A novel pulsatile blood pump design for cardiothoracic surgery: Proof-of-concept in a mock circulation.

BACKGROUND: Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. The present study investigated the properties of a novel positive displacement blood pump in a mock circulation. METHODS: The pump was attached to an aortic model with a human-like geometry and compliance as a pseudo patient. Hemodynamic data were recorded while the pump settings were adjusted systematically. RESULTS: Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mm Hg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mm Hg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F = 40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mm Hg and F = 40 bpm. At F = 40 bpm, PP was 58.7 mm Hg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings. CONCLUSIONS: The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications are planned to establish this concept for adult pulsatile perfusion.

Algorithm-based approach to focal liver lesions in contrast-enhanced ultrasound.

Focal liver lesions are commonly encountered. Grey-scale and Doppler sonographic characteristics of focal liver lesions are often non-specific and insufficient to conclusively characterise lesions as benign or malignant. Contrast-enhanced ultrasound is useful for the characterisation of FLLs in patients who are unable to undergo contrast-enhanced computed tomography or magnetic resonance imaging. It is also easily available and relatively cheap. However, interpretation of contrast-enhanced ultrasound can be challenging without a systematic approach. In this pictorial essay, we highlight an algorithm-based approach to FLLs and discuss the characteristic contrast-enhanced ultrasound features of commonly encountered and clinically significant focal liver lesions.

Outcomes of patent ductus arteriosus ligation in very low birth weight premature infants: A retrospective cohort analysis.

INTRODUCTION: Patent ductus arteriosus (PDA) can be a significant hemodynamic problem in preterm infants leading to increased morbidity and mortality. PDA ligation is therefore considered an urgent procedure in infants who have failed medical therapy. However, there is controversy regarding optimal timing and decision to operate. This study aimed to evaluate the outcomes and efficacy of PDA ligation in very low birth weight premature infants. METHODS: We performed a retrospective review of our institution's database and included very low birth weight premature infants (<1500 g) who underwent PDA ligation from 2008 to 2019 among 6 centers within the Southern California Kaiser Permanente network system. Indications for PDA ligation were variable but included congestive heart failure, respiratory failure, necrotizing enterocolitis, renal failure, and contraindications to medical therapy. PDA ligations were performed via thoracotomy incisions with ligations using a clip or tie. The primary outcome measure was mortality, and secondary outcomes included various postoperative morbidities. RESULTS: A total of 449 patients met criteria and were included in the study. The mean birth weight was 735 g (125 g-1460 g), and mean gestational age was 25 weeks (21-36 weeks). The mean operating room time was 28 min (9-84 min). 97% of PDAs were clipped, and 3% were tied. Comorbidities at the time of operation included bronchopulmonary dysplasia (59%), retinopathy of prematurity (39%), intraventricular hemorrhage (28%), and necrotizing enterocolitis (10%). There were 2 (0.4%) operative deaths, 15 (3%) deaths within 30 days, and 20 (4%) deaths within 1 year. Other postoperative outcomes included recurrent laryngeal nerve injury (1%), chylothorax (1%), pneumothorax (0.4%), and 3 (0.6%) reoperations. DISCUSSION: Very low birthweight premature infants with hemodynamically and clinically significant PDA are complicated patients. The risks of surgical ligation must be weighed against the potential clinical benefits. The mortality rate in our patient group within our hospital system is lower than those reported in the literature. Surgical ligation appears to be a safe and acceptable option for treatment of this complex problem, especially when medical therapy fails. Further studies are needed to elucidate specific independent risk factors that are associated with morbidity and mortality to further improve outcomes. LEVEL OF EVIDENCE RATING: Level II TYPE OF STUDY: Prognosis study.

Pediatric Surgeons' Adoption of an Innovative Laparoscopic Technique for Inguinal Hernia Repair: A Mixed Methods Study.

