Clot Embolization Research Articles

Continuous Monitoring of Changes in Plasma Nitrite Following Cerebral Ischemia in a Rabbit Embolic Stroke Model

In this proof-of-concept study, we investigated direct, continuous monitoring of plasma nitrite as an indicator of cerebral ischemia following clot embolization of rabbits via an indwelling carotid catheter. Two groups of rabbits were studied to compare the effects of embolization on nitrite levels. In the control group, blood was continuously obtained from a jugular venous catheter. The blood was immediately passed through an ultrafiltration filter; the filtrate was chemically reduced to convert free nitrite to nitric oxide (NO) and then measured using a NO-specific electrode. In the embolized group, after a baseline nitrite level was achieved, blood clots were injected into the brain via the carotid artery catheter, and then nitrite levels were continuously measured from jugular venous blood. The stroke group showed a significantly greater increase in nitrite as compared to controls (p=0.017). Using the area-under-the-curve (AUC) method, results reached statistical significance (p<0.05) within 3 min of embolization. In embolized rabbits, NO(2) levels increased 424±256% compared to baseline. This study shows that nitrite can be measured immediately following a stroke and that our system measures nitrite independent of the extent of the stroke. This study provides evidence for the feasibility of using nitrite as a marker of ischemic stroke.

Three cases of stroke following peripheral venous interventions

We report three cases of stroke in association with peripheral venous interventions that each included foam ultrasound-guided sclerotherapy (UGS). All three female patients experienced a right middle cerebral artery (MCA) stroke causing dysphasia and left hemiparesis. A patent foramen ovale was found in each patient. The first incident occurred two days after foam UGS to treat small tributaries of a great saphenous vein (GSV). Paradoxical clot embolism was presumed in this case where concurrent deep vein thrombosis with non-occlusive thrombus in a medial gastrocnemius vein extending to the popliteal vein was detected on ultrasound. The second case occurred immediately at the completion of foam UGS and ambulatory phlebectomy to treat GSV tributaries. Paradoxical gas embolism was demonstrated in this patient confirmed by visualization of bubbles in the right MCA on CT angiography. The third case occurred one day after endovenous laser ablation (1470 nm) and foam UGS to treat both great and small saphenous veins. No specific cause could be confirmed in this patient. Sodium tetradecyl sulphate foam was used in all three cases (3%, 16 mL; 1.5%, 4 mL and 3%, 25 mL, respectively). All three patients recovered completely within a few days.

Abstract No. 321: Posttraumatic high-flow priapism in pediatric patients treated with autologous blood clot embolization: Long-term results

Abstract No. 321: Posttraumatic high-flow priapism in pediatric patients treated with autologous blood clot embolization: Long-term results

Transcranial duplex sonography for monitoring circle of Willis artery occlusion in a rat embolic stroke model

BackgroundHemodynamic monitoring of circle of Willis arteries during clot embolization in experimental embolic stroke models (ES) is of major importance to assess their reproducibility and to test new recanalization strategies. We sought to assess the potential of transcranial duplex sonography (TDS) in comparison with laser Doppler flowmetry (LDF) to monitor the time of recanalization after occlusion of the right distal intracranial internal carotid artery (rICA) and to predict infarct volume at 24h after ischemia. MethodsTwenty nine male Sprague–Dawley rats were submitted to ES. Right and left ICA, posterior cerebral arteries, and basilar trunk (BT) were monitored by TDS and regional cerebral blood flow was monitored by LDF at baseline, 1, 4 and 24h after the ES onset. Infarct volume was measured at 24h after stroke. ResultsAmong the 25 rats, 3 died during surgery, 5 did not show any significant brain infarct (failure of the stroke model) and absence of occlusion of the rICA was detected in all 5 rats by TDS at 1h whereas only 4 of 5 were detected by LDF. Among the remaining 17 rats, the recanalization time of the occluded rICA assessed by TDS correlated with the infarct volume at 24h, r=0.70, P=0.0013 by contrast to results with LDF, r=0.11, P=0.55. ConclusionAlthough both TDS and LDF can be used for in vivo assessment of occlusion in a rat ES model, TDS was more reliable as it allowed more accurate monitoring of arterial recanalization, and prediction of infarct volume.

