Effects of calcium dobesilate and diosmin-hesperidin on apoptosis of venous wall in primary varicose veins.

BACKGROUND: Evaluation of the therapeutic effects of calcium dobesilate and diosmin-hesperidin through regulation of apoptosis. PATIENTS AND METHODS: 56 Patients were divided into four groups; Group 1 consisted of patients (n = 18) with the recent diagnosis of primary varicose disorder who have never used medications, Group 2 consisted of patients (n = 14) who have used diosmin-hesperidin for at least six weeks prior to the operation, Group 3 consisted of patients (n = 14) who have used calcium dobesilate for at least six weeks prior to the operation and finally Group 4 (Control group) consisted of normal saphenous vein biopsies (n = 10). All biopsies were stained with Hematoxylin and Eosin. Tissue samples from 56 patients were immunohistochemically stained with antibodies of anti-bcl-2, anti-bax and anti-p53. Apoptosis was evaluated by TUNEL method. RESULTS: There were no statistically significant differences among the groups in respect to gender distribution and smoking status. Immunohistochemical evaluation of apoptosis related proteins revealed a statistically significant difference between Group 4 and the other groups with respect to the apoptag staining on venous wall (p = 0.026). There were significant differences in the presence of bcl-2 protein expression between groups 4 and Group 1 (p = 0.0002) and between Group 1 and Group 3 (p = 0.023). CONCLUSIONS: Our study highlights the significance of apoptosis in varicose disorders and suggests that calcium dobesilate, which is used in the treatment of varicose veins, could be of benefit by regulating apoptosis.

Biochemical and hemodynamic effects of ascorbic acid and alpha-tocopherol in coronary artery surgery.

This study was undertaken to evaluate the effects of alpha-tocopherol and ascorbic acid on markers of myocardial reperfusion injury and myocardial contractile function after coronary artery surgery. Forty-eight patients were divided into 4 groups; 300 mg/day alpha-tocopherol was given orally to the patients in group I for 14 days. In groups II and III, 4g of ascorbic acid was administered intravenously prior to induction and in the cardioplegic solution, respectively. Group IV was the control group. Blood samples were taken to determine the concentrations of creatine phosphokinase MB isoenzyme, malondialdehyde, uric acid, ascorbic acid and alpha-tocopherol in the perioperative period. Left ventricular functions were determined by means of MUGA scans and echocardiography preoperatively and on the 3rd and 7th days, postoperatively. The changes in serum creatine phosphokinase MB and malondialdehyde were significantly lower in study groups. when compared with the control group. We observed no significant changes in ventricular function, requirement for (+) inotropic agents and the incidence of ventricular arrhythmias among the groups, postoperatively. Biochemical findings are consistent with the free radical hypothesis. But we could not confirm these data with hemodynamic findings. This is probably due to the population of low-risk elective coronary surgery patients in this study.

Comparison of the hematological effects of a sustained release chitosan formulation of pentoxifylline with a commercial formulation.

In the present study the hematological effects of a sustained release chitosan formulation of pentoxifylline (CAS 6493-05-6) were examined and compared with those of a commercial product. The study was carried out on 12 healthy volunteers. Both formulations were tolerated well clinically. The results demonstrated no antiaggregatory effect of the two different formulations of pentoxifylline in platelet rich plasma. Both drugs resulted in a decrease of plasma fibrinogen levels. A remarkable side effect of the new formulation was mild basophilia, without any clinical problems.

Long-term effects of combined iliac dilatation and distal arterial surgery.

