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Home , Abdominal angina, Bowel infarction, Intestinal ischemia

A SPECIAL ARTICLE

Acute Mesenteric : A Diagnostic Challenge in Clinical Practice

by Mamata Ravipati, Srikanth Katragadda, Betty Go, Edwin J. Zarling

Mesenteric ischemia remains a difficult condition to diagnose clinically. It can be clas- sified as occlusive and non-occlusive, depending on the presence or absence of vascular occlusion. Occlusion due to embolic clot is the most common form, and accounts for nearly half the cases of acute mesenteric ischemia (AMI). Early diagnosis is essential as delay in diagnosis can result in bowel and irreversible damage. The clinical presentation, serum markers and plain films may be non-specific in mesenteric ischemia. , ultrasonography and CT/MRI imaging are being increasingly used in its diagnosis. Although pharmacological therapy can be helpful, especially in the initial hours, is usually advised. Despite new diagnostic and therapeutic modalities, the mortality and morbidity have remained high. This article reviews the anatomy, pathophysiology and clinical presentation of acute mesenteric ischemia, with a note on various diagnostic and therapeutic modalities.

INTRODUCTION spleen); the superior mesenteric artery (which supplies esenteric ischemia is a morbid abdominal ill- the and proximal mid-colon) (Figure 1) ness that poses a diagnostic challenge and a and the inferior mesenteric artery (which supplies the Mhigh rate of mortality. The term denotes a wide distal colon and ) (Figure 2). array of clinical symptoms ranging from mild abdom- Anatomically, there are rich collateral flow path- inal pain to severe rigidity and guarding, depending on ways between the superior and inferior mesenteric the visceral vascular compromise. In the past three arteries. The gastroduodenal branch of the celiac decades, AMI has been diagnosed more frequently artery and the pancreaticoduodenal artery of the perhaps due to enhanced radiologic tools. superior mesenteric artery provide a potential source of collateral flow between mesenteric and non-mesenteric vessels. Due to this collateral ANATOMY blood flow in the intestine, at least two of the three Mesenteric blood flow is derived from the celiac artery major vessels have to be occluded to create mesenteric (which supplies the foregut, hepatobiliary system and ischemia.

Mamata Ravipati, M.D.*, **; Srikanth Katragadda, M.D.***; Betty Go, M.D.*; Edwin J. Zarling, M.D.*, **. *Lovell Federal Health Care Center, 3001 Green Bay Road, North Chicago, IL (Drs. Ravipati and Go are staff physicians in Primary Care. Dr. Zarling is the Assistant Chief Medical Executive for Ambulatory Care. All can be reached at 224-610-3085). **Chicago Medical School, 3333 Green Bay Road, North Chicago, IL (Dr. Ravipati is Assistant Professor of Medicine, Dr. Zarling is Professor of Medicine). *** Mercy St Vincent Medical Center, 2213 Cherry St., Toledo, OH. (Dr. Srikanth Katragadda is a third year internal medicine resident).

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A SPECIAL ARTICLE

Figure 1. Schematic diagram of superior mesenteric artery Figure 2. Schematic diagram of inferior mesenteric artery and its branches. and its branches.