Are Underlying Assumptions of Current Animal Models of Human Stroke Correct: from STAIRs to High Hurdles?

Animal models of acute ischemic stroke have been criticized for failing to translate to human stroke. Nevertheless, animal models are necessary to improve our understanding of stroke pathophysiology and to guide the development of new stroke therapies. The rabbit embolic clot model is one animal model that has led to an effective therapy in human acute ischemic stroke, namely tissue plasminogen activator (tPA). We propose that potential compounds that demonstrate efficacy in non-rabbit animal models of acute ischemic stroke should also be tested in the rabbit embolic blood clot model and, where appropriate, compared to tPA prior to investigation in humans. Furthermore, the use of anesthesia needs to be considered as a major confounder in animal models of acute ischemic stroke, and death should be included as an outcome measure in animal stroke studies. These steps, along with the current STAIRs recommendations, may improve the successful translation of experimental therapies to clinical stroke treatments.

In vivo efficacy of platelet-delivered, high specific activity factor VIII variants

AbstractEctopically expressed, human B-domainless (hB) factor 8 (F8) in platelets improves hemostasis in hemophilia A mice in several injury models. However, in both a cuticular bleeding model and a cremaster laser arteriole/venule injury model, there were limitations to platelet-derived (p) hBF8 efficacy, including increased clot embolization. We now address whether variants of F8 with enhanced activity, inactivation resistant F8 (IR8) and canine (c) BF8, would improve clotting efficacy. In both transgenic and lentiviral murine model approaches, pIR8 expressed at comparable levels to phBF8, but pcBF8 expressed at only approximately 30%. Both variants were more effective than hBF8 in cuticular bleeding and FeCl3 carotid artery models. However, in the cremaster injury model, only pcBF8 was more effective, markedly decreasing clot embolization. Because inhibitors of F8 are stored in platelet granules and IR8 is not protected by binding to von Willebrand factor, we also tested whether pIR8 was effective in the face of inhibitors and found that pIR8 is protected from the inhibitors. In summary, pF8 variants with high specific activity are more effective in controlling bleeding, but this improved efficacy was inconsistent between bleeding models, perhaps reflecting the underlying mechanism(s) for the increased specific activity of the studied F8 variants.

Posttraumatic high-flow priapism in children treated with autologous blood clot embolization: long-term results and review of the literature

Usually high-flow priapism is caused by perineal or penile blunt trauma with direct cavernosal artery injury and formation of an arterial-lacunar fistula. Rarely, cavernosal artery injury may result from penetrating trauma. Treatment of high-flow priapism is not considered an emergency because patients are at low risk for permanent complications. For this type of priapism there are several options for treatment including embolization or surgical ligation. To describe the technique of superselective transcatheter embolization with the use of autologous blood clot and to discuss the long-term results. Seven children with a mean age of 10 years suffering from high-flow priapism were treated with superselective transcatheter embolization with autologous blood clot. In all cases, colour Doppler US was performed to demonstrate increased cavernous blood flow with definitive diagnosis established by superselective arteriography. After the angiographic diagnosis, superselective transcatheter embolization of the fistula with autologous blood clot was performed during the same session. The children were followed up on a monthly basis up to 1 year with clinical findings and penile colour Doppler US examinations. After 1 year, they were followed up annually with clinical assessment only. The mean follow-up period was 6.0 years. Following embolization complete detumescence was achieved in all but one child, who was treated with a second embolization 3 d after the initial session. In addition, for one child a second session of embolization was performed due to the recurrence of partial erection during the 1 week period after the initital embolization. In both cases, complete detumescence was achieved after the second embolization, and no recurrence of priapism was observed in the follow-up period. Selective arterial embolization with autologous clot achieved treatment for high-flow priapism in this study with 100% occlusion rate with a maximum of two sessions and no signs of erectile dysfunction were observed in any of the children during long-term follow-up.

