Intralesional Epidermal Growth Factor for Diabetic Foot Ulcers.

OBJECTIVE: To determine the role of the intralesional recombinant epidermal growth factor (rEGF) in the healing and prevention of extremity amputation in advanced diabetic foot ulcer patients. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Cardiovascular Surgery, Duzce State Hospital, Duzce, Turkey, between November 2018 and September 2019. METHODOLOGY: A total of 58 patients with diabetic foot ulcers that were treated at the study place were enrolled. The lesions were graded with Wagner Classification System. EGF (75 microg of Heberprot-P) vials were stored at +4°C and cold-chain requirements were followed. EGF 5 mL was dissolved with 0.09% saline solution; and 0.5-1 ml of the solution was injected into the tissues and edge of the lesions regularly. The data was evaluated at the end of two years of the treatment period. The primary objective was wound healing, formation of granulation tissue; and the secondary objective was the prevention of lower extremity amputation. RESULTS: Diabetic foot ulcers wound healing was achieved in 93.1% (n=54) of patients with the formation of granulation tissue. The complete recovery was observed in 94.1% (n=32) of the patients who had Grade III and IV lesions. Lower extremity amputation was performed in two (3.4%) subjects. The lesions of two patients required flap surgery. The most common adverse events were tremor and syncope. CONCLUSION: Recombinant epidermal growth factor is highly effective for the treatment of diabetic foot ulcers and prevention of extremity amputation. Intralesional rEGf provides efficient and safe wound healing/closure in patients with diabetic foot ulcers. Key Words: Amputation, Epidermal growth factor, Diabetic foot, Wound healing.

The effectiveness of vacuum-assisted closure therapy in patients with infected venous leg ulcers.

AIM: In this study, we aimed to investigate the effect of vacuum-assisted closure therapy on venous stasis wound healing in patients with chronic venous leg ulcers. METHODS: Vacuum-assisted closure therapy was applied on a total of 14 venous leg ulcers. All patients had post-thrombotic syndrome. Quantitative wound culture samples were obtained before the procedure and local wound assessments were performed. The primary outcome measures included wound healing as assessed by a local wound examination during each dressing change and the rate and velocity of ulcer reduction. Wound healing was defined as the complete closure of the ulcer, while rapid wound healing was defined as a ≥ 30% reduction in the ulcer size by week four. RESULTS: No surgical debridement or surgical corrective procedure was applied in any patient. The mean length of hospital stay was 32.3 days. The mean number of vacuum-assisted closure therapies for each case was 17.8 and the mean time to dressing change was 72.3 hours. Multidrug-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were detected in three and four patients, respectively. Wound culture results became negative after a mean duration of vacuum-assisted closure therapy of 12.1 days. None of the patients needed antibiotic therapy until the procedure was completed. Compared to baseline, the mean ulcer reduction rates were 46.4% for the first six applications and 72.8% for the subsequent applications. CONCLUSIONS: Our study results suggest that vacuum-assisted closure therapy promotes rapid wound healing in patients with severe post-thrombotic syndrome with venous stasis leg ulcers, and reduces the need for antibiotics by reducing the biological burden.

The effect of single aortic cross-clamp technique versus multiple clamp technique on postoperative stroke in octogenarians undergoing coronary artery bypass grafting.

AIM: In this study, we aimed to investigate the effect of the single aortic cross-clamp technique (SCT) (aortic cross-clamp only) versus the multiple-clamp technique (MCT) (aortic cross-clamp + side-biting clamp) on postoperative stroke in octogenarians undergoing coronary artery bypass grafting (CABG). METHODS: A total of 171 patients aged 80 years and older who underwent isolated CABG were retrospectively analysed. The patients were divided into two groups according to the technique used during surgery: group 1 (n = 88) received the SCT, and group 2 (n = 83) received the MCT. Postoperative stroke was evaluated. RESULTS: Of the patients, 127 were men and 44 were women. The mean age was 83.05 ± 8.81 years in group 1 and 82.14 ± 8.92 years in group 2. There was no statistically significant difference in the rate of postoperative stroke between the two techniques (p > 0.05). CONCLUSIONS: Postoperative stroke in octogenarians may result from not only the cross-clamp technique used but also several other factors. We found that both techniques yielded similar outcomes.

The Outcomes of Patients Incidentally Confirmed with Covid-19 After Cardiac Surgery.

