The angiogenic effects of ischemic conditioning in experimental critical limb ischemia.

OBJECTIVES: Ischemic conditioning (IC) is a method of angiogenic stimulus for limb ischemia. Here, we aimed to investigate the effects of short-term repeated ischemic stimulus on critical lower limb ischemic injury. METHODS: Rats were divided into four groups consisting of 40 animals in each group: sham, ischemia, local IC, and remote IC groups. Right-leg critical limb ischemia was achieved through ligation of the iliac artery and vein in male Sprague-Dawley rats except the sham group. Repeated transient ischemia using the tourniquet method was used for IC of lower extremities in the local and remote groups. IC was performed on the right leg for the local group and on the left leg for the remote group. Ten rats in each group were sacrificed for evaluation on days 1, 7, 14, and 30. Endothelial progenitor cell (EPC) counts were measured. Gastrocnemius muscles were evaluated for the degree of ischemia. Laser Doppler blood flow measurements were performed in order to make comparison between the blood flows of the limbs of the groups. RESULTS: The blood flow in the right limb of rats in the sham (1.65 perfusion units [PU]) and local IC (1.67 PU) groups was significantly higher than the ischemic group (1.17 PU) (p = .001 and p = .022 respectively). The levels of EPCs in the ischemia (1.09 ± 0.5) and remote IC groups (1.36 ± 0.8) were significantly higher than the sham (0.38 ± 0.2) group on day 7 (p = .026 and p = .002 respectively). Remote IC and local IC groups exhibited increased histopathological ischemia on day 7 when compared with sham group (p = .001, p = .01 respectively). The angiogenic scores on the 7th, 14th and 30th days for local IC and remote IC groups were significantly higher than sham and ischemia groups. CONCLUSIONS: IC seems to be the potent activator of angiogenesis in ischemic tissue. This study provides preliminary data showing that repeated short ischemic stimuli may reduce critical ischemic injury by promoting angiogenesis.

Surgical treatment of peripheral aneurysms in patients with Behcet's disease.

INTRODUCTION: Our aim was to report our experience with 23 patients presenting with 32 peripheral aneurysms secondary to Behcet's disease (BD) and their outcome after vascular surgery. METHODS: The study was retrospective in nature. Except for those presenting with aneurysm rupture, patients underwent surgery after treatment of acute inflammatory lesions. All aneurysms appeared to be pseudo-aneurysms. Graft interposition with polytetrafluoroethylene or saphenous vein was most commonly employed. Postoperatively, all patients were put on immunosuppressive and antiplatelet therapy. Follow-up was done every 6-12 months, complications recorded and managed appropriately. RESULTS: All the patients were males. The mean age at diagnosis of a peripheral aneurysm was 41.0 ± 9 years. There were 17 (53%) femoral, 8 (25%) popliteal, two carotid, two external iliac, two brachial and one internal iliac aneurysms. Fourteen (61%) patients had a single peripheral aneurysm while nine had two. Surgery was performed for all initially presenting 23 aneurysms. Six patients with multiple peripheral aneurysms had surgery for their second asymptomatic aneurysm. The mean follow-up period was 84 ± 62 months. Of 29 aneurysms operated on, 7 (24%) anastomotic pseudo-aneurysms and 11 (38%) graft occlusions developed. Five (22%) patients underwent major lower extremity amputations. Six (26%) mortalities were recorded. CONCLUSION: Surgery for peripheral aneurysms in BD is warranted in many instances. Results of operation can be improved by prolonged monitoring. However, despite all efforts, peripheral aneurysm involvement in BD worsens the prognosis.

Hand ischemia caused by solitary humeral exostosis irritating the brachial artery.

A 39-year-old woman presented with ischemia of the left hand. Angiography revealed thrombosis of forearm arteries. Surgical intervention was unsuccessful. CT angiography revealed an exostosis on the distal humerus close to the brachial artery which we believe was the cause of repetitive minor trauma to the brachial artery leading to embolic occlusion of the radial and ulnar arteries. Early diagnosis of the underlying cause is the key to successful treatment of hand ischemia. For patients without risk factors for arterial occlusive disease, imaging of bony structures must be performed in order not to miss the likely cause of an insidious repetitive vascular trauma.

