Evaluation of Electrocardiogram Parameters and Heart Rate Variability During Blood Pressure Elevation by Phenylephrine in Cirrhotic Rats.

Cirrhotic cardiomyopathy is a myocardial disease that may go undetected in the early stages due to peripheral vasodilatation. The aim of the study was to evaluate the electrocardiogram (ECG) and heart rate variability (HRV) after raising blood pressure by phenylephrine injection in rats with liver cirrhosis. Twenty male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 44 days, animals were anesthetized and the right femoral artery and vein catheterized. After a steady-state period, a bolus injection of phenylephrine (PHE, 10 µg/µl/IV, baroreflex maneuver) was followed by a slow injection of PHE (100 µg/ml/5 min/IV, sustained maneuver). Rapid and slow injections of PHE resulted in a greater increase in mean arterial pressure (MAP) and a weaker bradycardia response in the CBDL group than in the Sham group. ECG analysis showed increased QT, QTc, JT, and T peak to T end in the CBDL group, which remained unchanged after PHE injection. On the other hand, the parasympathetic indices of the HF band and RMSSD, and the sympathetic index of the LF band after PHE injection were lower in the CBDL group than in the Sham group.ECG data indicated prolonged ventricular depolarization and repolarization, independent of blood pressure levels in cirrhosis. On the other hand, after PHE injection, the parasympathetic and sympathetic components of HRV decreased, regardless of the duration of elevated blood pressure. We suggest that HRV analysis can provide a useful approach to assess cardiac dysfunction associated with elevated blood pressure in cirrhosis.

Demographic, clinical, and paraclinical features of patients operated with the diagnosis of acute descending necrotizing mediastinitis: a retrospective study in Southern Iran.

INTRODUCTION: Descending necrotizing mediastinitis (DNM) is a type of acute mediastinitis that is rarely reported but is regarded as a fatal disease despite improvements in technological methods and antibiotic therapies. We aimed to determine the demographic, clinical, and paraclinical features of patients diagnosed with acute DNM. METHODS: In this retrospective study, patients' hospital records with a diagnosis of DNM admitted to the Namazi hospital in southern Iran during 18 years (2002-2019) were reviewed. Demographic and clinical features were recorded and subsequently analyzed via SPSS 22. RESULTS: Out of 67 mediastinitis patients, 25 (37.3%) were diagnosed as DNM with an average age of 37.2 ± 16.7 years, and 68% were male. Regarding etiology, 52.0% were due to neck infection. Based on the technique of surgery, 52% of the patients underwent the combined method, which was mostly among type I and IIA DNM, while thoracotomy was mostly performed on type IIB DNM (P = 0.08). Based on the incision, type IIA and IIB had the highest frequency of thoracotomy and cervicothoracic incisions (P = 0.02 and 0.002). Puss discharge was significantly lower in type I DNM (P = 0.01). Based on the presenting symptoms of our patients, the majority (72.0%) had a chief complaint of neck pain, followed by chills and fever (48%). There were no reports of mortality during our short-term follow-up. CONCLUSION: We report one of the largest retrospective studies of DNM patients in our referral center, with a high prevalence of the disease among younger populations, especially under 40 years. The method of treatment should be chosen based on the extent of infection and can be limited to neck exploration in upper mediastinal infections, though thoracic or combined approach in more broad infections.

The Validity of Heart Rate Variability Obtained from Electrocardiography and Blood Pressure in Rats Subjected to Isoproterenol-Induced Heart Ischemia.

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.

The effect of suture techniques on the outcome of tracheal reconstruction: An observational study and review of literature.

BACKGROUND: Tracheal resection and anastomosis surgery is a safe operation and is used to treat various benign and malignant diseases of the trachea. However, tracheal stenosis is among the main anastomotic complications following this procedure. Surgeons use both the continuous and the interrupted suture techniques for tracheal anastomosis, but contradicting results in each technique's complications have been reported in various studies. In this study, we aimed to compare the outcome of these two different suture techniques and a relevant literature review. METHODS: Surgical records during a period of 15 years (2005-2019) were screened for tracheal reconstruction surgery in affiliated hospitals of Shiraz University of Medical Sciences, Shiraz, Iran. A total of 82 patients were evaluated based on surgical and suture features, along with their follow-up bronchoscopy for anastomotic complications. RESULTS: Post-operational subclinical restenosis occurred in 8 (15.3%) out of 52 and 10 (33.3%) of 30 patients who underwent continuous and interrupted suturing techniques, respectively. Also, 6 (20%) patients in the interrupted group developed symptomatic restenosis, while in the continuous group, only one patient was clinically symptomatic. The patients with continuous suture technique had a shorter surgery time than patients whose interrupted technique was used (P < 0.001). CONCLUSIONS: Based on our results, we conclude that restenosis is significantly reduced when the continuous technique is applied for tracheal anastomosis; However, the results are contradicting in relevant literature and due to the retrospective nature of our study, further human studies and clinical trials are warranted.

