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Full median sternotomy (FMS) is the common surgical access for patients undergoing replacement of the ascending aorta (AA) with or without aortic valve replacement (AVR). The right anterior mini-thoracotomy (RAMT) approach has been increasingly adopted for AVR. This approach has been shown to decrease blood loss and hospital length of stay (LOS) compared with FMS. The RAMT approach may also be beneficial in selected patients requiring AA procedures with or without AVR. We present our initial clinical experience of patients who have undergone a RAMT for supracommissural replacement of the tubular AA with or without AVR.This is a single-center retrospective review of 10 patients who underwent an elective RAMT for replacement of the tubular AA with or without AVR between November 2019 and January 2022. Clinical outcomes evaluated include 30-day mortality, intensive care and hospital LOS, time to extubation, operative times, as well as postoperative complications such as stroke and bleeding.Median cross-clamp and cardiopulmonary bypass times were 109 and 148 min, respectively. Median time to extubation was 2.5 h and median intensive care unit and hospital stay were 2 and 10 days, respectively. There were two re-thoracotomies for postoperative bleeding and two cases of sub-xiphoidal pericardial drainage for pericardial effusion. There were no strokes and no in-hospital nor 30-day mortalities.The replacement of the AA with or without concomitant AVR can be performed through a RAMT in carefully selected patients. However, the safety of this approach, as compared to full/partial median sternotomy, remains to be proven.

BACKGROUND: Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. METHOD: This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. FINDINGS: taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13). INTERPRETATION: Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. FUNDING: None of the authors have a financial relationship with a commercial entity that has an interest in the subject. ispartof: ECLINICALMEDICINE vol:58 ispartof: location:England status: published

Background Heart transplantation (HTx) in adults with congenital heart disease (ACHD) remains challenging because of structural anomalies and often previous procedure. The aim of this retrospective study was to describe the outcomes of heart transplantation (HTx) in a cohort of ACHD patients at our tertiary centre. Patients and methods Between January 1993 and December 2010, 223 consecutive adult patients (age > 18 years) underwent HTx at our institution. Fifteen (6.7%) were ACHD patients. Outcomes were reviewed using our institution's HTx database. We looked at 30-day, 1, 5 and 10-years survival, as well as post-transplantation complications. Results The mean age at HTx of the groups of ACHD was 42 ± 14.4 years, vs 54.2 ± 9.8 years for the non-CHD patients. Prior to transplant, thirteen of the fifteen ACHD had undergone one or more surgical procedures including palliative or corrective open-heart procedures in 66.6% of them. Seven of the fifteen ACHD (47%) required additional surgical procedures at transplantation. The mean follow-up was 95,44 ± 84.3 months. There was no significant difference in survival (ACHD vs non-CHD) at 30 days (87% vs. 90%), 1 year (73% vs. 74.5%) or 5 years (53% vs. 55%). Survival at 10 years was respectively 53% and 41% for ACHD patients and non-CHD patients. Conclusion Despite the surgical challenge, HTx in ACHD has a good long-term result. However, the small sample size of our cohort limits any definitive conclusions.

Ascending aorta mycotic aneurysm is a rare entity. It is a life-threatening condition because of the possibility of aortic dissection, or rupture. Escherichia coli is recognised as an uncommon cause of aortic mycotic aneurysm. An 81-year-old woman with a history of Escherichia coli pyelonephritis 4 months previously, was admitted to our centre for a mycotic aneurysm of the ascending aorta caused by Escherichia coli. She was successfully treated by urgent in situ replacement of the ascending aorta with a cryopreserved homograft, combined with antibiotics. Although infrequent, Escherichia coli mycotic aneurysm should be suspected in older patients with atherosclerosis and who developed septicaemia. Prompt treatment with a combination of appropriate antibiotics and surgery is required.

BACKGROUND Isolated pulmonary artery vasculitis is an uncommon cause of pulmonary artery aneurysm with very few reported cases in the literature. PATIENTS AND METHODS We hereby present the case of a 70-year-old man with occasional episodes of exertional chest discomfort. Our investigations revealed an expanding aneurysm of the main pulmonary artery extending to the proximal portion of the right branch. The patient successfully underwent replacement of the main pulmonary artery with a homograft. RESULTS Histopathological examination revealed images of vasculitis with numerous multinucleated giant cells. The patient's postoperative course was uneventful. CONCLUSION Management of pulmonary artery aneurysm secondary to isolated pulmonary artery vasculitis is not well studied, and no clear guidelines currently exist in the literature.

Heart donation after circulatory death (DCD) can significantly expand the heart donor pool, helping to overcome the problem of organ shortage and the increase in waiting list mortality and morbidity. To improve the outcome of DCD heart transplantation, thoraco-abdominal normothermic regional perfusion (TA-NRP) can be performed by selectively restoring circulation followed by in vivo functional heart assessment. Here, we report on the use of periprocedural transoesophageal echocardiography (TOE) as a minimally invasive cardiac assessment tool during different stages of a DCD heart procurement procedure using TA-NRP. We conclude that TOE is a valuable method to assess the donor heart for transplantation eligibility before and after withdrawal of life-sustaining therapy and during subsequent TA-NRP.

Background There are limited data on Coronavirus disease 2019 (COVID-19) in solid organ transplant patients, especially in heart transplant recipients, with only a few case reports and case series described so far. Heart transplant recipients may be at particular high risk due to their comorbidities and immunosuppressed state. Case presentation This report describes the clinical course and the challenging management of early COVID-19 infection in two heart transplant recipients who tested positive for the SARS-CoV-2 virus in the perioperative period of the transplant procedure. The two patients developed a severe form of the disease and ultimately died despite the initiation of an antiviral monotherapy with hydroxychloroquine coupled with the interruption of mycophenolate mofetil. Conclusions These two cases illustrate the severity and poor prognosis of COVID-19 in the perioperative period of a heart transplant. Thorough screening of donors and recipients is mandatory, and the issue of asymptomatic carriers needs to be addressed.

Streptococcus agalactiae (GBS) infective endocarditis (IE) is a rare clinical entity. It is associated with a high mortality rate compared to other streptococci endocarditis. The aim of this study ...

