Doses Of Atropine Research Articles

Sinus arrest with intrathecal dexmedetomidine.

Sir, Dexmedetomidine, a highly selective α2 adrenoceptor agonist, is being increasingly used as an adjuvant in neuraxial blocks as it prolongs the sensory and motor block in a dose-dependent manner.[1] Severe bradycardia and cardiac arrest has been reported with the intravenous use of dexmedetomidine.[23] However, severe bradycardia progressing to sinus arrest after intrathecal administration of dexmedetomidine has not been reported. A 40-year-old female, 155 cm in height and weighing 65 kg, was scheduled for total abdominal hysterectomy. She had been operated for myomectomy under spinal anaesthesia 5 years back. Her general physical examination and all routine investigations were unremarkable. Upon arrival in the operating room, monitors were attached and her vitals were recorded. A peripheral venous access was established and pre-loaded with 500 mL of Ringer lactate. The subarachnoid space was reached in the L2-L3 interspace using a 25G Quincke's needle with the patient in the left lateral position. After ensuring free flow of cerebrospinal fluid, 2.5 mL of hyperbaric bupivacaine with 10 μg of dexmedetomidine was administered. The patient was positioned supine and oxygen was administered via a face mask at a rate of 5 L/min. The level of sensory block to pinprick was T10 after 2 min, and T6 was the highest level of sensory block achieved. The surgery commenced and the patient's heart rate remained in the range of 50-60/min, with the blood pressure at around 130/80 mmHg. After about 70 min, when the surgeons were suturing the peritoneum, there was a sudden drop in her heart rate to 40/min. Immediately, the surgical handling was stopped and injection atropine 0.6 mg was given intravenously, to which there was no response for 3 min. Meanwhile, she complained of some discomfort in her epigastrium and her heart rate further dropped to 34/min while her blood pressure was 124/76 mmHg with SpO2 of 99%. Another dose of inj. atropine 0.6 mg was given intravenously but her heart rate dropped to 18/min over 5 s followed by sinus arrest. Then, the third dose of inj. atropine 0.6 mg was given, which led to an increase in her heart rate to 86/min. The level of sensory blockade was T10 at this time and the SpO2 was consistently 99%. The surgery was completed in the next 15 min uneventfully and the estimated blood loss was around 200 mL. The patient remained comfortable with a heart rate of around 74/min and blood pressure of 124/86 mmHg. Her post-operative Holter monitoring and echocardiography were unremarkable. Intrathecal dexmedetomidine when combined with spinal bupivacaine produces earlier onset and prolonged duration of sensory and motor block with excellent quality of post-operative analgesia without significant haemodynamic alterations.[14] Although episodes of sinus arrest and severe bradycardia progressing to asystole have been reported in patients receiving intravenous dexmedetomidine,[23] no severe cardiovascular complications have been observed with intrathecal dexmedetomidine. Two cases of bradycardia (heart rate 50/min) have been observed by Gupta et al. when they used 5 μg of dexmedetomidine as an intrathecal adjuvant for post-operative analgesia.[5] The two very unusual features observed in our case were the time to the occurrence of sinus arrest and the high dose of atropine required for its treatment. As 1 h had elapsed between the intrathecal administration of drugs and the sinus arrest, sinus arrest due to sympathetic blockade due to bupivacaine was less likely. The level of sensory block had also receded to T10 by that time. We therefore speculate that a centrally mediated decrease in sympathetic outflow and increase in parasympathetic outflow due to dexmedetomidine may be the cause. The patient's autonomic response to peritoneal stretching could also be a contributing factor responsible for the severe bradycardia in this case. However, the bradycardia did not respond to the cessation of surgical handling and the usual dose of atropine. A fall in blood pressure and heart rate has been reported with various interventions like displacement of liver, insertion of hand into the peritoneal cavity, placement of packing and retraction of the wound edges. A vagally mediated reflex has been implicated in most cases, but exact pathways have not been established so far.[6] To conclude, although dexmedetomidine is an attractive intrathecal adjuvant for post-operative analgesia, we recommend meticulous use of this drug with vigilant monitoring in the operating room as well as in the post-anaesthesia care unit keeping in mind the possibility of delayed occurrence of severe bradycardia.