Anesthetic management of children with in situ Berlin Heart EXCOR™

Modern mechanical devices can support children with severely impaired cardiac function until a donor heart is found for transplantation or native function recovers. Pediatric heart transplantation offers a good chance of survival with a high quality of life to individuals with limited life expectancy and/or severe limitation to daily activities, but many die on the transplant list or are not listed because of a shortage of donor organs. In recent cohorts, there is better outcome when ventricular assist devices (VADs) rather than extracorporeal membrane oxygenation are used as a 'bridge' to transplantation. Anesthesiologists working in centers where VADs are available may increasingly be asked to provide anesthesia to children with such devices in situ, including procedures outside the cardiac surgical operating room. The Berlin Heart EXCOR device is a VAD system with increasing popularity in pediatric practice and has system components available in sizes suitable even for neonates. Postimplantation considerations include hemodynamics, thromboembolic complications and their prevention by anticoagulation, antimicrobial therapy, and the rehabilitation and mobilization of recipients. VAD-specific emergencies must be recognized and managed appropriately by anesthesiologists looking after Berlin Heart recipients. These include malignant dysrhythmias, sudden loss of VAD output, air or clot embolism, and sudden cyanosis. Provision of anesthesia for patients with an in situ Berlin Heart requires attention to particular considerations in preoperative assessment, induction, maintenance, and postoperative care.

Dots are not clots: the over-diagnosis and over-treatment of PE

The purpose of this work is to question the conventional theory that all pulmonary emboli (PE) are abnormal, and to test the hypothesis that small peripheral PE are a function of life. Most radiologists report any filling defect, independent of size, as clinically significant PE when detected in the pulmonary arteries. We sought to reinforce the theory that small dots in the pulmonary arteries are not clinically significant clots in the conventional setting. The necessity for anticoagulation should be balanced against the risk of bleeding. This retrospective HIPAA-compliant study was approved by the institutional review board; informed consent was not required. All patients diagnosed with PE by 16-slice or 64-slice multidetector computed tomography (CT) over a 6-month period who also had a lower extremity venous ultrasound (US) performed within 7 days of CT were identified. The study group included 26 women and 24 men (mean, 56 years; range, 21-90 years). The locations of the PE were plotted on a pulmonary arterial diagram, and width of the most proximal clot for each patient was measured. Of 1,273 consecutive CT studies, 101 were positive (7.9%) and 50 patients underwent lower extremity US. Thirty-three (66%) patients had PE in the central pulmonary arteries, of which 19 (58%) had deep vein thrombosis (DVT). Seventeen (34%) patients had peripheral PE; DVT was detected in 0 (0%) patients. The peripheral clots measured 1.0-3.8 mm (mean, 2.5 mm). These clots appeared focal and rounded with a "dot-like" appearance. Peripheral, focal filling defects in the pulmonary arteries, which we termed "dots," are not traditional embolic clots, are not associated with detectable lower-extremity clot load, and may represent "normal" embolic activity originating from the lower extremity venous valves. We suggest that more in-depth understanding about small peripheral PE is needed. The necessity of conventional anticoagulation should be critically reviewed in patients with subsegmental PE and minimal clot burden.

Strategies to Enhance the Efficacy of Platelet-Derived Factor (F) VIII: Studies with Inactivation Resistant FVIII (IR8) and Canine FVIII in Hemophilia A Mice.

