Peri-operative massive pulmonary embolism management: is veno-arterial ECMO a therapeutic option?

Pulmonary embolism remains an important clinical problem with a high mortality rate. The potential for sudden and fatal hemodynamic deterioration highlights the need for a prompt diagnosis and appropriate intervention. The purpose of the present case report is to describe a successful peri-operative veno-arterial extra corporeal membrane oxygenation (VA-ECMO) implantation for assumed massive pulmonary embolism associated with high hemodynamic instability and severe hypoxemia. A 52-year-old female victim of a motorcycle accident had been operated on for unstable fractures that required optimal repair. Despite subcutaneous administration of 40 mg enoxaparin on day 0 and day 1, the patient developed a massive pulmonary embolism leading to peri-operative pulseless activity. As intravenous thrombolysis was strictly contraindicated, a VA-ECMO was successfully implanted and permitted to stabilize the patient's hemodynamics. The hemodynamic and respiratory status improved by day 3, and the ECMO was removed. A vena cava filter was implanted before successful and definitive stabilization of the femoral fracture and the L2 fracture on days 4 and 5. The patient was able to be mobilized 2 days after the surgery and was transferred to a rehabilitation ward on day 15. At that time, her cognitive functions had fully recovered. ECMO can provide lifesaving hemodynamic and respiratory support in patients with massive pulmonary embolism who are too unstable to tolerate other interventions, who have failed other therapies or for whom other therapies are contraindicated.

["Mobile" ECMO]. / Extracorporeal membrane oxygenation "mobile".

ECMO (extracorporeal membrane oxygenation) is a cardiac or respiratory support which uses the principle of extracorporeal circulation (ECC). It consists of a pump generating an output as well as a membrane oxygenating blood and removing CO2. Thanks to an ECMO mobile team, expert caregivers can now perform the circulatory support in primary centers and then transfer patients under assistance to the referral center. After a brief summary of the two different anatomical approaches (veno-arterial and veno-venous) as well as their indications, the authors will share their experience of two transferred patients under ECMO to Geneva. Referral center and ECMO mobile team concepts will then be detailed focusing on the present situation in Switzerland.

Surfactant protein B and RAGE increases in the plasma during cardiopulmonary bypass: a pilot study.

Surfactant derived protein B (SPB) and plasma receptor for advanced glycation end products (RAGE) have been proposed as markers of lung injury. The former is produced specifically by pneumocytes while RAGE production is present in several body tissues. Cardiopulmonary bypass (CPB) generates a transient lung injury. We measured SPB and RAGE in plasma before surgery and after CPB, as well as 24 h and 48 h later. We analysed plasma samples from 20 subjects scheduled for elective coronary artery bypass grafting. We performed a quantitative analysis of plasma levels of RAGE and SPB mature form (8 kDa) by ELISA and a semi-quantitative analysis of SPB immature form (~ 40 kDa) by Western blotting. Surgery procedures were uneventful. After CPB RAGE median (75th-25th interquartile difference) increased from 633 (539) pg·mL⁻¹ to 1,362 (557) pg·mL⁻¹ (p < 0.01), while mature SPB increased from 5,587 (3,089) ng·mL⁻¹ to 20,307 (19,873) ng·mL⁻¹ (p < 0.01). RAGE and mature SPB returned to normal values within 48 h. This behaviour was confirmed when RAGE and SPB were normalised for protein content. Parallel changes were observed for immature SPB. Plasma RAGE and SPBs are sensitive and rapid markers of lung distress.

Prenylcysteine oxidase 1, an emerging player in atherosclerosis.

