Vascular activity of infusion and fractions of Cymbopogon citratus (DC) Stapf. in human arteries.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC.) Stapf has been traditionally used mainly for inflammatory diseases and hypertension. However, the mechanisms underlying its vascular activity remain to be fully characterized and the fractions responsible for its cardiovascular activity are still unknown. AIM OF THE STUDY: In this study, we aimed to assess the vascular activity of Cymbopogon citratus in human arteries and to study the role of cyclooxygenase in its vasorelaxant effects. MATERIALS AND METHODS: Vascular effects of leaves infusion and three fractions (phenolic acids, flavonoids and tannins) were studied using distal segments of human internal thoracic arteries harvested from patients undergoing coronary revascularization, which were mounted as rings in tissue organ baths and maintained at 37 °C in Krebs Henseleit buffer. The effect on basal vascular tone, the effect on the noradrenaline-induced contraction and the vasorelaxant effects were assessed. The role of cyclooxygenase was evaluated with indomethacin. RESULTS: Our results showed a mild effect on the basal vessel tone of the infusion. A significant inhibition on the adrenergic-mediated vasoconstriction was observed for the infusion (0.0002 mg/mL) and the flavonoid fraction (0.2 mg/mL), despite a potentiation was observed in some conditions. A vasorelaxant effect was observed for both the infusion (6.46% of maximal relaxation) and the tannin fraction (26.91% of maximal relaxation, P < 0.05 vs. infusion). Incubation with indomethacin (10 µM) elicited a decrease in the vasorelaxation to the infusion (P < 0.05). CONCLUSIONS: These results suggest that cyclooxygenase may be involved in the vasorelaxation to the infusion of Cymbopogon citratus and that tannins are the compound fraction mainly responsible for this vasorelaxation.

Polyphenolic characterisation and bioactivity of an Oxalis pes-caprae L. leaf extract.

The present work is focused on the characterisation of the polyphenolic content of an Oxalis pes-caprae L. leaf extract and on the evaluation of its bioactivity with particular interest on its vascular activity and antioxidant potential. The polyphenolic content was characterised by HPLC-DAD and LC-MS/MS. The vascular activity was evaluated according to the influence on the serotonergic and adrenergic systems of the human internal mammary artery (HIMA). Antioxidant and neuroprotective studies were also conducted. Several luteolin and apigenin derivatives were identified as main constituents of the extract, which did not present any contractile effect nor had any effect on the serotonergic system of HIMA. However, it showed antagonistic effect on the adrenergic system, inhibiting the contraction to noradrenaline (reduction of 58.44% of maximum contraction). The extract showed antioxidant activity and standardised luteolin and apigenin derivatives showed neuroprotective potential, particularly homoorientin.

Blood transfusions may impair endothelium-dependent vasodilatation during coronary artery bypass surgery.

OBJECTIVE: The hemolytic product free-hemoglobin (fHb) reduces nitric oxide (NO) bioavailability. The present study aims to establish whether administration of different blood transfusions result in increased circulating fHb levels and NO consumption with effects on arterial NO-dependent blood flow in patients undergoing CABG surgery. METHODS: Ninety-five consecutive patients undergoing elective CABG surgery were prospectively divided in four groups based on blood transfusion requirements during surgery: stored blood cells (SBC, n. 21), intraoperative autologous salvaged blood (ASB, n. 25), SBC and ASB (n.22), no transfusion (control, n. 27). Blood samples were collected before and after intervention to analyse plasma levels of fHb and NO consumption. Endothelium-dependent relaxation was assessed in left internal mammary artery (LIMA) rings harvested before chest closure. Peripheral artery tonometry was assessed after intervention. RESULTS: Transfusions with SBC increased plasma fHb (p<0.05). Transfusions of ASB resulted in higher plasma fHb compared to SBC (p<0.01). fHb concentrations directly correlated with NO consumption (r=0.65, p<0.001). Maximal endothelium-dependent relaxation in LIMA was significantly attenuated in SBC and ASB patients compared to control (15.2±3.1% vs 21.1±2.5% vs 43±5.0% respectively; p<0.01). Significant correlations were identified between the aortic pressure wave velocity, plasma fHb concentration and NO consumption (p<0.01). CONCLUSIONS: Intraoperative blood transfusions and particularly autologous salvaged blood impair endothelium-dependent relaxation through NO scavenging by fHb. These findings obtained in vitro and in vivo provide new insights into the adverse relation between blood transfusions and patient outcome.

Effect of Benidipine in Human Internal Mammary Artery and Clinical Implications.