Comparison between different atropine doses as an antisialagogue for patients receiving ketamine-midazolam undergoing gamma knife radiosurgery

Objectives Comparing different atropine doses to detect the least effective dose as an antisialagogue, in patients receiving ketamine-midazolam sedation for gamma knife radiosurgery. Patients and methods The study included 120 American Society of Anesthesiologists Physical Status I, II patients (age range 1860 years) undergoing gamma knife radiosurgery. The patients were randomly divided into three equal groups. Patients in group A received atropine 0.5 mg intravenously, atropine 0.3 mg intravenously in group B, whereas patients in group C received 0.1 mg atropine intravenously. All patients received intravenous ketamine 0.5 mg/kg, plus intravenous midazolam 1 mg. Baseline heart rate and blood pressure, change in heart rate, and occurrence of increased secretions were recorded. Results A total of 120 patients undergoing gamma knife radiosurgery were included in the study. Only one patient in group A and two patients in group B showed increased secretions (2.5 and 5%, respectively), whereas in group C 15 patients experienced increased secretions (37.5%). None of the patients who experienced increased secretions required suctioning of secretions. With regard to the change in heart rate, group A patients had significant increase in heart rate, whereas the changes in heart rate in group B and C were not significant. Conclusion The dose of 0.3 mg atropine used in group B showed the same efficacy as an antisialagogue as the dose of 0.5 mg atropine that was used in group A, and was significantly more efficient than the dose of 0.1 mg atropine used in group C patients, who experienced significant increase of secretions. In addition, group B patients did not experience the significant increase in heart rate that was experienced by group A patients.

Open-label randomized controlled study comparing continuous infusion versus intermittent bolus dose of atropine with or without pralidoxime in the treatment of organophosphorus poisoning in a teaching hospital

Background: Severe organophosphorus (OPC) poisoning is one of the serious problems in developing world, taking great toll on life. Though Atropine is used as an antidote, there are no clear guidelines. We conducted an open label randomized controlled clinical study to compare the efficacy of continuous infusion of atropine to that of intermittent bolus dose in the treatment of OPC poisoning. Methods and Material: Patients aged above 12 years with clinical evidence of OPC poisoning were studied. Both the groups received initial bolus of 1to3 mg of atropine. Then, Group-A received intermittent bolus and group-B, continuous infusion, until adequately atropinized. Results: Out of 743 patients (group-A: 356 and group-B: 387), females were 54%. 83% had suicidal intent. Mean atropine dose was 126.6mg in group-A and 78mg in group-B (P < 0.0001) . 21.07% (group-A) and 12.92% (group-B) developed intermediate syndrome (P = 0.003) , mortality was 27.25%(97) in group-A v/s 13%(50) in group-B (P < 0.0001) . Ventilator support needed in 36%(group-A) against 17% in group-B (P < 0.0001) and duration of ventilation was 1.5 days lesser in group B (P < 0.0001) . 23.03% had atropine toxicity in group-A as compared to 8% in group-B (P < 0.0001) . Hospital stay was 1.67 (P < 0.0001) days shorter for group-B. Conclusion: Continuous atropine infusion should be standard of care in treating OPC poisoning.

Efficiency of anisodamine for organophosphorus-poisoned patients when atropinization cannot be achieved with high doses of atropine

Poisoning by organophosphorus insecticides is a major global public health problem. Although atropine has been widely used to treat organophosphate (OP) poisoning, sometimes atropinization cannot be achieved, even with high doses of atropine. Hence, we aimed to assess the effect of anisodamine for organophosphorus poisoned patients for whom atropinization could not be achieved through high doses of atropine. In this study, sixty-four OP-poisoning patients, all of whom accepted routine treatments but who did not attain atropinization after high doses of atropine for 12h, were enrolled. The result showed that the time to atropinization was 24.3±4.3h in the anisodamine group, significantly shorter than in the atropine group (29.2±7.0h, p<0.05); the hospital stay in the anisodamine group was 5.3±2.5 days, significantly shorter than the 6.9±2.3 days needed by the atropine group (p<0.05). We draw a conclusion that anisodamine can shorten the process of atropinization and hospital stay in organophosphorus poisoned patients for whom atropinization cannot be achieved with high doses of atropine.

