The effects of glyceryl trinitrate,isosorbide dinitrate and sodium nitroprusside on haemodynamics,coronary blood flow and myocardial oxygen consumption — An experimental study

The influences of glyceryl trinitrate, isosorbide dinitrate and sodium nitroprusside intravenously on haemodynamics, coronary circulation and myocardial oxygen consumption were investigated in closed chest dogs (n=8). In an attempt to simulate heart failure the dogs received blood transfusion (15 ml/kg) in the presence of halothane-induced myocardial depression. All three nitrates reduced the loads for the left ventricle. With isosorbide dinitrate and sodium nitroprusside the preload and pulmonary pressure decreased to a greater extent than with glyceryl trinitrate. The haemodynamic results suggest that sodium nitroprusside is the favourable nitrate in left ventricular failure because it produces a balanced reduction in the ratio of pre- and afterload. Four μg/kg·min sodium nitroprusside induced marked coronary dilatation; glyceryl trinitrate had only a slight coronary vasodilating effect. With isosorbide dinitrate the myocardial blood flow remained well adapted to oxygen demand, the coronary vascular resistance did not change. Sodium nitroprusside produced a significant change of the transmural myocardial blood distribution-expressed as the epi/endocardial blood flow ratio. The ratio was increased by sodium nitroprusside, much more than by glyceryl trinitrate or isosorbide dinitrate.     

Does amyl nitrite have a role in the management of pre-hospital mass casualty cyanide poisoning?

Context. Amyl nitrite has been recommended as a cyanide antidote for several decades. Its antidotal properties were initially attributed to induction of methemoglobin and later to a nitric oxide mediated hemodynamic effect. The ease of administration and alleged rapid clinical effect would recommend its wide use in the pre-hospital management of mass casualty cyanide poisoning; yet there are concerns regarding the use of amyl nitrite for this indication. Objective. Review the data on amyl nitrite in cyanide poisoning and evaluate its efficacy and safety in mass casualty cyanide poisoning. Methods. A literature search utilizing PubMed, Toxnet, textbooks in toxicology and pharmacology, and the bibliographies of the articles retrieved identified 17 experimental studies and human reports on the use of amyl nitrite in cyanide poisoning, and 40 additional articles on amyl nitrite's properties and adverse effects. One paper was excluded as it was a conference abstract with limited data. Mechanisms of action. The antidotal properties of amyl nitrite were attributed initially to induction of methemoglobinemia and later to nitric oxide mediated vasodilation. Efficacy: experimental studies. Animal studies on the use of amyl nitrite in cyanide poisoning are limited, and their results are inconsistent, which makes their extrapolation to humans questionable. Efficacy: human studies. Clinical reports are limited in number and the part played by amyl nitrite relative to the other treatments administered (e.g. life support, sodium nitrite, and sodium thiosulfate) is unclear. Adverse effects. Amyl nitrite can be associated with potentially serious adverse reactions such as hypotension, syncope, excessive methemoglobinemia, and hemolysis in G6PD deficient patients. These effects are more pronounced in young children, in the elderly, and in patients with cardiac and pulmonary disorders. Dose regimen. The method of administration of amyl nitrite (breaking pearls into gauze or a handkerchief and applying it intermittently to the victim's nose and mouth for a few minutes) is not easily controlled, might result in under- or over-dosing, can prevent the caregiver from administering life support, and possibly expose him/her to amyl nitrite's adverse effects. Conclusions. Administration of amyl nitrite in mass casualty cyanide poisoning can result in unnecessary morbidity and may interfere with the proper management of the incident and the required supportive treatment and rapid evacuation. In the authors' opinion these drawbacks make the use of amyl nitrite in pre-hospital mass casualty cyanide poisoning unwarranted.     

Antidotal use of methemoglobin forming cyanide antagonists in concurrent carbon monoxide/cyanide intoxication

An estimated 35% of all fire victims in the United States have toxicologically significant blood levels of CO and CN. However, the treatment of concurrent CO/CN intoxication has been paid scant attention. The suggestion has been made that these victims should be treated for CN poisoning. The current therapeutic management of CN poisoning in this country includes the utilization of two methemoglobin formers: amyl nitrite and sodium nitrite. This study was undertaken to determine if the administration of methemoglobin formers is advisable, as the victim is already suffering from O2 deprivation due to the presence of carboxyhemoglobin. Groups of 28 male ICR mice (22-24 g) were injected i.p. with 5.0 mg/kg of KCN and then were exposed immediately to 0.35% CO for 8.5 min in a dynamic inhalation chamber. Half of the animals were marked randomly for antidotal intervention, the other 14 animals acted as controls. Treatment of survivors with amyl nitrite (12 mg/l of chamber air) for 1 min increased mortality 43%, whereas treatment for 2 min resulted in a 59% increase in mortality. A 25% increase in mortality was noted among those animals treated with sodium nitrite (80 mg/kg i.p.), as compared to the nontreated control survivors. Treatment with dimethylaminophenol (49 mg/kg i.p.) did not statistically affect mortality.     