Graphical abstract, Highlights • SVD is a main limitation of bioprostheses. • Routine use of bioprostheses in younger patients (

The improvement in survival rates for heart transplant recipients (HTRs) has increased their risk of developing extracardiac diseases such as abdominal aortic aneurysms (AAAs). The purposes of this study were to evaluate the prevalence and to describe the clinical features and natural history of AAA in HTRs.A retrospective review of all patients (375) who underwent heart transplantation (HT) at our center over a 32-year period (1983-2015) was carried out.We identified 20 patients (5.3%) with AAA. All but one patient were male (95%), and most of them (80%) had a history of ischemic heart disease (IHD) prior to transplantation. The mean age of the patients with AAA at transplant was 57.2 ± 7.3 years (range: 42-62 years). Seven of the 20 patients with AAA already had an AAA (30-55 mm) prior to transplantation. The average aneurysm size at the time of diagnosis was 40.9 ± 9.6 mm, and the average patient age at the time of diagnosis was 62.2 ± 8.3 years. The mean linear expansion rate was 10.6 ± 2.12 mm/y, and the exponential expansion rate was 0.220 ± 0.040 yearThe natural history of AAA in HTR is characterized by an increased expansion rate. Male HTR with end-stage IHD are particularly at risk and should be closely followed-up after HT.

Ascending aorta mycotic aneurysm is a rare entity. It is a life-threatening condition because of the possibility of aortic dissection, or rupture.

BACKGROUND Heart transplantation (HT) from donation after circulatory death (DCD) has yet to achieve wide clinical application despite the encouraging resultsreported recently. In this study we describe 2 cases of successful adult DCD HT performed at our institution using an original protocol. METHODS Our local abdominal DCD protocol was updated to allow DCD heart procurement, and was accepted by the institutional ethics committee. The main features of the protocol include: pre-mortem insertion of peripheral venoarterial extracorporeal membrane oxygenation cannulas ; thoracoabdominal normothermic regional perfusion (NRP) by clamping the 3 aortic arch vessels to exclude cerebral circulation ; and in-situ heart resuscitation. The retrieved hearts were directly transplanted into recipients located in an adjoining operating room. RESULTS The procurement warm ischemic time was 25 minutes for the first donor, and 26 minutes for the second donor. The cold ischemic time was 16 minutes for the first recipient and 17 minutes for the second recipient. The suture time was 30 minutes for the first recipient, and 53 minutes for the second recipient. Both recipients were easily weaned off cardiopulmonary bypass in sinus rhythm and inotropic support. Post-operative evaluation of cardiac function was excellent and the patients were subsequently discharged home. CONCLUSIONS Transplantation of hearts from DCD donors is now a clinical reality.NRP is a useful tool for resuscitation, reperfusion, and preservation of transplanted hearts. It also offers the opportunity to assess the function and viability of organs before transplantation. However,due to ethical issues, some may object to ante-mortem intervention.

Cardiac intimal sarcoma is extremely rare and aggressive primary malignant cardiac tumors. Here, we reported the case of a young man initially operated for a tumor of the left atrium, causing a dynamic obstruction of the mitral valve and (mis-)diagnosed as a myxoma at the histopathological analysis. Patient presented a local recurrence at 3 months and was reoperated. Pathology revealed this time the presence of an intimal sarcoma. Patient received adjuvant chemotherapy. Despite a good local control, the 1-year follow-up positron emission tomography scan revealed the presence of a metastasis in the left adrenal gland that was surgically resected. This article aims to highlight the risk of misdiagnosis in case of cardiac tumors, the hypothetical concept of malignant transformation of a cardiac myxoma, the aggressive course of the extremely rare cardiac intimal sarcoma, and the therapeutic modalities available to treat this pathology.

Background Constrictive pericarditis (CP) is a disease characterized by inflammation, progressive fibrosis, and thickening of the pericardium. Constrictive pericarditis after heart transplantation (HT) is a rare phenomenon, with a reported incidence of 1.4–3.9%. It is an important clinical problem which shares similar clinical features with entities such as restrictive cardiomyopathy. Therefore, it poses diagnostic challenges and therapeutic dilemmas even for experienced clinicians. Case summary A 53-year-old patient developed a zoster infection with pericardial effusion 9 months after HT for idiopathic dilated cardiomyopathy. Two months later, he presented with leg oedema and ascites and was treated by diuretics for volume overload. He was readmitted 8 months later with features of right heart failure. Multimodal imaging investigations were suggestive of CP. He successfully recovered after a radical pericardiectomy. Discussion Constrictive pericarditis is a rare complication in HT. Heart transplant recipients (HTR) with a history of post-operative pericardial effusion, or with rejection episodes are at high risk of developing CP. Differentiating CP from other conditions that cause apparent congestive heart failure in HTR is challenging. Management of CP is mainly surgical pericardiectomy.