The research into the pathophysiology of atherosclerosis has considerably increased our understanding of the disease complexity, but still many questions remain unanswered, both mechanistically and pharmacologically. Here, we provided evidence that the pro-oxidant enzyme Prenylcysteine Oxidase 1 (PCYOX1), in the human atherosclerotic lesions, is both synthesized locally and transported within the subintimal space by proatherogenic lipoproteins accumulating in the arterial wall during atherogenesis. Further, Pcyox1 deficiency in Apoe-/- mice retards atheroprogression, is associated with decreased features of lesion vulnerability and lower levels of lipid peroxidation, reduces plasma lipid levels and inflammation. PCYOX1 silencing in vitro affects the cellular proteome by influencing multiple functions related to inflammation, oxidative stress, and platelet adhesion. Collectively, these findings identify the pro-oxidant enzyme PCYOX1 as an emerging player in atherogenesis and, therefore, understanding the biology and mechanisms of all functions of this unique enzyme is likely to provide additional therapeutic opportunities in addressing atherosclerosis.

Video recording of cardiac surgical procedures: what the surgeon needs to know.

In the past, rudimentary devices were used to record surgical operations. Currently, the introduction of technologic advances such as high-definition television and the miniaturization of high-resolution digital video cameras provides an opportunity for making significantly enhanced surgical records. These enhancements, coupled with the recent advances in telemedicine and surgical simulation, will improve cardiac surgery training and skill acquisition, decrease operative times and costs, minimize morbidity, and improve overall patient care. The present paper provides a discussion of the media technology offered to surgeons for recording a surgical procedure on video. Hardware technology, including different types of cameras and analogical or digital post processing methods, are reviewed with a surgical ''eye''. This ''how to'' paper provides practical suggestions to surgeons in order to enhance surgical video recording.

Tissue factor induction by protease-activated receptor 1 requires intact caveolin-enriched membrane microdomains in human endothelial cells.

BACKGROUND: Protease-activated receptors (PARs) comprise a family of G-protein-coupled receptors with a unique mechanism of proteolytic activation. PARs regulate a broad range of cellular functions and are active in the pathogenesis of disorders characterized by chronic inflammation or activation of the coagulation cascade. Signaling through PAR1 and PAR2 shifts the endothelium towards a prothrombotic phenotype, thereby exacerbating the initial pathophysiologic condition. OBJECTIVES: This study aimed to analyze the localization of PARs in the cell membrane and how their compartmentalization affects tissue factor (TF) in human endothelial cells. METHODS: TF expression was determined by quantitative real-time polymerase chain reaction analysis and by activity assays. The interaction of PARs with caveolin was investigated through: (i) caveolin-1 gene knockdown performed by transfection with specific small interfering RNA (siRNA); (ii) caveolin-enriched membrane microdomain disruption; and (iii) coimmunoprecipitation assay. RESULTS: We have shown that PAR1, but not PAR2, is present in endothelial caveolin-enriched membrane microdomains, where it is bound to caveolin-1, and that these structures must be intact if PAR1-induced signaling is to increase TF activity. Cholesterol depletion of endothelial cells by cholesterol-sequestering agents caused the PAR1 to relocate to high-density membranes, and impaired the induction of TF (P < 0.01) without affecting the PAR2-mediated procoagulant effect. In addition, siRNA directed against caveolin-1 inhibited TF activation by PAR1 (P < 0.01 and P < 0.01, respectively). CONCLUSIONS: PAR1 localization in the caveolin-enriched membrane microdomain, bound to caveolin-1, represents a crucial requirement for TF induction in endothelial cells.

Lipomatous hypertrophy of the interatrial septum. Description of a clinical case and literature review.

UNLABELLED: Lipomatous hypertrophy of the interatrial septum is a rare benign cardiac disorder characterised by the accumulation of adipose tissue; data from several post mortem surveys report how the disorder represents 0.6% of all benign cardiac tumours. Generally asymptomatic, it frequently constitutes an incidental post mortem finding. The disorder may at times lead to a pumping deficit associated to congestive heart failure or determine an abnormal heart rhythm leading even to sudden death. Lipomatous hypertrophy can at times lead to problems in differential diagnosis of the disorder from other tumours or heart diseases. Surgical removal produces excellent short and long-term RESULTS: We describe a case of lipomatous hypertrophy of the interatrial septum associated to coronary disease diagnosed by means of transesophageal echocardiography. The diagnostic and treatment techniques applied are discussed and a literature review is done.

