Extracorporeal life support for massive pulmonary embolism during pregnancy.

Massive pulmonary embolism is a leading cause of death during pregnancy. While the prevention of thromboembolic disease during the peripartum period is codified, there is no consensus regarding its treatment. We report two cases of pregnant women who had massive pulmonary embolisms (PE) and shock treated with veno-arterial extracorporeal life support (ECLS) and heparin therapy.Haemodynamic and oxygenation parameters were rapidly restored. The patients completely recovered and the pregnancies continued. The patients did not develop pulmonary hypertension. ECLS can be considered as a successful treatment option of massive pulmonary embolism during pregnancy.

[Management of Stent-graft migration with obstruction of supra-aortic vessel during an endovascular procedure for aortic isthmus rupture]. / Migration d'endoprothèse thoracique avec occlusion des troncs supra-aortiques en per-procédure pour rupture isthmique ; prise en charge.

The endovascular approach is widely used in the management of aortic isthmic rupture. Even if it remains less invasive than conventional surgery, a life-threatening complications are possible. We report the case of a young female patient presenting a stent-graft migration during the deployment with total obstruction of the supra-aortic vessels. We describe the therapeutic management with a cerebral rescue procedure followed by a delayed surgical repair.

[Constrictive pericarditis and disseminated nocardiosis]. / Péricardite constrictive et la nocardiose disséminée.

Human nocardiosis usually involves the respiratory tract or the skin but may disseminate to virtually any organ, it occurs in immunocompromised hosts as well as individuals with no apparent predisposition. Involvement of the pericardium is uncommon, having been reported infrequently in the past, but mandates a special management. This report describes the first case in Europe of a patient with chronic constrictive pericarditis from nocardia brasiliens, successfully treated with pericardiectomy and appropriate antibiotic therapy.

Early postoperative bleeding after isolated coronary bypasses: Changes over a period of 20 years - An observational study.

OBJECTIVES: The objectives were to analyze the evolution of the postoperative bleeding after coronary artery bypass grafting and to determine which factors impacted on this evolution. METHODS: This is a single-center retrospective study including 4590 patients undergoing coronary bypass surgery between 1995 and 2017. The study period was divided into 3 same-sized periods. We analyzed the evolution of the bleeding according to: the chest volume bleeding over the first 24hours, the severity and the rate of transfusion during the hospital stay. Intrahospital outcomes were compared between "minor" and "major" bleedings. The risk factors of major bleeding were analyzed by multiple logistic regression. RESULTS: The chest volume decreased particularly during the first years of the study period. Major bleedings decreased over the periods (7.3%, 4.9% and 3.8% respectively, P<0.0001), as did the rate of transfusion (26.4%, 23.5% and 19.6% respectively, P<0.0001). Major bleedings were correlated with hospital mortality (8.2% versus 1.1%, P<0.0001). The risk factors of major bleeding were the period 1 (1995 to 2003), a renal failure, a resternotomy, the EuroSCORE, the hematocrit prior to cardiopulmonary bypass and the duration of cardiopulmonary bypass. CONCLUSIONS: Postoperative bleeding decreased mainly in the 1990s. Progressive changes in bleeding prevention and blood recovery, surgical techniques, haemoglobin threshold for transfusion decision and practitioners' experience have contributed to these results and must be continued to optimize the postoperative outcomes.

[ECMO for post cardiotomy refractory cardiogenic shock: Experience of the cardiac surgery department of the Grenoble Alpes University Hospital]. / ECMO pour choc cardiogénique réfractaire post cardiotomie : expérience du service de chirurgie cardiaque du CHU de Grenoble Alpes.

