Although exercise reduces several cardiovascular risk factors associated with obesity/diabetes, the metabolic effects of exercise on the heart are not well-known. This study was designed to investigate whether high-intensity interval training (HIT) is superior to moderate-intensity training (MIT) in counteracting obesity-induced impairment of left ventricular (LV) mechanoenergetics and function. C57BL/6J mice with diet-induced obesity (DIO mice) displaying a cardiac phenotype with altered substrate utilization and impaired mechanoenergetics were subjected to a sedentary lifestyle or 8–10 weeks of isocaloric HIT or MIT. Although both modes of exercise equally improved aerobic capacity and reduced obesity, only HIT improved glucose tolerance. Hearts from sedentary DIO mice developed concentric LV remodeling with diastolic and systolic dysfunction, which was prevented by both HIT and MIT. Both modes of exercise also normalized LV mechanical efficiency and mechanoenergetics. These changes were associated with altered myocardial substrate utilization and improved mitochondrial capacity and efficiency, as well as reduced oxidative stress, fibrosis, and intracellular matrix metalloproteinase 2 content. As both modes of exercise equally ameliorated the development of diabetic cardiomyopathy by preventing LV remodeling and mechanoenergetic impairment, this study advocates the therapeutic potential of physical activity in obesity-related cardiac disorders.

1 Clinical studies have shown di erent e ects of b-blockers on the b-adrenergic system, tolerability and outcome in patients with heart failure. 2 The study examines b-adrenoceptor-G-protein coupling and intrinsic activity of bucindolol, carvedilol and metoprolol in human ventricular myocardium. 3 Radioligand binding studies ([ 125 I]-Iodocyanopindolol) were performed in membrane preparations of human failing and nonfailing myocardium. Functional experiments were carried out in isolated muscle preparations of human left ventricular myocardium from failing hearts. 4 Bucindolol and carvedilol bound non-selectively to b 1 -and b 2 -adrenoceptors and exerted guanine nucleotide modulatable binding. Metoprolol was 35-fold b 1 -selective and lacked guanine nucleotide modulatable binding. 5 All b-blockers antagonized isoprenaline-induced enhancement of contractility. 6 In preparations in which the coupling of the stimulatory G-protein to adenylate cyclase was facilitated by forskolin, bucindolol increased force of contraction in three and decreased it in ®ve experiments. Carvedilol increased force in one and decreased it in six experiments. Metoprolol decreased force in all experiments by 89.4+2.2% (P50.01 metoprolol vs carvedilol and bucindolol). The negative inotropic e ect of metoprolol was antagonized by bucindolol. 7 It is concluded that di erences in intrinsic activity can be detected in human myocardium and have an impact on cardiac contractility. In human ventricular myocardium, bucindolol displays substantially higher intrinsic activity than metoprolol and carvedilol. Bucindolol can behave as partial agonist or partial inverse agonist depending on the examined tissue. 8 Di erences in intrinsic activity may contribute to di erences in b-adrenoceptor regulation and possibly to di erences in tolerability and outcomes of patients with heart failure.

AimThe aim of this study was to investigate if working in a cold environment and feeling cold at work are associated with chronic pain (ie, lasting ≥3 months).MethodsWe used data from the sixth survey (2007–2008) of the Tromsø Study. Analyses included 6533 men and women aged 30–67 years who were not retired, not receiving full-time disability benefits and had no missing values. Associations between working in a cold environment, feeling cold at work and self-reported chronic pain were examined with logistic regression adjusted for age, sex, education, body mass index, insomnia, physical activity at work, leisure time physical activity and smoking.Results779 participants reported working in a cold environment ≥25% of the time. This exposure was positively associated with pain at ≥3 sites (OR 1.57; 95% CI 1.23 to 2.01) and with neck, shoulder and leg pain, but not with pain at 1–2 sites. Feeling cold sometimes or often at work was associated with pain at ≥3 sites (OR 1.58; 95% CI 1.22 to 2.07 and OR 3.90; 95% CI 2.04 to 7.45, respectively). Feeling cold often at work was significantly and positively associated with pain at all sites except the hand, foot, stomach and head.ConclusionWorking in a cold environment was significantly associated with chronic pain. The observed association was strongest for pain at musculoskeletal sites and for those who often felt cold at work.

Background-The functional significance of cross-regulation between the renin-angiotensin system (RAS) and tumor necrosis factor (TNF) has been established in nonmyocyte cell types; however, the degree and functional significance of the interaction between RAS and TNF has not been characterized in the heart. Methods and Results-We examined the expression of components of the RAS in a line of transgenic mice (MHCsTNF) with cardiac restricted overexpression of TNF. When examined at 4, 8, and 12 weeks of age, the MHCsTNF mice had increased activation of myocardial RAS, as shown by an increase in ACE mRNA level and ACE activity and increased angiotensin II peptide levels. Furthermore, myocardial angiotensin receptor mRNA and protein levels were reduced in the MHCsTNF mice, consistent with homologous desensitization of the receptors. However, expression of renin and angiotensinogen was not increased in MHCsTNF mice compared with littermate controls. To determine the functional significance of RAS activation in the MHCsTNF mice, we treated the mice with an angiotensin type I receptor antagonist, losartan (30 mg/kg), or diluent from 4 to 8 weeks of age. Analysis of cardiac structure with MRI showed that treatment with losartan normalized left ventricular mass and wall thickness. Furthermore, treatment with losartan reduced myocardial collagen content and reduced the incidence of myocyte apoptosis. Conclusions-Taken together, these results show that there are functionally significant interactions between RAS and TNF in the heart and that these interactions play an important role in the development and progression of left ventricular remodeling. (Circulation. 2003;108:598-604.)