PURPOSE: When standard aortofemoral surgical procedure is combined with lower extremity vascular surgery, problems related with the hospital stay, morbidity, mortality and the cost of treatment will exist. The number of reports relating to combined iliac artery PTA and distal bypass surgery is limited. After the development of stenting procedures, the results of arterial system plasty have much more improved. This report reviews our preliminary experience with iliac artery angioplasty with distal bypass procedures. PATIENTS AND METHODS: A total of 41 patients have undergone combined iliac artery dilatation and distal arterial revascularization. Angioplastic procedures were performed in the angiography suite and distal surgery was carried out at the same day or the day after. Of all patients, 29 underwent percutaneous transluminal angioplasty (PTA) and 12 underwent combined PTA and stent placement. Ipsilateral femoropopliteal bypass was performed as a distal revascularization procedure in all patients. RESULTS: Mean systolic iliac artery pressure gradients improved from 34.7+/-8.6 mmHg to 3.9+/-3.2 mmHg after angioplastic procedures (P < 0.0001). Six patients needed reangioplasty because of restenosis in the follow-up period. Thrombectomy was performed on 1 patient in the early postoperative period and re-do femoropopliteal bypass was performed on two patients in the 2nd and 23rd months. Three minor wound infections were successfully treated with antibiotics and local care. Mean follow-up was 21.4 months (range 1-48 months). By life-table analyses, the overall 4-year cumulative primary patency of combined procedures was 78.1%. CONCLUSION: The results show that the combined procedure is a suitable method for the treatment of patients with multiple stenotic lesions at the iliac and distal arterial levels. We believe that the combined use of PTA and distal vascular surgery by an experienced surgical team will give beneficial results and a highly satisfactory outcome in this group of patients.

Transdiaphragmatic graft replacement for coarctation suprarenal abdominal aorta.

A 17-year-old boy was referred to us with severe hypertension, headache and intermittent lower extremity claudication. Approximately 3 months prior to admission, he began to experience headache and pain in the posterior aspect of the right thigh and calf upon walking only 20 m. Occasionally, similar symptoms developed in the left leg which were nearly always of the same intensity as on the right. Arterial blood pressure on admission to our hospital was 220/140 mmHg in the arm. After physical examination and diagnostic tests, he was operated on with the diagnosis of coarctation of the abdominal aorta. The purpose of this paper is to report on a patient having an area of coarctation just above the level of renal arteries who presented with severe hypertension and intermittent claudication and in whom there was complete relief of signs and symptoms after appropriate surgical intervention.

Evaluation of heparin-coated circuits with full heparin dose strategy.

Heparin-coated cardiopulmonary circuits (HCC) in combination with a reduced systemic heparin dose has been demonstrated to reduce postoperative hemorrhage after cardiac surgery. But, it has still been equivocal whether this effect was related to the improved bio-compatibility or to the reduced exposure of the circulating heparin. Sixty patients undergoing elective coronary artery bypass grafting were randomly allocated into two groups either to be operated by HCC (30 patients) or uncoated but otherwise identical circuits (NHCC). Full systemic heparinization was induced in both groups. Hemodynamic parameters, hematological and biocompatibility tests were monitored within 24 hours. Postoperative blood loss, requirements for transfusions, clinical performance were recorded. Arterial filters were examined electron microscopically. Platelet levels remained significantly higher in the HCC group starting at the tenth minute following the institution of cardiopulmonary bypass until postoperative 24 hours. Electron microscopy showed significantly more platelet adhesion and pseudopod formation in the NHCC group. The mean amount of shed pleural and mediastinal blood measured from the time of the sternal closure was significantly lower in the HCC group (316 +/- 30 cc for HCC and 550 +/- 35 cc for NHCC). Mean postoperative transfusion requirements were also lower in the HCC group (230 +/- 23 cc for HCC and 320 +/- 25 cc for NHCC). The use of HCC and full systemic heparinization did not change the inflammatory response or biocompatibility but demonstrated benefits in platelet preservation and postoperative bleeding.

Eight year experience with the CarboMedics bileaflet valvular prosthesis.

Two hundred and two patients (97 female and 105 male; mean age: 45. 5+/-9 years) received CarboMedics bileaflet valves during a period of eight years. Ninety-one patients received mitral, 72 aortic and 39 aortic+mitral valve prosthesis. Tricuspid plasty and coronary artery bypass surgery were the concomitant operations in 17 and 12 patients, respectively. The mean follow-up period was 24.7 months and the ratio was 91%. Overall operative mortality was 3.96% (8 patients); 2.78% for aortic valve replacement (AVR), 3.29% for mitral valve replacement (MVR) and 7.7% for double valve replacement (DVR). The late mortality rate was 2.89% for AVR, 2.2% for MVR and 8. 3% for DVR. The main cause of mortality was low cardiac output. The overall survival rate was 91.5% in 2 years. The actuarial freedom from thromboembolism in 2 years was 97% for AVR, 95% for MVR and 84% for DVR. No mortality due to heamorrhagic events was observed. CarboMedics prosthetic heart valves may be used satisfactorily with a low incidence of valve-related morbidity and mortality.

The dose-dependent effects of L-carnitine in myocardial protection in normothermic ischemia.