Diastolic and autonomic dysfunction in early cirrhosis: a dobutamine stress study

Objective. Presence of cardiac dysfunction in patients with advanced cirrhosis is widely accepted, but data in early stages of cirrhosis are limited. Systolic and diastolic functions, dynamics of QT-interval, and pro-atrial natriuretic peptide (pro-ANP) are investigated in patients with early stage cirrhosis during maximal β-adrenergic drive. Material and methods. Nineteen patients with Child A (n = 12) and Child B cirrhosis (n = 7) and seven matched controls were studied during cardiac stress induced by increasing dosages of dobutamine and atropine. Results. Pharmacological responsiveness was similar in cirrhosis and controls and the heart rate (HR) increased by 66 ± 15 versus 67 ± 8 min−1. HR-blood pressure product increased equally by 115% in both cirrhotic patients and controls. However, time to resume HR of 100 beats/min was significantly longer in cirrhosis, p < 0.01. The QTc interval increased after dobutamine infusion in cirrhosis (0.41 ± 0.02 vs. 0.43 ± 0.02 s, p = 0.001) but similar electrophysiological changes were seen in controls. Cardiac volumes increased with the severity of disease. The increased cardiac output was primarily attributed to increased stroke volume. The ejection fraction was similar in patients and controls. Peak filling rate was longer in cirrhosis compared to controls (1.8 ± 0.4 and 1.4 ± 0.2 end-diastolic volume/s, p < 0.01). Pro-ANP was higher in cirrhosis and increased during stress by 13% compared to 0% in controls, p < 0.01. Conclusions. These findings indicate that patients with early stage cirrhosis exhibit early diastolic and autonomic dysfunction as well as elevated pro-ANP. However, the cardiac chronotropic and inotropic responses to dobutamine stress were normal. The dynamics of ventricular repolarization appears normal in patients with early stage cirrhosis.

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Organophosphorus compound is used for committing suicidal are on upswing in developing countries A grading system of severity of OP poisoning suggests that most cases can be managed in the ICU which cannot be applied to developing countries, where facilities for ICU management are rather limited. Hence, the present study is undertaken to identify the factors both clinical and biochemical, which help in predicting the need for ventilator support and thus helping to reduce the mortality by timely institution of ventilator support. AIMS OF THE STUDY: To study the clinical and biochemical parameters in organophosphate poisoning, which help to predict the need for ventilator support. MATERIAL AND METHODS: This is a Descriptive Study done at Kempegowda Institute of Medical Sciences, Bangalore, with a sample size of 50 cases. Patients who fulfilled the inclusion criteria are assessed as per proforma specifically designed for the study. RESULTS: In this study population, 12 patients who reached the hospital for treatment > 4 hour of consumption, 11(91.7%) required ventilator support. In this study, out of patients with pinpoint pupils at admission required ventilator support. In this study, all patients ( required ventilator support with a fasciculation score of more than as compared to none with absent fasciculation. In this study, lower the Glasgow coma scale at admission, more vulnerable are the patients for ventilator support. In This study, patients with reduced levels of Pseudo cholinesterase i.e. out of patients ( required ventilator support. CONCLUSION: Clinical and biochemical parameters such as Greater the time lag from consumption of OP poison till getting specific treatment, Lower GCS scoring, Generalized Fasiculations, Low Pseudo cholinesterase levels, Larger initial dose of Atropine required for Atropinization were strong predictors for the need for Assisted Ventilation in OP poisoning. Grading of the degree of the poisoning taking the above parameters into consideration can help to identify high risk patients who may go in for Respiratory failure and require ICU admission and Ventilator support.