BACKGROUND: The aim of this study was to investigate the clinical outcomes of cardiac surgery in patients who were incidentally diagnosed with Covid-19 in the postoperative period. PATIENTS AND METHODS: We performed 826 open cardiac surgeries in five tertiary centers. Most of the surgeries were elective coronary artery bypass grafting (CABG) (93.8%). A preoperative RT-PCR test and transcutaneous oxygen saturation were routinely investigated prior to surgery. We also investigated whether the patients already received Covid-19 treatment or had any contact with a Covid-19 patient in the last two weeks. We analyzed high sensitive C-reactive protein (hs-CRP), d-dimer, and fibrinogen, which plays a main role in the activation of procoagulant state after surgeries. RESULTS: Acute lung injury related to Covid-19 activation was observed in 48 out of 826 patients (5.8%). The median age of 48 patients was 63.9±12.4 years. Euro-Score and body mass index (BMI) were 6.1±1.1 and 29.2±4.1kg/m², respectively. RT-PCR test results were positive in 29 patients (60.4%). We performed thoracic computed tomography (CT) in all patients with or without positive RT-PCR test results. Thoracic CT images showed that there was a different degree of ARDS (mild, moderate, and serious). The median time of extracorporeal circulation (ECC) was 93.2±14.6 min. in on-pump surgery (IQR, 68-155 min.). Common symptoms included dyspnea (N = 22; 45.8%) and fever (N = 12; 25%). Eleven patients needed readmission to ICU. Compared with non-admitted to ICU patients, ICU patients were higher comorbidities and severe laboratory abnormalities (eg, high blood d-dimer and fibrinogen). We also detected significantly low oxygen saturation, hypercapnia, and severe acidosis in readmitted patients. Radiologic investigations showed that there were severe ARDS with bilateral pneumonic infiltration resistant to medical treatment in 6 out of 11 patients who died (54.5%). CONCLUSION: Diffuse pneumonic infiltration related to Covid-19 may develop in asymptomatic cardiac surgery patients with negative RT-PCR test results. Immunologic disorders resulting from ECC, physiologic distress, and anesthesia may activate Covid-19 during the incubation period. We need randomized clinical trials to explain Covid-19 activation in the latent period of the virus, and clinical outcomes in cardiac surgery.

SYNTAX and Coronary Artery Calcium Score Predict Atherosclerotic Plaque Formation in the Ascending Aorta.

BACKGROUND: There is no study about the relationship between the complexity of coronary artery disease (SYNTAX SCORE; SS), and coronary artery calcium (CAC) score, accompanied with aortic calcium score (ACS) levels. The objective of this study was to investigate the relationship between the preoperative SS and CAC scores accompanying ACS in isolated CABG patients and their postoperative clinical results. METHODS: This study included 130 consecutive CABG patients. The mean age of the patients was 62.3 ± 8.62 years (range: 47-84 years). SS was measured using coronary angiography by an experienced cardiologist. We investigated the ACS accompanied with CAC scores using a multidetector computed tomography (MDCT) in the same session, preoperatively. Measurements of the CAC score and ACS were measured by an experienced radiologist, who was unaware of the study in the same session. In order to investigate aortic wall pathology in patients with positive aortic calcification, we provided aortic tissue samples prior to the proximal anastomosis of bypass grafts using No:11 scalpel. RESULTS: Overall median SS was 39 ± 7.2 (range: 15-41). CAC score was zero in 34 patients (26.1%). For the patients with a CAC score of zero, the median SS was 32 ± 9.4. There was no evidence of aortic calcification or plaque formation in 62 patients (47.6%). In these patients, the median SS was 35.6 ± 11.3. No significant difference was found when both groups were compared and for those patients with a calcific score of zero (P = .85). The median CAC score and ACS were 238 ± 122 AU (range: 0-1238 AU) and 112 ± 40 AU (range: 0-730 AU), respectively (P = .0033). For patients with a CAC score and ACS ≥400 AU, the mean SYNTAX score was ≥ 37. SS was correlated with CAC score (R:0.585; P < .0001). SYNTAX was correlated with ACS (R:0.557; P < .001). In multivariate analysis of SS (OR 1.053, 95% CI: 1.003-1.106, P = .039), gender (OR 0.189, 95% CI: 0.053-0.678, P = 0.011), age (OR 1.454, 95% CI: 1.256-1.632, P = .012), and diabetes mellitus (OR 0.341, 95% CI: 1.006-1.124, P = .014) were independent predictors for CAC score and aortic calcification. CONCLUSIONS: CAC score and ACS are strongly correlated with the complexity of coronary arteries in CABG patients. The total CAC score (≥ 400 AU) was independently associated with the degree of SS (>37). To prevent MACCE and mortality in CABG patients, we suggest the measurement of CAC score accompanied with ACS using MDCT as a non-invasive method. Highlight points: • Atherosclerotic plaque formation in aorta and coronary arteries are the main risk factors for stroke and infarction in CABG operations. •SYNTAX score value and aortic atherosclerosis levels are directly correlated. •SYNTAX score may predict the complications due to atherosclerosis during heart surgery.

Urgent Percutaneous Coronary Artery Intervention and Coronary Artery Bypass Grafting in STEMI Patients with Confirmed COVID-19.

BACKGROUND: Our aim of this study was to evaluate the cardiac symptoms, coronary angiographic results, and clinical outcomes of patients with confirmed COVID-19 and ST-segment elevation with myocardial infarction (STEMI) or myocardial ischemia. MATERIAL AND METHODS: Thirty-seven patients, who already were confirmed with COVID-19 using reverse transcriptase-polymerase chain reaction (RT-PCR), were admitted to our hospital due to chest pain with STEMI. The median patient age was 66 years (range: 27-84 years). Female/male ratio was 22/15. We performed a second RT-PCR test in all patients. We investigated myocardial enzymes (creatine kinase myocardial band (CK-MB), cardiac troponin-I (c-TnI), and C-reactive protein (CRP), and liver enzymes (alanine amino transferase (ALT) and aspartate amino transferase (AST) also were measured. Blood d-dimer, thromboplastin time (PT), partial thromboplastin time (PTT), and fibrinogen were investigated. Transcutaneous oxygen saturation was monitored for each patient in the emergency department (ED). To evaluate myocardial wall abnormalities, transthoracic echocardiography was performed. RESULTS: Coronary artery disorders requiring revascularization were detected in 25 patients (67.5%). There was no evidence of coronary artery disease in the remaining 12 patients. Out of 25, nine coronary artery disease patients had a history of coronary intervention (24.3%). All patients had high levels of myocardial enzyme release. Percutaneous coronary interventions (PCI) were performed in patients with culprit lesion(s). Success rate of PCI was 87.5% (N = 21). The median number of stent use was 2.9±0.7 (range: 1-4). Because PCI failed in four patients, we suggested elective coronary artery bypass grafting (CABG) surgery after medical treatment. Six patients required re-intervention owing to early stent thrombosis (30%). Seven patients died after PCI (33.3%). For patients with negative or positive RT-PCR test results, we performed thoracic computed tomography (CT), which is a sensitive diagnostic method for COVID-19. Interlobular septal and pleural thickening with patchy bronchiectasis in the bilateral or unilaterally lower and/or middle lobe(s) were the main pathologies in 24 patients. D-dimer, fibrinogen, and CRP levels were high in 11 PCI patients with bilaterally pulmonary involvement by COVID-19 (52.3%), while fibrin degradation products did not significantly change. For three patients with normal coronary arteries with a transient hypokinesia or hypokinesia as result of myocarditis, we decided to perform atypical Takotsubo cardiomyopathy. We medically treated using inodilator (levosimendan), diuretic, angiotensin-converting enzyme inhibitors and beta-blockers. To prevent the risk of thromboembolism, we also administered a heparin drip. The myocardial contractility of the apex did improve, and patients were discharged from the hospital, with the exception of one young female patient. She is following in the ICU with stabil hemodynamics. CONCLUSION: Chest pain with STEMI can develop in patients with confirmed COVID-19. Nearly one-third of patients had COVID-19 with chest pain and concomitant STEMI and normal coronary angiography (32.4%). Urgent PCI may be performed in hemodynamically unstable patients with high mortality. Complications, including sudden cardiac arrest, severe ventricular arrhythmia, and Takotsubo cardiomyopathy, related to COVID-19 patients with normal coronary arteries.

Clinical Outcomes of Extrapleural Closure of a Patent Ductus Arteriosus Concomitant with Aortic Coarctation Repair.