PATHOPHYSIOLOGY mesenteric ischemia5: alpha adrenergic stimuli causing vasoconstriction, and beta adrenergic stimuli causing General Factors vasodilatation with altered bowel absorption, secretion 6 Intestinal blood flow may be reduced as result of and motility ; systemic from any cause decreased circulating blood volume and poor systemic stimulating the release of vasopressin which can further perfusion (hypovolemic, cardiogenic, or neurogenic exacerbate the splanchnic vasoconstriction. Factors that ). The intestinal mucosa has a narrow range of can affect splanchnic circulation include angiotensin II, 7 oxygen tension and the low oxygen availability in the generated by the renin-angiotensin system , arachi- setting of may not be sufficient to donic acid metabolites and cAMP. Substances such as meet needs of basal metabolism1. , prostaglandin E1 and glucagon can poten- Several theories have been proposed to explain tis- tiate the vasodilating action of cAMP. sue injury in intestinal ischemia: neutrophil mediated injury to visceral organs2 reperfusion injury resulting ; Specific Factors in free radicals which cause disruption of cell mem- branes and thus damage the mucosal barrier; increased Acute mesenteric ischemia is more common than chronic flux of fluid into the lumen3 due to increased mucosal ischemia. On analysis of various causes for AMI, supe- permeability; and proliferation of intestinal bacteria4. rior mesenteric embolism accounts for 40–50%, supe- Intestinal ischemia can progress in a transmural fash- rior mesenteric artery for 18–25%, ion from mucosa to serosa. non-occlusive mesenteric ischemia for 20% and mesen- 8 These autonomic, humoral and local factors can teric accounts for 5% of all cases . collectively affect the clinical outcome in a patient with (continued on page 38)

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(continued from page 36)

Table 1. The Four Causes of Abdominal Ischemia

Types of Non-occlusive Mesenteric Mesenteric Acute mesenteric Acute mesenteric mesenteric venous Ischemia arterial embolism arterial thrombosis ischemia thrombosis Pathology , Atherosclerotic Systemic hypoperfusion Hypercoagulable MI, valvular disease, disease, superimposed from cardiac failure, states, blunt trauma, left ventricular aneurysm on trauma, infection , medications infection, , , portal malignancy Clinical Manifestation Early Abrupt onset of Gradual onset of Gradual onset of Subacute onset of ; postprandial pain, malaise and abdominal pain; , bowel changes; abdominal discomfort; Minimal physical Minimal physical Minimal physical Minimal physical findings findings findings findings Late Increasing pain, gross Increasing pain, gross Increasing pain, gross Increasing pain, gross distention, absence distention, absence distention, absence distention, absence of bowel sounds, of bowel sounds, of bowel sounds, of bowel sounds, mental status changes, mental status changes, mental status changes, mental status changes, peritoneal signs, sepsis peritoneal signs, sepsis peritoneal signs, sepsis peritoneal signs, sepsis Diagnostic Study Angiography Angiography Angiography Angiography Treatment All types Superior Surgical Vasodilator Hemodynamic mesenteric revascularization therapy therapy support, correction embolectomy; (Papaverine) () of acidosis, Chronic antibiotics, gastric anticoagulation decompression

Presence of Surgery Surgery Surgery Surgery Bowel Infarct

Acute mesenteric arterial embolism: Nearly half chronic mesenteric ischemia, including pain after food the cases of AMI are attributed to an embolism, usu- intake, and early satiety. In contrast to ally in the superior mesenteric artery. Emboli most embolic mesenteric ischemia, patients with acute commonly originate from cardiac abnormalities such mesenteric thrombosis often have delayed attention as atrial fibrillation, , left ventric- and diagnosis due to slow onset of symptoms. ular aneurysm with mural and mitral steno- Non-occlusive mesenteric ischemia (NOMI): sis. Untreated acute occlusion of the superior Non occlusive mesenteric injury usually occurs in sys- mesenteric artery carries a poor prognosis in patients temic hypoperfusion resulting from cardiac failure, with no pre-existing visceral artery occlusive disease. sepsis, or use of medications such as digitalis, ergota- Acute mesenteric arterial thrombosis: Patients mine, cocaine and alpha adrenergic agents9. These having acute thrombosis of the mesenteric vessels usu- patients may not have the classic symptom of severe ally have an underlying atherosclerotic disease. Most abdominal pain. The mortality is relatively high due to of them have a history of symptoms suggestive of underlying systemic illness and delay in diagnosis.