Purpose: We studied adoption of an innovative laparoscopic technique for pediatric inguinal hernia repair by pediatric surgeons and pediatric urologists following dissemination of evidence for its benefits. Methods: This mixed methods study included children who received inguinal hernia repairs during 2017-2019 and their surgeons. We examined surgeons' adoption and use of the innovative technique and rates of ipsilateral recurrence and metachronous contralateral repair. In-depth interviews with surgeons were used to identify themes regarding attitudes and practices regarding the adoption of surgical innovations. Results: No ipsilateral recurrences were noted among open repairs after 1.5 years of average follow-up, while 1.54% (7/453) of unilateral and 0.50% (3/606 sides) of bilateral innovative surgeries required ipsilateral repair after 1.3 years of average follow-up. Among unilateral cases, metachronous contralateral repairs were performed in 1.63% (8/490) of open and 0.44% (2/453) of innovative surgeries. Surgeon interviews identified approaches to continued learning and change; the role of departmental culture, norms, and resources; and technical issues specific to pediatric surgery and pediatric inguinal hernia repair. Conclusions: Outcomes may have improved over time as a consequence of learning. Differences among surgeons and departments influenced the speed of adoption. Surgeons linked the collegial model used when adopting the new technique to the apprenticeship model used during their training. We propose research into the collegial model to improve translation of evidence-based surgical innovations into practice. Level of Evidence: Level III.

Long-term follow-up of pediatric open and laparoscopic inguinal hernia repair.

BACKGROUND: Pediatric laparoscopic inguinal hernia repair is not widely accepted. STUDY DESIGN: Children 0-14 years who underwent inguinal hernia repair during 2010-2016 at Kaiser Permanente Northern California were classified into five groups: (1) open unilateral repair without contralateral exploration; (2) open unilateral repair with contralateral laparoscopic exploration ("open+explore"); (3) open bilateral repair; (4) laparoscopic unilateral repair; and (5) laparoscopic bilateral repair. Outcomes included ipsilateral reoperation, metachronous contralateral repair, incision time, and complications. RESULTS: The study included 1697 children. Follow-up averaged 3.6 years after open (N = 1156) and 2.6 years after laparoscopic (N = 541) surgery. Metachronous contralateral repair was performed in 3.8% (26/683) of patients with open unilateral surgery without contralateral exploration, 0.7% (2/275) of open+explore patients, and 0.9% (3/336) of laparoscopic unilateral patients (p < 0.01). Ipsilateral repair was performed in 0.8% (10/1156) of open repairs and 0.3% (2/541) of laparoscopic repairs. Chart review confirmed 5 postoperative infections in 1156 patients with open surgery (0.43%) and 6 infections in 541 patients with laparoscopic surgery (1.11%) (p = 0.11). CONCLUSION: Our study's laparoscopic and open approaches have similar low ipsilateral reoperation rates, incision times, and complications. The use of laparoscopy to visualize the contralateral side resulted in a significantly lower rate of metachronous contralateral repair. LEVEL OF EVIDENCE: Level III.

New astroglial injury-defined biomarkers for neurotrauma assessment.

Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.

Minimal access laparoscopic surgery for treatment of ulcerative colitis and familial adenomatous polyposis coli in children and adolescents.

BACKGROUND: Laparoscopic restorative proctocolectomy is standard surgical treatment for patients with ulcerative colitis (UC) and familial adenomatous polyposis coli (FAP). Scar burden can be minimized by reducing the number of laparoscopic ports. The aim of this study is to review the authors' experience with reduced-port laparoscopy in this setting and to compare it with conventional laparoscopy using multiple ports. MATERIALS AND METHODS: Charts of pediatric patients undergoing colectomy for UC or FAP between 2009 and 2012 were retrospectively reviewed. Patients who had the operation performed through one or two multichannel ports were assigned to the minimal access (MA) study group. Patients who had four or five single-channel ports with or without an additional small laparotomy were assigned to the LAP group. RESULTS: Twenty-two patients were identified. Ages at first operation were 2-18 years (median, 13.5 years). There were no conversions to laparotomy and no mortality. Mean operative times for the MA and LAP groups, respectively, were 250 and 284 minutes for abdominal colectomy with end ileostomy (P=.15), 198 and 301 minutes for completion proctectomy with diverting loop ileostomy (DLI) (P=.26), and 455 and 414 minutes for proctocolectomy with ileal pouch-anal anastomosis and DLI (P=.72). A major complication requiring laparotomy occurred in 1 patient (9%) in the MA group and in 2 patients (18%) in the LAP group. CONCLUSIONS: Minimal access laparoscopic surgery for UC and FAP is safe and feasible. A slightly larger incision at the ostomy site facilitates extraction of the specimen and extracorporeal construction of a J-pouch. Operative times and hospital stay are comparable to those with multiport laparoscopy.