BACKGROUND: The aim of this study was to present an extrapleural approach for the closure of patent ductus arteriosus (PDA), with the repair of aortic coarctation (CoA) in the same session, in critically ill newborns and infants as an alternative to the transpleural surgical technique. METHODS: Between December 2007 and November 2010, 44 critically ill patients with PDA and coarctation of the aorta were operated on during the same session with the extrapleural approach. The diagnoses of the patients were made by transthoracic echocardiography (TTE). We investigated the aortic arch, the length of the coarctation segment, peak-to-peak gradients, the aortic valve, and intracardiac defects prior to the surgery using TTE. Cardiac angiography was performed to determine whether the patients were suitable for an interventional approach in hemodynamically stable patients. Twenty-eight patients had congestive heart failure with mild to moderate pulmonary and systemic hypertension. The median gestational age and weight of neonates were 2.1 kg (range: 1.4 to 2.9 kg), and 31.4 weeks (range, 28.6 to 37 weeks), respectively. During the operations, PDA was closed using double clips. Resection of coarctation with an extended end-to-end anastomosis was performed in 27 patients. Subclavian flap angioplasty was performed in four patients, and an aortic patch repair was performed in two infants. Postoperative PDA flow and residual aortic gradient were evaluated using echocardiography prior to discharge from the hospital and during the follow-up period. RESULTS: There were three in-hospital deaths (6.8%). During the follow-up period, two patients died (4.8%). The mean follow-up period was 48.3±21.5 months (range: 29-56 months). Patent foramen ovale, atrial septal defect, and ventricular septal defect were the additional cardiac pathologies. These were hemodynamically insignificant. We detected that the intracardiac defects closed spontaneously. During the follow-up period, recoarctation developed in six patients (20%). We found that the risk factors for recoarctation in patients were to have a gradient from coarctation area, which was higher than ≥ 50 mmHg, and the length of coarctation segment that was longer than 1 cm in their first operation (P = 0.033). The median time from the first surgery to recoarctation was 25.4±13.2 months (range: 16-36 months). Balloon dilatation was performed in four patients. We performed redo-surgery in the remaining two patients with recoarctation. The mean intubation time was 9.1±13.4 hours (range: 5.8-19.8 hours). Transthoracic echocardiography showed normal left ventricular dimensions and systolic function in 34 patients during follow up (87.1%). CONCLUSION: Our experiences show that surgical repair of aortic coarctation and PDA closure at the same session may be performed safely and with acceptable mortality and morbidity via an extrapleural approach. Interventional approach as a less invasive method may be used in patients who have developed recoarctation.

Should We Postpone Elective Cardiovascular Procedures and Percutaneous Coronary Interventions During the COVID-19 Pandemic?

BACKGROUND: Prioritization among patients with coronary artery disease represents a difficult issue during the SARS-CoV-2 pandemic. We present our clinical practices and patients' outcomes after elective, emergent, and urgent cardiovascular surgery and percutaneous coronary interventions (PCI). We also investigated the rate of nosocomial infection of SARS-CoV-2 in health workers (HWs), including surgeons after cardiovascular procedures and percutaneous interventions (PCI). MATERIAL AND METHODS: We performed 186 cardiovascular operations and PCI between March 15 and October 15. According to the level of priority (LoP), we performed urgent and emergent coronary artery bypass grafting (CABG) and cardiac valve repair or replacement surgery in 44 patients. In one patient with acute chordae rupture with pulmonary edema, we performed mitral valve replacement. We performed the aortic arch repair in two patients with type-I aortic dissection in urgent situations. Therefore, in 47 patients we performed cardiac operations in urgent or emergent situations. Elective CABG (N = 28) and elective cardiac valve (N = 10) surgeries were performed (total: 38). While rescue PCI was urgently performed in 47 patients with ST-segment elevation myocardial infarction (STEMI), it was performed in elective or emergent situations in 40 patients with myocardial ischemia. Endovascular treatment was performed in four patients with deep venous thrombosis (DVT) and in four patients with chronic arterial occlusion, respectively. Surgical vascular repair and embolectomy were performed in patients with peripheral artery injury (N = 6) and acute arterial embolic events (N = 4), respectively. We performed thoracic computed tomography followed by reverse transcriptase-polymerase chain reaction (RT-PCR) test in patients with irregular diffuse reticular opacities with or without consolidation on chest X-ray. Blood coagulation disorders including d-dimer, thromboplastin time (TT), and partial thromboplastin time (aPTT) were measured prior to procedures. RESULTS: No mortality and morbidity was seen after percutaneous and surgical arterial or venous procedures. The total mortality rate was 4.1% (8 of 186 CAD patients or valve surgery) after urgent and emergent CABG (N = 4), an urgent valve replacement (N = 1), and PCI (N = 3). Low cardiac output syndrome (LOS) and major adverse cardiac cerebrovascular event (MACCE) were the mortality factors after cardiac surgery. The reasons for death after PCI were sudden cardiac arrest related to the dissection of the left main coronary artery during procedure and pneumonia due to COVID-19 (N = 2). Ground-glass opacities in combination with pulmonary consolidations were detected in seven patients. Interlobular septal and pleural thickening with patchy bronchiectasis in the bilateral lower lobe involvement was found after thoracic computed tomography in these patients. We confirmed in-hospital COVID-19 using a PCR test in two patients with STEMI prior to PCI. PT and aPTT increased, but fibrin degradation products did not in those two patients. We confirmed COVID-19 via phone call in six CABG patients and one PCI patient after discharge from the hospital. None of the patients diagnosed with COVID-19 died after being discharged from the hospital. CONCLUSION: Cardiovascular surgery and PCI can safely be performed with acceptable complications and mortality rates in elective situations, during the COVID-19 pandemic. Preoperative control of OR traffic, careful evaluation of the patient's history, consultation, and precautions taken by healthcare professionals are important, during and after procedures. Also important is wearing a mask and face shield and careful disinfection of equipment and space.