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Acute mesenteric venous thrombosis: Hyper- Fever, hypotension, , tachypnea and altered coagulable states including anti-thrombin III, protein mental status may be observed. Putrefaction of undi- C and S deficiency, lupus anticoagulant, polycythemia gested alimentary material accumulated proximal to vera and homocysteinemia increase the risk of venous the pathologic site can cause foul breath. Risk factors thrombosis10. Other risk factors include visceral infec- for acute mesenteric ischemia may be noted, such as tions and perforations, pancreatitis, portal hyperten- atrial fibrillation, heart murmurs, abdominal bruits, sion, use of oral contraceptive pills, malignancy evidence of tumor, DVT or recent surgery. The differ- involving the portal system and nephritic syndrome. ential diagnosis for AMI is listed in Table 2. Acute mesenteric arterial embolism: Acute mesenteric ischemia from an embolic cause usually DIAGNOSIS OF MESENTRIC ISCHEMIA: occurs in patients over 50 years of age with a history of cardiac disease. The presence of sudden abdominal Clinical Symptoms pain in patients with history of atrial fibrillation, recent To some extent, all types of acute mesenteric ischemia MI, or previous embolic disease should raise the suspi- have similar clinical presentation. Differences for each cion of acute mesenteric ischemia. Increasing abdomi- type are discussed below, and summarized in Table 1. nal pain, guarding and rigidity may point to underlying The most important finding is abdominal pain that is loss of intestinal viability and transmural infarction. disproportionate to findings. The Absence of peritoneal signs early on in mesenteric pain is typically moderate to severe, diffuse, non-local- ischemia may mislead to an alternative diagnosis. ized, and constant and sometimes described as colicky; Mesenteric artery thrombosis: Patients with it may or may not respond to narcotics. Nausea and thrombosis of mesenteric vessels usually present with (75%), anorexia and progressing to less clinical intensity. They have a history of postpran- obstipation, abdominal distention and GI bleeding dial pain, nausea and change in bowel frequency, (25%) are also commonly associated symptoms. AMI symptoms more suggestive of chronic mesenteric should be highly suspected in any patient with abdom- ischemia. Symptoms gradually progress over 12–24 inal pain disproportionate to physical findings, vomit- hours of onset and as the bowel becomes more ing or diarrhea. Factors that make AMI more likely include oral contraceptive use, hypercoagulable states, Table 2. atrial fibrillation, atherosclerosis, decreased cardiac Differential Diagnosis for Acute Mesenteric Ischemia output from myocardial infarction or congestive , , intussusception, tumor compression Abdominal Abscess Cholelithiasis and ). Abdominal Colonic Obstruction Abdominal Aortic Aneurysm Colonic Obstruction Acute Clinical Signs Ectopic Pregnancy Physical findings in patients with acute mesenteric Acute Pyelonephritis ischemia are similar among the different etiologies. Aortic Dissection The clinical distinction is made based on time of pre- Helicobacter Pylori Infection sentation. Early in the course of the disease, in the Bacterial Pneumonia absence of , physical signs are few and non- Intestinal Perforation specific. There is minimal or no tenderness and stool Biliary Obstruction Myocardial Infarction may contain occult or gross blood. Late in its course, Boerhaave Syndrome Pneumothorax when necrosis or perforation occurs, peritoneal signs Cholangitis Pregnancy develop: tenderness becomes severe, a palpable mass Sepsis may be present, bowel sounds may be absent to hyper- Choledocholithiasis Testicular Torsion active, voluntary and involuntary guarding appear.

