Time course of necrosis/apoptosis and neovascularization during experimental gastric conditioning

Abstract

Apoptosis, necrosis and neovascularization are three processes that occur during ischemic preconditioning in a range of organs. In the stomach, the effect of this preconditioning (the delay phenomenon) has helped to improve gastric vascularization prior to esophagogastric anastomosis after esophagectomy. Here we present a sequential study of the histological recovery of the gastric fundus and the phenomena of apoptosis, necrosis and neovascularization in an experimental model of partial gastric ischemia. Partial gastric devascularization was performed by ligature of the left gastric vessels in Sprague-Dawley rats. Rats were assigned to groups in accordance with their evaluation period: control, 1, 3, 6, 10, 15 and 21 days. Histological analysis, caspase-3 activity, DNA fragmentation and vascular endothelial cell proliferation (Ki-67) were measured in tissue samples after sacrifice. After 24 h of partial gastric ischemia, rates of apoptosis and necrosis were higher in the experimental groups than in controls. Tissue injury was higher 3 and 6 days post-ischemia. From day 10 after partial gastric ischemia, apoptosis and necrosis started to decrease, and on days 15 and 21 showed no differences in relation to controls. Neovascularization began between days 1 and 3, reaching its peak at 15 days after ischemia and coinciding with complete histological recovery. Both necrosis and apoptosis play a role in tissue injury during the first days after partial gastric ischemia. After 15 days, the evolution of both the histology and the neovascularization suggested that this is the optimal time for performing gastric transposition.

Randomized controlled trial of laparoscopic gastric ischemic conditioning prior to minimally invasive esophagectomy, the LOGIC trial

“…After ligation of the left gastric vessels, there seems to be an immediate diversion of blood toward the greater curve of the stomach, which mirrors the observations made by other researchers [22,23,32,34]. Dilatation of the right gastroepiploic arcade has been demonstrated on angiography and histology after ischemic conditioning of the stomach.…”

“…The upper part of the transposed stomach is particularly at risk from rarefaction of intramural vessels, as demonstrated by anatomical studies [17]. Urschel and others [18][19][20] have explored the role of gastric ischemic conditioning in animals and demonstrated that this may have a potential benefit [21][22][23][24][25][26]. Akiyama in 1992 [27] reported the first human clinical series, and more recent studies have confirmed a beneficial impact of conditioning [28][29][30][31][32][33][34].…”

Ischemic conditioning shows a time-dependant influence on the fate of the gastric conduit after minimally invasive esophagectomy

“…A 5-day LIC could represent an inadequate time for ischemic conditioning of the gastric fundus (future conduit tip) to take place. This line of thought is backed by the recent work of Lamas et al [21], strongly suggesting the need to delay an esophagectomy until about 2 weeks after ischemic conditioning. Five days may simply be exposing the gastric conduit to ''ischemic stress,'' which becomes more apparent in a proportion of patients (Fig.…”

“…Numerous animal experiments have pondered the merits of gastric ischemic conditioning [17][18][19][20], most notably the work by Urschel [43], and more recently, the work of Lamas et al [21].…”

“…The discovery of the ''delay phenomenon'' in plastic surgery, whereby a graft is rendered ischemic before translocation to increase its eventual vascularity through the dilation of choke vessels [16], is recognized as having potential benefit for the gastric conduit [17]. Further animal studies by Urschel et al [18], Alfabet et al [19], Reavis et al [20], and more recently, Lamas et al [21] have shown a potential benefit.…”