OBJECTIVE: The objective of our study is to detail our experience relating to ECMO implantations for post-cardiotomy refractory shock, by analyzing the pre-ECMO factors (history, type of surgery, LVEF), factors relating to ECMO (implantation time, duration) and post-ECMO factors (weaning, complications) in order to highlight those possibly associated with high mortality. METHODS: This is a univariate and multivariate retrospective study of ECMO data implemented between 2011 and 2019 at the Grenoble Alpes University Hospital Center following cardiac surgery. The time to implantation of ECMO was less than 3hours (intraoperative) between 3 and 24hours (early postoperative) and between 24 and 48hours after aortic unclamping (late postoperative). Preoperative or postoperative intra-aortic balloon counterpulsation (CPBIA) could be associated. RESULTS: 114 veino-arterial ECMOs were implanted for refractory cardiogenic shock after 5702 cardiac surgeries (1.9%) with a survival rate of 30.7%. The mean age of the patients was 68.6+- 10.5 years. The implantation of ECMO was performed intraoperatively in 71 patients (62.2%), early postoperatively in 22 patients (19.2%) and late postoperatively in 21 patients (18.4%). The duration of assistance was less than 48hours in 27 patients (23.6%), between 48hours and one week in 58 patients (50.9%) and more than one week in 29 patients (25.5%). Univariate analysis revealed a statistically significant association between mortality rate and male sex (P=0.002), association absent with other preoperative characteristics, delay in implantation of ECMO, installation of CPBIA, post-operative characteristics and resuscitation suites. Multivariate analysis of the entire study population demonstrated that the use of ECMO for cardio-respiratory arrest was the only independent risk factor for mortality (OR=7.57 [1.41-40, 62]). After multivariate reanalysis excluding patients with ECMO placement for cardio respiratory arrest, age, preoperative renal failure, type of procedure and EuroSCORE II were risk factors for mortality. CONCLUSION: In this study, male gender, type of intervention, occurrence of cardiac arrest were significantly associated with the death rate. A study of greater power, multicentric, and with a larger sample, will have to be carried out to reach significance.

[The association of VAC® therapy, titanium plates osteosynthesis and bilateral pectoral muscle flaps in the management of postoperative mediastinitis in an obese and diabetic patient]. / Intérêt de l'association VAC®-thérapie, ostéosynthèse sternale et lambeaux pectoraux d'avancement dans la prise en charge d'une médiastinite postopératoire après chirurgie cardiaque chez une obèse diabétique.

Postoperative mediastinitis is one of the most worrisome complications after heart surgery. Until now there is no universally accepted strategy in the management of this infectious complication. Recently, various novel techniques like negative pressure therapy and titanium plates sternal reconstruction have allowed a dramatic decrease of mortality and morbidity after mediastinitis. We report the case of a diabetic patient suffering from morbid obesity who developed a severe postoperative mediastinitis after a coronary artery bypass; she was successfully treated by combining negative pressure therapy, titanium plates osteosynthesis and bilateral pectoral muscle flaps.

[Type A acute aortic syndromes: Assessment of the management delays in an emergency medicine network]. / Syndromes aortiques aigus de type A : évaluation des délais de prise en charge dans un réseau de médecine d'urgence.

OBJECTIVE: To assess the diagnostic delay (between first hospital medical contact and diagnosis) and the surgical delay (between diagnosis and incision) of type A acute aortic syndromes (AAAS) within the RENAU (REseau Nord Alpin des Urgences), organizing the management of emergency medicine care in the French North Alpine Arc. PROCEDURE: Multicenter retrospective study between 2012 and 2016 on the AAAS operated in the RENAU heart surgical centers (Annecy, Grenoble). Post-traumatic, iatrogenic or chronic lesions, incidental discoveries and deaths before surgery were excluded. RESULTS: One hundred and ninety-seven patients were included with a median age [IQR] of 65 years [58; 73] of which 67% were men. The median diagnosis delay was 88min [46;241] and the median surgical delay was 193min [146;249]. Initial management was performed by the SMUR for 102 patients (52%), 7% of whom received a pre-hospital transthoracic ultrasound. 52 patients (26%) presented themselves spontaneously to the emergency department. Patients were initially admitted in a center without cardiac surgery in 65% of cases. The CT scan was the diagnostic test in 81% of cases. The postoperative hospital mortality was 16%. CONCLUSION: Referring to IRAD data reporting a median diagnostic and surgical delay of 258min each, our study suggests that the RENAU organization may be associated with reduced diagnostic and surgical delays for patients with SAAA.

Dramatic improvement in survival after lung transplantation over time: a single center experience.