Abstract 3496Poster Board III-433Hemophilia A is the most common, inherited severe bleeding diathesis and is due to deficient FVIII. We and others have shown that targeted delivery of ectopic human B-domainless (hBD) FVIII from within platelet α-granules is effective at improving clotting in several injury models using FVIIInull mice. Importantly, platelet-derived (p) hBDFVIII is ∼100-fold more effective than comparable levels of plasma hFVIII against circulating inhibitors, a significant problem in the hemophilia A population. However, we have also shown in both a cuticular injury model and an in situ cremaster laser arteriole/venule injury model that there are certain limitations to pFVIII therapy, especially concerns of clot stability and risks of clot embolization. In the present study, we examined the efficacy of platelet-delivered inactivation resistant FVIII (IR8), resistant to inactivation by thrombin and activated protein C, and canine (c) BDFVIII, a species of FVIII that has 3-5-fold greater specific activity than hBDFVIII. Both FVIIIs were expressed in platelets using both a transgenic mouse approach and lentiviral gene therapy, and compared to similarly expressed phBDFVIII mice. Multiple founder lines of mice were generated for pIR8 and pcBDFVIII using the platelet-specific glycoprotein Ibα proximal promoter to drive platelet-specific expression. Lentiviral studies involved transducing FVIIInull murine hematopoietic cells with an HIV-1 based self-inactivating lentivirus encoding the previously mentioned FVIIIs driven by either a ubiquitin promoter or by the platelet-specific platelet factor 4 (PF4) proximal promoter; lethally irradiated FVIIInull mice were rescued by injection of virally transduced bone marrow. FVIII antigenic levels in both platelet lysates and releasates were measured, and free, plasma FVIII levels were detected by a FVIII ELISA. Maximum pIR8 levels achieved were comparable to those seen with hBDFVIII in spite of the fact that IR8 binds poorly to von Willebrand factor (vWF), supporting prior observations that pFVIII is stored in α-granules independent of the presence of vWF in α-granules. Surprisingly, maximal pcBDFVIII levels were 1/3rd of those of phBDFVIII. The basis for this observation is presently being determined. The ability of the pFVIII to correct hemophilia A in vivo was tested by a FeCl3 carotid artery injury model and a cuticular bleeding model. In addition, laser injury studies to cremaster arterioles and venules are on-going. FeCl3 carotid artery and cuticular studies demonstrated that both pIR8 and pcBDFVIII were more potent than phBDFVIII in improving outcome in FVIIInull mice. For pcBDFVIII, this occurred despite the low levels of pcBDFVIII. In the cremaster laser injury model, lentiviral-based gene therapy using the three FVIII variants, markedly improved clot formation compared to FVIIInull mice, but further studies are needed to define whether a specific FVIII variant is particularly efficacious. Prior studies of plasma IR8 correction using an adenoviral delivery system showed no improved outcome relative to hBDFVIII. We propose that this difference for IR8 between plasma and platelet expression is due to IR8 binding vWF poorly and that vWF binding is important for maintaining plasma FVIII levels. The higher specific activity of pcBDFVIII appears to more than compensate for its lower level in circulating platelets. We now intend to define the molecular basis for the greater efficacy of pIR8 and pcBDFVIII compared to phBDFVIII and to use these insights to further optimize the efficacy and safety of this delivery strategy in the care of patients with hemophilia A. Disclosures:Poncz:Diagnostica Stago: Patents & Royalties.

A multifaceted approach to intracoronary thrombus: Use of pharmacology, an aspiration catheter and an embolic protection device

A 50-year-old smoker sustained an acute coronary syndrome. A culprit lesion (Figure 1A) with a column of attached thrombus (Figure 1B) was demonstrated at angiography. Figure 1) Several pharmacological and mechanical options were considered (1). An inappropriately long stent would be required to ‘direct stent’ the lesion and to ‘trap the thrombus’ behind the stent struts. Use of a proximal protection device (Proxis, St Jude Medical, USA) to arrest coronary flow, aspirate the thrombus and deploy a shorter stent was also considered (2). The favoured approach was to deploy a distal embolic protection device below the thrombus (Spider EX, ev3 Inc, USA). The device was passed across the lesion on a guidewire, and the sheath encasing the device was withdrawn to allow the basket or ‘windsock’ to open (Figure 1C). Despite ballooning the lesion (Figure 1D), a globular filling defect remained (Figure 1E). An aspiration catheter (Pronto, Vascular Solutions, USA), primed by negative pressure, was used to extract the clot (Figure 1F) (3). The lesion was stented and the basket resheathed and withdrawn. The contents of the aspiration catheter syringe revealed a column of thrombus and debris (Figure 1E). Irrigation of the basket demonstrated further embolized material (Figure 1H). A satisfactory final angiographic appearance was obtained (Figure 1G) with prompt distal flow. Distal clot embolization is a known complication of percutaneous coronary intervention. Although no therapy has been shown to ‘solve’ this problem, appropriate pharmacological therapy, use of aspiration catheters (3) and selected use of embolic protection devices (4,5) may be considered on a case-by-case basis.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin reduces thrombolytic-induced intracerebral hemorrhage in embolized rabbits

