The effect of mesenteric ischaemia on the levels of neurotensin, vaso-active intestinal polypeptide and gastrin in portal venous blood and in the peripheral circulation was studied in two groups of 7 and 6 baboons (Papio ursinus). In peripheral blood a decreasing trend in levels of neurotensin was observed, while vaso-active intestinal polypeptide and gastrin levels were unchanged. There was a similar trend in neurotensin levels in portal venous blood, together with an increasing trend in levels of vaso-active intestinal polypeptide. Gastrin levels were unchanged. Further investigation of these apparent trends in a larger number of animals is warranted

de Beer, R

Morrison, G

Strachan, A.F.

van Rensburg, L.C.J.

English

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31S SAMJ VOL 79 16 MAR 1991L. C. J. VAN RENSBURG, G. MORRISON, R. DE BEER, A. F. STRACHANNeurotensin, vaso-active intestinal polypeptide andgastrin levels in plasma and portal venous blood inexperimental mesenteric ischaemiaII·II,I,,,,,,,,IIIIIIIIIIIIIchanging levels of NT and VIP might be seen in mesentericisc.haemia. In these pilot experiments (using a small number ofarumals) no changes could be demonstrated in the peripheralblood levels of these hormones. As it has been shown experi-ment~y that VIP is extracted by the liver,? it was notsurpnsmg to fmd no significant alterations in peripheral VIPlevels, although a trend of increasing levels occurred in portalvenous blood. Our findings are in keeping with other reportsthat VIP levels rise in the portal venous blood in mesentericischaemia. 6 The mean NT levels in the peripheral venoussamp!es in group I showed a decreasing trend, which was alsosee~ m the por::~ venous blood levels in group 11; a fmdingwhIch .was annc.lpated. The high degree of variability andsmall sIze effect m NT measurements (Table I) indicates thatmuch larger sample sizes will be necessary in order to reachstatistical significance. The apparent trend in NT levels canthen be verified. Gastrin levels remained unchanged in spite ofthe theo~et.ical po~sibility that diminished NT output inmesentenc IschaemIa could precipitate a rise in gastrin levelsthrough pH changes in the lumen of the stomach. Sincegastric pH tended towards the alkaline in controls and in theanimals :vith mesenteric ischaemia, these changes are probablynonspecific.In this group of animals the small sample size precluded astatistical analysis of the results. We would suggest that anextended study of a larger number of animals would increasethe probability of a statistically significant conclusion regardingthe diagnostic potential for measurements of levels of thesehormones in the peripheral blood in mesenteric ischaemia. Atpres~~t it t~~s up to 48 hours to analyse these gut hormones,but It IS antiCIpated that more rapid analysis will be possible. inthe future. The sampling of portal veQous blood through apercutaneous transhepatic route cannot be considered feasibleas a future special investigation in the diagnosis of earlymesenteric ischaemia.1. Pola!< JM, Bloom SR. Neuropeptides of the gut: a newly discovered majorcontrol system. World] Surg 1979; 3: 393-406.2. B!ackb~ AM, Bloom SR, Long RG, Fletcher DR, Christofides ND,FltZpatnck ML. Effect of neurotensin on gastric function in man Lam;er1980; 1: 987-989. .3. Fahrenkrug]. Vasoactive. intestinal. polypeptide: measurement, distributionand pmanve neurotranslIll~er funcnon. Digesricm 1979; 19: 149-169.4. Modlin IM, Bl~m S~, M,itchell ~. Plasma vasoactive intestinal polypeptide(VIP) levels and mtestina!lschaelIlla. Experiemia 1978; 34: 535-5365. Graeber GM, Cafferry PJ, Reardon MJ, Curley CP, Harmon IW. Elevationof serum creanmne phosphokinase (CPK) in experimental mesenteric infarc-non. Surg Forum 1980; 31: 148-150.6. Boley SJ, Sprayregan ~, Siegelman SS, Veith F]. Initial results from~ess.lve roentgenologlcaJ and surgical approach to acute mesentericIschelIll3. Surgery 1977; 82: 848-855.7. Bitar KN, Said SI, Weir B, Saffouri B, Maklouf GM. Neural release ofvasoacnve mtesnnal peptide from the gut. Gascroencerolo"" 1980' 79.1288-1294. OJ ,.This project was supponed by a grant from the South AfricanMedical Research Council.REFERENCES55442 3Sample2 3SampleControl12,3 ± 11,914,3 ± 15,213,3 ± 14,610,0 ± 15,511,S± 12,912,3 ± 13,21TABLE I. SERUM LEVELS (pmolll) OF NT, VIP AND GASTRIN (MEAN ± SO IN GROUP I ANIMALS)NT VIP GastrinExperiment Control \Experiment Control Experiment14,5±10,9 4,S±O,5 4,5±1,O 4,4±1,1 4,O±1,512,S ± 11,2 4,3 ± 0,5 4;3:±: 1,3 3,7 ± 1,5 4,4 ± 3,111,3±13,S 4,O±O,O 4,5±0,6 5,7±3,4 3,O±O,77,S ± 7,5 4,3 ± 0,5 4,3 ± 1,5 5,1 ± 3,7 2,5 ± 0,39,0 ± S,O 4,0 ± O,S 4,5 ± 1,7 6,4 ± 1,3 4,2 ± 1,29,S ± 10,2 4,3 ± 1,0 4,S ± 1,0 6,4 ± 2,7 3,4 ± 1,31Sample No.123456(])~ 10CO~8(5E~ 6I-Z 4161412210(j)0.. 8ECO~ 6(5E 4~Cl...:> 2Fi~. 1. Neurotensin levels in portal venous blood in group 11an!mals (above). VIP levels in portal venous blood in group 11animals (below).SAMJ VOL 79 16 MAR 1991 319The average volume of the intravenous infusion and urinaryoutput and the pH changes in group 11 animals were similar tothe animals in group I. Fig. 1 shows the changes in the portalvenous blood serum levels before and after induction ofmesenteric ischaemia. An initial decline in mean NT levelsand an increasing trend in mean VIP levels was seen. Gastrinlevels were unchanged (data not shown)~DiscussionIn spite of the advent of special serological tests,5 early angio-graphy6 and the awareness of this condition in the differentialdi~osis of the acute abdomen in elderly patients, the prog-nosIs of mesenteric ischaemia is generally poor because of adelayed diagnosis. With increasing knowledge of gut hormonesand the availability of diagnostic kits, it was postulated thatwith hourly intravenous doses of pentobarbitone sodium 6%(m/v) 4,25 mglkg/h. A nasogastric tube was passed, a peri-pheral venous line for infusion of Ringer's lactate introduced,and a urinary catheter inserted. Venous samples were takenfrom an indwelling catheter in the femoral vein. A midline.abdominal incision was made as a sham procedure and theanaesthetic sustained for 6 hours. A fasting sample of bloodwas taken followed by samples at induction of anaesthesia, onthe completion of the laparotomy incision, within the 1st hourand then 2-hourly, with the 6th and last sample 6 hours afterthe laparotomy incision. Gastric pH was continuously measuredwith a pH probe positioned in the antrum of the stomach.Three weeks later the baboons underwent re-operation. Thesuperior mesenteric artery was isolated for the injection ofmicrospheres. Debrisan beadlets 1 g (dextranomer beads0,1 - 0,3 mm diameter), suspended in 2 00 saline, wereinjected and the artery ligated. This produced marked ischaemiaof the whole of the small intestine except for a few centimetresof proximal jejunum, the caecum and colon as far as thesplenic flexure. Venous samples were taken as before, with thelast specimeil taken 6 hours after the introduction of mesentericischaemia. For hormonal assay, all the samples were preparedin the following manner before despatch to the Francis FraserLaboratories at Hammersmith Hospital, London: 200 ~l sterileTrasylol (20000 KIU aprotinin/OO) was placed in commercialheparin blood tubes. Blood was added (5 00) and mixed andthe plasma was separated by centrifugation at room tempera-ture. The plasma samples were stored at -20°C. After briefthawing, 1 00 aliquot samples were placed into freeze-driertubes. Mter freeze-drying the aliquots were sealed under drynitrogen for despatch.GroupllIn this group of 6 animals blood was taken from the portalvein for