Aparna Akella

Mesobuthus tamulus venom induces acute respiratory distress syndrome in rats involving additional mechanisms as compared to oleic acid model

The present study was undertaken to determine whether acute respiratory distress syndrome (ARDS) is produced after Mesobuthus tamulus (MBT) envenomation and compared it with oleic acid (OA)-induced ARDS. The trachea, jugular vein and femoral artery were cannulated in anesthetized adult rats. Lethal dose of MBT venom (5 mg/kg) or OA (75 μL) was administered intravenously and the time-dependent changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were recorded. Minute ventilation (MV) and the PaO2/FiO2 (P/F) ratio were also determined. At the end lungs were excised, one lung was used for histopathological examination and the other was used for determination of pulmonary water content physically. MBT venom or OA produced hypoxemia, pulmonary pathology (alveolar damage, infiltration of inflammatory cells, capillary damage and exudation) and pulmonary edema implicating for ARDS. However, the hypoxemia in MBT venom group was associated with decreased MV, apnea/bradypnea, and bradycardia whereas, in OA group it was seen with increased MV, tachypnea, and tachycardia. Lack of effect of hypoxemic drive on RF/MV or HR in MBT venom group unlike OA group, suggests the involvement of medullary centers. The present results demonstrate that MBT venom produces ARDS. However MBT venom-induced ARDS involves pulmonary as well as extrapulmonary mechanisms.

Mechanisms underlying the augmentation of phenylbiguanide and capsaicin induced cardiorespiratory reflexes by Mesobuthus tamulus venom

Phenylbiguanide (PBG) and capsaicin evoke cardiorespiratory reflexes utilizing two separate pathways. It is known that Indian Red Scorpion (Mesobuthus tumulus; MBT) venom augments PBG (5-HT(3)) responses but, the effect of MBT venom on capsaicin (TRPV1)-induced response is not known. Therefore, the present study was undertaken to ascertain whether MBT venom also augments the capsaicin-induced reflex responses involving mechanisms similar to PBG. Experiments were performed on anaesthetized adult rats. Blood pressure, respiratory excursions and ECG were recorded. At the end of each experiment pulmonary water content was determined. PBG (10 μg/kg) produced hypotension, bradycardia and apnoea-bradypnoea. Capsaicin (10 μg/kg) also produced hypotension, bradycardia and apnoea-bradypnoea. MBT venom (100 μg/kg) augmented PBG as well as capsaicin-induced responses and produced pulmonary oedema (increased pulmonary water content). Prostaglandin synthase inhibitor (indomethacin; 10 mg/kg) blocked the venom-induced augmentation of PBG and capsaicin reflexes. Kinin synthase inhibitor (aprotinin; 6000 KIU) and guanylate cyclase (GC) inhibitor (methylene blue; 5 mg/kg) blocked the venom-induced augmentation of PBG response but not the capsaicin response. However, pulmonary oedema was blocked by these antagonists. Phosphodiesterase V inhibitor (sildenafil; 100 μg/kg) augmented the PBG response but not the capsaicin response, though pulmonary oedema was seen in both the groups. The present results indicate that MBT venom also augments the capsaicin-induced responses. The augmentation of capsaicin response involves PGs and pulmonary oedema-independent mechanisms whereas, the augmentation of PBG response involves kinin mediated GC-cGMP pathway and pulmonary oedema-dependent mechanisms.

A study to investigate capsaicin-induced pressure response in vagotomized rats

Objectives: Capsaicin is used to evoke pulmonary C reflexes and produces complex pressure responses along with apnea/tachypnea, and bradycardia. In the present study, the mechanisms involved in capsaicin-induced pressure responses were explored. Materials and Methods: Tracheal, jugular venous, and femoral artery cannulations were performed in anesthetized adult rats. Blood pressure, respiratory excursions, and electrocardiogram were recorded. Cardiorespiratory reflex changes evoked by jugular venous injection of capsaicin (10 μg/kg) were recorded in vagotomized and antagonist pretreated animals. Results: Capsaicin produced triphasic pressure response exhibiting immediate hypotension, intermediate recovery, and delayed hypotension. Time-matched respiratory changes showed apnea, bradypnea, and tachypnea, respectively. Bradycardia occurred at immediate and intermediate phases. After vagotomy, immediate hypotension was abolished; the intermediate recovery was potentiated as hypertensive response; and the delayed hypotension persisted. In case of respiration, the immediate bradypnea persisted and delayed tachypnea was abolished; while heart rate changes at immediate and intermediate phases were abolished. Antagonists of α1-adrenoceptor (prazosin or terazosin, 0.5 mg/kg), β-adrenoceptor (propranolol, 1 mg/kg), AT1 receptor (losartan, 10 mg/kg) and Ca2+ channel (diltiazem, 1 mg/kg) failed to block the capsaicin-induced intermediate hypertensive response in vagotomized animals. Conclusions: These observations implicate the existence of mechanisms other than adrenergic, angiotensinergic, or Ca2+ channel-dependent mechanisms for mediating the capsaicin-induced intermediate hypertensive response in vagotomized animals.