Lung transplantation (LT) is a recognized procedure for selected patients with end-stage respiratory failure. We performed 123 LT, including 32 single lung, 84 double lung, and 7 heart-lung transplantations in 48 patients with chronic obstructive pulmonary disease (COPD), 13 patients with pulmonary hypertension (PH), 33 with cystic fibrosis (CF), and 29 with interstitial lung disease (ILD) between July 1990 and January 2008. Survival was compared for periods before and after December 2001. The mean age of patients was 44.4 years (range 16-66.5 years); 84 (69%) were men. Before LT, 1 second forced expiratory volume was 28.7% +/- 18.1% and PaCO(2) = 6.3 kPa. Fifty-five patients were on noninvasive ventilation. Cold ischemia time was 320 +/- 91 minutes. Cardiopulmonary bypass (CPB) was used in 77 patients (64%). There were 18 early surgical reinterventions, 8 extracorporeal membrane oxygenations, and 38 bronchial stent insertions among 206 at-risk bronchial sutures. Crude survivals were 69%, 58%, 41%, and 18% at 1, 2, 5, and 10 years, respectively. Comparing before (n = 70 with 15 CF) vs after December 2001 (n = 53 with 17 CF), survivals were 63% vs 78%, 51% vs 71%, and 33% vs 60% at 1, 2, and 5 years, respectively (P = .01) and for CF patients, 52% vs 100%, 52% vs 94%, and 25% vs 94% at 1, 2, and 5 years, respectively (P = .005). There was significant improvement in survival before and after 2001 in 123 LT and particularly among CF patients. Improvement in survival after LT may be related to the sum of numerous changes in our practice since December 2001, including the use of pulmonary rehabilitation pre-LT, extracellular pneumoplegia, statins, macrolides for chronic rejection, monitoring of Epstein-Barr blood load, changes in maintenance immunosuppressants, as well as position movement up the coordinator nurse and learning curve.

Angiotensin II-induced contractions in human internal mammary artery: effects of cyclooxygenase and lipoxygenase inhibition.

OBJECTIVE: This study investigated, in isolated human internal mammary artery, the involvement of the cyclooxygenase and the lipoxygenase pathways of arachidonic acid metabolism in the contraction induced by angiotensin II. METHODS: Rings of human internal mammary arteries were suspended in organ baths for recording of isometric tension. In addition, the release of eicosanoids in response to angiotensin II (0.3 microM) was measured by enzyme immunoassay. RESULTS: In human arterial rings without endothelial dependent relaxation in response to substance P or acetylcholine, the angiotensin II-induced contractions were significantly (P<0.05) reduced by 27% in the presence of GR32191 0.3 microM (thromboxane A(2) (TXA(2)) receptor antagonist) but remained unchanged in the presence of dazoxiben 100 microM (thromboxane synthase inhibitor). In addition, angiotensin II failed to modify TXB(2) and 6-keto-PGF(1alpha) production. These results suggest the contribution of a TXA(2)/PGH(2) agonist other than TXA(2) in angiotensin II-induced contractions. However, indomethacin increased (P<0.05) angiotensin II-mediated contractile response and cysteinyl leukotriene production, suggesting a redirection of arachidonic acid metabolism from the cyclooxygenase pathway to the lipoxygenase pathway. Indeed, the contractions induced by angiotensin II were inhibited (P<0.05) by phenidone 100 microM (cyclooxygenase and lipoxygenase inhibitor), baicalein 100 microM (5-, 12- and 15-lipoxygenases inhibitor), AA861 10 microM (5-lipoxygenase inhibitor) and MK571 1 microM (CysLT(1) receptor antagonist). Cysteinyl leukotrienes were released in response to angiotensin II (pg/mg dry weight tissue: 32+/-9 (basal, n=6) vs. 49+/-9 (angiotensin II 0.3 microM, n=6), P<0.05). LTD(4), and at a lesser degree LTC(4), induced contractions of internal mammary artery and MK571 1 microM abolished the contraction to LTD(4). CONCLUSIONS: This study suggests that the in vitro vasoconstrictor effects of angiotensin II in human internal mammary artery are enhanced at least in part by eicosanoids produced by the cyclooxygenase pathway, probably PGH(2), acting on TXA(2)/PGH(2) receptors, and by lipoxygenase-derived products, particularly cysteinyl leukotrienes acting on CysLT(1) receptors.

Is intra-aortic balloon pump absolutely contraindicated in type A aortic dissection?

