The value of endothelin 1 in the early diagnosis of severe intestinal strangulation
- M Grigoriou1,
- I Koutelidakis1,
- V Papaziogas1,
- C Lazaridis1,
- A Souparis1,
- G Chatzimavroudis1,
- C Atmatzidis1,
- G Koliakos2,
- D Gerasimidou3
- 12nd Department of Surgery, Thessaloniki Medical School, Thessaloniki, Macedonia, Greece
- 2Laboratory of Biochemistry, Thessaloniki Medical School, Thessaloniki, Macedonia, Greece
- 3Department of Pathology, Thessaloniki Medical School, Thessaloniki, Macedonia, Greece
- Correspondence to:
Laboratory of Biochemistry, Thessaloniki Medical School, Thessaloniki, Macedonia, Greece;
In patients with intestinal strangulation, early diagnosis and prompt intervention can play a key role in the final outcome. Physical signs and routine laboratory findings only raise the level of suspicion to the presence of intestinal ischaemia. Several markers such as alkaline phosphtase,1 creatinine phosphokinase,2 and lactate dehydrogenase3 and procalcitonin (Pct) serum levels have been proposed for the early diagnosis of intestinal ischaemia.4
Plasma levels of endothelin 1 (ET1) have been recently associated with cardiac ischaemia.5 It has also been reported that ET1 plays a central role in the pathophysiology of intestinal ischaemic injury.6 Wang et al7 recently reported that ligation of mesenteric vessels caused an increase in serum ET1 levels in rats. On the other hand, other researchers reported that in spite of increased release of ET1 from the strangulated loop, no statistically significant increase of ET1 in peripheral blood samples can be established.8 These controversial results may be attributed to the occlusion of the local venous vessels.
In an attempt to further study these controversial data, we performed concomitant ligation of the arterial and venous vessels that correspond to the occluded loop. It is also noted that this approach may better reflect the sequence of events that follow the onset of severe strangulation.
In 11 New Zealand rabbits, the intestinal lumen and the corresponding mesenteric vessels were occluded using silk sutures, one at 30 cm from the duodenum and one 15 cm distal to the first ligation. This model reproduces the phenomenon of the obstruction of intestinal wall perfusion due to severe strangulation and the pathophysiological processes at the onset of ischaemia that complicates the natural history of the disease. For the six controls, the steps of the operation were exactly the same, except the strangulation of the jejunum was not performed.
Blood samples were drawn preoperatively and consequently at 30, 60, 180 and 360 min after strangulation. At the same time intervals, a transmural biopsy specimen was obtained from the strangulated loop. Tissue samples were embedded in paraffin wax and submitted for H&E staining. Ischaemic injury of the intestine was scaled in four degrees of severity.9
The plasma concentration of ET1 was estimated with a commercial immunoassay kit (Assay Designs, Ann Arbor, Michigan, USA).
The comparison of ET1 values between the two groups revealed higher concentrations in the ischaemia group, at every time interval, which were statistically significant for all postoperative samples (p<0.05; fig 1). ET1 levels in plasma increased as early as 30 min after intestinal strangulation, and continued to increase with time up to 10-fold in the next 360 min. By contrast, in the control group no statistically significant alteration of ET1 levels, within the measured samples, was observed.
According to the analysis of histopathological grading of ischaemic injury, the ischaemia group samples were graded as follows: at 30 min, 2 samples of grade I; at 60 min, 8 of grade II and 2 of grade I; at 180 min, 3 of grade II and 8 of grade III; and, finally, at 360 min 1 of grade I and 10 of grade IV. No evidence of ischaemic injury was detected in specimens derived from the control group. ET1 plasma levels correlated with histopathological damage. Mild increase in ET1 levels reflected mild, mainly mucosal intestinal ischaemic injury graded in this study as grade I and II, whereas a twofold or higher increase in circulating ET1 is consistent with extensive epithelial injury affecting the mucosa and the submucosa, and the muscle layers of the intestinal wall classified as grade III and IV.
It is evident that plasma levels ET1 rise at 30 min of strangulation before any histological damage is observed. This makes ET1 an additional useful marker for severe intestinal strangulation than other hitherto reported markers including procalcitonin.4 According to these results, measurement of plasma ET1 in a clinical setting is justified to further evaluate its value in the early diagnosis of intestinal ischaemia due to strangulation.