Occlusion of the celiac trunk, the inferior mesenteric artery and stenosis of the superior mesenteric artery in peripheral thrombangiitis obliterans.

Buerger's disease is an inflammatory occlusive disease which commonly involves medium-sized or smaller vessels of extremities. Mesenteric involvement in Buerger's disease is very rare. It can occur at any time during the course of the disease and presents with acute mesenteric ischaemia. In this study, a case of Buerger's disease with mesenteric involvement diagnosed before the onset of acute mesenteric ischaemia and managed endovascularly is reported.

Surgical repair of a giant renal artery aneurysm: a case report.

A case of a giant renal artery aneurysm and multiple small branch aneurysms in a 48-year old man is presented. The largest aneurysm was repaired successfully with kidney preservation. Small branch aneurysms were left alone. Subsequent CT scans 6, 12 and 20 months after the operation revealed the same aneurysms without any increase in size and shape.

Thromboxane synthase inhibitor, UK 38485, prevents renal injury in the rabbit isolated perfused kidney exposed to cold ischemia.

Recent studies have indicated that, the administration of thromboxane A2 (TxA2) inhibitors improved renal functions in experimental renal allograft transplantation. Thus TxA2, a vasoconstrictor metabolite of arachidonic acid, may play a role in renal function and blood flow during hypothermic storage. The aim of the present study was to evaluate the cytoprotective effect of TxA2 synthase inhibitor, UK 38485, on altered renal function due to cold ischemia for 24 and 72 h. Experiments were performed in isolated perfused kidney from adult rabbits. Kidneys were perfused with Euro-Collins (EC) containing UK 38485 and incubated with the same solution in a beaker exposed to cold ischemia for 24 and 72 h. The same procedure was applied to the control kidneys in EC solution alone. Vascular responses and urinary output to noradrenaline, angiotensin II, endothelin-1, acetylcholine, and sympathetic stimulation were assessed as the functional activity of kidney. The addition of UK 38485 to EC solution increased the preservation time of kidney and protects the vascular endothelial regulatory functions and urine excretion when compared to EC alone. The results of the present study can be taken as an evidence of the cytoprotective effect of the UK 38485 and might be useful for kidney preservation.

Poly(adp-ribose) synthetase inhibition reduces bacterial translocation in rats after endotoxin challenge.

We investigated whether 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, reduces bacterial translocation (BT) after intraperitoneal endotoxin administration. Wistar rats were randomized to receive intraperitoneal saline (control, n = 6); endotoxin (n = 8); 3-AB (n = 6); and 3-AB plus endotoxin (n = 8). Six hours later, to evaluate the endotoxin-related intestinal injury and BT, tissue and blood samples were collected. Administration of intraperitoneal endotoxin caused severe intestinal injury and BT to mesenteric lymph nodes. PARS inhibition with 3-AB completely prevented endotoxin-induced BT. No colony-forming bacteria was isolated from the samples obtained from 3-AB-pretreated animals under endotoxin challenge. Treatment with 3-AB significantly reduced the endotoxin-induced intestinal mucosal injury. The inhibition of PARS by its blocker 3-aminobenzamide during endotoxemia prevents bacterial translocation and intestinal injury in rats. PARS activation may provide a novel therapeutic approach in reducing gut barrier failure seen in endotoxemia.

Ischemia and reperfusion injury: prevention of pulmonary hypertension and leukosequestration following lower limb ischemia.