AIM: Circulatory failure following surgery for type A aortic dissection is frequent and associated with a high mortality rate. The intra-aortic balloon pump (IABP) is used to treat postcardiotomy cardiogenic shock but aortic dissection is traditionally a contraindication. In 10 patients we used IABP for severe cardiogenic shock following aortic dissection surgery, here we report on the short and midterm results. METHODS: From January 2000 to April 2008, among 151 patients with type A aortic dissection 10 received a postoperative IABP. False lumen extension was limited to the ascending aorta for 3 patients, reached the arch for 1 and the descending aorta for 6. RESULTS: The device was placed in the operative room (7 patients), intensive care unit (2) and preoperatively (1). IABP was introduced percutaneously except for one who required surgical placement. The mean duration of IABP therapy was 3.8 days. Four patients died, but no death was directly related to IABP. Improvement in hemodynamics allowed 8 patients to be weaned off IABP. None suffered extension of the dissection. Two patients developed IABP-related complications. Six required extrarenal purification. Among the survivors, one died of a stroke at 38 months, 2 recovered the same quality of life and 3 had neurological sequelae without loss of autonomy. CONCLUSION: IABP should only be used as a salvage option in cases of severe cardiogenic shock following type A aortic dissection. No patient suffered device-related aortic rupture or extension of the dissection. High mortality and morbidity underline the gravity of cardiogenic shock in this setting.

EBV-B cells as antigen presenting cells in characterization of the self/donor context of allorecognition by T lymphocytes.

Alloreactivity is caused by T cell recognition of foreign histocompatibility antigens according to two models: (i) indirect recognition, in which processed allogeneic antigens are presented by self-major histocompatibility complexes like any other foreign antigen, and (ii) direct recognition, where the foreign MHC itself is recognized breaking the T cell recognition rule of self-restriction. This paper uses these two cases of alloantigen presentation as illustrative examples to investigate (i) the capacity of Epstein-Barr virus-transformed B cells (EBV-B cells) to process alloantigens, and (ii) in vitro assays with EBV-B cell lysate as a source of alloantigen, in order to characterize alloreactive T cell populations. A microculture system was established using donor EBV-B cell lysate as a source of the allogeneic antigen and donor or recipient EBV-B cells as antigen presenting cells to investigate whether alloantigen is recognized by effector T cells from the recipient. T lymphocytes produced after expansion in the presence of interleukin-2 from four samples of liver biopsies (three patients) and four samples of bronchoalveolar lavages (four patients) were used as effector cells. Upon human leucocyte antigen class II typing, these expressed the patient phenotype. When the T lymphocytes were from liver grafts, the recognition involved donor antigens presented by donor EBV-B cells (direct recognition). On the other hand, when the T lymphocytes were cultured from lung grafts, they mainly recognized antigens of donor EBV-B cell lysates in a self-restricted context (indirect recognition). These data suggest that EBV-B cells can provide allogeneic determinants recognized by T cells in donor or self-contexts, i.e. through either direct or indirect recognition.

Increased incidence of acute ascending aortic dissection with off-pump aortocoronary bypass surgery?

BACKGROUND: An apparent increase in the incidence of acute ascending aortic dissection following off-pump coronary artery bypass grafting (OPCAB) led us to assess retrospectively the rate and circumstances of this complication in our institution on a consecutive series of patients undergoing aortocoronary bypass performed with and without extracorporeal circulation (ECC). METHODS: A retrospective analysis of acute ascending aortic dissections complicating coronary artery bypass grafting surgery in 3,031 patients in our institution since April 1, 1995, was performed using the database of the Montreal Heart Institute. RESULTS: There was a greater frequency of hypertension in the OPCAB group. Iatrogenic acute aortic dissection occurred in 3 patients among 308 operated on without ECC (0.97%) and 1 patient among 2,723 operated on under ECC (0.04%). This difference was statistically significant (p < 0.00001). CONCLUSIONS: The risk of aortic dissection may be increased in OPCAB. Careful manipulation of the aorta with a single side-clamping and a control of the arterial pressure should be used to minimize aortic trauma. High-risk patients should undergo CABG without side-clamping of the aorta or CABG with ECC to prevent this redoubtable complication of myocardial revascularization.

Arterial balloon catheter: a new atraumatic device for dilating arterial grafts.