Bicarbonate therapy for the cardiovascular toxicity of amitriptyline in an animal model

The beneficial hemodynamic effects of sodium bicarbonate as treatment for tricyclic antidepressant poisoning were investigated in an animal model. Seven adult dogs (17.5 to 20 kg) were poisoned by an intravenous infusion of amitriptyline. Toxicity was defined as a doubling of the initial QRS width. A continuous infusion was used to maintain toxicity for 30 minutes after which 44.5 mEq of sodium bicarbonate was administered intravenously. Five of the animals survived to completion of the experiment. Three of the surviving animals developed dysrhythmias. All dysrhythmias ceased within one minute of administration of sodium bicarbonate. An increase in mean blood pressure (P less than .05) and serum pH (P less than .05) and a decrease in mean QRS width (P less than .05) occurred following administration of sodium bicarbonate. The maintenance of toxicity for 30 minutes suggests that this model can be used for future studies of tricyclic antidepressant poisoning.     

Intramuscular cobinamide versus saline for treatment of severe hydrogen sulfide toxicity in swine

Introduction: Hydrogen sulfide (H₂S) is found in petroleum, natural gas, and decaying organic matter. Terrorist groups have attempted to use it in enclosed spaces as a chemical weapon. Mass casualty scenarios have occurred from industrial accidents and release from oil field sites. There is no FDA approved antidote for sulfide poisoning. We have previously reported that intravenous cobinamide is effective for sulfide poisoning. A rapid-acting antidote that is easy to administer intramuscularly (IM) would be ideal for use in a prehospital setting. In this study, we assessed survival in sulfide-poisoned swine treated with IM cobinamide.

Methods: Eleven swine (45–55?kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals ventilated spontaneously with a FiO₂ of 0.21. Sodium hydrosulfide (NaHS, 8?mg/mL) was infused intravenously at 0.9?mg/kg.min until apnea or severe hypotension. Animals were randomly assigned to receive cobinamide (4?mg/kg), or no treatment at the apnea/hypotension trigger. The NaHS infusion rate was sustained for 1.5?min post trigger, decreased to 0.2?mg/kg.min for 10?min, and then discontinued.

Results: The amount of NaHS required to produce apnea or hypotension was not statistically different in both groups (cobinamide: 9.0?mg/kg ±6.1; saline: 5.9?mg/kg ±5.5; mean difference: ?3.1, 95% CI: ?11.3, 5.0). All of the cobinamide treated animals survived (5/5), none of the control (0/6) animals survived (p?Conclusion: Intramuscular cobinamide was effective in improving survival in this large swine model of severe hydrogen sulfide toxicity.     

Life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite in the construction sites

Context. Construction workers are exposed to a wide variety of health hazards such as poisoning at the construction sites. Various forms of poisoning incidents in construction workers have been reported. However, studies on methemoglobinemia caused by unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites have not been reported yet. Objective. The aim of this study was to evaluate life-threatening methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites and describe similar incidents involving ingestion of antifreeze admixtures in Korea. Materials and methods. Retrospective observational case series study on patients with methemoglobinemia after unintentional ingestion of antifreeze admixtures containing sodium nitrite admitted to the emergency department (ED) from January 1, 2010 to December 31, 2012 and cases reported to the Korea Occupational Safety and Health Agency (KOSHA) was performed. Results. Six victims were admitted to our ED. They had methemoglobin levels ranging from 32.4% to 71.5% and all of them recovered after receiving one (2 mg/kg) or two doses infusion of methylene blue. From the data of the KOSHA, six incidents that caused 27 victims were identified. Of 27 victims, five were included in the ED cases. For all incidents, antifreeze admixtures were not contained in their original containers and all new containers did not have a new label. All workers mistook antifreeze admixtures for water. Among the 28 victims included in this study, four died. Conclusion. Unintentional ingestion of antifreeze admixtures containing sodium nitrite at the construction sites can cause life-threatening methemoglobinemia. There is a need to store and label potentially hazardous materials properly to avoid unintentional ingestion at the construction sites.     