Maximum Atropine Dose Without Clinical Signs or Symptoms

Atropine 1% has been used to slow the progression of myopia; however, it has not gained worldwide clinical acceptance because it results in clinically significant pupillary mydriasis and accommodative paralysis. Lower concentrations of atropine (0.5 to 0.01%) have been reported to be associated with fewer symptoms, while still controlling myopia. It is the purpose of this study to find the highest concentration of atropine that does not result in significant symptoms from pupillary dilation and accommodative paralysis. A 3 × 3 phase I clinical trial paradigm was used in 12 subjects, to determine the maximum dosage of atropine which could be prescribed without creating symptoms or clinical signs of insufficient accommodation or excessive pupillary dilation. Accommodation was measured by pushouts and pupillary dilation by photography. Prior to this study, we established the following criteria for comfort: 5D or more of residual amplitude of accommodation, less than or equal to a 3 mm pupillary difference between the eyes, and a report of minimal symptoms of near vision blur or outside photophobia. Our results indicate that atropine 0.02% is the highest concentration that did not result in clinical symptoms and findings associated with higher dosages. Mean pupillary dilation was 3 mm, and mean accommodative amplitude was 8 diopters with this concentration. Further, reduction of the concentration of atropine from 0.02 to 0.01% did not seem to result in a decrease in clinical signs or symptoms associated with atropine. Atropine 0.02% is the highest concentration that does not produce significant clinical symptoms from accommodation paresis or pupillary dilation. This would be an appropriate starting point in evaluating a low dosage of atropine to slow myopic progression.

A Study on Two Dose Regimens of Pralidoxime in the Management of Organophosphate Poisoning

Background: The role and proper dose of pralidoxime in the treatment of Organophosphorus (OP) compounds poisoning is an unresolved issue .This study was designed to compare the regimen recommended by the World Health Organization (WHO) with the commonly used standard regimen of pralidoxime. Methods: This was a randomized open labeled prospective study on OP poisoned patients admitted to JSS Hospital, Mysore, India during November 2009 to January 2012. WHO regimen of 2 g pralidoxime bolus followed by 8mg/kg/h infusion (study group) compared with standard regimen of 2 g pralidoxime bolus followed by 1g 6 hourly (control group). Results: In total, 82 patients were studied. Thirty-seven patients were randomized into the study group and 45 patients to the control group. All patients had moderate clinical severity. Although fewer patients in the study group required mechanical ventilation in comparison to the controls (12 vs. 22), the difference was not significant (P = 0.13). The death rate was lower in the study group though the difference was not also significant (P = 0.17). Mean (SD) duration of mechanical ventilation in the study group was significantly lower than controls (4.1 (1.6) vs. 6.6 (1.7) days; P = 0.01). Mean dosage of atropine administered was significantly lower in the study group compared to controls (345.0 (90.6) vs. 933.1 (162.3) mg; P = 0.001). Furthermore, 15 controls (33.3%) developed intermediate syndrome whereas no patient (0%) in the study group had such complication, which showed a significant difference (P < 0.001). Conclusion: A dose regimen of pralidoxime consisting of 2 g pralidoxime bolus followed by 8mg/kg/h infusion reduces morbidity and mortality in moderate cases of OP poisoning. The WHO dose regimen had significantly better outcomes compared to the standard dose regimen. How to cite this article: Mahesh M, Gowdar M, Venkatesh CR. A Study on Two Dose Regimens of Pralidoxime in the Management of Organophosphate Poisoning. Asia Pac J Med Toxicol 2013;2:121-5.

Comparison of Current Recommended Regimens of Atropinization in Organophosphate Poisoning

Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.'s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4mg) and the highest dose (75mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75mg was over 18h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.