Ischemia is a common clinical event with potentially serious consequences. The major part of tissue damage occurs upon reperfusion and is mediated by activated neutrophils. Ischemia reperfusion injury is manifested by oedema and increased microvascular permeability. This study tested cardiopulmonary functions following 2 h of lower limb ischemia. Anesthetized dogs were randomized into three groups: nonischemic sham dogs (n = 4), ischemic control dogs (n = 8) and ischemic dogs pretreated with prostaglandin (PG)E1 (n = 8). In control animals, mean pulmonary artery pressure (mPAP) increased 1 min after declamping from 13.37 +/- 2.61 mmHg to 16.88 +/- 3.68 mm Hg (P < 0.05). Pulmonary microvascular pressure (Pmv) increased within 1 minute of reperfusion from 7.71 +/- 1.87 mm Hg to 10.54 +/- 3.71 mm Hg (P < 0.05). These changes are consistent with increased lung microvascular permeability. White blood cell count fell slightly but not significantly and lung histology showed leukosequestration in alveoli of 171 +/- 22 polymorphonuclear leukocyte (PMN)/10 high powered fields (HPF) in the ischemic control group compared with 121 +/- 56 PMN/10 HPF in the sham group (P < 0.05). Systemic arterial pressure, cardiac output, central venous pressure and pulmonary artery wedge pressure were unaffected. In animals pretreated with PGE1, mPAP and Pmv were unchanged during reperfusion. Lung histologic findings appeared normal and leukosequestration was not observed. PMN counts in alveoli showed 95 +/- 26 PMN/10 HPF, lower than in ischemic control animals (P < 0.05). These data indicate that lower limb ischemia during reperfusion leads to pulmonary hypertension and leukosequestration, PGE1 infusion is effective in limiting ischemia reperfusion injury.

Management of thoracic aortic graft infections.

BACKGROUND: We reviewed our experience managing patients with thoracic aortic graft infections to evaluate their clinical characteristics and outcomes of treatment. METHODS: Records of 20 consecutive patients with thoracic aortic graft infections managed over a 7 year period were retrospectively reviewed. Current follow-up status was obtained for all survivors. RESULTS; Nineteen patients (95%) underwent surgical treatment. Graft excision and in situ replacement were performed using Dacron grafts (10/19, 53%) or cryopreserved homografts (5/19, 26%). Three pseudoaneurysms were managed by debridement and primary repair. Although 30 day postoperative survival was 89% (17/19), in-hospital mortality occurred in 8 patients (42%). Infected thoracoabdominal aortic grafts were universally fatal. Of 6 patients with infected composite valve grafts, both patients who received new composite valve grafts died and all 4 who received homografts survived (p = 0.067). CONCLUSIONS: Infections involving thoracic aortic grafts continue to carry a high mortality rate, especially in patients with polymicrobial infections, thoracoabdominal aortic graft infections, and composite valve graft infections. Use of homografts in the latter situation may improve outcome.

S100beta correlates with neurologic complications after aortic operation using circulatory arrest.

BACKGROUND: Astrocyte protein S100beta is a potential serum marker for neurologic injury. The goals of this study were to determine whether elevated serum S100beta correlates with neurologic complications in patients requiring hypothermic circulatory arrest (HCA) during thoracic aortic repair, and to determine the impact of retrograde cerebral perfusion (RCP) on S100beta release in this setting. METHODS: Thirty-nine consecutive patients underwent thoracic aortic repairs during HCA; RCP was used in 25 patients. Serum S100beta was measured preoperatively, after cardiopulmonary bypass, and 24 hours postoperatively. RESULTS: Neurologic complications occurred in 3 patients (8%). These patients had higher postbypass S100beta levels (7.17 +/- 1.01 microg/L) than those without neurologic complications (3.63 +/- 2.31 microg/L, p = 0.013). Patients with S100beta levels of 6.0 microg/L or more had a higher incidence of neurologic complications (3 of 7, 43%) compared with those who had levels less than 6.0 microg/L (0 of 30, p = 0.005). Retrograde cerebral perfusion did not affect S100beta release. CONCLUSIONS: Serum S100beta levels of 6.0 microg/L or higher after HCA correlates with postoperative neurologic complications. Using serum S100beta as a marker for brain injury, RCP does not provide improved cerebral protection over HCA alone.

A new predictive model for adverse outcomes after elective thoracoabdominal aortic aneurysm repair.

BACKGROUND: Recent recommendations have emphasized individualized treatment based on balancing a patient's risk of thoracoabdominal aortic aneurysm rupture with the risk of an adverse outcome after surgical repair. The purpose of this study was to determine which preoperative risk factors currently predict an adverse outcome after elective thoracoabdominal aortic aneurysm repair. METHODS: A single, composite end point termed adverse outcome was defined as the occurrence of any of the following: death within 30 days, death before discharge from the hospital, paraplegia, paraparesis, stroke, or acute renal failure requiring dialysis. A risk factor analysis was performed using data from 1,108 consecutive elective thoracoabdominal aortic aneurysm repairs. RESULTS: The incidence of an adverse outcome was 13.0% (144 of 1,108 patients); predictors included preoperative renal insufficiency (p = 0.0001), increasing age (p = 0.0035), symptomatic aneurysms (p = 0.020), and extent II aneurysms (p = 0.0001). These risk factors were used to construct an equation that estimates the probability of an adverse outcome for an individual patient. CONCLUSIONS: This new predictive model may assist in decisions regarding elective thoracoabdominal aortic aneurysm operations. For patients who are acceptable candidates, contemporary surgical management provides favorable results.