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ischemic, and sepsis (i.e. tachycardia, Radiography tachypnea, hypotension, fever, and altered mental sta- Plain radiographs of the abdomen are commonly tus) develop. Catastrophic outcome results if not prop- ordered in patients presenting with acute abdominal erly and rapidly identified and treated. pain to rule out visceral pathologies like perforation Non-occlusive mesenteric ischemia: Patients that may require emergent intervention. Plain films are with NOMI usually have gradual onset of symptoms. usually normal in intestinal ischemia until the infarcted Usage of drugs such as digitalis, alpha adrenergic bowel undergoes irreversible ischemic changes. agents, ergot alkaloids or episodes of hypotension can Common radiographic findings include air-fluid lev- help in making a provisional diagnosis of non-occlu- els, distended adynamic ileus, and fixed dilated loops sive mesenteric ischemia. Nearly a quarter of patients on repeated films. Presence of gas in the portal vein with NOMI do not have abdominal pain initially, but if and intestines ( intestinalis) are poor prog- infarction occurs, patients develop increased pain nostic signs in mesenteric ischemia. Superior mesen- associated with vomiting, hypotension and tachycar- teric artery occlusions usually take 12 hrs before the dia. When these signs develop, bowel injury may be radiographic signs are elicited, whereas non-occlusive 11 severe and irreversible . mesenteric ischemia may take several days for such Mesenteric venous thrombosis: Patients with radiographic changes15. Classic findings in barium mesenteric venous thrombosis usually have subacute studies of ischemic bowel include “thumbprinting” onset of symptoms and nonspecific laboratory find- (due to mucosal edema) and delayed passage of con- ings. Patients may complain of intermittent episodes of trast material through the paralytic segment. Barium abdominal pain over a period of few days or prolonged studies should be avoided in patients having a clear period with gradual worsening. The chronic form may diagnosis of intestinal perforation or ischemia and manifest as esophageal variceal bleeding. Many those in whom angiography is planned. patients have risk factors for hypercoagulability i.e. oral contraceptive use, congenital hypercoagulable states, deep venous thrombosis, , tumor or Ultrasonography postcaval surgery. Doppler ultrasonography has emerged as a useful alternative to angiography in screening and diagnosis of visceral ischemia. This non-invasive diagnostic DIAGNOSTIC STUDIES modality can detect arterial narrowing and blood flow velocity to identify stenotic lesions in the visceral vas- Laboratory culature. Normal blood flow observed in all visceral Laboratory indices may be helpful in ruling out or sup- vessels may be sufficient to rule out mesenteric porting the diagnosis of mesenteric ischemia, but only ischemia. Obesity, vessel wall calcifications and in late stages. Elevated levels of , total leuko- intestinal gas can sometimes hinder proper visualiza- cytic count, hemoglobin or phosphate in the blood and tion of visceral vasculature. Ultrasonography is a fine also are some of the non-specific non-invasive imaging modality that can greatly help in indicators of mesenteric ischemia. Studies have shown reducing the latent period between the symptom onset that low lactate levels may help in ruling out the diag- and therapeutic intervention16. nosis of intestinal ischemia and avoid unnecessary laparotomies, especially in the elderly12,13,14. Enzymes such as creatine kinase (CPK), lactate dehydrogenase Angiography (LDH), and alkaline phosphatase may be helpful in Angiography has become a very important diagnostic diagnosis of transmural infarction, but are insensitive and therapeutic intervention in intestinal ischemia. The in early stages of ischemia. Currently, the role of labo- classic angiographic finding in superior mesenteric ratory markers in visceral ischemia is limited and the artery embolus is the mercury meniscus sign seen quest for a more definitive marker is still on. (continued on page 42)

