Comprehensive Review of the Mechanistic Approach and Related Therapies to Cardiovascular Effects of Aluminum Phosphide
Aluminum Phosphide (AlP) is an active ingredient of fumigant pesticide which is commonly used in developing countries in order to control pests in stored grain. Acute poisoning with AlP usually occurs in committed suicide through ingestion of its tablets. AlP releases fatal phosphine gas in contact with hydrochloric acid of the stomach. Its detrimental clinical features may range from nausea and headache to vital organ failure and death. However, cardiovascular complications and refractory hypotension are the main cause of death. The exact mechanism of phosphine has not been proved in humans. However, it seems to work as a mitochondrial toxin with inhibition of cytochrome oxidase and cellular oxygen utilization. Since there is no specific antidote for acute AlP poisoning, management of cardiovascular disorders can be an appropriate approach to save poisoned patients. This article reviews cardiovascular toxicities associated with AlP and current therapeutic approaches and tries to clarify possible ways to treat this complication.
Received: January 16, 2014;
Accepted: February 16, 2014;
Published: May 13, 2014
Aluminum Phosphide (AlP) is used as a fumigant insecticide and rodenticide
in protection of grains during the storage and transportation process (Mehrpour
and Singh, 2010). This agent is widely used in developing countries for
several reasons such as being highly potent and cost benefit, having no effect
on seed viability and leaving little residue on food grains (Bumbrah
et al., 2012; Mostafalou et al., 2013;
Birnbaum et al., 1997). Poisoning with this compound can occur through
ingestion of salts or inhalation of phosphine gas. Phosphine is generated from
AlP after exposure to the water or an acidic media such as the acidic contents
of the stomach (Proudfoot, 2009). Due to lack of a
specific antidote, the mortality rate is more than 70% of the intoxicated cases
(Anand et al., 2011; Singh
et al., 1989; Singh et al., 1991).
Typical features of AlP poisoning are gastrointestinal disorders, refractory
hypotension and cardiogenic shock (Mehrpour et al.,
2012). Left ventricle and septum hypokinesia, ejection fractions reduction
(Bhasin et al., 1991), raised systemic venous
pressure, normal pulmonary artery wedge pressure, inadequate systemic vasoconstriction
and electrocardiographic (ECG) abnormalities (Kalra et
al., 1991; Hosseinian et al., 2011)
are cardiovascular features of phosphine poisoning. This agent can cause a multi
organ failure such as heart failure that is the main cause of death within 12-24
h after acute exposure (Chugh et al., 1991;
Bogle et al., 2006; Mostafazadeh
and Farzaneh, 2012; Moghadamnia, 2012; Singh
et al., 1991). Thus, it is essential to focus on cardiovascular complications
of phosphine poisoning to find an effective and appropriate therapeutic strategy
because if cardiac dysfunction and arrhythmias improve, most likely the patients
will survive from acute phosphine poisoning through supportive cares. In this
study we reviewed all the studies related to cardiovascular toxicity of AlP.
Since the exact underlying mechanism of cardiotoxicity and peripheral circulatory
failure caused by phosphine is still unknown, this study can reveal the direction
of future studies.
The keywords aluminum phosphide,
were searched in bibliographic databases including PubMed, Web of Science, Google
Scholar and Scopus between years 1980 and 2014. The title and abstracts of all
paper were scrutinized and read initially and those that obviously did not meet
inclusion criteria were excluded.
RESULTS AND DISCUSSION
Electrocardiography findings and refractory hypotension: AlP poisoning
is known to be associated with various ECG abnormalities, ranging from acute
myocardial infarction, to atrial fibrillation, premature supraventricular or
ventricular contractions, ST segment elevation/depression, bundle branch blocks,
PR and QRS interval prolongation and sinoatrial block (Udriste
et al., 2013; Khosla et al., 1988;
Gurjar et al., 2011; Moghadamnia,
2012). The incidence of ECG and ECG abnormalities reported in various studies
are 45% (Shadnia et al., 2010; Soltaninejad
et al., 2012), 65% (Shadnia et al., 2009),
80% (Gupta et al., 1995) and 50% (Chugh
et al., 1991) in phosphine poisoned patients that summarized in the
Table 1. ECG changes are mostly non-specific indicator for
phosphide poisoning (Chugh et al., 1991; Anand
et al., 2011) but evaluations of ECG parameters can predict the severity
and usefulness of therapeutic strategies in the poisoned patients. Soltaninejad
et al. (2012) found that there was a significant correlation between
ECG abnormalities and mortality and subsequently, anti-arrhythmic agents can
be used as prophylactic treatment in acute AlP intoxication. In the survey by
Shadnia et al. (2009, 2010)
the ECG abnormalities were observed in 65.6% of cases who did not survive and
most of them had ST segment depression and sinus tachycardia and there was a
significant difference between survival and non-survival cases according to
ECG abnormality. On the other hand, Chugh et al.