Mortality and paraplegia after thoracoabdominal aortic aneurysm repair: a risk factor analysis.

BACKGROUND: Recent recommendations regarding thoracoabdominal aortic aneurysm (TAAA) management have emphasized individualized treatment based on balancing a patient's calculated risk of rupture with their anticipated risk of postoperative death or paraplegia. The purpose of this study was to enhance this risk-benefit decision by providing contemporary results and determining which preoperative risk factors currently predict mortality and paraplegia after TAAA surgery. METHODS: Risk factor analyses based on data regarding 1,220 consecutive patients undergoing TAAA repair from 1986 through 1998 were performed using multiple logistic regression with step-wise model selection. RESULTS: The 30-day mortality rate was 4.8% (58 of 1,220) and the incidence of paraplegia was 4.6% (56 of 1,206). For elective cases, predictors of operative mortality included renal insufficiency (p = 0.0001), increasing age (p = 0.0005), symptomatic aneurysms (p = 0.0059), and extent II aneurysms (p = 0.0054). Extent II aneurysms (p = 0.0023) and diabetes (p = 0.0402) were predictors of paraplegia. CONCLUSIONS: These risk models may assist in decisions regarding elective TAAA operations. For patients who are acceptable candidates, contemporary surgical management provides favorable results.

Reperfusion injury delays healing of intestinal anastomosis in a rat.

BACKGROUND: Revascularization of ischemic bowel may induce further local tissue damage due to reperfusion injury. Therefore, we aimed to investigate the effect of ischemia-reperfusion injury on the healing of intestinal anastomosis in experimental models. METHODS: One hundred and two male Wistar rats were divided into three groups: a control group (group I, n = 23); an ischemia group (group II, n = 32), in which only the superior mesenteric artery (SMA) was occluded for 30 minutes; and a profound ischemia group (group III, n = 47), in which SMA was occluded as well as collateral vessels for 30 minutes. The pulsations were seen to return to marginal vessels and the bowels began to appear pinker and healthier in all groups following the restoration of arterial flow. Then, all animals underwent a 3-cm ileal resection and primary anastomosis, 10 cm proximal to the ileocecal valve. Within each group, animals were anesthetized either on the third or seventh postoperative days. Abdominal wound healing, intraabdominal adhesions, anastomotic complications, anastomotic bursting pressure measurements, and bursting site were recorded. RESULTS: Statistically significant differences were detected in intraperitoneal adhesion scores in group II and III (P <0.001). Anastomotic dehiscence was found in 2 of 23 (9%) in group I, 5 of 32 (16%) in group II, and 16 of 47 (34%) in group III (P <0.001). On the third and seventh days, the median bursting pressures of the anastomosis were determined to be 42 mm Hg and 250 mm Hg in group I, 46 and 253 in group II, and finally 19 and 90 mm Hg in group III (P <0.01). The burst occurred at the anastomoses in all animals tested on the third postoperative day, none in group I, 4 (28%) in group II, and 8 (67%) in group III on the seventh postoperative day (P <0.005). CONCLUSION: The present study demonstrated that ischemia-reperfusion impairs anastomotic healing. Despite the fact that the intestines are well perfused and viable after revascularization, one must bear in mind that intestinal reperfusion may compromise anastomotic healing.

Direct trocar insertion versus Veress needle insertion in laparoscopic cholecystectomy.