Indomethacin-induced Exacerbation of ARDS in Rats not involving Vagally Mediated Mechanisms

Buses were the main mode of public transport in urban areas. Driving a bus in urban area is a highly demanding job and requires lot of physical and mental stability to perform the task with minimal hazards. The bus drivers are under continuous stress during the working hours and are prone for many diseases related to changes induced by stress, especially the cardiovascular and cerebrovascular diseases. The aim of our study is to estimate the blood pressure and lipid profile in bus drivers which are the markers of increased cardiovascular and cerebrovascular risk resulting from stress. The study design was a cross sectional study. The study group is divided into two groups. Group A consists of 50 male subjects who were professional bus drivers and Group B consists of 50 male subjects who were in control group. Blood pressure was measured and blood lipid profile were estimated for both study and control groups, in fasting blood sample. The test was done in our Biochemistry lab by standard enzymatic technique CHOD-PAP, End point method. Statistical analysis was done using the student “t” test. There was statistically significant increase in systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.001) in professional bus drivers compared to control. There was also a highly significant increase in Total cholesterol (p < 0.001), LDL-cholesterol (p < 0.001) and decrease in HDL-cholesterol level (p < 0.05) in bus drivers compared to controls. The study concludes that stress plays an important risk factor in professional bus drivers and can have cumulative effect to cause acute cardiovascular or cerebrovascular event which can be fatal to the driver.

Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats.

Objective: Pulmonary edema, a manifestation of scorpion envenomation syndrome, is attributed to cardiogenic or noncardiogenic factors. Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom-induced changes is not known. Therefore, we hypothesized that morphine blocks the MBT venom-induced augmentation of phenyldiguanide (PDG) reflex and pulmonary edema. Materials and Methods: Experiments were performed on anesthetized adult female rats. Trachea and jugular vein were cannulated, and the electrocardiographic potentials were recorded by connecting needle electrodes in limb lead II configuration. PDG (10 ΅g/kg, IV, bolus injection) responses were elicited by bolus injection initially, after saline/morphine (1 mg/kg) and after injecting MBT venom (100 μg/kg). The time-response area of the PDG-induced bradycardiac response after treatment was calculated as % of the initial PDG response area. At the end of experiments, lungs were excised for determination of pulmonary water content. Results: PDG produced bradycardiac response that lasted for >60 s. MBT venom augmented the PDG reflex response by 2.5 times. In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent. MBT venom increased the pulmonary water content, and the increase was absent in morphine pretreated animals. Conclusion: The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema.

Vagal efferent stimulation protects against Mesobuthus tamulus venom-induced acute respiratory distress syndrome in rats.

Mesobuthus tamulus (MBT) venom and oleic acid (OA) have been shown to produce acute respiratory distress syndrome (ARDS) involving different mechanisms. The role of vagally mediated anti-inflammatory pathway in ARDS is poorly understood. Therefore, the effects of vagal efferent stimulation on these two models of ARDS were examined. Experiments were performed on anesthetized adult rats. Parameters like ventilatory changes (respiratory frequency and minute ventilation), hypoxemic status (PaO2/FiO2 ratio; P/F ratio), survival time, pulmonary water content and histopathological evidences of lung injury were determined to assess the severity of ARDS. In addition, heart rate (HR) and mean arterial pressure (MAP) were monitored. Injection of OA/MBT venom produced respiratory alterations, hypoxemia, pulmonary edema and histopathological changes demonstrating the development of ARDS. In both the groups, animals died around 60 min. Tachypnea and hyperventilation were seen after OA while bradypnea and hypoventilation were seen after MBT venom. Pulmonary edema was absent in vagotomised animals in MBT venom group but not in OA group. Further, electrical stimulation of the cut peripheral ends of vagii prolonged the survival time and attenuated all the parameters of MBT venom-induced ARDS significantly. In case of OA, there was improvement in histopathological changes but the survival time of animals was not prolonged. Stimulation of α7-nicotinic receptors (by pretreatment with GTS-21) exacerbated OA as well as MBT venom-induced ARDS. The present results indicate that vagal efferent stimulation protects against MBT venom-induced ARDS.