Trace elements and toxic heavy metals play a role in Buerger disease and atherosclerotic peripheral arterial occlusive disease.

AIM: The aim of the present study was to define the roles of trace elements and toxic heavy metals in Buerger disease and atherosclerotic peripheral arterial occlusive disease (PAOD). METHODS: Seventy-five subjects who were identical in demographic charecteristics were selected for the study; 25 with Buerger disease, 25 with PAOD, 25 healthy volunteers. Serum selenium (Se), zinc (Zn), copper (Cu), iron (Fe),whole blood cadmium (Cd) and lead (Pb), erythrocyte glutathione (GSH), erythrocyte glutathione peroxidase (GSH-Px), erythrocyte and plasma malondialdehyde (MDA) levels were measured. RESULTS: Serum Se and Zn levels were significantly low in patients with Buerger disease compared to patients with PAOD and controls (P<0.001 and P<0.001 respectively). Serum levels of Fe and Zn were also significantly low in patients with PAOD compared to controls (p<0.001 and p<0.05 respectively). In contrast, Cu and Pb levels in Buerger disease group were significantly high compared to PAOD and control groups (P<0.001 and P<0.001 respectively). Erythrocyte GSH and GSH-Px levels were significantly lower in patients with Buerger disease compared to patients with PAOD and controls (P<0.001 and P<0.001 respectively), while erythrocyte and plasma MDA levels were significantly higher (P<0.001 and P<0.001 respectively). CONCLUSION: It can be concluded that the levels of trace elments and toxic heavy metals and oxidative stress influence the disease process in Buerger disease more than PAOD.

Serine protease inhibitor aprotinin ameliorates renal injury in a rat model of ischemia-perfusion injury.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. OBJECTIVE: To investigate the therapeutic effects of aprotinin on tissue protection against I/R injury in a rat model. N-acetylcysteine (NAC), a potent antioxidant, was also tested to assess the experimental model. MATERIALS AND METHODS: Twenty-four rats were categorized into 3 groups of 8 rats each: those receiving isotonic sodium chloride solution (control group); NAC, 150 mg/kg; and aprotinin, 40,000 KIU/kg. The animals underwent unilateral nephrectomy after 60 minutes of warm ischemia and 60 minutes of reperfusion of the kidney. Malondialdehyde, a lipid peroxidation marker, and antioxidant glutathione levels were measured in the kidney parenchyma. Tissue samples were obtained for histologic analysis. RESULTS: Compared with the control group, the NAC group demonstrated significantly low levels of malondialdehyde (P = .04) and high levels of glutathione (P = .01). At histopathologic analysis, less acute tubular necrosis (ATN) and cellular swelling was noted in the NAC group (P = .002 and P = .005, respectively). In the aprotinin group, histopathologic analysis revealed less tissue damage in terms of ATN (P < .001, cellular swelling (P < .001), and vacuolysis (P = .002). Compared with the NAC group, ATN (P = .01), vacuolysis (P = .04), and congestion (P = .05) were significantly less in the aprotinin group. CONCLUSIONS: Our results suggest that administration of aprotinin attenuates renal I/R injury. This observation has potential application for kidney preservation for transplantation, for aortic surgery, and for renal artery interventions by protecting cells from free radical damage.

Attenuation of acute lung injury following lower limb ischemia/reperfusion: the pharmacological approach.

AIM: The purpose of this study was to examine the effects of N-acetylcysteine (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage following ischemia/reperfusion injury in a rat hind limb model. A well known antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison. METHODS: Ischemia was induced in the lower limb for 4 h by vascular clamping and followed by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. P<0.005 was considered statistically significant. RESULTS: Plasma TBARS values were found to be significantly lower in the DMSO (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also in the aprotinin group lung TBARS values were found to be significantly lower compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological examination showed less prominent peribronchial leukostasis (P<0.005) and interstitial leukostasis (P<0.005) in all drug groups compared to the control group. CONCLUSION: These observations indicate that DOBE and NAC, which are known to have antioxidant properties and aprotinin, a serine proteinase inhibitor, acted effectively on the prevention of lung injury in a rat hind limb ischemia/reperfusion model. The reason why aprotinin exerts a more protective effect than the other drugs is not clear, however, its clinical use may have the dual advantage of hemostasis and lung protection in surgical practice.

