Cardiac abnormalities in severe acute dichlorvos poisoning.

OBJECTIVE: Patients with organophosphorus poisoning sometimes die suddenly during rigorous treatment, possibly from myocardial injury. This study sought to elucidate the mechanisms underlying organophosphorus poisoning-induced cardiotoxicity. DESIGN: Prospective observational study. SETTING: Urban, tertiary teaching hospital emergency intensive care unit with 10 beds. PATIENTS: Forty-one patients with severe acute dichlorvos poisoning were consecutively enrolled (n = 92) at emergency intensive care unit and followed for 3 months. MEASUREMENTS AND MAIN RESULTS: Levels of serum creatine kinase isoenzyme myocardium, cardiac troponin I, acetylcholinesterase, acetylcholine, epinephrine, and norepinephrine were tested on hospital days 1, 3, and 5 and on discharge day. Electrocardiography was recorded on admission and then every other day. Transthoracic echocardiography was performed at admission, in the acute phase, before discharge, and during follow-up. Technetium 99m-sestamibi myocardial single photon emission computed tomography was conducted in four patients. Thirty-seven (90.2%) patients survived and four (9.8%) patients died during treatment. We observed sinus tachycardia in 37 (90.2%) patients and ST-T changes in 33 (80.4%) patients. Creatine kinase isoenzyme myocardium and cardiac troponin I levels peaked at day 3 postadmission and then decreased to normal levels. Serum acetylcholine, epinephrine, and norepinephrine peaked at day 1 after admission and then decreased. Echocardiography revealed marked decreases in wall motion of the interventricular septum and left ventricle in the acute phase but returned to normal in the recovery phase. The left ventricular ejection fraction improved significantly from 42 ± 5% to 59 ± 4% (p = .001). Single photon emission computed tomography showed abnormal left ventricle perfusion. CONCLUSION: Severe acute dichlorvos poisoning is associated with reversible myocardial dysfunction, possibly through an increase in catecholamine levels.

Effect of PON1 on dichlorvos toxicokinetics.

OBJECTIVES: To provide toxicokinetic and clinical evidence of the hydrolytic effect of paraoxonase-1 (PON1) on acute organophosphate poisoning in rats. METHODS: 40 male Wistar rats were randomised into four equal groups. Dichlorvos administration group (A group) underwent dichlorvos injection (dissolved in corn oil) using intraperitoneal (ip) dose of 10 mg/kg. PON1 pretreatment group (B group) was injected with PON1 in the tail vein (intravenous), dose 9600 U/kg, 30 min prior to dichlorvos administration. In the treatment group (C group), atropine 0.05 mg/kg and pyraloxime chloride (PAM-CI) 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Finally, in the co-treatment group (D group), PON1 was injected intravenously with a dose of 9000 U/kg 30 min prior to dichlorvos administration; atropine 0.05 mg/kg and PAM-CI 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Blood was collected after administration. Plasma dichlorvos concentration was detected by liquid chromatography-mass spectra (LC-MS) method and clinical signs were observed. Toxicokinetic parameters were calculated in a statistical moment model. RESULTS: AUC (0→∞) in group B was statistically different from that in groups A and C (p<0.05), while it was not different from group D (p>0.05); there was no statistical difference between group A and group C (p>0.05). The statistical results of Cmax were the same as those of AUC (0→∞). There were no differences of MRT between four groups (p>0.05). Clinical signs can be improved by PON1 and atropine + PAM-CI, and co-treatment can relieve signs more effectively. CONCLUSION: PON1 can decrease the amount of dichlorvos that entered the blood, lowered the peak concentration and relieved clinical signs.

Protective effects of Y-27632 on acute dichlorvos poisoning in rats.

Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase-MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning.

Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdose.