Al Hennawi HET, Mahdi EM, Memish ZA. Native valve Staphylococcus capitis infective endocarditis: a mini review. Infection. 2020;48:3–5. https://doi.org/10.1007/s15010-019-01311-8. Article PubMed Google Scholar Bandres JC, Darouiche RO. Staphylococcus capitis endocarditis: a new cause of an old disease. Clin Infect Dis Off Publ Infect Dis Soc Am. 1992;14:366–7. Article CAS Google Scholar Lina B, Celard M, Vandenesch F, Ribier A, Delahaye JP, Etienne J. Infective endocarditis due to Staphylococcus capitis. Clin Infect Dis Off Publ Infect Dis Soc Am. 1992;15:173–4. Article CAS Google Scholar Latorre M, Rojo PM, Franco R, Cisterna R. Endocarditis due to Staphylococcus capitis subspecies ureolyticus. Clin Infect Dis Off Publ Infect Dis Soc Am. 1993;16:343–4. Article CAS Google Scholar Mainardi JL, Lortholary O, Buu-Hoi A, Desplaces N, Goldstein F, Gutmann L, et al. Native valve endocarditis caused by Staphylococcus capitis. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 1993;12:789–91. Article CAS Google Scholar Al-Rashdan A, Bashir R, Khan FA. Staphylococcus capitis causing aortic valve endocarditis. J Heart Valve Dis. 1998;7:518–20. PubMed CAS Google Scholar Breuer GS, Yinnon AM, Halevy J. Infective endocarditis associated with upper endoscopy: case report and review. J Infect. 1998;36:342–4. Article CAS Google Scholar Sandoe JA, Kerr KG, Reynolds GW, Jain S. Staphylococcus capitis endocarditis: two cases and review of the literature. Heart Br Card Soc. 1999;82:e1. CAS Google Scholar Terada Y, Mitsui T, Enomoto Y. Prosthetic valve endocarditis caused by Staphylococcus capitis. Ann Thorac Surg. 1996;62:324. Article CAS Google Scholar Dominguez Rodriguez A, Garcia Gonzalez MJ, Lara Padron A, Laynez Cerdena I, Barragan Acea A, Miralles Ibarra JM, et al. Infectious endocarditis of prosthetic valves due to Staphylococcus capitis: a new case. Rev Esp Cardiol. 1999;52:277–8. Article Google Scholar Cone LA, Sontz EM, Wilson JW, Mitruka SN. Staphylococcus capitis endocarditis due to a transvenous endocardial pacemaker infection: case report and review of Staphylococcus capitis endocarditis. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2005;9:335–9. Google Scholar Kamalesh M, Aslam S. Aortic valve endocarditis due to Staphylococcus capitis. Echocardiogr Mt Kisco N. 2000;17:685–7. Article CAS Google Scholar Kamalakannan D, Teklinski A, Johnson L, Rosman H, Saravolatz L. Staphylococcus capitis endocarditis: a case report and review of literature. Infect Dis Clin Pract. 2004;12:314–7. Article Google Scholar Konishi T, Nishihara H, Ito T, Tanaka Y. Infective endocarditis presenting initially with ileus complicated by dehiscence of annuloplasty ring. BMC Cardiovasc Disord. 2015;15:124. Article Google Scholar von Eiff C, Vaudaux P, Kahl BC, Lew D, Emler S, Schmidt A, et al. Bloodstream infections caused by small-colony variants of coagulase-negative Staphylococci following pacemaker implantation. Clin Infect Dis Off Publ Infect Dis Soc Am. 1999;29:932–4. Article Google Scholar Cho M-S, Kim S-H, Nam G-B, Choi K-J, Kim Y-H. Very late-onset lead-associated endocarditis. Can J Infect Dis Med Microbiol. 2011;22:147–8. Article Google Scholar Nalmas S, Bishburg E, Meurillio J, Khoobiar S, Cohen M. Staphylococcus capitis prosthetic valve endocarditis: report of two rare cases and review of literature. Heart Lung J Crit Care. 2008;37:380–4. Article Google Scholar Takano T, Ohtsu Y, Terasaki T, Wada Y, Amano J. Prosthetic valve endocarditis caused by Staphylococcus capitis: report of 4 cases. J Cardiothorac Surg. 2011;7:6–131. Google Scholar Demarie D, De Vivo E, Cecchi E, Marletta G, Forsennati PG, Casabona R, et al. Acute endocarditis of the patch caused by Staphylococcus capitis in treated tetralogy of Fallot. An unusual location by an unusual bacterium. Heart Lung Circ. 2012;21:189–92. Article Google Scholar Download references None. Department of Cardiovascular Surgery, CHU Liege, B35 Sart Tilman, 4000, Liege, Belgium Vincent Tchana-Sato & Jean Olivier Defraigne You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Vincent Tchana-Sato. All authors have no conflicts of interest to declare. Reprints and Permissions Tchana-Sato, V., Defraigne, J.O. Staphylococcus capitis causing infective endocarditis: not so uncommon. Infection (2020). https://doi.org/10.1007/s15010-020-01514-4 Download citation Received: 20 June 2020 Accepted: 24 August 2020 Published: 24 September 2020 DOI: https://doi.org/10.1007/s15010-020-01514-4

Background: Some studies focusing on the endovascular repair of abdominal aortic aneurysms (AAA) have demonstrated that cancer is often found in such patients. Retrospective investigations have also indicated that AAA patients have an increased risk of cancer. However, the incidence rate of cancer and survival rate in patients with AAA compared to the population remains unknown. Methods: We conducted a prospective, single center, non-randomized, comparative cohort study including 223 AAA patients and 1000 Coronary artery disease (CAD) patients enrolled in our department between 01/01/2008 and 31/12/2011 with annual follow-up until 31/12/2018. Based on statistics from the Belgian cancer registry Belgium, the incidence rate of cancer was calculated for both men and women in the general population. The primary endpoint was the cumulative incidence rate of cancer in all three groups and the secondary endpoint was overall survival. Results: After nine years of follow-up, the cancer incidence was 30·1% (95%CI: 21·6-39·3%) in AAA patients and 23·5% (95%CI: 20·0-27·1%) in CAD subjects, markedly higher than the Walloon population (17·4%). Moreover, the development of metastases among patients with AAA was higher compared to CAD patients (38·7% vs.18·6%, P=0·03). In terms of overall survival, the proportion of cancer deaths in AAA patients was twice as high as in CAD patients. Conclusions: This study confirms an increased incidence of cancers and decreased survival in AAA patients compared to the general population. Funding Statement: This work was supported by the European Program FP7 “Fighting aneurysmal diseases” (no. 200647). Audrey Courtois and Jacobine Munten were funded by the Aneurysmal Pathology Foundation. Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: The study was designed and conducted within the framework of the European program “Fighting Aneurysmal Disease (FAD; B70720095774 and B70720095773 9)” approved by the ethics committee (n°200647). All the participants were instructed on the study objectives and provided informed consent. The study was approved by the ethics board of the University hospital of Liege.