Ross procedure is a safe treatment option for aortic valve endocarditis: Long-term follow-up of 42 patients.

BACKGROUND: Aortic root replacement with a pulmonary autograft (Ross procedure) can be performed as a treatment of aortic valve endocarditis, avoiding prosthetic valve implantation in septic context. We sought to assess long-term outcomes of the Ross procedure in this indication. METHODS: From April 1992 to March 2009, the intervention was performed in 42 patients (mean age 34 ± 8 years) suffering from an active or ancient aortic valve endocarditis. 36% of the patients had extensive perivalvular involvement, and surgery was urgent in 18 patients (43%). We performed a prospective clinical and echocardiographic follow-up of this population. RESULTS: Median follow-up was 10 years (4-21 years). Overall survival at 10 and 15 years was respectively 87 ± 5% and 81 ± 8%. Perioperative mortality was 4.7% (2 patients) and no late cardiac death was reported. Eight patients (19%) underwent repeat surgery for autograft and/or homograft dysfunction at a median time of 8.4 years (3 months-18 years). Rate of recurrent endocarditis was low (7%-3 patients), including 1 in a context of persistent intravenous drug abuse. Clinical follow-up showed good functional status for all patients with NYHA ≤ II, and less than 25% of patients requiring cardiovascular medication. Late echocardiographic follow-up demonstrated well-functioning autograft and homograft, with only one severe aortic regurgitation, and one significant increase in pulmonary mean gradient. CONCLUSION: The Ross procedure in aortic valve endocarditis is an interesting alternative to prosthetic valvular replacement in a selected population, with a high rate of survival free from any cardiovascular event or medication requirement.

Apolipoprotein A-II modulates HDL remodeling in plasma.

Native and reduced-carboxamidomethylated (RCM) HDL3 are incubated with a lipoprotein-depleted plasma fraction in the presence of triacylglycerol-rich particles isolated from Intralipid. Unmodified HDL3 are mainly converted into large HDL2b particles (diameter: 9.84 +/- 0.15 nm); RCM-HDL3 are transformed into both large HDL2b (9.76 +/- 0.10 nm) and small HDL3c (7.68 +/- 0.07 nm). These findings indicate that the apo A-II dimers participate in the remodeling of HDL, by inhibiting the formation of small HDL particles.

Transcriptional regulation of plasminogen activator inhibitor type 1 gene by insulin: insights into the signaling pathway.

Impairment of the fibrinolytic system, caused primarily by increases in the plasma levels of plasminogen activator inhibitor (PAI) type 1, are frequently found in diabetes and the insulin-resistance syndrome. Among the factors responsible for the increases of PAI-1, insulin has recently attracted attention. In this study, we analyzed the effects of insulin on PAI-1 biosynthesis in HepG2 cells, paying particular attention to the signaling network evoked by this hormone. Experiments performed in CHO cells overexpressing the insulin receptor indicate that insulin increases PAI-1 gene transcription through interaction with its receptor. By using inhibitors of the different signaling pathways evoked by insulin-receptor binding, it has been shown that the biosynthesis of PAI-1 is due to phosphatidylinositol (PI) 3-kinase activation, followed by protein kinase C and ultimately by mitogen-activated protein (MAP) kinase activation and extracellular signal-regulated kinase 2 phosphorylation. We also showed that this pathway is Ras-independent. Transfection of HepG2 cells with several truncations of the PAI-1 promoter coupled to a CAT gene allowed us to recognize two major response elements located in the regions between -804 and -708 and between -211 and -54. Electrophoretic mobility shift assay identified three binding sites for insulin-induced factors, all colocalized with putative Sp1 binding sites. Using supershifting antibodies, the binding of Sp1 could only be confirmed at the binding site located just upstream from the transcription start site of the PAI-1 promoter. A construct comprising four tandem repeat copies of the -93/-62 region of the PAI-1 promoter linked to CAT was transcriptionally activated in HepG2 cells by insulin. These results outline the central role of MAP kinase activation in the regulation of PAI-1 induced by insulin.