The goal of this study was to develop a method to detect pesticide adducts in tryptic digests of butyrylcholinesterase in human plasma from patients poisoned by pesticides. Adducts to butyrylcholinesterase in human serum may serve as biomarkers of pesticide exposure because organophosphorus and carbamate pesticides make a covalent bond with the active site serine of butyrylcholinesterase. Serum samples from five attempted suicides (with dichlorvos, Aldicarb, Baygon and an unknown pesticide) and from one patient who accidentally inhaled dichlorvos were analyzed. Butyrylcholinesterase was purified from 2 ml serum by ion exchange chromatography at pH 4, followed by procainamide affinity chromatography at pH 7. The purified butyrylcholinesterase was denatured, digested with trypsin and the modified peptide isolated by HPLC. The purified peptide was analyzed by multiple reaction monitoring in a QTRAP 4000 mass spectrometer. This method successfully identified the pesticide-adducted butyrylcholinesterase peptide in four patients whose butyrylcholinesterase was inhibited 60-84%, but not in two patients whose inhibition levels were 8 and 22%. It is expected that low inhibition levels will require analysis of larger serum plasma volumes. In conclusion, a mass spectrometry method for identification of exposure to live toxic pesticides has been developed, based on identification of pesticide adducts on the active site serine of human butyrylcholinesterase.

Cellular and molecular mechanisms of dichlorvos neurotoxicity: cholinergic, nonchlolinergic, cell signaling, gene expression and therapeutic aspects.

Inappropriate use of toxic chemicals is common in developing countries, where it leads to excessive exposure and high risks of unintentional poisoning. Risks are particularly high with the pesticides used in agriculture, poor rural populations live and work in close proximity to these compounds and often store these compounds in and around their homes. It is estimated that most of the death from pesticide poisoning occur in developing countries. Organophosphate insecticides have been extensively used in agriculture in developing countries. Dichlorvos is a synthetic insecticide and belongs to a family of chemically related organophosphate pesticides (OP). Toxicity of dichlorvos has been documented in accidental human poisoning, epidemiological studies, and animal models. In this review, molecular mechanisms of dichlorvos neurotoxicity have been described. Usage, biotransformation, environmental levels, general population and occupational exposure, effects on cell signaling receptors, mitochondrial metabolism, oxidative stress and gene expression of dichlorvos have been reviewed. Assessment of acute and chronic exposures as well as neurotoxicity risk for lifetime exposures to dichlorvos have also been considered. In addition special emphasis has been given to describe, the role of dichlorvos in the chronic neurotoxicity and its molecular targets that ultimately lead to neurodegeneration.

Parenteral ophthalmic tropicamide or cyclopentolate protects rats from lethal organophosphate poisoning.

We determine the efficacy of parenteral ophthalmic antimuscarinic agents (tropicamide ophthalmic 1% and cyclopentolate hydrochloride ophthalmic 1%) on survivability in a rat model of acute, lethal organophosphate pesticide (OP) poisoning. After obtaining an appropriate dose-response for study comparison, rodents were randomized to receive 1 of 4 intraperitoneal antidotes; (1) 0.3 mL normal saline, (2) atropine 10 mg/kg, (3) ophthalmic tropicamide 20 mg/kg, or (4) ophthalmic cyclopentolate 20 mg/kg. Five minutes after pretreatment, 15 mg/kg of dichlorvos was administered subcutaneously. Mortality rates and time to death were compared using Fisher exact test and the Kaplan-Meier method with log-rank test, respectively. If alive at 120 minutes, survival was assumed and the study was terminated. Survival in rats pretreated with atropine (10 mg/kg) was 90%. Survival in rats pretreated with tropicamide (20 mg/kg) and cyclopentolate (20 mg/kg) were 90% [P < 0.01; 95% confidence interval (CI) 0.71-1.09] and 90% (P < 0.01; 95% CI 0.71-1.09), respectively, compared with controls (10% survival; 95% CI 0.04-0.45). Time of death ranged between 6 and 13 minutes in nonsurvivors. Overall comparison of survival time revealed a statistically significant improvement in experimental groups compared with controls (P < 0.0001). Pretreatment with parenteral ophthalmic solutions (tropicamide or cyclopentolate) was equivalent to standard atropine in preventing lethality in this rat model of acute, lethal OP poisoning.