Heart transplantation (HT) from donation after circulatory death (DCD) is a promising alternative to expand the heart donor pool. Cold storage can be used in a strategy to successfully retrieve and transplant DCD hearts after reconditioning using normothermic regional perfusion for distant procurement. Herein, we present the first report of a pediatric DCD heart reconditioned with normothermic regional perfusion, preserved using only cold storage while being transported to a neighboring center, and then successfully transplanted after nearly 2 hours of cold static storage. If supported by an appropriate trial, this finding could obviate the need to use expensive perfusion devices for short interhospital distances for DCD heart transportation and stimulate more centers across the world to embrace DCD HT. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:38 issue:10 pages:1112-1115 ispartof: location:United States status: published

We here report the case of a stenosis of the CoreValve® system due to reduced mobility of prosthesis cusps for which a surgical replacement of the aortic valve was proposed. The exact mechanism leading to this impaired mobility of the leaflets is yet to be determined. We also underline the fact a transcatheter aortic valve implantation (TAVI) device can be replaced by a surgical replacement without excessive operative risks despite the patient being initially considered as high-risk.

Background Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ventilation at lower tidal volume enhances pulmonary hypertension and might induce right ventricular (RV) failure. We investigated if extracorporeal veno-venous CO2 removal therapy could have beneficial effects on pulmonary circulation and RV function. Methods This study was performed on an experimental model of ARDS obtained in eight anaesthetized pigs connected to a volume-cycled ventilator. A micromanometer-tipped catheter was inserted into the main pulmonary artery and an admittance micromanometer-tipped catheter was inserted into the right ventricle. RV–arterial coupling was derived from RV pressure-volume loops. ARDS was obtained by repeated bronchoalveolar lavage. Protective ventilation was then achieved, and the pigs were connected to a pump-driven extracorporeal membrane oxygenator (PALP, Maquet, Germany) in order to achieve CO2 removal. Results ARDS induced severe hypercapnic acidosis. Systolic pulmonary artery pressure significantly increased from 29.6 ± 1.8 to 43.9 ± 2.0 mmHg (P

Early diagnosis of infected abdominal aortic aneurysm (IAAA) is still a medical challenge due to its diverse and non-specific symptoms and signs. The most common responsible pathogens are Salmonella, Staphylococcus, Campylobacter and Streptococcus species. The authors report the case of a 67-year-old man, admitted for high fever and finally diagnosed with Escherichia coli (E.coli)-related IAAA. The IAAA ruptured during the general anaesthesia induction, leading to an emergency surgery. The authors successfully proceeded to an open aneurysmectomy with extensive debridement and in situ graft replacement. This case emphasizes the potential for rapid IAAA expansion, its high-rupture risk and the importance of computed tomography as a diagnostic tool.

Precise assessment of left ventricular (LV) contractility during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support is crucial. However, changes in loading conditions may mask changes in LV function when assessed with load-dependent parameters. We compared end-systolic elastance (Ees, mm Hg/ml), the reference load-independent parameter of LV contractility, with LV ejection fraction (LVEF) in two patients. The first patient was a 54-year-old patient supported with femoro-femoral VA-ECMO for a cardiogenic shock. Afterload was calculated by using arterial elastance (Ea, mm Hg/ml). Although Ees near doubled from day 0 to day 3, no significant change was observed in LVEF. The second patient was a 61-year-old patient supported with femoro-femoral VA-ECMO for severe heart failure complicated with sepsis. We retrospectively showed that discrepancy between LVEF and Ees resulted from changes in LV-arterial coupling. We concluded that LVEF may be misleading in the assessment of LV function during VA-ECMO for heart failure.

Although reperfusion after coronary occlusion is mandatory for myocardial salvage, reperfusion may trigger a cascade of harmful events (reperfusion injury) adding to myocardial injury. We investigated effects of reperfusion on left ventricular (LV) haemodynamics and ventriculo-arterial (VA) coupling in pigs following acute myocardial ischaemia induced by coronary artery occlusion. Experiments were performed in six animals, with measurements of cardiac and arterial function at baseline, after 60 min of ischaemia (T60) and after 2 (T180) and 4 h of reperfusion (T300). Ventriculo-arterial coupling was assessed using the ventriculo-arterial elastance ratio of paper, as well as using a ‘stiffness coupling’ and ‘temporal coupling’ index. Reperfusion following ischaemia (T180 versus T60) induced a progressive decline in cardiovascular function, evidenced by a decrease in mean arterial blood pressure, cardiac output and ejection fraction which was not restored at T300. Although reperfusion also induced an increase in slope of the end-systolic pressure–volume relationship (ESPVR), the ESPVR curve shifted to the right, associated with a depression of contractile function. Histology demonstrated irreversible myocardial damage at T300. The ventriculo-arterial elastance ratio and the ‘stiffness coupling’ index were unaffected throughout the protocol, but the ‘temporal coupling’ parameter indicated a relative shift between heart period and the time constant of the arterial system. It is unlikely that these alterations are attributable to ischaemic injury alone. The combination of both the stiffness and temporal coupling index may provide more information when studying ventriculo-arterial coupling than the more commonly used ventricular end-systolic stiffness/effection arterial elastance (Ees/Ea) ratio.

Aims: To investigate whether BM-573 ( N-tert -butyl-N' -[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea), an original combined thromboxane A 2 synthase inhibitor and receptor antagonist, prevents reperfusion injury in acutely ischemic pig s. Methods: Twelve animals were randomly divided in two groups: a control group (n = 6) intravenously infused with vehicle, and a BM-573 -treated group ( n = 6) infused with BM-573 (10 mgkg -1 h -1 ). In both groups, the left anterior descending (LAD ) coronary artery was occluded for 60 min and reperfused for 240 min. Either vehicl e or BM-573 was infused 30 min before LAD occlusion and throughout the experiment. Platelet aggregation ind uced by arachidonic acid ex vivo measured was prevented by BM-573. Results: In both groups, LAD occlusion decreased cardiac output, ejection fraction, slope of stroke work—end-diastolic volume relationship, and induced end-systolic pressure-volume relationship (ESPVR) rightward shift, while left ventricular afterload i ncreased. Ventriculo-arterial coupling and mechanic al efficiency decreased. In both groups, reperfusion further decr eased cardiac output and ejection fraction, while ES PVR displayed a further rightward shift. Ventriculo-art erial coupling and mechanical efficiency remained i mpaired. Area at risk, evidenced with Evans blue, was 33.2 ± 3.4% of the LV mass (LVM) in both groups, and mean infarct size, revealed by triphenyltetrazolium chlo ride (TTC), was 27.3 ± 2.6% of the LVM in the BM-573treated group (NS). Histological examination and im munohistochemical identification of desmin revealed necrosis in the anteroseptal region similar in both groups, while myocardial ATP dosages and electron microscopy also showed that BM-573 had no cardioprotective effect. Conclusions: These data suggest that BM573 failed to prevent reperfusion injury in acutely ischemic pigs.

