Abstract 15221: Pulmonary Artery Banding Induces NF-κB activated Inflammation and Deteriorates RV Function

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Keimei Yoshida ◽  
Kohtaro Abe ◽  
Mariko Tanaka ◽  
Masako Shinoda ◽  
Yukimitsu Kuwabara ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Chronic Administration ◽  
Inflammatory Cells ◽  
Macrophage Infiltration ◽  
Pulmonary Artery Banding ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Background: Right ventricular (RV) dysfunction contributes to poor prognosis in patients with pulmonary hypertension. Although pulmonary artery banding (PAB) induces RV inflammation, its mechanisms are poorly understood. Hypothesis: We assessed the hypothesis that RV pressure overload induced by PAB leads to RV dysfunction through NF-κB-mediated inflammation and fibrosis. Methods and Results: We banded the main PA using an 18-gauge needle in adult Sprague-Dawley rats (BW: 180-220g). We measured hemodynamics and analyzed immunohistochemistry of RV at Day 1, 3, 7 and 14 after PAB (n=4-6, each group). PAB time-dependently increased RV systolic pressure (sham: 31.1±5.7 vs. Day14: 73.2±11.8mmHg, p<0.01), RV end-diastolic pressure (RVEDP) (sham: 1.5±0.9 vs. Day14: 5.8±2.1mmHg, p<0.05) and RV hypertrophy (ratio of RV/LV+septum weight) (sham: 0.29±0.04 vs. Day14: 0.68±0.08, p<0.01) with high expression of activated p65 (NF-κB). PAB increased inflammatory cells, mainly CD68 positive macrophages (sham: 5.6±1.6 vs. Day1: 46.4±9.7 cell/mm2, p<0.01), and fibrosis areas (Masson trichrome staining) time-dependently (sham: 0.7±0.2 vs. Day14: 7.6±0.8%, p<0.01). Chronic administration of NF-κB inhibitor, pyrrolydine-dithiocarbamate (PDTC, 200mg/kg/day, orally, from Day 0 to 28), in PAB rats (n=4-7, each group) markedly decreased RVEDP (vehicle: 9.0±0.7 vs. PDTC: 3.4±1.3mmHg, p<0.01), attenuated the expression of activated p65 and infiltration of CD68 positive macrophages (vehicle: 24.1±10.4 vs. PDTC: 5.6±2.0 cell/mm2, p<0.01), and reduced fibrosis (vehicle: 8.7±1.1 vs. PDCT: 2.4±0.8%, p<0.01) (Figure). Conclusions: These findings indicate that PAB immediately activates NF-κB and increases macrophage infiltration. Second, chronic treatment with PDTC attenuates NF-κB activation and macrophage infiltration in RV, leading to reduced fibrosis as well as RVEDP. NF-κB inhibition may be a therapeutic target for the RV dysfunction.

scholarly journals Novel Model of Pulmonary Artery Banding Leading to Right Heart Failure in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Masataka Hirata ◽  
Daiki Ousaka ◽  
Sadahiko Arai ◽  
Michihiro Okuyama ◽  
Suguru Tarui ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Heart Diseases ◽  
Pressure Overload ◽  
Right Heart Failure ◽  
Pulmonary Artery Banding ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Artery Ligation ◽  
Sprague Dawley Rats ◽  
The Right

Background. Congenital heart diseases often involve chronic pressure overload of the right ventricle (RV) which is a major cause of RV dysfunction. Pulmonary artery (PA) banding has been used to produce animal models of RV dysfunction. We have devised a new and easier method of constricting the PA and compared it directly with the partial ligation method.Methods. Eight-week-old male Sprague-Dawley rats (240–260 g) were divided into three groups: sham operation, partial pulmonary artery ligation (PAL) procedure, and pulmonary artery half-closed clip (PAC) procedure. RV function and remodeling were determined by echocardiography and histomorphometry.Results. Surgical mortality was significantly lower in the PAC group while echocardiography revealed significantly more signs of RV dysfunction. At the 8th week after surgery RV fibrosis rate was significantly higher in the PAC group.Conclusions. This procedure of pulmonary artery banding in rats is easier and more efficient than partial ligation.

