Recombinant human erythropoietin reduces plasminogen activator inhibitor and ameliorates pro-inflammatory responses following trauma

Besides its hematopoietic effects, erythropoietin [EPO] by mobilization of iron and modulation of some inflammatory cytokines has antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate these effects of erythropoietin and its impact on organ function in traumatized patients. Twenty-six ICU-admitted traumatized patients within 24 hrs after trauma were randomly assigned to the EPO [received EPO, 300 units/Kg/day] and Control [not received EPO] groups. The inflammatory biomarkers including Tumor Necrosis Factor alpha [TNF-alpha], Interleukin 1 [IL-1], Plasminogen Activator Inhibitor 1 [PAI-1] and Nitrotyrosine were recorded at the admission, 3, 6 and 9 days thereafter. Acute Physiology and Chronic Health Evaluation [APACHE II] and Sequential Organ Failure Assessment [SOFA] scores were also recorded. Results: Among 12 patients [EPO group] TNF-alpha level at the day of 9 [P=0.046], and within EPO group at the days of 3 [P=0.026 ameliorate], 6 [P=0.016], and 9 [P=0.052] were significantly lowered. Level of IL-1 and PAI-1 decreased significantly at days of 3, 6 and 9 post intervention. Also there were significant differences between two groups in the SOFA score during three measured time intervals [the first, third and seventh days]. From the results of this study it seems that injection of erythrocyte stimulating agent is well tolerated and inhibits the inflammatory response and oxidative stress following trauma

[Rate - dependent electrophysiological effects of Crocus sativus on extracellular field potential of isolated rabbit heart in-vitro]

Herbal remedies are suitable alternatives for synthetic drugs due to their availability, minimal side effects and lower price. Biologically active substances of plant origin represent an essential branch of modern cardiovascular pharmacotherapy. The aim of the present study is to investigate rate-dependent electrophysiological effects of Crocus sativus on extra-cellular field potential of isolated rabbit heart in-vitro. Male Newsland rabbits [1.5-2 kg] were used in all of experiments; various experimental stimulating protocols [WBCL, recovery, rate-dependent protocols] were applied to study electrophysiological properties of Node [N=25]. All of the stimulated protocols repeated in the presence and absence different concentration of saffron [54,108 mg]. Results were shown as mean +/- SE. Saffron inhibited basic and rate-dependent electrophysiological properties of AV-Node. Significant prolongation of WBCL from 141 +/- 4.7 to 165.9 +/- 6.7 msec [in control and saffron group] was recorded [p<0.05]. Rate-dependent protective role of plant to increases difference between atrial and nodal effective refractory period and was observed [from 10 +/- 5.5 to 23.6 +/- 7.4 msec in control and saffron] [p<0.05]. Rate-dependent minor inhibitory role of Crocus sativus in AV-Node can modify protective role of AV-Node during arrhythmia

[ effects of liquid extract of Allium sativum on the basic and speed-dependent electrophysiological properties of islolated atrioventicular nodal of rabbit]

Herbal treatments are suitable replacement for synthetic drugs due to their availability, minimal side effects and low price. Previous studies about pharmacologic and biochemical effects of Allium sativum [garlic] have shown antihypertensive, anti arrhythmic, negative inotropic and chronotropic activities. The aim of this study was to assess the effects of liquid extract of Allium sativum on the basic and rate-dependent electrophysiological properties of isolated atrioventricular [AV] nodal of rabbit. In the present study we used isolated perfused AV-Nodal rabbit [1.5-2 kg] preparation including right atrium, intra-atrial septum and His bundle of rabbit as an experimental model to determine the effects of various concentration of aqueous extract of Allium Sativum. Selective stimulation protocols [recovery, facilitation and fatigue] were used to independently assess AV nodal properties in 14 rabbits [two groups]. In the first group of experiment [n=8 rabbits], different concentrations [20, 30, 100, 850 mg/lit] of Allium Sativum and in the second group verapamil [0.1 m] [n=6 rabbits] was applied. Data were analyzed using ANOVA and Wilcaxon tests. The results of this research indicate a significant effect of various concentrations of Allium sativum on basic electrophysiological parameters of atrioventricular node [WBCL, recovery, facilitation, fatigue] and fatigue [P<0.05]. In the presence of garlic [20 mg/lit], AVCT [atrioventricular conduction time] increased from 41.3 +/- 5.3 to 45.6 +/- 5.1msec and FRP [functional refractory period] increased from 108.6 +/- 14.4 to 167 +/- 1.1 msec [P<0.05]. The Allium sativum extract has less inhibitory effect in comparison with verapamil on the basic parameters [P<0.05] of Node. The above results showed potential antiarrhythmic properties of Allium sativum by increasing fatigue and refractory period. Therefore, it may be considered for treatment of supraventricular arrhythmias

[ study on lidocaine pharmacokinetic behavior following endotracheal administration in ICU]

Introduction: the endotracheal route for drug delivery is a valuable alternative in emergency conditions in which intravenous access is difficult or impossible. Liodcaine is an antiarrhythmic agent with tracheal absorbency, commonly used in cardiac emergenices

Objective: the purpose of this study was to investigate Lidocaine pharmacokinetic behavior following endotracheal administration in critically ill patients

Materials and Methods: 14 mechanically ventilated critically ill patients received 2mg/kg lidocaine 2% [diluted as necessary with 0.9% Saline up to total volume of 5-10 ml] via an endotracheal tube. Five positive pressure breaths were provided immediately after instillation of the drug into the airway and then patients connected to the ventillator again. Venous blood samples were drawn for 4 hours after lidocaine administration and plasma concentrations determined by HPLC method

Results: after 5 min, average lidocaine concentrations reached the therapeutic range [1.5-5 ?g/ml] and remained in this range for 30 minutes. Volume of distribution [Vd] was found to be 0.7 +/- 0.3 L/Kg, and clearance [Cl] 4.29 +/- 1.4 ml/min /kg. These valuse are lower than those described previously for healthy volunteers [P< 0.001], but similar to those described in ICU patients [P > 0.05]. Half life was 113.1 +/- 34.1 min and was not different from parameters published previously for healthy and ICU patients [P > 0.05]

Conclusion: in conclusion, endotracheal administration of Lidocaine can provide therapeutic levels in critically ill patients.It is not definitely clear that the technique of endotracheal drug administration or the unstable physiologic condition of the patients alters the pharmacokinetics of lidocaine