BACKGROUND: Graft spasm remains challenging in coronary artery bypass grafting (CABG). Calcium antagonists are commonly used in patients with coronary artery disease. This study investigated the inhibitory effect of third-generation dihydropyridine calcium channel antagonist benidipine on the vasoconstriction induced by various vasoconstrictors in the human internal mammary artery (IMA). METHODS: Isolated human IMA rings (N = 65, taken from 37 patients undergoing CABG) were studied in a myograph in 2 ways: the relaxing effect of benidipine on vasoconstrictor-induced precontraction by KCl and U46619 and the depressing effect of benidipine at plasma concentrations on the contraction. Enzyme-linked immunosorbent assay (ELISA) was used to measure the change of the protein related to the L-type calcium channel. RESULTS: Benidipine caused more relaxation in KCl-contracted (86.7% ± 3.3%; n = 12) than in U46619-contracted (63.8% ± 5.3%; n = 8; p < 0.001) IMA rings. Pretreatment of IMA with plasma concentrations of benidipine (-6.92 log M) significantly depressed subsequent contraction by KCl (from 17.3 ± 2.7 mN to 7.4 ± 1.2 mN; n = 6; p < 0.05) but did not significantly affect the contraction caused by U46619. Benidipine also caused a decrease of caveolin (CaV)1.2 protein content (0.55 ± 0.02 versus 0.63 ± 0.02 mg/mL; p < 0.05). CONCLUSIONS: We conclude that in human IMA, the third-generation dihydropyridine calcium channel antagonist benidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Use of benidipine in patients undergoing CABG may provide vasorelaxant or antispastic effects in the grafts.

Distinct and complementary roles for α and ß isoenzymes of PKC in mediating vasoconstrictor responses to acutely elevated glucose.

BACKGROUND AND PURPOSE: We investigated the hypothesis that elevated glucose increases contractile responses in vascular smooth muscle and that this enhanced constriction occurs due to the glucose-induced PKC-dependent inhibition of voltage-gated potassium channels. EXPERIMENTAL APPROACH: Patch-clamp electrophysiology in rat isolated mesenteric arterial myocytes was performed to investigate the glucose-induced inhibition of voltage-gated potassium (Kv ) current. To determine the effects of glucose in whole vessel, wire myography was performed in rat mesenteric, porcine coronary and human internal mammary arteries. KEY RESULTS: Glucose-induced inhibition of Kv was PKC-dependent and could be pharmacologically dissected using PKC isoenzyme-specific inhibitors to reveal a PKCß-dependent component of Kv inhibition dominating between 0 and 10 mM glucose with an additional PKCα-dependent component becoming evident at concentrations greater than 10 mM. These findings were supported using wire myography in all artery types used, where contractile responses to vessel depolarization and vasoconstrictors were enhanced by increasing bathing glucose concentration, again with evidence for distinct and complementary PKCα/PKCß-mediated components. CONCLUSIONS AND IMPLICATIONS: Our results provide compelling evidence that glucose-induced PKCα/PKCß-mediated inhibition of Kv current in vascular smooth muscle causes an enhanced constrictor response. Inhibition of Kv current causes a significant depolarization of vascular myocytes leading to marked vasoconstriction. The PKC dependence of this enhanced constrictor response may present a potential therapeutic target for improving microvascular perfusion following percutaneous coronary intervention after myocardial infarction in hyperglycaemic patients.

Evolución de los pacientes sometidos a cirugía de revascularización de miocardio con doble arteria mamaria interna en el Instituto Nacional Cardiovascular en el periodo 2012-2015 / Evolution of the patients undergoing to surgery of revascularization of myocardium with internal mammary artery double at the National Institute Cardiovascular in the period 2012-2015

Introducción: La revascularización de miocardio con utilización de una arteria mamaria interna es considerada actualmente el tratamiento quirúrgico de elección de la enfermedad isquémica coronaria multiarterial severa. Ya que la aplicación de esta técnica se ha asociado con resultados clínicos superiores en comparación con otros injertos, múltiples investigadores reportan que el empleo de doble arteria mamaria interna (AMI) podría mejorar dichos resultados. Metodología: La presente investigación es de tipo transversal en donde se revisaron historias clínicas. La población estuvo conformada por 36 pacientes con enfermedad isquémica coronaria multiarterial crónica quienes cumplieron con los criterios de selección. Resultados: La mortalidad a 30 días fue 0 por ciento. Se presentaron dos casos (5.56 por ciento) de infarto agudo de miocardio perioperatorio. No se presentó ningún caso de stroke ni de reintervención coronaria a 30 días. El 19.44 por ciento del total presentó infección de herida esternal superficial. Se presentaron 5 casos (13.88 por ciento) de sangrado postoperatorio excesivo. Conclusiones: La revascularización de miocardio con doble AMI no incrementa la mortalidad ni la incidencia de complicaciones mayores a 30 días. No existen diferencias significativas en la incidencia de infección de herida esternal tanto en el grupo de pacientes diabéticos/no diabéticos como en el grupo de pacientes con sobrepeso/IMC normal.

