title: The effect of inhibition of renin-angiotensin system by valsartan during hypovolemic shock and low flow sigmoideal ischaemia in pigs.
abstract: The aim of this experiment was to study the effect of Renin-Angiotensin System (RAS) blockade by means of valsartan on the colonic and systemic circulation in pigs during low flow sigmoideal ischemia in combination with hypovolemic shock. This condition resembles the situation that occurs in patients suffering from a ruptured aneurysm and a compromised colonic circulation. An experimental study in pigs was performed : 6 pigs with low flow sigmoideal ischemia and hypovolemic shock were treated with valsartan and a control group of 5 pigs with low flow sigmoideal ischemia and hypovolemic shock without medical treatment.Valsartan, 3 mg/kg, was administered intravenously. The operation was performed via left sided lumbotomy. The distal aorta was partially occluded to a flow reduction of 30% of the initial value. Hypovolemic shock was induced by withdrawing 20 ml/kg blood in 45 min. Resuscitation with 30 ml/kg haemaccel was iniated after 2 h of shock. The following parameters were measured: blood pressure, cardiac output; hemoglobin, lactate, angiotensin II in mixed venous blood (obtained from pulmonary artery) and in splanchnic blood (obtained from caudal mesenteric vein); and endoluminal pulse oximetry of the sigmoideal mucosa. Statistical analysis was performed by ANOVA and Wilcoxon signed rank test. There was a significant increase of lactate levels both in systemic and splanchnic circulation (P<0.05) in both groups. In the control group, the mean angiotensin II concentrations in the systemic circulation increased, after induction of ischaemia and shock. In the experimental group, the increase in angiotensin concentrations after resuscitation was significantly more prominent. In the colonic circulation, in both groups, there was a significant increase in angiotensin II levels in the splanchnic circulation following ischaemia and reperfusion (P<0.05), but there was no significant difference between the groups. There were no detectable mucosal signals measured by pulse oximetry after induction of shock throughout the experiment, whereas in the experimental group, median mucosal oxygen saturations of 81, 74.5 and 85% were achieved after resuscitation and declamping (P<0.01).In conclusion, angiotensin II inhibition during hypovolemic shock improves the colonic circulation, measured by pulse oximetry. However, other parameters of tissue ischaemia did not improve.
authors.affiliation: Department of Vascular Surgery, Free University Medical Center, Amsterdam, The Netherlands.
authors.forename: E N
authors.initials: EN
authors.lastname: Yilmaz
authors.forename: A C
authors.initials: AC
authors.lastname: Vahl
authors.forename: G L
authors.initials: GL
authors.lastname: van Rij
authors.forename: G Q M
authors.initials: GQ
authors.lastname: Vink
authors.forename: H L F
authors.initials: HL
authors.lastname: Brom
authors.forename: J A
authors.initials: JA
authors.lastname: Rauwerda
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001019:Aortic Rupture / Q000188:drug therapy / Q000503:physiopathology; D012809:Colon, Sigmoid / Q000098:blood supply*; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D010092:Oximetry; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012769:Shock / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D006454:Hemoglobins; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine