Distinct load dependence of relaxation rate and diastolic function in Oryctolagus cuniculus and Ratus norvegicus

This study investigated potential differences on load dependence of relaxation rate and diastolic function between Oryctolagus cuniculus and Ratus norvegicus, which have constitutive differences in the mechanisms involved in myocardial inactivation. Load dependence of relaxation rate and diastolic function were evaluated with the response of left ventricular time constant tau and diastolic pressure-dimension relation to beat-to-beat aortic constrictions in open-chest rabbits and rats. Afterload levels were normalized, being expressed as a percentage of peak isovolumetric pressure (relative load). In control heartbeats, relaxation rate and diastolic function were similar in the two animal species. They presented, however, distinct responses to afterload elevations. In rabbits, time constant decreased similar to7% and diastolic pressure-dimension relation remained unchanged when afterload was elevated to a relative load of 73-76%. Above this afterload level, a significant deceleration of relaxation rate (increase of time constant) and an upward shift of diastolic pressure-dimension relation were observed. In rats, afterload elevations accelerated pressure fall up to a relative load of 97-100% and no afterload-induced shift of the diastolic pressure-dimension relation was observed. This study provides, therefore, evidence that Oryctolagus cuniculus has lower afterload reserve of myocardial relaxation and diastolic function than Ratus norvegicus

Evaluation of biventricular function in the rat: a new experimental model

The use of small animals in cardiovascular research has increased over recent years. This might be a limitation when evaluation of biventricular function is required. Although evaluation of left ventricular (LV) pressure and volume is already possible in small animals, concomitant evaluation of right ventricle function has been limited to large animals. The study describes a new model to assess pressures and dimensions of both ventricles simultaneously in the adult rat. Adult Wistar rats (n = 12), weighing 372 +/- 16 g, were anesthetized with pentobarbital (60 mg/kg, i.p.) and ventilated through a tracheostomy (60 cpm, 1 ml/100 g). Under a dissecting microscope (6x) the right jugular vein was catheterized. After sternotomy and pericardiotomy, three crystals were placed along the major cardiac transverse diameter: in the right subendocardium of the interventricular septum and on the epicardial surfaces of the RV and LV free walls. In addition, two high-fidelity catheters were introduced through the apex into the RV (2F, Millar) and LV (3F, Millar) cavities. This allowed the measurement of all parameters derived from pressure and dimension curves of the RV and LV, including pressure-dimension loops. This study describes, for the first time, a model that allows simultaneous evaluation of biventricular pressure and dimensions in an animal model as small as an adult rat. This model opens up new perspectives for the establishment of correlations between molecular biology and hemodynamic data in both ventricles, which is particularly important as more differences between the two ventricles are being found

Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

We investigated the endogenous production of ghrelin as well as cardiac and pulmonary vascular effects of its administration in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). Adult Wistar rats randomly received a subcutaneous injection of MCT (60 mg/kg) or an equal volume of vehicle. One week later, animals were randomly assigned to receive a subcutaneous injection of ghrelin (100 mug/kg bid for 2 wk) or saline. Four groups were analyzed: normal rats treated with ghrelin (n = 7), normal rats injected with saline (n = 7), MCT rats treated with ghrelin (n = 9), and MCT rats injected with saline (n = 9). At 22-25 days, right ( RV) and left ventricular (LV) pressures were measured, heart and lungs were weighted, and samples were collected for histological and molecular analysis. Endogenous production of ghrelin was almost abolished in normal rats treated with ghrelin. In MCT-treated animals, pulmonary expression of ghrelin was preserved, and RV myocardial expression was increased more than 20 times. In these animals, exogenous administration of ghrelin attenuated PH, RV hypertrophy, wall thickening of peripheral pulmonary arteries, and RV diastolic disturbances and ameliorated LV dysfunction, without affecting its endogenous production. In conclusion, decreased tissular expression of ghrelin in healthy animals but not in PH animals suggests a negative feedback in the former that is lost in the latter. A selective increase of ghrelin mRNA levels in the RV of animals with PH might indicate distinct regulation of its cardiac expression. Finally, ghrelin administration attenuated MCT-induced PH, pulmonary vascular remodeling, and RV hypertrophy, indicating that it may modulate PH

Potencial hidrogeniônico de antimicrobianos, segundo os fatores ambientais temperatura e luminosidade