Single-incision pediatric endosurgery (SIPES) splenectomy: a case-control series.

BACKGROUND/PURPOSE: Single-incision pediatric endosurgery (SIPES) is gaining popularity. The aim of this study was to review the authors' experience with SIPES splenectomy and compare it with conventional laparoscopic splenectomy. SUBJECTS AND METHODS: After institutional review board approval, data on SIPES splenectomy in children were collected prospectively. The study group was compared with a control group of patients who were retrospectively identified as having undergone conventional laparoscopic splenectomy during the same time period. RESULTS: Sixteen children underwent SIPES splenectomy. Ages ranged from 1 to 15 years, with a median of 7 years, and weights were between 10 and 70 kg, with a median of 24 kg. The control group was similar in age and weight characteristics. The most common diagnoses were hereditary spherocytosis, sickle cell disease, and immune thrombocytopenic purpura. There were two conversions to open splenectomy in the SIPES group and one in the laparoscopic group. Operative times were 40-190 minutes (median, 84 minutes) in the SIPES group and 51-154 minutes (median, 99 minutes) in the conventional laparoscopic group. CONCLUSIONS: The SIPES technique is well suited for splenectomy. Despite instruments and camera being in-line, working angles are not compromised, and visualization is adequate. Operating time and hospital stay are comparable to those with standard laparoscopic splenectomy, but the cosmetic result may be superior.

Laparoscopic surgery in children with congenital heart disease.

PURPOSE: The study aim was to determine outcomes of children with congenital heart disease who underwent laparoscopic procedures. METHODS: A single-institution, institutional review board-approved, retrospective review was conducted including children younger than 5 years with congenital heart disease who underwent laparoscopic or open abdominal procedures. Patient demographics, operative details, complications, and 30-day mortality were examined. RESULTS: Over 10 years, 111 children with congenital heart disease underwent 121 laparoscopic procedures. Median age was 2.5 months, with 87% being infants. Laparoscopic gastrostomy was the most common procedure (101). There was no intraoperative hemodynamic instability, median operative time was 70 minutes, postoperative complications were low (5%), and all children were alive at 30 days. Only 8 patients required conversion from laparoscopic to open, all secondary to technical issues, not hemodynamic instability. There were 42 children with cardiac disease who underwent 45 open procedures during the study period. There were no significant differences between patient demographics, type of procedure, operative time, complications, or 30-day mortality comparing the open and laparoscopic groups. CONCLUSION: In this review, there were no major contraindications to performing laparoscopic procedures in children with congenital heart disease, and we conclude that it is reasonably safe to perform laparoscopic surgery on these children.

APASL and AASLD Consensus Guidelines on Imaging Diagnosis of Hepatocellular Carcinoma: A Review.

Consensus guidelines for radiological diagnosis of hepatocellular carcinoma (HCC) have been drafted by several large international working groups. This article reviews the similarities and differences between the most recent guidelines proposed by the American Association for Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver. Current evidence for the various imaging modalities for diagnosis of HCC and their relevance to the consensus guidelines are reviewed.

Gadoxetate Acid-Enhanced MR Imaging for HCC: A Review for Clinicians.

