Celiprolol augments the effect of physical exercise on insulin sensitivity and serum lipid levels in chronic heart failure

Pietilä, Mikko; Malminiemi, Kimmo; Huupponen, Risto; Rouru, Juha; Pulkki, Kari; Pere, Erkki; Voipio‐Pulkki, Liisa‐Maria

doi:10.1016/s1388-9842(00)00054-4

Cited by 20 publications

(18 citation statements)

References 30 publications

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“…18 In the present study, we could not find a significant correlations between the decrease in insulin level or HOMA IR and an increase in exercise tolerance after physical training. However, improvement in IR tended to correlate with a reduction of resting heart rate.…”

Section: Discussioncontrasting

confidence: 82%

“…Previous studies have reported conflicting results regarding the effect of physical training on insulin sensitivity in CHF patients. [16][17][18] Kemppainen et al demonstrated that physical training elicited a 25% improvement in insulin sensitivity, 16 but Sabelis et al failed to show a beneficial effect of physical training on insulin sensitivity in patients with CHF. 17 In the study by Pietila et al, the combined use of physical training and -blocker, celiprolol, improved insulin sensitivity, but the effect was not clear in the physical training group with -blockade.…”

Section: Discussionmentioning

confidence: 99%

“…17 In the study by Pietila et al, the combined use of physical training and -blocker, celiprolol, improved insulin sensitivity, but the effect was not clear in the physical training group with -blockade. 18 These conflicting results are possibly caused by different groups of study patients with various etiologies and severity of heart failure. The present study demonstrated that physical training improved IR in patients with mild to moderate heart failure, mostly caused by non-ischemic heart disease.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Because it improve insulin sensitivity in healthy subjects and in athletes, [13][14][15] exercise is potentially an appealing method of improving IR in patients with CHF, but there have been few reports of the effect of physical training in such cases. [16][17][18] …”

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confidence: 99%

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Effect of Physical Training on Insulin Resistance in Patients With Chronic Heart Failure

Nishiyama

Minohara

Ohe

et al. 2006

Circ J

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hronic heart failure (CHF) is characterized by depressed left ventricular performance and changes in peripheral tissue, such as impaired peripheral blood flow, 1,2 abnormalities of mitochondrial structure and function, alterations in the oxidative metabolism of skeletal muscle and atrophy of predominantly oxidative insulinsensitive slow twitch (type I) fibers, resulting in a relatively larger proportion of glycolytic, less insulin-sensitive fast twitch (type IIb) fibers. [3][4][5][6] These peripheral changes are associated with decreased exercise tolerance 7 and are also related to the insulin resistance (IR) observed in patients with CHF. 8,9 Physical training has beneficial effects on exercise capacity and quality of life in patients with CHF. [10][11][12] Because it improve insulin sensitivity in healthy subjects and in athletes, [13][14][15] exercise is potentially an appealing method of improving IR in patients with CHF, but there have been few reports of the effect of physical training in such cases. [16][17][18] Methods PatientsThe study group comprised 20 consecutive patients with CHF who were admitted to Kurume University Medical Center. Criteria for the diagnosis of heart failure were: New York Heart Association functional class II or III, echocardiographic left ventricular diastolic diameter ≥50 mm and left ventricular ejection fraction ≤50%. Underlying heart diseases causing CHF were dilated cardiomyopathy in 7, hypertensive heart disease in 4, coronary artery disease in 4, hypertrophic cardiomyopathy in 2, valvular heart disease in 2, and chronic myocarditis in 1. Patients were excluded from the study if they had fasting blood sugar >110 mg/dl, inflammatory diseases, or any other organ failure. Informed consent was given by each patient.Of the 20 patients, 14 were eligible for physical training and the remaining 6 who were unable to perform the exercise stress test and physical training because of orthopedic or neuromuscular diseases were allocated to the control group. Left ventricular function was determined by echocardiography before and after physical training in the training group.All patients received conventional drug therapy as required throughout the study. Medications included angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (n=16), diuretics (n=12), digitalis (n=9), -adrenergic blocking agents (n=9), antiarrhythmic agents (n=7), calcium-channel antagonists (n=6), isosorbide dinitrate (n=7), nicorandil (n=3), -adrenergic blocking agents (n=1) and vesnarinone (n=1). Blood Samples and Hormone MeasurementsBlood samples were collected in the morning following an overnight fast. After supine rest for at least 20 min, a sample was taken from the antecubital vein and after immediate centrifugation, aliquots were stored at -70°C until analysis. Fasting levels of glucose and uric acid were measured by enzymatic methods and fasting levels of insulin were measured by radioimmunoassay kits (Linco Research, Inc, St Charles, MO, USA). Norepinephrine were measured with high-perf...