(1991) reported no relationship between the ECG abnormalities and mortality.
In another study, the ECG abnormalities were noted in 28 cases (58.7%) at the
time of admission and was considered as prognostic factor along with other factors
such as shock, low Glasgow coma scale for AlP poisoning (Louriz
et al., 2009). In Kaushiks case report, ECG abnormalities along
with T-wave abnormalities were observed which is attributed to subendocardial
infarction rather than toxic myocarditis alone, because subendocardium which
is the well-perfused zone of myocardium, is most vulnerable to any reduction
in coronary flow and cellular hypoxia (Kaushik et al.,
2007). In another case report, broad QRS complex, ST-T changes along with
raised CK-mb were observed which indicates severe myocardial injury (Shah
et al., 2009). In three other cases, Brugada type pattern in combination
with various ECG abnormalities were observed in AlP poisoning (Mahajan
et al., 2012; Udriste et al., 2013;
Nayyar and Nair, 2009). Brugada syndrome is a disorder
presenting with ST segment elevation, right bundle branch block, susceptibility
to ventricular tachycardia and structurally normal heart (Mahajan
et al., 2012). It is most probably due to hypomagnesaemia caused
by direct toxic effect of phosphine on cardiac tissue (Mahajan
et al., 2012). Khosla et al. (1988)
reported that ECG abnormalities were detected in 6 of their 11 patients and
there was metabolic acidosis in all 6. ECG changes completely associate with
|| Cardiac electrophysiology disorders and evidences of hypotension
in associated with AlP poisoning
|BP: Blood pressure, SBP: Systolic blood pressure (mmHg), DBP:
Diastolic blood pressure (mmHg), BBB: Bundle branch block, LVEF: Left ventricle
Metabolic acidosis which is probably caused by blockage of oxidative phosphorylation
and cellular hypoxia (Mehrpour et al., 2008),
should be treated by administering sodium bicarbonate (Bumbrah
et al., 2012; Gurjar et al., 2011;
Mehrpour et al., 2008).
Refractory hypotension and shock which have been increasingly seen, are other
fatal cardiovascular complications following acute AlP poisoning (Khosla
et al., 1988). Death after 24 h occurs usually owing to shock, cardiac
dysrhythmia, metabolic acidosis and acute respiratory distress syndrome (Moghadamnia,
2012). Non-survivors have more refractory hypotension and acidosis than
the survivors (Moghadamnia, 2012). The exact mechanism
of refractory hypotension and intractable shock is not clear; however, they
possibly occur due to arrhythmia, conduction disturbance and myocardial damage
and myocardial depression. Moreover, the peripheral circulatory failure owing
to capillary dysfunction or widespread small vessel damage can lead to peripheral
vasodilatation, resulting in refractory hypotension and shock (Anand
et al., 2011). Refractory hypotension and shock are usually unresponsive
to conventional treatment; however, managing AlP poisoning, especially resuscitation
of shock and institution of supportive measures should be started as soon as
the patients arrival. All acute AlP poisoned patients require continuous
invasive hemodynamic monitoring and early resuscitation with fluid and vasoactive
agents. Norepinephrine or phenylephrine, dopamine, dobutamine and anti-arrhythmic
agents can be used to treat refractory hypotension and shock.
Several studies which have been published about the beneficial effect of magnesium,
show that treatment of hypomagnesaemia by magnesium sulphate can decrease AlP
cardiac toxicity (Katira et al., 1990;
Gupta and Ahlawat, 1995; Chugh et al., 1994b)
and reduce the mortality rate from 90-50% of poisoned patients (Jadhav
et al., 2012; Anand et al., 2011;
Chugh et al., 1994a; Chugh
et al., 1997; Singh et al., 1990;
Siwach et al., 1994). Baeeri
et al. (2013) reported that 25Mg2+-carrying
nanoparticle significantly elevates blood pressure and heart rate of rats poisoned
with AlP (Baeeri et al., 2013). There is only
one study in 1994 that claimed supplemental magnesium cannot improve the survival
rate of AlP poisoned patients (Siwach et al., 1994).