Central cholinergic involvement in sequential behavior: Impairments of performance by atropine in a serial multiple choice task for rats

Two experiments examined whether muscarinic cholinergic systems play a role in rats’ ability to perform well-learned highly-structured serial response patterns, particularly focusing on rats’ performance on pattern elements learned by encoding rules versus by acquisition of stimulus–response (S–R) associations. Rats performed serial patterns of responses in a serial multiple choice task in an 8-lever circular array for hypothalamic brain-stimulation reward. Two experiments examined the effects of atropine, a centrally-acting muscarinic cholinergic receptor antagonist, on rats’ ability to perform pattern elements where responses were controlled by rules versus elements, such as rule-inconsistent “violation elements” and elements following “phrasing cues,” where responses were controlled by associative cues. In Experiment 1, 3-element chunks of both patterns were signaled by pauses that served as phrasing cues before chunk-boundary elements, but one pattern also included a violation element that was inconsistent with pattern structure. Once rats reached a high criterion of performance, the drug challenge was intraperitoneal injection of a single dose of 50mg/kg atropine sulfate. Atropine impaired performance on elements learned by S–R learning, namely, chunk-boundary elements and the violation element, but had no effect on performance of rule-based within-chunk elements. In Experiment 2, patterns were phrased and unphrased perfect patterns (i.e., without violation elements). To control for peripheral effects of atropine, rats were treated with a series of doses of either centrally-acting atropine or peripherally-acting atropine methyl nitrate (AMN), which does not cross the blood–brain barrier. Once rats reached a high criterion, the drug challenges were on alternate days in the order 50, 25, and 100mg/kg of either atropine sulfate or AMN. Atropine, but not AMN, impaired performance in the phrased perfect pattern for pattern elements where S–R associations were important for performance, namely, chunk-boundary elements. However, in the structurally more ambiguous unphrased perfect pattern where rats had fewer cues and presumably relied more on S–R associations throughout, atropine impaired performance on all pattern elements. Thus, intact muscarinic cholinergic systems were shown to be necessary for discriminative control previously established by S–R learning, but were not necessary for rule-based serial pattern performance.

Epileptic seizures induced by cycloplegic eye drops

Objective: To assess the incidence of seizures induced by cycloplegic ophthalmic drops.Materials and methods: A survey among members of the American Association for Pediatric Ophthalmology and Strabismus yielded five patients who received cycloplegic eye drops between 1998 and 2010 and who consequently developed a seizure.Results: The median age of the patients was 5 years (range 3 months to 12 years). Cyclopentolate hydrochloride 1% was the only causative agent. The seizure happened on average 12 min after the instillation of dilating eye drops. Three were generalized convulsions, and two patients had a focal seizure. Past medical history was unremarkable in four cases. In total, 16 previous cases of seizures induced by cycloplegic drugs were identified in reports published between 1890 and 2004, implicating atropine in nine reports, tropicamide and phenylephrine eye drops in one and cyclopentolate in six.Discussion: A small amount of cyclopentolate drops could induce convulsions in young children after only minutes to less than an hour, while a larger dosage of atropine over the span of several hours could cause this rare and unpredictable complication. Predisposing factors were rare and those developing the seizures were healthy subjects. Generalized seizures were much more frequent than focal convulsions.Conclusions: Seizures after instillation of cycloplegic drops are extremely rare.

Pharmacological study of cholinergic system on cardiovascular regulation in the cuneiform nucleus of rat

In the present study the effect of cholinergic system of Cuneiform nucleus (CnF) on central regulation of cardiovascular system was investigated. Two doses of acetylcholine (Ach; 90 and 150nmol), atropine (3 and 9nmol) and hexamethonium (Hexa; 100 and 300nmol) were microinjected into the CnF. The maximum changes of MAP and HR were compared with control group (independent t-test). Both doses of Ach significantly decreased MAP but had no significant effect on HR. Administration of atropine and Hexa by themselves did not alter the MAP or HR. However, both doses of atropine and higher dose of Hexa significantly attenuated the hypotensive effect of Ach with no significant effect on HR. Our results suggest the involvement of CnF cholinergic system only on central blood pressure regulation that strongly mediated by muscarinic receptors.

