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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: 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. [ABSTRACT FROM AUTHOR]

Acute respiratory disorders and permissive hypercapnic strategy may lead to alveolar hypoxia and hypercapnic acidosis. However, the effects of hypercapnia with or without acidosis on hypoxic pulmonary vasoconstriction (HPV) and oxygen diffusion capacity of the lung are controversial. We investigated the effects of hypercapnic acidosis and hypercapnia with normal pH (pH corrected with sodium bicarbonate) on HPV, capillary permeability, gas exchange, and ventilation-perfusion matching in the isolated ventilated-perfused rabbit lung. No alteration in vascular tone was noted during normoxic hypercapnia with or without acidosis compared with normoxic normocapnia. Hypercapnia with normal pH resulted in a transient increase in HPV during the course of consecutive ventilation maneuvers, whereas hypercapnic acidosis increased HPV over time. Hypercapnic acidosis decreased exhaled NO during hypoxia more than hypercapnia with normal pH and normocapnia, whereas intravascular NO release was unchanged. However, inhibition of NO synthesis by nitro-L-arginine (L-NNA) resulted in a loss of the increased HPV caused by hypercapnic acidosis but not that caused by hypercapnia with normal pH. Furthermore, capillary permeability increased during hypoxic hypercapnia with normal pH but not hypoxic hypercapnic acidosis. This effect was NO-dependent because it disappeared during L-NNA administration. Ventilation-perfusion matching and arterial Po2 were improved according to the strength of HPV in hypercapnia compared with normocapnia during Tween nebulization-induced lung injury. In conclusion, the increased HPV during hypercapnic acidosis is beneficial to lung gas exchange by improving ventilation-perfusion matching and preserving the capillary barrier function. These effects seem to be linked to NO-mediated pathways. hypoxia; hypercapnic acidosis; pH; capillary permeability doi: 10.1152/ajplung.00074.2009.

Abstract Background The summary measure approach (SMA) is sometimes the only applicable tool for the analysis of repeated measurements in medical research, especially when the number of measurements is relatively large. This study aimed to describe techniques based on summary measures for the analysis of linear trend repeated measures data and then to compare performances of SMA, linear mixed model (LMM), and unstructured multivariate approach (UMA). Methods Practical guidelines based on the least squares regression slope and mean of response over time for each subject were provided to test time, group, and interaction effects. Through Monte Carlo simulation studies, the efficacy of SMA vs. LMM and traditional UMA, under different types of covariance structures, was illustrated. All the methods were also employed to analyze two real data examples. Results Based on the simulation and example results, it was found that the SMA completely dominated the traditional UMA and performed convincingly close to the best-fitting LMM in testing all the effects. However, the LMM was not often robust and led to non-sensible results when the covariance structure for errors was misspecified. The results emphasized discarding the UMA which often yielded extremely conservative inferences as to such data. Conclusions It was shown that summary measure is a simple, safe and powerful approach in which the loss of efficiency compared to the best-fitting LMM was generally negligible. The SMA is recommended as the first choice to reliably analyze the linear trend data with a moderate to large number of measurements and/or small to moderate sample sizes.

Abstract Background Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined. Method We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability. Results In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-NG-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W. Conclusion Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent.

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 (Kfc) 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. Kfc 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. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a cardiotoxic drug. To reduce the harmful effects of DOX, two plant‐derived components, including curcumin (CUR) and carvacrol (CAR), were considered. This study aimed to assess the protective effects of CUR and CAR on DOX‐induced cardiotoxicity using physiological and stereological evaluations. Male rats were randomly allocated to six groups. Group's I‐VI received phosphate‐buffered saline (PBS), CUR (100 mg kg−1 day−1), CAR (50 mg kg−1 day−1), DOX (4 mg kg−1 week−1), DOX‐CUR, and DOX‐CAR, respectively. On day 24, plasma troponin I and ECG were analyzed and the left ventricle underwent stereological assessment. The results showed a fivefold increase in troponin I in the DOX‐treated animals compared to the PBS ones. Additionally, heart rate and QRS amplitude, respectively, reduced by 18% and 31% and QT interval and QRS duration, respectively, increased by 41% and 24% in the DOX group in comparison with the PBS rats (p < .05). The total volume of the myocardium and vessels and the number of cardiomyocyte nuclei also, respectively, decreased by 30%, 45%, and 43% in the DOX group compared to the PBS animals (atrophy of the ventricular tissues, p < .01). Besides, the mean volumes of the connective tissue and cardiomyocytes, respectively, increased by 46% and 52% in the DOX group (p < .01). In the DOX‐CUR and DOX‐CAR groups, the changes were prevented extensively in comparison with the DOX group (p < .01). Co‐administration of CUR or CAR and doxorubicin for 24 days could improve the heart function and structural changes. [ABSTRACT FROM AUTHOR]

Both renal and respiratory diseases are common with high mortality rate around the world. This study was the first to compare effects of two kidneys, one clip (2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right ventricular pressure during normal condition and mechanical ventilation with hypoxia gas. Male Sprague–Dawley rats were subjected to control, 2K1C, or 1K1C groups. Twenty-eight days after the first surgery, animals were anesthetized, and femoral artery and vein, and right ventricle cannulated. Systemic arterial pressure and right ventricular systolic pressures (RVSP) were recorded during ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was significantly more than the control and 2K1C groups during baseline conditions and ventilation the animals with hypoxic gas. Administration of antioxidant Trolox increased RVSP in the 1K1C and control groups compared with their baselines. Furthermore, there was no alteration in RVSP during hypoxia in the presence of Trolox. This study indicated that RVSP only increased after 28 days induction of 1K1C but not 2K1C model. In addition, it seems that the response to hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest that effects of 1K1C may partially be related to reactive oxygen species (ROS) pathways. [ABSTRACT FROM AUTHOR]

