Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis.

AIM: The factors mediating the paracrine effects of perivascular adipose tissue (PVAT) in atherosclerosis are largely unknown. The adipokine leptin has been implicated in the increased cardiovascular risk in obesity and may locally promote neointima formation independently of circulating leptin levels. In patients with established coronary artery disease, we examined the expression of leptin as well as of its possible inducers in 'cardiac' PVAT surrounding the aortic root and coronary arteries (C-PVAT), and compared it to the PVAT surrounding the internal mammary artery (IMA-PVAT), a vessel resistant to atherosclerosis. METHODS AND RESULTS: Tissue specimens collected from male patients undergoing coronary artery bypass surgery were processed for real-time PCR, ELISA, in situ hybridization, and immunohistochemistry analysis. Leptin protein expression was elevated in C-PVAT compared to IMA-PVAT, independent of serum leptin levels. Compared to IMA-PVAT, C-PVAT exhibited more pronounced angiogenesis and inflammation, as indicated by significantly higher numbers of PECAM1-positive vessels and CD68-positive macrophages, and was characterized by a greater extent of fibrosis and hypoxia. Increased expression of hypoxia-inducible factor-1α and Fos-like antigen (FOSL)2, factors known to enhance leptin gene transcription, was observed in C-PVAT. As a proof of concept, exposure of human adipocytes to chemical hypoxia resulted in significantly increased FOSL2 and leptin mRNA levels. CONCLUSIONS: A higher degree of local tissue hypoxia and up-regulation of leptin expression in the perivascular adipose tissue, along with increased vascularization, inflammation, and fibrosis, may contribute to the increased atherosclerotic plaque burden in the coronary arteries compared to the IMA.

Re-do aortic operation in a young patient for aggressive Takayasu's arteritis.

Takayasu's arteritis is an inflammatory arteriopathy which involves the aorta and its major branches, causing mainly stenosis of their lumen, though aneurysmal lesions can also occur. A young female with Takayasu's disease presented to our hospital with acute lung oedema due to severe aortic insufficiency and ascending aorta dilatation. She had already undergone distal ascending aorta and hemiarch replacement due to Standford type A aortic dissection five years ago. The patient had also undergone reconstruction of abdominal arteries' stenoses with extraanatomical bypass. We performed a Bentall procedure with a valved conduit and implantation of the coronary ostia as buttons on the conduit. A mechanical valved graft was used instead of a bioprosthesis, due to possible early degradation of a bioprosthesis. The postoperative course was uneventful and the one year follow-up was normal. Valve-sparing aortic root replacement should be avoided in Takayasu's arteritis due to high rate of recurrent regurgitation.

Adenocarcinoma in pulmonary sequestration.

A 67-year-old male smoker presented with hemoptysis and recurrent pneumonia. Chest computed tomography showed an emphysematous cyst and air-fluid level cavities in the left lower lobe. A left lower lobectomy was performed. The intraoperative finding was intralobar sequestration. Histopathology revealed adenocarcinoma within the sequestrated lobe. Only 8 cases of lung cancer and sequestration have been reported since 1963.

Attenuation of propofol tolerance conferred by remifentanil co-administration does not reduce propofol toxicity in rabbits under prolonged mechanical ventilation.

BACKGROUND: Prolonged sedation with propofol at high doses may lead to fatal multi-organ dysfunction, know as propofol infusion syndrome. We tested the hypothesis that propofol plus remifentanil co-administration attenuates propofol tolerance to its sedative effect and assessed if such an effect has an impact on propofol toxicity in rabbits under prolonged mechanical ventilation. MATERIALS AND METHODS: Eighteen healthy male rabbits were mechanically ventilated and received propofol (group P, n = 6), propofol plus remifentanil (group PR, n = 6), or remifentanil plus sevoflurane (group RS, n = 6) in order to be kept under sedation (group P) or sedation/analgesia (groups PR and RS) for up to 48 h. Initial propofol and remifentanil infusion rates (IRs) were adjusted, if needed, to maintain the desired level of sedation and analgesia, respectively (groups P and PR). In group RS, remifentanil was infused at IRs equivalent to those of group PR. Propofol IRs were recorded, propofol concentrations were measured in the arterial plasma, and blood biochemical parameters and organ histopathology were assessed. RESULTS: Animals survived for 29-36 h in group P and 22-38 h in group PR (100% mortality rate). Tolerance was developed to propofol's sedative effect. The onset of tolerance was delayed and its magnitude was decreased in group PR compared with group P. Propofol was accumulated in the systemic circulation. Propofol clearance rate was gradually decreased. Arterial lactate, and serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, cholesterol, triglycerides, and creatine kinase (CK) levels were increased. The heart, lungs, liver, gallbladder, kidneys, urinary bladder, and skeletal muscles were seriously injured in groups P and PR. In group RS, mortality was 0%, while there was only mild injury of the lungs, liver, gallbladder, kidneys, and urinary bladder. CONCLUSIONS: Although propofol tolerance is attenuated in propofol plus remifentanil receiving rabbits under prolonged mechanical ventilation, fatal multi-organ injury occurs resembling human propofol infusion syndrome.