BACKGROUND: Direct insertion of the trocar is an alternative method to Veress needle insertion for the creation of pneumoperitoneum. The safety of direct disposable shielded trocar insertion for the creation of pneumoperitoneum was assessed by comparing with Veress needle insertion during laparoscopic cholecystectomy (LC). METHODS: One thousand five hundred patients undergoing LC with pneumoperitoneum were included in this study. In 470 patients the Veress needle insertion technique was used, and in 1,030 patients direct trocar insertion technique was used. Patients having indications for open trocar insertion were excluded from the study. RESULTS: Complication rate was significantly higher in the Veress needle group (14% versus 0.9%; P <0.01), and the two major complications, gastric perforation and iliac artery laceration, were also encountered in this group. CONCLUSIONS: Our results suggest that with a lower complication rate, direct insertion of the disposable trocar is a safe alternative to Veress needle insertion technique for the creation of pneumoperitoneum. Such an approach has further advantages such as less cost/instrumentation and rapid creation of pneumoperitoneum.

Cerebrospinal fluid drainage in thoracoabdominal aortic surgery.

Paraplegia caused by spinal cord ischemia remains a devastating complication after surgical repair of thoracoabdominal aortic aneurysms. Cerebrospinal fluid (CSF) drainage has been advocated as a protective adjunct to reduce the incidence of postoperative neurologic deficits. Studies in animals have shown that CSF drainage during thoracic aortic clamping reduces CSF pressure, improves spinal cord blood flow, and prevents paraplegia. Previous retrospective and randomized clinical studies, however, have been inconclusive because of confounding factors and other limitations. A recent prospective randomized trial focusing solely on CSF drainage during repair of extent I and II thoracoabdominal aortic aneurysms indicated an 80% reduction in the relative risk of paraplegia and paraparesis in patients who received this adjunct. Consequently, CSF drainage has emerged as an important addition to the multimodality strategy for preventing postoperative spinal cord deficits.

Effects of intestinal ischemia-reperfusion on major conduit arteries.

Intestinal ischemia-reperfusion (I-R) is a common and serious clinical condition associated with simultaneous remote organ dysfunction. The purpose of this study was to investigate the effects of intestinal I-R on the vasomotor functions of major conduit arteries. Anesthetized rabbits were randomly assigned to one of three groups: sham-operated controls (Group I), and one-hour intestinal ischemia with two-hour reperfusion (Group II) or four-hour reperfusion (Group III). The following mechanisms of vasomotor functions were studied in abdominal aorta, superior mesenteric, renal, pulmonary, and carotid arterial rings: (1) endothelial-dependent vasodilation response to acetylcholine, (2) endothelial-independent vasodilation response to nitroprusside, (3) beta-adrenergic vasodilation response to isoproterenol, and (4) phenylephrine-induced vasoconstriction. Intestinal injury was quantified using malondialdehyde (MDA) concentration and wet-to-dry intestine weight ratio. Intestinal I-R did not affect the maximal responsiveness or the sensitivity to acetylcholine, nitroprusside, and isoproterenol in all the vessels studied. The maximal contractile response to phenylephrine increased significantly in mesenteric artery in Group II, (227.1+/-15.1% vs. 152.8+/-11.7% in controls) (p<0.05). Intestinal MDA concentration, a marker of oxidant injury, increased from 39.87+/-9.41 nmol/g to 67.8+/-8.8 nmol/g in group II (p<0.01), and to 94.8+/-7.56 nmol/g in Group III (p<0.001). Wet-to-dry intestine weight ratio increased from 3.62+/-0.12 to 4.28+/-0.17 in Group II (p<0.01), to 4.62+/-0.14 in Group III (p<0.001). These data indicate that although the intestines of the animals subjected to intestinal I-R are seriously injured, the smooth muscle relaxation of major conduit arteries was not affected.

Obstructive jaundice promotes bacterial translocation in humans.

