Acute Ischemic Group Research Articles

Bone Marrow Mononuclear Stem Cell Transplant in Acute and Chronic Arterial Insufficiency in Rabbits

Introduction: There is a high incidence of Peripheral Obstructive Arterial Disease (POAD) in patients with atherosclerosis. In more complex cases for which surgical revascularization is not possible, the only option involves clinical treatment that in the majority of cases evolves to amputation of the limb. Transplant of mononuclear stem cells from bone marrow has presented favorable results in chronic obstructions. Objective: To perform a functional analysis of the effect of bone marrow mononuclear stem cell transplant on acute arterial occlusion immediately and 48 hours after occlusion, comparing between groups and with controls. Materials and methods: Twenty New Zealand rabbits were anesthetized with ketamine and xylazine (50 mg/ kg) and underwent occlusion of the right iliac artery. Those animals that presented absence of arterial flow after ligation were included in the study. These animals were then randomized and divided into four groups: Group 1(n=5) control of acute ischemia group–injection of saline solution, Group 2(n=5) control of chronic ischemia–injection of saline solution 48hrs after occlusion. Group 3(n=5) transplant of stem cell in acute ischemia group, and Group 4(n=5) transplant of stem cells in the chronic ischemia group, 48hrs after occlusion. The animals were evaluated by the Tarlov’s movement scale, degree of tissue ischemia, and degree of modified ischemia on the seventh, fourteenth and thirtieth day after arterial occlusion. This evaluation was performed in a blind and randomized fashion by two different observers. The animals underwent another vascular Doppler exam on the thirtieth day after arterial occlusion. Results: All animals were considered homogeneous in the pre-transplant period. No statistical differences were identified between groups G1 and G3 (p=109) with respect to Tarlov scale. Regarding the intergroup analysis, a clinical improvement was observed in Group 4 when compared to Groups 1, 2, and 3, p=0.003, p=0.0025, and p=0.055 respectively, on the thirtieth day after occlusion. No significant difference was observed for the degree of ischemia and modified ischemia parameters after transplant. Conclusion: Clinical improvement in the chronic ischemia group receiving cell transplant of mononuclear stem cells was observed in comparison to the control group and in relationship to the acute ischemia group, suggesting a functional improvement in the affected limb.

Changes of monophasic action potential duration and effective refractory period of three layers myocardium of canine during acute ischemiain Vivo

The effect of acute ischemia on the electrophysiological characteristics of the three layers myocardium of canine in vivo was investigated. Twelve canines were divided into two groups randomly: acute ischemia (AI) group and sham operation (SO) group. By using the monophasic action potential (MAP) technique, MAP and effective refractory period (ERP) of the three layers myocardium were measured by specially designed plunge needle electrodes and the transmural dispersion of repolarization (TDR) and transmural dispersion of ERP (TDE) were analyzed. The results showed that in the AI group, MAP duration (MAPD) was shortened from 201.67 +/- 21.42 ms to 169.50 +/- 13.81 ms (P < 0.05), but ERP prolonged to varying degrees and TDE increased during ischemia. In the SO group, MAPD and ERP did not change almost. Among of the three layers myocardium of canine, MAPD was coincident in two groups. It was concluded that during acute ischemia, MAPD was shortened sharply, but there was no significant difference among of the three layers myocardium. The prolonged ERP was concomitant with increased TDE during acute ischemia, which may play an important role in the occurrence of arrhythmias induced by acute ischemia. These findings may have important implications in arrhythmogenesis.

The effect of gradual or acute arterial occlusion on skeletal muscle blood flow, arteriogenesis, and inflammation in rat hindlimb ischemia