One-lung ventilation and HIF1alpha expression in lung cancer and pneumothorax.

BACKGROUND/AIM: A prospective study was designed to investigate the effects of anesthesia, particularly that of the one-lung ventilation procedure (OLV), on the expression of hypoxia-inducible factor 1alpha (HIF1alpha) in patients with lung carcinomas and pneumothorax. MATERIALS AND METHODS: The immunohistochemical expression of HIF1alpha was studied in formalin-fixed paraffin-embedded tissues from 60 patients who had undergone thoracic surgery for lung cancer (n=48) or pneumothorax (n=12) under OLV general anesthesia. RESULTS: There was a significant, and rather unexpected, association of HIF1alpha expression with high body mass index (BMI) (p=0.01) and high body weight (p=0.01) of patients with lung carcinomas, but other anesthesia-related parameters, including analysis of arterial oxygen partial tension and anthropometric factors remained insignificant. With regard to pneumothorax cases, these were immunohistochemically unreactive and, hence, no relationship was noted between HIF1alpha and anesthesia parameters. CONCLUSION: Anesthesia and OLV procedure performed for lung cancer or pneumothorax does not affect the expression of HIF1alpha. However, the significant link between high BMI and HIF1alpha expression noted in patients with lung carcinomas brings forward a possible connection between obesity and hypoxia-related molecular pathways.

A rare case of late right ventricular perforation by a passive-fixation permanent pacemaker lead.

The present paper is an interesting and rare complication of implantation of a permanent pacemaker lead. The rarity of the case is based upon that ventricular perforation is usually present during implantation, whereas in our case, it was presented late--1 month after implantation. Furthermore, in our case, the pacemaker lead had migrated through the left hemidiaphragm into the peritoneal cavity.

Elective bridging to recovery after repair: the surgical approach to ventricular reverse remodeling.

We described our "surgical approach to reverse ventricular remodeling" in advanced chronic heart failure, based on the unique idea that "downstaging" class IV heart failure by supporting patients with left ventricular assist devices (LVADs) allows treatments mainly indicated for class III patients. The types of surgeries include mitral valve repair, surgical ventricular remodeling, coronary artery bypass grafting, and cardiac resynchronization. This approach has been applied to two patients with class IV chronic heart failure due to idiopathic dilated cardiomyopathy who were supported with the magnetically levitated Levacor LVAD. These were the first in-human implantations of this device. Sustained short- to medium-term recovery has been achieved in both patients.

Surgical treatment of pulmonary aspergillosis/mycosis in immunocompromised patients.

Invasive pulmonary aspergillosis is a severe complication in immunosuppressed patients. Surgical resection can be curative in certain patients after antifungal treatment. Over a 7-year period, ten patients with suspected invasive pulmonary aspergillosis of two university hospitals were retrospectively reviewed. A literature review was undertaken. Patient's age was 48.1 years (mean); the cause of immunosuppression was a hematological disease with consecutive therapy in seven patients and chronically corticoid therapy in three patients. After an antifungal therapy, surgical resection was performed with lobectomy/segmentectomy in 60% and with wedge-resection in 40%. Postoperative course were uneventful in seven patients, two patients died due to infectional circumstances, and one patient was reoperated because of empyema. The underlying disease marked long-term follow-up. Resection of focal pulmonary invasive aspergillosis can be curative. Clinical circumstances and dissemination must be taken into consideration to indicate surgery. To point out the best pathway randomised prospective studies are necessary.