Comparison of Nitrite Treatment and Stroma-Free Methemoglobin Solution as Antidotes for Cyanide Poisoning in a Rat Model

Abstract

The standard nitrite/thiosulfate regimen for cyanide poisoning was tested in our rat model. By modifying the treatment regimen and the nitrite solution an effective antidote against an LD of cyanide could be produced. However, this treatment was effective against two times the LD only when administered ten minutes prior to cyanide injection. These results are in marked contrast to our results with stroma-free methemoglobin solutions (SFMS) which showed SFMS to be a highly effective antidote against four times the LD ₉₀, when administered 30 seconds after an intravenous injection of cyanide. SFMS proved to be an effective antidote for two times the LD when administered up to sixty seconds after the cessation of respiration.     

Arteriolization of venous blood gases: a clue to the diagnosis of cyanide poisoning

Prompt diagnosis and treatment of cyanide poisoning is essential for a successful therapeutic outcome. We present a patient with acute cyanide poisoning in whom venous blood gases disclosed an abnormally high pO2. Prompt treatment of the patient with the cyanide antidote, sodium nitrite plus sodium thiosulfate, rapidly reversed the cardiovascular and central nervous system manifestations of cyanide toxicity. The pathogenesis of cyanide-induced blood gas abnormalities and their potential value in the recognition of cyanide intoxication are discussed. Current treatment recommendations for cyanide poisoning are also reviewed.     

Severe methemoglobinemia due to ingestion of toxicants

Background. Toxin-induced methemoglobinemia is seen in poisoning with oxidizing agents. We report the clinical features and outcome of patients admitted with severe methemoglobinemia due to intentional ingestion of toxicants. Methods. In this observational case series, patients admitted with toxin-induced methemoglobinemia between September 2011 and January 2014 were identified from the institutional poisoning database. Clinical profile and outcome of patients with methemoglobin concentration greater than or equal to 49% is reported. Results. Of the 824 patients admitted with poisoning, 5 patients with methemoglobin concentration greater than or equal to 49% were included. The implicated compounds were nitrobenzene, benzoylphenylurea, flubendamide and Rishab^TM. One patient refused to name the compound. All patients were managed in the intensive care unit. Altered sensorium [Glasgow coma scale (GCS) < 10] was common (80%); 2 patients presented with a GCS greater than 4. All patients manifested cyanosis, low oxygen saturation and chocolate-brown-colored blood despite supplemental oxygen therapy. The median methemoglobin concentration was 64.7% (range 49.8–91.6%); 2 patients had methemoglobin concentration greater than 70%. One patient needed inotropes. Four patients required mechanical ventilation for 4–14 days. All patients were treated with methylene blue; 4 received more than one dose. Three patients also received intravenous ascorbic acid 500 mg, once daily, for 3 days. Following treatment, there was evidence of haemolysis in all patients; 2 required blood transfusion. All patients survived. Conclusion. Patients with severe toxin-induced methemoglobinemia present with altered sensorium and cyanosis and may require ventilatory support and inotropes. Though methemoglobin concentrations greater than 70% are considered fatal, aggressive management with methylene blue and supportive therapy can lead to survival.     

Auditory Neurotoxicity and Hepatotoxicity After MSMA (Monosodium Methanarsenate) High Dose Oral Intake

Context.?Human butyrylcholinesterase (huBuChE) has potential utility as a post-exposure therapy following percutaneous nerve agent poisoning as there is a slower absorption of agent by this route and hence a later onset of poisoning. Methods.?We used surgically implanted radiotelemetry devices to monitor heart rate, EEG, body temperature and locomotor activity in guinea pigs challenged with VX via the percutaneous route. Results.?Treatment with huBuChE (24.2 mg/kg, i.m.) at 30 or 120 min following percutaneous VX (~2.5 × LD₅₀) protected 9 out of 10 animals from lethality. When i.m. huBuChE administration was delayed until the onset of observable signs of systemic cholinergic poisoning, only one out of six animals survived to 7 days. Survival increased to 50% when the same dose of huBuChE was given intravenously at the onset of signs of poisoning. This dose represents approximately 1/10th the stoichiometric equivalent of the dose of VX administered (0.74 mg/kg). Intramuscular administration of huBuChE (24.2 mg/kg) alone did not produce any changes in heart rate, brain electrical activity, temperature or locomotion compared to saline control. Survival following VX and huBuChE treatment was associated with minimal incapacitation and observable signs of poisoning, and the mitigation or prevention of detrimental physiological changes (e.g. seizure, bradycardia and hypothermia) observed in VX + saline-treated animals. At 7 days, cholinesterase activity in the erythrocytes and most brain areas of guinea pigs that received huBuChE at either 18 h prior to or 30 min following VX was not significantly different from that of naïve, weight-matched control animals. Conclusion.?Percutaneous VX poisoning was successfully treated using post-exposure therapy with huBuChE bioscavenger. The opportunity for post-exposure treatment may have particular relevance in civilian settings, and this is a promising indication for the use of huBuChE.     

