The effect of inhibition of renin-angiotensin system by valsartan during hypovolemic shock and low flow sigmoideal ischaemia in pigs.

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.

New segmental long bone defect model in sheep: quantitative analysis of healing with dual energy x-ray absorptiometry.

An appropriate animal model is required for the study of treatments that enhance bone healing. A new segmental long bone defect model was developed for this purpose, and dual energy x-ray absorptiometry was used to quantify healing of this bone defect. In 15 sheep, a 3-cm segmental defect was created in the left tibia and fixed with an interlocking intramedullary nail. In seven animals, the defect was left empty for the assessment of the spontaneous healing response. In eight animals serving as a positive control, autologous bone grafting was performed. After 12 weeks, healing was evaluated with radiographs, a torsional test to failure, and dual energy x-ray absorptiometry. The mechanical test results were used for the assessment of unions and nonunions. Radiographic determination of nonunion was not reliably accomplished in this model. By means of dual energy x-ray absorptiometry, bone mineral density and content were measured in the middle of the defect. Bone mineral density was 91+/-7% (mean +/- SEM) and 72+/-6% that of the contralateral intact tibia in, respectively, the autologous bone-grafting and empty defect groups (p = 0.04). For bone mineral content, the values were, respectively, 117+/-18 and 82+/-9% (p = 0.07). Torsional strength and stiffness were also higher, although not significantly, in the group with autologous bone grafting than in that with the empty defect. Bone mineral density and content were closely related to the torsional properties (r2 ranged from 0.76 to 0.85, p < or = 0.0001). Because interlocking intramedullary nailing is a very common fixation method in patients, the newly developed segmental defect model has clinical relevance. The interlocking intramedullary nail provided adequate stability without implant failure. This model may be useful for the study of treatments that affect bone healing, and dual energy x-ray absorptiometry may be somewhat helpful in the analysis of healing of this bone defect.

The renin-angiotensin system in swine during hypovolaemic shock combined with low-flow ischaemia of the sigmoid colon.

Colonic ischaemia is a serious complication after aortic surgery, and is most frequent after repair of ruptured aortic aneurysms. It was felt that the increased risk of colonic ischaemia during shock might be the result of a local effect of the renin-angiotensin system in the splanchnic circulation, which is exacerbated by poor perfusion. In order to evaluate the activity of the renin-angiotensin system in the colonic circulation, a subtotal occlusion of the distal aorta was induced in nine pigs. A colonic flow reduction of 70% was created for 4 hours. In the experimental group (n = 6), induce hypovolaemic shock, 20 cm3/kg blood was sampled at 45 min before resuscitation was performed with 20 cm3/kg haemaccel. The sham group (n = 3) did not have hypovolaemic shock induced. Blood samples were taken for determinations of angiotensin II, haemoglobin and lactate. Blood gas was obtained from the pulmonary artery and the caudal mesenteric vein for blood gas analysis and lactate determinations. ANOVA and the Wilcoxon sum rank test were used for statistical analysis. There was a significant increase in angiotensin II after induction of ischaemia in both groups. The increase in angiotensin II in the splanchnic circulation was more prominent than the increase in the systemic circulation (P < 0.01). In the experimental group, there was a sustained increase in angiotensin II levels in the splanchnic circulation following shock and reperfusion (P < 0/01). The increase in lactate concentrations, which was significantly higher in the experimental group (P < 0.05), was evidence of intestinal ischaemia. There was a significant decline in cardiac output and blood pressure during the period of shock (P < 0.05). The combination of colonic ischaemia and hypovolaemic shock followed by reperfusion leads to an increase in angiotensin II activity. The increase of the local activity of the renin-angiotensin system in the splanchnic circulation is more prominent after ischaemia and reperfusion. This is probably caused by a selective response of the splanchnic vasculature to shock, ischaemia and reperfusion.

Local colonic blood pressure degree through aortic reconstruction procedures: a porcine model.

Sigmoideal ischemia after aortic grafting is a severe complication with high morbidity and mortality. To investigate the basics of this circulatory problem an animal model was created with sigmoideal ischemia that could be quantified. For this purpose a new pig model was developed with stable general circulatory and ventilatory parameters for several hours, while at the same time controlled sigmoideal ischemia was induced. In five pigs a left retroperitoneal approach to the aorta was performed to isolate the caudal mesenteric artery (CMA). Sigmoideal ischemia was achieved by ligating the collateral circulation and constricting the distal aorta. A flow probe was applied to the CMA. An intravascular saturation probe was introduced in the caudal mesenteric vein (CMV) and a pulse oximeter was applied to the serosal surface of the sigmoid. Every hour, blood gas analyses from the carotic artery, CMA, and CMV were completed. Registrations of all circulatory and ventilatory parameters were performed with the help of a computer. The mean flow in the CMA was 29 mL/min (13-45) and decreased to 5 mL/min (3-7) after aortic constriction. Parameters reflecting the stability of the model, such as the cardiac index (mean 89 mL/min kg-1), the mixed venous oxygen saturation (mean 67%), and the total body oxygen consumption (mean 3.3 mL/min kg-1), did not change with statistical significance during 4 h of partial aortic constriction. The conclusion is that a new model has been developed of quantitative sigmoideal ischemia in the pig that was stable for several hours.

Endoluminal pulse oximetry in ischemic colon in a swine model.

BACKGROUND: Postoperative sigmoidal ischemia after aortic grafting is a severe complication. No simple methods are available to detect this entity at an early stage. This study was done to monitor for sigmoidal ischemia with a new endoluminal probe based on pulse oximetry (SmO2). STUDY DESIGN: A prospective controlled animal study was done. Five pigs with low flow in the caudal mesenteric artery (20 percent of the basal flow) and four pigs in a control group were included. General and local circulatory parameters were monitored in the carotid and pulmonary artery and in the caudal mesenteric vein (CMV). Mucosal biopsy specimens were taken for histologic examination. Statistical analysis was done with the Wilcoxon and Mann-Whitney rank sum test and with analysis of variance. RESULTS: During the first two hours of ischemia, no sigmoidal pulse was detected. During the third hour, in three pigs the pulse curve reappeared with a SmO2 of 48 to 88 percent. After two hours, the mean oxygen saturation in the CMV of the ischemic group was 64 percent (compared with the control group, 77 percent, p < 0.05). After one hour, the mean lactate concentrations were 2.0 and 1.3 mmol per L, respectively (p < 0.05). Significant histologic changes occurred with neutrophilic infiltration in the crypts, in the lamina propria, and in the submucosa. CONCLUSIONS: Low-flow sigmoidal ischemia can be detected and monitored with endoluminal pulse oximetry in this model of early sigmoidal ischemia.