Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun poisoning

Worek, Franz; Kleine, A.; Szinicz, L.

doi:10.1177/096032719501400803

Cited by 11 publications

(3 citation statements)

References 36 publications

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“…Our results showing an initial hypertensive response with a more delayed hypotension effect are consistent with a number of studies, including studies of rats with DFP intoxication (Yen et al 2001 ), rabbits with paraoxon exposure (Kullmann and Uerdingen 1978 ), and hens with tabun exposure (Worek et al 1995 ). Smith and colleagues showed that administration of a muscarinic receptor agonist decreased BP but a hypertensive response was observed when co-administered with a peripheral muscarinic receptor antagonist, suggesting that activation of central muscarinic receptors increased BP (Smith et al 2001 ).…”

Section: Discussionsupporting

confidence: 91%

Cardiovascular responses of adult male Sprague–Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone

Pan,

Bruun,

Lein

et al. 2024

Arch Toxicol

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Recent experimental evidence suggests combined treatment with midazolam and allopregnanolone is more effective than midazolam alone in terminating seizures triggered by acute organophosphate (OP) intoxication. However, there are concerns that combined midazolam and allopregnanolone increases risk of adverse cardiovascular events. To address this, we used telemetry devices to record cardiovascular responses in adult male Sprague–Dawley rats acutely intoxicated with diisopropylfluorophosphate (DFP). Animals were administered DFP (4 mg/kg, sc), followed immediately by atropine (2 mg/kg, i.m.) and 2-PAM (25 mg/kg, i.m.). At 40 min post-exposure, a subset of animals received midazolam (0.65 mg/kg, im); at 50 min, these rats received a second dose of midazolam or allopregnanolone (12 mg/kg, im). DFP significantly increased blood pressure by ~ 80 mmHg and pulse pressure by ~ 34 mmHg that peaked within 12 min. DFP also increased core temperature by ~ 3.5 °C and heart rate by ~ 250 bpm that peaked at ~ 2 h. Heart rate variability (HRV), an index of autonomic function, was reduced by ~ 80%. All acute (within 15 min of exposure) and two-thirds of delayed (hours after exposure) mortalities were associated with non-ventricular cardiac events within 10 min of cardiovascular collapse, suggesting that non-ventricular events should be closely monitored in OP-poisoned patients. Compared to rats that survived DFP intoxication without treatment, midazolam significantly improved recovery of cardiovascular parameters and HRV, an effect enhanced by allopregnanolone. These data demonstrate that midazolam improved recovery of cardiovascular and autonomic function and that the combination of midazolam and allopregnanolone may be a better therapeutic strategy than midazolam alone.

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Section: Discussionsupporting

confidence: 91%

Cardiovascular responses of adult male Sprague–Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone

Pan,

Bruun,

Lein

et al. 2024

Arch Toxicol

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“…The most dramatic increases in PR with PB pretreatment and postexposure antidotal administration are seen with exposure to soman (GD). PB also significantly enhanced the efficacy of atropine and 2-pralidoxime chloride against tabun (GA) both in mice and in guinea pigs (Koplovitz et al 1992a) and achieved PRs of 4 to 12 in exposed animals (Joiner et al 1988;Koplovitz and Stewart 1994), although a subsequent study (Worek et al 1995b) warned that PB pretreatment in guinea pigs could enhance circulatory depression induced by postexposure treatment with atropine and oximes. The PR of postexposure antidotal treatment with atropine and an oxime in poisoning by GF was found to be 1.4 in the mouse and 2.7 in the guinea pig (Stewart and Koplovitz 1993); the addition of PB pretreatment in these species did not change the PR in the mouse and raised the PR in the guinea pig from 2.7 only minimally (and not significantly), to 3.4 (Stewart and Koplovitz 1993).…”

Section: How Does Pb Work As a Pretreatment For Nerve-agent Intoxicatmentioning

confidence: 99%

Clinical Considerations in the Use of Pyridostigmine Bromide as Pretreatment for Nerve-Agent Exposure

Madsen¹,

Hurst²,

MacIntosh³

et al. 2003

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“…¤ Signi cant, p • :05 versus baseline, ANOVA with Dunnett's post hoc tests. Worek, Kleine, and Szinicz (1995) also studied the effects of PB (0.05 ¹mol/kg) in urethane-anesthetized guinea pigs. They demonstrated a decrease in mean arterial pressure, but found no change in heart rate or respiratory minute volume.…”

Section: Figurementioning

confidence: 99%

Cardiorespiratory Effects Following Acute Exposure to Pyridostigmine Bromide and/or N,N-Diethyl-m-toluamide (DEET) in Rats

2002

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The acute lethal interaction that occurs in rodents when high doses of a peripherally restricted cholinesterase inhibitor, pyridostigmine bromide (PB), and the insect repellent N, N-diethyl-m-toluamide (DEET) are combined was first described during studies of chemical mixtures that were targeted as potential causative agents of Gulf War illnesses. This study was intended to provide insight into possible mechanisms of that lethal interaction. Following a single intraperitoneal injection of PB (2 mg/kg) and/or DEET (300 or 500 mg/kg), respiratory activity was measured in conscious freely moving rats using whole-body plethysmography. Cardiovascular function was also monitored simultaneously through an arterial catheter. PB (2 mg/kg) given alone stimulated respiration and increased blood pressure. Arterial pH levels were decreased, whereas pO(2) and pCO(2) remained at control levels. Administration of DEET (300 mg/kg) alone increased tidal volume and decreased blood pressure. Blood gases and pH levels were unaltered. A higher dose of DEET (500 mg/kg) also decreased respiratory and heart rate. Coadministration of PB (2 mg/kg) and DEET (300 mg/kg) increased tidal volume, decreased arterial pH, and elevated pCO(2). Heart rate and blood pressure declined progressively after drug coadministration. Pretreatment with atropine methyl nitrate (AMN), a peripherally selective competitive antagonist at nicotinic and muscarinic receptor sites, reduced the individual effects of PB or DEET, and significantly increased survival after coexposure to these agents. Although changes in respiratory function may have contributed to the lethal interaction, it was concluded that the primary cause of death was circulatory failure.

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Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun poisoning

Cited by 11 publications

References 36 publications

Cardiovascular responses of adult male Sprague–Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone

Cardiovascular responses of adult male Sprague–Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone

Clinical Considerations in the Use of Pyridostigmine Bromide as Pretreatment for Nerve-Agent Exposure

Cardiorespiratory Effects Following Acute Exposure to Pyridostigmine Bromide and/or N,N-Diethyl-m-toluamide (DEET) in Rats

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