BACKGROUND: Harvesting of the internal mammary artery (IMA) for use in myocardial revascularization may result in spasm, which can impair early graft flow. Hydrostatic and mechanical dilatation can exert an intraluminal shear force, causing denudation of the IMA endothelium. A new long balloon dilatation technique (LB) has been developed to mechanically increase IMA diameter and flow without exerting any shear force on the endothelium. METHODS: Vascular rings of porcine IMA were divided into four groups: no manipulation (control), metal dilators (MD), short balloon (SB), or LB intraluminal dilation. In situ flows after dilation and percentage of intact endothelium after silver nitrate staining were determined. Endothelium-dependent contractions with arachidonic acid, relaxations with acetylcholine, endothelium-independent contractions with norepinephrine, and relaxation with sodium nitroprusside were recorded in organ chamber experiments. RESULTS: Increases in IMA flows were similar in all dilated groups. Endothelium-independent contractions and relaxations of IMA smooth muscle were unaffected by any type of mechanical dilation. However, endothelium-dependent contractions and relaxations were significantly impaired after MD and SB but preserved after LB dilation compared with control. Silver nitrate staining showed a greater preservation of the endothelial coverage after LB dilation. CONCLUSIONS: IMA dilatation with the novel arterial LB catheter increases IMA flow and preserves endothelial cell integrity, making it an effective and atraumatic method to relieve IMA spasm before use for coronary artery bypass grafting.

Effect of low-dose positive inotropic drugs on human internal mammary artery flow.

BACKGROUND: Dobutamine (a beta-receptor agonist), enoximone (a type III selective phosphodiesterase inhibitor), and epinephrine (an alpha- and beta-mimetic) frequently are used in the perioperative management of patients undergoing coronary artery bypass grafting. METHODS: We performed a double-blind clinical study to compare the effects on internal mammary artery free flow of low doses of these three positive inotropic drugs. Thirty patients in whom the left internal mammary artery was used for coronary artery bypass grafting were randomized into three groups. Internal mammary artery free flow and hemodynamic measurements were evaluated before and 10 minutes after the intravenous infusion of dobutamine (3 microg x kg(-1) x min(-1)), enoximone (200 microg/kg), or epinephrine (0.05 microg x kg(-1) x min(-1)). RESULTS: A significant increase in free flow occurred only in the dobutamine group (33 +/- 7.5 and 42.2 +/- 7.9 mL/min before and after drug infusion, respectively; p = 0.013). Comparison of the increase in flow between the groups, however, showed no difference. These drugs, at doses designed to produce a positive inotropic effect, caused little increase in the free flow of the internal mammary artery. CONCLUSIONS: The use of dobutamine, enoximone, and epinephrine as low-dose positive inotropic treatments in the perioperative and postoperative periods of coronary artery bypass grafting should depend on their positive inotropic effects rather than their vasodilative effects on the arterial grafts.

Effect of topical vasodilators on gastroepiploic artery graft.

BACKGROUND: Mobilization of the gastroepiploic artery (GEA) often results in a vasospasm with reduction of early graft flow. In order to prevent or suppress this highly reactive artery's spasm, we have compared the effect of 4 vasodilators, used in external application to prepare the GEA graft, prior to myocardial revascularization. METHODS: WE performed a double-blind clinical study to compare the effects of external application of vasodilators on gastroepiploic artery grafts. Fifty patients, whose gastroepiploic artery was used for coronary artery bypass grafting, were randomized into 5 groups of 10 patients. Gastroepiploic artery free flow and hemodynamic measurements were evaluated immediately after harvesting, before any pharmacological manipulation, and 10 minutes after the topical application of vasodilators, respectively: papaverine, linsidomine, nicardipine, glyceryl trinitrate, and normal saline solution. RESULTS: A significant increase in free flow occurred in all groups except for the normal saline solution group with measurements from 26.1+/-3.6 mL/min to 26.4+/-6.5 mL/min; p = 0.9. The most important increase in flow before and after local application occurred with glyceryl trinitrate and papaverine: from 25.5+/-2 mL/min to 50+/-6.1 mL/min (p < or = 0.01) and from 36.8+/-3.2 mL/min to 62+/-7.8 mL/min (p < 0.01) respectively. Nicardipine and linsidomine produced a less significant increase in flow: from 33.1+/-3.6 mL/min to 47.7+/-8.9 mL/min (p < 0.05) and from 28+/-3.8 mL/min to 39.8+/-7.5 mL/min (p < 0.05) respectively. When comparing percentage of flow increase, glyceryl trinitrate appeared to be significantly more efficient than nicardipine and linsidomine (p < 0.01 versus both groups). Although papaverine was more efficient than nicardipine and linsidomine, it did not reach statistical significance. CONCLUSIONS: During intraoperative preparation of the GEA graft, glyceryl trinitrate and papaverine to a lesser extent, used as topical vasodilators, appear to be more efficient in external application to increase the free flow of the GEA.