Repeated pulse intramuscular injection of pralidoxime chloride in severe acute organophosphorus pesticide poisoning

ObjectiveThis study aimed to clarify the efficacy of 2 therapies for patients with severe acute organophosphorus pesticide poisoning, including atropine adverse effects, the length of intensive care unit (ICU) stay, complications, and mortality. MethodsA retrospective cohort study of 152 cases collected from May 2008 to November 2012 at 2 urban university hospitals was conducted. Patients admitted to the hospital for organophosphate poisoning were divided into 2 groups with different therapeutic regimens: group A was administered a repeated pulse intramuscular injection of pralidoxime chloride, and group B received the same initial dosage of atropine and pralidoxime chloride, but pralidoxime chloride intravenous therapy was administered for only 3 days, regardless of the length of atropine therapy. Subsequently, atropine adverse effects, length of ICU stay, complications, and mortality were statistically analyzed and compared between the 2 groups. ResultsThe total dose of atropine was 57.40 ± 15.14 mg in group A and 308.26 ± 139.16 mg in group B; group A received less atropine than did group B (P = .001). The length of ICU stay in group A was reduced (P = .025), and group A had fewer atropine adverse effects (P = .002). However, there was no significant difference in the mortality or complication rate between the 2 groups (P > .05). ConclusionIn patients with severe poisoning, group A used less atropine, had fewer atropine adverse effects, and had a shorter ICU stay. We suggest that therapy should be started as early as possible using a sufficient amount of pralidoxime chloride started intramuscularly in combination with atropine and that the drugs should not be prematurely discontinued.

An evaluation of the non-invasive faecal pellet assessment method as an early drug discovery screen for gastrointestinal liability

IntroductionGastrointestinal adverse effects contribute significantly to drug attrition as well as reduced patient compliance. Determination of gastrointestinal liability early in a compound's preclinical development would be a valuable tool. We evaluated the non-invasive faecal pellet method in the rat, assessed the feasibility of adding the endpoint to other study types and investigated correlation with the charcoal meal method. MethodsHan Wistar rats, pair housed in metabolism cages, received a single dose of vehicle, atropine, bethanechol, loperamide or metoclopramide. The number, weight and appearance of pellets produced were assessed over 10h and at 24h post-dose. The endpoint was also added to a modified Irwin screen (testing atropine, theophylline, clonidine, amphetamine, baclofen or quinine) and a whole body plethysmography study (testing theophylline or bethanechol). Pellets were collected from home cages out to 4h post-dose (Irwin) or following a 45minutes plethysmography session. To assess correlation with stomach emptying and intestinal transit charcoal meal data was generated where published data was not available. ResultsAtropine decreased, while bethanechol and metoclopramide increased the number and weight of faecal pellets produced. Atropine produced darker, harder pellets and bethanechol lighter, softer pellets. Loperamide reduced pellet production at later time points only. Theophylline increased (Irwin and plethysmography) and atropine (Irwin) decreased pellet number and weight. Effects were maximal at the Tmax and detected in all study environments. Primary data generation was not affected by pellet collection. Pellet findings were generally comparable to charcoal meal transit data, with compounds showing an inhibition (atropine, loperamide, amphetamine, baclofen, clonidine, quinine) or stimulation (bethanechol) in both models. DiscussionWe have demonstrated that the faecal pellet method can detect expected reference compound induced changes in pellet transit. The technique is a useful non-invasive ‘add-on’ to other study types allowing gastrointestinal effects to be flagged earlier in preclinical development.

RAISING THE ‘DEAD’ – REPERFUSION FROM TORPOR

> Kelly Drew discusses Paul Chatfield and Charles Lyman's classic paper ‘Circulatory changes during the process of arousal in the hibernating hamster’, published in the American Journal of Physiology in 1950. Over 60 years ago, Paul Chatfield and Charles Lyman described fundamental

The Selective Rho-kinase Inhibitor Azaindole-1 Has Long-lasting Erectile Activity in the Rat

