Exploring at the molecular level the effects of blood and blood-insulin cardioplegias used during open-heart surgeries on myocardial prevention.

AIM: The aim of this study was to measure the changes in the levels of soluble adhesion molecules involved in acute inflammation during ischemia-reperfusion in adults who underwent open-heart surgery using blood and blood-insulin cardioplegia and to examine the differences in tissue damage at the molecular level as a consequence of insulin's effect on myocardial energy metabolism. METHODS: Non diabetic 36 patients were enrolled. Blood cardioplegia was used at all cases; insulin and glucose were added at the study group. Blood samples were taken from the coronary sinus and the radial artery before cross-clamp (T1), at 1st (T2) and 30th(T3) minutes after reperfusion. Soluble intercellular adhesion molecules-1 (sICAM-1), soluble vascular adhesion molecules-1 (sVCAM-1), soluble platelet/endothelial cells adhesion marker-1 (sPECAM-1) and serum lactate levels were measured in these samples. Cardiac enzymes (CK-MB, troponin, and myoglobin) were measured at postoperative 1th, 8th and 16th hours. The total duration of mechanical ventilatory support during postoperative period, and the number of days in the intensive care unit and hospital were recorded. RESULTS: No significant differences were observed in sVCAM-1 levels in blood taken from the radial artery at T1, T2 and T3 in either group. There were significant increases between T1 and T3 and between T2 and T3 in samples obtained form the coronary sinus (P=0.000 and P=0.003, respectively). Significant increases in sPECAM-1 in samples obtained from both sites between T2 and T3 in both groups (P=0.000) were observed. These differences were similar in both groups. Troponin levels at 8th and 16th hours in the blood-insulin cardioplegia group were higher than the blood cardioplegia group (P=0.003 and P=0.032, respectively). CONCLUSION: Supplementation of blood cardioplegia with insulin did not yield a significant improvement in adhesion molecules. Therefore, superiority of one cardioplegia over the other in delivering myocardial protection during open-heart surgery has not been shown.

Insulin-blood cardioplegia decreases matrix metalloproteinase activity in ischaemia-reperfusion injury during coronary artery bypass surgery.

Reperfusion of myocardium during coronary bypass activates matrix metalloproteinases (MMPs) with changes occurring in the levels of tissue inhibitors of metalloproteinases (TIMPs) in the myocardium. This study investigated the effects of insulin-blood cardioplegia on MMP activity and TIMP levels during reperfusion. Non-diabetic patients undergoing coronary artery bypass graft with cardiopulmonary bypass were randomized into a control group (n = 12) or an insulin group (n = 12). Blood cardioplegia was used for both groups; insulin and glucose were added to the insulin group. Blood samples were obtained from the coronary sinus just before aortic cross clamping and after 1 and 30 min of reperfusion. Plasma proenzyme MMPs (proMMP-2 and -9) and TIMPs (TIMP-1 and TIMP-2) levels were measured. There were no differences between groups for MMP-2 and TIMP-2 levels. However, insulin diminished proMMP-9 activation, although some still occurred. TIMP-1 consumption lessened during reperfusion which, we conclude, was as a result of the diminished MMP activation. This is the first open heart surgery study in which diminished MMP activation was achieved via a metabolic change.

Mutation analysis of the Vangl2 coding region revealed no common cause for Tetralogy of Fallot.

Vangl2 (Van Gogh-like 2) protein acts via non-canonical Wnt signalling to regulate polarized cell movements during development of the proximal outflow tract in vertebrate embryos. Recently, it has been shown that mutations of the Vangl2 gene cause aortic arch defects that are characteristic of the loop-tail (Lp) mouse and they have also became a strong candidate for causing congenital outflow tract defects in humans. Thus, in this study Tetralogy of Fallot (ToF), which comprises a group of syndromes that constitutes the most frequent cause of congenital cardiac outflow abnormalities in humans, was analysed for mutations within all coding regions of the Vangl2 gene. Based on direct sequencing data from a combination of 20 patients with ToF and 22 healthy people, three polymorphisms have been identified in exon 6 and exon 7 which do not change the amino acid sequence. It was concluded, therefore, that there is no specific mutation responsible for the ToF phenotype in the Vangl2 gene.

Effects of basic fibroblast factor (bFGF) on MMP-2, TIMP-2, and type-I collagen levels in human lung carcinoma fibroblasts.

Matrix metalloproteinases (MMP's) and tissue inhibitors of metalloproteinases (TIMP's) possess a preponderant role in the metabolism of the major extracellular matrix protein, collagen, and are thought to be important in the mechanism of tumor invasion. Lung cancer occupies the first position in mortality and the second position in incidence, among all cancers. In the present investigation, we studied the effect of basic fibroblast growth factor (bFGF) on collagen, matrix metalloproteinase-2 (MMP-2), and tissue metalloproteinase inhibitor-2 (TIMP-2) levels in normal and carcinoma lung tissue fibroblast cultures. MMP-2 was selected because of its high specificity in the degradation of type IV collagen, major component of the basal membrane. The effect of bFGF on MMP-2, TIMP-2, total collagen, and type I collagen levels of normal and carcinoma lung fibroblast cultures was investigated at 0, 10, and 100 ng/ml. Statistical analysis was carried out using the Mann-Whitney-U test and possible correlations were searched using the Spearman correlation analysis method. MMP-2, TIMP-2, total collagen, and type-1 collagen levels based on cell counts (10(3) cells) showed no statistically significant differences between the carcinoma and normal fibroblast cultures. However, positive correlations were found between MMP-2 and TIMP-2 in normal (P = 0.016) and carcinoma (P = 0.001) tissue fibroblast cultures. Positive correlations were also found between total collagen and TIMP-2 levels in normal and carcinoma tissue fibroblast cultures (P = 0.002 and P = 0.032). Total collagen and TIMP-2 levels also showed positive and strong correlations in all cultures except in 100 ng/ml bFGF concentrations. In addition, type I collagen and MMP-2 levels showed positive significant correlations only in normal and carcinoma control cultures, while type I collagen and TIMP-2 levels showed positive correlations in all cultures except carcinoma fibroblasts at 100 ng/ml bFGF. It may be concluded that bFGF does not affect MMP-2, TIMP-2, total collagen, and type-1 collagen levels in fibroblast cultures grown from human carcinoma and normal lung tissues. However, bFGF was noted, in vitro, to disturb the equilibrium which normally exists between the four parameters, both in normal and carcinoma tissue fibroblasts.

Evaluation of some antioxidant enzymes in lung carcinoma tissue.

This investigation was effected to determine the levels of the two antioxidant enzymes, superoxide dismutase (SOD) (EC 1.15.1.1) and catalase (CAT) (EC 1.11.1.6) in lung cancerous tissues and to compare with normal lung tissue in order to evaluate the antioxidant status in lung cancer. Fifteen lung carcinoma tissue samples and the normal counterparts from the same cases were homogenized and the cytosols obtained by ultracentrifugation (100,000 x g). SOD was assayed using a modification of the indirect nitroblue tetrazolium assay method, while CAT was measured by a spectrophotometric method. The data obtained are as follows: 1.42 +/- 0.24 U/mg protein (means +/- SEM) of SOD in lung cancer and 3.13 +/- 0.51 U/mg protein in normal lung tissue and 33.53 +/- 6.09 U/mg protein of CAT in lung cancer and 71.33 +/- 14.38 in normal lung tissue. The differences were found to be significant at the level of P < 0.01 for both enzymes. These low levels of the antioxidant enzymes in lung cancerous tissues can lead to elevated levels of reactive oxygen metabolites, resulting in damage to the key subcellular structures such as DNA, cell membranes, and other vital cellular components.