Cardiac damage in acute organophosphate poisoning in rats: effects of atropine and pralidoxime.

Anticholinesterase poisoning is an important health problem in our country, and a complete understanding of its underlying mechanisms is essential for the emergency physician. Thus, we aimed to investigate the cardiac biochemical parameters and mortality in dichlorvos-induced poisoning in rats. Rats were randomly divided into 5 groups as control (corn oil), dichlorvos, atropine, pralidoxime, and atropine+pralidoxime groups. Immunohistochemical analyses of apoptosis and inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Serum cholinesterase levels were suppressed with dichlorvos, and these reductions were inhibited with atropine and/or pralidoxime pretreatment. Serum levels of creatine kinase, creatine kinase-MB, cardiac troponin I, myoglobin, and N-terminal probrain natriuretic peptide were not affected with poisoning. Malondialdehyde and glutathione levels were not statistically significant between the groups. Although serum nitric oxide levels in the dichlorvos group were lower than those in the control group, cardiac nitric oxide levels in the atropine+pralidoxime group were markedly higher than those in the dichlorvos group. Atropine, pralidoxime, and atropine+pralidoxime pretreatments markedly reduced the mortality. In conclusion, our results implied that measured cardiac markers especially N-terminal probrain natriuretic peptide may not contribute to the early (first 6 hours) diagnosis of cardiotoxicity in dichlorvos-induced poisoning in rats. These results also showed that acute dichlorvos administration did not cause significant cardiac damage, and oxidative stress does not play a marked role in dichlorvos-induced poisoning. Besides, cardiac nitric oxide may produce protective effect on myocardium with atropine+pralidoxime therapy in rats.

Myeloneuritis due to acute organophosphate (DDVP) intoxication.

Given the importance of agriculture and widespread use of pesticides, intoxication due to organophosphate insecticides is common in Turkey. Organophosphorus compounds may cause late-onset distal polyneuropathy occurring 2 or more weeks after the acute exposure. An 18-year-old woman and a 22-year-old man were admitted to the hospital with weakness, paresthesia, and gait disturbances at 35 and 22 days, respectively, after ingesting dimethyl-2,2-dichloro vinyl phosphate (DDVP). Neurological examination revealed weakness, vibration sense loss, bilateral dropped foot, brisk deep tendon reflexes, and bilaterally positive Babinski sign. Electroneurography demonstrated distal motor polyneuropathy with segmental demyelination associated with axonal degeneration prominent in the distal parts of both lower extremities.

Homicide by organophosphorus compound poisoning: a case report.

Pesticides are responsible for less than 1% of deaths from poisoning in the UK while various studies in India indicate that the figures range from 20% to a staggering 70% (Sharma, 1998). Organophosphorus compounds are reported to be the most commonly used substances for suicidal purposes (Dixit, 2007). Homicidal poisoning involving pesticides has always been rare owing to the disagreeable odour and taste rendered to them by their hydrocarbon solvents (Pillay, 2008). An unusual case of homicide using an organophosphorus compound is presented here. The body of a 28-year-old woman was brought for post-mortem examination at the mortuary of the Government Medical College and New Civil Hospital, Surat, Gujarat, India. It had been exhumed after forty-five days of burial under the supervision of a medical officer from the nearby primary health centre, the police and a magistrate. There was a history of marital discord between the deceased and her husband. Their ten-year-old daughter, who was the only witness to the incident, revealed later that her mother was struck by a wooden block and forcibly made to ingest some medicine. The 'medicine' was identified on chemical analysis as an organophosphorus compound (dichlorvos).

[Therapeutic effects of benthiactzine against respiratory failure induced by cholinesterase inhibitor in rats].

