Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study

<p>Abstract</p> <p>Aim</p> <p>Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin-stimulated endothelial function in patients with type 2 diabetes.</p> <p>Method</p> <p>24 patients with type 2 diabetes were randomized to receive either 200 mg metoprolol succinate or 50 mg carvedilol daily. Endothelium-dependent vasodilation was assessed by using venous occlusion plethysmography with increasing doses of intra-arterial infusions of the agonist serotonin. Insulin-stimulated endothelial function was assessed after co-infusion of insulin for sixty minutes. Vaso-reactivity studies were done before and after the two-month treatment period.</p> <p>Results</p> <p>Insulin-stimulated endothelial function was deteriorated after treatment with metoprolol, the percentage change in forearm blood-flow was 60.19% ± 17.89 (at the highest serotonin dosages) before treatment and -33.80% ± 23.38 after treatment (p = 0.007). Treatment with carvedilol did not change insulin-stimulated endothelial function. Endothelium-dependent vasodilation without insulin was not changed in either of the two treatment groups.</p> <p>Conclusion</p> <p>This study shows that vascular insulin sensitivity was preserved during treatment with carvedilol while blunted during treatment with metoprolol in patients with type 2 diabetes.</p> <p>Trial registration</p> <p>Current Controlled Trials NCT00497003</p

The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive

Britt Falskov1, Thomas Steffen Hermann1, Christian Rask-Madsen2, Atheline Major-Pedersen1, Buris Christiansen1, Jakob Rauns&oslash;1, Lars K&oslash;ber3, Christian Torp-Pedersen1, Helena Dominguez41Department of Cardiology, Gentofte Hospital, Denmark; 2Joslin Diabetes Center, Boston (MA), USA; 3Department of Cardiology, Rigshospitalet, Copenhagen, Denmark; 4Department of Cardiology, Herlev Hospital, Herlev, DenmarkAim: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes.Methods: Twenty-three patients with systolic heart failure and no history of diabetes, seven patients with both systolic heart failure and type 2 diabetes, 19 patients with type 2 diabetes, and ten healthy controls were included in the study. Endothelial function was studied by venous occlusion plethysmography. Insulin-stimulated endothelial function was assessed after intra-arterial infusion of insulin followed by co-infusion with serotonin in three different dosages. Forearm glucose uptake was measured during the insulin infusion.Results: Patients with systolic heart failure had impaired insulin-stimulated endothelial function. The percentage increase in blood flow during co-infusion with insulin and serotonin dose response study was 24.74% &plusmn; 6.16%, 23.50% &plusmn; 8.32%, and 22.29% &plusmn; 10.77% at the three doses respectively, compared to the healthy control group 45.96% &plusmn; 11.56%, 67.40% &plusmn; 18.11% and 84.57% &plusmn; 25.73% (P = 0.01). Insulin-stimulated endothelial function was similar in heart failure patients and patients with type 2 diabetes, while it was further deteriorated in patients suffering from both heart failure and diabetes with a percentage increase in blood flow of 19.15% &plusmn; 7.81%, -2.35% &plusmn; 11.76%, and 5.82% &plusmn; 17.70% at the three doses of serotonin, respectively. Forearm glucose uptake was impaired in patients with heart failure compared to healthy controls (P = 0.03) and tended to be further impaired by co-existence of diabetes (P = 0.08).Conclusion: Systolic heart failure and type 2 diabetes result in similar vascular insulin resistance and reduced muscular insulin-stimulated glucose uptake. The effects of systolic heart failure and type 2 diabetes appear to be additive.Keywords: insulin resistance, diabetes, heart failure, endothelial functio

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study

<p>Abstract</p> <p>Background</p> <p>Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF.</p> <p>Methods</p> <p>Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period.</p> <p>Results</p> <p>Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after treatment (p = 0.74) and in the metoprolol succinate group 1.82 ± 0.29 and 2.10 ± 0.37 before and after treatment, respectively (p = 0.27). Diurnal blood pressures as well as heart rate were also unchanged by changing from carvedilol to metoprolol tartrate or metoprolol succinate.</p> <p>Conclusion</p> <p>Endothelial function remained unchanged when switching the beta blocker treatment from carvedilol to either metoprolol tartrate or metoprolol succinate in this study, where blood pressure and heart rate also remained unchanged in patients with mild HF.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.clinicaltrials.gov/ct2/show/NCT00497003">NCT00497003</a></p

Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

<p>Abstract</p> <p>Background</p> <p>The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia.</p> <p>Methods</p> <p>First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion.</p> <p>Results</p> <p>Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours.</p> <p>Conclusions</p> <p>Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.</p

Hormone replacement therapy and risk of new-onset atrial fibrillation after myocardial infarction--a nationwide cohort study.

OBJECTIVES: Our aim was to assess the association between use of hormone replacement therapy (HRT) and risk of new-onset atrial fibrillation (AF) after myocardial infarction. DESIGN, SETTING AND PARTICIPANTS: We used Danish nationwide registers of hospitalizations and prescriptions to identify all women admitted with myocardial infarction in the period 1997 to 2009 and with no known diagnosis of AF. Their use of overall HRT and HRT categories was assessed. Multivariable Cox proportional hazards analysis was used to calculate the risk of new-onset AF first year after discharge, comparing use of HRT to no use. MAIN OUTCOME MEASURES: New-onset atrial fibrillation. RESULTS: In the period 1997 to 2009, 32 925 women were discharged alive after MI. In the first year after MI, new-onset AF was diagnosed in 1381 women (4.2%). Unadjusted incidence rates of AF decreased with use of HRT (incidence rate 37.4 for use of overall HRT and 53.7 for no use). Overall HRT was associated with a decreased risk of AF (HR 0.82, 95% confidence interval [CI] 0.68-1.00). The lowest risk of AF was found in women ≥80 years old for use of overall HRT and vaginal estrogen (HR 0.63, CI 0.42-0.94, and HR 0.58, CI 0.34-0.99, respectively). Decreased risk of AF with use of overall HRT and HRT categories was also found in other age groups. CONCLUSIONS: Use of HRT is associated with a decreased risk of new-onset AF in women with myocardial infarction first year after discharge. The underlying mechanisms remain to be determined. Unmeasured confounding might be one of them