Retrograde cerebral perfusion with hypothermic circulatory arrest in a child.

This report describes a 4-year-old boy who presented with infective endocarditis involving the ascending aorta and the arch vessels, with supravalvular aortic stenosis as the underlying pathology. Operation was indicated because of the embolic potential of the vegetations inside the aorta. Retrograde cerebral perfusion was utilized in conjunction with hypothermic circulatory arrest, to flush particulate materials from the arch vessels during operation.

Amikacin administration in open heart surgery.

Amikacin is usually administered to the patients during open heart surgery immediately after cardiopulmonary bypass (CPB) because the serum levels of this drug may decrease due to the volume overload and hemodilution caused by intravenously administered fluids (1.2-2 liters prime solution). We investigated whether this application of amikacin is necessary immediately after CPB. A total of ten patients from Dokuz Eylül University Hospital, Department of Thoracic and Cardiovascular Surgery, who were scheduled for open heart surgery were studied. Serum sodium, potassium, blood urea nitrogen and creatinine values of the patients were found to be within normal limits before the operation. Amikacin was administered to patients just before open heart surgery and 2 ml blood samples were collected from all patients 15 minutes after the drug administration, just before cardiopulmonary by-pass (CPB), at the 30th and 60th minutes of the CPB, after CPB and after the cessation of operation, 4 hours after drug administration. A significant decrease was observed between the values of 10 patients by ANOVA (p < 0.05). Serum amikacin values were found to be 9.80 +/- 0.96 micrograms/ml at the end of the operation, 4 hours after the drug administration. Since serum amikacin levels do not fall below the trough concentrations at the end of the fourth hour we conclude that it is unnecessary to repeat the dose at the end of the operation.

A new closure technique for limited thoracotomy where the ribs are spread minimally.

An alternative closure technique for limited thoracotomy incisions is described below. This technique consists of fixing the intercostal muscles with horizontal mattress sutures. Also the described technique can be applied where the ribs are spread minimally in such limited thoracotomy incisions.

Aortic ruptured following lung resection in invasive aspergillosis.

Invasive pulmonary aspergillosis, although rare in the general population, can prove to be an important cause of morbidity and mortality in immunosuppressed patients. In this paper we represent a case of aortic rupture for a fungal invasion of the aorta after a pulmonary resection procedure. Although a few cases are documented in the literature, we report our experience to make our colleagues aware of this complication.

The role of autologous blood injection on postoperative air leak at lung resections.

BACKGROUND: The effects of autologous blood injection beneath the stapling lines on postoperative air leak after lung resections, especially in emphysematous lungs, were prospectively investigated. METHODS: The study was carried out on 16 randomized patients. The mean age of the study group was 58 and the mean forced expiratory volume at one second (FEV1) at the spirometry was 2.05 L. In the control group, the mean age was 60 and the mean FEV1 was 1.97 L. All 16 cases were males and had a history of smoking. In the study group, 10-20 ml of autologous venous blood was drawn by the anesthesist and transferred to the operation team. The blood was gently injected underneath the staple line and ultimately 1 cm thickened layer of the lung was obtained. In the control group only staplers were applied. RESULTS: There was no air leak at the end of the operation at the study group, whereas additional sutures which were pledgetted with Gore-tex patches were needed at four cases at the control group. There were minimal air leaks at three cases at the control group at the postoperative period, while there was no postoperative air leak problem at the study group. Thorax tubes were removed at the 3rd and the 3.9th days at the study and the control groups, respectively. CONCLUSIONS: We believe this simple and cheap method could be used at least in some instances where additional staple reinforcement would be necessary. It may also be remembered when air leaks are encountered at suture holes after suturing the lung.

Ligation of patent ductus arterious by the method of video-assisted thoracoscopic surgery and our other VATS experiences.