Human internal mammary artery contraction by isoprostaglandin f(2alpha) type-III [8-iso-prostaglandin F(2alpha)].

Isoprostaglandin F(2alpha) type-III (formerly known as 8-iso-prostaglandin F(2alpha)) is produced in large quantities in vivo in clinical situations associated with oxidant stress such as atherosclerosis, hypercholesterolemia, and myocardial reperfusion. Isoprostaglandin F(2alpha) type-III may alter smooth muscle and platelet functions. The aim of this study was to evaluate the effects of isoprostaglandin F(2alpha) type-III on isolated human internal mammary arteries, and to characterise the signalling underlying mechanisms. In organ baths, concentration-dependent contractions of human internal mammary arteries were obtained in response to isoprostaglandin F(2alpha) type-III stimulation. The responses to isoprostaglandin F(2alpha) type-III were inhibited in a concentration-dependent manner by the thromboxane A(2) receptor antagonist, GR 32191 ([1R-[1 alpha(Z), 2beta,3beta,5 alpha(+)-7-[[1, 1'-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1-piperidinyl) cyclo pentyl]-4-4heptanoic acid], hydrochloride), 3x10(-9) to 3x10(-7) M). However, this effect was associated with a decreased maximal contraction. AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid, 10(-6) to 3x10(-5) M), an EP(1)-DP receptor antagonist had no effect on isoprostaglandin F(2alpha) type-III-induced contractions. The maximal responses to isoprostaglandin F(2alpha) type-III were significantly reduced in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) (E(max): 147+/-20% vs. 213+/-19% in control group, P<0.05). Isoprostaglandin F(2alpha) type-III stimulated thromboxane B(2) release (5.7-fold increase) from human internal mammary arteries. Baicaleine, a non-specific lipoxygenase inhibitor, (10(-4) M) and AA 861 (2,3,5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1,4 benzoquinone), a 5-lipoxygenase inhibitor (10(-5) M) did not affect isoprostaglandin F(2alpha) type-III response. In conclusion, this study shows that (1) isoprostaglandin F(2alpha) type-III is a vasoconstrictor in human internal mammary arteries, with a potency equivalent to prostaglandin F(2alpha), (2) the contractions induced by isoprostaglandin F(2alpha) type-III are mediated by TP receptor but not EP(1)-DP-receptor activation, (3) thromboxane A(2) but not cysteinyl leukotrienes production is involved in the vascular effects of isoprostaglandin F(2alpha) type-III. Isoprostaglandin F(2alpha) type-III, produced at sites of free radical generation, may play an important role in internal mammary artery spasm in situations of oxidant stress such as coronary bypass surgery.

Glibenclamide inhibits thromboxane A2-induced contraction in human internal mammary artery and saphenous vein.

Glibenclamide, like other hypoglycemic sulfonylurea derivatives, is a potent blocker of ATP-regulated K+ channels. In addition, it is reported to inhibit prostanoid-induced contractions of isolated vascular smooth muscle from different animal species. We investigated the effect of glibenclamide on the thromboxane A2-mimetic U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy-prostaglandin F2alpha)-induced contractions in human isolated internal mammary arteries and saphenous veins. In the two vascular preparations, glibenclamide (3, 10 and 30 microM) caused a concentration-dependent shift to the right of the U-46619 contraction-response curve with a reduction, at the highest concentrations, in the maximal responses. This inhibitory effect appears selective for thromboxane A2-induced contractions since glibenclamide (30 microM) did not alter the contraction of internal mammary arteries in response to norepinephrine and of saphenous veins in response to 5-hydroxytryptamine (5-HT) and endothelin-1. However, glibenclamide reduced the endothelin-1-induced contraction in internal mammary arteries. The endothelin-1-induced contractions were similarly inhibited by GR 32191 ([1R-[1alpha(Z),2beta,3beta,5alpha]]-(+)-7-[5-([1,1'-b iphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-++ +heptonoic acid, a thromboxane A2 receptor antagonist. These results suggest that glibenclamide also reduced the endothelin-1-induced contractions by inhibiting a thromboxane A2 receptor-mediated component of the contraction elicited by this peptide. In conclusion, glibenclamide clearly appears to exert a specific inhibitory influence on prostanoid-induced contractions in human internal mammary arteries and saphenous veins.