Cyanide poisoning successfully treated without 'therapeutic methemoglobin levels'

A 24-year-old woman ingested an unknown amount of potassium cyanide in a suicide attempt. Coma and metabolic acidosis developed. Administration of the Lilly Cyanide Antidote kit (Eli Lilly and Co, Indianapolis) resulted in prompt resolution of symptoms and full recovery. Whole blood cyanide level was 13 micrograms/mL approximately one hour after ingestion. The highest measured methemoglobin level after sodium nitrite administration was 9.2%, demonstrating that attaining a "therapeutic methemoglobin level" of 25% is unnecessary to insure a satisfactory clinical outcome. Because severe hypotension or excessive methemoglobinemia can be caused by the sodium nitrite component of the Lilly kit, only enough to produce an acceptable clinical response should be administered.     

Nitrite/Thiosulfate Treated Acute Cyanide Poisoning: Estimated Kinetics After Antidote

Abstract

A 34 year old, 73 kg man ingested a 1 gram potassium cyanide pellet in a suicide attempt. Within one hour, coma, apnea, metabolic acidosis, and seizures developed. Sodium nitrite and sodium thiosulfate were administered. Dramatic improvement in the clinical condition occurred by the completion of antidote infusion. Methemoglobin level was 2% immediately after nitrite administration. Serial whole blood cyanide levels were obtained, documenting a highest measured level of 15.68 mcg/mL. Estimations of toxicokinetic parameters including terminal half-life (t 1/2) (19 hours), clearance (163 mL/minute), and volume of distribution (Vd) (0.41 L/kg) were calculated. The nitrite/thiosulfate combination was clinically efficacious in this case and resulted in complete recovery.     

The combination of cobinamide and sulfanegen is highly effective in mouse models of cyanide poisoning

Context. Cyanide is a component of smoke in residential and industrial fires, and accidental exposure to cyanide occurs in a variety of industries. Moreover, cyanide has the potential to be used by terrorists, particularly in a closed space such as an airport or train station. Current therapies for cyanide poisoning must be given by intravenous administration, limiting their use in treating mass casualties. Objective. We are developing two new cyanide antidotes – cobinamide, a vitamin B₁₂ analog, and sulfanegen, a 3-mercaptopyruvate prodrug. Both drugs can be given by intramuscular administration, and therefore could be used to treat a large number of people quickly. We now asked if the two drugs would have an augmented effect when combined. Materials and methods. We used a non-lethal and two different lethal models of cyanide poisoning in mice. The non-lethal model assesses neurologic recovery by quantitatively evaluating the innate righting reflex time of a mouse. The two lethal models are a cyanide injection and a cyanide inhalation model. Results. We found that the two drugs are at least additive when used together in both the non-lethal and lethal models: at doses where all animals died with either drug alone, the combination yielded 80 and 40% survival in the injection and inhalation models, respectively. Similarly, drug doses that yielded 40% survival with either drug alone, yielded 80 and 100% survival in the injection and inhalation models, respectively. As part of the inhalation model, we developed a new paradigm in which animals are exposed to cyanide gas, injected intramuscularly with an antidote, and then re-exposed to cyanide gas. This simulates cyanide exposure of a large number of people in a closed space, because people would remain exposed to cyanide, even after receiving an antidote. Conclusion. The combination of cobinamide and sulfanegen shows great promise as a new approach to treating cyanide poisoning.     