Sternoclavicular joint septic arthritis and mediastinitis. A case report and review of the literature.

Septic arthritis of the sternoclavicular joint is rare. Its causes have been reported to include immuno-compromizing diseases, intravenous drug abuse, fractures of the clavicle or catheterization of the subclavian vein. We report a case of septic arthritis of the SCJ in a diabetic patient following periarticular injection of steroids in the ipsilateral shoulder, as this route of infection has not been documented, to our knowledge, in the literature to date. We review the literature regarding epidemiology and methods of surgical treatment that have been proposed, and present our own surgical experience. Bacterial infection should always be suspected in cases of SCJ arthritis. If surgery is required, it is important to remember that bony procedures leave vascular structures exposed, making their cover by myoplasty mandatory.

Feasibility study of a temporary percutaneous left ventricular assist device in cardiac surgery.

BACKGROUND: The aim of this study is to evaluate a percutaneous left ventricular assist device (Tandem Heart pVAD; Cardiac Assist, Pittsburgh, Pennsylvania) in the postcardiotomy setting. METHODS: Between August 2001 and August 2004, 11 high-risk male patients who had undergone heart failure surgery or surgical revascularization were supported by the TandemHeart postcardiotomy. The major indication for pVAD insertion was failure to wean from cardiopulmonary bypass. Three different techniques were employed for cannulation: the closed percutaneous technique, the "open transeptal" technique with percutaneous cannulas insertion, and direct central cannulation. RESULTS: The mean duration of support was 88 hours. The mean pump flow was 3.09 L/min. The weaning rate was 72.72%. Survival to discharge and at 1 and 4 years was 54.54%, 45.45%, and 36.36%, respectively. The main complication was pericardial bleeding, noted mainly in patients receiving antiplatelet treatment preoperatively. CONCLUSIONS: The TandemHeart appears to be safe for temporary support after cardiotomy. It is a versatile device allowing different techniques of insertion. Device application yielded high weaning rate and satisfactory early and long-term survival.

Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma.

Immunohistochemical evaluation of lung carcinomas for key enzymes involved in cellular metabolism (lactate dehydrogenase LDH 1 and 5, pyruvate dehydrogenase PDH, pyruvate dehydrogenase kinase PDHK-1, monocarboxylate transporters MCT 1, 2 and 4, glucose transporter GLUT1, hypoxia inducible factors HIF1alpha and 2alpha) show a complementary metabolic profile between cancer cells and tumor-associated stroma. Cancer cells share enzyme/transporter activities suggestive of an anaerobic metabolism with high affinity for glucose absorption, anaerobic glycolysis and lactate extrusion. On the other hand, the tumour-associated fibroblasts express patterns involved in aerobic pathways and lactate oxidation. These findings bring forward the hypothesis that tumor associated stroma is an accomplice in tumor growth and survival sustaining an independent cellular and metabolic tumor domain. The development of agents exploiting such cancer specific metabolic pathways may prove of importance in the treatment of lung cancer.

Internal thoracic artery side branch ligation for post coronary surgery ischemia.

Two cases of internal thoracic artery side-branch ligation in patients with recurrent angina after coronary bypass are reported with long-term follow-up. Ligation was performed with clips via a left thoracotomy. Treadmill stress testing after 3 and 4 years did not provoke any myocardial ischemia. These findings suggest that an unligated side-branch can produce a steal phenomenon.

Angiogenic growth factors in the treatment of peripheral arterial disease.

Peripheral arterial disease (PAD) remains a major cause of morbidity. Despite advances in revascularisation procedures and medical treatment, limb salvage and relief of pain are still not satisfactory in patients with severe disease. This has prompted the exploration of alternative modes of treatment including enhancement of new vessel formation (angiogenesis). Angiogenic Growth Factors (AGF), mainly Vascular Endothelial Growth Factor (VEGF), basic Fibroblast Growth Factor (bFGF) and Hepatocyte Growth Factor (HGF) have emerged as exciting therapeutic modalities. Both experimental and clinical studies have demonstrated that topical (mainly intramuscular) AGF gene therapy results in improved peripheral vasculature and alleviation of symptoms. However, most clinical work is limited to small patient series and the long-term safety and efficacy are still unclear. Clinical benefit must be balanced against potential untoward effects, such as tumour growth and atherosclerotic plaque angiogenesis leading to plaque instability. VEGF is important in the pathogenesis of diabetic microvascular disease. Further studies are required before implementation of AGF therapy in clinical practice.

