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.

A method for the aerodynamic design of dry powder inhalers.

An inhaler design methodology was developed and then used to design a new dry powder inhaler (DPI) which aimed to fulfill two main performance requirements. The first requirement was that the patient should be able to completely empty the dry powder from the blister in which it is stored by inspiratory effort alone. The second requirement was that the flow resistance of the inhaler should be geared to optimum patient comfort. The emptying of a blister is a two-phase flow problem, whilst the adjustment of the flow resistance is an aerodynamic design problem. The core of the method comprised visualization of fluid and particle flow in upscaled prototypes operated in water. The prototypes and particles were upscaled so that dynamic similarity conditions were approximated as closely as possible. The initial step in the design method was to characterize different blister prototypes by measurements of their flow resistance and particle emptying performance. The blisters were then compared with regard to their aerodynamic performance and their ease of production. Following selection of candidate blisters, the other components such as needle, bypass and mouthpiece were dimensioned on the basis of node-loop operations and validation experiments. The final shape of the inhaler was achieved by experimental iteration.

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.

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.

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.

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.

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.

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.

Prevention of deleterious effects of reperfusion injury using one-week high-dose allopurinol.

Allopurinol has been widely used to reduce the severity of the reperfusion injury. However, conflicting data have been reported regarding the dosage, the duration of the timing, and the administrative regimen of the drug. The aim of this study was, therefore, to evaluate the effects of short versus long periods of allopurinol pretreatment on the anastomotic healing of intestines, directly after being subjected to ischemia-reperfusion (IR) stress. Furthermore, the effects of an allopurinol pretreatment on the survival rate following IR stress, was also assessed. One hundred thirty-seven male Wistar rats with a median weight of 235 (range, 180-275) g used in the study. In group I (control group, N = 20) superior mesenteric artery (SMA) and collateral vessels were isolated but not occluded. In group II, the profound IR group (PIR, N = 42), the SMA was occluded immediately distal to the aorta with collateral interruption using an atraumatic arterial clip for 30 min. In group III [two days of allopurinol (ALL) pretreatment group, 2ALL, N = 38], allopurinol (100 mg/kg body wt) was given intraperitoneally on a daily basis for two days prior to the experiment. In group IV (seven days of allopurinol pretreatment group, 7ALL, N = 37), the same pretreatment and the allopurinol schedule was performed for seven days before surgery. All animals underwent 3 cm of ileal resection and primary anastomosis, 10 cm proximal to 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 as were the histopathologic evaluation. No rats in group I, 20 rats in group II, 18 rats in group III, and 7 rats in group IV died (P = 0.0003). Anastomotic dehiscence was found in one of 20 group I, in 11 of 22 in group II, in 9 of 20 in group III, and in 3 of 30 in group IV (P = 0.0003). On the third and seventh days, the median bursting pressures of the anastomosis were determined: 42 and 235 mm Hg in group I, 17 and 105 mm in Hg in group II, 22 and 183 mm Hg in group III, and 36 and 214 mm Hg in group IV (P < 0.0001). The burst occurred at the anastomoses in all animals tested on the third postoperative day, one in group I, six in group II, four in group III and one in group IV on the seventh postoperative day (P < 0.01). All deleterious effects of reperfusion injury on intestinal anastomosis healing, including survival rates and the histopathological parameters, were significantly prevented by seven days, but not two days, of high-dose allopurinol pretreatment.

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.

Role of tumour necrosis factor in lung injury caused by intestinal ischaemia-reperfusion.

