Beneficial hemodynamic effects of inhibiting ANP catabolism in congestive heart failure

Pepper, Beverly (escultora)Primer pla de l'obra. També conegut com a "Cel caigut, Espiral arbrada", realitzat amb ceràmica

Impact of timing administration of mesenchymal stromal cells on serum creatinine following renal ischemia/ reperfusion in rats

peer reviewedExperimental models of renal ischemia/reperfusion (I/R) have suggested protective effects of mesenchymal stromal cells (MSC) therapy. Still, param- eters of MSC injection, including volume, route and timing of cell administration, remain largely debated. Particularly, MSC infusion in mouse has been shown to be beneficial “a priori” but deleterious “a posteriori” of renal I/R injury. In order to further investigate the influence of the timing of MSC administration, we used 10-week-old Lewis rats categorized in 4 groups. Groups 1 (MSC D-7, n = 10) and 2 (MSC D + 1, n = 7) received caudal i.v. injection of MSC (1.5 9 106 in 1 ml of saline) 7 days before or 1 day after renal I/R, respectively. Control groups 3 (saline D-7, n = 6) and 4 (saline D + 1, n = 6) received equal volume of saline at similar time points. Left renal ischemia (by clamping of the renal pedicle) lasted 45 min. Right nephrectomy was simultaneously performed. Blood sample was collected from inferior vena cava at 48 h post reperfusion. MSC phenotype was confirmed by FACS analysis. In groups 1 and 3, serum creatinine (SCr) reached 1.4 ` 0.7 versus 2.4 ` 0.8 mg/dl, respectively (p < 0.05). In groups 2 and 4, SCr was 4.9 ` 0.7 versus 3.3 ` 0.9 mg/dl, respectively (p < 0.001). Furthermore, SCr levels were statistically worse when MSC were administered after renal I/R in comparison to a priori infusion (p < 0.0001). In conclusion, MSC administration 7 days prior to renal I/R attenuates kidney injury in comparison to (i) saline infusion or (ii) MSC infusion 1 day after renal I/R. Conversely, on the basis of SCr levels, MSC therapy performed after renal I/R worsens kidney injury in rats

Increased risk of interstitial fibrosis and tubular atrophy in controlled donation after circulatory death kidney transplantation

Introduction: Comparable transplant outcomes between controlled donation after circulatory death (cDCD) and donation after brain death (DBD) kidney transplantation (KT) have been confirmed. However, few data describes the histology of cDCD-KT which is subjected to prolonged procurement warm ischemia. This study aimed to evaluate the rate of interstitial fibrosis (IF) and tubular atrophy (TA) on the surveillance biopsy performed in our unit between the 2 and 6 months post KT. Acute rejection was considered as secondary endpoint. Patients and Methods: 330 KT (226 DBD and 104 DCD) have been performed between 2008 and 2014. Surveillance or per-cause biopsy was performed in 272 recipients. Among them, the rate of adequate (≥8 glomeruli and ≥1 large-sized artery) was 76.8%. Results: IFTA was found in 11.5% and 25.7% of DBD and cDCD-KT, respectively (p = 0.004). Considering IF and TA separately, the corresponding rates were 20.4% vs 32% (p = 0.04) and 23% vs 36% (p = 0.03), respectively. If acute rejection before routine biopsy was excluded, either IF or TA rate was significantly higher in cDCD- than DBD-KT (12.6% vs 27.1%, p = 0.006; 17.6% vs 31.4%, p = 0.016; and 20.9% vs 35.7%, p = 0.015 in case of IF-TA, IF, and TA, respectively). A cDCD-KT compared to a DBD-KT was 3.11 (95%CI 1.51– 6.43, p = 0.002), 2.34 (95%CI 1.21–4.53, p = 0.011) and 2.29 (95%CI 1.23– 4.27, p = 0.009) times more likely to have IFTA, IF, and TA, respectively. Extended criteria donor (ECD) vs standard criteria donor (SCD) was also an independent risk factor for IFTA (OR = 3.11, 95%CI 1.51–6.43, p = 0.002), IF (OR = 4.86, 95%CI 1.96–12.05, p = 0.001), and TA (OR = 4.09, 95%CI 1.68– 9.93, p = 0.002). The rate of acute rejection diagnosed by SB was 7.1% and 8.9% in DBD and cDCD kidney grafts (p = ns), respectively.Conclusion: KT from cDCD increased the risk of IF-TA between 3 and 6 months post-transplant. Further studies are warranted to investigate the evolution of this phenomenon over time and its effect on graft function

Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT

Comparative Effects of University of Wisconsin and Euro-Collins Solutions on Pulmonary Mitochondrial Function after Ischemia and Reperfusion

peer reviewedBACKGROUND: The aim of this study was to compare the effects of Euro-Collins and University of Wisconsin solutions on pulmonary mitochondrial function after cold ischemia and subsequent warm reperfusion. METHODS: Seventeen pigs underwent lung harvesting after classical lung flush with either University of Wisconsin or Euro-Collins solutions. The mitochondria were isolated from fresh swine lungs, from swine lungs subjected to 24 hr of cold ischemia, and from swine lungs subjected to 24 hr of ischemia followed by 30 min of subsequent ex vivo reperfusion at 37 degrees C with Krebs-Henseleit buffer solution and air ventilation. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption rates. During reperfusion, the lung function was assessed by the pulmonary aerodynamic parameters and the pulmonary vascular resistance. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain. However, the yield of oxidative phosphorylation was conserved. After reperfusion, pulmonary mitochondria underwent a significant worsening in the oxidoreductase activities of the respiratory chain, and a decrease in the respiratory control and the efficiency of oxidative phosphorylation. Meanwhile, the reperfused lungs showed evidence of early dysfunction, assessed by the aerodynamic parameters and pulmonary vascular resistance. In this model, there was no advantage of University of Wisconsin solution over Euro-Collins solution. CONCLUSIONS: The mild mitochondrial alterations after cold ischemia were not sufficient to explain the limited tolerance of lung to ischemia. After reperfusion, the mitochondrial damage was more severe and could be involved in the posttransplant lung dysfunction

Effects of helium-oxygen on respiratory mechanics, gas exchange, and ventilation-perfusion relationships in a porcine model of stable methacholine-induced bronchospasm

Objective: To explore the consequences of helium/oxygen (He/O2) inhalation on respiratory mechanics, gas exchange, and ventilation-perfusion (VA/Q) relationships in an animal model of severe induced bronchospasm during mechanical ventilation. Design: Prospective, interventional study. Setting: Experimental animal laboratory, university hospital. Interventions: Seven piglets were anesthetized, paralyzed, and mechanically ventilated, with all ventilator settings remaining constant throughout the protocol. Acute stable bronchospasm was obtained through continuous aerosolization of methacholine. Once steady-state was achieved, the animals successively breathed air/O2 and He/O2 (FIO2 0.3), or inversely, in random order. Measurements were taken at baseline, during bronchospasm, and after 30min of He/O2 inhalation. Results: Bronchospasm increased lung peak inspiratory pressure (49±6.9 vs 18±1cmH2O, P<0.001), lung resistance (22.7±1.5 vs 6.8±1.5cmH2O.l−1.s, P<0.001), dynamic elastance (76±11.2 vs 22.8±4.1cmH2O.l−1, P<0.001), and work of breathing (1.51±0.26 vs 0.47±0.08, P<0.001). Arterial pH decreased (7.47±0.06 vs 7.32±0.06, P<0.001), PaCO2 increased, and PaO2 decreased. Multiple inert gas elimination showed an absence of shunt, substantial increases in perfusion to low VA/Q regions, and dispersion of VA/Q distribution. He/O2 reduced lung resistance and work of breathing, and worsened hypercapnia and respiratory acidosis. Conclusions: In this model, while He/O2 improved respiratory mechanics and reduced work of breathing, hypercapnia and respiratory acidosis increased. Close attention should be paid to monitoring arterial blood gases when He/O2 is used in mechanically ventilated acute severe asthm

Felodipine-metoprolol combination tablet: A valuable option to initiate antihypertensive therapy?

The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/β-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic ≤90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment. Am J Hypertens 1999;12:915-920 © 1999 American Journal of Hypertension, Lt