A randomized trial of intravenous iloprost (a stable prostacyclin analogue) versus lumbar sympathectomy in the management of Buerger's disease.

AIM: The aim of this study was to compare the effects of iloprost and lumbar sympathectomy (LS) in the treatment of Buerger's disease. METHODS: Two hundred patients with rest pain and/or ischemic ulcers were randomized to undergo LS or 28-day intravenous treatment of iloprost. The primary endpoint was complete healing without pain or major amputation at 4 and 24 weeks. The secondary endpoints were analgesic requirement, reduction in the ulcer size, 50% reduction of the ulcer, and shift in the modified SVS/ISCVS clinical status grading scale. RESULTS: The comparison was carried out in 162 patients (iloprost: n=84; LS: n=78). Complete healing rate was 61.9% in the iloprost group, but 41% in the LS group at the 4th week (P=0.012); respective values for the 24th week were 85.3%, 52.3%, P<0.001. Analgesic requirement was lower in the iloprost group at the 4th and 24th weeks (P=0.01, and P=0.098, respectively). The size of the ulcers decreased more in the iloprost group than the LS group (P=0.044 and P=0.035 at 4th and 24th weeks); 50% reduction in the ulcer size in the iloprost group was greater than in the LS group (P=0.001 and P=0.009 at 4th and 24th weeks). SVS/ISCVS grading scale demonstrated a better clinical benefit in patients treated with iloprost (P<0.001 at 4th week, and P<0.001 and at 24th week). CONCLUSIONS: The results of this independent study indicate that using iloprost relieves ischemic symptoms better than LS. In the era of stable prostacyclin analogues, there is no reliable evidence to support the use of LS in Buerger's disease.

The effects of clopidogrel and calcium dobesilate on intimal hyperplasia following vascular injury.

BACKGROUND: Neo-intimal hyperplasia is one of the most common causes of failure of arterial patency following cardiovascular interventions. It has been proposed that clopidogrel and calcium dobesilate may play an important role in the amelioration of intimal hyperplasia. The aim of this study is to examine the effect of these agents on intimal hyperplasia occurring after experimental balloon catheter injury. MATERIAL AND METHODS: Twenty-four male New Zealand rabbits were divided into three groups. Endothelial injury was caused by introducing a 2.5 x 20 mm balloon angioplasty-catheter into the left iliac artery. After the procedure, clopidogrel (25 mg/kg/day/orally) or calcium dobesilate (100 mg/kg/day/orally) were given for 2 weeks. Eight rabbits were given a placebo and served as controls. The contralateral non-injured iliac arteries of the control group were considered as normal iliac artery samples. Iliac artery specimens were examined planimetrically and the intima/media ratio was obtained for each vessel. RESULTS: In the control group, the intima/media ratio was still significantly higher (p < 0.05) than the contralateral normal artery 14 days after the balloon catheter injury. In the clopidogrel and calcium dobesilate groups, this ratio had significantly decreased when compared with the control group (p < 0.05). No significant difference was found when the clopidogrel and calcium dobesilate groups were compared. CONCLUSION: The anti-agregant agent clopidogrel, and the venous endothelial regulator calcium dobesilate, ameliorate intimal hyperplasia after experimentally induced vascular injury in rabbit iliac arteries.

Histopathological and immunohistochemical detection of protective effects of University of Wisconsin solution supplemented with iloprost on donor lung damage.

