Fifty Shadows of Mesenteric Ischemia

A 66-year-old female presented to the emergency department with sudden onset of central abdominal pain irradiated to the back. Blood tests were unremarkable. Computed tomography scan showed acute focal ischaemia of small bowel loops sustained by an encircling omental band around a mid ileal loop, which was released on urgent mini-laparotomy. The ischaemic loops were covered with hot moist gauzes for several minutes until the normal luster and peristaltic wave returned. Indocyanine green fluorescence angiography confirmed sufficient bowel perfusion and viability. The patient was discharged 5 days after surgery and did not experience any symptom recurrence up to 6 months later. Mesenteric or colonic ischaemia may respectively affect the small or large intestine. The small intestine is able to compensate for a 75% reduction in mesenteric perfusion for up to 12 hours. If promptly treated, resection may be successfully avoided.

Compartment syndrome of the hand following iatrogenic intra-arterial administration of epinephrine during cardiopulmonary resuscitation

A 26-year-old woman developed acute compartment syndrome (ACS) of her right hand secondary to reperfusion syndrome. She suffered an out-of-hospital cardiac arrest following a pregabalin overdose. Attending paramedics mistakenly gave intra-arterial epinephrine into her right brachial artery. On resolution of her brachial artery spasm, she developed a reperfusion injury to her right hand and subsequently ACS. A four-incision fasciotomy with carpal tunnel decompression was performed and was successful in reversing focal ischaemia and an irreversible functional deficit. This case demonstrates an unusual case of hand ACS secondary to temporary limb ischaemia and reperfusion syndrome following iatrogenic intra-arterial epinephrine administration. We also summarise the current available literature on ACS of the hand including the aetiology, treatment and use of an intracompartmental monitor.

The flavonoid, 2′-methoxy-6-methylflavone, affords neuroprotection following focal cerebral ischaemia

Tonic inhibitory currents, mediated by extrasynaptic GABAA receptors, are elevated at a delay following stroke. Flavonoids minimise the extent of cellular damage following stroke, but little is known about their mode of action. We demonstrate that the flavonoid, 2′-methoxy-6-methylflavone (0.1–10 µM; 2′MeO6MF), increases GABAA receptor tonic currents presumably via δ-containing GABAA receptors. Treatment with 2′MeO6MF 1–6 h post focal ischaemia dose dependently decreases infarct volume and improves functional recovery. The effect of 2′MeO6MF was attenuated in δ−/− mice, indicating that the effects of the flavonoid were mediated via δ-containing GABAA receptors. Further, as flavonoids have been shown to have multiple modes of action, we investigated the anti-inflammatory effects of 2′MeO6MF. Using a macrophage cell line, we show that 2′MeO6MF can dampen an LPS-induced elevation in NFkB activity. Assessment of vehicle-treated stroke animals revealed a significant increase in circulating IL1β, TNFα and IFγ levels. Treatment with 2′MeO6MF dampened the stroke-induced increase in circulating cytokines, which was blocked in the presence of the pan-AKT inhibitor, GSK690693. These studies support the hypothesis that compounds that potentiate tonic inhibition via δ-containing GABAA receptors soon after stroke can afford neuroprotection.

Hypothermia revisited: Impact of ischaemic duration and between experiment variability

To assess the true effect of novel therapies for ischaemic stroke, a positive control that can validate the experimental model and design is vital. Hypothermia may be a good candidate for such a positive control, given the convincing body of evidence from animal models of ischaemic stroke. Taking conditions under which substantial efficacy had been seen in a meta-analysis of hypothermia for focal ischaemia in animal models, we undertook three randomised and blinded studies examining the effect of hypothermia induced immediately following the onset of middle cerebral artery occlusion on infarct volume in rats (n = 15, 23, 264). Hypothermia to a depth of 33℃ and maintained for 130 min significantly reduced infarct volume compared to normothermia treatment (by 27–63%) and depended on ischaemic duration (F(3,244) = 21.242, p < 0.05). However, the protective effect varied across experiments with differences in both the size of the infarct observed in normothermic controls and the time to reach target temperature. Our results highlight the need for sample size and power calculations to take into account variations between individual experiments requiring induction of focal ischaemia.