Hepatocellular carcinoma (HCC) is increasingly being detected at an earlier stage, owing to the screening programs and regular imaging follow-up in high-risk populations. Small HCCs still pose diagnostic challenges on imaging due to decreased sensitivity and increased frequency of atypical features. Differentiating early HCC from premalignant or benign nodules is important as management differs and has implications on both the quality of life and the overall survival for the patients. Gadoxetate acid (Gd-EOB-DTPA, Primovist(®), Bayer Schering Pharma) is a relatively new, safe and well-tolerated liver-specific contrast agent for magnetic resonance (MR) imaging of the liver that has combined perfusion- and hepatocyte-specific properties, allowing for the acquisition of both dynamic and hepatobiliary phase images. Its high biliary uptake and excretion improves lesion detection and characterization by increasing liver-to-lesion conspicuity in the added hepatobiliary phase imaging. To date, gadoxetate acid-enhanced MRI has been mostly shown to be superior to unenhanced MRI, computed tomography, and other types of contrast agents in the detection and characterization of liver lesions. This review article focuses on the evolving role of gadoxetate acid in the characterization of HCC, differentiating it from other mimickers of HCC.

The Cross-technique for single-incision pediatric endosurgical pyloromyotomy.

BACKGROUND: Single-incision pediatric endosurgical (SIPES) pyloromyotomy is frequently used for the treatment of hypertrophic pyloric stenosis at our center. Our initial SIPES approach mirrored the conventional, triangulated laparoscopic pyloromyotomy. Because an increased number of perforations were noted on our initial analysis, a more straightforward Cross-technique SIPES pyloromyotomy was developed. This study compares the current Cross-technique SIPES pyloromyotomy to the previous standard SIPES operation. METHODS: The Cross-technique entails grasping the antrum with the surgeon's left hand instrument, retracting toward the left lower quadrant, and thereby orienting the pylorus obliquely toward the right upper quadrant. The serosal incision and muscular spreading is accomplished using a right-hand instrument that crosses over the left hand grasper. Demographic variables, operative times, estimated blood loss (EBL), complications, conversion rate, and postoperative length of stay were compared. RESULTS: Twenty-nine Cross-technique patients were compared with 23 in the standard group. The Cross-technique was faster than the standard procedure (21 ± 5 vs. 27 ± 12 min, p = 0.03) and EBL was lower (1.3 ± 0.5 vs. 1.7 ± 0.6 ml, p = 0.02). There were two mucosal perforations requiring conversions to triangulated 3-access-site laparoscopy in the standard, and one conversion to open surgery in the Cross-technique group. Patients who underwent cross-technique pyloromyotomy weighed less (3.6 ± 0.6 vs. 4.0 ± 0.5 kg, p = 0.012), but there were no differences in age, gender ratio, conversion rate, or length of stay. There was one postoperative wound infection in the cross-technique, but none in the standard group. No patients required reoperation. All participating surgeons felt that the cross-technique was more ergonomic and easier to perform than the standard SIPES technique. CONCLUSIONS: The Cross-technique appears superior to standard SIPES pyloromyotomy and should be preferentially used for single-incision endosurgical pyloromyotomy for hypertrophic pyloric stenosis.

An evidence-based clinical protocol for diagnosis of acute appendicitis decreased the use of computed tomography in children.

PURPOSE: The increased use of computed tomography (CT) to diagnose appendicitis in children has led to a concern for the possibility of increased CT-related cancer morbidity. We designed a clinical protocol for the diagnosis and treatment of appendicitis in children in an attempt to decrease the use of CT scans at our institution. METHODS: Patients who had surgical consultation for suspected appendicitis were placed on the clinical protocol. Data concerning diagnosis and treatment were collected prospectively. Retrospective data from patients admitted to our institution with acute appendicitis before the clinical protocol were collected as historical controls. RESULTS: One hundred twelve patients were diagnosed and treated by our protocol between June and November 2009. Of these, 100 patients underwent an appendectomy for acute appendicitis. They were compared with 146 patients from 2007. In-house CT use decreased from 71.2% to 51.7% (P = .01). Preoperative ultrasound use increased from 2.7% to 21% (P < .001). The negative appendectomy rate increased (6.8% vs 11%, P = .25). CONCLUSIONS: Our findings suggest that the implementation of an evidence-based clinical protocol for the diagnosis and treatment of acute appendicitis in children may safely decrease the use of CT scans and increase the use of ultrasound.