OBJECTIVE: Histopathological evaluation and immunohistochemical markers of surfactant B and CD34 were used to detect alveolar type II cell and pulmonary endothelial cell damage in order to assess the efficacy on donor lung protection of University of Wisconsin (UW) solution supplementation with iloprost. METHODS: Twelve rats were divided into two groups: UW solution was used alone in group I, and UW iloprost solution in group II. Lung samples were taken at regular intervals for pathological examination to evaluate alveolar cell integrity with hematoxylin and eosin staining. Preservation, of alveolar type II cell and pulmonary endothelial cells was assessed using surfactant B and CD34 immunomarkers, respectively. RESULTS: In both groups, alveolar integrity, surfactant, and CD34 revealed time-dependent, progressive damage, although this deterioration was less apparent among the iloprost-supplemented group. Alveolar integrity was better preserved at 4, 6, 8, 12, and 48 hours among group II rate. Surfactant staining showed significantly more deterioration at 12 and 24 hours in group I. Similarly, CD34 demonstrated significantly more injury at 6, 12, 24, and 48 hours in group I. CONCLUSION: Although progressive lung tissue damage assessed by histopathological and immunohistochemical methods was observed in both groups, our findings suggest less deterioration in the iloprost-supplemented group.

Cardiac echinococcosis in a 3-year-old child.

A 3-year-old girl was admitted with the diagnosis of left ventricular hydatid cyst. She also had pulmonary, hepatic and splenic cysts. The diagnosis of the left ventricular cyst was made by means of computerized tomography and confirmed using cardiac magnetic resonance imaging and transthoracic echocardiography. The patient was submitted to cystectomy on beating heart with a straightforward postoperative period.

The role of antioxidant supplementation in cardiac transplantation: an experimental study in rats.

BACKGROUND: We investigated three antioxidants, inositol hexaphosphate (IP6), superoxide dismutase (SOD), and catalase (CAT), using a Langendorf model of heart transplantation. METHODS: Rat hearts were mounted on a Langendorf perfusion apparatus with addition of IP6, SOD+CAT, IP6+SOD+CAT to St. Thomas Hospital solution (n=6 for each) versus a control group (n=6), not containing supplementation. Global ischemia was achieved for 6 hours. RESULTS: The worst peak-to-peak (PP) and +dp/dt maximum values were observed in the IP6+SOD+CAT group, the values being significantly lower than those in the SOD+CAT group. The lowest plasma creatine kinase (CK), CK-muscle-band (CK-MB), and lactate dehydrogenase levels were measured from the SOD+CAT group. The highest values for CK were in the control group, and those for CK-MB were in the IP6 group. The lowest myocardial malondialdehyde and adenosine triphosphate values were observed in the SOD+CAT group. CONCLUSIONS: Supplementing St. Thomas Hospital solution with IP6 did not ameliorate myocardial damage following global ischemia. The contractility deteriorated further when IP6+SOD+CAT were used together; however, SOD+CAT improved cardiac mechanical functions, and significantly reduced myocardial damage.

Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial disease [correction of disase].

The aim of this study was to investigate the relationship between plasma viscosity and lipoprotein and apolipoprotein pattern in normo- and hypercholesterolemic patients with peripheral occlusive arterial disease (POAD). 40 patients with POAD have been selected (8 females and 32 males, mean age: 54+/-3.2 years) with clinically evident superficial femoral occlusive artery disease. They were separated into two groups as normocholesterolemic (plasma total cholesterol <200 mg/dl) and hypercholesterolemic (plasma total cholesterol >200 mg/dl). Plasma total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, total protein, and albumin levels were determined by enzymatic methods using commercial kits. Levels of apolipoprotein AI (apo AI), and apolipoprotein B (apo B) were measured using a immunoturbidometric method. Plasma viscosity (PV) was measured by capillary viscometer. Classifying the patients with PAOD according to the cholesterol levels; hypercholesterolemic (mean total-cholesterol: 227.90+/-26.97 mg/dl) patients had significantly higher LDL-C, PV and triglyceride levels compared with nornocholesterolemic patients (p<0.001, p<0.001, p<0.001, respectively). HDL-C and apo B were significantly lower in hypercholesterolemic patients than in normocholesterolemic patients (p<0.001, p<0.001, respectively). PV was positively correlated with total cholesterol (r=0.485, p<0.05), atherogenic index (r=0.624, p<0.01), total-C/HDL-C ratio (r=0.624, p<0.05), and LDL-C/HDL-C ratio (r=0.707, p<0.001) in hypercholesterolemic patients with POAD. PV was higher in hypercholesterolemic patients with POAD than in normocholesterolemic patients with POAD. We suggest that POAD patients should be regarded as a heterogenous group with lipid and lipoprotein parameters in order to assess the microcirculation in the affected limb. In case of dyslipidemia in POAD patients an elevated plasma viscosity should be considered as coexisting risk factor.