the measurement of NT, VIP and gastrin. The pre-operative preparation and anaesthesia was similar to that carriedout in the animals in group I. Mter opening the abdomen, the·superior mesenteric vessels and portal vein were exposed. Asmall mesenteric venous branch of the upper jejunum waschosen for the insertion of a thin polythene catheter into theportal vein in such a fashion that ;the portal venous blood flowwas not interfered with. Two samples of blood were taKenbefore the introduction of mesenteric ischaemia and then at2-hourly intervals until the termination of the experiment after6 hours.ResultsWith continuous pH monitoring, it was found that.the pHchanged from an average low level of 1,9 to an average high of6,6. Gastric output was no more than an average of 4 nivh.The average volume of Ringer's lactate infused was 100 ml/hand the urinary output ranged between 150 00 and 350 00over 6 hours. The serum levels of NT, VIP and gastrin areshown in Table I. There was no difference between the"control animals and the animals with mesenteric ischaemia.Subjects and methodsAs the major site of neurotensin (NT) production is in theterminal ileum,l it could be postulated that mesentericischaemia would bring about its reduction in the portal venousblood and possibly in the peripheral circulation. One of theproperties of ~TT is inhibition of pentagastrin-stimulated secre-tion of gastrin acid.2 Gastrin originates mainly in the stomach,duodenum and pancreas and, theoretically, its secretion shouldnot be affected by mesenteric ischaemia alone, although itsserum level could rise because of a suppressed NT secretion inmesenteric ischaemia. Vaso-active intestinal polypeptide (VIP)has a wide distribution throughout the gastro-intestinal tract3and several factors cause its release into the portal venousblood, including mesenteric ischaemia.4 A preliminary studywas carried out to establish whether serum levels of NT, VIPand gastrin in the peripheral and portal venous blood changedin mesenteric ischaemia in the experimental animal.Adult baboons (Papio ursinus) with an average weight of 16 kgwere divided into two groups. In group I peripheral serumlevels of NT, VIP and gastrin were measured. After thesestudies a decision was made to measure the hormone levels inportal venous serum (group 11).SummaryGroup IThis group comprised 7 animals and each acted as its owncontrol. Anaesthesia was induced (after a lO-hour fast) withketamine hydrochloride 100 mg intravenously and sustainedS Atr Med J 1991; 79: 318-319.The effect of mesenteric ischaemia on the levels of neuro-tensin, vaso-active intestinal polypeptide and gastrin in portalvenous blood and in the peripheral circulation was studied intwo groups of 7 and 6 baboons (Papio ursinus). In peripheralblood a decreasing trend in levels of neurotensin wasobserved, while vaso-active intestinal polypeptide and gastrinlevels were unchanged. There was a similar trend in neuro-tensin levels in portal venous blood, together with anincreasing trend in levels of vaso-active intestinal polypeptide.Gastrin levels were unchanged. Further investigation of theseapparent trends in a larger number of animals is warranted.Department of Surgery, University of Stellenbosch, Parow-vallei, CPL. C. J. VAN RENSBURG, M.B. CH.B., M.MED. (SURG.), F.e.S. (S.A.),F.R.e.S.G. MORRISON, M.B. CH.B., M.MED. (SURG.)R. DE BEER, M.B.CH.B.A. F. STRACHAN, PH.D.Aca:pted 22 May 1990.

Neurotensin, vaso-active intestinal polypeptide and gastrin levels in plasma and portal venous blood in experimental mesenteric ischaemia

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Neurotensin, vaso-active intestinal polypeptide and gastrin levels in plasma and portal venous blood in experimental mesenteric ischaemia

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