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Feldman, Marc D., John M. Erikson, Yi Mao, Claudia E. Korcarz, Roberto M. Lang, and Gregory L. Freeman. Feldman. Am J Physiol Heart Circ Physiol 279: H1698-H1707, 2000.--The application of left ventricular pressure-volume analysis to transgenic mice to characterize the cardiac phenotype has been problematic due to the small size of the mouse heart and the rapid heartbeat. Conductance technology has been miniaturized for the mouse and can solve this problem. However, there has been no validation of this technique. Accordingly, we performed echocardiography followed by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD-1 mice. Raw conductance volumes were corrected for an inhomogenous electrical field (a) and parallel conductance ([G.sub.pi]) yielding a stroke volume of 14.1 [+ or -] 3.7 [micro]/beat, end-diastolic volume of 20.8 [+ or -] 6.5 [micro]l, and end-systolic volume of 9.0 [+ or -] 5.8 [micro]l. The mean conductance volumes were no different from those derived by flow probe and echocardiography but did differ from ultrasonic crystals. [G.sub.pi] was determined to be 14.9 [+ or -] 8.7 [micro]l. However, hypertonic saline altered dimension and pressure in the mouse left ventricle. Although [G.sub.pi] can be determined by the hypertonic saline method, saline altered hemodynamics, questioning its validity in the mouse. Although mean measures of absolute volume may be similar among different techniques, individual values did not correlate. conductance catheter; pressure-volume analysis; ultrasonic crystals; electrocardiography; transgenic mouse

Objective To delineate daily and cumulative glucocorticoid dose thresholds associated with increased mortality rates in rheumatoid arthritis (RA). Methods We studied RA patients recruited from rheumatology clinics. Annually, we assessed the glucocorticoid dose, demographic, socioeconomic, clinical, and laboratory features of RA, cardiovascular (CV) risk factors, and vital status. We used Cox proportional hazards regression to assess associations between the daily or cumulative glucocorticoid dose and death, adjusting for potential confounders and for the propensity to receive glucocorticoids. We tested strata of the glucocorticoid dose to delineate the threshold associated with death. Results We studied 779 RA patients with a total of 7,203 person-years of observation, during which 237 of them died, yielding a mortality rate of 3.2 per 100 person-years (95% confidence interval [95% CI] 2.8-3.7). One hundred twenty of the deaths were due to CV causes, yielding a CV mortality rate of 1.8 (95% CI 1.5-2.1). Exposure to glucocorticoids was associated with a dose-dependent increase in death from all causes, with a ratio (HR) of 1.07 per mg of prednisone per day (95% CI 1.05-1.08). Compared to patients who were not receiving corticosteroids, the minimum daily prednisone dose threshold associated with an increase in all-cause mortality was 8-15 mg, with an adjusted HR of 1.78 (95% CI 1.22-2.60). For the cumulative dose of glucocorticoids, the minimum dosage associated with all-cause mortality was 40 gm (HR 1.74 [95% CI 1.25-2.44]). Conclusion Glucocorticoid use in RA is associated with a dose-dependent increase in mortality rates, with a daily threshold dose of 8 mg, at which the number of deaths increased in a dose-dependent manner. These findings may assist clinicians in selecting the appropriate glucocorticoid dosage for RA patients who require these agents. [ABSTRACT FROM AUTHOR]

An increase in oxidative stress and decrease in antioxidant enzymes have been suggested to be involved in the pathophysiology of myocardial infarction (MI). In this study in rats, treadmill exercise training and losartan treatment began 1 week post-myocardial infarction (MI) and lasted 8 weeks. We evaluated the changes in the mRNA and protein expressions for the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase after exercise and losartan treatment post-MI. Our results demonstrated that GPx and catalase mRNA levels were comparable among all the groups, while the mRNA level for manganese SOD (MnSOD) was significantly increased in exercise training with/without losartan treatment compared with the sedentary post-MI group. Moreover, the mRNA level for gp91phox was dramatically decreased by a combination of exercise and losartan treatment. The protein levels for MnSOD were significantly elevated by exercise training in combination with losartan treatment. The protein levels for catalase were significantly increased in response to exercise, and further augmented by exercise together with losartan treatment. Thiobarbituric acid-reactive substances in plasma were significantly increased in the post-MI rats, but were decreased by exercise or losartan treatment, indicating that both exercise and losartan may reduce lipid oxidative damage. In addition, catalase and SOD enzymatic activities were significantly enhanced by exercise combined with losartan treatment. Our results suggest that exercise training improves catalase and MnSOD expression and attenuates oxidative stress. These effects are potentiated when combining exercise with angiotensin II receptor blockade. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to test the hypothesis that angiotensin II receptor blockade combined with exercise training after myocardial infarction (MI) could attenuate post-MI left ventricular remodelling and preserve cardiac function. [ABSTRACT FROM PUBLISHER]

The authors comment on a study which examined the influence of cysteine-rich domains 1 and Lens Intrinsic Membrane (LIM) domain proteins on calcineurin activity. It mentions that LIM domain proteins have been assigned roles in cell growth, differentiation as well as cytoskeletal remodeling. The authors found that several LIM proteins have been determined by proteomic and functional screens of left ventricles subjected to pressure overload.