Alpha-tocopherol (Vitamin E) and iloprost attenuate reperfusion injury in skeletal muscle ischemia/reperfusion injury.

BACKGROUND: The aim of this study was to clarify the role of a-tocopherol (vitamin E) and iloprost on skeletal muscle ischemia/reperfusion injury. SETTING: animal research laboratory of a university hospital. EXPERIMENTAL DESIGN: the iliac arteries of the 24 adult Sprague-Dawley rats were clamped and 4 hours of ischemia followed by 1 hour of reperfusion was applied. In an attempt to decrease reperfusion injury, the rats were given either a-tocopherol (n=8), iloprost (n=6) and 8 rats were given normal saline and served as control group (n=8). MEASURES: blood pH, pO2, pCO2, HCO3, Na, K, creatine kinase (CPK), lactate dehydrogenase (LDH) values were determined at the end of the reperfusion period. Malondialdehyde (MDA), a product of lipid peroxidation, was measured in blood, muscle and lung as an indicator of free radicals. RESULTS: Blood pO2 and HCO3 levels were significantly high (p<0.05); CPK, LDH and MDA levels were significantly low (p<0.05) in both a-tocopherol and iloprost groups when compared to the control group. Similarly, the MDA levels in the gastrocnemius muscle were significantly low in both treatment groups when compared to the controls (p<0.05). There was no significant difference between groups in other parameters. CONCLUSIONS: The results suggest that, both a-tocopherol and iloprost are useful for attenuating oxidative muscle damage occurring after a period of ischemia/ reperfusion.

Hemorrheological variables in critical limb ischemia.

BACKGROUND: Impaired hemorrheological properties may worsen the tissue hypoxia distal to an arterial narrowing in patients with peripheral arterial occlusive disease (PAOD). The objective of this study was to investigate the changes in red blood cell rigidity, blood viscosity and plasma viscosity as contributing factors in the development of hypoxia in patients with critical limb ischemia (CLI). METHODS: Forty patients with critical limb ischemia and 40 healthy subjects were included in the study. The subjects included in the study were non-diabetic with blood pressure measurements within the normal range. Compound known to interfere with hemorrheological parameters were not taken by the patients for at least 7 days prior to investigation. Routine blood counts (WBC, RBC, Hb, Hct), plasma fibrinogen levels, plasma total cholesterol levels, red blood cell rigidity, blood and plasma viscosity were determined in both groups. Statistical evaluation of the results of both groups was compared by student's "t"-test. The level of significance was set at p<0.05. RESULTS: Blood viscosity at a shear rate of 6.00 sec(-1) was found to be significantly lower in the CLI group (p<0.001), whereas no significant difference was encountered when blood viscosity was measured at a shear rate of 225 sec(-1). Plasma viscosity and plasma fibrinogen levels were comparable. Plasma total cholesterol levels were found to be significantly higher in the CLI group (p<0.05) and red blood cell rigidity significantly lower (p<0.001). CONCLUSIONS: These findings may provide new insights into the role of blood viscosity in patients with CLI contrary to the previous reports in the literature. Therapies that address red blood cell rigidity more directly may decrease tissue hypoxia distal to arterial narrowing by preventing hemolysis, improving microcirculation, and increasing oxygen carrying capacity and may be more beneficial for these patients.