Also, Jadhav et al. (2012) reported that in
addition to magnesium sulfate and electrocardioversion, amiodarone has beneficial
role in treatment of ventricular tachycardia caused by AlP poisoning (Jadhav
et al., 2012). In another study, Mehrpour et al. reported that digoxin
by elevation of myocardial contractility and blood pressure is useful in management
of cardiogenic shock (Mehrpour et al., 2011,
2012). Although the use of digoxin does not seem to
be logical, it can be considered as an alternative treatment of the cardiogenic
shock induced by AlP poisoning. Another approach in management of acute AlP
poisoning is administration of high doses of glucagon (Arefi
and Tabrizchi, 2012; Torabi, 2013). Glucagon is
usually used as cardiac inotropic agent in the treatment of shock caused by
beta-blockers and calcium channel blockers poisoning (Arefi
and Tabrizchi, 2012). Inotropic action of glucagon is mediated by elevation
of intracellular cAMP and calcium (Arefi and Tabrizchi, 2012).
At the end, there is an interesting study about the beneficial effect of Intra-aortic
Balloon Pump (IABP) as a cardiocirculatory assist device for treatment of cardiogenic
shock following AlP poisoning (Siddaiah et al., 2009). IABP can mechanically
support the heart, decrease the afterload and improve perfusion to the vital
organs and coronary arteries (Siddaiah et al., 2009;
Elabbassi et al., 2013; David
et al., 2000). Intravascular hydroxyethyl starch solution (a colloid
volume expander) is another route for treatment of severe hypotension that decrease
the extravascular leakage of albumin and fluids (Marashi
et al., 2011).
Possible mechanisms of cardiotoxicity: The exact mechanism of toxicity
of phosphine remains still unclear. It seems that main part of its toxicity
is done through non-specific mechanisms due to the small size of the phosphine
molecule (Nath et al., 2011). However, several
mechanisms have been proposed for phosphine toxicity which is discussed in below.
Mitochondrial disorders and energy depletion: As previously mentioned,
one of the main target organs of phosphine is heart. The heart needs large amounts
of energy to maintain its contractile performance. Adenosine Triphosphate (ATP)
works as immediate source of energy, however intracellular ATP is limited. Phosphine
has been reported to decrease cardiac energy reserves such as ATP (Anand
et al., 2011; Baeeri et al., 2013).
Phosphine can cause myocardial energy depletion due to changes in mitochondrial
morphology (Anand, 2009; Bumbrah
et al., 2012). Ultrastructural changes which were observed in the
heart and other tissues, showed mitochondrial injury (Anand
et al., 2011), including dysmorphic and swollen mitochondria with
enlarged and disrupted cristae (Anand et al., 2011;
Bumbrah et al., 2012; Proudfoot, 2009).
In view of the fact that oxidative phosphorylation is strictly dependent on
the structure and integrity of the inner mitochondrial membrane, even if the
activity of mitochondrial complexes is not inhibited directly following phosphine
exposure, it can be affected by changes in mitochondrial morphology (Proudfoot,
2009). Numerous studies demonstrated that phosphine can cause myocardial
energy depletion due to inhibition of activity of cytochrome c oxidase as an
enzyme of the Electron Transport Chain (ETC) (Singh et
al., 2006; Bumbrah et al., 2012; Gurjar
et al., 2011). Phosphine disturbs the mitochondrial morphology,
inhibits complexes I, II, IV of the mitochondrial ETC and reduces the oxidative
respiration by 70% leading to severe drop in the mitochondrial membrane potential
(Proudfoot, 2009; Bumbrah et
al., 2012). Some other agents which are known to protect mitochondrial
oxidative phosphorylation such as hydroxycobalamine (Jones,
2008), mitoQ (Tauskela, 2007; Smith
and Murphy, 2010) and vitamin C should also be tried (Singh,
Oxidative stress: Like other kinds of pesticides (Mostafalou
et al., 2013; Mostafazadeh and Farzaneh, 2012),
there is strong evidence that oxidative stress can be induced by phosphine and
the heart is not secure from damaging effects of these reactive radicals that
increased through reduction of glutathione level (Chugh
et al., 1995; Mehrpour et al., 2012;
Kariman et al., 2012). Phosphine induces the production of free radicals
not only through inhibition of the antioxidant enzymes (catalase and peroxidase)
and reduction of glutathione level, but also via disruption of oxidative phosphorylation
(Nath et al., 2011; Anand
et al., 2011; Mehrpour et al., 2012).