Prophylactic and therapeutic effects of garlic extract on Nerium oleander-induced arrhythmia: a new approach to antiarrhythmic therapy in an ovine model

Abstract

Context. Oleander is a potent cardiotoxic plant and is a common cause of poisoning in human and animals. There is no affordable and cost-effective treatment for oleander poisoning. Objective. To evaluate the prophylactic and therapeutic effects of garlic extract (Allium sativum) on Nerium oleander (a potent cardiotoxic plant) intoxication in sheep. Materials and methods. Eight sheep were intravenously infused with an unsterilized hydro-ethanol extract of garlic (50 mg/kg) before or after receiving a lethal dose of dried leaves (as a powder) of oleander (100 mg/kg, orally). The cardiac rhythm was continuously monitored using biopotential wireless transmitters and telemetry system. For evaluation of therapeutic effects, six sheep received the lethal dose of oleander and were administered with garlic extract after development of cardiac arrhythmias. Subsequently, the survived animals from the therapeutic study (four sheep) were administered with oleander without receiving any medication. Some blood constituents, including total antioxidant capacity, malondialdehyde, and troponin I, were compared between treated and untreated animals. Results. Pretreatment with garlic extract reversed the arrhythmia caused by oleander to its previous normal rhythm in seven sheep, but, one sheep died of ventricular fibrillation. On therapeutic treatment, four sheep survived while two died of ventricular fibrillation. Dosing with oleander without receiving garlic extract resulted in death of all sheep due to ventricular fibrillation. Blood constituents did not show any significant changes between treated and untreated sheep, and before and after intoxication. Conclusions. Garlic extract reduced the case fatality from 100% to 12.5% and 33.3% as a prophylactic or therapeutic agent, respectively. Additionally, garlic extract delayed the time of onset of arrhythmias and prolonged the interval between intoxication and death of the animals. Garlic extract could be considered to be a potential and affordable antidote in oleander poisoning. However additional studies with a larger sample size and in other species need to be performed to confirm the results in this study.     

Fatal methaemoglobinaemia induced by self‐poisoning with sodium nitrite

Inadvertent ingestion of sodium nitrite is known to precipitate metheamoglobinaemia. No cases exist, however, of intentional suicide by methaemoglobinaemia following self‐poisoning with sodium nitrite. A 76‐year‐old man collapsed and rapidly developed brady‐asystolic cardiac arrest 25 min following self‐poisoning with an unknown quantity of crystalline sodium nitrite. On arrival in the ED the patient was asystolic with cardiopulmonary resuscitation in progress. Haemoglobin concentration was 110 g/L, arterial methaemoglobin measured 82.6% and serum lactate 9.6 mmol/L. Antioxidative treatment was undertaken with total 5 mg/kg intravenous methylene blue administered in divided aliquots. Despite prolonged resuscitative efforts the patient died. Resuscitation from methaemoglobinaemia‐induced asystole following self‐poisoning presents a unique therapeutic challenge. Treatment of methaemoglobinaemia‐induced cardiovascular instability and overt cardiopulmonary arrest are discussed.     

An Activated Charcoal Hemoperfusion System for the Treatment of Barbital or Ethylene Glycol Poisoning in Dogs

Abstract

The efficacy of activated charcoal (AC) hemoperfusion therapy was studied in dogs acutely poisoned with lethal doses of barbital or ethylene glycol (EG). Two of three barbital-poisoned dogs treated with AC hemoperfusion survived; the dog that died was only hemoperfused for 1.5?h. Although AC hemo'perfusion of EG-poisoned dogs reduced the blood level of the toxicant considerably, this was not enough to effect survival. The use of AC hemoperfusion was an effective therapeutic measure for dogs poisoned with lethal doses of barbital. The use of the AC hemoperfusion system with existing drugs of therapy for EG poisoning may be beneficial.     

Rapid determination of toxic cyanide concentrations in blood

This method for the rapid colorimetry of cyanide in blood, applicable to patients exposed to toxic levels of cyanide, is based on the K?nig reaction, which produces a chromophore from cyanide as well as thiocyanate. The latter compound, normally present in blood, is confined to plasma. Thus, its interference with determination of cyanide was eliminated by performing the assay on the erythrocytes, which contain most of the blood cyanide. Furthermore, cyanide was trapped in the erythrocytes and stabilized during the initial washing steps by conversion of hemoglobin to methemoglobin with inorganic nitrite.     