Calcium dobesilate ameliorates lung injury following lower limb ischemia/reperfusion.

We examined the effects of calcium dobesilate on ameliorating the lung damage following ischemia-reperfusion injury in skeletal muscle of rats. A well known antioxidant, dimethyl sulfoxide, was also tested for comparison. The study included three groups: normal saline, dimethyl sulfoxide and calcium dobesilate. Plasma bicarbonate, creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS), as well as muscle and lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. The dimethyl sulfoxide group showed significant amelioration of plasma (p = 0.004), skeletal muscle (p = 0.006) and lung TBARS (p = 0.004) levels, compared with controls. Calcium dobesilate-treated rats showed significantly low level muscle (p = 0.025) and lung TBARS (p = 0.004), compared with the control group. The extent of lung injury according to the histological findings was less in the dimethyl sulfoxide (p = 0.004) and calcium dobesilate (p = 0.003) groups. These observations indicated that calcium dobesilate acted effectively in the prevention of lung damage following ischemia-reperfusion injury in the rat skeletal muscle.

Subcutaneous hydatidosis due to iatrogenic spreading of cystic fluid during surgery.

Subcutaneous involvement is a rare manifestation of echinococcosis. We report a rare case of a 28-year-old woman with widespread hydatidosis of the lung, liver, and subcutaneous adipose tissue. The patient underwent surgical excision of multiple hepatic and pulmonary cysts with a thoraco-abdominal incision two years earlier. The subcutaneous cyst was located over the incision, and it is likely that resulted from accidental rupture of the primary cyst and spreading of scolices during surgery.

A brachial aneurysm in childhood caused by Ehlers-Danlos syndrome.

A case of an 11-year-old boy with Ehlers-Danlos syndrome (EDS) type IV is presented. He was referred with a pulsatile mass above the right antecubital fossa and Doppler revealed a saccular aneurysm. Excision and ligation of the brachial artery aneurysm was performed. The diagnosis was confirmed by skin fibroblast cultures and histopathologic evaluation. We conclude that arteriography should be avoided in EDS and color-Doppler should be the sole means of diagnosis. Ligation rather than arterial reconstruction should be preferred.

Benefits of supplementing St Thomas' Hospital cardioplegic solution with tetraethylammonium on functional and metabolic recovery of isolated rat hearts.

This study was designed to evaluate whether the addition of potassium channel blockers, tetraethylammonium, 4-aminopyridine or glibenclamide, to St Thomas' cardioplegia improved myocardial preservation over that achieved by St Thomas' cardioplegic solution alone. Initially, isolated rat hearts were subjected to 30 min of continuous normothermic hypoxic cardioplegia. Control hearts were arrested with St Thomas' cardioplegia followed by tetraethylammonium, glibenclamide or 4-aminopyridine-enriched cardioplegia. Subsequently, in a second experiment, hearts were subjected to 45 min of normothermic global ischaemia, after 3 min of cardioplegia with either tetraethylammonium-enriched or standard St Thomas' cardioplegia. In both regimens, hearts arrested with tetraethylammonium-enriched St Thomas' cardioplegia showed better recovery of contractile function than controls (P<0.001). Creatine kinase levels were significantly lower in the tetraethylammonium group (P<0.001). 4-Aminopyridine treatment caused similar contractility to that of the control group but raised creatine kinase and lactate dehydrogenase levels (P<0.001). Glibenclamide diminished coronary flow autoregulation, and increased lactate dehydrogenase leakage in reperfusion (P<0.05) with similar contractility to controls. The results of this preliminary in vitro study demonstrate that, in rat heart, St Thomas' cardioplegia enriched with tetraethylammonium improves post-ischaemic contractile function and reduces creatine kinase release. It is concluded that high potassium blocks the membrane at the rapid depolarization phase with rapid sodium influx and tetraethylammonium further prevents repolarization by blocking voltage-dependent potassium channels.