Long‐Term Exposure to Biomass Fuel and Its Relation to Systolic and Diastolic Biventricular Performance in Addition to Obstructive and Restrictive Lung Diseases

Background: Previous studies have demonstrated an increased risk for cardiovascular events and pulmonary disease in patients with biomass fuel exposure (BFE). However, biventricular heart function has yet to be investigated in these patients. Left ventricular (LV) myocardial performance index (LVMPI), which is an index of global ventricular function, incorporates ejection, isovolumic relaxation, and contraction times. In this study, pulmonary function and biventricular heart function were investigated in nonsmoking female patients with BFE. Methods: Our study population consisted of 46 female patients with BFE (group 1) and 31 control subjects (group 2). Pulmonary function tests and transthoracic echocardiographic examination were performed. Right ventricular myocardial performance index (RVMPI) and LVMPI were obtained by tissue Doppler imaging echocardiography (TDI). Results: BFE caused obstructive and restrictive spirometric impairments. RVMPI was higher in group 1 (0.55 ± 0.07) than group 2 (0.46 ± 0.06) (P = 0.042) and LVMPI was higher in group 1 (0.54 ± 0.08) than group 2 (0.47 ± 0.05) (P = 0.032). Also, pulmonary artery systolic pressure was higher in group 1 than group 2 (P = 0.02). Conclusions: BFE causes both obstructive and/or restrictive lung disease and systolic and diastolic biventricular dysfunction. Nonetheless, long‐term studies are needed to understand on BFE‐related ventricular dysfunctions and to document subsequent cardiovascular events. (Echocardiography 2011;28:52‐61)     

Acute anterior myocardial infarction due to aortosaphenous vein graft occlusion with very large thrombus burden

A 75-year-old man, with a previous history of myocardial infarction and three-vessel coronary artery bypass grafting, presented with an acute anterior ST-elevation myocardial infarction. The vein graft to the left anterior descending artery was occluded with heavy thrombus burden, and the other grafts were patent. After administering a bolus dose of tirofiban and then undergoing percutaneous coronary intervention without stenting to the left anterior descending artery saphenous vein graft, intracoronary thrombolytic infusion was performed to maintain the patency of the vein graft. The patient was asymptomatic after medical follow-up. This may be an effective treatment option in patients with large thrombus burden and requires further investigation through large-scale trials.     

Metabolic profiles in closely controlled diabetic pregnancies during the third trimester

Summary In 5 closely controlled pregnant diabetics (duration of pregnancy 237–266 days) and 5 pregnant non-diabetics (duration of pregnancy 210–278 days) 4-hourly blood samples were taken throughout a 24 h period and analyzed for blood glucose, lactate, pyruvate, 3-hydroxybutyrate and acetoacetate, plasma non-esterified fatty acids (NEFA), glucagon and cortisol. 24 h urine specimen was analyzed for total catecholamines and 4-hydroxy-3-methoxymandelic acid. There were few significant differences in concentrations of metabolites and hormones in the two groups at any time, although the variations about the mean was usually greater in the diabetics. Thus for blood glucose in diabetics, mean value was 4.4 mmol/l, coefficient of variation 43%; in non-diabetics 4.1 mmol/l and 10% respectively. Mean plasma 3-hydroxybutyrate in diabetics was 0.47 mmol/l, coefficient of variation 55%; in non-diabetics 0.44 mmol/l and 37% respectively. Plasma non-esterified fatty acid levels were significantly higher in the diabetics (0.47 mmol/l) than in the non-diabetics (0.26 mmol/l). Coefficients of variation were 46% and 33% respectively. Two conclusions can be drawn; first, when near normal mean values for blood glucose are achieved, other metabolite and hormone levels are also near normal; second, even when the available means for diabetic control, strict diet and insulin-mixtures twice daily, are used at their maximum, metabolism in diabetics is more unstable than in non-diabetics.     

Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability

We demonstrated recently that chronic administration of aldosterone to rats induces glomerular mesangial injury and activates mitogen-activated protein kinases including extracellular signal-regulated kinases 1/2 (ERK1/2). We also observed that the aldosterone-induced mesangial injury and ERK1/2 activation were prevented by treatment with a selective mineralocorticoid receptor (MR) antagonist, eplerenone, suggesting that the glomerular mesangium is a potential target for injuries induced by aldosterone via activation of MR. In the present study, we investigated whether MR is expressed in cultured rat mesangial cells (RMCs) and involved in aldosterone-induced RMC injury. MR expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. Cell proliferation and micromechanical properties were determined by [3H]-thymidine uptake measurements and a nanoindentation technique using an atomic force microscope cantilever, respectively. ERK1/2 activity was measured by Western blotting analysis with an anti-phospho-ERK1/2 antibody. Protein expression and immunostaining revealed that MR was abundant in the cytoplasm of RMCs. Aldosterone (1 to 100 nmol/L) dose-dependently activated ERK1/2 in RMCs with a peak at 10 minutes. Pretreatment with eplerenone (10 micromol/L) significantly attenuated aldosterone-induced ERK1/2 phosphorylation. Aldosterone (100 nmol/L) treatment for 30 hours increased [3H]-thymidine incorporation and decreased the elastic modulus, indicating cellular proliferative and deforming effects of aldosterone, respectively. These aldosterone-induced changes in cellular characteristics were prevented by pretreatment with eplerenone or an ERK (MEK) inhibitor, PD988059 (100 micromol/L). The results indicate that aldosterone directly induces RMC proliferation and deformability through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury.     

Acute Nicotine Administration Increases BOLD fMRI Signal in Brain Regions Involved in Reward Signaling and Compulsive Drug Intake in Rats

Background:

Acute nicotine administration potentiates brain reward function and enhances motor and cognitive function. These studies investigated which brain areas are being activated by a wide range of doses of nicotine, and if this is diminished by pretreatment with the nonselective nicotinic receptor antagonist mecamylamine.

Methods:

Drug-induced changes in brain activity were assessed by measuring changes in the blood oxygen level dependent (BOLD) signal using an 11.1-Tesla magnetic resonance scanner. In the first experiment, nicotine naïve rats were mildly anesthetized and the effect of nicotine (0.03–0.6mg/kg) on the BOLD signal was investigated for 10min. In the second experiment, the effect of mecamylamine on nicotine-induced brain activity was investigated.

Results:

A high dose of nicotine increased the BOLD signal in brain areas implicated in reward signaling, such as the nucleus accumbens shell and the prelimbic area. Nicotine also induced a dose-dependent increase in the BOLD signal in the striato-thalamo-orbitofrontal circuit, which plays a role in compulsive drug intake, and in the insular cortex, which contributes to nicotine craving and relapse. In addition, nicotine induced a large increase in the BOLD signal in motor and somatosensory cortices. Mecamylamine alone did not affect the BOLD signal in most brain areas, but induced a negative BOLD response in cortical areas, including insular, motor, and somatosensory cortices. Pretreatment with mecamylamine completely blocked the nicotine-induced increase in the BOLD signal.

Conclusions:

These studies demonstrate that acute nicotine administration activates brain areas that play a role in reward signaling, compulsive behavior, and motor and cognitive function.     

Alterations in serum sodium in relation to atrial natriuretic factor and other neuroendocrine variables in experimental pacing-induced heart failure

The pathophysiologic role of atrial natriuretic factor and other neuroendocrine variables in relation to serum sodium and renal function was evaluated in 15 conscious dogs with severe chronic ventricular pacing-induced heart failure (250 beats/min for 5.1 +/- 0.4 weeks). Six sham-operated dogs observed over an 8 week period served as controls. Development of heart failure was characterized by a progressive increase in plasma norepinephrine, renin activity and aldosterone from control values of 293 +/- 15 pg/ml, 1.4 +/- 0.4 ng/ml per h and 124 +/- 42 pg/ml, respectively, to 1,066 +/- 96 pg/ml, 10.2 +/- 2.4 ng/ml per h and 577 +/- 151 pg/ml (all p less than 0.01), respectively, at severe heart failure. In contrast to other neuroendocrine variables, plasma atrial natriuretic factor increased from a control level of 243 +/- 74 pg/ml to a peak concentration of 724 +/- 149 pg/ml (p less than 0.01) at 2 weeks, then declined and plateaued at twice the level of the control value as severe heart failure developed. At severe heart failure, serum sodium decreased from 147 +/- 0.6 to 141.8 +/- 2.1 mmol/liter (p less than 0.05), whereas urea increased from 6.0 +/- 0.5 to 7.8 +/- 0.6 mmol/liter (p less than 0.05). The change in serum sodium concentration correlated with plasma renin activity and aldosterone (r = -0.77, -0.88, respectively, both p less than 0.01), but not with norepinephrine or atrial natriuretic factor. When sinus rhythm was restored, 14 dogs were observed for 48 to 72 h and 8 dogs were followed up for another 4 weeks after cessation of pacing.(ABSTRACT TRUNCATED AT 250 WORDS)