scholarly journals Rats are protected from the stress of chronic pressure overload compared with mice

2020 ◽  
Vol 318 (5) ◽  
pp. R894-R900 ◽  
Author(s):  
Koichi Nishimura ◽  
Marko Oydanich ◽  
Jie Zhang ◽  
Denis Babici ◽  
Diego Fraidenraich ◽  
...  
Keyword(s):  
Troponin I ◽  
Diastolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Pressure Gradients ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Systolic And Diastolic Function ◽  
Systolic Wall Stress

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats ( n = 7) and mice ( n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats ( n = 12) and mice ( n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats ( n = 6) than in mice ( n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC ( n = 4), but they were preserved in rats ( n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.

Right and left ventricular function after chronic pulmonary artery banding in rats assessed with biventricular pressure-volume loops

2006 ◽  
Vol 291 (4) ◽  
pp. H1580-H1586 ◽  
Author(s):  
Matthijs J. Faber ◽  
Michiel Dalinghaus ◽  
Inge M. Lankhuizen ◽  
Paul Steendijk ◽  
Wim C. Hop ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Ventricular Function ◽  
Time Derivative ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Pulmonary Artery Banding ◽  
Contractile Reserve ◽  
Stroke Work ◽  
Systemic Hemodynamic

In many patients with congenital heart disease, the right ventricle (RV) is subjected to abnormal loading conditions. To better understand the state of compensated RV hypertrophy, which could eventually progress to decompensation, we studied the effects of RV pressure overload in rats. In the present study, we report the biventricular adaptation to 6 wk of pulmonary artery banding (PAB). PAB resulted in an RV pressure overload to ∼60% of systemic level and a twofold increase in RV mass ( P < 0.01). Systemic hemodynamic parameters were not altered, and overt signs of heart failure were absent. Load-independent measures of ventricular function (end-systolic pressure-volume relation, preload recruitable stroke work relation, maximum first time derivative of pressure divided by end-diastolic volume), assessed by means of pressure-volume (PV) loops, demonstrated a two- to threefold increase in RV contractility under baseline conditions in PAB rats. RV contractility increased in response to dobutamine stimulation (2.5 μg·kg−1·min−1) both in PAB and sham-operated rats in a similar fashion, indicating preserved RV contractile reserve in PAB rats. Left ventricular (LV) contractility at baseline was unaffected in PAB rats, although LV volume in PAB rats was slightly decreased. LV contractility increased in response to dobutamine (2.5 μg·kg−1·min−1), both in PAB and sham rats, whereas the response to a higher dose of dobutamine (5 μg·kg−1·min−1) was blunted in PAB rats. RV pressure overload (6 wk) in rats resulted in a state of compensated RV hypertrophy with preserved RV contractile reserve, whereas LV contractile state at baseline was not affected. Furthermore, this study demonstrates the feasibility of performing biventricular PV-loop measurements in rats.

GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure

2005 ◽  
Vol 289 (4) ◽  
pp. H1643-H1651 ◽  
Author(s):  
Xiang-Bin Xu ◽  
Jin-Jiang Pang ◽  
Ji-Min Cao ◽  
Chao Ni ◽  
Rong-Kun Xu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Chronic Administration ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Cardiomyocyte Apoptosis ◽  
Lv Function ◽  
Cardiac Cachexia

