Surgical repair of an asymptomatic giant right coronary artery aneurysm.

Background Coronary artery aneurysm (CAA) is a rare finding, being mostly diagnosed on angiography or at autopsies. It is defined as being a dilation of the coronary artery that exceeds the diameter of the patient's largest coronary vessel by 1.5 to 2 times. Case Report We describe the operative correction of a giant right CAA measuring in excess of 10 cm. Conclusion Management of giant CAAs is not standardized and surgical strategy remains controversial. In our case, the patient has a successful surgical repair with no postoperative shunts on follow-up investigations.

Thoracic vasculitis presenting as surgical problems.

We present four patients with vasculitis manifesting with unusual clinical or pathological features, generating surgical problems. Two cases presented with pulmonary hypertension, with investigations and radiological evidence prompting clinical suspicion of pulmonary thrombo-embolic disease. First case, with an antecedant history of Wegener's granulomatosis (WG), demonstrated following "embolectomy", WG involving the large pulmonary elastic arteries. The second case of inoperable "pulmonary thrombo-embolic disease" was subsequently found at limited post mortem to have giant cell arteritis, which affected widespread small peripheral pulmonary arterial vessels. The other two cases were of aortitis occurring in the background of immune-mediated disease, which had been treated with aggressive immunosuppression regimens. The first of these was a case of Cogan's syndrome complicated by descending aortitis, a rarely reported phenomenon, with co-existent acute endocarditis of the aortic valve leaflets. Most cases of endocarditis in this context occur secondary to and in continuity with ascending aortitis. That this case, and a case of ascending aortitis occurring in the context of relapsing polychondritis occurred in the face of aggressive immunosuppression with an apparent clinical response, underscores the need to not accept a clinical picture at face value. This has implications for clinical management, particularly in the follow-up of surgical prosthetic devices such as grafts which may be used in these cases. All four cases emphasise the continued importance of histology and the post-mortem examination in elucidating previously undetected or unsuspected disease.

Characterization of the effects of cyclooxygenase-2 inhibition in the regulation of apoptosis in human small and non-small cell lung cancer cell lines.

BACKGROUND: Cyclooxygenase-2 enzyme (COX-2) is overexpressed in human non-small cell lung cancer (NSCLC) but is not expressed in small cell lung cancer. Selective COX-2 inhibitors have been shown to induce apoptosis in NSCLC cells, an effect which is associated with the regulation of intracellular MAP kinase (MAPK) signal pathways. Our aims were to characterize the effects of COX-2 inhibition by rofecoxib on apoptosis in human NSCLC and small cell lung cancer cell lines. METHODS: The human NSCLC cell line NCI-H2126 and small cell lung cancer cell line DMS-79 were used. Constitutive COX-2 protein levels were first determined by Western blot test. Levels of apoptosis were evaluated by using propidium iodide staining on FACScan analysis after incubation of NCI-H2126 and DMS-79 with p38 MAPK inhibitor SB202190 (25 ?microM), NF-kappaB inhibitor SN50 (75 microg/mL), and rofecoxib at 100 and 250 microM. All statistical analysis was performed by analysis of variance. RESULTS: Western blot test confirmed the presence of COX-2 enzyme in NCI-H2126 and absence in DMS-79. Interestingly, rofecoxib treatment demonstrated a dose-dependent increase in apoptosis in both cell lines. Given this finding, the effect of rofecoxib on NF-kappaB and p38 MAPK pathways was also examined. Apoptosis in both cell lines was unaltered by SN50, either alone or in combination with rofecoxib. A similar phenomenon was observed in NCI-H2126 cells treated with SB202190, either alone or in combination with rofecoxib. In contrast, p38 MAPK inhibition greatly upregulated DMS-79 apoptosis in a manner that was unaltered by the addition of rofecoxib. CONCLUSIONS: Rofecoxib led to a dose-dependent increase in apoptosis in both tumor cell lines. This effect occurred independently of COX-2, NF-kappaB, and p38 MAPK pathways in DMS-79 cells. As such, rofecoxib must act on alternative pathways to regulate apoptosis in human small cell lung cancer cells.

Variations in battery life of a heart-lung machine using different pump speeds, pressure loads, boot material, centrifugal pump head, multiple pump usage, and battery age.