Fundamentals and Applications of Isolated Perfused Lung (IPL) Model in the Development of Pulmonary Drug Delivery.

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.

Therapeutic Approaches in COVID-19 Patients: The Role of the Renin-Angiotensin System.

Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the disease. The catalytic activity of cellular ACE2 (cACE2) and soluble ACE2 (sACE2) prevents angiotensin II and Des-Arg-bradykinin from accumulating in the body. On the other hand, SARS-CoV-2 mainly enters cells via cACE2. Thus, inhibition of ACE2 can prevent viral entry and reduce viral replication in host cells. The benefits of bradykinin inhibitors (BKs) have been reported in some COVID-19 clinical trials. Furthermore, the effects of cyclooxygenase (COX) inhibitors on ACE2 cleavage and prevention of viral entry into host cells have been reported in COVID-19 patients. However, the administration of COX inhibitors can reduce innate immune responses and have the opposite effect. A few studies suggest benefits of low-dose radiation therapy (LDR) in treating acute respiratory distress syndrome in COVID-19 patients. Nonetheless, radiation therapy can stimulate inflammatory pathways, resulting in adverse effects on lung injury in these patients. Overall, progress is being made in treating COVID-19 patients, but questions remain about which drugs will work and when. This review summarizes studies on the effects of a recombinant ACE2, BK and COX inhibitor, and LDR in patients with COVID-19.

Roles of alpha-7 nicotinic acetylcholine receptors and spleen in the lung injury induced by a repeated saline lavage in rat.

BACKGROUND: The study aimed to determine whether or notα7 nicotinic acetylcholine receptors (α7nAChR) induce anti-inflammatory effects directly in the lung or through the spleen pathway in a sterile model of lung injury by saline lavage. METHODS: Male Sprague Dawley rats were divided into seven groups; Sham, splenectomy (SPX), saline lavage (LAV), LAV treated with α7nAChR agonist nicotine (LAV + NIC), and LAV treated with NIC and a selective α7nAChR antagonist MLA (LAV+MLA+NIC), LAV and splenectomy (LAV+SPX), and LAV+SPX treated with nicotine (LAV+SPX+NIC). Tracheostomy and catheterization of the femoral artery were performed under deep anesthesia. Animals were subjected to volume-controlled ventilation and lung injury by 10 repeated saline lavages. Splenectomy was achieved one week before the induction of lung injury. The recovery phase lasted for 3 h, and drugs were injected 1 h after the last lavage. RESULTS: Mean arterial blood pressure (MBP), heart rate (HR), PaO2, PaO2/FiO2 ratio, and pH decreased, whereas, maximal inspiratory (MIP) and expiratory (MEP) pressures, and PaCO2 increased 1 h after the saline lavage. Nicotine corrected entirely all the above parameters in the LAV + NIC group. MLA or SPX prevented the effects of nicotine on the above parameters, except that MLA had no extra effect on MIP or MEP. In addition, nicotine improved lung compliance in the LAV + NIC and LAV + SPX + NIC groups, though it was inhibited by MLA in the LAV + MLA + NIC group. The increases of plasma and lung tissue malondialdehyde (MDA) in the LAV group were diminished by nicotine, whereas, MLA and SPX prevented these reductions. Besides, nicotine could reduce plasma MDA in the LAV + SPX + NIC group. Total BAL cell count, protein BAL/protein plasma ratio, and lung histological scores were attenuated by nicotine in the LAV + NIC group, whereas, MLA reversed the mentioned alterations in the LAV + MLA + NIC group. However, splenectomy could not stop the decreasing effect of nicotine on the total BAL cell in the LAV + SPX + NIC group. CONCLUSIONS: In this study, we indicated that α7nAChR and spleen play roles in cholinergic anti-inflammatory pathways in saline lavage-induced lung injury. However, our results are in favor of at least some direct effects of α 7nAChR in the lung.

The effect of subdiaphragmatic vagotomy on heart rate variability and lung inflammation in rats with severe hemorrhagic shock.

