-induced myocardial remodeling in two experimental models. Wistar rats were treated with Aldo-salt (1 mg·kg−1·day−1) with or without spironolactone (200 mg·kg−1·day−1) for 3 wk. Wild-type (WT) and CT-1-null mice were infused with Aldo (1 mg·kg−1·day−1) for 3 wk. Hemodynamic parameters were analyzed. LVH, fibrosis, inflammation, and CT-1 expression were evaluated in both experimental models by histopathological analysis, RT-PCR, Western blot analysis, and ELISA. Hypertensive Aldo-treated rats exhibited increased LV end-diastolic pressure and −dP/d t compared with controls. The cardiac index, LV cross-sectional area and wall thickness, cardiomyocyte size, collagen deposition, and inflammation were increased in Aldo-salt-treated rats. Myocardial expression of molecular markers assessing LVH and fibrosis as well as CT-l levels were also augmented by Aldo-salt. Spironolactone treatment reversed all the above effects. CT-1 correlated positively with hemodynamic, histological, and molecular parameters showing myocardial remodeling. In WT and CT-1-null mice, Aldo infusion did not modify blood pressure. Whereas Aldo treatment induced LVH, fibrosis, and inflammation in WT mice, the mineralocorticoid did not provoke cardiac remodeling in CT-1-null mice. In conclusion, in experimental hyperaldosteronism, the increase in CT-1 expression was associated with parameters showing LVH and fibrosis. CT-1-null mice were resistant to Aldo-induced LVH and fibrosis. These data suggest a key role for CT-1 in cardiac remodeling induced by Aldo independent of changes in blood pressure levels.

Blockade of NF-κB improves cardiac function and survival after myocardial infarction

2006 ◽  
Vol 291 (3) ◽  
pp. H1337-H1344 ◽  
Author(s):  
Shunichi Kawano ◽  
Toru Kubota ◽  
Yoshiya Monden ◽  
Takaki Tsutsumi ◽  
Takahiro Inoue ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Diastolic Pressure ◽  
Interstitial Fibrosis ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Targeted Disruption ◽  
Ventricular Rupture ◽  
Inflammatory Processes

NF-κB is a key transcription factor that regulates inflammatory processes. In the present study, we tested the hypothesis that blockade of NF-κB ameliorates cardiac remodeling and failure after myocardial infarction (MI). Knockout mice with targeted disruption of the p50 subunit of NF-κB (KO) were used to block the activation of NF-κB. MI was induced by ligation of the left coronary artery in male KO and age-matched wild-type (WT) mice. NF-κB was activated in noninfarct as well as infarct myocardium in WT + MI mice, while the activity was completely abolished in KO mice. Blockade of NF-κB significantly reduced early ventricular rupture after MI and improved survival by ameliorating congestive heart failure. Echocardiographic and pressure measurements revealed that left ventricular fractional shortening and maximum rate of rise of left ventricular pressure were significantly increased and end-diastolic pressure was significantly decreased in KO + MI mice compared with WT + MI mice. Histological analysis demonstrated significant suppression of myocyte hypertrophy as well as interstitial fibrosis in the noninfarct myocardium of KO + MI mice. Blockade of NF-κB did not ameliorate expression of proinflammatory cytokines in infarct or noninfarct myocardium. In contrast, phosphorylation of c-Jun NH2-terminal kinase was almost completely abolished in KO + MI mice. The present study demonstrates that targeted disruption of the p50 subunit of NF-κB reduces ventricular rupture as well as improves cardiac function and survival after MI. Blockade of NF-κB might be a new therapeutic strategy to attenuate cardiac remodeling and failure after MI.