The aim of our study was to evaluate the effects of thromboxane A 2 (TXA 2 ) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA 2 receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group ( n = 6), the animals received six consecutive injections of U-46619 at 30 min interval, while in Anta group ( n = 6) they received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. The effects of each dose of BM-573 on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were also evaluated. Vascular properties such as characteristic impedance, peripheral resistance, compliance, arterial elastance were estimated using a windkessel model. Intravenous injections of 0.500 mg/ml of BM-573 and higher doses resulted in a complete inhibition of platelet aggregation induced by arachidonic acid. In the same conditions, BM-573 completely blocked the increase of arterial elastance, and stabilized both mean aortic blood pressure and mean systemic blood flow. In conclusion, BM-573 could therefore be a promising therapeutic approach in pathophysiological states where TXA 2 plays a main role in the increase of vascular resistance like in pathologies such as systemic hypertension.

Objective: It was investigated whether pharmacologically induced changes in right ventricular contractility can be detected by a so-called “single-beat” method that does not require preload reduction. Design: Prospective animal research. Setting: Laboratory at a large university medical center. Subjects: Eight anesthetized pigs. Interventions: End-systolic elastance values obtained by a recently proposed single-beat method (Eessb) were compared with those obtained using the reference multiple-beat method (Eesmb). Measurements and Main Results: Administration of dobutamine increased Eesmb from 1.6 0.3 to 3.8 0.5 mm Hg/mL (p .001), whereas there was only a trend toward an increase in Eessb from 1.5 0.2 to 1.7 0.4 mm Hg/mL. Esmolol decreased Eesmb from 1.7 0.3 to 1.1 0.2 mm Hg/mL (p .006), whereas there was only a trend for a decrease in Eessb from 1.5 0.2 to 1.3 0.1. Conclusions: The present method using single-beat estimation to assess right ventricular contractility does not work as expected, since it failed to detect either increases or decreases in right ventricular contractility induced by pharmacologic interventions. (Crit Care Med 2004; 32:1886 –1890)

The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [ N - tert -butyl- N ′-[2-(4′-methylphenylamino)-5-nitrobenzenesulfonyl]urea], an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor in rats, and to determine its effects on mice bleeding time. Intraperitoneal injection of a single dose of 5 mg/kg BM-573 to rats inhibited U-46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F2)-induced washed platelet aggregation 30 min and 1, 2, and 4 h after drug administration with a maximum antiplatelet effect observed after 1 and 2 h. In a rat model of thrombosis induced by ferric chloride application on the abdominal aorta, BM-573 significantly reduced the thrombus weight by 92.53, 80.20, 64.75, and 18.21% at doses of 5, 2, 0.5, and 0.2 mg/kg, respectively. Time to occlusion of abdominal aorta in the BM-573-treated group (41.50 ± 5.21 min) was significantly prolonged compared with the vehicle-treated rats (16.16 ± 0.79 min). Like furegrelate, seratrodast, and acetylsalicylic acid, BM-573 did not affect the tail bleeding time induced by tail transection in mice compared with vehicle-treated mice. Moreover, BM-573, a close derivative of the loop diuretic torasemide, failed to induce a significant increase in diuresis in rat and did not produce a decrease in blood glucose concentration as observed with the sulfonylurea glibenclamide. In conclusion, we have demonstrated that the nitrobenzenic sulfonylurea BM-573, an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor, is a potent antithrombotic agent that does not affect bleeding time. Moreover, BM-573 lost the diuretic property of torasemide and has no impact on glycemia.

We investigated the effects of a dual thromboxane (TX)A2 synthase inhibitor and TXA2 receptor antagonist (BM-573) on right ventricular-arterial coupling in a porcine model of endotoxic shock. Thirty minutes before the onset of 0.5 mg/kg endotoxin infusion, six pigs (Endo group) received an infusion with a placebo solution, and six other pigs (Anta group) with BM-573. Right ventricular pressure-volume loops were obtained by the conductance catheter technique. The slope (Ees) of the end-systolic pressure-volume relationship and its volume intercept at 25 mmHg were calculated as measures of right ventricular systolic function. RV afterload was quantified by pulmonary arterial elastance (Ea), and Ees/Ea ratio represented right ventricular-arterial coupling. Mechanical efficiency was defined as the ratio of stroke work and pressure-volume area. In this model of endotoxic shock, BM-573 blunted the early phase of pulmonary hypertension, improved arterial oxygenation, and prevented a decrease in right ventricular myocardial efficiency and right ventricular dilatation. However, the drug could not prevent the loss of homeometric regulation and alterations in right ventricular- arterial coupling. In conclusion, dual TXA2 synthase inhibitor and receptor antagonists such as BM-573 have potential therapeutic applications, improving right ventricular efficiency and arterial oxygenation in endotoxic shock. KEYWORDS—Hemodynamics, pigs, pulmonary circulation, right ventricular dysfunction, septic shock

Maximal left ventricular (LV) hydraulic power output (PWRmax), corrected for preload as PWRmax/(Ved)β (where Ved is the end-diastolic volume and β is a constant coefficient), is an index of LV contractility. Whereas preload-adjusted maximal power (PAMP) is usually calculated with β = 2, there is uncertainty about the optimal value of β (β = 1 for the normal LV and 2 for the dilated LV). The aim of this work is to study the determining factors of β. The data set consisted of 245 recordings (steady state and vena cava occlusion) in 10 animals in an ischemic heart pig model. The occlusion data yielded the slope ( E es; 2.01 ± 0.77 mmHg/ml, range 0.71–4.16 mmHg/ml) and intercept (V0; −11.9 ± 22.6 ml; range −76 to 39 ml) of the end-systolic pressure-volume relation, and the optimal β-factor (assessed by fitting an exponential curve through the Ved-PWRmax relation) was 1.94 ± 0.88 (range 0.29–4.73). The relation of β with Ved was weak [β = 0.60 + 0.02(Ved); r 2 = 0.20]. In contrast, we found an excellent exponential relation between V0 and β [β = 2.16[Formula: see text] r 2 = 0.70]. PAMP, calculated from the steady-state data, was 0.64 ± 0.40 mW/ml2 (range 0.14–2.83 mW/ml2) with a poor correlation with E es ( r = 0.30, P< 0.001). An alternative formulation of PAMP as PWRmax/(Ved − V0)2, incorporating V0, yielded 0.47 ± 0.26 mW/ml2 (range 0.09–1.42 mW/ml2) and was highly correlated with E es ( r = 0.89, P< 0.001). In conclusion, correct preload adjustment of maximal LV power requires incorporation of V0 and thus of data measured under altered loading conditions.