Current experimental models of critical limb ischemia are based on acute ischemia rather than on chronic ischemia. Human peripheral vascular disease is largely a result of chromic ischemia. We hypothesized that a model of chronic hindlimb ischemia would develop more collateral arteries, more blood flow, and less necrosis and inflammation than would acute hindlimb ischemia. We therefore developed a rat model of chronic hindlimb ischemia and compared the effects of chronic ischemia with those of acute ischemia on hindlimb skeletal muscle. Acute or chronic ischemia was induced in 36 male Sprague-Dawley rats. Chronic ischemia caused blood flow, as measured by laser Doppler scanning and confirmed by muscle oxygen tension measurements, to gradually decrease over 1 to 2 weeks after operation. Histologic analysis showed chronic hindlimb ischemia better preserved muscle mass and architecture and stimulated capillary angiogenesis, while lacking the muscle necrosis and inflammatory cell infiltrate seen after acute ischemia. Surprisingly, the chronic ischemia group recovered dermal blood flow more slowly and less completely than did the acute ischemia group, as measured by laser Doppler (0.66 +/- 0.02 vs 0.76 +/- 0.04, P < .05) and tissue oxygen tension (0.61 +/- 0.06 vs 0.81 +/- 0.05, P < .05) at 40 days postoperatively. Consistent with poorer blood flow recovery, chronic ischemia resulted in smaller diameter collateral arteries (average diameter of the five largest collaterals on angiogram was 0.01 +/- 0.0003 mm vs 0.013 +/- 0.0007 mm for acute, P < .005 at 40 days postoperatively). Acute ischemia resulted in decreased tissue concentrations of vascular endothelial growth factor (VEGF) (0.96 +/- 0.23 pg/mg of muscle for acute vs 4.4 +/- 0.75 and 4.8 +/- 0.75 pg/mg of muscle for unoperated and chronic, respectively, P < .05 acute vs unoperated), and in increased tissue concentrations of interleukin (IL)-1beta (7.3 +/- 4.0 pg/mg of muscle for acute vs undetectable and 1.7 +/- 1.6 pg/mg of muscle for unoperated and chronic, respectively, P < 0.05 acute vs unoperated). We describe here the first model of chronic hindlimb ischemia in the rat. Restoration of blood flow after induction of hindlimb ischemia is dependent on the rate of arterial occlusion. This difference in blood flow recovery correlates with distinct patterns of muscle necrosis, inflammatory cell infiltration, and cytokine induction in the ischemic muscle. Differences between models of acute and chronic hindlimb ischemia may have important consequences for future studies of mechanisms regulating arteriogenesis and for therapeutic approaches aimed at promoting arteriogenesis in humans suffering from critical limb ischemia. Despite the substantial clinical differences between acute and chronic ischemia, researchers attempting to develop molecular therapies to treat critical limb ischemia have only tested those therapies in experimental models of acute hindlimb ischemia. We present here a novel model of chronic hindlimb ischemia in the rat. We further demonstrate that when hindlimb ischemia is developed chronically, collateral artery development is poorer than when hindlimb ischemia is developed acutely. These findings suggest that further tests of molecular therapies for critical limb ischemia should be performed in chronic hindlimb ischemia models rather than in acute hindlimb ischemia models.

Magnetic resonance imaging of bowel ischemia induced by ligation of superior mesenteric artery and vein in a cat model.

To assess the usefulness of magnetic resonance (MR) imaging for detecting bowel ischemia with strangulation compared with histopathologic findings in an experimental cat model. Fourteen cats were assigned to the normal control group (n = 3), acute ischemic group (induced by ligation of superior mesenteric vessels for 3 hours, n = 7), and subacute ischemic group (induced by ligation of superior mesenteric vessels for 10 hours, n = 4). Using a 4.7-T MR scanner, contrast-enhanced T1-weighted images were obtained at 0, 10, 20, 30, and 60 minutes after bolus injection of contrast media. T1- and T2-weighted images were obtained from the extracted bowel wall and compared with histopathologic findings. On contrast-enhanced MR images, the target-like bowel wall layers were clearly demonstrated and the submucosal layer showed the most prominent enhancement. At 10 minutes after administration of contrast media, the subacute ischemic group showed significantly lower enhancement of the submucosal layer than the normal or acute ischemic group (P <0.05). On T1-weighted images, there were not significant differences between the normal and ischemic bowel groups (P >0.05). On T2-weighted images, the signal intensity of all layers of acute ischemic bowel wall was significantly higher than that of the normal control or subacute ischemic group (P <0.05). Delayed contrast-enhanced MR images and T2-weighted images were helpful for detecting subacute and acute bowel ischemia with strangulation, respectively.

MR Findings of Bowel Ischemia with Mesenteric Vascular Occlusion: Comparison with Pathologic Findings in a Cat Model

Purpose : In order to determine the characteristic MR findings for the early diagnosis of bowel ischemia, we analysed the dynamic enhanced MR images of ischemic bowel induced by mesenteric vascular occlusion in a cat model, and compared the T1-and T2- weighted images (WI) of extracted bowel with the pathologic findings. Materials and Methods : According to the ischemic period, twelve cats were assigned to either the normal control group (no ischemic period, n=2), the acute ischemic group (ligation of mesenteric vessels for 3 hours, n=6) or the subacute ischemic group (ligation of mesenteric vessels for 10 hours, n=4). Under general anes-thesia,laparotomy was performed. The ileal artery and vein were ligated, and a columnar surface coil was ap-plied to the expected bowel ischemia. Using a 4.7 T MR scanner, contrast-enhanced T1WI were obtained, after bolus injection of contrast media, at 10, 20, 30, 60, and 90minutes. After formalin fixation of the extracted bowel, T1- and T2WI were obtained, and the specimens were pathologically examined. MR signal intensity at each layer of the bowel wall was measured and compared with the histopathologic findings. Results : On contrast enhanced MR images, the submucosal layer showed most intensive enhancement, fol-lowed-in decreasing order of signal intensity- by muscle and mucosa. Time to peak enhancement of bowel wall was 10-minutes in the normal control group, and 20 and 60minutes in the acute and subacute bowel is-chemia groups, respectively. On T1WI, no significant differences in signal intensity were observed between the ischemic group and the normal control group. On T2WI, the signal intensity of the submucosal layer of the acute ischemic group was significantly higher than that of the normal control or subacute ischemic group, and the signal intensity of the muscular layer of the ischemic group was significantly higher than that of the normal control group. Conclusion : Time to peak enhancement of bowel wall was a helpful criterion for assessment of the ischemic period. Analysis of the signal intensity of the bowel wall layer was useful for the early detection of bowel ischemia.