OBJECTIVE: To investigate the therapeutic effects of benthiactzine against respiratory failure induced by cholinesterase inhibitor dimethyl dichloro-vinyl phosphate (DDVP) in rats. METHODS: Forty-five male Wistar rats were divided into five groups randomly: control group, model group, and benthiactzine 0.5, 1.0, 2.0 mg/kg treatment groups (each n=9). Rats were treated with DDVP by intraperitoneal injection to reproduce respiratory failure model. The symptoms, respiratory rate (RR), blood gas analysis, electrolyte and plasma superoxide dismutase (SOD), malondialdehyde (MDA) and the pathological changes were observed before poisoning, during respiratory failure, and in different periods after the treatment. RESULTS: In rats with respiratory failure induced by DDVP, cyanosis and convulsion occurred in all groups. The success rates in three benthiactzine groups were 66.7% (6/9), 77.8% (7/9) and 88.9% (8/9). The rats of benthiactzine treatment groups recovered in 1-5 minutes after treatment and returned to normal state in 30 minutes. RR also returned to normal in 30 minutes. When respiratory failure occurred, arterial oxygen partial pressure (PaO2), arterial oxygen saturation (SaO2) and plasma SOD were decreased, plasma MDA was increased, and mixed acidosis was found. Thirty minutes after the treatment of benthiactzine, all above parameters in three groups returned to normal (all P<0.01). In respiratory failure rats, pathological examination of lung tissue revealed dilatation of pulmonary vessels with aggregation of erythrocytes, widening of alveolar space with presence of red blood cells in alveoli with heavy infiltration of inflammatory cells, and pulmonary edema and hemorrhage. The lungs of rats treated with benthiactzine showed less intense pathological changes. CONCLUSION: The new medicine against poisoning benthiactzine can be a favourable drug against respiratory failure induced by organophosphorus pesticides.

OpdA, a bacterial organophosphorus hydrolase, prevents lethality in rats after poisoning with highly toxic organophosphorus pesticides.

Organophosphorus (OP) pesticides poison more than 3,000,000 people every year in the developing world, mostly through intentional self-poisoning. Advances in medical therapy for OP poisoning have lagged, and current treatment is not highly effective with mortality of up to 40% in even the most advanced Western medical facilities. Administration of a broadly active bacterial OP hydrolase to patients in order to hydrolyze OPs in circulation might allow current therapies to be more effective. The objective of this work was to evaluate the efficacy of a new recombinant bacterial OP hydrolase (OpdA), cloned from Agrobacterium radiobacter, in rat models of two chemically distinct but highly toxic and rapidly acting OP pesticides: dichlorvos and parathion. Without OpdA treatment, median time to death in rats poisoned with 3x LD(50) of dichlorvos or parathion was 6 min and 25.5 min, respectively. Administration of a single dose of OpdA immediately after dichlorvos resulted in 100% survival at 24h, with no additional antidotal therapy. After parathion poisoning, OpdA alone caused only a delay to death. However, an additional two doses of OpdA resulted in 62.5% survival at 24 h after parathion poisoning. In combination with pralidoxime therapy, a single dose of OpdA increased survival to 75% after parathion poisoning. Our results demonstrate that OpdA is able to improve survival after poisoning by two chemically distinct and highly toxic OP pesticides.

Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress parameters in acute dichlorvos poisoning in rats.

This study examined the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced acute toxicity in rats. Rats were randomly divided into four groups as control (corn oil), dichlorvos (30 mg kg(-1) i.p.), 1 and 10 mg kg(-1) Y-27632 + dichlorvos groups. Cholinergic signs (fatigue, tremor, cyanosis, hyper-secretion, fasciculations) were observed in all the rats in the dichlorvos group and the mortality rate was 50%. No cholinergic findings and deaths were observed in the control and Y-27632 groups. Plasma cholinesterase activities were suppressed with dichlorvos and these reductions were attenuated with Y-27632 pretreatment. There was a marked increase in plasma malondialdehyde level in the dichlorvos group, but Y-27632 pretreatment abolished this elevation. Dichlorvos markedly depressed cardiac paraoxonase activity, but these changes were not markedly modified with Y-27632. Total antioxidant capacities, total oxidant status, oxidative stress index, total free sulfhydryl groups and catalase activities in plasma and cardiac tissues were not markedly different between the groups. No significant changes were observed with cardiac myeloperoxidase activities or plasma arylesterase and ceruloplasmin activities. In conclusion, our results suggest that Rho-kinase pathway is involved in organophosphate intoxication, and a decrease in cardiac paraoxonase activities may play a role in the pathogenesis of acute organophosphate poisoning in rats.