Inhibition of NF-κB improves left ventricular remodeling and cardiac dysfunction after myocardial infarction

2007 ◽  
Vol 292 (1) ◽  
pp. H530-H538 ◽  
Author(s):  
Yasuyuki Onai ◽  
Jun-ichi Suzuki ◽  
Yasuhiro Maejima ◽  
Go Haraguchi ◽  
Susumu Muto ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Transforming Growth Factor ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Treated Group ◽  
Transforming Growth Factor Β1 ◽  
Left Ventricular ◽  
Monocyte Chemoattractant Protein 1 ◽  
Lv Remodeling

Several studies have demonstrated that NF-κB is substantially involved in the progression of cardiac remodeling; however, it remains uncertain whether the continuous inhibition of NF-κB is effective for the prevention of myocardial remodeling. Myocardial infarction (MI) was produced by ligation of the left anterior coronary artery of rats. IMD-0354 (10 mg/kg per day), a novel phosphorylation inhibitor of IκB that acts via inhibition of IKK-β, was injected intraperitoneally starting 24 h after induction of MI for 28 days. After 28 days, the IMD-0354-treated group showed significantly improved survival rate compared with that of the vehicle-treated group ( P < 0.05). Although infarct size was similar in both groups, improved left ventricular (LV) remodeling and diastolic dysfunction, as indicated by smaller LV cavity (LV end-diastolic area: vehicle, 74.13 ± 3.57 mm2; IMD-0354, 55.00 ± 3.73 mm2; P < 0.05), smaller peak velocity of early-to-late filling wave (E/A) ratio (vehicle, 3.87 ± 0.26; IMD-0354, 2.61 ± 0.24; P < 0.05), and lower plasma brain natriuretic peptide level (vehicle, 167.63 ± 14.87 pg/ml; IMD-0354, 110.75 ± 6.41 pg/ml; P < 0.05), were observed in the IMD-0354-treated group. Moreover, fibrosis, accumulation of macrophages, and expression of several factors (transforming growth factor-β1, monocyte chemoattractant protein-1, matrix metalloproteinase-9 and -2) in the noninfarcted myocardium was remarkably inhibited by IMD-0354. In conclusion, inhibition of NF-κB activation may reduce the proinflammatory reactions and modulate the extracellular matrix and provide an effective approach to prevent adverse cardiac remodeling after MI.

OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling

2015 ◽  
Vol 309 (1) ◽  
pp. H213-H221 ◽  
Author(s):  
Atsushi Ogino ◽  
Genzou Takemura ◽  
Ayako Hashimoto ◽  
Hiromitsu Kanamori ◽  
Hideshi Okada ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Control Group ◽  
Proliferating Cells ◽  
Angiogenic Activity ◽  
Adrenergic Antagonist ◽  
Peripheral Vasodilator

Although OPC-28326, 4-( N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with α2-adrenergic antagonist properties, it also reportedly exhibits angiogenic activity in an ischemic leg model. The purpose of this study was to examine the effect of OPC-28326 on the architectural dynamics and function of the infarcted left ventricle during the chronic stage of myocardial infarction. Myocardial infarction was induced in male C3H/He mice, after which the mice were randomly assigned into two groups: a control group receiving a normal diet and an OPC group whose diet contained 0.05% OPC-28326. The survival rate among the mice ( n = 18 in each group) 4 wk postinfarction was significantly greater in the OPC than control group (83 vs. 44%; P < 0.05), and left ventricular remodeling and dysfunction were significantly mitigated. Histologically, infarct wall thickness was significantly greater in the OPC group, due in part to an abundance of nonmyocyte components, including blood vessels and myofibroblasts. Five days postinfarction, Ki-67-positive proliferating cells were more abundant in the granulation tissue in the OPC group, and there were fewer apoptotic cells. These effects were accompanied by activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia within the infarct issue, assessed using pimonidazole staining, was markedly attenuated in the OPC group. In summary, OPC-28326 increased the nonmyocyte population in infarct tissue by increasing proliferation and reducing apoptosis, thereby altering the tissue dynamics such that wall stress was reduced, which might have contributed to a mitigation of postinfarction cardiac remodeling and dysfunction.

Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice

2003 ◽  
Vol 284 (1) ◽  
pp. H364-H371 ◽  
Author(s):  
Esther E. J. M. Creemers ◽  
Jeniffer N. Davis ◽  
Andrea M. Parkhurst ◽  
Peter Leenders ◽  
Kathryn B. Dowdy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Pressure ◽  
Failure Process ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Significant Loss ◽  
Contributory Factor ◽  
Similar Degree ◽  
Cross Sectional ◽  
Lv Remodeling

Recent studies have been directed at modulating the heart failure process through inhibition of activated matrix metalloproteinases (MMPs). We hypothesized that a loss of MMP inhibitory control by tissue inhibitor of MMP (TIMP)-1 deficiency alters the course of postinfarction chamber remodeling and induced chronic myocardial infarction (MI) in wild-type (WT) and TIMP-1−/− mice. Left ventricular (LV) pressure-volume loops obtained from WT and TIMP-1−/− mice demonstrated that LV end-diastolic volume [52 ± 4 (WT) vs. 71 ± 6 (TIMP-1−/−) μl] and LV end-diastolic pressure [9.0 ± 1.2 (WT) vs. 12.7 ± 1.4 (TIMP-1−/−) mmHg] were significantly increased in the TIMP-1−/− mice 2 wk after MI. LV contractility was reduced to a similar degree in the WT and TIMP-1−/− groups after MI, as indicated by a significant fall in the LV end-systolic pressure-volume relationship. Ventricular weight and cross-sectional areas of LV myocytes were significantly increased in TIMP-1−/− mice, indicating that the hypertrophic response was more pronounced. The observed significant loss of fibrillar collagen in the TIMP-1−/−controls may have been an important contributory factor for the observed LV alterations in the TIMP-1−/− mice after MI. These findings demonstrate that TIMP-1 deficiency amplifies adverse LV remodeling after MI in mice and emphasizes the importance of local endogenous control of cardiac MMP activity by TIMP-1.

Ventricular remodeling in a mouse model of myocardial infarction

1998 ◽  
Vol 274 (5) ◽  
pp. H1812-H1820 ◽  
Author(s):  
Richard D. Patten ◽  
Mark J. Aronovitz ◽  
Luz Deras-Mejia ◽  
Natesa G. Pandian ◽  
George G. Hanak ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Body Weight ◽  
Mouse Model ◽  
Sham Group ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Right Ventricular Mass

We investigated the suitability of studying ventricular remodeling in a mouse model of myocardial infarction (MI). We performed left coronary ligation ( n = 22) or a sham procedure ( n = 21) on normal C57BL/6J mice. Six weeks later, animals underwent echocardiography and hemodynamic evaluation. Left ventricular (LV) volume at a common distending pressure was calculated from passive pressure-volume curves. The MI group exhibited lower systolic blood pressure ( P < 0.05), higher LV end-diastolic pressure ( P < 0.05), and lower peak first derivative of LV pressure (dP/d t, P < 0.05) than the sham group. Mice with moderate (<40%, n = 11) and large (≥40%, n = 11) MIs displayed increased LV mass-to-body weight ratio ( P < 0.02 and P < 0.01, respectively, vs. sham group), whereas only the large-MI group exhibited increased right ventricular mass-to-body weight ratio ( P < 0.01). LV volumes were increased in the moderate-MI group ( P= 0.059 vs. sham group) and to a much greater extent in the large-MI group ( P < 0.0001 vs. sham group). The moderate- and large-MI groups also exhibited increases in LV end-diastolic diameter ( P < 0.03 and P < 0.0001, respectively, vs. sham group) and LV end-systolic diameter ( P< 0.01 and P < 0.0001, respectively, vs. sham group) with decreased fractional shortening ( P < 0.01 for both). These data demonstrate ventricular remodeling in a mouse model of MI and confirm the feasibility of quantifying indexes of remodeling in vivo and postmortem. This model will be of particular usefulness when applied to transgenic strains.

scholarly journals The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Carmen Asensio-Lopez ◽  
Yassine Sassi ◽  
Fernando Soler ◽  
Maria Josefa Fernandez del Palacio ◽  
Domingo Pascual-Figal ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Specific Treatment ◽  
Left Ventricular ◽  
Acute Stage ◽  
Soluble St2 ◽  
Underlying Mechanisms

AbstractLeft ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure.

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