Diagnostic accuracy of contrast-enhanced ultrasound in differentiating benign and malignant focal liver lesions: a retrospective study.

PURPOSE: The purpose of this study was to assess the diagnostic accuracy of our early experience with contrast-enhanced ultrasound (CEUS) in the characterisation of focal liver lesions (FLLs) using histopathology, contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI) or other imaging follow-up as the standard of reference. MATERIALS AND METHODS: Seventy-three patients with 82 FLLs who underwent liver CEUS from January 2006 to December 2008 were retrospectively reviewed. CEUS was performed with up to 4.8 mL of SonoVue® (Bracco, Milan, Italy) using a low mechanical index mode. The CEUS findings were compared with histopathology, or where histopathology was not available, clinical and imaging follow-up over at least 12 months was used as the standard of reference. RESULTS: Of the 82 FLLs, 50 were malignant and 32 were benign at final diagnosis. CEUS correctly identified 43 malignant FLLs, with final diagnosis confirmed by histopathology in 13 lesions and clinico-radiological follow-up in 30 lesions. Twenty-nine lesions were correctly identified as benign on CEUS, with all these lesions confirmed on clinico-radiological follow-up. CEUS demonstrated a sensitivity of 86.0% and a specificity of 90.6% in the characterisation of liver lesions as malignant, with an overall accuracy of 87.8% (P < 0.05). CONCLUSION: Our early experience has shown that CEUS can be accurate in differentiating malignant from benign FLLs and may become a useful first-line imaging tool where CT or MRI are not available or contra-indicated.

Single-incision laparoscopic endorectal pull-through (SILEP) for hirschsprung disease.

BACKGROUND: Over the last 15 years, the laparoscopic-assisted endorectal pull-through procedure first described by Georgeson has become the standard treatment for Hirschsprung disease in many centers around the world. We report the first six patients who were operated using a single-incision endosurgical approach. METHODS: Six infants (one female) diagnosed with Hirschsprung disease underwent laparoscopic endorectal pull-through via a single 1 cm horizontal skin incision in the umbilicus. Firstly, laparoscopic seromuscular leveling biopsies of the rectum and sigmoid were obtained. The affected rectosigmoid colon and rectum was then mobilized distally beyond the peritoneal reflection, facilitating the subsequent perineal dissection, pull-through, and coloanal anastomosis. Operative variables were compared between single-incision and conventional laparoscopic endorectal pull-through. RESULTS: The patients' average age and weight was 28 days and 3.8 kg, respectively. Operative time ranged from 90 to 220 min, with a mean estimated blood loss of 3.7 ml. There were no intraoperative complications. Postoperatively, all six patients recovered uneventfully and were discharged home on full feeds after a median of 7 days. On follow-up, the patients had virtually no appreciable scar, were feeding well, stooling, and gaining weight appropriately. The results were similar to those of conventional laparoscopic endorectal pull-through. CONCLUSION: Although technically challenging, laparoscopic-assisted endorectal pull-through in infants with Hirschsprung disease can be performed safely through a single umbilical incision with good postoperative results and excellent cosmesis.

Single-incision laparoscopic pyloromyotomy: initial experience.