To investigate the effects of the selective Rho-associated protein kinase (ROCK) inhibitor azaindole-1 on erectile function under physiologic and pathophysiologic conditions in the rat. The effect of intracavernosal (i.c.) injections of azaindole-1 on change in intracavernous pressure (ICP), ICP/mean arterial pressure (MAP), area under the curve (AUC), and response duration were investigated in the anesthetized rat under control conditions and when nonadrenergic noncholinergic neurotransmission and cholinergic function or soluble guanylyl cyclase (sGC) were inhibited or after cavernosal nerve crush injury. The i.c. injections of azaindole-1 produced dose-related increases in ICP/MAP and AUC that were long-lasting at the highest doses studied compared with the prototypical ROCK inhibitor fasudil. Erectile responses were not altered by 7-nitroindazole and atropine in doses that reduced the response to cavernosal nerve stimulation by 86%, indicating that they were independent of NO release by cavernosal nerves or activation of muscarinic receptors in the corpora cavernosa. Erectile responses to azaindole-1 were not altered by the sGC inhibitor ODQ in a dose that attenuated responses to the NO donor sodium nitroprusside, indicating that they were independent of an action on sGC. The erectile response to i.c. injections of azaindole-1 or Y-27632, which was reported to be NO/cyclic guanosine monophosphate-dependent, was not attenuated after cavernosal nerve crush injury. The present studies indicate that azaindole-1 has long-lasting erectile activity that is independent of NO release, muscarinic receptor, or sGC activation or the integrity of the cavernosal nerves.

Enhancement of Intestinal Motility and Transit Time in Streptozotozin-Induced Diabetic Rats Treated with Ocimum gratissimum

Aims: Acute changes in the blood glucose co ncentration have a substantial effect on intestinal motility in both diabetic and healthy subjects. This research work was therefore designed to assess the effect of DM on GIT motor activity and the impact of treatment with OG on same. Methodology: The phytoconstituents and median lethal dose of the plant extract was determined before administration. Eighteen rats were used; the animals were divided into three groups of six rats each. Group 1 served as the control which was fed with normal feed. Group 2 wasdiabetic untreated rats (DM) while group 3 was OG treated diabetic rats (DMT). At the end of 28 days, the intestinal transit and motility were determined using graded doses of acetylcholine, adrenaline and atropine. Results: The DMT intestine showed greater increase in contraction with increase in concentration of acetylcholine, application of adrenaline showed that the ileum of the DMT had a significantly lower (P=.001) percentage change in relaxation when compared

Full-field electroretinogram findings in children in the atropine treatment for myopia (ATOM2) study

The aims of this study were to determine the longitudinal effects of myopia on full-field electroretinogram (ffERG) in children, and whether there were any effects due to atropine treatment. Fifty children, enrolled in the atropine treatment for myopia study, were randomly selected and 35 children consented to undergo ffERG at baseline (prior to atropine treatment), 24 months (at end of treatment) and 32 months (8 months after cessation of treatment). An extended ISCEV ffERG protocol was used for all recordings. The relationship between axial length (AL) and the following scotopic and photopic ffERG responses was analyzed: a- and b-wave amplitude and implicit time, saturated amplitude (V max), and retinal sensitivity (logK). Reliable ffERG recordings with acceptable level of noise were obtained on all 3 visits from 29 children (mean age: 9.5 ± 0.8 years and mean spherical equivalent: -5.0 ± 1.6 D). At baseline, the correlation detected between AL and logK was 0.37 (p = 0.047). There was no significant correlation between AL and V max or any scotopic and photopic ffERG amplitude and implicit time measures. Longitudinal data suggested a reduction in photopic a- and b-wave and 30 Hz flicker response amplitudes over time. Multivariate analysis showed that the change in 30 Hz flicker response amplitude was likely to be associated with AL change. There was no evidence that changes in other responses were associated with age, baseline AL, or atropine dose used. Retinal sensitivity was reduced in myopic children. There was a gradual decline in cone function over time which was not influenced by atropine treatment.