BACKGROUND: Despite the well known inflammatory effects of tumour necrosis factor alpha (TNF), the mechanism of TNF-mediated lung injury following ischaemia-reperfusion (I/R) is still unclear. In this study, the role of TNF in the development of acute lung injury following intestinal I/R was investigated. METHODS: Male Wistar rats underwent either sham operation (n = 10), 1 h of superior mesenteric artery occlusion and 2 h of reperfusion (I/R, n = 10), or pretreatment with anti-TNF polyclonal antibody 2 mg/kg and I/R (n = 6). Lung injury was evaluated by Evans blue dye concentration, immunohistochemical staining and morphometric analysis. Intestinal injury was assessed by Evans blue dye concentration and histological examination. RESULTS: Intestinal I/R resulted in lung injury characterized by an increase in Evans blue dye concentration, neutrophil sequestration, and obvious staining for expression of pulmonary CD11b and CD18. Pretreatment of animals with anti-TNF antibody led to a reduction in the sequestration of neutrophils, and a decrease in expression of pulmonary intracellular adhesion molecule 1 and CD18. Anti-TNF antibody pretreatment also reduced the intestinal microvascular injury but not histological grade after intestinal I/R. CONCLUSION: Treatment with an anti-TNF antibody resulted in a significant attenuation of lung injury following intestinal I/R. The data indicate that TNF is an important trigger for upregulation of pulmonary endothelial and neutrophil adhesion molecules after intestinal I/R.

Effect of ischemia/reperfusion as a systemic phenomenon on anastomotic healing in the left colon.

Intestinal ischemia/reperfusion provokes a local inflammatory response leading to a systemic inflammatory state. In this study we aimed to assess the effects of intestinal ischemia/reperfusion injury on anastomotic healing in the left colon with an intact vascular supply. A total of 94 Wistar albino rats were divided into three groups: sham-operated control (group I, n = 25), 30 minutes of intestinal ischemia/reperfusion (group II, n = 40), and 7-day allopurinol pretreatment and intestinal ischemia/reperfusion (group III, n = 29). After the reperfusion experiment, a segmental left colon resection and anastomosis were done. On postoperative days 3 and 7 anastomotic bursting pressure, anastomotic and operative complications, and intraabdominal adhesions were assessed. Mortality rates were 1/25, 16/40, and 4/29 for groups I, II, and III, respectively (p = 0.001). There was no difference among the groups for wound and anastomotic healing parameters evaluated by macroscopic criteria. On postoperative day 7 the mean bursting pressures were 220.3 +/- 18.5, 162.0 +/- 21.0, and 213.9 +/- 24.7 for groups I, II, and II, respectively (p = 0.000). Significantly dense adhesions were found in group II (p = 0.000). Allopurinol pretreatment prevented the effects of ischemia/reperfusion on anastomotic healing of the left colon. Intestinal/ischemia reperfusion causes impairment of anastomotic healing of the left colon. In addition to remote organ effects, reperfusion injury may affect anastomotic healing in the viscera with an intact vascular supply.

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.

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.

Intestinal ischemia and reperfusion impairs vasomotor functions of pulmonary vascular bed.

OBJECTIVE: To investigate the effects of intestinal ischemia and reperfusion (I/R) on the pulmonary vascular endothelium and smooth muscle. SUMMARY BACKGROUND DATA: Respiratory failure is an important cause of death and complications after intestinal I/R. Although the mechanism of respiratory failure in this setting is complex and poorly understood, recent studies of lung injury suggest that endothelial dysfunction may play a significant role. METHODS: A rat model of acute lung injury was studied after 60 minutes of superior mesenteric arterial occlusion followed by either 120 or 240 minutes of reperfusion. The pulmonary vasomotor function was examined in isolated lungs perfused at a constant flow rate. RESULTS: Sixty minutes of intestinal ischemia followed by 120 or 240 minutes of reperfusion led to a significant reduction in the ability of the pulmonary vasculature to respond to angiotensin II, acetylcholine, and calcium ionophore but not to nitroglycerin. The vasoconstriction response to N(G)-nitro-L-arginine methyl ester, which is a measure of basal nitric oxide release, was diminished in the 240-minute reperfusion group. Intestinal I/R was also associated with pulmonary leukosequestration and increased pulmonary microvascular leakage. CONCLUSIONS: Basal and agonist-stimulated release of nitric oxide from the pulmonary vascular endothelium and the ability of pulmonary smooth muscle to contract in response to angiotensin II were impaired by intestinal I/R. Such functional impairment in both pulmonary vascular endothelium and smooth muscle may contribute to the alveolocapillary dysfunction and pulmonary hypertension found in acute lung injury after intestinal I/R.

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.

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.