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(continued from page 40) approximately 3–8 cm distal to the origin of the supe- MANAGEMENT OF ACUTE MESENTERIC rior mesenteric artery, best seen in anterio-posterior ISCHEMIA view. The embolus appears as the shape of a crescent Acute arterial mesenteric ischemia: (thrombotic or that is convex on the surface much like the meniscus embolic): In patients presenting with acute mesenteric formed by mercury. However, lateral angiographic ischemia, hypovolemia and hypotension need to be views are more helpful in superior mesenteric artery corrected first by appropriate administration of IV flu- thrombosis, which classically show occlusion just dis- ids and supportive care. Broad spectrum antibiotics, tal to the origin of the superior mesenteric artery. nasogastric tube decompression, foley catheter and Angiography can be used preoperatively in embolic or supplemental oxygen should also be considered. 17 thrombotic occlusions of the mesenteric artery . Transcatheter administration of papaverine during The role of angiography in mesenteric venous angiography has been shown to be effective in both thrombosis is unclear and evidence from most recent occlusive and non-occlusive mesenteric ischemia20. studies emphasized the need of laparotomy in venous Higher survival rates have been observed when 18 thrombosis . Angiography has a definite diagnostic vasodilators have been added to the treatment plan21. and therapeutic role (infusion of Papaverine and Papaverine inhibits the phosphodiesterase enzyme and thrombolytics through the angiogram catheter) in non- thus increases the tissue levels of C-AMP, a vascular occlusive mesenteric ischemia. Papaverine is the only smooth muscle relaxant22. Clinically and angiographi- treatment of non-occlusive mesenteric ischemia other cally guided papaverine therapy is generally given for than resection of gangrenous bowel. Angiographic a period of 24–48 hours, through angiographic catheter findings in non-occlusive mesenteric ischemia include at a rate of 30–60 mg/hour. Repeat angiograms are diffuse or focal narrowing of mesenteric vessels, advised every 24 hours until patient improves clini- showing alternating segments of narrowing and dilata- cally. Surgical intervention should be undertaken in tion, sometimes referred to as the classic “sausage patients who exhibit any signs of clinical deterioration. sign.” Necrotic bowel is surgically removed and primary Angiography can sometimes precipitate emboliza- anastomosis is preferred in uncomplicated cases. tion and worsen ischemia. Opting for angiography in Intestines appearing marginally viable at initial opera- case of severe acute occlusion can sometimes lead to tion should be allowed to remain, with the intent of delayed diagnosis and resulting in worsening of undertaking a “second-look operation” 24–36 hours ischemia. Laparoscopy is a better option whenever later. A second-look operation is indicated whenever angiography is precluded. bowel of questionable viability is resected. In case of large embolus in the SMA, embolectomy should follow papaverine to maintain the intestinal viability. Some CT/MRI studies have shown that management of acute mesen- In addition to helping establish the diagnosis of intesti- teric ischemia with revascularization and open surgical nal ischemia, CT and/or MRI imaging have the ability techniques may result in improved survival rates23. to rule out other causes of acute abdomen. CT imaging Although percutaneous angioplasty may be success- with IV and oral contrast could be a valuable diagnos- fully tried in acute mesenteric ischemia24, is usually not tic modality and predictor of outcome in acute mesen- recommended due to high risk of thromboembolus. teric ischemia19. Similarly, the findings on MRI Thrombolytic therapy with streptokinase, uroki- imaging could include edema and increased thickness nase or recombinant tissue plasminogen activator in of the bowel wall, free fluid in the abdomen, or pres- acute arterial mesenteric ischemia is still in experi- ence of collateral vessels. MRI imaging is being mental phase25 and is limited to patients with con- increasingly used in the diagnosis of chronic mesen- traindication to surgery and who present in the early teric ischemia. MRI angiography is rapid and non- phase of ischemia before infarction of bowel develops. invasive, and may supplant traditional angiography in There is no role for heparin in acute management the future. of bowel ischemia. It is not compatible with papaver-