The Effects of Amino Acids Enriched Del Nido Cardioplegia on Myocardial Leucocyte Accumulation and Ventricular Functions in Patients Undergoing Coronary Artery Bypass Grafting Surgery.

BACKGROUND: One of the main sources of ischemia/reperfusion injury (IRI) and release of free oxygen radicals (FORs) during extracorporeal circulation (ECC) during cardiac surgery is neutrophils. In this study, we investigated the potential effects of our modification of del Nido cardioplegia (mDNC) (amino acids enriched del Nido cardioplegia) on myocardial polymorphonuclear leucocyte (PMNL) accumulation. We also compared the effects of our mDND and classical del Nido cardiplegia (cDNC) on ventricular contractile functions in coronary artery bypass grafting (CABG) surgery. PATIENTS AND METHODS: Our study included 100 isolated CABG patients with similar characteristics, including age, gender, preoperative medications, diabetes, hypertension, and left ventricular ejection fraction (LVEF). The patients were divided into two groups. Amino acids supplemented del Nido cardioplegia (L-aspartate and L-glutamate at a dose of 13 milimol/L) in 50 patients (study group, G1). In the remaining 50 patients, we used a classical del Nido cardioplegic solution (cDNC) (control group, G2). Myocardial Tru-Cut biopsy from the right ventricle was taken before the institution of ECC and after weaning from ECC in all patients. Cardiac troponine-I (cTn-I), tumor necrosis factor-alpha (TNF-Alpha), Pro-Brain Natriuretic Peptide (Pro-BNP), and lactate levels were measured pre- and postoperatively. Invasive monitoring was performed to provide the left ventricular functions in both groups in the operating room and noted by a blinded anaesthesiologist. RESULTS: Five patients died post-surgery (5%) (two from SG and three from CG (P = .67), due to low cardiac output syndrome or multiorgan failure. At the postoperative period, cardiac output (CO) and stroke volume index (SVI) was higher in mDNC (mean ± SDS; 32.1 ± 7 versus 22.2 ± 6.9 mL/min/m² (P < .001). CI was significantly higher in mDNC after surgery (3.10 ± 0.76 versus 2.40 ± 0.30L/min/m² (P = .002). Ten patients (20%) in mDNC and 16 patients (32%) in cDNC required inotropic support (P < .001). The postoperative inotropic requirement was less in mDNC (6.1 ± 1.8 mg/kg versus 9.2 ± 1.9 mg/kg, P < .004). Blood gas analyses from the coronary sinus showed that myocardial acidosis was more severe in the control group [pH (0.10 ± 0.09 versus 0.054 ± 0.001; P = .34)]. Blood lactate levels were significantly high in the control group (1.01 ± 0.007 mmol/L versus 1.92 ± 0.35 mmol/L) (P = .22). No difference was found when compared with cardioplegia volume in the mDNC and cDNC groups (mDNC= 990.00 ± 385 mL in DNC = 960 ± 240 mL, P = .070). An aortic cross-clamp time in the mDNC and cDNC groups were 88.4 ± 8.9 min, and 93 ± 11 min, (P = .76), but cardiopulmonary bypass time was significantly low in mDNC (mDNC = 98.3 ± 22.5 min, DNC = 126 ± 19.5 min, P = .0020). TNF-Alpha and Pro-BNP levels in patients received mDNC were significantly low (P = .022). Postoperative cardiac enzyme levels (creatine kinase-MB and high sensitive troponin-I) were significantly low in the mDNC group (P = .0034). Myocardial biopsy results showed that myocardial PMNL accumulation was significantly high in the control group (P = .001). The amount of inotropic agent use was significantly high in the control group (P = .003). After weaning from ECC, the left ventricular stroke work index (LVSWI), cardiac index (CI), and heart rate (HR) were significantly high in the study group (P = .032; P = .002; P = .01). Postoperative blood and blood products requirements were significantly low in the mDNC group (P = .002). At pre-discharge echocardiography, the mDNC group demonstrated significantly higher ventricular ejection fraction (37.9 ± 4.3% and 29.7 ± 3.8%, respectively (P = .003). CONCLUSION: Our study findings show that glutamate-aspartate supplemented del Nido cardioplegia significantly decrease myocardial PMNL accumulation with reduced release of biochemical markers, including cardiac troponin-I, TNF-alpha, and Pro-Bnp. Our study results demonstrated that amino acids supplementation in del Nido cardioplegia has some advantages in CABG patients, including the decrease of perioperative myocardial infarction and increase significantly the left ventricular functions including ventricular SVI and CI.