Statins were designed as cholesterol-lowering drugs for the prevention of coronary artery disease. It is estimated that there are currently 33.5 million U.S. patients on chronic statin treatment regimens. Recently, statins have been shown to have pleiotropic including anti-inflammatory and neuroprotective effects. In this study, we assessed the pharmacological effects of simvastatin administered alone and in combination with tissue plasminogen activator (tPA) on measures of ischemia and hemorrhage in large clot embolized New Zealand white rabbits. For these studies, simvastatin (20 mg/kg, SC in DMSO) was administered 24 and 4 h prior to large clot embolization in order to achieve a “loading dose” pretreatment with the drug. In combination studies, tPA (3.3 mg/kg, IV) was administered 1 h following embolization. Intravenous tPA administration significantly increased hemorrhage volume by 175% (p=0.015) and hemorrhage incidence by 60% (p>0.05) compared to control, but did not affect infarct incidence or volume. Simvastatin treatment significantly decreased tPA-induced hemorrhage incidence (p=0.022) and volume (p=0.0001) following embolization. The study suggests that simvastatin treatment blocks or attenuates mechanisms involved in tPA-induced hemorrhage. Based upon our results, patients on simvastatin treatment may have significantly reduced tPA-induced side effects should they require tPA administration following an embolic stroke.

The RE-LY study: Randomized Evaluation of Long-term anticoagulant therapY: dabigatran vs. warfarin

This commentary refers to ‘Dabigatran versus warfarin in patients with atrial fibrillation’†, by S.J. Connolly, published in the New England Journal of Medicine , 2009; 361:1139–1151 Atrial fibrillation is an increasingly common arrhythmia, now said to stand at epidemic proportion in Western societies: >2.3 million people in the USA and >4.5 million people in Western Europe. It is an expression of underlying heart disease and a threat to life and living. In particular it is associated with 4.5-fold risk of stroke,1 predominantly ischaemic in nature, largely due to embolization of a left atrial clot. Over the last several decades a formidable evidence base has been developed for the use of anticoagulant therapy,2 mostly warfarin/coumadin, and antiplatelet therapy, predominantly aspirin and more recently clopidogrel plus aspirin.3 Although warfarin is undoubtedly an effective anticoagulant therapy, its application is associated with a highly significant risk of bleeding such that it has been necessary to provide regular and sometimes intense monitoring of coagulation parameters, and stringent control of diet, alcohol, and co-medications. Recently it has been suggested that it might be necessary to apply modern pharmacogenomic principles of personalized medicine to warfarin recipients to optimize the safety of anticoagulant control.4 Despite all this, warfarin therapy remains problematic, especially in the elderly because of non-adherence to medication, falls, and polypharmacy. The alternative approach is aspirin, the efficacy of which is doubted unless combined with clopidogrel, although the bleeding risk when used alone is not negligible, and is considerable in combination with clopidogrel. As a result, neither physicians nor patients have been confident about anticoagulant/antithrombotic therapy, and its utilization for atrial fibrillation has been inconsistent and often inappropriate.5 There has been a very determined effort on …

Effect of internal carotid artery reperfusion in combination with Tenecteplase on clinical scores and hemorrhage in a rabbit embolic stroke model