Prognostic significance of estimation of pseudocholinesterase activity and role of pralidoxime therapy in organophosphorous poisoning

Background:Organophosphorous (OP) poisoning is one of the most common poisonings seen in India. OP compounds act through inhibition of enzyme acetylcholinesterase and estimation of pseudocholinesterase (PCE) activity strengthens the diagnosis in clinically uncertain cases of OP poisoning. The role of pralidoxime (PAM) therapy in OP poisoning has been controversial.Study Objectives:This study was aimed to determine the prognostic significance of estimation of PCE activity and also to assess the role of PAM therapy in OP poisoning.Materials and Methods:Patients of suspected OP poisoning of age >12 years admitted to emergency unit at a tertiary healthcare center of north India were enrolled. Patients were categorized into two groups; group A who were given intravenous atropine and group B who were given injectable PAM along with atropine. Serum PCE level was estimated at the time of admission in all patients and severity of OP poisoning was assessed according to PCE level. Requirement of atropine, oxygen inhalation, intubation and ventilatory support, total hospital stay, and mortality were compared between different classes of severity and also between Groups A and B.Results:This study included a total of 70 subjects, 35 in each group with mean age of 24.99 ± 8.7 years. Out of 70 subjects 49 (70%) were male and 21 (30%) were female. Forty nine patients (70%) of OP poisoning were with suicidal intent while 21 (30%) cases were accidentally poisoned. In all suicidal cases route of poisoning was ingestion whereas in all the accidental cases route of exposure was inhalational. PCE levels were reduced in all the cases and the mean level was 3,154.16 ± 2,562.40 IU/L. The total dose of atropine required, need for oxygen inhalation and need for intubation and ventilatory support, mean duration of hospital stay and mortality rate (P = 0.003) were higher in moderate to severe cases and did not have significant difference between Groups A and B.Conclusion:The study recommends estimation of PCE level at admission to classify severity of OP poisoning and to estimate prognosis. This study did not find any beneficial role of PAM therapy in reducing morbidity as well as mortality.

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CONTEXT: Preloading of crystalloid is a traditional practice to prevent spinal anaesthesia induced hypotension. But coloading seems to be more physiological and rational approach as effect was achieved during the time of spinal anaesthesia. AIMS: To compare crystalloid preload and coload for the prevention of spinal block induced hypotension in lower limb surgeries. Secondary outcomes included no. of dose of mephenteramine & atropine, bradycardia, nausea, vomiting, total volume of infusion, blood loss & urine output. SETTINGS AND DESIGN: Tertiary level, teaching hospital. Prospective, randomized study. MATERIALS AND METHODS: Total sixty patients of either sex, aged 20 to 60 years, scheduled for lower limb surgery under spinal anaesthesia were randomized into preload and coload group, 30 patients in each group. In preload group, 20 ml/kg of Ringer lactate was preloaded 20 minutes before commencement of spinal anaesthesia. In group Coload, 20 ml/kg of Ringer lactate was coloaded in 20 minutes just after lumbar puncture. STATISTICAL ANALYSIS USED: Quantitative data were compared with student's t test and qualitative data with chi-square or fisher exact test. P 0.05). Mean baseline value and trends at various time intervals of heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure were comparable in both groups. Total incidence of hypotension in group Preload and group Coload were 13.33% and 10% respectively (p=0.463). Total incidence of bradycardia in group Preload and group Coload were 6.67% and 10% respectively (p=0.394). No. of dose of atropine to treat bradycardia was 2 out of 30 patients (6.67%) and 3 out of 30 patients (10%) for group P and C respectively (p=0.394). No. of dose of mephenteramine to treat hypotension was 4 out of 30 patients (13.33%) for each group (p=1). Incidence of nausea was 6.67% for group Preload and 10% for group Coload (p=0.394). Incidence of vomiting was 3.33% for group Preload and 6.67 % for group Coload (p=0.278). Total volume used for preloading was about 1474 ± 206 ml and for coloading was 1386 ± 176 ml (p=0.0805). Urine output in preloading and coloading groups was 223 ± 100 and 173 ± 89 ml respectively (p=0.0453). CONCLUSIONS: Coloading with 20 ml/kg of Ringer's lactate was as effective as preloading of same amount 20 minute before lumber puncture to prevent spinal induced hypotension.