Risk factors for delayed graft function and their impact on graft outcomes in live donor kidney transplantation

International Urology and Nephrology - Delayed graft function (DGF) is a manifestation of acute kidney injury uniquely framed within the transplant process and a predictor of poor long-term graft...     

Erythropoietin attenuates motor impairments induced by bilateral renal ischemia/reperfusion in rats

Neurologic sequelae remain a common and destructive problem in patients with acute kidney injury. The objective of this study was to evaluate the possible neuroprotective effect of erythropoietin (EPO) on motor impairments following bilateral renal ischemia (BRI) in two time points after reperfusion: short term (24 h) and long term (1 week). Male Wistar rats underwent BRI or sham surgery. EPO or saline administration was performed 30 min before surgery (1000 U/kg, i.p.). Explorative behaviors and motor function of the rats were evaluated by open field, rotarod, and wire grip tests. Plasma concentrations of blood urea nitrogen (BUN) and creatinine (Cr) were significantly enhanced in BRI rats 24 h after reperfusion. BRI group had only an increased level of BUN but not Cr 1 week after reperfusion. Impairment of balance function by BRI was not reversed by EPO 24 h after reperfusion, but counteracted 7 days after renal ischemia. Muscle strength had no significant differences between the groups. BRI group had a decrease in locomotor activity, and EPO could not reverse this reduction in both time points of the experiment. Although EPO could not be offered as a potential neuroprotective agent in the treatment of motor dysfunctions induced by BRI, it could be effective against balance dysfunction 1 week after renal ischemia.     

Protective role of simvastatin on isolated rabbit atrioventricular node during experimental atrial fibrillation model: role in rate control of ventricular beats

The purpose of the present study was to determine (1) whether simvastatin (SV) modifies the rate-dependent conduction time and refractoriness of the atrioventricular (AV) node and (2) how it can change the protective mechanism of the AV node during atrial fibrillation (AF). Predefined stimulation protocols were applied to detect the electrophysiological parameters of the AV node, including atrial-His conduction time, effective refractory period (ERP), functional refractory period (FRP), concealed conduction, excitable index, and fatigue in two groups of isolated, perfused rabbit AV nodal preparations (N=16). The stimulation protocols (fatigue, recovery) were carried out during control and in the presence of SV (0.5, 0.8, 3, and 10 μM). Simulated AF was executed in a separate group (N=8), and specific indexes, including H-H mean, zone of concealment (ZOC), and concealed beats were recorded. SV, in a concentration-dependent manner, prolonged ERP, FRP, and Wenckebach cycle lengths. It (10 μM) significantly increased fatigue and the excitable index. In addition, SV elicited prolongation of ZOC and H-H mean at 3 and 10 μM. SV-evoked prolongation of nodal refractoriness and concealed conduction caused rate-dependent ventricular slowing effects during AF. The ability of simvastatin to decrease the excitable gap by its heterogeneous effects on nodal dual pathways proposes its protective role in AF.     

Effects of beta-adrenergic receptor stimulation and blockade on rate-dependent atrioventricular nodal properties.

Recent work has shown that alterations in the dynamic atrioventricular (AV) nodal response to changes in heart rate can significantly modify AV nodal function. The present study was designed to evaluate the nature and potential importance of sympathetic regulation of the rate-dependent properties of the AV node. Selective stimulation protocols and mathematical formulations were used to independently quantify AV nodal recovery, facilitation, and fatigue in 12 morphine-chloralose-anesthetized dogs. Vagal effects were prevented by bilateral vagal transection and intravenous atropine, and the sinus node was crushed to allow a broader range of pacing cycle lengths. In seven dogs with sympathetic nerves intact, beta-adrenergic receptor blockade increased the recovery time constant (tau rec) for the conduction of premature test beats from 47 +/- 2 (mean +/- SEM) msec (control) to 62 +/- 1 msec (p less than 0.001), whereas isoproterenol decreased tau rec to 38 +/- 1 msec (p less than 0.001). In addition, beta-blockade increased the maximum amount of rate-dependent AV nodal fatigue from 7 +/- 1 msec (at a cycle length of 198 +/- 9 msec [control]) to 17 +/- 2 msec (p less than 0.001). In five dogs with decentralized stellate ganglia, tau rec was decreased from 71 +/- 3 msec (control) to 57 +/- 4 msec and 48 +/- 2 msec (p less than 0.001 for each) by left stellate ganglion stimulation at 5 and 10 Hz, respectively. Maximum fatigue was similarly reduced from 16 +/- 1 msec (control) to 12 +/- 2 msec (p = NS) and 8 +/- 1 msec (p less than 0.01), respectively. Stellate ganglion stimulation, isoproterenol, and beta-blockade did not alter AV nodal facilitation. A mathematical model incorporating quantitative indexes of AV nodal function accurately accounted for tachycardia-dependent increases in the atrial-His activation interval, which were enhanced by beta-adrenergic receptor blockade and reduced by isoproterenol. Furthermore, this model showed that beta-adrenergic effects were increased by increasing heart rate, with the majority of the rate-dependent action being due to changes in the time course of AV nodal recovery. We conclude that beta-adrenergic receptor stimulation alters functional properties that govern the AV nodal response to changes in heart rate. These changes in functional properties alter the ability of the AV node to conduct impulses during tachycardia and, as such, could play a major role in the ability of sympathetic stimulation to promote and beta-adrenergic receptor blockade to prevent the occurrence of AV nodal reentrant arrhythmias.     

