farzaneh ketabchi

Pulmonary diseases are among the most common diseases that are associated with the disability of patients and, in severe cases, with high mortality. In recent years, the role of the autonomic nervous system in aggravating or modulating the inflammatory reactions of various body organs, including the lungs, has been discussed. Some reports indicate the anti-inflammatory role of the parasympathetic nervous system, while other studies have suggested the inflammatory role of this system. Also, some studies highlight the role of the spleen in reducing inflammation, while others have considered the role of the spleen in exacerbating inflammation and tissue damage. Meanwhile, the role of alpha-7 nicotinic receptor in spleen and lung is controversial. The contradictory results of these studies can be attributed to the differences in the timing of stimulation and inhibition of the parasympathetic nervous system, the severity of the lung injury, and the type of pathogenic and non-pathogenic factors in different animal models of lung injury. In this review, we have discussed the role of the parasympathetic nervous system, spleen and a7 nicotinic acetylcholine receptor in the pathogenic and non-pathogenic lung diseases and the underlined mechanisms. According to the data of this article, more studies are needed to clarify the inflammatory or anti-inflammatory role of the cholinergic system in various inflammatory lung diseases.
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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.

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.

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.

BP-HRV was not as valuable as ECG-HRV in assessing cardiac ischemia.

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. 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. 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). 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.

Liver diseases may lead to a wide spectrum of pulmonary disorders with a high incidence in women. The aim of this study was to evaluate the effect of liver damage and ovariectomy with or without estradiol on pulmonary hemodynamics during ventilation of animals with normoxia and hypoxia gas. Forty Sprague Dawley female rats were randomly divided into four groups of ovariectomy (OVX); ovariectomy with a daily injection of sesame oil, a solvent of estradiol (OVX+Oil); bile duct ligation with ovariectomy (CBDL+OVX) and associated with estradiol (CBDL+OVX+E2). After 28 days of the first surgery, animals were anesthetized. Tail blood samples were taken to measure liver enzymes, estradiol and NO metabolites. Animals were tracheostomized and femoral vessels were cannulated. Then, arterial pressure and right ventricular systolic pressure were recorded during mechanical ventilation with normoxic and hypoxia gas (10% oxygen). AST, AST/ALT ratio, direct and total bilirubins, and estradiol in the CBDL+OVX and CBDL+OVX+E2 groups were significantly higher than those in the OVX group, and they were higher in the CBDL+OVX+E2 group than those in the CBDL+OVX group. Ventilation of animals with hypoxia gas resulted in an increase in right ventricular systolic pressure (RVSP) only in the OVX group compared to its own base values. The plasma concentration of NO metabolites in the CBDL+OVX+E2 group was significantly higher than that in other groups. Estradiol worsen the liver disorders. Furthermore, pulmonary vascular response to hypoxia gas is disrupted in liver disorders, which may be partly linked to the effect of estradiol and NO productions.

Air pollution is the result of the emission of chemicals, particulate matter, and biologic material into the atmosphere, which caused adverse effects on the environment and health. Major air pollutants that threaten human health are carbon monoxide, Nitrogen oxide, ozone, Sulfur dioxide, chemical vapors, and particulate matter. Air pollution is an important risk factor for cardiovascular health, therefore in this review article; we discuss air-polluting particles and the adverse effects of them on cardiovascular disease.

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. 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. 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). 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.

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. 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. 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. 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.

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. 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. 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. 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.

Acute respiratory disorders such as obstructive pulmonary diseases and hypoventilation may lead to alveolar hypoxia and hypercapnia which their effects on pulmonary vascular beds are controversial. The aim of this study was to establish the isolated perfused lung setup and investigate the effects of alveolar hypoxia and hypercapnia on pulmonary vascular resistance. White New Zealand rabbits anaesthetized and anticoagulated with heparin and trachea cannulated. Then the lung exposed and perfused with Krebs solution through pulmonary artery cannula. The ventilated-perfused lung was carefully excised from the chest and the healthy lungs were randomly divided into three groups (n=7 for each). Ventilation performed for 30 min with normoxic-normocapnic, or hypoxic-normocapnic, or hypoxic-hypercapnic gas mixtures. The percent changes of pulmonary vascular resistance per min (%PVR) and their maximum values were evaluated. Hypoxic-normocapnic ventilation resulted in an initial sharp rise in PVR that after 8 min of exposure reversed to a slow decline. After 12 min of exposure a second steady rise in PVR occurred and continued until the end of the experiment. The rate of rise of PVR during hypoxic-hypercapnia was steeper (17.3±2.4% /min) compared to hypoxic-normocapnia (8.86±1.6% /min), but the maximum increases observed in PVR were similar in both conditions. In the isolated ventilated perfused lung, acute alveolar hypoxia had a complex influence on PVR and combination of hypoxia with hypercapnia transiently strengthened PVR without affecting its maximum level.