Electrical failure during cardiopulmonary bypass (CPB) has previously been reported to occur in 1 of every 1500 cases. Most heart-lung machine pump consoles are equipped with built-in battery back-up units. Battery run times of these devices are variable and have not been reported. Different conditions of use can extend battery life in the event of electrical failure. This study was designed to examine the run time of a fully charged battery under various conditions of pump speed, pressure loads, pump boot material, multiple pump usage, and battery life. Battery life using a centrifugal pump also was examined. The results of this study show that battery life is affected by pump speed, circuit pressure, boot stiffness, and the number of pumps in service. Centrifugal pumps also show a reduced drain on battery when compared with roller pumps. These elements affect the longevity and performance of the battery. This information could be of value to the individual during power failure as these are variables that can affect the battery life during such a challenging scenario.

Can surgery for cancer accelerate the progression of secondary tumors within residual minimal disease at both local and systemic levels?

BACKGROUND: Surgical removal remains the principal treatment modality in the management of lung cancer. Our aim is to characterize the effects of tumor removal on subsequent tumor recurrence at both local and systemic levels. METHODS: C57/BL6 mice [10/group] underwent a mammary fat pad inoculation of 3LL cells [5 x 10(5)/animal] and were divided into two groups. Group 1 served as control while mice in group 2 were further subdivided into groups 2A and 2B. After 2 weeks, all mice in 2A were killed, and primary tumors and lungs were excised. At 2 weeks, primary tumors were excised completely for all mice in group 2B. These mice were then recovered and recurrent tumor growth evaluated for a further 2 weeks. Four weeks from the onset of the study, all remaining primary tumors and lungs were excised from groups 1 and 2. RESULTS: After 4 weeks undisturbed growth, primary tumors in group 1 reached a mean size of 2.85 +/- 0.33 cm. After 2 weeks growth, primary tumors in groups 2A and 2B were comparable at 1.36 +/- 0.44 m and 1.53 +/- 0.29 cm, respectively. Two weeks after primary tumor excision, recurrent tumors in group 2B had reached a mean size of 2.65 +/- 0.74 cm. Moreover, for several animals, recurrent tumors rapidly reached similar volumes to that of primary tumors in group 1. Primary tumors were typically encapsulated and nonadherent. In contrast, recurrent tumors were locally invasive and adherent to chest wall and wound. Interestingly, pulmonary metastatic burden was increased in group 2B relative to group 1. Histologic examination revealed increased mitosis in recurrent tumors when compared with primary tumors. CONCLUSIONS: Tumor removal is followed by accelerated growth of locally recurrent tumors and metastases. Moreover, recurrent tumors are more locally invasive than primary tumors. These findings strongly indicate that resection may be followed by tumor progression in residual disease.

Surgically induced accelerated local and distant tumor growth is significantly attenuated by selective COX-2 inhibition.

BACKGROUND: Even after apparently curative resection, lung cancer recurrence continues to lead to high mortality levels. The aim of this study was to assess the effects of cyclooxygenase-2 (COX-2) inhibitor on local and systemic recurrent tumor growth. METHODS: C57BL/6 mice underwent mammary fat pad inoculation with 3LL cells. After two weeks growth, flank tumors were resected completely and followed for recurrent tumor growth. Postresection mice were randomized to receive placebo alone (group 1) or the selective COX-2 inhibitor, rofecoxib (group 2), daily for two weeks by tube feeding. Recurrent tumor growth kinetics were compared for both groups. Two weeks following primary tumor excision animals were sacrificed, after which lungs were resected and pulmonary metastatic burden was assessed using the lung-body weight ratio. Apoptotic and mitotic indices were established for recurrent tumors and lungs, using hematoxylin and eosin histology. RESULTS: Two weeks postexcision of the primary tumor, recurrent tumors in the placebo group were significantly greater than the treatment group (p = 0.002). While primary tumors were typically encapsulated and not adherent, recurrent tumors in the placebo group were invasive, adherent to the chest wall and the overlying wound. In contrast, recurrent tumors in the treatment group were nonadherent to the chest wall. Moreover, postoperative pulmonary metastatic burden was significantly reduced in treated animals. Histologic examination revealed increased apoptosis as well as an increase in the apoptosis-mitosis ratio in treated animals. CONCLUSIONS: Primary tumor excision was associated with accelerated local and systemic tumor recurrence. However, these effects were significantly attenuated using selective COX-2 inhibition. The COX-2-inhibition was associated with increased levels of apoptosis. These findings endorse a role for COX-2 inhibition in the secondary prevention of lung cancer recurrence at both local and systemic levels.

Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass: a pilot randomized controlled study.