In April and May 1996, two cases of PDA ligation were performed firstly in Turkey by the method of video assisted thoracoscopic surgery (VATS) in Dokuz Eylül Medical Faculty, Thoracic and Cardiovascular Surgery Department. There was not any complication in these patients in the postoperative period and they were discharged on the second day in symptom-free condition by the detection of closed ductus in their echocardiographic examination. Between February 1993 and October 1996, a total of 46 patients have undergone interventional application by VATS. While in six of these patients the procedure could not be manipulated because of massive pleural fibrosis, there was no mortality or morbidity among the patients, and they were discharged on average on the second day. The ratio of complications, such as bleeding, air leak, arrhythmia and empyema are so low in these operations, and hospital stay, with return to work time are shorter than with the open technique.

Cervical aortic arch. A case report.

Cervical aortic arch is a rare type of aortic arch anomaly that is presumed to result from persistence of the third aortic arch and regression of the normal fourth arch. Most of the patients with this anomaly are asymptomatic, but symptoms of dysphagia and respiratory distress due to the compression by the vascular ring have been reported. Other findings such as a supraclavicular pulsatile mass, blood pressure discrepancies between the upper limbs, and loss of femoral or opposite-upper-limb pulses with compression of the cervical mass may also be present. In this article a twenty-two-year-old woman with symptomatic cervical aortic arch is presented. The patient had a left cervical pulsatile mass and elevated blood pressure on her right upper limb and was treated surgically with reanastomosis of the aorta.

Transthoracic colour Doppler ultrasonography in the evaluation of internal thoracic artery bypass graft patency.

The internal thoracic artery (ITA) is the most important conduit for coronary artery bypass grafting. The quality of the anastomosis joining the ITA to the left anterior descending coronary artery has a major impact on left ventricular perfusion. The rapid detection of flow disturbances due to sub-optimal anastomosis is, therefore, of great prognostic significance. In this study, 47 coronary bypass patients were examined using colour Doppler ultrasonography peri-operatively and 4-6 months post-operatively. Findings were correlated with clinical observations and a treadmill exercise test. The pre-operative ITA flow pattern was normally triphasic, but changed post-operatively to simulate the normal biphasic flow pattern of left anterior descending coronary artery. A 35-case-control group was used to compare pre-operative ITA flow characteristics. The authors conclude that Doppler parameters, clinical findings and the treadmill test can be used in combination for the routine evaluation of graft patency, and to select cases that require more invasive coronary angiography.

Cost-effectiveness of minimally invasive-intervention in aortofemoral revascularization.

Minimally invasive surgical procedures have become popular recently because they offer several advantages over conventional operative techniques. A person undergoing a minimally invasive procedure usually experiences less pain, is discharged earlier from hospital, returns to work sooner and has a less obtrusive post-operative scar. Excluding highly technical techniques (e.g. laparoscopic surgery), operations performed using mini-laparotomy are usually more cost-effective than conventional procedures, largely because they are less expensive to perform. Our paper investigates cost-effectiveness and other parameters relating to minimally invasive aortofemoral revascularization procedures performed at our clinic. We compared 20 similar cases, half where revascularization was undertaken using mini-laparotomy and half where conventional laparotomy was selected. From our findings we conclude that mini-laparotomy is safe and reliable for aortobifemoral bypass procedures and has several advantages over traditional techniques; namely, shorter operating time, earlier resumption of intestinal function, shorter duration of in-patient stay and reduced costs.

Surgical management of giant aneurysms complicating arteriovenous fistulae.

The creation of an arteriovenous fistula (AVF) is frequently used to achieve easier access for haemodialysis in patients with chronic renal insufficiency. The most frequent late complication of AVFs is aneurysm formation, which carries the risk of spontaneous rupture. This study reports on 18 patients with giant aneurysms that developed on antebrachial AVFs who were operated on over a period of 6 years. Colour duplex ultrasonographic examination of the upper extremity was performed in all but one patient in the preoperative period. Surgical management included resection of the aneurysm and re-establishment of arterial continuity. There were no complications such as infection, ischaemic extremity loss, neurological sequelae or mortality. Colour duplex ultrasonographic examinations after 6 months were all normal. The mean follow-up period was 29.1 months (range 7-50 months). There were no additional vascular complications observed during follow-up. Early surgical intervention is the recommended treatment of choice for giant aneurysm complicating antebrachial AVF.