Growth hormone (GH)-releasing peptides (GHRP), a class of synthetic peptidyl GH secretagogues, have been reported to exert a cardioprotective effect on cardiac ischemia. However, whether GHRP have a beneficial effect on chronic heart failure (CHF) is unclear, and the present work aims to clarify this issue. At 9 wk after pressure-overload CHF was created by abdominal aortic banding in rats, one of four variants of GHRP (GHRP-1, -2, and -6 and hexarelin, 100 μg/kg) or saline was injected subcutaneously twice a day for 3 wk. Echocardiography and cardiac catheterization were performed to monitor cardiac function and obtain blood samples for hormone assay. GHRP treatment significantly improved left ventricular (LV) function and remodeling in CHF rats, as indicated by increased LV ejection fraction, LV end-systolic pressure, and diastolic posterior wall thickness and decreased LV end-diastolic pressure and LV end-diastolic dimension. GHRP also significantly alleviated development of cardiac cachexia, as shown by increases in body weight and tibial length in CHF rats. Plasma CA, renin, ANG II, aldosterone, endothelin-1, and atrial natriuretic peptide were significantly elevated in CHF rats but were significantly decreased in GHRP-treated CHF rats. GHRP suppressed cardiomyocyte apoptosis and increased cardiac GH secretagogue receptor mRNA expression in CHF rats. GHRP also decreased myocardial creatine kinase release in hypophysectomized rats subjected to acute myocardial ischemia. We conclude that chronic administration of GHRP alleviates LV dysfunction, pathological remodeling, and cardiac cachexia in CHF rats, at least in part by suppressing stress-induced neurohormonal activations and cardiomyocyte apoptosis.

Catheterization of pulmonary artery in rats with an ultraminiature catheter pressure transducer

2003 ◽  
Vol 285 (5) ◽  
pp. H2212-H2217 ◽  
Author(s):  
Alexander Deten ◽  
Huntly Millar ◽  
Heinz-Gerd Zimmer
Keyword(s):  
Pulmonary Artery ◽  
Pressure Transducer ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Sprague Dawley ◽  
Control Value ◽  
Pulmonary Arterial ◽  
Long Evans ◽  
Infusion Of Norepinephrine ◽  
The Right

Utilizing new materials and miniaturization techniques, an ultraminiature catheter pressure transducer for catheterization of the pulmonary artery (PA) has been developed and applied in intact, spontaneously breathing, anesthetized rats. The catheter arrangement consists of three components: 1) an SPR-671 ultraminiature pressure transducer (measuring catheter), 2) a plastic introducer (sheath) that is slipped over the measuring catheter, and 3) an external wire mounted on the outside of the introducer for bending its tip. The measuring catheter is first inserted through the right jugular vein into the right ventricle. The introducer is then slipped over it. The tip of the introducer is bent so that there is an angle of ∼90° or less to the shaft. The measuring catheter is advanced across the pulmonary valve into the PA. Measurements of pulmonary arterial pressure were made in five male Long Evans (364 ± 7 g body wt) and five female Sprague-Dawley (244 ± 7 g body wt) rats under control conditions. The effects of infusion of norepinephrine (0.1 mg·kg–1·h–1 iv for 20-min duration) were tested in Long Evans rats. Pulmonary arterial systolic pressure measurements were 34.0 ± 0.8 and 29.5 ± 0.4 mmHg, and diastolic pressure values were 23.6 ± 0.8 and 18.1 ± 0.6 mmHg in male Long Evans and female Sprague-Dawley rats, respectively. Norepinephrine induced an increase in pulmonary arterial systolic (40.8 ± 0.1 mmHg) and diastolic (28.6 ± 0.4 mmHg) pressures and an elevation in pulmonary vascular resistance from a control value of 0.093 ± 0.003 to 0.103 ± 0.004 mmHg·kg·min·ml–1.

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

2007 ◽  
Vol 292 (6) ◽  
pp. H2737-H2744 ◽  
Author(s):  
Masahito Kajiya ◽  
Masanori Hirota ◽  
Yousuke Inai ◽  
Takahiko Kiyooka ◽  
Taro Morimoto ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Suppressive Effect ◽  
Protective Role ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Sprague Dawley Rats ◽  
Endothelial Nitric Oxide ◽  
Arteriolar Vasodilation

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline ( n = 126) to induce PH or with saline as controls ( n = 114). After 3 wk, coronary arterioles (diameter = 30–100 μm) and small arteries (diameter = 100–200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of Nω-nitro-l-arginine methyl ester (l-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without l-NAME, and in the presence of SOD. The degree of suppression in vasodilation by l-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.