Organ toxicity and mortality in propofol-sedated rabbits under prolonged mechanical ventilation.

BACKGROUND: Prolonged administration of propofol at large doses has been implicated in propofol infusion syndrome in intensive care unit patients. In this study we investigated organ toxicity and mortality of propofol sedation at large doses in prolonged mechanically ventilated rabbits and determined the role of propofol's lipid vehicle. METHODS: Eighteen healthy male rabbits were endotracheally intubated and sedated with propofol 2% (Group P), sevoflurane (Group S) or sevoflurane while receiving Intralipid 10% (Group SI). Sedation lasted 48 h or until death (Group P) or the maximum surviving period of Group P (Groups S and SI). The initial propofol infusion rate (20 mg x kg(-1) x h(-1)) or sevoflurane concentration (1.5%) was adjusted, if needed, to maintain a standard level of sedation. Blood biochemical analysis was performed in serial blood samples and histologic examination in the heart, lungs, liver, gallbladder, kidneys, urinary bladder, and quadriceps femoris muscle at autopsy. RESULTS: The mortality rate was 100% (surviving period, 26-38 h) for Group P, whereas 0% for Groups S and SI. The initial propofol infusion rate had to be increased up to 65.7 +/- 4.6 mg x kg(-1) x h(-1) and sevoflurane concentration up to 4%. Serum liver function indices, lipids and creatine kinase were significantly increased (P < 0.05) in Groups P and SI and lactate was increased only in Group P, whereas amylase was increased in all groups. In Group P, histologic examination revealed myocarditis, pulmonary edema with interstitial pneumonia, hepatitis, steatosis, and focal liver necrosis, cholangitis, gallbladder necrosis, acute tubular necrosis of the kidneys, focal loss of the urinary bladder epithelium, and rhabdomyolysis of skeletal muscles; in Group S, low-grade bronchitis and incipient inflammation of the liver and the kidneys; and in Group SI, low-grade bronchitis, liver steatosis and hepatitis, and incipient inflammation of the gallbladder, kidneys, and urinary bladder. CONCLUSIONS: Continuous infusion of 2% propofol at large doses for the sedation of rabbits undergoing prolonged mechanical ventilation induced fatal multiorgan dysfunction syndrome similar to the propofol infusion syndrome seen in humans. Our novel findings including lung, liver, gallbladder, and urinary bladder injury were also noted. The role of propofol's lipid vehicle in the manifestation of the syndrome was minor. Sevoflurane proved to be a safe alternative medication for prolonged sedation.

Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium.

BACKGROUND: Myocardial angiogenesis after the systemic administration of basic fibroblast growth factor or vascular endothelial growth factor at high therapeutic doses has been implicated in the occurrence of side effects that may undermine their safety. The aim of this study was to investigate the angiogenic effects of the intramyocardial administration of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, at low doses, in the infarcted rabbit myocardium. METHODS AND RESULTS: Twenty-five New Zealand White rabbits were divided into five groups (n=5) and subjected to coronary artery ligation after lateral thoracotomy, inducing acute myocardial infarction. Five minutes later, the following substances were injected intramyocardially into the infarcted area: (a) normal saline (controls); (b) 6.25 or 12.5 mug of recombinant human basic fibroblast growth factor protein (basic fibroblast growth factor-1 group or basic fibroblast growth factor-2 group); or (c) 5 or 10 microg of recombinant human vascular endothelial growth factor 165 protein (vascular endothelial growth factor-1 group or vascular endothelial growth factor-2 group). On the 21st postoperative day, the animals were euthanized, and their hearts were subjected to histopathological examination and immunohistochemical assessment of vascular density in the infarcted area. The alkaline phosphatase anti-alkaline phosphatase procedure and the primary monoclonal antibody JC70 were used. Histopathological examination confirmed the induction of myocardial infarction. Vascular density was significantly increased (P<.004) in all treatment groups (in mean+/-S.E. vessels/x 200 optical field: basic fibroblast growth factor-1: 85.8+/-10.9; basic fibroblast growth factor-2: 76.6+/-3.7; vascular endothelial growth factor-1: 73.4+/-3.2; vascular endothelial growth factor-2: 89.5+/-5.2) compared to that in controls (58.9+/-4.9 vessels/x 200 optical field). Vascular density in the vascular endothelial growth factor-2 group was significantly higher than that in the vascular endothelial growth factor-1 group (P<.001). CONCLUSIONS: Low doses of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, when administered intramyocardially, stimulate angiogenesis in the infarcted myocardium.