BACKGROUND: The influence of cutting the sub-diaphragmatic branch of the vagus nerve on heart rate variability (HRV) and inflammatory reaction to severe hemorrhagic shock has not been determined prior to this study. METHODS: Male Sprague-Dawley rats were divided into four groups of Sham, sub-diaphragmatic vagotomized (Vag), subacute (135 ± 2 min) hemorrhagic shock (SHS), and sub-diaphragmatic vagotomized with SHS (Vag + SHS). Hemodynamic parameters were recorded and HRV calculated during multiple phases in a conscious model of hemorrhagic shock. The expressions of TNF-α and iNOS were measured in the spleen and lung tissues at the conclusion of the protocol. RESULTS: Decreases in blood pressure during blood withdrawal were identical in the SHS and Vag + SHS groups. However, heart rate only decreased in the Nadir-1 phase of the SHS group. HRV indicated increased power in the very-low, low, and high (VLF, LF, and HF) frequency bands during the Nadir-1 phase of the SHS and Vag + SHS groups, albeit the values were higher in the SHS group. In the recovery phase, the HF bands were only lower in the SHS group. After hemorrhagic shock followed by resuscitation, the expression of TNF-α and iNOS increased in the spleen and lung of the SHS group, and the expression of these genes was significantly lower in the Vag + SHS group than in the SHS group. CONCLUSION: Parasympathetic activity increases during the hypotensive phase of hemorrhagic shock, whereas the cardiac vagal tone decreases in the recovery phase. Sub-diapragmatic vagotomy blunts the cardiac vagal tone during hemorrhagic shock, but its effect is reversed in the recovery phase. The vagus nerve plays a role in proinflammatory responses in the lungs and spleen in subacute hemorrhagic shock followed by resuscitation.

Vagotomy Improves Hypoxic Pulmonary Vasoconstriction in Rats Subjected to Brain Ischemia-Reperfusion Injury.

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.

Roles of glutamate and GABA of the Kölliker-Fuse nucleus in generating the cardiovascular chemoreflex.

The Kölliker-Fuse (KF) nucleus is a part of the parabrachial complex, located in the dorsolateral pons. It is involved in the chemoreflex-evoked cardiovascular and respiratory changes, but the role of GABA and glutamate in cardiovascular chemoreflex has not been shown yet. This study was performed to determine the role of GABA, glutamate, and their interaction in the KF, in cardiovascular chemoreflex in anesthetized rat. The antagonists were microinjected into the KF, and arterial pressure, heart rate, and single-unit responses were recorded simultaneously. The chemoreflex was evoked by i.v. injection of KCN, consisted of a short pressor followed by long bradycardia responses. Both responses were significantly attenuated by injection of a synaptic blocker (CoCl2) into the KF, confirming involvement of the KF in generating the reflex. Microinjection of AP5, an NMDA receptor antagonist, into the KF significantly attenuated the pressor and bradycardia responses, while blocking the AMPA receptors by CNQX had no significant effect. Blockade of GABAA receptors by bicuculline methiodide (BMI) potentiated both responses. Co-injection of BMI and CNQX potentiated the responses too. Co-injection of BMI and AP5 had no significant effect on the pressor response but significantly attenuated the bradycardia response. In conclusion, the KF plays a role in generating cardiovascular chemoreflex via its glutamate NMDA but not AMPA receptors. GABA inhibits both components of this reflex through GABAA receptors. There is an interaction between GABAA and NMDA receptors in regulating the bradycardia response of the reflex. Single-unit results were also presented which were correlated with and supported the homodynamic findings.

Heart rate variability and pulmonary dysfunction in rats subjected to hemorrhagic shock.

BACKGROUND: The activity of autonomic nervous system and its association with organ damage have not been entirely elucidated in hemorrhagic shock. The aim of this study was to investigate heart rate variability (HRV) and pulmonary gas exchange in hemorrhagic shock during unilateral subdiaphragmatic vagotomy. METHODS: Male Sprague Dawley rats were randomly assigned into groups of Sham, vagotomized (Vag), hemorrhagic shock (HS) and Vag + HS. HS was induced in conscious animals by blood withdrawal until reaching to mean arterial blood pressure (MAP) of 40 ± 5 mmHg. Then, it was allowed to MAP returning toward the basal values. MAP and heart rate (HR) were recorded throughout the experiments, HRV components of low (LF, sympathetic index), high (LH, parasympathetic index), and very low (VLF, injury index) frequencies and the LF/HF ratio calculated, and the lung histological and blood gas parameters assessed. RESULTS: In the initial phases of HS, the increase in HR with no change in MAP were observed in both HS and Vag + HS groups, while LF increased only in the HS group. In the second phase, HR and MAP decreased sharply in the HS group, whereas, only MAP decreased in the Vag + HS group. Meanwhile, LF and HF increased relative to their baselines in the HS and Vag + HS groups, even though the values were much pronounced in the HS group. In the third phase, HR, MAP, LF, HF, and the LF/HF ratio were returned back to their baselines in both HS and Vag + HS groups. In the Vag + HS group, the VLF was lower and HR was higher than those in the other groups. Furthermore, blood gas parameters and lung histology indicated the impairment of gas exchange in the Vag + HS group. CONCLUSIONS: The sympathetic activity is predominant in the first phase, whereas the parasympathetic activity is dominant in the second and third phases of hemorrhagic shock. There is an inverse relationship between the level of VLF and lung injury in vagotomized animals subjected to hemorrhagic shock.