L-Carnitine has been shown to improve the post-ischemic recovery of myocardial function and metabolic measurements that are reduced in the course of ischemia and reperfusion of the heart. In this study we used 40 male guinea-pigs in order to determine if the effect of L-carnitine which is used in the protection of the post-ischemic reperfused heart, is dose-dependent or not. All harvested hearts were perfused for 30 min on modified Langendorf apparatus with oxygenized Krebs-Henseleit solution. After this period, in (n = 10), 5 mmol and 10 mmol (group B, n = 10) of L-carnitine were added into a Krebs-Henseleit solution. After 20 min, perfusion was complete and the hearts were then exposed to normothermic ischemia for 20 minutes. Following the ischemia, hearts were reperfused with the same solutions for 30 min. In group C (n = 10), 10 mmol of L-carnitine was added into the solution at the post-ischemic reperfusion step. In the control group, the same procedures were performed without using L-carnitine. Matching was done according to the contractile force of the heart rate and the levels of malondialdehyde and adenosine deaminase. When 10 mmol L-carnitine was added into the perfusion solutions at the pre-ischemic period, the best results were obtained and myocardial damage was much less than the control group. The protective effects of L-carnitine in normothermic ischemia is dose-dependent and it must be given at the pre-ischemic period.

Effects of selenium enriched reperfusion solutions on isolated guinea pig hearts.

A comparative study on isolated guinea pig hearts was carried out to determine the role of selenium enriched reperfusion solutions on postischemic reperfusion injury. The hearts of 20 control and 20 study group guinea pigs were mounted on a Langendorff perfusion apparatus and were perfused by gassed Krebs-Henseleit solution at 37 degrees C. The hearts were then arrested by discontinuing the Krebs-Henseleit perfusion. After 20 minutes of normothermic ischemia, in the study group, the hearts were reperfused by selenium enriched Krebs-Henseleit solution (10(-3) mMol/L) and in the control group only Krebs-Henseleit solution was used. Postischemic percentage recovery of mechanical cardiac functions (heart rate and contractile force) and postischemic tissue degeneration indicators. Malondialdehyde (MDA) and Adenosine deaminase (ADA) were compared between the groups. Mean percentage change of heart rate, contractile force and heart work were significantly higher (p < or = 0.0001) and tissue MDA and ADA levels were lower (p < or = 0.001) in the selenium reperfused group. Our results demonstrated that addition of selenium to reperfusion solutions significantly improved cardiac functional recovery and decreased postischemic myocardial injury.

Bland-White-Garland syndrome in an adult. Case report and review of diagnostic and predictive strategies.

In a 27-year-old man with Bland-White-Garland syndrome (anomalous origin of the left coronary artery from the pulmonary artery), comparison was made between conventional diagnostic techniques and radionuclide imaging for selection of surgical procedure and evaluating the outcome. Dynamic 99mTc imaging exactly located the left coronary artery orifice, which was not seen on angiography, thereby determining the surgical approach, and 123I study revealed that, despite absence of symptoms, the adrenergic activity of the heart was globally diminished, with limited response to revascularization.

Psychiatric complications of cardiac surgery postoperative delirium syndrome.

Psychiatric disturbances due to cardiopulmonary bypass, especially postoperative delirium syndrome, are among the immediate complications of open-heart surgery. In a series of 32 male and 18 female patients the prevalence of such disorders was investigated and search was made for possible risk factors for their occurrence. Psychiatric, neurologic and electroencephalographic evaluation was made pre- and postoperatively, in addition to haemodynamic, echocardiographic, angiographic and regional cerebral blood flow studies. Nine of the 50 patients had significantly reduced perfusion of certain cerebral lobes in single photon emission computed tomography, and in six of them the psychiatric tests indicated postoperative delirium; three of these six also had moderate electroencephalographic changes. The cerebral hypoperfusion persisted on day 15 in four patients, while psychiatric tests were negative. The study showed possible risk factors to be patient age, long aortic cross-clamp time, high-dose inotropic support and excessive transfusion of blood or blood products.

The role of selenium added to pulmonary preservation solutions in isolated guinea pig lungs.