Endothelially Derived Nitric Oxide Affects the Severity of Early Acetaminophen-induced Hepatic Injury in Mice

Objectives: The precise mechanism of hepatocellular toxicity following acetaminophen (APAP) poisoning remains unclear. Nitric oxide is implicated in APAP toxicity as an inflammatory signaling molecule and as a precursor to the free radical peroxynitrate. The effects of inducible nitric oxide synthase (iNOS)‐derived NO in APAP toxicity are known; however, the role of endothelial nitric oxide synthase (eNOS)‐derived NO is unknown. The authors sought to evaluate the effect of eNOS‐derived NO during APAP toxicity. Methods: C57BL6/J mice deficient in eNOS (eNOS KO) or iNOS (iNOS KO) and wild‐type mice (WT) were treated with 300 mg/kg APAP. Alanine aminotransferase levels and plasma nitrate and nitrite levels were measured. Hypoxia inducible factor (HIF)‐1α and Glucose Transporter 1 (Glut‐1) levels were determined by Western blot. Results: Alanine aminotransferase levels were significantly elevated in all treated animals. Alanine aminotransferase levels were significantly lower in eNOS KO and iNOS KO than in treated WT animals. Plasma nitrate/nitrite levels were significantly higher in WT animals than in iNOS KO and eNOS KO animals. HIF‐1α expression was increased in WT mice and decreased in iNOS KO mice. Glut‐1 is a downstream, indirect marker of HIF function. Glut‐1 expression was increased in WT and eNOS KO mice. Conclusions: Deficiency of either iNOS or eNOS results in decreased NO production and is associated with reduced hepatocellular injury following APAP poisoning. HIF‐1α and Glut‐1 levels are increased following APAP poisoning, implying that HIF‐1α is functional during the pathogenic response to APAP poisoning.     

Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine

A controlled study was performed to assess the involvement of the nitric oxide pathway in migraine pathophysiology. Thirteen patients with migraine without aura and seven clinically healthy subjects (C) were selected. All of the migraine patients were studied both before, during an asymptomatic phase (t ₀), and 1 h after the administration of 5 mg isosorbide dinitrate, a nitric oxide donor able to induce an experimental migraine attack (t ₁). The nitric oxide levels were analyzed as nitrite accumulation in serum samples, in peripheral blood mononuclear cell extracts, and culture supernatants. Basal nitrite levels in serum samples and peripheral blood mononuclear cell culture supernatants of migraine patients and healthy subjects indicated that migraine patients possess an activated nitric oxide synthesis pathway (t ₀ vs. C F=8.16,P<0.01 and F=16.2,P<0.01, respectively). As expected, in the migraine patients treated with the nitric oxide donor, a marked increase of nitrite levels was observed in sera (t ₁ vs.t ₀ P<0.05,t=3.05). In contrast, during the nitric oxide donor-induced migraine attacks a statistically significant decrease of nitrite levels in peripheral blood mononuclear cell culture supernatants was observed (t ₁ vs.t ₀ P<0.01,t=−4.03), whereas a significant increase of nitrite in total cell extracts was detected (t ₁ vs.t ₀ P<0.001,t=−6.89). These preliminary data suggest that nitric oxide could be involved in the neurovascular modifications leading to a migraine attack.     

Effect of pirfenidone on pulmonary fibrosis due to paraquat poisoning in rats

Background. This study investigated the effectiveness of pirfenidone compared with antioxidants, in the prevention of pulmonary fibrosis and increasing the survival in acutely paraquat poisoned rats. Methods. Five groups of ten rats were included in this study. Three groups were poisoned with intraperitoneal injection of 15 mg/kg paraquat. Among these poisoned groups, one group was treated with vitamin C (500 mg/kg, intraperitoneal), vitamin E (200 mg/kg, intraperitoneal) and N-acetylcysteine (250 mg/kg, intravenous); two others were treated with either normal saline or pirfenidone (200 mg/kg, intravenous); two groups were not poisoned and received normal saline or pirfenidone (200 mg/kg, intravenous). All injections except paraquat were repeated in four consecutive days. On the 15th day of study a semi-quantitative determination of lung fibrosis was done using Ashcroft staging criteria on the lung sections. Results. Pirfenidone decreased paraquat induced lung fibrosis (p?<?0.001) while antioxidants did not decrease the lung fibrosis (p =?0.413). Life expectancy decreased in paraquat + normal saline (11 days, 95% CI 7.94–14.05) and paraquat + antioxidant (11 days, 95% CI 7.77–14.23) groups. The increase in the survival of rats in paraquat/pirfenidone group was insignificant (13.4 days, 95% CI 11.13–15.67). Conclusion. This study showed that pirfenidone is able to decrease pulmonary fibrosis following paraquat poisoning in a rat model.