Data for proteomic analysis of Human monocyte-derived macrophages.

This data article is referred to the research article entitled Human monocyte-derived macrophages are heterogeneous: proteomic profile of different phenotypes by Eligini et al. Eligini S., Brioschi M., Fiorelli S., Tremoli E., Banfi C., Colli S. Human monocyte-derived macrophages are heterogeneous: proteomic profile of different phenotypes. J. Proteomics 124, 2015, 112-123. Macrophages obtained in vitro from blood monocytes are largely used as surrogate model of tissue macrophages that are heterogeneous and not easy to obtain and handle. Under spontaneous differentiation in vitro, monocyte-derived macrophages (MDMs) display two dominant subsets (round and spindle) that show different transcriptional, antigenic, and functional profiles mimicking, at least in part, the heterogeneity of tissue macrophages. This article reports the nano-LC-MS(E) analysis of the proteome of round and spindle MDMs allowing a deeper comprehension of macrophage heterogeneity.

Human monocyte-derived macrophages are heterogenous: Proteomic profile of different phenotypes.

Tissue macrophages play a key role in many aspects of human physiology and pathology. These cells are heterogeneous both in term of morphology and function. As an example, heterogeneity has been reported within the atherosclerotic lesions where distinct populations exert opposite functions driving plaque progression or stability. Tissue macrophages are not easily obtained and differentiated blood-derived monocytes are largely used as surrogate model. We previously reported that human macrophages spontaneously differentiated from adherent monocytes show two dominant subsets, distinct for morphology (spindle and round) and functions. The aim of this study was to evaluate the intracellular proteome of these two macrophage subsets by means of a microproteomic workflow properly set up to simultaneously identify and quantify proteins from a minimal number of morphotypically heterogeneous cells in culture. We report two distinct proteomic profiles that distinguish round from spindle macrophages. In particular, differential abundances were observed for proteins involved in membrane traffic regulation, lipid handling, efferocytosis, and protection against stress conditions. Results reinforce and extend previous data on the functional and antigenic profile of these macrophage phenotypes strengthening the suitability of our model to focus on macrophage heterogeneity. BIOLOGICAL SIGNIFICANCE: Tissue macrophages patrol homeostatic functions, immune surveillance, and resolution of inflammation. The spectrum of macrophage activation states is, therefore, wide and gives ground for the heterogeneity of these cells, documented in health and disease. This study provides knowledge of the distinct proteome that characterises the two dominant morphotypes (round and spindle) of human macrophages that, in our culture condition, are generated by spontaneous differentiation from blood-derived monocytes. Results extend previous data about the different antigenic, transcriptional, and functional profiles of these morphotypes and further strengthen the suitability of this in vitro model to study macrophage heterogeneity and to address the effects of environmental challenges and drugs.

ECMO as a bridge to decision: Recovery, VAD, or heart transplantation?

