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Acute kidney injury is usually associated with distant organ dysfunction. The roles of inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in this phenomenon were investigated following 2 h unilateral renal ischemia and 24 h reperfusion. There were 3 groups of rats subjected to either unilateral ischemia/reperfusion (UIR group), unilateral nephrectomy (UNX group), or sham operation. Two further groups were given α-tocopherol and aminoguanidine with UIR (treated- UIR group) and UNX (treated-UNX group). Plasma nitrite/nitrate and malondialdehyde were elevated only in the UIR group. Creatinine clearance and blood flow increased in non-ischemic kidney of the UIR, but not to the same extent as remnant kidney of the UNX group, while they had equal compensatory rises in absolute [Na.sup.+] and [K.sup.+] excretion and urine flow. Non- ischemic kidney of the treated-UIR group, but not remnant kidney of the treated-UNX group, showed more elevation in blood flow, whereas both kidneys had reductions in absolute [Na.sup.+] excretion and urine flow. Respiratory functional variable were not different between all groups. Therefore, 2 h unilateral renal ischemia and 24 h reperfusion did not affect lung but had distant effects on contralateral kidney partly mediated by ROS and NO-derived from iNOS to dampen compensatory increases in renal hemodynamics and to decrease tubular reabsorption. Key words: acute kidney injury, acute lung injury, alpha-tocopherol, aminoguanidine, inducible nitric oxide synthase, ischemia/ reperfusion, reactive oxygen species, unilateral nephrectomy, unilateral renal ischemia. Le dommage renal aigu est normalement associe a un dysfonctionnement d'organes situes a distance. Les roles de la synthase d'oxyde nitrique inductible (iNOS) et des especes reactives d'oxygene (ERO) dans ce phenomene ont ete examines a la suite d'une ischemie unilaterale renale de 2 h et d'une reperfusion de 24 h. Trois groupes de rats ont ete soumis soit, a une ischemie/reperfusion unilaterale (groupe IRU), soit a une nephrectomie unilaterale (NXU) ou a une operation fictive. Deux autres groupes ont recu de l'α-tocopherol et de l'aminoguanidine en plus de l'IRU (groupe IRU traite) ou la NXU (groupe NXU traite). Le rapport nitrite/nitrate plasmatique et les niveaux de malonaldehyde etaient eleves chez le groupe IRU seulement. La clairance de la creatine et le debit sanguin augmentaient dans le rein non-ischemique du groupe IRU, mais dans une ampleur moindre que dans le rein restant du groupe NXU, alors qu'ils presentaient des augmentations compensatoires egales sur le plan de l'excretion absolue de [Na.sup.+] et de [K.sup.+] et du debit urinaire. L'augmentation du debit sanguin etait plus importante dans le rein non-ischemique du groupe IRU traite, contrairement au rein restant du groupe NXU traite, alors que l'excretion absolue de [Na.sup.+] et le debit urinaire etaient reduits dans les deux types de reins. Les variables respiratoires fonctionnelles n'etaient pas differentes entre tous les groupes. Ainsi, une ischemie renale unilaterale de 2 h et une reperfusion de 24 n'affectent pas le poumon mais exercent des effets a distance sur le rein contra-lateral medies en partie par les ERO et le NO produit par la iNOS afin d'attenuer les augmentations compensatoires dans l'hemodynamique renale et de diminuer la reabsorption tubulaire. [Traduit par la Redaction] Mots-cles : dommage renal aigu, dommage pulmonaire aigu, alpha-tocopherol, aminoguanidine, synthase d'oxyde nitrique inductible, ischemie/reperfusion, especes reactives d'oxygene, nephrectomie unilaterale, ischemie renale unilaterale., Introduction Acute kidney injury (AKI) comprises 30%-50% of admissions to critical care units. Despite advances in the renal replacement therapies and intensive care support, patients with AKI still have mortality [...]