The objective of this experimental study was to measure the pH of antibiotics administered by intravenous infusion - ceftriaxone sodium, vancomycin hydrochloride, metrodinazole, penicillin G potassium and amikacin sulfate - after reconstitution with sterile water and dilution with NaCl 0.9% or dextrose 5% in water, according to temperature and luminosity of the environment. The results showed that variation in the drugs' pH was less than 1.0 value and that some antibiotics remained acidic after dilution and maintained this chemical profile in all situations studied, suggesting that the studied environmental factors did not change the solutions' acid base characteristic. Some pH values measured characterize risk for the development of chemical phlebitis and infiltration, and it is important for clinical practice to emphasize the profile of intravenous solutions of antibiotics, considering method of dilution, and time to infusion.El objetivo de este estudio experimental fue medir el pH de los antibióticos de administración intravenosa ceftriaxona sódica, clorhidrato de vancomicina, metronidazol, penicilina G potásica y sulfato de amikacina, después de reconstitución con agua destilada y dilución con NaCl a 0,9%, o suero glucosado a 5%, considerando la influencia de la temperatura y luminosidad ambientales, así como el tiempo de exposición, en el comportamiento químico de esos fármacos. Los resultados demostraron variaciones que no ultrapasaron 1,0 (valor de pH) y que algunos antimicrobianos, eminentemente ácidos después de la dilución, mantuvieron ese comportamiento en todas las situaciones estudiadas, no sugiriendo la influencia de factores ambientales en el comportamiento químico de las soluciones. Considerando que algunos valores de pH encontrados pueden contribuir para el desarrollo de flebitis química e infiltración, es importante enfatizar que para la práctica clínica en salud, existe la necesidad de conocer las características de las soluciones de infusión intravenosa, considerando el tipo de dilución y el tiempo de infusión.O objetivo deste estudo experimental foi medir o pH dos antibióticos de administração intravenosa ceftriaxona sódica, cloridrato de vancomicina, metronidazol, penicilina G potássica e sulfato de amicacina, após reconstituição com água destilada e diluição com NaCl 0,9%, ou soro glicosado 5%, considerando a influência da temperatura e luminosidade ambientais, assim como do tempo de exposição, no comportamento químico desses fármacos. Os resultados demonstraram variações que não ultrapassaram 1,0 valor de pH e que alguns antimicrobianos, eminentemente ácidos após a diluição, mantiveram esse comportamento em todas as situações estudadas, não sugerindo a influência de fatores ambientais no comportamento químico das soluções. Como alguns valores de pH encontrados podem contribuir para o desenvolvimento de flebite química e infiltração, é importante enfatizar para a prática clínica em saúde, a necessidade de conhecer as características das soluções de infusão intravenosa, considerando tipo de diluição e tempo de infusão.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Departamento de EnfermagemUNIFESP, Depto. de EnfermagemCNPq: 476295/2004-1CNPq: 502382/2007-4SciEL

Should C-reactive protein concentration at ICU discharge be used as a prognostic marker?

<p>Abstract</p> <p>Background</p> <p>About one third of hospital mortality in critically ill patients occurs after Intensive Care Unit (ICU) discharge. Some authors have recently hypothesized that unresolved or latent inflammation and sepsis may be an important factor that contributes to death following successful discharge from the ICU.</p> <p>Aim</p> <p>The aim of our study was to determine the ability of the clinical and inflammatory markers at ICU discharge to predict post-ICU mortality.</p> <p>Methods</p> <p>A prospective observational cohort study was conducted during a 14-month period in an 8 bed polyvalent ICU. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, Therapeutic Intervention Scoring System-28 (TISS-28), C-reactive protein (CRP), white cell count (WCC) and body temperature of the day of ICU discharge were collected from patients who survived their first ICU admission.</p> <p>Results</p> <p>During this period 156 patients were discharged alive from the ICU. A total of 29 patients (18.6%) died after ICU discharge. There were no differences in clinical and demographic characteristics between survivors and nonsurvivors. C-reactive protein levels at ICU discharge were not significantly different between survivors and nonsurvivors. The area under receiver operating characteristics curves of APACHE II, SAPS II, SOFA, TISS-28, CRP, WCC and body temperature at ICU discharge as prognostic markers of hospital death were 0.76 (95% confidence interval (CI) 0.67-0.86); 0.75 (95% CI 0.66-0.85); 0.72 (95% CI 0.62-0.83); 0.64 (95% CI 0.52-0.77); 0.55 (95% CI 0.43-0.67); 0.55 (95% CI 0.42-0.66) and 0.54 (95% CI 0.44-0.67) respectively. The hospital mortality rate of the patients with CRP <5, 5-10, >10 mg/dL was 15.1%, 16.1% and 33.3% respectively (p = NS).</p> <p>Conclusions</p> <p>At ICU discharge serum CRP concentration was a poor marker of post-ICU prognosis. Post-ICU death appears to be unrelated to the persistent inflammatory response.</p

Ghrelin reverses molecular, structural and hemodynamic alterations of the right ventricle in pulmonary hypertension

Ghrelin is an endogenous peptide that has a dual effect by activating specific receptors and by stimulating release of growth hormone. There is increasing evidence that ghrelin has a potent vasodilator effect. Recently, we demonstrated that exogenous administration of ghrelin modulates its endogenous levels and attenuates the majority of alterations induced by monocrotaline (MCT). In the present study, we evaluate the effects of chronic administration of ghrelin on hemodynamic and morphometric parameters of the right ventricle, as well as on myocardial levels of SERCA2a and endothelin-1. Adult Wistar rats were injected with MCT (60 mg/kg, sc) or just the vehicle (day 0). One week later, the animals treated with MCT were randomly divided into two groups and treated with ghrelin (100 microg/kg, bid, sc) or with a similar volume of vehicle. Between days 21-25 the animals were instrumented to record right ventricular (RV) pressures and samples were collected for morphological and molecular analysis. Ghrelin treatment attenuated the effects of MCT, namely: RV myocyte fiber diameter, pulmonary vascular remodeling (evaluated by % medial wall thickness of peripheral arteries), RV peak systolic pressure, RV end-diastolic pressure, time constant tau, and SERCA2a and endothelin-1 mRNA levels. Chronic ghrelin administration attenuates MCT-induced pulmonary hypertension, vascular remodeling and RV hypertrophy. These results suggest a potential therapeutic role for the ghrelin-growth hormone axis in pulmonary hypertension