PURPOSE: Cognitive deficit after coronary artery bypass surgery (CABG) has a high prevalence and is persistent. Meta-analysis of clinical trials demonstrates a decreased incidence of stroke after CABG when aprotinin is administrated perioperatively. We hypothesized that aprotinin administration would decrease the incidence of cognitive deficit after CABG. METHODS: Thirty-six ASA III-IV patients undergoing elective CABG were included in a prospective, randomized, single-blinded pilot study. Eighteen patients received aprotinin 2 x 10(6) KIU (loading dose), 2 x 10(6) KIU (added to circuit prime) and a continuous infusion of 5 x 10(5) KIU.hr(-1). A battery of cognitive tests was administered to patients and spouses (n = 18) the day before surgery, four days and six weeks postoperatively. RESULTS: Four days postoperatively new cognitive deficit (defined by a change in one or more cognitive domains using the Reliable Change Index method) was present in ten (58%) patients in the aprotinin group compared to 17 (94%) in the placebo group [95% confidence interval (CI) 0.10-0.62, P = 0.005); (P = 0.01)]. Six weeks postoperatively, four (23%) patients in the aprotinin group had cognitive deficit compared to ten (55%) in the placebo group (95% CI 0.80-0.16, P = 0.005); (P = 0.05). CONCLUSION: In this prospective pilot study, the incidence of cognitive deficit after CABG and cardiopulmonary bypass is decreased by the administration of high-dose aprotinin.

The effects of propofol on lipid peroxidation and inflammatory response in elective coronary artery bypass grafting.

OBJECTIVE: To determine whether the antioxidant and anti-inflammatory properties of propofol confer benefit in adult patients undergoing elective coronary artery bypass grafting. DESIGN: Prospective, blinded, randomized, controlled clinical investigation. SETTING: Single-center, university teaching hospital and academic research laboratory. PARTICIPANTS: Twenty-one adult patients (11 control, 10 intervention) with chronic stable angina and normal ventricular function scheduled to undergo elective coronary artery bypass grafting. INTERVENTIONS: All patients received a standardized fentanyl-isoflurane anesthetic. Fifteen minutes before reperfusion, patients in the intervention group received a target-controlled infusion of propofol, continued for 4 hours after cross-clamp release. Patients in the control group received saline administered in a similar fashion. MEASUREMENTS: Serum concentration of malondialdehyde (MDA) (from systemic and coronary sinus blood); systemic concentrations of interleukins 4, 6, 8, and 10; and systemic leukocyte functions (respiratory burst, phagocytosis, and beta(2) integrin expression) were measured up to 36 hours after reperfusion. RESULTS: A high serum malondialdehyde concentration was detected in the coronary sinus in control patients, 10 minutes after reperfusion; serum malondialdehyde was not detected in the coronary sinus at this time in patients who received propofol (41.4 [15.6-1,150] micromol/L v 0, p = 0.004). Interleukin-8 concentrations increased 2 and 4 hours after reperfusion in the control group. Interleukin-6 concentrations were greater in the control group than the propofol group 4 hours after clamp release (289.1 [165.2-561] rhog/mL v 153.2 (58.2-280.3) rhog/mL, respectively, p = 0.003). Mean dose of propofol was 31.7 mg/kg during the study period. CONCLUSION: Clinically relevant concentrations of propofol may attenuate free radical-mediated and inflammatory components of myocardial reperfusion injury in patients undergoing elective coronary artery bypass graft surgery.

Coronary grafts flow and cardiac pacing modalities: how to improve perioperative myocardial perfusion.

OBJECTIVE: Aim of this study was to investigate modifications of coronary grafts flow during different pacing modalities after CABG. MATERIALS AND METHODS: Two separate prospective studies were conducted in patients undergoing CABG and requiring intraoperative epicardial pacing. In a first study (22 patients) coronary grafts flows were measured during dual chamber pacing (DDD) and during ventricular pacing (VVI). In a second study (10 patients) flows were measured during DDD pacing at different atrio-ventricular (A-V) delay periods. A-V delay was adjusted in 25 ms increments from 25 to 250 ms and flow measurements were performed for each A-V delay increment. A transit time flowmeter was used for the measurements. RESULTS: An average of 3.4 grafts/patient were performed. In the first study, average coronary graft flow was 47.4+/-20.8 ml/min during DDD pacing and 41.8+/-18.2 ml/min during VVI pacing (P = 0.0004). Furthermore average systolic pressure was 94.3+/-10.1 mmHg during DDD pacing and 89.6+/-12.2 mmHg during VVV pacing (P = 0.0007). No significant differences in diastolic pressure were recorded during the two different pacing modalities. In the second study, maximal flows were achieved during DDD pacing with an A-V delay of 175 ms (54+/-9.6 ml/min) and minimal flows were detected at 25 ms A-V delay (38.1+/-4.7 ml/min) (P=ns). No significant differences in systolic or diastolic blood pressure were noticed during the different A-V delays. CONCLUSION: Grafts flowmetry provides an extra tool to direct supportive measures such as cardiac pacing after CABG. DDD mode with A-V delay around 175 ms. should be preferred to allow for maximal myocardial perfusion via the grafts.