Thromboxane A(2) modulates cyclic AMP relaxation and production in human internal mammary artery.

Two forms of thromboxane A(2) (TP) receptors, TPalpha and TPbeta receptors, have recently been cloned. These receptors regulate adenylate cyclase activity in two opposite ways: TPalpha receptors activate, whereas TPbeta receptors inhibit adenylate cyclase and cAMP generation. The aim of this study was to examine the effects of the thromboxane A(2) analogue, U46619 (9,11-dideoxy-9alpha,11 alpha-methanoepoxy-prostaglandin F(2alpha)), on forskolin-induced relaxation and cAMP accumulation in human internal mammary artery (IMA) and saphenous vein (SV). In organ baths, IMA rings precontracted with U46619 (3.10(-9) and 3.10(-8) M) were less sensitive to forskolin than rings precontracted with methoxamine (3. 10(-6) M). In contrast, the sensitivity to forskolin was similar in SV rings contracted with the same concentrations of these agonists. U46619 reduced significantly the ten-fold increase in cAMP induced by forskolin in IMA but not in SV rings. Sensitivity and maximal relaxation in response to sodium nitroprusside were not altered in either IMA or SV. In summary, stimulation of TP receptors with the thromboxane A(2) analogue, U46619, inhibited the cAMP pathway of relaxation through the inhibition of cAMP synthesis in human IMA but not in SV. It is suggested that thromboxane A(2) may play a role in the control of muscle tone in IMA both by its potent contractile effect and by its inhibitory effect on the cAMP pathway of relaxation.

Isoprostaglandin E2 type-III (8-iso-prostaglandin E2) evoked contractions in the human internal mammary artery.

E2-isoprostanes are recently discovered compounds that are produced in vivo from free radical-catalysed peroxidation of arachidonic acid. One such compound whose formation is favoured by this mechanism is isoprostaglandin E2 type III (iPE2-III, also named 8-iso-prostaglandin E2 or 15-E2t-isoprostaglandin). The aim of this study was to evaluate the vasomotor properties of iPE2-III in isolated human internal mammary artery. In organ bath, iPE2-III was approximately 10 times more potent than isoprostaglandin F2alpha-III and 27 times more potent than prostaglandin E2, whereas both isoprostaglandin F3alpha-III and 15-epi-isoprostaglandin F2alpha-II induced weak contractions. The responses to iPE2-III were inhibited in a concentration-dependent manner by the thromboxane A2 receptor antagonist GR 32191 (3.10(-9) to 3.10(-7) M). Indomethacin, a cyclooxygenase inhibitor and phosphoramidon, an endothelin converting enzyme inhibitor, did not affect iPE2-III response. These data shows that iPE2-III is a more potent vasoconstrictor of human internal mammary arteries than isoprostaglandin F2alpha-III. These effects are mediated by TP receptors, but involve neither cyclooxygenase products nor endothelins. iPE2-III production may induce more pronounced vasomotor effects than isoprostaglandin F2alpha-III in situations of oxidative stress, and in particular may modulate internal mammary artery tone following coronary bypass surgery.

Exposed prosthesis of a complex reconstruction of the ascending aorta and aortic arch in a sternal wound infection: Successful treatment by a pectoral muscle flap.

A local wound infection developed in a 42-year-old female patient after replacement of ascending aorta, aortic arch and supra-aortic vessels, following aortic dissection. Because of the high risk of infection due to the vascular prosthesis and its location at the upper part of the sternum, a right pectoral muscular flap, detached from the humerus and vascularized by medial perforators originating from the internal mammary artery, was isolated. The postoperative course was uneventful and the patient remains well 16 months after the operation.