BACKGROUND/AIMS: Significant bacterial translocation was demonstrated following experimental biliary obstruction, however very little is known about the importance and the prevalence of gut-origin sepsis in obstructive jaundice patients. Therefore, the aim of this study was to investigate the concept of gut-origin sepsis in obstructive jaundiced patients and its clinical importance. METHODOLOGY: Twenty-one patients requiring laparotomy for obstructive jaundice (group I) and thirty patients operated on electively mainly for chronic cholecystitis (group II) were studied. Peritoneal swab, mesenteric lymph node, portal venous blood, liver wedge biopsy and bile were sampled for culture immediately after opening the peritoneum. Additionally, peripheral blood samples were taken pre- and post-operatively from all patients. Post-operatively, patients were monitored for infectious complications. RESULTS: The mean serum bilirubin concentration, gamma glutamyl transferase and alkaline phosphatase levels in jaundiced patients before therapeutic intervention were significantly higher than in control patients. Five patients demonstrated bacterial translocation in group I (24%), whereas only one did so in group II (3.5%, p < 0.05). Septic complications were detected in three patients, but only in two with bacterial translocation in group I. There was one patient with bacterial translocation who had septic complication in group II. CONCLUSIONS: The present study demonstrated that obstructive jaundice significantly promotes bacterial translocation in humans, however, its clinical importance has yet to be defined.

Colonic anastomotic healing after preoperative chemo-radiotherapy in rat.

PURPOSE: To prevent micrometastasis at an earlier stage and to increase the lateral or circumferential tumor free margins, there is a rationale for neo-adjuvant chemo-radiotherapy in patients with colorectal cancer. In order to investigate the effects of such a protocol on colonic anastomotic healing, an experimental study resembling the clinical use of neo-adjuvant concomitant 5-FU+ irradiation treatment of colorectal cancer was conducted. MATERIALS AND METHODS: Seventy-one male Wistar rats were divided into three groups: a control group (I) underwent left colon resection and primary anastomosis (n = 20); a sham-treated group (II, n = 20); and a study group (III) which received fractionated irradiation to the whole pelvis to a total dose of 22 Gy, 5.5 Gy per fraction, in four consecutive days with linear accelerator and concomitant intra-peritoneal 5-FU (20 mg/kg/day) for five consecutive days. The last fraction of irradiation and the last injection were given four and three days before colonic resection and anastomosis, respectively. Within each group one-half of the animals were anesthetized on the third postoperative day and one-half on the seventh postoperative day. Abdominal wound healing, intraperitoneal adhesions, anastomotic complications, and anastomotic bursting pressure measurements were recorded. Following these measurements the anastomotic segment was resected for hydroxyproline content, myeloperoxidase activity, and histopathological evaluation. RESULTS: There were no differences in the abdominal wound healing, intraperitoneal adhesions, and anastomotic complications between groups. At three and seven days, the mean bursting pressures of the anastomoses were 36.5 mm Hg and 208 mm Hg in group I, 34.5 and 228 in group II, and 27 and 167 in group III, respectively (p < 0.01, group III vs both groups I and II on day seven). The burst occurred at the anastomosis in all animals tested on the third postoperative day, and one in group I (10%), none in group II, and four in group III (40%) on the seventh postoperative day. CONCLUSION: Preoperative pelvic fractionated irradiation and concomitant 5-FU delays anastomotic healing.

Simultaneous manifestation of an aortocaval and aortoduodenal fistula.

An unusual case of traumatic aortocaval and aortoduodenal fistula is presented in which the two conditions occurred simultaneously. A 19-year-old man was admitted with acute upper gastrointestinal bleeding and a pulsatile abdominal mass. An aortography revelead an aortocaval fistula and at the operation an aortocaval and aortoduodenal fistula was found. An aortocaval fistula can be discovered when a patient presents with an abdominal bruit or cardiomegaly with or without heart failure. The diagnosis of an aortoenteric fistula is difficult because of the subtleties in manifestation. The presence of an abdominal pulsatile mass and acute gastrointestinal bleeding should indicate that an aortoenteric fistula is possible.

A late onset carotido-jugular fistula following shotgun injury.

The incidence of arteriovenous fistulae (AVF) is quite rare in the head and neck region comprising less than 4% of all the traumatic AVF encountered elsewhere in the body. A 42-year-old man presented with a palpable thrill in the cervical region and headache. He had a shotgun injury 10 years ago and had no problem until the previous three months. Diagnosis of a high output traumatic AVF between right common carotid artery and internal jugular vein was made arteriographically. Presence of a neighbouring traumatic aneurysm on the common carotid artery and 9 mm diameter of the fistula tractus suggested open surgery. At the operation ligation of the tractus and aneurysmorraphy was performed and the patient was discharged in the third postoperative day. He has still no problem. This case documented that a shotgun injury even 10 years later may result with an AVF.