An experimental comparative study on isolated guinea pig lungs has been undertaken to determine the probable beneficial effects of adding selenium to pulmonary preservation solutions in lung ischemia. The isolated lungs (n = 10 in each group) previously being perfused by oxygenated Krebs-Henseleit solution were put in normothermic ischemic conditions just after the infusion of 30 ml of pulmonary preservation solution (Euro-Collins in the control group, Euro-Collins plus selenium 10(-3) mol in the experiment group). After 3 hours of normothermic ischemia the lungs were reperfused with the same buffer for 20 minutes. Pulmonary artery pressures, tissue malondialdehyde levels, and adenosine deaminase levels of the perfusate were measured before and after the ischemic period and also at the end of reperfusion. An electron microscopic analysis was performed on the lung tissues at the end of the experimental procedure. According to our data, the addition of selenium to pulmonary preservation solution showed a significant protective effect regarding both ischemic and reperfusion injury.

The effect of selenium added cardioplegia in guinea pigs.

1. The aim of the study was to determine the effect of selenium added cardioplegic solutions on postischemic myocardial recovery. 2. The hearts were mounted on Langendorf perfusion apparatus and perfused with Krebs-Henseleit solution. The hearts were arrested by one of the following cardioplegic solutions; (a) K+ 20 mmol/l (control group); (b) K+ 20 mmol/l+selenium 10(-3) mol/l (experimental group). After 20 min of normothermic ischemia the hearts were reperfused by the same buffer. 3. Postischemic percentage changes of heart rate, contractile force and heart work were compared between the groups. 4. Addition of selenium to the cardioplegic solution significantly decreased the postischemic myocardial injury.

The effects of thyroid hormones on the heart following global ischemia. A clinical and experimental study.

Cardiopulmonary bypass is associated with a reduction in plasma thyroid hormone concentrations in patients undergoing cardiac surgery. However, studies of the effects of cardiopulmonary bypass on thyroid function are limited and many studies report conflicting data concerning only the period of cardiopulmonary bypass. In this study, we tried to clinically determine the effects of cardiopulmonary bypass on concentrations of thyroid hormones by comprehensive thyroid function tests in 10 patients before and after surgery, and observed the benefits of triiodothyronine supplementation after global ischemia on myocardial function experimentally in guinea pigs. In patients undergoing surgery, concentrations of total triiodothyronine and free triiodothyronine decreased progressively on the institution of cardiopulmonary bypass and remained below normal levels until 24 hours postoperatively. In the guinea pig hearts studied in a Langendorf perfusion apparatus, T3 supplementation enhanced percentage recovery of ventricular contractile force, heart work and heart rate with respect to other groups receiving no T3 supplementation or T3 supplementation without any ischemic interval.

Decision-making for surgery in patients with end-stage coronary artery disease: the role of dual isotope myocardial perfusion SPECT after dobutamine infusion.

Dobutamine pharmacologic stress test coupled with dual isotope-stress hexakis 2-methoxy-isobutyl-isonitrile (MIBI), rest Thallium 201-perfusion SPECT was performed to a patient with an end-stage coronary artery disease who has physical limitations and cannot achieve a desired stress level with conventional stress protocols. Although this patient was assessed to be an inoperable case according to coronary angiography or echocardiography data, he was operated on the basis of imaging of a viable myocardium and reversible coronary ischemia to a significant extent in the dobutamine stress coupled with dual isotope study. The objective benefits of the operation was also shown on the postoperative data. We'd like to discuss an alternative diagnostic option contributing more appropriate solutions for patients with an end-stage coronary artery disease.

Dual isotope myocardial perfusion SPECT in the detection of coronary artery disease: comparison of separate and simultaneous acquisition protocols.

A time-saving dual isotope acquisition protocol was carried out for the simultaneous assessment of stress and rest myocardial perfusion, and the diagnostic value of the technique was evaluated using coronary angiography results as a reference. Fifty-five patients undergoing coronary angiography before surgery were included in the study. Stress tests were applied, either with a treadmill (25 patients) or dobutamine infusion (30 patients in 5-40 micrograms/kg/min doses). All patients received 3 mCi of thallium-201 at rest. Stress tests were applied 30 minutes later, and at peak stress 7 mCi of 99mTc-MIBI was administered. A dual isotope SPECT study was carried out one hour after the administration of 99mTc-MIBI. Tracer doses were optimised with phantom studies, and the down-scatter of each radioisotope on the other data was investigated. In 30 patients, 10 minutes after the 201Tl injection a separate rest 201Tl acquisition was also performed, to compare the data with dual acquisition. 201Tl rest imaging SPECT data was evaluated by segmental analysis according to coronary artery regions. In 55% of the segments stress defects were observed. Similar results were obtained for the detection of defect reversibility; i.e. stress MIBI/rest 201Tl (75%) and stress MIBI/simultaneous 201Tl (78%). The overall sensitivity and specificity of simultaneous dual isotope SPECT with respect to coronary angiography results were 88% and 84%, respectively. A good correlation and no significant difference was observed between the two acquisition methods. However, the simultaneous acquisition protocol has many advantages, i.e. halving the acquisition time, shortening the overall decision-making time, and decreasing unmatched stress-rest artifacts.