scholarly journals Investigation of hemotoxicologic potential of an ayurvedic preparation Kutajarista used in Sprue syndrome after chronic administration to male Sprague-Dawley rats

2020 ◽  
Vol 14 (8) ◽  
pp. 308-315
Author(s):  
Tohidul Amin Mohammad ◽  
Fatema Kaniz ◽  
karmakar Palash ◽  
Abdur Rahman Md. ◽  
Haque Tazmel ◽  
...  
Keyword(s):  
Chronic Administration ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Acute cyclosporine-induced renal vasoconstriction: lack of effect of theophylline

1990 ◽  
Vol 258 (1) ◽  
pp. F41-F45
Author(s):  
P. C. Churchill ◽  
N. F. Rossi ◽  
M. C. Churchill ◽  
A. K. Bidani ◽  
F. D. McDonald
Keyword(s):  
Renal Plasma Flow ◽  
Left Kidney ◽  
Chronic Administration ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Adenosine Receptor Antagonist ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Group 1

Both acute and chronic administration of cyclosporine A (CSA) lead to renal vasoconstriction, but the mechanism is not fully understood. The present studies were designed to explore the possible role of adenosine in acute CSA-induced renal vasoconstriction in rats. Six groups of anesthetized Sprague-Dawley rats were studied using standard clearance techniques: group 1 rats were controls; groups 2, 4, and 6 received CSA intravenously at 20, 30, and 40 mg.h-1.kg body wt-1, respectively; groups 3 and 5 were identical to groups 2 and 4 except that a priming injection of theophylline was given (56 mumol/kg body wt) and theophylline was included in the intravenous infusate (0.56 mumol.min-1.kg body wt-1). CSA produced acute and concentration-dependent reductions in renal plasma flow (left kidney) and in the clearances of p-aminohippuric acid and inulin (both kidneys). Except in group 6, these changes were observed in the absence of a decrease in arterial blood pressure, demonstrating that CSA produced an acute and concentration-dependent increase in renovascular resistance. Theophylline not only failed to block CSA-induced renal vasoconstriction, if anything, it potentiated it. Because theophylline is an adenosine receptor antagonist, these findings contradict the hypothesis that adenosine mediates acute CSA-induced renal vasoconstriction.

Colchicine attenuates left ventricular hypertrophy but preserves cardiac function of aortic-constricted rats

2003 ◽  
Vol 94 (4) ◽  
pp. 1627-1633 ◽  
Author(s):  
Beatriz S. Scopacasa ◽  
Vicente P. A. Teixeira ◽  
Kleber G. Franchini
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Colchicine Treatment ◽  
Average Diameter ◽  
Left Ventricular ◽  
Lv Function ◽  
Right Ventricular Mass ◽  
Lv Mass ◽  
Phenylephrine Infusion

To investigate the effects of colchicine on left ventricular (LV) function and hypertrophy (LVH) of rats subjected to constriction of transverse aorta (TAoC), we evaluated SO (sham operated, vehicle; n = 25), SO-T (sham operated, colchicine 0.4 mg/kg body wt ip daily; n = 38), TAoC (vehicle; n = 37), and TAoC-T (TAoC, colchicine; n = 34) on the 2nd, 6th, and 15th day after surgery. Colchicine attenuated LVH of TAoC-T compared with TAoC rats, as evaluated by ratio between LV mass (LVM) and right ventricular mass, LV wall thickness, and average diameter of cardiac myocytes. Systolic gradient across TAoC (∼45 mmHg), LV systolic pressure, LV end-diastolic pressure, and rate of LV pressure increase (+dP/d t) were comparable in TAoC-T and TAoC rats. However, the baseline and increases of LV systolic pressure-to-LVM and +dP/d t-to-LVMratios induced by phenylephrine infusion were greater in TAoC-T and SO-T compared with SO rats. Baseline and increases of +dP/d t-to-LVM ratio were reduced in TAoC compared with SO rats. TAoC rats increased polymerized fraction of tubulin compared with SO, SO-T, and TAoC-T rats. Our results indicate that colchicine treatment reduced LVH to pressure overload but preserved LV function.

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