Rosuvastatin Lowers Systemic Inflammatory Response in Coronary Artery Bypass Graft Accompanied by Cardiopulmonary Bypass Surgery: A Randomized Controlled Study.

PURPOSE: Cardiopulmonary bypass (CPB) is commonly associated with a systemic inflammatory response that may lead to severe complications. Classic signs of systemic inflammatory response syndrome are complement activation and changes in cytokine and acute phase reactant levels. The effects of rosuvastatin after CPB on interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-18 (IL-18) and High Sensitivity C-Reactive Protein (hs-CRP) levels were investigated. METHODS: Thirty-seven male and thirteen female patients (total=50) aged 42 to 78 years, who had coronary bypass surgery due to coronary artery disease were randomly divided into two groups. The 25 patients in the control group were administered placebos. The 25 in the treatment group were administered 20 mg rosuvastatin tablets daily between preoperative day 7 and postoperative day 28. Blood samples were taken at six time points; before induction of anesthesia (T1), during CPB (T2), five minutes after removal of cross clamp (T3), after protamine infusion (T4), postoperative day three (T5) and postoperative day 28 (T6). Data points were expressed as mean ± standard deviation (SD). RESULTS: Rosuvastatin lowered IL-6 levels at T4, T5 and T6 time points (T4, T5, T6 p < 0.05), and elevated IL-10 levels at T3 and T4 (T3, T4 p < 0.05). IL-18 levels were also elevated at multiple time points. Rosuvastatin also lowered hs-CRP levels and cholesterol levels at T6 (p < 0.05). CONCLUSION: Administering 20 mg/day of rosuvastatin between preoperative day 7 and postoperative day 28 may result in fewer complications in certain (especially intraoperative) cases of systemic inflammatory response caused by the CPB technique used in coronary bypass surgery.

In vitro effects of sodium nitroprusside and leptin on norepinephrine-induced vasoconstriction in human internal mammary artery.

AIM: The biological and pharmacological properties of vessels used in coronary artery bypass graft (CABG) surgery are as important as their mechanical properties. The aim of this study was to investigate the possible role of protein kinase C (PKC)-dependent mechanisms in leptin-induced relaxation in the human internal mammary artery (IMA). METHODS: IMA rings, obtained from patients undergoing CABG surgery, were suspended in isolated tissue baths containing Krebs-Henseleit solution, which were continuously gassed with 95% O2 and 5% CO2 at 37(°)C. RESULTS: The IMA rings were pre-contracted with increasing concentrations of norepinephrine (NE 10(-9)-10(-4) mol/l) and the relaxation responses to sodium nitroprusside (SNP), a nitrosovasodilator, and leptin were studied in the presence and absence of a PKC inhibitor. Leptin (1 µM) caused a dose-dependent relaxation in NE pre-contracted IMA rings. Pre-treatment with a PKC inhibitor significantly attenuated this vasorelaxatory response to leptin in human isolated IMA. CONCLUSION: It was found that SNP and leptin caused significant relaxation of the NE pre-contracted human IMA rings, and PKC was probably the sub-cellular mediator for this effect. Our findings may have clinical or pharmacological importance as it could be hypothesised that obese subjects who have a left IMA bypass graft would have better myocardial perfusion.

Relationship between mean platelet volume elevation and left ventricular mass index in hypertensive patients.

OBJECTIVES: To compare the mean platelet volume (MPV; a general marker of platelet activation) in groups of patients with and without hypertension and to analyse its relationship with left ventricular mass index (LVMI). METHODS: This cross-sectional, observational study enrolled newly diagnosed patients with untreated stage I-II hypertension and healthy control subjects without hypertension. MPV was measured using a haematology analyser. Echocardiography was performed on all of the study participants. RESULTS: A total of 50 newly diagnosed patients with hypertension and 50 healthy control subjects were enrolled in the study. The majority of the demographic characteristics and laboratory findings were not significantly different between the two groups. The mean ± SD MPV was significantly higher in the hypertensive group compared with the control group (10.3 ± 1.4 fl versus 9.2 ± 1.8 fl, respectively). The mean ± SD LVMI was significantly higher in the hypertensive group compared with the control group (115.9 ± 23.0 g/m(2) versus 95.7 ± 23.4 g/m(2), respectively). There was no significant correlation between MPV and LVMI. CONCLUSION: In patients with untreated hypertension, despite elevated MPV levels there was no correlation between LVMI and MPV.

