Carvedilol Decreases Elevated Oxidative Stress in Human Failing Myocardium

Nakamura, Kazufumi; Kusano, Kengo; Nakamura, Yoichi; Kakishita, Mikio; Ohta, Keiko; Nagase, Satoshi; Yamamoto, Mika; Miyaji, Kagami; Saito, Hironori; Morita, Hiroshi; Emori, Tetsuro; Matsubara, Hiromi; Toyokuni, Shinya; Ohe, Tohru

doi:10.1161/01.cir.0000018605.14470.dd

Cited by 263 publications

(177 citation statements)

References 40 publications

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“…A direct interaction with free radical, such as superoxide and hydroxyl would neutralize those dangerous radical scavanger, as previously study by Kukin et al, 1999;Dandona et al, 2000;and Nakamura et al 2002. In this study, carvedilol has no significant difference in improving pulmonary vascularity. This was due to different degree of pulmonary hypertension in each subjects, depend on naturally history of pulmonary hypertension.…”

supporting

confidence: 67%

The Improvement Chest X-Ray After Carvedilol Theraphy in Heart Failure Due to Left to Right Shunt.

Rahman¹,

Zuraedah²,

Hidayat³

et al. 2017

IJAR

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heart failure, left to right shunt congenital heart defect, carvedilol, cardio-thoracic ratio.Background: Heart failure due to left to right shunt congenital heart defect will increase pulmonary blood flow and cause volume overload. This condition activated the sympathetic nervous system and the reninangiotensin-aldosteron system. Conventional therapy has not blocked the sympathetic system yet. Carvedilol, a novel non selective β-blocker, reduced mortality and hospitalization in adults with heart failure. Limited information was available about its use in children. Objective: To evaluate the effect of carvedilol on chest x-ray in children with heart failure due to left to right shunt congenital heart defect. Methods: A randomized, double-blind, placebo-controlled study was done. In addition to conventional therapy, patients were assigned to receive placebo or carvedilol. Carvedilol was initiated at a dose of 0.05 mg/kg/day, with a target dose of 0.2 mg/kg/day. Chest x-ray was done before-after treatment and evaluated for cardio-thoracic ratio and pulmonary vascularity. The data was analyzed using independent sample t-test and Chi-square test, with confidence interval 95%. Results: Of 30 patients, 15 in each group. The mean age was 57.6(SD 43.57) months, 19(63.3%) were boys. There were 21(70%) children with VSD and 9(30%) children with PDA. Compared to control group, children in the carvedilol group had a significant decrease of cardiothoracic ratio (-2.94±2.34% versus -0.48±3.19%, p=0.023, CI 95%:-4.556 to-0.360). However, there was no significant change of pulmonary vascularity(p=0.153). Conclusion: Carvedilol decreased the cardio-thoracic ratio on chest xray, but did not improve the pulmonary vascularity in children with heart failure due to left to right shunt Congenital heart defect.

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supporting

confidence: 67%

The Improvement Chest X-Ray After Carvedilol Theraphy in Heart Failure Due to Left to Right Shunt.

Rahman¹,

Zuraedah²,

Hidayat³

et al. 2017

IJAR

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“…Cardiac oxidative stress Cardiac 4-hydroxy-2-nonenal-modified protein expression, a marker of reactive oxygen species production, 30 was significantly increased in the DM and HT+DM groups as compared with that in the control and HT groups, indicating that hyperglycemia enhanced cardiac oxidative stress (Figure 5a). Olmesartan treatment significantly ameliorated the 4-hydroxy-2-nonenal level (Figure 5a).…”

Section: Proinflammatory Cytokinesmentioning

confidence: 99%

Diabetes mellitus accelerates left ventricular diastolic dysfunction through activation of the renin–angiotensin system in hypertensive rats