Oxidative stress and especially mitochondrial cytochrome C oxidase inhibition
can lead to morphological and functional disorder of heart. The membrane action
potential damage caused by AlP is due to lipid peroxidation of cell membrane
(Mehrpour et al., 2012) and it seems that probable
mechanism of magnesium in improvement of arrhythmias is to stabilize the membrane
action potential (Katira et al., 1990; Chugh
et al., 1997). Based on these studies, oxidative stress and lipid
peroxidation can be considered as a main cause of myocardial injury due to AlP
poisoning. There are several studies focused on these pathways for planning
new therapeutic strategies; N-acetyl cysteine as an antioxidant and cytoprotective
agent (Azad et al., 2001; Hsu
et al., 2002) can reduce myocardial oxidative injury and increase
survival time (Bogle et al., 2006). Other options
for the management of cardiac complication of AlP are antiischemic drugs such
as trimetazidine. These agents have protective effects on myocardium through
decreasing the production of oxygen-derived free radicals and stimulating the
oxidative metabolism of glucose (Moghadamnia, 2012; Duenas
et al., 1999). Magnesium nanoparticle in addition to treatment of
hypotension and cardiac shock can elevate the intracardiac magnesium levels,
reduce lipid peroxidation and improve mitochondrial function (Baeeri
et al., 2013).
Histopathological and biochemical changes: Mild to severe myocyte vacuolation,
areas of myocytolysis and degeneration were specially revealed in the left ventricle
and interventricular septum following AlP poisoning which are all indicative
of myocardial injury (Shah et al., 2009). Other
histopathological findings showed varying degrees of congestion in the heart
and other organs, similar to those produced by hypoxic injury (Louriz
et al., 2009; Bumbrah et al., 2012)
and myocardial necrosis (Khosla et al., 1988;
Abder-Rahman, 2009). There were some reports regarding
inhalation of phosphine gas and cardiovascular findings varying from congestion,
focal myocardial infiltration, to small-vessel injury (Chugh
et al., 1991; Wilson et al., 1980;
Abder-Rahman, 2009). In a study by Abder-Rahman
(2009) autopsy findings revealed subendocardial flame hemorrhages in the
heart of two sisters and minimal neutrophil inflammatory in the cardiac muscle
of the 6-year-old child. Anand et al. (2012)
reported myocyte swelling, disarray and interstitial edema in cardiac tissue
using electron microscopy and they thought tissue histology findings are non-specific.
In Rahbar Taromsaris study, histopathological findings in myocardium showed
congestion (86%), necrosis (7%) and leukocyte infiltration (7%) (Taromsari
et al., 2011). Jadhav et al. (2012)
disclosed contraction band necrosis, edema, hemorrhage and pyknosis of cardiac
myocyte nuclei in the postmortem histological examination of myocardium. It
seems there is a direct correlation between heart tissue injury and cellular
hypoxia-induced mitochondrial dysfunction. Biochemical findings also confirm
myocardial injury following AlP poisoning. Creatine phosphokinase (CPK), CPK-myocardial
band (CPK-mb) and troponin-T (TnT) are considered as biochemical markers of
cardiac muscle injury (Soltaninejad et al., 2012).
Elevation of serum levels of CPK-mb and LDH by many folds has been seen in AlP
poisoning and indicates myocardial damage (Anand et
al., 2012; Shah et al., 2009; Wilson
et al., 1980). However, Duenas et al.
(1999) reported that CPK levels were elevated without any changes in CPK-mb
fraction. Soltaninejad et al. (2012) revealed
that the serum cardiac TnT has a positive relationship to the mortality but
increase in CPK or the CPK to CPK-mb ratio does not have such relationship (Soltaninejad
et al., 2012). In another case reported by Nayyar
and Nair (2009) TnT and CPK levels were normal at admission. Changing in
CPK, CPK-mb, TnT levels as a clinical and laboratory indicator of cardiac muscle
injury is sometimes observed, but reports are controversial.
|| Cardiotoxicity mechanisms involved in phosphine poisoning
and its possible treatment strategies
Because in some case reports which were reported by Nayyar
and Nair (2009) Bogle et al. (2006) serum
levels of these markers were in normal range following acute AlP poisoning (Bogle
et al., 2006; Nayyar and Nair, 2009) but
in other reports, their levels were elevated, indicating myocardial damage (Kaushik
et al., 2007; Shah et al., 2009;
Akkaoui et al., 2007; Singh
et al., 2011). On the other hand, some researchers did not discover
any evidence about myocardial damage on autopsy in any of their patients (Khosla
et al., 1988; Singh, 1989). Thus, it is
concluded that elevated levels of these enzymes confirm myocardial injury but
their normal levels cannot disprove phosphine cardiotoxicity.
