Attenuation of intestinal ischemic injury and shock by physostigmine

Verhaegh, Rabea; Petrat, Frank; Groot, Herbert de

doi:10.1016/j.jss.2014.11.003

Cited by 11 publications

(8 citation statements)

References 58 publications

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“…Protective effects by PHY have already been described in various experimental models of injury, among others during sepsis/systemic inflammation,15–17 hemorrhagic shock,18–21 and ischemia–reperfusion injury 24–26. However, in all these experimental animal studies, PHY has been administered in a prophylactic manner or early after the injury.…”

Section: Discussionmentioning

confidence: 99%

“…However, when the intervention with PHY was delayed beyond 6 hours, any beneficial effects in either survival or organ dysfunction were lost 31. During hemorrhagic shock18–21 and partly also during ischemia–reperfusion injury,24,25 PHY improves survival by increasing blood pressure and circulating blood volume (eg, due to a general adrenergic effect/central activation of the sympathetic nervous system or due to changes in the pre- and postcapillary resistance). This hypertensive effect of PHY was to be very sensitive to the applied amount,24 but acted somewhat independently to the time point of the PHY intervention 21,24,32.…”

Section: Discussionmentioning

confidence: 99%

“…Endou et al concluded that low concentrations of neostigmine may stimulate the muscarinic acetylcholine receptors directly, and that at higher concentrations, neostigmine may act as an antimuscarinic agent 34. This may explain why PHY or neostigmine doses between 30 and 100 µg/kg are predominantly protective,15–21,24–26 whereas higher (cumulative) doses of PHY or neostigmine (300 µg/kg and more) worsened the outcome from ischemia–reperfusion35 or sepsis/systemic inflammation31,36 and even caused a state of shock 37…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic effects of physostigmine during systemic inflammation

Effenberger-Neidnicht

Jägers

Verhaegh

et al. 2018

JIR

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IntroductionUsually, physostigmine is used as antidote for anticholinergic poisons in order to improve hemodynamics and cardiac output. In addition, it causes beneficial effects during sepsis when added timely. Here, we studied whether physostigmine improves hemodynamics when treatment during systemic inflammation was delayed.MethodsTwo series of randomized studies with overall 44 rats were conducted. Systemic inflammation was induced by lipopolysaccharide (LPS) infusion (0.5 mg LPS/kg×h). Physostigmine (PHY) was intravenously applied after an LPS infusion period of 90 minutes (50 µg PHY/kg within 10 minutes) with (series 1) and without (series 2) additional volume loading. Hemodynamic parameters, blood gases, and parameters for tissue damage were periodically determined for up to 180 minutes.ResultsEven though volume was additionally administered (series 1), LPS caused a reduction of peripheral blood flow. Treatment with PHY improved hemodynamics in macrocirculation (mean arterial blood pressure) and microcirculation (peripheral blood flow). PHY neither affected alterations in blood gases, electrolyte homeostasis, and glucose metabolism nor prevented intestinal damage induced by LPS. In series 2, without any additional volume loading, PHY likewise resulted in an improvement of the LPS-induced alterations in macro- and microcirculation, but finally worsened the LPS-mediated effects on plasma parameters for tissue damage such as creatine kinase, probably due to the lack of volume and a further damage to the heart.ConclusionThe present results demonstrated that hemodynamic responses to PHY may not only be visible in patients with anticholinergic drug overdose but also be visible in septic patients, provided that fluid intake of these patients is adequate.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Therapeutic effects of physostigmine during systemic inflammation

Effenberger-Neidnicht

Jägers

Verhaegh

et al. 2018

JIR

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“…Subsequent to the determination of the macroscopic score, each segment of the small intestine was cut in the middle, and the resulting 20 specimens were homogenized in 1 mL cold homogenization buffer on ice as described previously [15]. The following determination of tissue saccharase activity has been described in detail elsewhere [16].…”

