Regional pre- and postganglionic sympathetic activity during experimental paraoxon poisoning

Kullmann, R.; Uerdingen, Uta

doi:10.1007/bf00351769

Cited by 4 publications

(1 citation statement)

References 19 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 central effects of paraoxon on blood pressure of rabbits after intravenous administration or infusion via a vertebral artery

1982

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In the present study paraoxon (28-825 micrograms/kg, i.v.) was administered into rabbits treated with N-methylatropine (1 mg/kg). In urethane-anaesthetized rabbits pressor and depressor effects were observed. In pentobarbitone-anaesthetized rabbits, however, only depresssor effects were noticed. Dexetimide (0.25-0.5 mg/kg) prevented the pressor and depressor action of paraoxon. Furthermore, paraoxon (83-825 micrograms) was infused into a vertebral artery of pentobarbitone-anaesthetized animals. After administration via this route the depressor effect was similar to i.v. administration. 30 min after administration of paraoxon acetylcholinesterase activity was determined in the medulla oblongata, the pons and the hypothalamus. The enzyme has to be inhibited almost completely to induce an effect on blood pressure. It is concluded that the vascular effects of paraoxon seem to be mediated by a mechanism involving stimulation of central muscarinic receptors, probably by accumulated acetylcholine, which in turn induces a decrease in blood pressure.

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Regional blood flow during paraoxon infusion in rabbits

1982

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In anaesthetized and artificially ventilated rabbits an intravenous infusion of paraoxon (0.8 mg/kg) was given over 30 min. The effects on cardiac output, blood flow to various vascular beds, and on the mass discharge of the postganglionic sympathetic efferents to the spleen and kidney were monitored. Immediately following paraoxon infusion atropine (0.5 mg/kg) was injected intravenously. Within 20 min of commencing the infusion signs of increased cholinergic stimulation were observed. Between the 20th and 25th min mean arterial blood pressure, heart rate, and cardiac output fell markedly. Even before arterial blood pressure fell total peripheral resistance and regional resistance to flow through the subclavian and coeliac arteries increased significantly, whereas resistance was below control, increased regional resistance being found only in the vascular beds of the subclavian and splenic arteries. The activity in the splenic sympathetic efferents increased, while the activity in the renal efferents was sharply reduced. While an effective antidote, atropine elicited transient intestinal vasodilation and a further transient decrease in total peripheral resistance. These and other results suggest that muscarinic mechanisms are mainly responsible for the paraoxon-induced changes in regional blood flow and regional sympathetic activity. The vasodilatory effect of atropine in the intestine was probably due to a local autoregulatory mechanism.

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Regional pre- and postganglionic sympathetic activity during experimental paraoxon poisoning

Cited by 4 publications

References 19 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

The central effects of paraoxon on blood pressure of rabbits after intravenous administration or infusion via a vertebral artery

Regional blood flow during paraoxon infusion in rabbits

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