A comparison of digoxin concentration--time curves before and after open-heart surgery.

The effects of open heart surgery on serum digoxin concentration--time curves were investigated in 10 cardiac patients receiving 0.25 mg/day digoxin. Blood samples were obtained from the patients immediately before and 1, 2, 3, 5, 8, 16 and 24 h after digoxin administration, both before open-heart surgery and 7 days after surgery. Serum digoxin concentrations, determined by fluorescence polarization immuno-assay, significantly (P < 0.05) increased after surgery, as did the maximum serum concentrations and the areas under the concentration-time curves. After surgery there was a significant increase in the serum gamma-glutamyl transferase concentration and a significant reduction in the total protein concentration. A reduction of digoxin dose may be appropriate for patients who have undergone open-heart surgery.

A comparison of the serum concentration time-curves of amikacin-administered patients before and after open heart surgery.

The effects of open heart surgery on amikacin concentration time-curves were investigated in eight patients who were scheduled for open heart surgery at a Thoracic and Cardiovascular Surgery Department. A 500 mg single dose of amikacin was administered parenterally to the volunteers pre- and postoperatively and the serum concentration time-curves were compared. Serum amikacin levels after pre-operative intramuscular (IM) administration did not reach therapeutic values. By comparison, preoperative and postoperative IM or intravenously (IV) administration resulted in therapeutic serum amikacin levels. It was concluded that IM administration preoperatively was not appropriate. Serum levels of amikacin were also shown to fall below therapeutic values 8 h after administration. It is recommended that dosing intervals with amikacin should not exceed 8 h.

Lung-volume reduction in parallel with coronary heart surgery: a case report.

For patients with severe disabling emphysema, lung-volume reduction surgery has recently been introduced as an alternative to transplantation. Performing parenchyma resection from appropriate areas can improve pulmonary functions in selected patients having severe emphysema with a flattened diaphragm. We report the case of a patient, who urgently needed coronary revascularization and was otherwise inoperable because of severe chronic obstructive pulmonary disease (COPD). We carried out lung-volume reduction surgery at the same time as the coronary bypass.

Acid phosphatase production by Rhizopus delemar: a role played in the Ni(II) bioaccumulation process.

The microbial growth and activity of acid phosphatase enzyme during the growth of Rhizopus delemar in the presence or absence of Ni(II) ions were investigated. An increase in initial Ni(II) ion concentration inhibited both growth rate of R. delemar and acid phosphatase activity. The maximum-intrinsic specific growth rate (µ(m)) and Monod constant (K(s)) of microorganism in Ni(II)-free medium were found as 0.0649 h(-1) and 1.8928 g/L, respectively. The inhibition of Ni(II) ions on growth rate of R. delemar was found to be a competitive inhibition and the inhibition constant was found to be 67.11 mg Ni(II)/L. The intrinsic Michaelis-Menten constant (K(m)) and maximum forward velocity of the reaction (v(m)) were determined as 3.17 mM and 833.3 µmol/L min, respectively, in Ni(II)-free medium. In the presence of Ni(II) ions, the activity of acid phosphatase was inhibited. Addition of Ni(II) ions decreased the maximum reaction velocity, v(m), showed noncompetitive-type inhibition kinetics and the inhibition constant was determined as 50mg Ni(II)/L. Maximum Ni(II) uptake was obtained by the growing cells of R. delemar, while the uptake capacity of resting cells was lowest. This study proved that acid phosphatase enzyme participated in the Ni(II) bioaccumulation mechanism of growing R. delemar.