In the present study, we used a modification of the rabbit small clot embolic stroke model (RSCEM), a multiple infarct ischemia model to achieve reperfusion (REP) through the internal carotid artery (ICA) following small clot embolization. We determined if increasing regional cortical blood flow (RCBF) following an embolic stroke is beneficial to neurological outcome. We compared this to cerebral reperfusion induced by the administration of the thrombolytic Tenecteplase (TNK, 1.5 mg/kg, IV bolus) in the presence or absence of REP. In this study, we also measured the incidence of ICH following REP and thrombolytic treatment. Following embolization, RCBF was reduced to 48–55% of baseline. When REP was induced by removal of a CCA ligature, RCBF initially increased to 185% of baseline. REP (P 50 = 1.18 ± 0.43 mg) had no effect on embolization-induced behavior measured 24 h following embolization compared to control (P 50 = 1.01 ± 0.48 mg). However, TNK treatment (2-hours post-embolization) in the absence or presence of REP (initiated 2 h following embolization) significantly ( p < 0.05) increased the group P 50 to 2.92 ± 0.55 mg and 2.42 ± 0.40 mg, respectively. In addition, ICH was increased in the REP (42%, p < 0.05) and REP-TNK (35%, p > 0.05) group compared to either the control group (5.5%) or TNK group (10%). This study show that reperfusion of ICA can increase RCBF following embolization, but this is not associated with improved neurological outcome measured using quantal analysis. However, TNK administration significantly increased behavioral outcome when given 2 h following embolization; an increase that is not affected by combining TNK with REP.

Thrombosis and Anticoagulation: Essentials for the General Cardiologist

Deep vein thrombosis (DVT) occurs in approximately 2 million Americans each year. Nearly 600,000 of these patients will develop a pulmonary embolism (PE), and almost 60,000 will die of this complication [Hirsh H & Hoak J. Circulation 1996]. The goal of antithrombotic therapy for venous thromboembolic (VTE) disease is the prevention of clot propagation, embolism, and recurrent thrombosis. This article reviews the 2008 ACCP evidence-based clinical practice guidelines regarding VTE disease, which established new strategies for the treatment of acute DVT and PE [Chest 2008;133 (6 suppl)].

Cosmic Implications of NXY-059

The SAINT studies on NXY-0591,2 have reinvigorated debate over the momentous issues of neuroprotection and the development of novel stroke therapeutics. Some may argue there is little new ground that NXY-059 has unearthed and, in fact, the clinical trials merely confirm that as a strategy, neuroprotection has not been shown to be effective. Editorials in high-profile journals have sent out the clarion call to terminate research on neuroprotection given decades of work, which has uniformly led to failure after failure in clinical studies.3 These sentiments are premature and ignore studies showing that hypothermia improves outcome in patients after cardiac arrest, a major cause of global cerebral ischemia.4,5 Proof for the neuroprotection concept has therefore already been established. Despite decades of neutral clinical trials, there still remains optimism among the stroke academic community. A majority of university-affiliated stroke neurologists in the United States in a recent survey still believe neuroprotection is a viable therapeutic strategy, although admittedly, that survey was conducted between the SAINT I and SAINT II publications.6 However, the question whether neuroprotection will ever work in stroke has been overshadowed by the larger issue of whether animal studies, which serve as the foundation for the development of stroke therapeutics, are even relevant to our patients with acute stroke. In the discussion section of the SAINT II article, the authors write, “it is possible that the animal models of acute focal infarction are not relevant to the patient population; they certainly are insufficient to guarantee a positive clinical-trial result.” Have all prior neuroprotective agents failed in clinical studies because rodent stroke is not relevant to human stroke? This is a key question. Substantial reductions in infarct size in rodents with stroke treated with various types of purported neuroprotective agents would seem to support this view. There …

Rabbit Subselective Angiography Stroke Model

To the Editor: We congratulate Jahan et al1 on their description of a subselective angiographic rabbit stroke model using microcatheters. Their feasibility study is a good step toward a badly needed improved model of acute stroke, as we suggested in our previous work.2 We are eager to hear more of the many details that are necessary to put this model into routine use. Based on our own angiographic experience in >300 rabbits, several questions must be answered relating to the mechanics of the technique and the applicability as a model of human stroke. The primary goal of this model is to mimic the human situation of ischemic stroke, usually an embolic event in fairly …