Effect of right atrial appendicectomy on the release of atrial natriuretic peptide in humans.

The present study evaluated the effect of right atrial appendicectomy on the release of atrial natriuretic peptide (ANP) and subsequent changes in postoperative haemodynamics in 20 men undergoing coronary artery bypass graft surgery. The right atrial appendix was removed in ten patients and saved in ten. Serum ANP, sodium levels and urinary sodium excretion were measured before and on days 1, 7 and 30 after surgery. Haemodynamic parameters were monitored before surgery and on day 30. Serum ANP levels fell significantly in patients undergoing appendicectomy (P < 0.05); haemodynamic parameters were unchanged. Hence, appendicectomy reduced serum ANP levels in the short term, though these tended to rise again with time; cardiac function was not affected by lowered levels of serum ANP. Consequently, saving the appendix in right atrial appendicectomy improves natriuresis and may decrease diuretic requirement.

Effect of allopurinol on myocardial recovery during reperfusion.

A comparative study on isolated guinea pig hearts was carried out to determine the effect of allopurinol added to reperfusion solution on myocardial recovery after global ischaemia. After 20 min of normothermic ischaemia two groups of solutions (1-Krebs Solution 2-Krebs Solution + Allopurinol 1 mmol l-1) were used for reperfusion (10 animals in each group). Post-ischaemic myocardial functions (ventricular contractile force and heart work) and enzyme activities (CK-MB, LD) were compared with their preischemic values. Addition of allopurinol 1 mmol l-1 to reperfusion solution improved post-ischaemic myocardial functions and decreased myocardial injury.

Cardioplegia with adenosine and adenosine triphosphate in the isolated guinea pig heart.

In order to determine the effect of adenosine triphosphate (ATP) and adenosine in cardioplegic solutions, a comparative study has been undertaken in isolated guinea pig hearts using the Langendorff perfusion technique as a model of cardiopulmonary bypass. The hearts (n = 10 in each group) previously being perfused by Krebs-Henseleit solution, were arrested by one of the following cardioplegic solutions: 1) Potassium 20 mM/L (Plegisol), 2) Potassium 20 mM/L+ATP 10 mM/L, 3) Adenosine 10 mM/L, 4) Adenosine 10 mM/L+ATP 10 mM/L. After 45 min of hypothermic ischemia, postischemic recovery of heart rate, ventricular contractility, heart work and postischemic changes in tissue enzymes (LDH, SGOT, SGPT) were compared among the 4 different cardioplegic solutions. Arrest time and number of arrest beats were also recorded and compared among the groups. Although similar beneficial results on postischemic recovery were achieved with adenosine cardioplegia and with ATP supplemented potassium cardioplegia, ATP supplemented adenosine cardioplegia did not show any beneficial effects on postischemic recovery.

Effect of ATP and verapamil as cardioplegic additives in the isolated guinea pig heart.

1. A comparative study on isolated guinea pig hearts was carried out to determine the effects of ATP and verapamil as cardioplegic additives. 2. The hearts were arrested by one of the plegic solutions: I, potassium 20 mmol/l; II, potassium 20 mmol/l+verapamil 1.1 mumol/l; III, potassium 20 mmol/l+ATP 10 mmol/l. After 45 min of hypothermic ischemia, the hearts were reperfused by Krebs-Henseleit buffer. 3. Postischemic percentage change of myocardial functions (heart rate, contractility, heart work) and tissue enzymes (LDH, SGOT, SGPT) were compared between the groups. 4. Although a rapid cardiac arrest could be obtained by verapamil added cardioplegia. Postischemic myocardial recovery was much better with ATP added cardioplegic solutions.