Enhanced coronary vasoconstriction after PTCA in patients with acute ischemia.

Coronary vasoconstriction of the distal vessel segment has been reported after percutaneous transluminal coronary angiography (PTCA), which was explained by increased vasoconstrictor influences. In patients with acute ischemia these changes may be even enhanced. Thus, vasomotion of the epicardial coronary arteries was studied before and after PTCA in patients with acute ischemia due to unstable angina or acute infarction. 52 patients were divided into 2 groups: Group 1 (controls) consisted of 31 patients who underwent elective (PTCA) and group 2 of 21 patients who underwent emergency PTCA for unstable angina or acute infarction. Coronary artery dimensions proximal and distal to the culprit lesion were determined by quantitative coronary angiography before and after PTCA as well as after 0.2 mg nitroglycerin i.c. at the end of the procedure. Stenosis severity was similar before and after PTCA in both groups (before, 91 +/- 8% in group 1 vs 90 +/- 9% in group 2; after, 28 +/- 9% vs 23 +/- 10%, resp.). Heart rate and mean blood pressure remained unchanged. In the group with acute ischemia no vasodilation of the proximal (2 +/- 3%) and distal vessel (-1 +/- 4%) occurred after PTCA, whereas in the control group significant vasodilation of both vessel segments (11 +/- 2% resp. 13 +/- 3%) was found. The response to nitroglycerin was maintained in both groups. In the control group there was a significant correlation between stenosis severity and percent diameter change of the distal vessel segment. However, in the acute ischemic group this relationship was shifted downwards suggesting an enhanced vasoconstrictor response in these patients. Epicardial coronary arteries in patients with acute ischemia show an enhanced vasoconstriction after PTCA. Nevertheless, the response to nitroglycerin is maintained suggesting that functional (endothelial dysfunction) rather than structural factors are responsible for this phenomenon.

Ischemic conditioning (delay phenomenon) improves esophagogastric anastomotic wound healing in the rat.

Esophagogastric anastomotic leaks are a major source of morbidity after esophagectomy. Occult ischemia of the mobilized gastric fundus is an important etiological factor for this failure of healing. To test the hypothesis that ischemic conditioning (delay phenomenon) could improve esophagogastric anastomotic healing, anastomotic healing was studied in a rodent model of partial gastric devascularization. Thirty-four Sprague-Dawley rats (two groups of 17 rats) underwent partial gastric devascularization and creation of esophagogastric anastomoses. In the acute ischemia group, devascularization and anastomosis were done at the same laparotomy. In the ischemic conditioned group, devascularization was done 3 weeks before anastomosis. Gastric tissue perfusion was assessed by laser-Doppler flowmetry before and after devascularization in both groups, and 3 weeks after devascularization in the ischemic conditioned group. All rats were killed 4 days after anastomosis, and the wounds assessed for dehiscence, breaking strength, and hydroxyproline concentration. Gastric tissue perfusion, measured in tissue perfusion units (TPU) decreased immediately after devascularization (before: 73.6 +/- 12.1 TPU; after: 25.0 +/- 6.5 TPU; P < 0.001). After 3 weeks, gastric tissue perfusion returned to baseline values in the ischemic conditioned rats (before: 72.3 +/- 11.0 TPU; 3 weeks, 71.1 +/- 15.1 TPU; P < 0.80). Ischemic conditioned rats had fewer anastomotic leaks (2 vs. 9, P < 0.023) and higher anastomotic wound breaking strengths (2.35 +/- 1.05 N vs. 1.56 +/- .76 N, P < 0.02) than the acute ischemic rats. Anastomotic would hydroxy-proline concentration was not significantly different in the two groups (acute ischemic--0.111 +/- .033 mumol/mg, ischemic conditions--0.097 +/- .026 mumol/mg, P < 0.20). In this rodent model of partial gastric devascularization, ischemic conditioning (delay phenomenon) ameliorated the harmful effect of ischemic on esophagogastric anastomotic wound healing.