Background: Some respiratory diseases may induce alveolar hypoxia thereby hypoxic pulmonary vasoconstriction (HPV). However, the mechanisms of this physiologic phenomenon are not fully understood. This study was the first to investigate the role of anion exchanger in sustained HPV. Methods: Experiments were performed in the isolated perfused rabbit lung. After preparation, the lungs were divided into six groups: two DIDS (4,4-diisothiocyanostilbene 2,2-disulfonic acid, anion exchanger inhibitor)-treated [200 μM (n=5) or 400 μM (n=3)] hypoxic groups, two HCO3 - free hypoxic groups, one control hypoxic group (n=7) and one control normoxic group (n=4). DIDS were added to the perfusate at 10 minutes before starting the experiments. In the HCO3 - free groups, HEPES (4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid) were added to the perfusate instead of bicarbonate. Furthermore, in the HEPES1 (n=4) and HEPES2 (n=4) groups, the lungs were ventilated with hypoxic gas with or without CO2, respectively. Results: Ventilation of the lungs with hypoxic gas resulted in biphasic HPV, the acute (0-20 minutes) and sustained (20-60 minutes) phases. No alteration in both phases of HPV was detected by DIDS (200 μM). However, DIDS (400 μM), extended the ascending part of acute HPV until min 24. Both phases of HPV were decreased in the HEPES1 group. However, in the HEPES 2 group, HPV tended to increase during the rising part of the acute phase of HPV. Conclusion: Since DIDS (400 μM) extended acute phase of HPV, and HCO3 - free perfusate buffer enhanced rising phase of it, therefore it can be suggested that anion exchanger may modulate HPV especially during the acute phase. The abstract of this article was presented as a poster in the congress of European Respiratory Society (ERS) on Monday, 08 September 2014, Munich, Germany and was published in the ERJ September 1, 2014 vol. 44 no. Suppl 58 P2343. [ABSTRACT FROM AUTHOR]

Background: Pulmonary dysfunction is one of the critical complications of a stroke. However, it remains unclear whether the mechanism is caused by either neurogenic or inflammatory reactions. The present study aimed to determine the effect of cerebral ischemia-reperfusion injury and the role of the vagus nerve on hypoxic pulmonary vasoconstriction (HPV) in rats. Methods: This study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, 2018. Male Sprague Dawley rats (n=56) were divided into four groups, namely the sham, vagotomy (Vag), 1 hour of ischemia followed by 23 hours of reperfusion without vagotomy (I/R) and with vagotomy (I/R+Vag). Neurological deficit scores and total infarct volumes of brains were measured in the I/R and I/R+Vag groups. Pulmonary artery pressure and lung weight were continuously registered during ventilation with normoxic and hypoxic gases in the isolated lungs. The blood gas parameters and the lung malondialdehyde (MDA) level of each group were also evaluated. ANOVA, with Tukey's post hoc test and t test, was used to compare the variables in the experimental groups. Results: The infarct volume of the brains in the I/R and I/R+Vag groups were similar. HPV in the I/R group was lower than those in the sham and Vag groups, while vagotomy reversed this response in the I/R+Vag group (P=0.004). In the I/R group, PO2 and pH were lower, and PCO2 was higher than those in the sham and Vag groups. The lung MDA level in the I/R group was higher than that in the Vag group (P=0.019). Conclusion: Brain ischemia-reperfusion injury decreased HPV independent of increased MDA in the lung, whereas vagotomy improved HPV by repairing the blood-gas barrier and oxygen sensing. [ABSTRACT FROM AUTHOR]

Background: The mechanism of hypoxic pulmonary vasoconstriction (HPV) is still debatable. It has been proposed that reactive oxygen species (ROS) might be involved in HPV. However, there is no special transporter for superoxide anion in the cell membrane and it may release from the cells via anion exchanger. Therefore, the aim of this study was to investigate the interaction of ROS and anion exchanger in acute HPV. Methods: The present study was performed in the isolated rabbit lung. After preparation, the lungs were divided into four hypoxic groups of control, Trolox (antioxidant)-treated, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, anion exchanger inhibitor)-treated, and Trolox+DIDS-treated. Pulmonary artery pressure, left atrial pressure, and lung weight were continuously registered and PVR was then calculated. PO2, PCO2, HCO3-, pH, and NO metabolites of the perfusate were measured during steady-state and at the end of experiments (30 minutes). All data were compared with ANOVA and t-test and significance was considered when P<0.05. Results: Ventilation ofthe lungs with hypoxic gas induced HPV in the control group. DIDS did not have a further effect on HPV compared with the control group. The combination of Trolox and DIDS decreased HPV rather than Trolox per se at 5 minutes. Furthermore, HPV was abolished in both the Trolox and Trolox+DIDS groups at 30 minutes. Concentrations of NO metabolites in the Trolox+DIDS group were more than other groups. Conclusion: The present study indicates a possible interaction between ROS and anion exchanger in acute HPV. It also suggests the modulatory effect of NO at above condition. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability (HRV) is calculated by electrocardiography (ECG-HRV) or blood pressure (BP-HRV). The purpose of this study was to determine the validity of the above methods in rats with normal and ischemic hearts during the baroreflex maneuver., Methods: The study was conducted at Shiraz University of Medical Sciences, Shiraz, Iran, in 2021. Sprague-Dawley rats were divided into a sham group and an isoproterenol-mediated cardiac ischemia (ISO) group. Saline and isoproterenol (150 mg/kg) injected subcutaneously for 2 consecutive days in the sham and ISO groups, respectively. Then, the animals were anesthetized with an intraperitoneal injection of sodium thiopental (60 mg/kg), and the femoral artery and vein were cannulated. Baroreflex was activated using an intravenous injection of phenylephrine (10 μg/100 μL saline). ECG, BP, and heart rate (HR) were recorded, and the time domain of HRV and baroreflex gain were calculated., Results: Baroreflex gain in the ISO group (male, weight=275.8±2.8 g, n=8) was lower than that in the sham group (male, weight=258±2.3 g, n=8) (P<0.05). ECG-HRV indicated an increase in the standard deviation of the RR interval (SDRR), the index of overall HRV, and the parasympathetic index of the root mean square of successive differences (RMSSD) in both groups. However, the rise in SDRR and RMSSD in the ISO group was less than that in the sham group (P<0.05). SDRR and RMSSD obtained from BP did not show a difference between the sham and ISO groups, nor did they correspond with the results seen in baroreflex gain., Conclusion: BP-HRV was not as valuable as ECG-HRV in assessing cardiac ischemia., (Copyright © 2023 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Estimating parameters such as pulmonary drug disposition and deposited dose, as well as determining the influence of pulmonary pharmacokinetics (PK) on drug efficacy and safety, are critical factors for the development of inhaled drug products and help to achieve a better understanding of the drugs' fate in the lungs. Pulmonary disposition and PK have remained poorly understood due to the difficulty to access pulmonary fluids, compared to other biological fluids, such as plasma, for direct or surrogate measurement of the concentration of the active compounds and their metabolites in the lung. The use of the isolated perfused lung model (IPL) has become more common, and it is considered a useful tool to increase understanding in this area since it offers the possibility of controlling the administration and easier sampling of perfusate and lavage fluid. The model also provides an opportunity to study the relationship between PK and pharmacodynamics. This review describes the fundamentals of the IPL model, such as preparation and setting up the method, species selection, drug administration, and lung viability investigation. Besides, different applications of the IPL model like pharmacodynamic studies, pharmacokinetic parameters studies such as absorption, distribution, and metabolism, and evaluation of inhaled formulation have also been reviewed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ischemic stroke is one of the most frequent causes of injury in the central nervous system which may lead to multiorgan dysfunction, including in the lung. The aim of this study was to investigate whether brain ischemia/reperfusion with or without mechanical ventilation leads to lung injury. Male Sprague-Dawley rats were assigned to four groups: Sham, 1-h brain ischemia (MCAO)/24-h reperfusion (I/R), mechanical ventilation with moderate tidal volume (MTV), and I/R+MTV. The pulmonary capillary permeability ( K fc ) was measured in the isolated perfused lung. Mean arterial blood pressure (MAP), heart rate (HR), blood-gas variables, histopathological parameters, lung glutathione peroxidase, and TNF-α were measured. K fc in the I/R, MTV, and I/R+MTV groups were higher than that in the Sham group. In the I/R, MTV, and I/R+MTV groups, arterial partial pressures of oxygen and the arterial partial pressure of oxygen/fraction of inspired oxygen ratios were lower, whereas arterial partial pressures of carbon dioxide were higher than those in the Sham group. The histopathological score in the I/R group was more than that in the Sham group, and in the MTV and I/R+MTV groups were higher than those in the Sham and I/R groups. Furthermore, there were stepwise rises in TNF-α in the I/R, MTV, and I/R+MTV groups, respectively. There was no significant difference in MAP between groups. However, HR in the MTV group was higher than that in the Sham group. Brain ischemia/reperfusion leads to pulmonary capillary endothelial damage and the impairment of gas exchange in the alveolar-capillary barrier, which is exacerbated by mechanical ventilation with moderate tidal volume partially linked to inflammatory reactions.