Taking collectively, AlP is used as insecticide and rodenticide and is very
common in suicide attempts. The heart is the predominantly affected organ and
the most of the poisoned patients die due to cardiovascular complications (Bumbrah
et al., 2012). Clinical manifestation of cardiac failure varies depending
on the dosage and duration of consumption and include peripheral circulatory
failure and hypotension (Alter et al., 2001;
Bayazit et al., 2000; Ragone
et al., 2002), congestion of the heart, separation of myocardial
fibres by edema, fragmentation of fibres, non-specifc vacuolation of myocytes,
focal necrosis, neutrophil and eosinophil infiltration (Katira
et al., 1990; Sinha et al., 2005).
The ECG changes have been studied in several studies and include atrial fibrillation,
tachycardia, QRS complex and ST-T changes and bundle branch blocks. Although
the exact underlying mechanism of cardiotoxicity and peripheral circulatory
failure caused by phosphine is still unknown, the possible mechanisms are discussed
in this article and summarized in Fig. 1. It seems that the
main effect of this poison is disruption of cellular oxygen utilization and
hypoxia through refractory hypotension and respiratory system insufficiency.
This hypoxia can cause irreparable damages on mitochondria as the main site
of oxygen consumption. Therefore, the first priority in treatment of phosphine
poisoning is correction of hypotension and improvement of tissue oxygen levels
through ventilation support and oxygenation. Extracorporal Membrane Oxygenation
(ECMO) is a novel technique for supplying oxygen and it may have a beneficial
role in management of AlP poisoning (Elabbassi et al.,
2013). On the other hand, direct effects of phosphine on cardiac tissue
mediated through inhibition of mitochondrial toxins, induction of oxidative
damage and reduction of energy production should be discussed further in the
future studies. Focus on the inhibition of oxidative stress and mitochondrial
injuries along with the remediation of refractory hypotension can be a useful
therapeutic strategy in treatment of AlP poisoned patient.
This invited study is the outcome of an in-house financially non-supported
study. Authors thank Tehran University of Medical Sciences, National Elite Foundation,
Iran National Science Foundation. Authors have no conflict of interest.
Abder-Rahman, H.A., 2009.
Alumnium phosphide fatalities at mild exertion in asymptomatic children: A clue to understand the variations of the autopsy findings. J. Forensic Legal Med., 16: 312-315.CrossRef | Direct Link |
Akkaoui, M., S. Achour, K. Abidi, B. Himdi, A. Madani, A.A. Zeggwagh and R. Abouqal, 2007.
Reversible myocardial injury associated with aluminum phosphide poisoning. Clin. Toxicol., 45: 728-731.CrossRef | Direct Link |
Alter, P., W. Grimm and B. Maisch, 2001.
Lethal heart failure caused by aluminium phosphide poisoning. Intensive Care Med., 27: 327-327.CrossRef | Direct Link |
Anand, R., B.K. Binukumar and K.D. Gill, 2011.
Aluminum phosphide poisoning: An unsolved riddle. J. Applied Toxicol., 31: 499-505.CrossRef | PubMed | Direct Link |
Anand, R., P. Kumari, A. Kaushal, A. Bal and W.Y. Wani et al
Effect of acute aluminum phosphide exposure on rats: A biochemical and histological correlation. Toxicol. Lett., 215: 62-69.CrossRef | Direct Link |
Arefi, M. and N. Tabrizchi, 2012.
Could glucagon be a therapeutic option in the management of acute aluminium phosphide toxicity? Endocrinol. Metab. Synd., Vol. 1.Direct Link |
Azad, A., S.B. Lall and S. Mittra, 2001.
Effect of N-acetylcysteine and L-NAME on aluminium phosphide induced cardiovascular toxicity in rats. Acta Pharmacol. Sin., 22: 298-304.PubMed | Direct Link |
Baeeri, M., M. Shariatpanahi, A. Baghaei, S.F. Ghasemi-Niri and H. Mohammadi et al
On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide. Toxicol. Ind. Health, 29: 126-135.CrossRef | PubMed | Direct Link |
Bayazıt, A.K., A. Noyan and A. Anarat, 2000.
A child with hepatic and renal failure caused by aluminum phosphide. Nephron, 86: 517-517.CrossRef | Direct Link |
Bhasin, P., H.S. Mita and A. Mitra, 1991.
An echocardiographic study in aluminium phosphide poisoning. J. Assoc. Physicians. India, 39: 851-851.
Birnbaum, Y., S. Sclarovsky, B. Zlotikamien, I. Herz, A. Chetrit, L. Olmer and G.I. Barbash, 1997.
