Specific Mechanisms underlying Right Heart Failure

AIMS: Research into right ventricular (RV) physiology and identification of pathomechanisms underlying RV failure have been neglected for many years because function of the RV is often considered to be less important for overall hemodynamics and maintenance of blood circulation. In view of this, the present study focuses on identifying specific adaptive mechanisms of the right and left ventricle (LV) during a state of chronic nitric oxide (NO) deficiency, one of the main causes of cardiac failure. NO deficiency was induced in rats by L-NAME feeding over a four weeks period. The cardiac remodeling was then characterized separately for the RV/LV using qRT-PCR, histology, and functional measurements. RESULTS: Only the RV underwent remodeling that corresponded morphologically and functionally with the pattern of dilated cardiomyopathy. Symptoms in the LV were subtle and consisted primarily of moderate hypertrophy. A massive increase in reactive oxygen species (ROS) (+4.5+/-0.8 fold, vs. control) and a higher degree of oxidized tropomyosin (+46+/-4% vs. control) and peroxynitrite (+32+/-2% vs. control) could be identified as the cause of both RV fibrosis and contractile dysfunction. The expression of superoxide dismutase-2 was specifically increased in the LV by 51+/-3% and prevented the ROS increase and the corresponding structural and functional remodeling. INNOVATION: This study identified the inability of the RV to increase its antioxidant capacity as an important risk factor for developing RV failure. CONCLUSION: Unlike the LV, the RV did not display the necessary adaptive mechanisms to cope with increased oxidative stress during a state of chronic NO deficiency

Irreversible renal damage after transient renin-angiotensin system stimulation:involvement of an AT1-receptor mediated immune response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4-8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4-8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension

Reinforced concrete beams strengthened with externally bonded natural flax FRP plates

This paper reports an investigation on the use of natural flax fabric reinforced polymer (FFRP) composite plates as external strengthening material of reinforced concrete (RC) beams. The flexural behaviour of 2 m-long RC beams with and without FFRP plates are evaluated under four-point bending. The test variables include FFRP thickness (4 and 6 layer), the amount of internal steel reinforcement ratio (0.223% and 0.503%) and a pre-cracking of RC beams (i.e. by applying 80% yielding load of the control RC beam before the bond of FFRP plates to the RC beams). The test results indicated that FFRP plates enhance the ultimate load, deflection and ductility of the beams significantly. The increase in load and ductility is more effective for RC beams with a lower steel ratio. The strengthened beams show a similar failure mode, i.e. steel yielding and then rupture of the FFRP plate. Pre-cracking of the RC beams has no obvious effect on the ultimate load and energy absorption capacity of the FFRP strengthened beams, indicating that FFRP will be effectively to retrofit damaged RC beams (e.g. after earthquake-attack). In addition, the experimental results are compared with the predictions based on the equations given in ACI 440.2R-08 for RC beams strengthened with synthetic FRP composites. This study therefore concludes that natural flax FRP composite is an effective external reinforcement material for strengthening deficiently-designed and/or damaged RC members after earthquakes