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Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of Physical Training on Insulin Resistance in Patients With Chronic Heart Failure

Nishiyama

Minohara

Ohe

et al. 2006

Circ J

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“…Considering its excellent level of safety, 36 the favorable effect on serum lipid metabolism and insulin sensitivity in chronic heart failure, 37 the benefit from the blockade of ␤ 1 -ARs confirmed in large-scale clinical trials, 38 and its ability to activate the eNOS signaling pathway, a further large-scale and long-term clinical trial is needed to provide conclusive evidence for the effect of celiprolol in patients with chronic heart failure, especially those with hypertension, cardiac hypertrophy, diabetes mellitus, or hyperlipidemia. …”

Section: Discussionmentioning

confidence: 99%

Celiprolol, A Vasodilatory β-Blocker, Inhibits Pressure Overload–Induced Cardiac Hypertrophy and Prevents the Transition to Heart Failure via Nitric Oxide–Dependent Mechanisms in Mice

et al. 2004

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Background-The blockade of ␤-adrenergic receptors reduces both mortality and morbidity in patients with chronic heart failure, but the cellular mechanism remains unclear. Celiprolol, a selective ␤ 1 -blocker, was reported to stimulate the expression of endothelial NO synthase (eNOS) in the heart, and NO levels have been demonstrated to be related to myocardial hypertrophy and heart failure. Thus, we aimed to clarify whether celiprolol attenuates both myocardial hypertrophy and heart failure via the NO-signal pathway. Methods and Results-In rat neonatal cardiac myocytes, celiprolol inhibited protein synthesis stimulated by either isoproterenol or phenylephrine, which was partially suppressed by N G -nitro-L-arginine methyl ester (L-NAME). Four weeks after transverse aortic constriction (TAC) in C57BL/6 male mice, the ratio of heart weight to body weight (mg/g) (8.70Ϯ0.42 in TAC, 6.61Ϯ0.44 with celiprolol 100 mg · kg Ϫ1 · d Ϫ1 PO, PϽ0.01) and the ratio of lung weight to body weight (mg/g) (10.27Ϯ1.08 in TAC, 7.11Ϯ0.70 with celiprolol 100 mg · kg Ϫ1 · d Ϫ1 PO, PϽ0.05) were lower and LV fractional shortening was higher in the celiprolol-treated groups than in the TAC group. All of these improvements were blunted by L-NAME. Celiprolol treatment significantly increased myocardial eNOS and activated phosphorylation of eNOS. Myocardial mRNA levels of natriuretic peptide precursor type B and protein inhibitor of NO synthase, which were increased in the TAC mice, were decreased in the celiprolol-treated mice. Conclusions-These findings indicated that celiprolol attenuates cardiac myocyte hypertrophy both in vitro and in vivo and halts the process leading from hypertrophy to heart failure. These effects are mediated by a selective ␤ 1 -adrenergic receptor blockade and NO-dependent pathway.

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Exercise training for patients with heart failure: a systematic review of factors that improve mortality and morbidity

Smart¹,

Marwick²

2004

The American Journal of Medicine

360

237

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Celiprolol augments the effect of physical exercise on insulin sensitivity and serum lipid levels in chronic heart failure

Cited by 20 publications

References 30 publications

Effect of Physical Training on Insulin Resistance in Patients With Chronic Heart Failure

Effect of Physical Training on Insulin Resistance in Patients With Chronic Heart Failure

Celiprolol, A Vasodilatory β-Blocker, Inhibits Pressure Overload–Induced Cardiac Hypertrophy and Prevents the Transition to Heart Failure via Nitric Oxide–Dependent Mechanisms in Mice

Exercise training for patients with heart failure: a systematic review of factors that improve mortality and morbidity

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