We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A2 (TXA2) agonist, before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Six anesthetized pigs (Ago group) received 6 consecutive injections of U-46619 at 30-min interval and were compared with six anesthetized pigs (Anta group) which received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. Consecutive changes in pulmonary hemodynamics, including characteristic resistance, vascular compliance, and peripheral vascular resistance, were continuously assessed during the experimental protocol using a four-element Windkessel model. At 2 mg/kg, BM-573 completely blocked pulmonary hypertensive effects of U-46619 but pulmonary vascular compliance still decreased. This residual effect can probably be explained by a persistent increase in the tonus of the pulmonary vascular wall smooth muscles sufficient to decrease vascular compliance but not vessel lumen diameter. Such molecule could be a promising therapeutic approach in TXA2 mediated pulmonary hypertension as it is the case in pulmonary embolism, hyperacute lung rejection and endotoxinic shock.

Acute respiratory distress syndrome (ARDS) is responsible for injuries to the alveolar epithelium and microvascular endothelium resulting in hypoxemia, decreased pulmonary compliance and increased pulmonary vascular resistance. Beneficial effects resulting from protective lung ventilation are counterbalanced by deleterious hemodynamic effects. Indeed, hypercapnia resulting from ventilation at lower tidal volume enhances pulmonary hypertension and is associated with right ventricular failure in ARDS[1].

Background— Stentless aortic bioprostheses were designed to provide enhanced hemodynamic performance and potentially greater longevity. The present report describes the outcomes of patients with the Freestyle stentless bioprosthesis followed for ≤18 years. Methods and Results— Between 1993 and 2011, 430 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis in the subcoronary position. Mean age was 68.2±8.2 years. All of the clinical and echocardiographic data were collected prospectively. Mean overall follow-up was 9.1±4.4 years and was complete in all of the patients. In-hospital mortality was 3.5% (n=15). Overall, 10- and 15-year survival were 60.7% and 35.0%, respectively. Fifty-one patients required reoperation during follow-up, including 27 for structural valve deterioration (SVD). Overall, freedom from reoperation was 91.0% and 75.0% at 10 and 15 years, whereas freedom from reoperation for SVD was 95.9% and 82.3%, respectively. At 10 and 15 years, freedom from reoperation for SVD was 94.0% and 62.6% for patients P =0.002). The median time to explant for SVD was 10.7 years. SVD presented mostly as acute, severe aortic insufficiency attributed to leaflet tear (77.8%). The independent risk factors for reoperation for SVD were age P =0.001) and dyslipidemia ( P =0.02). Conclusions— Aortic valve replacement with the Freestyle bioprosthesis in a subcoronary position provides good long-term clinical and echocardiographic outcomes for patients >60 years of age. Severe aortic insufficiency with leaflet tear is the major mode of SVD leading to reoperation in these patients.

The aim of this study was to test whether the simple ratio of right ventricular (RV) end-systolic pressure (Pes) to stroke volume (SV), known as the effective arterial elastance ( Ea), provides a valid assessment of pulmonary arterial load in case of pulmonary embolism- or endotoxin-induced pulmonary hypertension. Ventricular pressure-volume (PV) data (obtained with conductance catheters) and invasive pulmonary arterial pressure and flow waveforms were simultaneously recorded in two groups of six pure Pietran pigs, submitted either to pulmonary embolism ( group A) or endotoxic shock ( group B). Measurements were obtained at baseline and each 30 min after injection of autologous blood clots (0.3 g/kg) in the superior vena cava in group A and after endotoxin infusion in group B. Two methods of calculation of pulmonary arterial load were compared. On one hand, Ea provided by using three-element windkessel model (WK) of the pulmonary arterial system [ Ea(WK)] was referred to as standard computation. On the other hand, similar to the systemic circulation, Ea was assessed as the ratio of RV Pes to SV [ Ea(PV) = Pes/SV]. In both groups, although the correlation between Ea(PV) and Ea(WK) was excellent over a broad range of altered conditions, Ea(PV) systematically overestimated Ea(WK). This offset disappeared when left atrial pressure (Pla) was incorporated into Ea [ Ea * (PV) = (Pes − Pla)/SV]. Thus Ea * (PV), defined as the ratio of RV Pes minus Pla to SV, provides a convenient, useful, and simple method to assess the pulmonary arterial load and its impact on the RV function.

In acute pulmonary embolism, right ventricular (RV) failure may result from exceeding myocardial contractile resources with respect to the state of vascular afterload. We investigated the adaptation of RV performance in a porcine model of progressive pulmonary embolism. Twelve anesthetized pigs were randomly divided into two groups: gradual pulmonary arterial pressure increases by three injections of autologous blood clot (n=6) or sham-operated controls (n=6). Right ventricular pressure-volume (PV) loops were recorded using a conductance catheter. Right ventricular contractility was estimated by the slope of the end-systolic PV relationship (Ees). After load was referred to as pulmonary arterial elastance (Ea) and assessed using a four-element Windkessel model. Right ventricular-arterial coupling (Ees/Ea) and efficiency of energy transfer (from PV area to external mechanical work [stroke work]) were assessed at baseline and every 30 min for 4 h. Ea increased progressively after embolization, from 0.26+/-0.04 to 2.2+/-0.7 mmHg mL(-1) (P