Dopexamine increases internal mammary artery blood flow following coronary artery bypass grafting.

OBJECTIVE: Vasoactive agents and inotropes influence conduit-coronary blood flow following coronary artery bypass grafting (CABG). It was hypothesized that dopexamine hydrochloride, a dopamine A-1 (DA-1) and beta(2) agonist would increase conduit-coronary blood flow. A prospective randomized double blind clinical trial was carried out to test this hypothesis. DA-1 receptors have previously been localized to human left ventricle. METHODS: Twenty-six American Society of Anaesthesiology class 2-3 elective coronary artery bypass graft patients who did not require inotropic support on separation from cardiopulmonary bypass (CPB) were studied. According to a randomized allocation patients received either dopexamine (1 microg/kg per min) or placebo (saline) by intravenous infusion for 15 min. Immediately prior to and at 5,10 and 15 min of infusion, blood flow through the internal mammary and vein grafts (Transit time flow probes, Transonic Ltd.), heart rate, cardiac index, mean arterial pressure and pulmonary haemodynamics were noted. The data were analysed using multivariate analysis of variance. RESULTS: Low-dose dopexamine (1 microg/kg per min) caused a significant increase in mammary graft blood flow compared to placebo at 15 min of infusion (P=0.028, dopexamine group left internal mammary artery (LIMA) flow of 43.3+/-14.2 ml/min, placebo group LIMA flow at 26.1+/-16.3 ml/min). Dopexamine recipients demonstrated a non-significant trend to increased saphenous vein graft flow (P=0.059). Increased heart rate was the only haemodynamic change induced by dopexamine (P=0.004, dopexamine group at 85.2+/-9.6 beats/min and placebo group at 71.1+/-7.6 beats/min after 15 min of infusion). CONCLUSION: This study demonstrates that administration of dopexamine (1 microg/kg per min) was associated with a significant increase in internal mammary artery graft blood flow with mild increase in heart rate being the only haemodynamic change. Low-dose dopexamine may improve graft flow in the early post CABG period with minimal haemodynamic changes.

The role of COX-2 inhibitors in lung cancer.

BACKGROUND: Human lung cancer is a major cause of death worldwide with few known effective therapeutic modalities. The isoenzyme cyclooxygenase 2 (COX-2) is an inducible inflammatory enzyme with increased activity evidenced in lung carcinoma. The objective was to determine the effect of a selective COX-2 inhibitor on proliferation and apoptosis rates in the Lewis lung (3LL) tumor cell line in vitro. METHODS: First, 1 x 10(4) 3LL cells were plated in a 96-well plate. Cells were incubated for 24 hours with either a control or increasing doses of rofecoxib (0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, and 2.5 mmol/L) in complete Dulbecco's Modified Eagle's Medium culture medium. Cell proliferation was measured using BrdU enzyme-linked immunosorbent assay. Next, 1 x 10(6) 3LL cells were similarly treated. Cells were permeabilized, immunostained with propidium iodide and apoptotic rates were measured using flow cytometry. Then, 5 x 10(4) cells were plated on a 24-well plate. Cells were incubated for 24 hours with either control or increasing doses of rofecoxib (0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, and 2.5 mmol/L) in complete culture medium. Supernatant was collected and lactate dehydrogenase was measured for cell necrosis using a cytotoxicity detection kit. RESULTS: The selective COX-2 inhibitor rofecoxib resulted in a dose-dependent increase in apoptosis and dose and time-dependent growth inhibition in cell proliferation. However, rofecoxib did not cause cell necrosis. CONCLUSIONS: There was a significant decrease in proliferation and increase in apoptosis of 3LL tumor cells when treated with the highly selective COX-2 inhibitor rofecoxib. COX-2 inhibitors may have a potential role to play in the treatment of lung carcinoma.