Tolerance to propofol's sedative effect in mechanically ventilated Rabbits.

Propofol is commonly used for the sedation of critically ill patients undergoing mechanical ventilation. These patients may develop tolerance during long-term administration. Here, we describe the development of tolerance to propofol's sedative effect in rabbits during prolonged mechanical ventilation. Six healthy male New Zealand White rabbits were endotracheally intubated and received propofol by continuous IV infusion to maintain sedation for 48 h. The propofol infusion rate (IR) was adjusted to maintain the desired level of sedation. Assessments of the sedation level were made every 30 min or earlier if there were signs of awakening. Propofol concentrations were measured in arterial plasma after every other IR adjustment, provided there was an adequate level of sedation, using high performance liquid chromatography, and calculations of systemic clearance rates were made. The mortality rate was 100% with a survival period of 30.8 +/- 6.0 h (mean +/- sd). The course of IR adjustments followed a 5-phase pattern: 1) steady IR (mean +/- sd duration; 1.2 +/- 0.6 h), 2) increasing IR (9.4 +/- 5.5 h), 3) steady high-IR (2.3 +/- 1.2 h), 4) decreasing IR (13.7 +/- 1.9 h), and 5) steady low-IR (5.0 +/- 2.7 h). The course of propofol concentrations during the experiment in relation to propofol IR followed a 3-phase pattern: 1) steady concentration with increasing IRs (6.0 +/- 2.7 h), 2) increasing concentrations with increasing IR (5.8 +/- 2.5 h), and 3) increasing concentrations with decreasing IR (18.8 +/- 3.3 h). Propofol systemic clearance rates were progressively increased for 6.0 +/- 2.7 h and then gradually decreased for 24.6 +/- 4.7 h. In conclusion, all rabbits developed tolerance to propofol's sedative effect within the first hours of administration related to changes to the drug's metabolic clearance.

First human implantation of a new rotary blood pump: design of the clinical feasibility study.

Surgical treatment of heart failure is emerging as one of the most challenging clinical dilemmas for patients with end-stage cardiac failure not amenable to medical treatment. One of the most intriguing techniques is the use of implantable left ventricular assist devices (LVADs) as a bridge to recovery. The early experience from our centre has shown that even short term post-cardiotomy mechanical assistance, after heart failure surgery, improves patient outcome; thus, a clinical feasibility study was designed. The hypothesis of the study is that reparative heart failure surgery combined with postoperative mechanical support, ventricular resynchronisation where indicated, and pharmacological treatment can maximise myocardial recovery. In the study a new, implantable, magnetically levitated, rotary pump will be used as a bridge to recovery. In this manuscript the first worldwide human implantation of a new, continuous-flow LVAD, the WorldHeart Rotary Pump (Levacor, WorldHeart Inc., Oakland CA), is reported. The design and the rationale of the feasibility study, the inclusion and exclusion criteria, and the primary and secondary end points of the clinical investigation, are delineated. In addition, the design of the new rotary pump, its general principles of operation, and the implantation technique are described.

Diltiazem versus amiodarone to prevent atrial fibrillation in coronary surgery.

The prophylactic effect of amiodarone on atrial fibrillation after coronary bypass grafting with extracorporeal circulation was compared with that of diltiazem in two groups of 60 patients each. Patients were monitored continuously for 8 days. The incidence of atrial fibrillation was recorded retrospectively in a control group of 60 patients who received our standard prophylactic regimen of an oral beta blocker. The incidence of postoperative atrial fibrillation was not significantly different in the two test groups: 11.7% for the amiodarone group and 10% for the diltiazem group. The incidence of atrial fibrillation in the control group was 23.3% and the differences were marginally significant when compared to the amiodarone ( p = 0.093) and diltiazem groups ( p = 0.050). The prophylactic use of diltiazem or amiodarone is feasible and safe for patients undergoing coronary bypass, with similar rates of atrial fibrillation.