Introduction: Myocardial revascularization using internal mammary artery is currently considered the treatment of choice for severe multi-vessel ischemic coronary disease. Since the application of this technique has been associated with superior clinical outcomes compared with other grafts, multiple researchers report that the use of double internal mammary artery (IMA) could improve those results. Methodology: The current research is a cross-sectional study where medical records were reviewed. The population consisted of 36 patients who were diagnosed with multi-vessel chronic ischemic coronary disease who met the selection criteria. Results: The 30-day mortality was 0 per cent. Two cases (5.56 per cent) of acute perioperative myocardial infarction occurred. There were not any cases of stroke or coronary re-intervention after 30 days. 19.44 per cent of the total presented sternal wound infection. There were 5 cases (13.88 per cent) of excessive postoperative bleeding. Conclusion: Myocardial revascularization with double IMA does not increase mortality or the incidence of major complications after 30 days. There are no significant differences in the incidence of sternal wound infection both in the group of diabetic/non diabetic patients and in the group of overweight/normal BMI patients.

Arterial territory-specific phosphorylated retinoblastoma protein species and CDK2 promote differences in the vascular smooth muscle cell response to mitogens.

Despite recent advances in medical procedures, cardiovascular disease remains a clinical challenge and the leading cause of mortality in the western world. The condition causes progressive smooth muscle cell (SMC) dedifferentiation, proliferation, and migration that contribute to vascular restenosis. The incidence of disease of the internal mammary artery (IMA), however, is much lower than in nearly all other arteries. The etiology of this IMA disease resistance is not well understood. Here, using paired primary IMA and coronary artery SMCs, serum stimulation, siRNA knockdowns, and verifications in porcine vessels in vivo, we investigate the molecular mechanisms that could account for this increased disease resistance of internal mammary SMCs. We show that the residue-specific phosphorylation profile of the retinoblastoma tumor suppressor protein (Rb) appears to differ significantly between IMA and coronary artery SMCs in cultured human cells. We also report that the differential profile of Rb phosphorylation may follow as a consequence of differences in the content of cyclin-dependent kinase 2 (CDK2) and the CDK4 phosphorylation inhibitor p15. Finally, we present evidence that siRNA-mediated CDK2 knockdown alters the profile of Rb phosphorylation in coronary artery SMCs, as well as the proliferative response of these cells to mitogenic stimulation. The intrinsic functional and protein composition specificity of the SMCs population in the coronary artery may contribute to the increased prevalence of restenosis and atherosclerosis in the coronary arteries as compared with the internal mammary arteries.

Doxycycline prevents intimal hyperplasia in vitro and may improve patency of the internal thoracic artery.

OBJECTIVES: The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency. METHODS: Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10⁻5 M and 10⁻6 M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels. RESULTS: At the end of the culture period, neointimal thickness was significantly (P = 0.001) dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases. CONCLUSIONS: Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis.

Cutaneous complications after transcatheter arterial treatment for hepatocellular carcinoma via the internal mammary artery: how to avoid this complication.

PURPOSE: To lower the rate of cutaneous complications after transcatheter arterial treatment for hepatocellular carcinoma (HCC) via the internal mammary artery (IMA) we retrospectively assessed the complications. MATERIALS AND METHODS: We reviewed cutaneous complications in 14 patients with 18 HCCs who had undergone 17 treatment procedures via the IMA, including selective transcatheter arterial infusion chemotherapy with Lipiodol (Lip-TAI) (n = 3), selective Lip-TAI + transcatheter arterial embolization (TAE) (n = 3), nonselective Lip-TAI (n = 1), nonselective Lip-TAI + TAE (n = 5), and nonselective TAE (n = 5). The filling and nonfilling of subcutaneous vessels with Lipiodol was examined on postoperative computed tomography (CT) scans. RESULTS: Skin rash (n = 3) and ulceration (n = 1) occurred after 4 of 17 (24%) procedures: two of three selective Lip-TAI procedures and two of five nonselective Lip-TAI + TAE procedures. The doses of chemotherapeutic agents for tumor sizes in selective Lip-TAI procedures were higher than those in selective Lip-TAI + TAE procedures. Cutaneous complications were encountered after two of three procedures with filling but not after any of eight procedures without filling. CONCLUSION: A lower dose of chemotherapeutic agents may be less risky when undertaking a selective procedure via the IMA for HCC. If nonselective, TAE alone may be less risky. Postoperative CT may be helpful for predicting cutaneous complications.