Lung injury in brain ischemia/reperfusion is exacerbated by mechanical ventilation with moderate tidal volume in rats.

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.

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats.

BACKGROUND: Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases. METHODS: Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology. RESULTS: Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group. CONCLUSION: Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.

Cardioprotective effects of curcumin and carvacrol in doxorubicin-treated rats: Stereological study.

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.

Roles of Endothelin B Receptors and Endothelial Nitric Oxide Synthase in the Regulation of Pulmonary Hemodynamic in Cirrhotic Rats.

INTRODUCTION: Hepatopulmonary syndrome and portopulmonary hypertension are common complications of liver disorders. This study aimed to determine roles of ET-B receptors and endothelial-derived NO synthase in the regulation of pulmonary hemodynamic in cirrhotic rats. METHODS: Male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 28 days, animals were anesthetized, and the right ventricle, femoral artery, and vein cannulated. Then, intravenous injection of BQ-788 (a selective ET-B receptor antagonist) and L-NAME (eNOS inhibitor) were performed sequentially. RESULTS: After the first injection of BQ-788, the right ventricular systolic pressure (RVSP) and mean arterial systemic pressure increased only in the Sham group. L-NAME increased RVSP in the Sham and CBDL groups, whereas mean arterial systemic pressure elevated only in the Sham group significantly. Reinjection of BQ-788 increased RVSP in the Sham group, whereas it decreased RVSP in the CBDL group. Both plasma NO metabolites and lung endothelin-1 increased in the CBDL group. CONCLUSION: ET-B receptors on the endothelial cells play roles in the regulation of pulmonary and systemic vascular tone in normal condition through the NO-mediated pathway, whereas ET-B receptors on the smooth muscle cells have a role in the pulmonary vascular tone in liver cirrhosis.

Right ventricular pressure elevated in one-kidney, one clip Goldblatt hypertensive rats.

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.

The Interaction between Trolox and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic Acid on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung.

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 of the 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.

Renal ischemia/reperfusion against nephrectomy for induction of acute lung injury in rats.

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/FiO2 reduction 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.

Distant effects of unilateral renal ischemia/reperfusion on contralateral kidney but not lung in rats: the roles of ROS and iNOS.

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(+) and K(+) 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(+) 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.

The Effect of Blood Loss in the Presence and Absence of Severe Soft Tissue Injury on Hemodynamic and Metabolic Parameters; an Experimental study.

INTRODUCTION: The effect of severe soft tissue injury on the severity of hemorrhagic shock is still unknown. Therefore, the present study was aimed to determine hemodynamic and metabolic changes in traumatic/hemorrhagic shock in an animal model. METHODS: Forty male rats were randomly divided into 4 equal groups including sham, hemorrhagic shock, soft tissue injury, and hemorrhagic shock + soft tissue injury groups. The changes in blood pressure, central venous pressure (CVP) level, acidity (pH), and base excess were dynamically monitored and comparedsented. RESULTS: Mean arterial blood pressure decreased significantly in hemorrhagic shock (df: 12; F=10.9; p<0.001) and severe soft tissue injury + hemorrhagic shock (df: 12; F=11.7; p<0.001) groups 15 minutes and 5 minutes after injury, respectively. A similar trend was observed in CVP in severe soft tissue injury + hemorrhagic shock group (df: 12; F=8.9; p<0.001). After 40 minutes, pH was significantly lower in hemorrhagic shock (df: 12; F=6.8; p=0.009) and severe soft tissue injury + hemorrhagic shock (df: 12; F=7.9; p=0.003) groups. Base excess changes during follow ups have a similar trend. (df: 12; F=11.3; p<0.001). CONCLUSION: The results of this study have shown that the effect of hemorrhage on the decrease of mean arterial blood pressure, CVP, pH, and base excess is the same in the presence or absence of soft tissue injury.