Suicide attempt with injection of insecticide in both wrists.

Organophosphates that are commonly used in agriculture, houses, gardens, and in veterinary medicine worldwide, may be used for suicidal purposes. But suicide attempt with self-injection of organophosphates is rare. This article presents a case of a suicide attempt of a young man with self-injection of an organophosphate insecticide (dichlorvos) to both his wrists.

Pathophysiology of respiratory failure following acute dichlorvos poisoning in a rodent model.

Organophosphate (OP) poisoning causes a cholinergic crisis with a wide range of clinical effects including central apnea, pulmonary bronchoconstriction and secretions, seizures, and muscle weakness. The morbidity and mortality from acute OP poisoning is attributed to respiratory failure but the relative contributions of the central and peripheral effects in producing collapse of the respiratory system are unclear. In this study we used a novel adult rat model of acute OP poisoning to analyze the pathophysiology of acute OP poisoning. We found that poisoning caused rapidly lethal central apnea. In animals sustained with mechanical ventilation, we found that following central apnea there ensued progressive pulmonary insufficiency that was variable in timing and severity. Our findings support the hypothesis that OP poisoning in this animal model causes a sequential "two hit" insult, with rapid central apnea followed by delayed impairment of pulmonary gas exchange with prominent airway secretions.

[Different therapeutic efficacy of pralidoxime chloride PAM-Cl on AChE against acute toxicity of methamidophos, dichlorvos and omethoate].

OBJECTIVE: To observe the treatments on the patients with acute methamidophos dichlorvos (DDV) and omethoate poisoning and provide the reliable basis for the rational treatments on these three organophosphorus pesticides poisoning. METHODS: 101 patients with AOPP in 7 hospitals were divided into three groups: Group A, 59 patients with acute methamidophos poisoning, Group B, 32 patients with acute DDV/dipterex (DEP) poisoning, Group C, 10 patients with acute omethoate/dimethoate poisoning. The levels of erythrocyte AChE and the therapeutic efficacies of pralidoxime chloride (PAM-Cl) were compared among the three groups. RESULTS: The AChE activities of all the three groups were inhibited on level of (9.12 +/- 7.99) U/g Hb (group A), 7.32 +/- 4.62 U/g Hb (group B) and (12.01 +/- 9.53) U/g Hb (group C), among which no significant difference was found (P > 0.05). All the patients recovered from acute cholinergic excitation or crisis after the treatment of PAM-Cl. The erythrocyte AChE activities were obviously reactivated in group A three hours later after admission to hospital, each on level of (11.37 +/- 8.67) U/g Hb, (12.51 +/- 6.98) U/g Hb, (15.90 +/- 7.31) U/g Hb, (18.33 +/- 4.78) U/g Hb and (18.91 +/- 7.00) U/g Hb at the 12th, 24th, 48th, 72nd hour and discharge (P < 0.05), and the upgrade tendency was continuous. AChE activities in group B were also reactivated after treatment, each on level of (8.91 +/- 5.89) U/g Hb, (1.31 +/- 6.61) U/g Hb, (13.00 +/- 7.55) U/g Hb, (14.22 +/- 7.80) U/g Hb, (12.78 +/- 7.07) U/g Hb and (16.87 +/- 7.06) U/g Hb at the 3rd, 12th, 24th, 48th, 72nd hour and discharge, but the upgrade tendency turned slowly after 12 hours, the inhibited AChE activities were not reactivated in group C from the beginning to the end. CONCLUSION: After the treatment of PAM-Cl, the AChE activities of the patients with acute methamidophos poisoning could be continuously reactivated, the AChE activities of the patients with acute DDV/DEP poisoning could also be reactivated in 12 hours, and then keep stable, but the AChE activities of the patients with acute omethoate/dimethoate poisoning could not be reactivated. However, PAM-Cl has therapeutic efficacy against acute toxicity of all the three organophosphorus pesticides. Oximes should be vigorously used in the treatment of AOPP, including acute omethoate/dimethoate poisoning.

Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos.

The development of effective antidotes against organophosphates such as dichlorvos has been a persistent challenge over the past decades. Therapy of organophosphate poisoning is based on the administration of atropine and oxime as standard antidotes. The present study was undertaken to evaluate the ability of sodium bicarbonate to improve protective effects of standard antidotes in rats poisoned with dichlorvos. The aim of this experiment was to establish the correlation between protective effects and biochemical parameters relevant for acid-base status. In order to examine the protective effect of both standard antidotes and their combinations, groups of experimental animals were poisoned subcutaneously with increasing doses of dichlorvos. Immediately thereafter, rats were treated with atropine 10 mg/kg intramuscularly, oximes 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally. These antidotes were administered either as single doses or in combinations. In the biochemical part of the experiments, rats were poisoned with dichlorvos 1.3 LD(50) (10.64 mg/kg) subcutaneously and immediately thereafter treated with atropine 10 mg/kg intramuscularly, oximes (trimedoxime or obidoxime) 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally either as single doses or in combinations. Parameters relevant for acid-base status were measured 10 minutes after the administration of antidotes. The results of our study indicate that addition of sodium bicarbonate to standard antidotes significantly improves protective effects of atropine, obidoxime and trimedoxime. Correlation between protection and biochemical outcome is clearly evident when sodium bicarbonate is being added to atropine.

Magnetic resonance imaging changes in a case of extra-pyramidal syndrome after acute organophosphate poisoning.

Distal symmetrical polyneuropathy and neuromuscular weakness is common neurological problem in recovery phase of acute organophosphate (OP) poisoning. Various types of extra pyramidal syndromes are uncommon sequel after OP poisoning. These are reported to be reversible within few weeks and characteristically associated with normal magnetic resonance imaging (MRI). In this report we are presenting a case with extra pyramidal syndrome after acute OP poisoning with few interesting MRI changes in striatum.

Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos.

The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.

The comparison of therapeutic effects of atropine and pralidoxime on cardiac signs in rats with experimental organophosphate poisoning.

Organophosphate poisoning causes disturbances in cardiac conduction and potentially fatal severe cardiac rhythm abnormalities. This study investigated the cardiac effects of atropine and pralidoxime in the treatment of organophosphate poisoning in rats. Three groups of 10 adult male Wistar rats were anesthetized with an intraperitoneal injection of ketamine 100 mg/kg and xylazine 10 mg/kg and connected to a computerized electrocardiographic monitor. Each rat was then injected intraperitoneally with the pesticide dichlorvos 70 mg/kg. Sixty seconds after the injection, 10 rats were injected with saline, 10 with pralidoxime mesylate 20 mg/kg, and 10 with atropine 10 mg/kg. During the computerized electrocardiographic monitoring, each rat's heart rate and QT(c) intervals were recorded and analyzed as the injections were administered. The heart rates in all 3 groups did not differ before the dichlorvos was administered, nor at 60 seconds afterward, but in the atropine group, the time elapsed before the first decline in heart rate was significantly longer than that in the control group (P<.05). In addition, the interval before death was significantly longer in the atropine group than in either the control group or the pralidoxime group (P<.05 for both). The QT(c) was almost identical in each of the groups. Atropine has beneficial effects on the heart rate, prolongs the time before the heart rate declines, and delays death but has no effect on the QT(c) interval. Further research about the toxic effects of organophosphate compounds on myocardial cells is warranted.