Abnormal q waves on the admission electrocardiogram of patients with first acute myocardial infarction: Prognostic implications. Clin. Cardiol., 20: 477-481.CrossRef | Direct Link |
Bogle, R.G., P. Theron, P. Brooks, P.I. Dargan and J. Redhead, 2006.
Aluminium phosphide poisoning. Emerg. Med. J., 23: e3-e3.CrossRef | Direct Link |
Bumbrah, G.S., K. Krishan, T. Kanchan, M. Sharma and G.S. Sodhi, 2012.
Phosphide poisoning: A review of literature. Forensic Sci. Int., 214: 1-6.CrossRef | Direct Link |
Chugh, S.N., K. Chugh, S. Ram and K.C. Malhotra, 1991.
Electrocardiographic abnormalities in aluminium phosphide poisoning with special reference to its incidence, pathogenesis, mortality and histopathology. J. Indian Med. Assoc., 89: 32-35.Direct Link |
Chugh, S.N., P. Kamar, A. Sharma, K. Chugh, A. Mittal and B. Arora, 1994.
Magnesium status and parenteral magnesium sulphate therapy in acute aluminum phosphide intoxication. Magnesium Res., 7: 289-294.Direct Link |
Chugh, S.N., T. Kolley, R. Kakkar, K. Chugh and A. Sharma, 1997.
A critical evaluation of anti-peroxidant effect of intravenous magnesium in acute aluminium phosphide poisoning. Magnesium Res., 10: 225-230.Direct Link |
Chugh, S.N., P. Kumar, H.K. Aggarwal, A. Sharma, S.K. Mahajan and K.C. Malhotra, 1994.
Efficacy of magnesium sulphate in aluminium phosphide poisoning-comparison of two different dose schedules. J. Assoc. Phys. India, 42: 373-375.Direct Link |
Chugh, S.N., A. Mittal, S. Seth and K. Chugh, 1995.
Lipid peroxidation in acute aluminium phosphide poisoning. J. Assoc. Phys. India, 43: 265-266.PubMed |
David, J.S., P.Y. Gueugniaud, A. Hepp, P. Gaussorgues and P. Petit, 2000.
Severe heart failure secondary to 5-fluorouracil and low-doses of folinic acid: Usefulness of an intra-aortic balloon pump. Crit. Care Med., 28: 3558-3560.Direct Link |
Duenas, A., J.L. Perez-Castrillon, M.A. Cobos and V. Herreros, 1999.
Treatment of the cardiovascular manifestations of phosphine poisoning with trimetazidine, a new antiischemic drug. Am. J. Emerg. Med., 17: 219-220.CrossRef | PubMed | Direct Link |
Elabbassi, W., M.A. Chowdhury and A.A.N. Fachtartz, 2013.
Severe reversible myocardial injury associated with aluminium phosphide toxicity: A case report and review of literature. J. Saudi Heart Assoc.CrossRef |
Gupta, M.S., A. Malik and V.K. Sharma, 1995.
Cardiovascular manifestations in aluminium phosphide poisoning with special reference to echocardiographic changes. J. Assoc. Physicians India, 43: 773-774.PubMed |
Gupta, S. and S.K. Ahlawat, 1995.
Aluminum phosphide poisoning: A review. J. Toxicol. Clin. Toxicol., 338: 19-24.PubMed |
Gurjar, M., A.K. Baronia, A. Azim and K. Sharma, 2011.
Managing aluminum phosphide poisonings. J. Emerg. Trauma Shock, 4: 378-384.Direct Link |
Hosseinian, A., N. Pakravan, A. Rafiei and S.M. Feyzbakhsh, 2011.
Aluminum phosphide poisoning known as rice tablet: A common toxicity in North Iran. Indian J. Med. Sci., 65: 143-150.Direct Link |
Hsu, C.H., B.C. Chi, M.Y. Liu, J.H. Li, C.J. Chen and R.Y. Chen, 2002.
Phosphine-induced oxidative damage in rats: Role of glutathione. Toxicology, 179: 1-8.CrossRef | Direct Link |
Jadhav, A.P., M.B. Nusair, A. Ingole and M.A. Alpert, 2012.
Unresponsive ventricular tachycardia associated with aluminum phosphide poisoning. Am. J. Emergency Med., 30: e633-635.CrossRef | PubMed |
Jones, K.R., 2008.
Hydroxocobalamin (Cyanokit): A new antidote for cyanide toxicity. Adv. Emergency Nurs. J., 30: 112-121.CrossRef |
Kalra, G.S., I.S. Anand, I. Jit, B. Bushnurmath and P.L. Wahi, 1991.
