The RhoA-Rho kinase (ROCK) signaling pathway has an important role in cardiovascular diseases. However, the effect of Rho kinase inhibition on pressure overload-induced cardiac hypertrophy (POH) and associated diastolic dysfunction has not been evaluated. This study examined the effect of a selective ROCK inhibitor (GSK-576371) in a POH model, induced by suprarenal abdominal aortic constriction. POH rats were divided into the following four groups: 1 (GSK 1, n = 9) or 3 (GSK 3, n = 10) mg/kg bid GSK-576371, 1 mg.kg(-1).day(-1) ramipril (n = 10) or vehicle (n = 11) treatment for 4 wk. Sham animals (n = 11) underwent surgery without banding. Echocardiograms were performed before surgery and posttreatment, and hemodynamic data were obtained at completion of the study. Echocardiography showed an increase in relative wall thickness of the left ventricle (LV) following POH + vehicle treatment compared with sham animals. This was attenuated by both doses of GSK-576371 and ramipril. Vehicle treatment demonstrated abnormal diastolic parameters, including mitral valve (MV) inflow E wave deceleration time, isovolumic relaxation time, and MV annular velocity, which were dose dependently restored toward sham values by GSK-576371. LV end diastolic pressure was increased following POH + vehicle treatment compared with sham (6.9 +/- 0.7 vs. 3.2 +/- 0.7 mmHg, P = 0.008) and was reduced with GSK 3 and ramipril treatment (1.7 +/- 0.7, P < 0.01 and 2.9 +/- 0.6 mmHg, P < 0.01, respectively). Collagen I deposition in the LV was increased following POH + vehicle treatment (32.2%; P < 0.01) compared with sham animals and was significantly attenuated with GSK 1 (21.7%; P < 0.05), GSK 3 (23.8%; P < 0.01), and ramipril (35.5%; P < 0.01) treatment. These results suggest that ROCK inhibition improves LV geometry and reduces collagen deposition accompanied by improved diastolic function in POH.
Even though monosodium glutamate (MSG) is a prototypical umami substance, previous studies reported that a conditioned taste aversion (CTA) to MSG, mixed with amiloride to block the taste of sodium, generalizes to sucrose. These findings suggest that the taste of glutamate mimics the taste of sucrose and raise the question of whether glutamate has a broadly tuned sweet taste component. To test this hypothesis, CTA experiments were conducted to test for generalization between MSG and several sweet stimuli: sucrose, glucose, maltose, saccharin and SC-45647. Strong bidirectional generalization was seen between MSG mixed with amiloride and sucrose, glucose, saccharin and SC-45647. Weak generalization was seen between MSG and maltose, and sucrose and maltose. None of the CTAs generalized to NMDA. These findings support the hypothesis that the taste of MSG has broadly tuned, sweet-like characteristics, possibly due to the convergence of afferent signals for MSG, natural sugars and artificial sweeteners.
BackgroundGlobally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects younger Indigenous and older non-Indigenous Australians. Despite its impact there is limited understanding of the factors influencing outcome following surgery for RHD.MethodsThe Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed to assess outcomes following surgical procedures for RHD and non-RHD valvular disease. The association with demographics, co-morbidities, pre-operative status, valve(s) affected and operative procedure was evaluated.ResultsOutcome of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients had longer ventilation, experienced fewer strokes and had more readmissions to hospital and anticoagulant complications. Mortality following RHD surgery at 30 days was 3.1 % (95 % CI 2.2 – 4.3), 5 years 15.3 % (11.7 – 19.5) and 10 years 25.0 % (10.7 – 44.9). Mortality following non-RHD surgery at 30 days was 4.3 % (95 % CI 3.9 - 4.6), 5 years 17.6 % (16.4 - 18.9) and 10 years 39.4 % (33.0 - 46.1). Factors independently associated with poorer longer term survival following RHD surgery included older age (OR1.03/additional year, 95 % CI 1.01 – 1.05), concomitant diabetes (OR 1.7, 95 % CI 1.1 – 2.5) and chronic kidney disease (1.9, 1.2 – 2.9), longer invasive ventilation time (OR 1.7 if greater than median value, 1.1– 2.9) and prolonged stay in hospital (1.02/additional day, 1.01 – 1.03). Survival in Indigenous Australians was comparable to that seen in non-Indigenous Australians.ConclusionIn a large prospective cohort study we have demonstrated survival following RHD valve surgery in Australia is comparable to earlier studies. Patients with diabetes and chronic kidney disease, were at particular risk of poorer long-term survival. Unlike earlier studies we did not find pre-existing atrial fibrillation, being an Indigenous Australian or the nature of the underlying valve lesion were independent predictors of survival.
We have demonstrated that advanced patient age is associated with a decreased risk of postoperative SIRS among cardiac surgery patients, where patients aged over 72 yr had the lowest risk.
BackgroundGlobally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects older non-Indigenous Australians and Aboriginal Australians and/or Torres Strait Islander peoples. Factors associated with the choice of treatment for advanced RHD remain variable and poorly understood.MethodsThe Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. Demographics, co-morbidities, pre-operative status and valve(s) affected were collated and associations with management assessed.ResultsSurgical management of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients were younger, more likely to be female and Indigenous Australian, to have atrial fibrillation (AF) and previous percutaneous balloon valvuloplasty (PBV). Surgery was performed on one valve in 64.5%, two valves in 30.0% and three valves in 5.5%. Factors associated with receipt of mechanical valves in RHD were AF (OR 2.69) and previous PBV (OR 1.98) and valve surgery (OR 3.12). Predictors of valve repair included being Indigenous (OR 3.84) and having fewer valves requiring surgery (OR 0.10). Overall there was a significant increase in the use of mitral bioprosthetic valves over time.ConclusionsRHD valve surgery is more common in young, female and Indigenous patients. The use of bioprosthetic valves in RHD is increasing. Given many patients are female and younger, the choice of valve surgery and need for anticoagulation has implications for future management of RHD and related morbidity, pregnancy and lifestyle plans.
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