Evaluation of systemic inflammatory response in cardiovascular surgery via interleukin-6, interleukin-8, and neopterin.

AIM: The aim of this study was to evaluate the serum levels of interleukin-6 (IL-6), IL-8, and neopterin as a sign of systemic inflammatory response syndrome after open-heart surgery. In this study, we evaluated the influences on the levels of IL-6, IL-8, and neopterin of coronary artery bypass grafting (CABG) and valve replacement surgeries with and without the use of extracorporeal circulation (ECC). MATERIALS AND METHODS: This prospective study was performed in 30 patients. In this study, we evaluated patients who underwent valve replacement surgery (group 1, n = 10), CABG with ECC (group 2, n = 10), or CABG using the beating-heart technique (group 3, n = 10). With the Human Investigation Ethics Committee consent, blood samples were obtained from the patients before the surgery (T0) and after 1 hour (T1), 4 hours (T2), 24 hours (T3), and 48 hours (T4) of protamine injection. IL-6, IL-8, and neopterin levels were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: The demographic data and preoperative and operative characteristics of the patients were similar. Neopterin IL-6 and IL-8 levels significantly increased first at the fourth hour after the surgery. When compared to the levels before the surgery, this increase was statistically significant. Unlike the other 2 groups of patients, those who experienced CABG with the beating-heart technique (group 3) had decreased neopterin levels at the first hour after the surgery, but this decrease was not statistically significant. Neopterin levels increased later in the OPCAB group, but these increased levels were not as high as the neopterin levels of groups 1 and 2. Neopterin reached maximum levels at the 24th hour and, unlike groups 1 and 2, in group started to decrease at the 48th. CONCLUSIONS: Complement activation, cytokine production, and related cellular responses are important factors during open-heart surgery. It is certain that ECC activates the complement systems, and activated complement proteins cause the production of several cytokines. In our study, neopterin levels in patients who underwent beating-heart method surgery were lower than those in the other groups, and these levels started to decrease at the 48th hour. These data suggest that the systemic inflammatory response was less activated in that patient group. The beating-heart method might be an important alternative in CABG surgery to minimize the complications and mortality related to surgery.

Effects of rosuvastatin on ADMA, rhokinase, NADPH oxidase, caveolin-1, hsp 90 and NFkB levels in a rat model of myocardial ischaemia-reperfusion.

AIM: Endothelial dysfunction, oxidative stress and inflammation are among the most important mechanisms of ischaemia-reperfusion (I/R) injury. Besides their cholesterol-lowering effects, statins are known to provide protection against myocardial dysfunction and vascular endothelial injury via nitric oxide-dependent mechanisms. The aim of this study was to investigate the effects of rosuvastatin on certain intermediates involved in the generation of nitric oxide (asymmetrical dimethyl arginin, ADMA, caveolin-1 and hsp 90), oxidative stress (rhokinase, NADPH oxidase) and inflammation (NFkB), using an in vivo model of myocardial infarction in the rat. METHODS: Adult male Sprague Dawley rats were divided into three groups (control, I/R and I/R after 15 days of rosuvastatin administration). Reperfusion was applied for 120 min following left anterior descending coronary artery ischaemia for 30 min. Caveolin-1, hsp 90 and NFkB levels were evaluated with the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and ADMA, rhokinase and NADPH oxidase levels were evaluated with ELISA. RESULTS: While NFkB and hsp 90 levels were higher in the I/R group, their levels were significantly lower in the rosuvastatin group. While ADMA and NADPH oxidase levels significantly increased with I/R, they were lower in the rosuvastatin-treated group, but not statistically significant. Rhokinase levels were significantly lower in the rosuvastatin group. Caveolin-1 levels were not different between the groups. CONCLUSION: Our results suggest that ADMA, rhokinase, NADPH oxidase, hsp 90 and NFkB could facilitate I/R injury, and rosuvastatin significantly reduced levels of these parameters. These results indicate that rosuvastatin may have a protective role in I/R injury via mechanisms targeting inflammation, endothelial dysfunction and oxidative stress.

An experimental lymphoscintigraphy study in an acute unilateral deep venous thrombosis model.