BACKGROUND: Our 8-year experience with ECMO support as a bridge to decision was reviewed. METHODS: A cohort of 124 consecutive patients received ECMO for refractory cardiogenic shock in our institution. Twenty-six of these were out of hospital cardiac arrests and were excluded from this analysis. The median age was 43 years, in the range of 11 to 73 years. RESULTS: The median duration of ECMO support was 4.5 days. Mortality while supported by ECMO was 50% with a median support time of 2 days. Weaning from ECMO was achieved for 49 patients with the following outcomes: cardiac recovery (60%), heart transplantation (26%), and VAD implantation (14%). Median duration of support before weaning was 8 days. Hospital survival was 83%, 61.5% and 71% for cardiac recovery, heart transplantation and VAD implantation, respectively. ECMO weaning was significantly improved in all patients who had normalized their renal function, and when duration of support>6 days (HR: 4.255 [1.255-14.493], p=0.02 and HR: 2.164 [1.152-4.082], p=0.02, respectively). A creatinine level>14 mg/l the day of weaning was a significant predictor of death (HR: 5.807 [1.089-30.953]; p=0.04). Median follow up was 2.4 years; one-year survival rate was 78%, 51% and 75% for cardiac recovery, heart transplantation and VAD implantation, respectively. CONCLUSION: With at least 6 days of support, ECMO allowed a better patient selection for myocardial recovery, VAD implantation or heart transplantation. Whether VAD implantation or heart transplant in those patients is a better indication remains to be evaluated.

Fluvastatin inhibits basal and stimulated plasminogen activator inhibitor 1, but induces tissue type plasminogen activator in cultured human endothelial cells.

The effects of fluvastatin, a synthetic hydroxymethylglutaryl coenzyme A (HMG-CoA) inhibitor, on the biosynthesis of tissue plasminogen activator (t-PA) and of its major physiological inhibitor (plasminogen activator inhibitor type 1, PAI-1) were investigated in cultured human umbilical vein endothelial cells (HUVEC). Fluvastatin (0.1 to 2.5 microM), concentration-dependently reduced the release of PAI-1 antigen by unstimulated HUVEC, subsequent to a reduction in PAI-1 steady-state mRNA levels and de novo protein synthesis. In contrast, it increased t-PA secretion. The drug also reduced PAI-1 antigen secreted in response to 10 microg/ml bacterial lipopolysaccharide (LPS), 100 U/ml tumour necrosis factor alpha (TNFalpha) or 0.1 microM phorbol myristate acetate (PMA). Mevalonate (100 microM), a precursor of isoprenoids, added to cells simultaneously with fluvastatin, suppressed the effect of the drug on PAI-1 both in unstimulated and stimulated cells as well as on t-PA antigen. Among intermediates of the isoprenoid pathway, all-transgeranylgeraniol (5 microM) but not farnesol (10 microM) prevented the effect of 2.5 microM fluvastatin on PAI-1 antigen, which suggests that the former intermediate of the isoprenoid synthesis is responsible for the observed effects.

15-deoxy-delta12,14-Prostaglandin J2 inhibits tissue factor expression in human macrophages and endothelial cells: evidence for ERK1/2 signaling pathway blockade.

Basic and clinical evidence has provided insight into the molecular events that link inflammation and coagulation. Increased expression of tissue factor (TF) by circulating and vascular cells has been indicated as responsible for the thrombotic complications associated with acute and chronic inflammation. TF is indeed inducible in circulating and vascular cells by cytokines and bacterial lipopolysaccharide (LPS) and its expression triggers the coagulation. The cyclopentenone prostaglandins are naturally occurring prostaglandin D2 (PGD2) derivatives that comprises prostaglandin J2 (PGJ2) and its metabolites delta12-PGJ2 and 15-deoxy- delta12,14-prostaglandin J2 (15d-PGJ2). These compounds, detected in vivo in a later phase of the inflammatory response, are characterized by anti-inflammatory activity and participate to the resolution of inflammation. We have here investigated the effect of 15d-PGJ2 on TF expression in human macrophages and endothelial cells (HUVEC). Our results indicate that 15d-PGJ2 down-regulates LPS- and TNFalpha-induced TF activity, protein and mRNA through inhibition of TF gene transcription. The effect of 15d-PGJ2 is targeted to the NF-kappaB/I-kappaB pathway and to the mitogen activated protein kinase ERK1/2. A role of PPAR-gamma activation in TF inhibition by 15d-PGJ2 was excluded. We conclude that 15d-PGJ2 negatively affects TF expression in macrophages and endothelial cells through a PPARgamma-independent mechanism. This down-regulation may be crucial to limit excessive blood clotting activation in immuno-inflammatory diseases.