AIM: To report the experience of the CHU Sart Tilman, University of Liege, Belgium, in the management of appendiceal carcinoid tumor. METHODS: A retrospective review of 1237 appendectomies performed in one single centre from January 2000 to May 2004, was undertaken. Analysis of demographic data, clinical presentation, histopathology, operative reports and outcome was presented. RESULTS: Among the 1237 appendectomies, 5 appendiceal carcinoid tumors were identified (0.4%) in 4 male and 1 female patients, with a mean age of 29.2 years (range: 6-82 years). Acute appendicitis was the clinical presentation for all patients. Four patients underwent open appendectomy and one a laparoscopic procedure. One patient was reoperated to complete the excision of mesoappendix. All tumors were located at the tip of the appendix with a mean diameter of 0.6 cm (range: 0.3-1.0 cm). No adjuvant therapy was performed. All patients were alive and disease-free during a mean follow-up of 33 mo. CONCLUSION: Appendiceal carcinoid tumor most often presents as appendicitis. In most cases, it is found incidentally during appendectomies and its diagnosis is rarely suspected before histological examination. Appendiceal carcinoid tumor can be managed by simple appendectomy and resection of the mesoappendix, if its size is ≤ 1 cm.

Although reperfusion after coronary occlusion is mandatory for myocardial salvage, reperfusion may trigger a cascade of harmful events (reperfusion injury) adding to myocardial injury. We investigated effects of reperfusion on left ventricular (LV) haemodynamics and ventriculo-arterial (VA) coupling in pigs following acute myocardial ischaemia induced by coronary artery occlusion. Experiments were performed in six animals, with measurements of cardiac and arterial function at baseline, after 60 min of ischaemia (T60) and after 2 (T180) and 4 h of reperfusion (T300). Ventriculo-arterial coupling was assessed using the ventriculo-arterial elastance ratio of paper, as well as using a 'stiffness coupling' and 'temporal coupling' index. Reperfusion following ischaemia (T180 versus T60) induced a progressive decline in cardiovascular function, evidenced by a decrease in mean arterial blood pressure, cardiac output and ejection fraction which was not restored at T300. Although reperfusion also induced an increase in slope of the end-systolic pressure-volume relationship (ESPVR), the ESPVR curve shifted to the right, associated with a depression of contractile function. Histology demonstrated irreversible myocardial damage at T300. The ventriculo-arterial elastance ratio and the 'stiffness coupling' index were unaffected throughout the protocol, but the 'temporal coupling' parameter indicated a relative shift between heart period and the time constant of the arterial system. It is unlikely that these alterations are attributable to ischaemic injury alone. The combination of both the stiffness and temporal coupling index may provide more information when studying ventriculo-arterial coupling than the more commonly used ventricular end-systolic stiffness/effection arterial elastance (E(es)/E(a)) ratio.

To assess risk factors for early and late outcome after concurrent carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG).Records of all 311 consecutive patients having concurrent CEA and CABG from 1989 to 2002 were reviewed, and follow-up obtained (100% complete). In the group (mean age 67 years; 74% males), 62% had triple-vessel disease, 57% unstable angina, 31% left main coronary stenosis, 19% congestive heart failure, and 35% either a history of vascular procedures or existing vasculopathies. Preoperative assessment revealed transient ischaemic attack in 16%, stroke in 7%, and bilateral carotid disease in 20%. There were 7% emergent and 19% urgent operations, and ascending aorta was described as atheromatous or calcified in 21%. Hospital death occurred in 19 patients, myocardial infarction in seven, and permanent stroke in 12. Significant multivariable predictors of hospital death were aortic calcifications, coexisting vasculopathy, and emergent procedure. Significant predictors of postoperative stroke were calcified or dilated aorta, and of prolonged hospital stay were advanced age, unstable angina, and coexisting vascular disease. For hospital survivors, 10-year actuarial late event-free rates were: death, 50%; myocardial infarction, 84%; stroke, 93%; percutaneous angioplasty, 95%; redo CABG, 98%; and all morbidity and mortality, 48%. Significant multivariable predictors of late deaths were coexisting vasculopathy, age, renal insufficiency, previous cardiac surgery, tobacco abuse, calcified or atheromatous aorta, and duration of intensive care unit stay.Concurrent CEA and CABG can be performed with acceptable operative mortality and morbidity, and good long-term freedom from coronary and neurologic events. Atheromatous aortic disease is a harbinger of poor operative and long-term outcome.

BM-573 (N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a torsemide derivative, is a novel non-carboxylic dual TXA 2 synthase inhibitor and receptor antagonist. The pharmacological profile of the drug is characterized by a higher affinity for the thromboxane receptor than that of SQ-29548, one of the most powerful antagonists described to date, by a complete prevention of human platelet aggregation induced by arachidonic acid at a lower dose than either torsemide or sulotroban, and by a significantly prolonged closure time measured by the platelet function analyser (PFA-100®). Moreover, at the concentrations of 1 and 10 μM, BM-573 completely prevented production of TXB 2 by human platelets activated by 0.6 mM of arachidonic acid. BM-573 prevents rat fundus contraction induced by U-46619 but not by prostacyclin or other prostaglandins. Despite possessing a chemical structure very similar to that of a diuretic torsemide, BM-573 has no diuretic activity. BM-573 does not prolong bleeding time and, unlike some of the other sulfonylureas, and has no effect on blood glucose levels. In vivo, BM-573 appears to have antiplatelet and antithrombotic activities since it reduced thrombus weight and prolonged the time to abdominal aorta occlusion induced by ferric chloride. BM-573 also relaxed rat aorta and guinea pig trachea precontracted with U-46619. In pigs, BM-573 completely antagonized pulmonary hypertensive effects of U-46619 and reduced the early phase of pulmonary hypertension in models of endotoxic shock and pulmonary embolism. Finally, BM-573 protected pigs from myocardial infarction induced by coronary thrombosis. These results suggest that BM-573 should be viewed as a promising therapeutic agent in the treatment of pulmonary hypertension and syndromes associated with platelet activation.