Aluminium phosphide poisoning: Haemodynamic observations. Indian Heart J., 43: 175-178.Direct Link |
Kariman, H., K. Heydari, M. Fakhri, A. Shahrami, A.A. Dolatabadi, H.A. Mohammadi and M. Gharibi, 2012.
Aluminium phosphide poisoning and oxidative stress. J. Med. Toxicol., 8: 281-284.CrossRef | Direct Link |
Katira, R., G.P. Elhence, M.L. Mehrotra, S.S. Srivastava, A. Mitra, R. Agarwala and A. Ram, 1990.
A study of aluminum phosphide (AlP) poisoning with special reference to electrocardiographic changes. J. Assoc. Phys. India, 38: 471-473.Direct Link |
Kaushik, R.M., R. Kaushik and S.K. Mahajan, 2007.
Subendocardial infarction in a young survivor of aluminium phosphide poisoning. Human Exp. Toxicol., 26: 457-460.CrossRef |
Khosla, S.N., N. Nand and P. Kumar, 1988.
Cardiovascular complications of aluminum phosphide poisoning. Angiology, 39: 355-359.CrossRef |
Louriz, M., T. Dendane, K. Abidi, N. Madani, R. Abouqal and A.A. Zeggwagh, 2009.
Prognostic factors of acute aluminum phosphide poisoning. Indian J. Med. Sci., 63: 227-234.Direct Link |
Mahajan, D.S., J.B. Singh and R.K. Chaudhry, 2012.
Brugada type ecg pattern in a case of aluminium phosphide poisoning. J. Evol. Med. Dental Sci., 1: 932-935.Direct Link |
Marashi, S.M., M. Arefi, B. Behnoush, M.G. Nasrabad and Z.N. Nasrabadi, 2011.
Could hydroxyethyl starch be a therapeutic option in management of acute aluminum phosphide toxicity? Med. Hypotheses, 76: 596-598.CrossRef |
Mehrpour, O., M. Dolati, K. Soltannejad, S. Shadnia and B. Nazparvar, 2008.
Evaluation of histopathological changes in fatal aluminum phosphide poisoning. Indian J. Forensic Med. Toxicol., 2: 34-36.
Mehrpour, O., E. Farzaneh and M. Abdollahi, 2011.
Successful treatment of aluminum phosphide poisoning with digoxin: A case report and review of literature. Int. J. Pharmacol., 7: 761-764.CrossRef | Direct Link |
Mehrpour, O., M. Jafarzadeh and M. Abdollahi, 2012.
A systematic review of aluminium phosphide poisoning. Arch. Ind. Hygiene Toxicol., 63: 61-73.CrossRef | Direct Link |
Mehrpour, O. and S. Singh, 2010.
Rice tablet poisoning: A major concern in Iranian population. Hum. Exp. Toxicol., 29: 701-702.CrossRef | Direct Link |
Moghadamnia, A.A., 2012.
An update on toxicology of aluminum phosphide. DARU J. Pharma. Sci., Vol 20.CrossRef | Direct Link |
Mostafalou, S., S. Karami-Mohajeri and M. Abdollahi, 2013.
Environmental and population studies concerning exposure to pesticides in iran: A comprehensive review. Iran. Red Crescent Med. J., Vol 15.CrossRef | Direct Link |
Mostafazadeh, B. and E. Farzaneh, 2012.
A novel protocol for gastric lavage in patients with aluminum phosphide poisoning: A double-blind study. Acta Med. Iran., 50: 530-534.PubMed | Direct Link |
Nath, N.S., I. Bhattacharya, A.G. Tuck, D.I. Schlipalius and P.R. Ebert, 2011.
Mechanisms of phosphine toxicity. J. Toxicol.CrossRef | Direct Link |
Nayyar, S. and M. Nair, 2009.
Brugada pattern in toxic myocarditis due to severe aluminum phosphide poisoning. Pacing Clin. Electrophysiol., 32: e16-e17.CrossRef | PubMed | Direct Link |
Proudfoot, A.T., 2009.
Aluminium and zinc phosphide poisoning. Clin. Toxicol. (Phila), 47: 89-100.CrossRef | PubMed | Direct Link |
Ragone, S., J. Bernstein and E. Lew, 2002.
Fatal aluminum phosphide ingestion. J. Toxicol. Clin. Toxicol., 40: 690-690.
Taromsari, M.R., P. Teymourpour and R. Jahanbakhsh, 2011.
