In healthy subjects, plasma concentrations of dexmedetomidine that significantly exceed the recommended therapeutic level do not seriously attenuate myocardial perfusion below the level that is observed with usual therapeutic concentrations and do not induce evident myocardial ischemia.

Long-term CRT has beneficial effects on LV function and myocardial efficiency at rest in patients with HF. These effects are not associated with changes in myocardial perfusion or oxygen consumption. During dobutamine-induced stress, CRT does not affect functional parameters, but myocardial efficiency and metabolic reserve may be increased.

Aims/hypothesis Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This study aimed to examine whether α-tocopherol or β-carotene affected the occurrence of type 2 diabetes. Methods In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, controlled trial, 29,133 male smokers aged 50-69 years were randomised to receive either α-tocopherol (50 mg/day) or β-carotene (20 mg/day) or both agents or placebo daily for 5-8 years (median 6.1 years). Baseline serum samples were analysed for α-tocopherol and β-carotene using HPLC. Cases of diabetes were identified from a nationwide Finnish registry of patients receiving drug reimbursement for diabetes. Of 27,379 men without diabetes at baseline, 705 men were diagnosed with diabetes during the follow-up of up to 12.5 years. Results Baseline serum levels of α-tocopherol and β-carotene were not associated with the risk of diabetes in the placebo group: the relative risk (RR) between the highest and lowest quintiles of α-tocopherol was 1.59 (95% CI 0.89-2.84) and that for β-carotene was 0.66 (95% CI 0.40-1.10). Neither supplementation significantly affected the incidence of diabetes: the RR was 0.92 (95% CI 0.79-1.07) for participants receiving α-tocopherol compared with nonrecipients and 0.99 (95% CI 0.85-1.15) for participants receiving β-carotene compared with non-recipients. Conclusions/interpretation Neither α-tocopherol nor β-carotene supplementation prevented type 2 diabetes in male smokers. Serum levels of α-tocopherol and β-carotene were not associated with the risk of type 2 diabetes.ClinicalTrials.gov ID no. NCT00342992

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In the peripheral vasculature, insulin induces time-and dose-dependent vasodilation. We have recently demonstrated that insulin potentiates adenosine-stimulated myocardial blood flow. However, it is unknown whether insulin's effects on the coronary vasculature are dose dependent. In this study, we quantitated myocardial blood flow and adenosine-stimulated coronary flow (140 g ⅐ kg -1 ⅐ min -1 for 5 min) in 10 healthy men (age, 32 ؎ 6 years; BMI, 24.1 ؎ 1.8 kg/m 2 ) using positron emission tomography and 15 O-labeled water. Hyperemic myocardial blood flow was measured in the basal state, during euglycemic physiological hyperinsulinemia (serum insulin ϳ65 mU/l) and during supraphysiological hyperinsulinemia (serum insulin ϳ460 mU/l). Basal myocardial blood flow was 0.84 ؎ 0.17 ml ⅐ g ؊1 ⅐ min ؊1 . Physiological hyperinsulinemia increased the adenosine-stimulated flow by 20% (from 3.92 ؎ 1.17 to 4.72 ؎ 0.96 ml ⅐ g ؊1 ⅐ min ؊1 ; P < 0.05). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow by 19% (to 5.61 ؎ 1.03 ml ⅐ g ؊1 ⅐ min ؊1 ; P < 0.05). These effects were not explained by changes in systemic hemodynamics, since coronary resistance decreased during each insulin infusion (P < 0.05). In addition, hyperemic myocardial blood flow responses during insulin stimulation were positively correlated with whole-body glucose uptake. The results demonstrate that insulin is able to enhance hyperemic myocardial blood flow in a dosedependent manner in healthy subjects. These effects might contribute to the known beneficial dose-dependent effects of insulin on myocardial ischemia. Diabetes 51:1125-1130, 2002 I nsulin is known to be vasoactive in the peripheral vasculature, but its effects on myocardial perfusion are poorly known. Glucose-insulin-potassium (GIK) therapy has been found to be beneficial in the treatment of acute myocardial ischemia (1,2). Several metabolic mechanisms, such as changes in glucose (3,4) and free fatty acid (5,6) metabolism, may explain the beneficial effects of insulin. In addition to these actions on myocardial substrate metabolism, we have recently shown that insulin directly affects myocardial perfusion (7). In addition, Marano et al. (8) demonstrated using SPECT (single-photon emission computed tomography) that GIK therapy improved regional myocardial perfusion and function mainly in segments adjacent to the recently infarcted area.Insulin induces a dose-dependent vasodilation in the peripheral arteries (9 -11) that is blunted in insulin-resistant states (10,12,13). Insulin causes endothelium-dependent vasodilation by the L-arginine-nitric oxide pathway (14,15), and another important mediator of insulin-induced vasodilation is the sympathetic nervous system (14). Unlike studies of insulin's action on skeletal muscle perfusion, studies addressing insulin's action on myocardial perfusion are sparse. Because differences in the regulation of vasodilation between coronary and peripherial arteries have been observed (7), previous studies targeting insulin's effects on t...

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

Those reporting childhood adversities and poor parent-child relationships had less optimistic expectations, which may need to be addressed in clinical settings.

The normalization of C-reactive protein proved to be a good predictor of a favourable late outcome (surgery, death) of IE. Also WBC count proved useful in the assessment of patients with IE, but the value of ESR was negligible.