Frequency-dependent electrophysiological remodeling of the AV node by hydroalcohol extract of Crocus sativus L. (saffron) during experimental atrial fibrillation: the role of endogenous nitric oxide

The study assessed the hydroalcohol extract effects of Crocus sativus L. (saffron) on (i) the basic and rate‐dependent electrophysiological properties of the AV node, (ii) remodeling of the AV node during experimental atrial fibrillation (AF) and (iii) the role of nitric oxide (NO) in the effects of saffron on the AV node. Stimulation protocols in isolated AV node were used to quantify AV nodal recovery, facilitation and fatigue in four groups of rabbits (n = 8–16 per group). In addition, the nodal response to AF was evaluated at multiple cycle lengths and during AF. Saffron had a depressant effect on AV nodal rate‐dependent properties; further, it increased Wenckebach block cycle length, functional refractory period, facilitation and fatigue (p < 0.05). A NO‐synthase inhibitor (L‐NAME) prevented the depressant effects of saffron on the AV node (p < 0.05). Saffron increased the zone of concealment in experimental AF (p < 0.05). The present research showed, for the first time, established electrophysiological remodeling of the AV node during AF by saffron. Saffron increased the AV nodal refractoriness and zone of concealment. These depressant effects of saffron were mediated by endogenous NO. Copyright © 2011 John Wiley & Sons, Ltd.     

Prevention and Control of Infections in Patients with Severe Congenital Neutropenia; A Follow up Study

Severe Congenital Neutropenia is one of primary immunodeficiency disorders that characterized by severe neutropenia and is associated with severe systemic bacterial infections from early infancy. Granulocyte Colony Stimulating Factor (GCSF) is clinically used as a treatment for congenital and acquired neutropenia. The aim of this study was evaluation of GCSF (PD- Grastim) in treatment of these patients. Patients with severe congenital neutropenia referred to Immunology, Asthma and Allergy Research Institute between Jan 2007 and Dec 2010 enrolled the study. Other causes of neutropenia were excluded by serial CBC and bone marrow studies, medical and drug histories and immunological tests. Patients were visited and examined monthly to evaluate their CBC and ANC (Absolute Neutrophil Count), GCSF side effects and dosage adjustment. Cytogenetic studies were being done for all the patients for early detection of progression to AML/MDS. From twenty two patients who enrolled this study, 16 patients regularly evaluated. They were ten males and six females, range in age from 2 to 18 years old. Two patients failed to continue our follow up unfortunately and four patients died due to disease complications. Patients were followed for 24 to 48 months. In a period of 12-24 months before treatment, the mean of hospitalization frequency was 3.1 times and duration was 10 days; while during receiving treatment, they decreased to 0.2 times and 3 days, respectively (p<0.01). Also significant increase in mean ANC was observed during follow up (315/μl before treatment versus 1749/μl after 12 month regular treatment). Bone pain was the most common side effect. There have been no evidences of developing AML/MDS up to present time. Treatment with GCSF significantly reduced the duration and the frequency of hospitalization. Because of plausible progression to AML/MDS, regular follow-up of patients should be continued.     

Prolongation of AV nodal refractoriness by Ruta graveolens in isolated rat hearts. Potential role as an anti-arrhythmic agent

OBJECTIVE: To evaluate concentration-dependent effects of total extract of Ruta graveolens and its purified alkaloid fraction on the nodal basic and functional properties. METHODS: In the present experimental study, we used the Langendorff model for perfusion of isolated rat hearts to determine the effects of various concentrations of methanolic extract of Rue (1.25 x 10(-6) % weight per volume percent [W/V]; 2.5 x 10(-6) % W/V; 3.75 x 10(-6) % W/V) and total alkaloid of Rue (0.25 x 10(-6) % W/V; 0.5 x 10(-6) % W/V) on electrophysiological properties of cardiac tissue. Selective stimulation protocols were used to independently quantify atrioventricular AV nodal recovery, facilitation, and fatigue. We used 3 groups (N=24) of isolated perfused rat AV nodal preparations to assess the effect of Rue extracts. The study was carried out in October 2006 in the electrophysiology laboratory of the Cardiovascular Research Center of Golestan University of Medical Sciences, Golestan, Gorgan, Iran. RESULTS: Our results showed that both the total plant extract and the alkaloid fraction of Ruta graveolens had a similar trend of action on nodal conduction time and refractoriness. Furthermore, we observed increased atrioventricular conduction time (83+/-4 to 108+/-5) msec and functional refractory period (157.6+/-3 to 163.7+/-4 msec) at a maximum concentration of 3.75 x 10(-6) % W/V. CONCLUSION: The above results indicated a potential antiarrhythmic effect of Ruta graveolens in treating supra ventricular tachyarrhythmia.     

Comparison of hemodynamic and biochemical effects of furosemide by continuous infusion and intermittent bolus in critically ill patients.

Positive fluid balance in critically ill patients is a common problem in the intensive care unit (ICU) often associated with a poor outcome. In addition, clinically important changes in hemodynamic variables have been found to occur after diuretic therapy. This study was conducted to evaluate the safety and relative effectiveness of two diuretic protocols in the ICU. Twenty-two patients in the medical ICU with pulmonary edema or fluid overload and PaO2/FIO2 pressure less than 300, were randomized to diuretic therapy by either continuous infusion or intermittent bolus. Hemodynamic and biochemical measurements were recorded. Protocol-guided diuretic management can be readily and safely implemented in the ICU. Although both continuous and bolus diuretic regimens appear to be equally effective in achieving negative fluid balance, the clinician may consider a continuous infusion of furosemide in the hemodynamically and electrolytically unstable patient to ensure more controlled diuresis with less hemodynamic and electrolyte alteration. From a nursing perspective, a continuous infusion of furosemide is a more efficient means of drug delivery.