BACKGROUND: Laparoscopic pyloromyotomy has become the standard treatment for hypertrophic pyloric stenosis. Single-incision laparoscopic surgery is an emerging operative approach that utilizes the umbilical scar to hide the surgical incision. OBJECTIVE: To describe our initial experience with single-incision laparoscopic pyloromyotomy in 15 infants. MATERIALS AND METHODS: Laparoscopic pyloromyotomy was performed through a single skin incision in the umbilicus, using a 4-mm 30 degrees endoscope and a 5-mm trocar. The 3-mm working instruments were inserted directly into the abdomen via separate lateral fascial stab incisions. All patients were prospectively evaluated. RESULTS: The procedure was performed in 15 infants (13 male) with mean age of 45 +/- 16 days and mean weight of 4.04 +/- 0.5 kg. All procedures were completed laparoscopically, and one case was converted to a conventional triangulated laparoscopic work configuration after a mucosal perforation was noted. The perforation was repaired laparoscopically. On average, operating time was 29.8 +/- 13.6 min, and postoperative length of stay was 1.5 +/- 0.8 days. All patients were discharged home on full feeds. Follow-up was scheduled 2-3 weeks after discharge, and no postoperative complications were noted in any of the patients. CONCLUSIONS: Single-incision laparoscopic pyloromyotomy is a safe and feasible procedure with good postoperative results and excellent cosmesis. The main challenge is the spatial orientation of the instruments and endoscope in a small working space. This can be overcome by a more longitudinally oriented working axis than used in the conventional angulated laparoscopic configuration.

Computed tomography study of radial head morphology.

Computed tomography scans of 22 cadaveric adult elbows were obtained in 3 forearm positions: full supination, neutral, and full pronation. The radial head dimensions, the radiocapitellar joints, and the proximal radioulnar joints were measured. Multivariate analysis of variance was used to determine which portions of each articulation were the most congruent. The results showed that the radial head tended to become uncovered at the radial lip (P < .001). The radiocapitellar joint was tighter in pronation than in supination (P = .001). The proximal radioulnar joint was most congruent at the middle proximal radioulnar joint, at the midportion and posterior aspects rather than the anterior aspect (P < .001). The proximal radioulnar joint coverage was between 69 degrees and 79 degrees . Prosthesis trial sizing should be judged by the articulations providing the most congruency: (1) the ulnar lip or trough of the radiocapitellar joint in pronation and (2) the posterior or midportion of the middle proximal radioulnar joint.

Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats.

OBJECTIVES: p38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats. METHODS: Rats were divided into 4 groups: (1) the control group (daily 0.9% saline), (2) the FR group (daily FR167653, 2 mg . kg(-1) . d(-1)), (3) the MCT group (daily 0.9% saline the day after a single monocrotaline dose, 60 mg/kg), and (4) the MCT+FR group (daily FR167653, 2 mg . kg(-1) . d(-1), the day after a single MCT dose). Body weight, pulmonary artery pressure, and morphometric changes of the pulmonary artery with the histopathologic method were observed weekly for 4 weeks. Also, p38 mitogen-activated protein kinase activity and inflammatory cytokine expression in the lung were measured. RESULTS: Four weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT+FR group was lower than in the MCT group (MCT+FR vs MCT: 24.7 +/- 1.9 vs 36.5 +/- 2.1 mm Hg; P < .05). In morphometric analysis the percentage of medial wall thickness and the percentage of muscularization in the MCT+FR group were reduced compared with those in the MCT group after 4 weeks (P < .05); however, the number of macrophages was not significantly different. p38 mitogen-activated protein kinase activity was significantly attenuated in the MCT+FR group compared with in the MCT group (7.2 +/- 0.52 vs 2.1 +/- 0.23 fold-increase, P < .05, at 1 week). Although mRNA levels of tumor necrosis factor alpha and interleukin 1beta were reduced in the MCT+FR group compared with in the MCT group (tumor necrosis factor alpha: 1.18 +/- 0.36 vs 3.05 +/- 1.12 fold-increase, P < .05, at 2 weeks; interleukin 1beta: 2.2 +/- 0.34 vs 4.4 +/- 1.09 fold-increase, P < .05, at 1 week), FR167653 did not suppress increased monocyte chemotactic protein 1 mRNA expression induced by monocrotaline (3.2 +/- 0.62 vs 3.1 +/- 0.42 fold-increase, at 1 week). CONCLUSION: FR167653 significantly attenuates the expression of inflammatory cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38 mitogen-activated protein kinase might play a central role in the molecular events that underlie the development and progression of pulmonary hypertension.