Purpose:Acute kidney injury (AKI) induces acute lung injury (ALI) through releasing injurious mediators or impairing clearance of systemic factors. To determine the links between AKI and ALI, pulmonary and blood variables were evaluated following induction of AKI via different experimental models of bilateral renal ischemia/reperfusion (BIR: renal ischemia with uremia), unilateral renal ischemia/reperfusion (UIR: renal ischemia without uremia), bilateral nephrectomy (BNX: uremia without renal ischemia), and unilateral nephrectomy (UNX: without uremia and renal ischemia). Methods:Ninety male Sprague–Dawley rats were divided into six groups. Animals had 1-h bilateral or 2-h unilateral renal ischemia followed by 24-h reperfusion in the BIR and UIR groups, respectively, and 24-h period following bilateral or unilateral nephrectomy in the BNX and UNX groups, respectively. There were also sham and control groups with and without sham-operation, respectively. Results:Plasma malondialdehyde and nitric oxide were elevated by BIR more than UIR, but not changed by UNX and BNX. UIR slightly increased plasma creatinine, whereas BIR and BNX largely increased plasma creatinine, urea, K+ and osmolality and decreased arterial HCO3−, pH, and CO2. UNX and UIR did not affect lung, but BIR and BNX induced ALI with equal capillary leak and macrophages infiltration. However, there were more prominent lung edema and vascular congestion following BNX and more severe neutrophils infiltration and PaO2/FiO2reduction following BIR. Conclusion:Acutely accumulated systemic mediators following renal failure in the absence of kidneys vary from those due to combined renal failure with ischemic-reperfused kidneys and consequently they induce ALI with distinct characteristics. [ABSTRACT FROM AUTHOR]

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: Alveolar hypoxia induces monophasic pulmonary vasoconstriction in vivo, biphasic vasoconstriction in the isolated pulmonary artery, and controversial responses in the isolated perfused lung. Pulmonary vascular responses to sustained alveolar hypoxia have not been addressed in the isolated perfused rat lung. In this study, we investigated the effect of sustained hypoxic ventilation on pulmonary artery pressure in the present of phenylephrine, an α1-receptor agonist, under the above condition. Methods: We performed this study in the isolated perfused rat lung. After preparation, the lungs were divided randomly into five groups of normoxic-normocapnia, hypoxic-normocapnia, phenylephrine pre- or post-treated hypoxic-normocapnia and phenylephrine pre-treated normoxic-normocapnia. Pulmonary hemodynamic, airway pressure and lung weight were measured during 60 min of the experiment for each group. Results: In the phenylephrine-pre-treated hypoxic-normocapnia group we observed a gradual increase in pulmonary artery pressure which approximated the results seen in the phenylephrine-pre-treated normoxic-normocapnia group. In contrast, in the phenylephrine-post-treated hypoxic-normcapnic group, pulmonary artery pressure did not change during the first 3 min of hypoxic-normocapnia. However at 1.5 min after administration of phenylephrine, this pressure began to increase sharply and continued until the end of the experiment. This response was biphasic (0-10 min: acute phase, 10-60 min: sustained phase) with significantly higher pulmonary artery pressure compared to the other groups. Conclusion: This study, for the first time, showed biphasic hypoxic pulmonary vasoconstriction in the isolated perfused rat lung with the sole administration of phenylephrine after but not before hypoxic gas ventilation. This finding suggested a facilitative role of alveolar hypoxia on pulmonary vasoconstriction induced by an α1-receptor agonist. [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]

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.)

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.)

Background: Alveolar hypoxia induces monophasic pulmonary vasoconstriction in vivo, biphasic vasoconstriction in the isolated pulmonary artery, and controversial responses in the isolated perfused lung. Pulmonary vascular responses to sustained alveolar hypoxia have not been addressed in the isolated perfused rat lung. In this study, we investigated the effect of sustained hypoxic ventilation on pulmonary artery pressure in the present of phenylephrine, an α1-receptor agonist, under the above condition., Methods: We performed this study in the isolated perfused rat lung. After preparation, the lungs were divided randomly into five groups of normoxic-normocapnia, hypoxic-normocapnia, phenylephrine pre- or post-treated hypoxic-normocapnia and phenylephrine pre-treated normoxic-normocapnia. Pulmonary hemodynamic, airway pressure and lung weight were measured during 60 min of the experiment for each group., Results: In the phenylephrine-pre-treated hypoxic-normocapnia group we observed a gradual increase in pulmonary artery pressure which approximated the results seen in the phenylephrine-pre-treated normoxic-normocapnia group. In contrast, in the phenylephrine-post-treated hypoxic-normcapnic group, pulmonary artery pressure did not change during the first 3 min of hypoxic-normocapnia. However at 1.5 min after administration of phenylephrine, this pressure began to increase sharply and continued until the end of the experiment. This response was biphasic (0-10 min: acute phase, 10-60 min: sustained phase) with significantly higher pulmonary artery pressure compared to the other groups., Conclusion: This study, for the first time, showed biphasic hypoxic pulmonary vasoconstriction in the isolated perfused rat lung with the sole administration of phenylephrine after but not before hypoxic gas ventilation. This finding suggested a facilitative role of alveolar hypoxia on pulmonary vasoconstriction induced by an α1-receptor agonist.