Fatty acid composition of the internal mammary artery in relation to dietary intake of marine n-3 polyunsaturated fatty acids and association with flow-mediated vasodilation.

Some evidence suggests that long-chain marine n-3 polyunsaturated fatty acids (n-3 PUFA) may increase production of vasodilatory nitric oxide from vascular endothelium. Fatty acids may therefore play a role for the left internal mammary artery (LIMA) graft function in coronary artery bypass grafting (CABG). However, little is known about the composition of fatty acids in the vessel wall of the LIMA. Using gas chromatography we investigated fatty acid composition in segments of the LIMA, in plasma nonesterified fatty acids (NEFA), in plasma phospholipid (PL) and in the pericardial adipose tissue (PAT) from 22 patients undergoing CABG. Furthermore, we investigated whether there was an association between the n-3 PUFA composition in LIMA and flow-mediated vasodilation (FMD). Self-reported fish consumption and supplementation of eicosapentaenoic acid and docosahexaenoic acids were reflected by the fatty acid composition in NEFA, PL and in PAT, but less so in the LIMA. There was no association between FMD and fatty acid composition of the LIMA.

MTHFR 677 C>T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis.

BACKGROUND: The role of circulating homocysteine as an atherosclerosis risk factor has recently been questioned. However, 5-methyl-tetrahydrofolate (5-MTHF), the circulating metabolite of folic acid participating in homocysteine metabolism, has direct effects on vascular function. We sought to distinguish the effects of plasma versus vascular tissue 5-MTHF and homocysteine on vascular redox and endothelial nitric oxide bioavailability in human vessels. METHODS AND RESULTS: We used the methyl tetrahydrofolate reductase (MTHFR) gene polymorphism 677C>T as a model of chronic exposure of the vascular wall to varying 5-MTHF levels in 218 patients undergoing coronary artery bypass graft surgery. Vascular superoxide, vascular 5-MTHF, and total homocysteine were determined in saphenous veins and internal mammary arteries obtained during surgery. Nitric oxide bioavailability was evaluated by organ bath studies on saphenous vein rings. MTHFR genotype was a determinant of vascular 5-MTHF (not vascular homocysteine). Both MTHFR genotype and vascular 5-MTHF were associated with vascular nitric oxide bioavailability and superoxide generated by uncoupled endothelial nitric oxide synthase. In contrast, vascular homocysteine was associated only with NADPH-stimulated superoxide. CONCLUSIONS: Genetic polymorphism 677 C>T on MTHFR affects vascular 5-MTHF (but not homocysteine) and can be used as a model to distinguish the chronic effects of vascular 5-MTHF from homocysteine on vascular wall. Vascular 5-MTHF, rather than plasma or vascular homocysteine, is a key regulator of endothelial nitric oxide synthase coupling and nitric oxide bioavailability in human vessels, suggesting that plasma homocysteine is an indirect marker of 5-MTHF rather than a primary regulator of endothelial function.

The Effect of Thoracic Epidural Lidocaine on Blood Flow of Grafted Coronary Vessels in Coranary Artery Bypass Graft Surgery / 대한마취과학회지

BACKGROUND: Thoracic epidural anesthesia (TEA) is increasingly used to reduce stress response, pain and pulmonary complication of patients under coronary artery bypass graft (CABG). However, effects of TEA on blood flow of grafted coronary artery are scarcely noticed. Imbalance between blood flow of grafted coronary artery and myocardial oxygen demand can bring about perioperative myocardial ischemia. Thus we evaluated the effect of TEA on blood flow of coronary grafts. METHODS: Twenty seven patients with triple-vessel coronary artery disease under CABG were recruited. Left internal mammary artery, radial artery, and great saphenous vein were anastomosed to left anterior descending artery, obtuse marginalis, and posterior descending artery, respectively. Before surgery, an epidural catheter was inserted. Total intravenous anesthesia was undertaken using fentanyl, midazolam and vecuronium. After grafts anastomosis, blood flow of grafted coronary artery was measured using transit-time flowmeter (TTFM) before weaning from CPB. And then, mixture of 2% lidocaine 10 ml, fentanyl 50microgram and bicarbonate 1 mEq was injected via epidural catheter. Under the constant pump flow, the blood flow of grafted coronary artery before, 10 and 20 minutes after drug administration were measured using TTFM. RESULTS: The blood flow of coronary artery grafts was similar in three time interval, irrespective of grafted artery. There are no significant differences in changes in coronary blood flow associated with epidural lidocaine injection among 3 types of grafted artery. CONCLUSIONS: The present study shows that there are no significant effects of TEA on blood flow of newly grafted coronary artery after CABG.

Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity.

OBJECTIVE: This study investigated whether differences exist in atherogen-induced migratory behaviors and basal antioxidant enzyme capacity of vascular smooth muscle cells (VSMC) from human coronary (CA) and internal mammary (IMA) arteries. METHODS: Migration experiments were performed using the Dunn chemotaxis chamber. The prooxidant [NAD(P)H oxidase] and antioxidant [NOS, superoxide dismutase, catalase and glutathione peroxidase] enzyme activities were determined by specific assays. RESULTS: Chemotaxis experiments revealed that while both sets of VSMC migrated towards platelet-derived growth factor-BB (1-50 ng/ml) and angiotensin II (1-50 nM), neither oxidized-LDL (ox-LDL, 25-100 microg/ml) nor native LDL (100 microg/ml) affected chemotaxis in IMA VSMC. However, high dose ox-LDL produced significant chemotaxis in CA VSMC that was inhibited by pravastatin (100 nM), mevastatin (10 nM), losartan (10 nM), enalapril (1 microM), and MnTBAP (a free radical scavenger, 50 microM). Microinjection experiments with isoprenoids i.e. geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) showed distinct involvement of small GTPases in atherogen-induced VSMC migration. Significant increases in antioxidant enzyme activities and nitrite production along with marked decreases in NAD(P)H oxidase activity and O2- levels were determined in IMA versus CA VSMC. CONCLUSIONS: Enhanced intrinsic antioxidant capacity may confer on IMA VSMC resistance to migration against atherogenic agents. Drugs that regulate ox-LDL or angiotensin II levels also exert antimigratory effects.

Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.

Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.

Brachial plexus injury during open heart surgery--controlled prospective study.

BACKGROUND: Postoperative brachial plexus injury is often reported because the brachial plexus is stretched by sternotomy and the use of sternal retractors during open heart surgery. In many studies, brachial plexus injuries have been demonstrated by postoperative electrophysiological studies in susceptible patients. In this study, we estimated the incidence, severity, and type of brachial plexus injuries by routine preoperative and postoperative electrophysiological studies of patients undergoing open heart surgery. METHODS: Patients undergoing coronary artery bypass grafting (CABG) surgery (Group 1), heart valve surgery (Group 2), or peripheral vascular surgery (Group 3) were included in the investigation. Electrophysiological studies of both upper extremities were performed five days before and three weeks after the operation. RESULTS: Peripheral nerve problems were found preoperatively in 23 of the 112 patients (21 %). These problems persisted, but similar findings were obtained postoperatively from the left upper extremities of six of the 42 CABG (14 %) and two of the 24 heart valve (8 %) patients who had had normal preoperative evaluations. The patients with injured nerves were older and had undergone longer operation times. There were no differences between the patients with injured nerves and the others with respect to mammary artery harvesting or other operative variables. CONCLUSIONS: There are no reports in the literature of routine preoperative and postoperative electrophysiological studies in large patient groups to evaluate brachial plexus injury during open heart surgery. It is known that heart surgery sometimes causes partial brachial plexus injury, especially in the lower trunk. However, these peripheral nerve problems are usually not considered clinically important and are not investigated. Patients undergoing open heart surgery must be closely followed up for peripheral nerve injury during the postoperative period.

Differential effect of cerivastatin and L-arginine on the vascular function of human radial and left internal thoracic arteries.