BACKGROUND: The aim of this study is to investigate the effect of both inguinal exploration and deep venous thrombosis on lymphatic flow in an experimental model of unilateral acute obstruction of the femoral vein. METHODS AND RESULTS: Eighteen male New Zealand White rabbits were the subjects of this study. The rabbits were divided into three groups; Group 1 (n=6, control), Group 2 (n=6, sham), and Group 3 (n=6, operation). After the lymphoscintigraphy was performed on the Group 1 animals, the rabbits in Group 2 and Group 3 underwent intervention. In Group 3, the femoral vein was clipped and excised. In Group 2, an inguinal incision was performed and the clip materials were placed beneath the femoral vein. After the surgical intervention, lower extremity lymphoscintigraphy by subcutaneous administration of Tc-99m nanocolloid was performed in dynamic and static manner in Groups 2 and 3 on the second, fifteenth and thirtieth days after the operation. Unilateral impairment of the lymphatic flow in the operated extremity was observed in Group 3 in the early and late postoperative period but unilateral lymphatic impairment was observed in Group 2 in only the late postoperative period. CONCLUSION: The lymphatic impairment in an operated extremity might be the consequence of surgical intervention rather than acute venous obstruction in cases where both situations are observed.

Effects of high loading dose of clopidogrel in ST elevated myocardial infarction treated with fibrinolytic agent.

PURPOSE: The purpose of the present study was to evaluate the effects of different loading doses of clopidogrel on ST segment resolution on ECG, changes in cardiac enzyme levels and serum levels of high-sensitivity C-reactive protein (Hs-CRP) in patients with ST elevated myocardial infarction (STEMI) treated with fibrinolytic therapy. METHODS: Patients admitted to our cardiology clinic with a diagnosis of STEMI and treated with fibrinolytic therapy were included: Group 1 (n=58) received a 300 mg loading dose of clopidogrel, Group 2 (n=55) a 450 mg loading dose and Group 3 (n=59) a 600 mg loading dose. A 75 mg/d maintanence dose of clopidogrel was given in all groups. RESULTS: All demographic characteristics and baseline laboratory parameters were statistically similar among three groups (p > 0.05). When ST resolution periods were compared, most patients in Group 3 had ST resolution at 30 minutes; Group 2 at 60 minutes and Group 1 at 90 minutes (p < 0.05). Peak levels of creatine kinase (CK) and CK-MB were as follows: Group 3, 8(th) hour, Group 1 and 2, 12(th) hour. Peak levels of those enzymes were significantly lower in Group 3 than in Group 1 and 2 ( < 0.05). Although basal hs-CRP levels of all groups were similar, the increase in hs-CRP levels at 48 hours was lower with higher clopidogrel loading doses (p < 0.05). CONCLUSION: In this study comparing three different clopidogrel loading doses, the higher doses provided earlier ECG resolution, earlier and lower peak CK and CK-MB levels and lower levels of hs-CRP.

The effects of intra-operative amiodarone loading on the systemic inflammatory response syndrome induced by cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) leads to systemic inflammatory response syndrome (SIRS). In vitro studies showed that amiodarone blocked cytokine production. The aim of this study was to evaluate the effect of intra-operative amiodarone loading on SIRS. METHODS: This prospective randomized study included 24 patients who underwent on-pump coronary artery surgery. The patients were classified into control (n=12) and amiodarone (n=12) groups. Plasma levels of the pro-inflammatory (C-reactive protein - CRP, interleukin-6 - IL-6) and the anti-inflammatory markers (interleukin-10 - IL-10) were measured before the induction of anesthesia, 5 minutes after aortic declamping, after protamine administration and 24 hours after the CPB. The myocardial lactate production was calculated before CPB and 5 minutes after aortic declamping. Statistical analyses were performed using Mann-Whitney U, Fischer's exact and ANOVA tests. RESULTS: In both groups, the IL-6 levels significantly increased after declamping (91.18+/-16.27 pg/ml and 86.37+/-14.66 pg/ml, p<0.01) and reached peak values after infusion of protamine (329.07+/-32.24 pg/ml and 354.31+/-29.61 pg/ml, p<0.01). The highest values of IL-10 were detected after infusion of protamine in the control and amiodarone groups (265.58+/-85.63 pg/ml, p<0.01 and 287.44+/-65.26 pg/ml, p<0.01). Amiodarone did not have any significant effect on release of cytokines. The CRP levels were significantly elevated in both groups at 24th hour after CPB, but no significant difference was found between the groups. Compared with pre-CPB values, lactate production increased significantly in two groups after aortic declamping. However there was no significant difference between the groups. CONCLUSION: The results indicate that intraoperative loading of amiodarone, which is used for atrial fibrillation prophylaxis, does not seem to alter inflammatory response during CPB.