This study investigated the effects of dobutamine on left ventriculoarterial (VA) coupling and mechanical efficiency in acutely ischemic pigs. Experiments were performed in 12 pigs in which vascular properties, including peripheral resistance (R2), compliance (C), and arterial elastance (Ea), were estimated with a windkessel model, and left ventricular (LV) function by the slope (Ees) of the end-systolic pressure-volume relationship (ESPVR) and stroke work (SW). VA coupling was defined as Ees/Ea, and mechanical efficiency as SW/pressure-volume area (PVA). In all animals, the left anterior descending coronary artery was ligated after basal measures. The animals were then randomly divided into 2 groups: group CTRL (n = 6) was followed for 180 minutes without other intervention, whereas group DOBU (n = 6) was infused with dobutamine (5 microg x kg(-1) x min(-1)) starting after T60 measures. Coronary occlusion induced a rightward shift of ESPVR and a decrease in Ees from 3.67 +/- 0.33 to 1.92 +/- 0.20 mm Hg x mL(-1), while Ea changed from 3.33 +/- 0.56 to 4.65 +/- 0.29 mm Hg x mL, R2 from 1.72 +/- 0.30 to 2.38 +/- 0.16 mm Hg x s x mL(-1), and C from 0.78 +/- 0.16 to 0.46 +/- 0.08 mL x mm Hg(-1). This altered VA coupling from 1.22 +/- 0.11 to 0.44 +/- 0.07. SW decreased from 4056 +/- 223 to 2372 +/- 122 mm Hg x mL, and PVA and SW/PVA decreased from 5575 +/- 514 to 4830 +/- 317 mm Hg x mL, and from 0.76 +/- 0.04 to 0.49 +/- 0.03, respectively. In group DOBU, dobutamine restored Ees and the position of ESPVR to baseline values, while Ea decreased to 3.39 +/- 0.34 mm Hg x mL(-1) because of an R2 decrease to 1.60 +/- 0.24 mm Hg x s x mL(-1). VA coupling was restored. SW and PVA increased to 3833 +/- 180 mm Hg x mL and to 7498 +/- 442 mm Hg x mL, respectively, while SW/PVA was unchanged. In ischemic pigs, dobutamine restored VA coupling through an increase in LV contractility and decrease in arterial elastance as a result of peripheral vasodilatation. However, myocardial oxygen consumption was increased, and mechanical efficiency impaired.

Background Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely contributed to the discovery and to the validation of original treatments. The purpose of the present work was to develop and validate an original model of acute myocardial infarction provoked in pig by thrombosis of the left anterior descending (LAD) coronary artery induced by topical application of ferric chloride solution. Methods and results Myocardial infarction, resulting from an occlusive and adherent mixed thrombus formed in the LAD coronary artery, was examined at macroscopic level using dual staining technique (Evans blue dye; triphenyltetrazolium chloride) and at microscopic level using conventional histological analyses and immunohistochemical detection of desmin. Biochemical markers (troponin T and ATP), platelet reactivity and standard hemodynamic parameters (such as stroke volume, ejection fraction, stroke work and cardiac output) have also been evaluated. From these analyses, it was demonstrated that each pig developed a transmural area of irreversible damage mainly located in the anteroseptal region of the left ventricle. The more progressive development of coronary artery occlusion, as compared to an abrupt ligation, was accompanied by a correspondingly progressive impairment in hemodynamics. Conclusion We conclude that this original porcine model of myocardial infarction is quite close to clinical pathophysiological conditions, such as thrombus formation occurring after atherosclerotic plaque rupture. This certainly constitutes a further argument in favour of this model to assess pharmaceutical or mechanical support of an acutely ischemic heart.

The purpose of this study was to compare the hemodynamic effects of pentobarbital and propofol and their effects on cardiovascular adaptation to an abrupt increase in left ventricular afterload. Experiments were performedin 12 open-chest pigs instrumented for measurement of aortic pressure and flow, and left ventricular pressure and volume. In one group (n = 6), anesthesia was obtained with sodium pentobarbital (3 mg . kg - 1 . h - 1 ), and, in the second group B (n = 6), with propofol (10 mg . kg - 1 . h - 1 ). Both groups received sufentanil (0.5 μg . kg 1 . h 1 ) and pancuronium bromide (0.1 mg . kg 1 ). Left ventricular function was assessed by the slope of end-systolic pressure-volume relationship and stroke work. After baseline recordings, left ventricular afterload was increased by aortic banding. The cardiovascular adaptations triggered by the aortic banding, such as tachycardia, vasoconstriction, and augmentation of myocardial contractility were prevented with propofol, suggesting interference with the baroreflex. Increase in left ventricular afterload decreased mechanical efficiency, regardless of anesthetic agent. These results showed that pentobarbital at 3 mg . kg - 1 . h - 1 has less deleterious hemodynamic effects than propofol at 10 mg . kg - 1 . h - 1 .

The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea], a dual thromboxane A2 synthase inhibitor and receptor antagonist, on the hemodynamic response to acute pulmonary embolism. Six anesthetized pigs were infused with placebo (placebo group) and compared with six other pigs receiving a continuous infusion of BM-573 (BM group). Pulmonary embolization with 0.3 g/kg autologous blood clots was carried out 30 min after the start of the infusion. Right ventricular pressure-volume loops were recorded using a conductance catheter, and end-systolic ventricular elastance was periodically assessed by varying right ventricular preload. Pulmonary vascular properties were studied by use of a four-element windkessel model. Hemodynamic data, including assessment of right ventricular-arterial coupling, were collected at baseline and every 30 min for 4 h. Blood samples were collected to assess gas exchange, thromboxane A2, and prostacyclin plasma levels and to evaluate platelet aggregation. Mean pulmonary arterial pressure in the placebo group increased significantly more than in the BM group, mainly because of an additional increase in pulmonary vascular resistance. Arterial and end-systolic ventricular elastances increased also more in the placebo group, whereas right ventricular efficiency decreased. BM-573 prevented both platelet aggregation induced by U-46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha) or by arachidonic acid, and thromboxane A2 overproduction, whereas prostacyclin liberation was preserved. Oxygenation, however, was not significantly improved. We conclude that in this animal model of acute pulmonary embolism, infusion of BM-573 reduced pulmonary vasoconstriction. As a result, right ventricular-vascular coupling values were maintained at a maximal efficiency level.