BACKGROUND: There are a number of strategies to restore/preserve endothelial function. We have compared the effects of Cerivastatin (CS) to those of L-arginine (L-ARG) supplementation on the endothelial function of human arterial grafts. METHODS: During coronary artery bypass grafting, specimens of radial artery (RA) and left internal thoracic artery (LITA) were obtained. Specimens were divided into vascular rings, which were incubated with either 10(-6) mol/L CS, 10(-3) mol/L L-ARG, or vehicle (control) for 2 or 24 hours. Endothelial function was examined with acethylcholine (10(-9) to 10(-5) mol/L) following contraction by 3 x 10(-8) mol/L endothelin-1. RESULTS: Although no significant differences were observed in the RA at 2 hours, after 24 hours incubation, endothelium-dependent vasodilatation was significantly higher in CS group (68.4 +/- 5.0%; n = 6) compared to L-ARG group (49.9 +/- 5.4%; n = 7, p < 0.05) and control group (33.8 +/- 2.9%; n = 13, p < 0.0001). In addition, there was a significant increase in L-ARG group compared to control (p < 0.01). After 2 hours incubation of the LITA, CS failed to enhance endothelium-dependent vasodilatation compared to control (44.1 +/- 4.9%; n = 9, vs. 40.0 +/- 5.2%; n = 16, respectively, NS), while L-ARG increased it (64.7 +/- 4.9%; n = 7, p < 0.05 vs. CS and p < 0.01 vs. control). However, this increase disappeared at 24 hours although there was a higher trend of endothelium-dependent vasodilatation in CS group (30.3 +/- 3.7%; n = 8 in L-ARG, 56.5 +/- 8.8%; n = 9 in CS and 41.0 +/- 5.5%; n = 18 in control). CONCLUSIONS: CS preserved endothelium-dependent vasodilatation of RA greater than L-ARG. These findings suggest that the use of statins may be an effective therapeutic strategy to preserve endothelial function in the RA grafts, and could have important implications in the clinical practice.

Western array analysis of human atherosclerotic plaques: downregulation of apoptosis-linked gene 2.

OBJECTIVE: In recent years, microarray techniques have been used to characterize differences in mRNA populations between atherosclerotic plaques and normal arterial tissue. Because proteomics provide an attractive complementary approach to genomics, we used Western array technology as a global protein profiling method to identify differentially expressed proteins with potential pathobiological relevance in human atherosclerotic plaques. METHODS: Cell lysates from human carotid endarterectomy specimens and non-atherosclerotic mammary arteries were screened with monoclonal antibodies (823 in total) that were combined into unique cocktails. Hits were verified with traditional Western blotting. RESULTS: Seven proteins with a >5-fold relative expression difference were identified. One of the most apparent changes in human plaques was the downregulation of apoptosis-linked gene 2 (ALG-2), a positive mediator of apoptotic cell death. Differential expression of ALG-2 in human plaques relative to mammary arteries was not confirmed by real-time quantitative RT-PCR, suggesting post-transcriptional regulation. Uptake of aggregated LDL (agLDL) downregulated ALG-2 protein expression in THP-1 macrophages, but not in smooth muscle cells (SMCs). Transfection of THP-1 cells with ALG-2-specific small interfering RNA (siRNA) caused ALG-2 depletion and inhibited the execution phase of apoptosis (DNA fragmentation) but did not affect caspase-3 activation, annexin-V labeling and necrotic cell death. CONCLUSION: Western array screening of carotid endarterectomy specimens revealed a strong downregulation of ALG-2 protein. Because ALG-2 has pro-apoptotic potential, our results point to a novel survival mechanism against cell death in human atherosclerotic plaques.

Minimal dissection and continuous retrograde cardioplegia for aortic valve replacement in patients with a patent left internal mammary artery bypass graft.

BACKGROUND AND AIM OF THE STUDY: Aortic valve replacement (AVR) in patients with previous coronary artery bypass grafting (CABG) and a patent pedicled internal mammary artery (IMA) is often complicated by a need to dissect and clamp the IMA to achieve optimal myocardial protection. Eliminating this need may simplify and facilitate surgery; hence, a new surgical technique for use in these patients is described. METHODS: Five patients with previous CABG and functioning IMA who required AVR between January 1998 and October 2002 were studied. In all patients, the IMA was neither dissected nor clamped. Myocardial protection comprised an initial bolus of antegrade cardioplegia, followed by continuous retrograde infusion of tepid non-diluted oxygenated blood, supplemented with cardioplegic drugs to maintain cardiac arrest. The systemic and myocardial temperature was 30-32 degrees C. RESULTS: All patients underwent surgery as planned, and there was no operative mortality or myocardial infarction. One patient sustained a minor stroke. None of the IMA was injured. CONCLUSION: In patients requiring AVR, it is both possible and reasonable to leave the IMA undissected and unclamped. Limited experience suggests that this new technique provides adequate myocardial protection, while keeping surgery both simple and safe.