Posttraumatic Nonischemic Priapism Treated with Autologous Blood Clot Embolization

High-flow arterial priapism is rare and characterized by a prolonged nonpainful erection. Autologous clot embolization allows complete resolution of the problem in most of the cases. To review our experience with superselective transcatheter embolization in the treatment of nonischemic priapism. Advances in the understanding of the nonischemic priapism with the aid of newer techniques have altered the current management of nonischemic priapism. Between 2002 and 2006, 11 patients underwent superselective transcatheter embolization of nonischemic priapism with blunt trauma to the penis or perineum. All patients underwent diagnostic evaluation with color-flow Doppler ultrasound and superselective pudendal arteriography, revealing bilateral arteriocorporal fistula and pseudoaneurysm in two cases, bilateral arteriocorporal fistula in one case, unilateral arteriocorporal fistula in one case, and unilateral arteriocorporal fistula and pseudoaneurysm in seven cases. Autologous blood clot was used as an embolization agent in all cases combined with microcatheter guidance. The procedure was technically successful in all cases. In three (27.2%) cases, a second embolization was required due to recurrence of priapism. In all patients, erectile function was restored within 6 weeks of the procedure. Follow-ups at 6 and 12 months after the last procedure revealed that full erectile capacity was restored in 10 of 11 patients, and these patients did not experience further recurrence of priapism. One patient reported a slight decrease in the quality of his penile erection. Our experience revealed that superselective transcatheter embolization and transient occlusion of the fistula with autologous blood clot is an effective therapy for the treatment of nonischemic priapism. Furthermore, recovery of erectile function due to recanalization of the occluded vessel occurred weeks after the procedure.

Post‐surgical high‐flow priapism treated by embolization

Perineal and penile traumas are the commonest cause of high-flow priapism. The clinical symptom of this disease is generally a prolonged, painless, and semirigid penile erection without any other urogenital symptoms. In contrast, high-flow priapism is a quite uncommon condition after transurethral surgery and it may be presented with an unusual clinical manifestation. Herein, we report the first case of priapism associated with massive urethral hemorrhage requiring blood transfusion after internal urethrotomy. High-flow priapism was successfully treated by autologous clot embolization and the priapism associated with massive urethral hemorrhage resolved.

Severity dependent increases in circulating cardiac troponin I and MMP-9 concentrations after experimental acute pulmonary thromboembolism

Background Making the diagnosis of acute pulmonary thromboembolism (APT) and assessing its severity is very challenging. While cardiac troponin I (cTnI) concentrations are promising in risk stratification, no previous study has examined whether there is a linear relation between cTnI concentrations and the severity of APT. Moreover, matrix metalloproteinases (MMPs) are involved in the pathophysiology of APT. However, it is unknown whether the increases in MMP concentrations after APT reflect the severity of this condition. We examined whether the circulating concentrations of these biomarkers increase in proportion to the severity of experimental APT induced in anesthetized dogs. Methods APT was induced with autologous blood clots (saline, 1, 3, or 5 ml/kg) injected into the right atrium. Hemodynamic evaluations were carried out for 120 min. Gelatin zymography of MMP-2 and MMP-9 from plasma samples were performed and serum cTnI concentrations were determined at baseline and 120 min after APT. Results While no significant increases in pro-MMP-2 concentrations were found after APT, pro-MMP-9 concentrations increased by 80% only after 5 ml/kg of clot embolization. Serum cTnI and plasma pro-MMP-9 concentrations correlated positively with pulmonary vascular resistance ( P = 0.007 and rs = 0.833 for troponin I, and P = 0.034 and rs = 0.684 for pro-MMP-9) and with pulmonary artery pressure ( P = 0.005 and rs = 0.610 for troponin I, and P = 0.022 and rs = 0.720 for pro-MMP-9). Conclusions Circulating cTnI and pro-MMP-9 increase in proportion to the severity of APT, although the increases in plasma pro-MMP-9 are less clear with less severe APT. These findings may be relevant for clinical APT.