Oxidized LDLs influence thrombotic response and cyclooxygenase 2.

Oxidative modification of low-density lipoproteins (LDLs) plays a key role in the development of atherosclerosis and the onset of coronary artery disease. LDL oxidation alters the antithrombotic balance of human endothelial cells inducing surface tissue factor (TF) pathway activity, which results in enhanced fibrin deposition. Fibrinolysis, which is strictly regulated by plasminogen activator inhibitor-1 (PAL-1) and tissue-type plasminogen activator (tPA). Is also dysregulated by LDL oxidation with a net increase in the inhibitory rate. Oxidized LDLs (oxLDLs) also affect many aspects of macrophage function linked to the inflammatory response of these cells, In particular, oxLDLs downregulate inducible cyclooxigenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide. This observation may support the hypothesis that, within atheromata, the transformation macrophages into foam cells results in the attenuation of the inflammatory response, thus contributing to the progression of athrogenesis. Among lipid constituents of oxLDLs, Ox-PAPC, a mixture of oxidized arachidonic acid-containing phospholipids, prevents Cox-2 expression, suggesting that it could be considered responsible for the biological activity of oxLDLs.

Expandable prosthesis for sutureless anastomosis in thoracic aorta prosthetic substitution.

OBJECTIVE: Most complications of descending aorta prosthetic substitution seem mainly to be related directly (ischemia to distal organs, i.e. liver, kidney, spinal cord) or indirectly (extracorporeal circulation or shunts and systemic heparinization complications) to the duration of blood flow interruption. the purpose of this study is to report the results of animal experimentation of a new device for sutureless prosthetic substitution of the descending thoracic aorta, with a very short cross-clamping phase. METHODS: The device consists of expandable loops of stainless steel wires, sewn to the proximal end of a Dacron prosthesis. The stainless steel wire loops can be expanded and tightened by activating a removable guide in such a way that the prosthesis varies its diameter, while maintaining a regular cylindrical shape. The device was prepared in two different configurations, one for long segments (expandable prosthesis end) and the other to be used for very short segments or as an anastomotic ring between prosthetic or vascular stumps (quick anastomotic ring). The expandable prosthesis end was tested in swine experiments by performing the prosthetic substitution of the first 10 cm of descending cross-clamped aorta, the prosthesis being fixed with the device both at the proximal and the distal ends (six experiments). All animals survived the procedure, that was accomplished with a very short cross-clamping time. The quick anastomotic ring was used to anastomose two prosthesis ends, at the middle of the prosthetic segment used for descending aorta substitution (two swine), to perform the distal anastomosis in the same model of descending aorta substitution (one swine) and simply to re-anastomose a subtotally transected descending aorta (one swine). RESULTS: The present experience proved the reliability of the device to carry out a sutureless, accurate, simple and quick anastomosis. Its advantage over an intraluminal ringed prosthesis is much easier insertion of the retracted wired end into the vascular stumps, thus allowing for a prosthetic diameter appropriate to the substituted vessel. CONCLUSIONS: The reduced cross-clamping feature of the device would suggest its use mainly in thoracic aorta prosthetic substitution for the prevention of ischemic damage to distal organs; it can also be used to advantage wherever an end-to-end vascular or prosthetic anastomosis is indicated, providing an accurate, stented anastomosis.

Aortic wall structural strengthening by intraluminal net prosthesis to arrest aneurysm progression and to prevent dissection and rupture.