Section: Methodsmentioning

confidence: 99%

“…In the present manuscript, we used a rat model for AMI as described previously [11, 13, 15] and firstly analyzed the relationship between histological tissue damage, Ki-67-expression in enterocytes, and different lengths of reperfusion after an ischemic period of 60 min. Afterwards, it was proved whether glycine, sodium pyruvate, and resveratrol can support the regeneration process during the reperfusion period.…”

Section: Introductionmentioning

confidence: 99%

Effect of Glycine, Pyruvate, and Resveratrol on the Regeneration Process of Postischemic Intestinal Mucosa

Brencher

Petrat

Stych

et al. 2017

BioMed Research International

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Background Intestinal ischemia is often caused by a malperfusion of the upper mesenteric artery. Since the intestinal mucosa is one of the most rapidly proliferating organs in human body, this tissue can partly regenerate itself after the onset of ischemia and reperfusion (I/R). Therefore, we investigated whether glycine, sodium pyruvate, and resveratrol can either support or potentially harm regeneration when applied therapeutically after reperfusion injury. Methods I/R of the small intestine was initiated by occluding and reopening the upper mesenteric artery in rats. After 60 min of ischemia and 300 min of reperfusion, glycine, sodium pyruvate, or resveratrol was administered intravenously. Small intestine regeneration was analyzed regarding tissue damage, activity of saccharase, and Ki-67 positive cells. Additionally, systemic parameters and metabolic ones were obtained at selected periods. Results Resveratrol failed in improving the outcome after I/R, while glycine showed a partial beneficial effect. Sodium pyruvate ameliorated metabolic acidosis, diminished histopathologic tissue injury, and increased cell proliferation in the small intestine. Conclusion While glycine could improve in part regeneration but not proliferation, sodium pyruvate seems to be a possible therapeutic agent to facilitate proliferation and to support mucosal regeneration after I/R injury to the small intestine.

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Effects of pentoxifylline on oxidative stress in rats with abdominal compartment syndrome model

Eğin

Açıksarı

Ercan

et al. 2016

International Journal of Surgery Open

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Background Abdominal compartment syndrome (ACS) causes severe pathology in the cardiovascular, renal and pulmonary systems. Recent studies showed that pentoxifylline (PTX) has effects on increasing tissue oxygenation, healing capillary refill and reducing superoxides and hydroxyl radicals by inhibiting xanthine oxidase. In this study, our aim was to study the effects of PTX on free oxygen radicals and oxidative damage in rats with ACS model. Materials and methods ACS model was created in 32 male Wistar-Albino-rats, which were randomized into one of the four study groups: Group A (n:8), having ACS; Group B (n:8), having ACS and receiving PTX (50 mg/kg/day) intraperitoneal for 10 days; Group C (n:8), receiving PTX (50 mg/kg/day) intraperitoneal for 10 days without having ACS; Group D (n:8), having no ACS and not receiving PTX. On the 11th day blood samples were collected to measure alanine-amino-acid-transferase (ALT) and aspartate-amino-acid-transferase (AST) in the heart, malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) in the liver, lung and small bowel. Histopathologic injury scoring was done. Results Groups were compared in pairs. Group A compared to Group B: ALT increase, liver MDA, lung GSH and MPO decrease were statistically meaningful in Group B. Group A compared to Group C: ALT and liver MPO decrease and liver MDA increase were statistically meaningful in Group A. Group B compared to Group C: ALT increase, MDA and GSH decrease in the lung were statistically meaningful in Group B. Group B compared to Group D: ALT and MPO increase in the small bowel and MPO decrease in the lung were statistically meaningful in Group B. Group A had the highest histopathologic injury scoring. Conclusion Histopathologically confirmed pentoxifylline was effective in the treatment of ACS in these rat models. Highlights

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Attenuation of intestinal ischemic injury and shock by physostigmine

Cited by 11 publications

References 58 publications

Therapeutic effects of physostigmine during systemic inflammation

Therapeutic effects of physostigmine during systemic inflammation

Effect of Glycine, Pyruvate, and Resveratrol on the Regeneration Process of Postischemic Intestinal Mucosa

Effects of pentoxifylline on oxidative stress in rats with abdominal compartment syndrome model

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