et al. 2009

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Diabetes mellitus (DM) is a major risk factor for heart failure, independent of coronary artery disease or hypertension (HT). Therefore, our study was designed to examine the mechanisms of DM-induced left ventricular (LV) diastolic dysfunction. In this study, we made five different 10-week treatment groups of Dahl salt-sensitive rats as follows: Control; a low-salt (0.5% NaCl) diet, HT; a high-salt (5% NaCl) diet, DM; a low-salt diet with streptozotocin (STZ) injection (30 mg kg À1 i.p.), HT+DM; a highsalt diet with STZ injection, and the Olmesartan group; a high-salt diet with STZ treated with an angiotensin receptor blocker, olmesartan (1 mg kg À1 day À1 ). Cardiac diastolic dysfunction with a preserved systolic function was noted in the HT group, and was most prominently noted in the HT+DM group, characterized by enhanced cardiac fibrosis, whereas the extent of HT and myocardial hypertrophy was comparable between the two groups. Myocardial expressions of collagen III, transforming growth factor-b2, angiotensin-converting enzyme (ACE), angiotensin II type-1 receptor and myocardial oxidative stress (evaluated by 4-hydroxy-2-nonenal-modified protein) were mostly enhanced in the HT+DM group. Importantly, there was a positive correlation between the extent of diastolic dysfunction and that of myocardial ACE expression. All these cardiac abnormalities induced by DM and HT were ameliorated in the olmesartan group. These results indicate that DM accelerates diastolic dysfunction in hypertensive heart disease through activation of the renin-angiotensin system, with subsequent inflammatory and oxidative stresses and myocardial fibrosis, suggesting that an inhibition of the system is effective for the treatment of diastolic dysfunction in this combined disorder.

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“…Our results proved that inhibition of NADPH oxidase is one of the cardioprotective mechanisms by potassium supplementation. Along with those agents that possess both effects of ROS reduction and cardioprotection, such as ␤-blockers, 43 statins, 25 angiotensinconverting enzyme inhibitors, 20 or angiotensin 2 receptor blockers, 44 potassium supplementation can be the valuable therapeutic strategy even at the initial stage of cardiac dysfunction in the salt-sensitive patients. Figure 6.…”

Section: Perspectivesmentioning

confidence: 99%

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

et al. 2006

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Abstract-Potassium supplementation has a potent protective effect against cardiovascular disease, but the precise mechanism of it against left ventricular abnormal relaxation, relatively early functional cardiac alteration in hypertensive subjects, has not been fully elucidated. In the present study, we investigated the effect of potassium against salt-induced cardiac dysfunction and the involved mechanism. Seven-to 8-week-old Dahl salt sensitive rats were fed normal diet (0.3% NaCl) or high-salt diet (8% NaCl) with or without high potassium (8% KCl) for 8 weeks. Left ventricular relaxation was evaluated by the deceleration time of early diastolic filling obtained from Doppler transmitral inflow, the slope of the pressure curve, and the time constant at the isovolumic relaxation phase. High-salt loading induced a significant elevation of blood pressure and impaired left ventricular relaxation, accompanied by augmentation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity in the cardiac tissue, measured by the lucigenin chemiluminescence method. Blood pressure lowering by hydralazine could not ameliorate NADPH oxidase activity and resulted in no improvement of left ventricular relaxation. Interestingly, although the blood pressure remained high, potassium supplementation as well as treatment with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl, a superoxide dismutase mimetic, not only reduced the elevated NADPH oxidase activity but also improved the left ventricular relaxation. In conclusion, a high-potassium diet has a potent protective effect on left ventricular active relaxation independent of blood pressure, partly through the inhibition of cardiac NADPH oxidase activity. Sufficient potassium supplementation might be an attractive strategy for cardiac protection, especially in the salt-sensitive hypertensive subjects. Key Words: sodium Ⅲ blood pressure monitoring Ⅲ cardiac function Ⅲ heart failure Ⅲ oxidative stress Ⅲ potassium H igh-salt loading on the salt-sensitive subjects results in hypertension, left ventricular (LV) hypertrophy, and hypertensive heart failure. [1][2][3][4] The hypertensive heart failure is characterized by the LV diastolic dysfunction composed of the LV abnormal relaxation and the increased LV chamber stiffness. 5 The impaired LV active relaxation, which is observed in the patients with hypertension or diabetes, 6 has been reported recently to predict a poor prognosis, 7 thus, the preservation of the LV active relaxation from early stage may be a reasonable concept.High-salt loading on the salt-sensitive model also induces overproduction of reactive oxygen species (ROS) through activation of NADPH oxidase, 8 and ROS level had a significant positive correlation with the severity of heart failure. 9,10 In the pressure overload model by aortic banding, the impaired LV relaxation was improved effectively by antioxidant treatment, such as vitamin C or deferoxamine, indicating that excess ROS can induce LV abnormal relaxation. 11,12 To reduce ROS for cardioprotec...

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Carvedilol Decreases Elevated Oxidative Stress in Human Failing Myocardium

Cited by 263 publications

References 40 publications

The Improvement Chest X-Ray After Carvedilol Theraphy in Heart Failure Due to Left to Right Shunt.

The Improvement Chest X-Ray After Carvedilol Theraphy in Heart Failure Due to Left to Right Shunt.

Diabetes mellitus accelerates left ventricular diastolic dysfunction through activation of the renin–angiotensin system in hypertensive rats

Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction

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