The major limitation implicit in the endovascular procedures for aortic prosthetic substitution is that they cannot be used in those tracts of the aorta where important collateral branches originate (aortic arch, thoraco-abdominal tract, upper abdominal), that would be occluded by the prosthesis. In order to overcome this limitation we hypothesized the endovascular positioning of a prosthesis in the form of a wide mesh network that would be gradually and spontaneously covered by new intima and included in the aortic wall. The fabric framework linked to the aortic wall would then condition its significant, regular and uniform mechanical strengthening that fractionates and partially absorbs the centrifuge pulsatile stress of the bloodstream. The purpose of this paper is to report the results of the insertion of a braided Prolene net prosthesis in the first 7 cm of the descending aorta of ten swine. The animals were killed after 6 weeks, the substituted segment removed and aortic wall compliance measured under standardized conditions. The prosthesis was found entirely covered by new intima, well embodied in the aortic wall. The intercostal collateral included in the substituted segment was patent, as proved by bubble formation during underwater insufflation. Compliance of the prosthesis segment was significantly lower than that of the adjacent descending aorta. Histology showed a regular net prosthesis inclusion deep in the neo-intima layer. Present results indicate the technical feasibility of the procedure, achieving significant aortic wall strengthening without affecting the collateral (intercostal) circulation.

Results with the Novacor assist system and evaluation of long-term assistance.

OBJECTIVE: The great number of patients awaiting heart transplant and the shortage of donors has led to the increasing use of left ventricular assist devices (LVAD) for those patients that cannot wait only on medical therapy. In this study we analyze our experience in order to evaluate the possibility of long-term assistance. METHODS: We have implanted LVAD Novacor in 36 patients with a mean age of 50.4 years. They were all critical candidates for transplant on high doses of inotrops. We evaluated the clinical and hemodynamic results and studied statistically the relative risk of complications at different time intervals of support. RESULTS: In all cases we had a statistically significant improvement of: cardiac output, wedge pressure, pulmonary vascular resistance and mean pulmonary pressure. Eleven patients died on the device, 23 underwent heart transplant and two are still on the device. Causes of death were mostly related to cerebrovascular events or multiorgan failure. Seven of the 23 patients who underwent heart transplant died with a survival rate after transplant of 69.5% and an overall survival rate of 50%. Complications occurred in 33 patients with: 24 strokes, eight TIAs, four cerebral hemorrhages, three peripheral embolisms, seven cable infections, two pocket infections, two sepsis, two major lung infections, one mediastinitis, one right ventricular failure and three multiorgan failure. Time-related analysis showed that these complications occurred mostly during the first 3 months of assistance and this is particularly true for cerebrovascular events. The incidence of infections remained constant during the follow-up period. With a mean time of assistance of 203.1 days we had only two cases of device malfunction at 662 and 1297 days. CONCLUSIONS: LVAD Novacor has provided reliable mechanical performance and good hemodynamic improvement. Most complications seem to occur in the first 90 days, therefore long-term assistance could be considered. A reduction of the high rate of thromboembolic complications remains mandatory to improve the clinical results.

[PAI-1, the primary plasmatic inhibitor of fibrinolysis. Physiopathologic role and molecular mechanisms]. / PAI-1, il principale inibitore plasmatico della fibrinolisi. Ruolo fisiopatologico e meccanismi molecolari.

Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in blood. PAI-1 is known to contribute to thrombus formation and to the development and the clinical course of acute and chronic cardiovascular diseases. Plasma levels of PAI-1 are regulated on a genetic basis but, more important, is the dependence on a series of other atherosclerotic risk factors like hypertriglyceridemia, diabetes and insulin resistance. The insulin resistance syndrome, which is characterized partly by obesity with visceral fat accumulation, is considered as a major regulator of PAI-1 expression. At least in vitro, insulin is a potent inducer of PAI-1 synthesis by human hepatic cells, and, we have recently disentangled the molecular mechanisms responsible for enhanced PAI-1 gene expression by insulin. However, clinical data fail to support a direct acute contribution of insulin in regulating circulating PAI-1 levels. Recently, it has been proposed that adipose tissue could be responsible for the elevated plasma PAI-1 level observed in insulin resistance. It now seems reasonable to view PAI-1 as one of the factors contributing to the complex gene-environment interactions involved in the formation and dissolution of thrombi.