Survey the histopathological findings in autopsy of poisoned patients with rice tablet (Aluminium phosphide
). Gums Med., 19: 56-63.
Shadnia, S., O. Mehrpour and K. Soltaninejad, 2010.
A simplified acute physiology score in the prediction of acute aluminum phosphide poisoning outcome. Indian J. Med. Sci., 64: 532-539.PubMed | Direct Link |
Shadnia, S., G. Sasanian, P. Allami, A. Hosseini, A. Ranjbar, N. Amini-Shirazi and M. Abdollahi, 2009.
A retrospective 7-years study of aluminum phosphide poisoning in Tehran: Opportunities for prevention. Hum. Exp. Toxicol., 28: 209-213.CrossRef | PubMed | Direct Link |
Shah, V., S. Baxi and T. Vyas, 2009.
Severe myocardial depression in a patient with aluminium phosphide poisoning: A clinical, electrocardiographical and histopathological correlation. Indian J. Crit. Care Med., 13: 41-43.CrossRef | Direct Link |
Siddaiah, L., S. Adhyapak, S. Jaydev, G. Shetty, K. Varghese, C. Patil and S. Iyengar, 2009.
Intra-aortic balloon pump in toxic myocarditis due to aluminium phosphide poisoning. J. Med. Toxicol., 5: 80-83.PubMed |
Singh, N., R.K. Gupta and S.L. Margekar, 2011.
Myocardial injury in celphos poisoning. J. Ind. Acad. Clin. Med., 12: 54-55.Direct Link |
Singh, R.B., S.S. Rastogi and D.S. Singh, 1989.
Cardiovascular manifestations of aluminium phosphide intoxication. J. Assoc. Physicians Ind., 37: 590-592.Direct Link |
Singh, R.B., R.B. Saharia and V.K. Sharma, 1990.
Can aluminium phosphide poisoning cause hypermagnesaemia? A study of 121 patients. Magnesium Trace Elem., 9: 212-218.Direct Link |
Singh, R.B., R.G. Singh and U. Singh, 1991.
Hypermagnesemia following aluminum phosphide poisoning. Int. J. Clin. Pharmacol. Ther. Toxicol., 29: 82-85.PubMed | Direct Link |
Singh, S., 1989.
Aluminum phosphide poisoning. Indian J. Med. Res., 90: 289-294.
Singh, S., A. Bhalla, S.K. Verma, A. Kaur and K. Gill, 2006.
Cytochrome-C oxidase inhibition in 26 aluminum phosphide poisoned patients. Clin. Toxicol., 44: 155-158.CrossRef | Direct Link |
Sinha, U.S., A.K. Kapoor, A.K. Singh, A. Gupta and R. Mehrotra, 2005.
Histopathological changes in cases of aluminium phosphide poisoning. Indian J. Pathol. Microbiol., 48: 177-180.Direct Link |
Siwach, S.B., P. Singh, S. Ahlawat, A. Dua and D. Sharma, 1994.
Serum and tissue magnesium content in patients of aluminium phosphide poisoning and critical evaluation of high dose magnesium sulphate therapy in reducing mortality. J. Assoc. Physicians India, 42: 107-110.Direct Link |
Smith, R.A.J. and M.P. Murphy, 2010.
Animal and human studies with the mitochondria‐targeted antioxidant mitoq. Ann. New York Acad. Sci., 1201: 96-103.CrossRef | Direct Link |
Soltaninejad, K., M.R. Beyranvand, S.A. Momenzadeh and S. Shadnia, 2012.
Electrocardiographic findings and cardiac manifestations in acute aluminum phosphide poisoning. J. Forensic Legal Med., 19: 291-293.CrossRef | PubMed | Direct Link |
Tauskela, J.S., 2007.
Mitoq-a mitochondria-targeted antioxidant. IDrugs, 10: 399-412.Direct Link |
Torabi, M., 2013.
Successful treatment of aluminium phosphide poisoning: A case report. Iran. J. Pharmacol. Ther., 12: 77-79.
Udriste, A.S., S. Dumitriu, M. Ceausu, D. Radu and C.O. Capatina, 2013.
Aluminium phosphide fatal poisoning associated with a brugada-like ecg pattern. Case presentation. Rom. J. Leg.Med., 21: 249-252.Direct Link |
Wilson, R., F.H. Lovejoy Jr., R.J. Jaeger and P.L. Landrigan, 1980.
Acute phosphine poisoning aboard a grain freighter epidemiologic, clinical and pathological findings. JAMA, 244: 148-150.CrossRef | Direct Link |