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ine. Heparin anticoagulation is the main treatment of 8. McKinsey JF, Gewertz BL: Acute Mesenteric ischemia. The Surgical Clinics of North America, 1997; 77:307-318 mesenteric venous thrombosis. Heparin is usually rec- 9. Sai Sudhakar CB, Al Hakeem M, Mac Arthur JD et al: ommended 48 hrs after embolectomy or revasculariza- Mesenteric ischemia secondary to cocaine abuse: Case reports 26 and literature review. Am J Gastroenterol 1997; 92:1053-1054 tion to prevent recurrent thrombosis and emboli . 10. Ellis DJ, Brandt LJ: Mesenteric venous thrombosis. Heparin is to be followed by long term administration Gastroenterologist 1994; 2:293-298 of for a period of 3 to 6 months. Anticoag- 11. Kaleya RN, Boley SJ: Acute mesenteric ischemia: an aggressive diagnostic and therapeutic approach.1991 Roussel lecture. Can J ulant therapy markedly reduces the risk of emboliza- Surg 1992; 35:613-623 tion in patients with atrial fibrillation. 12. Newmann TS, Magnuson TH, Ahrendt SA et al: The changing face of mesenteric infarction. Am Surg 1998; 64:611-616 Non-occlusive mesenteric ischemia: In non-occlu- 13. Klein HM, Lensing R Klosterhalfen B et al: Diagnostic imaging sive mesenteric ischemia, predisposing and precipitat- of mesenteric infarction. Radiology 1995; 197:79-82 14. Murray MJ, Gonze MD, Nowak LR et al: Serum D(-) Lactate lev- ing factors should be corrected along with effective els as an aid to diagnosing acute intestinal ischemia. Am J Surg treatment of mesenteric vasoconstriction. NOMI may 1994; 167:575-578 15. Boley, SJ: Early diagnosis of acute mesenteric ischemia. Hosp be treated with papaverine alone and surgery is reserved Pract 1981; 16:63-70 for patients with suspected . 16. Alexander D. Nicoloff, MD, W. Kent Williamson, MD et al: Mesenteric venous thrombosis: Patients with no Dupplex ultrasonography in evaluation of splanchnic artery . Surgical Clinics of North America 1997; 77(2): 339- 355 clinical signs of bowel infarction can be effectively 17. Kazmers A: Operative management of acute mesenteric maintained with anticoagulant and thrombolytic ther- ischemia. Ann Vasc Surg 1998; 12:187-197 18. Divino CM, Park IS, Angel LP et al: A retrospective study of apy. Thrombolytics can be administered either intra- diagnosis and management of mesenteric vein thrombosis. Am J venously or directly into the mesenteric venous Surg 2001; 181(1):20-23. 27 19. Taourel PG, Deneuville M, Pradel JA, et al: Acute mesenteric circulation, through a transjugular or percutaneous ischemia: diagnosis with contrast enhanced CT. Radiology 1996; approach. should be followed by antico- 199:632-636 20. Clark RA, Gallant TE: Acute mesenteric ischemia: angiographic agulants for 3–6 months. In the presence of bowel spectrum. American Journal of Roentgenology 1984; 142(3):555- infarction surgical resection is advised. 562 21. Boley SJ, Sprayregan S, Siegelman SS et al: Initial results from an aggressive roentgenological and surgical approach to acute mesenteric ischemia. Surgery 1977; 82:848-55 SUMMARY 22. Miyamoto M, Takayanagi I, Ohkubo H, Takagi K: Actions of papaverine on intestinal smooth muscle and its inhibition of Ischemic injury to the intestines can occur when blood cyclic AMP and cyclic GMP phosphodiesterases. Jpn J flow is compromised by a variety of mechanisms. Pharmacol 1976; 26:114–117 23. Levy PJ, Krausz MM, Manny J: Acute mesenteric ischemia: Symptoms are often nonspecific, so clinicians must improved results—a retrospective analysis of ninety-two patients. maintain a high degree of suspicion in order to identify Surgery 1990; 107(4):372-80 and treat this potentially fatal condition. n 24. VanDeinse WH, Zawacki JK, Phillips D: Treatment of acute mesenteric ischemia by percutaneous transluminal angioplasty. Gastroenterology 1986; 91(2):475-8 References 25. Klempnauer J, Grothues F, Bektas H: Results of portal thrombec- 1. Wilcox MG, Howard TJ, Plaskon LA et al: Current theories of tomy and splanchnic thrombolysis for the surgical management pathogenesis and treatment of non-occlusive mesenteric of acute mesentericoportal thrombosis. British J Surgery 1997; ischemia. Dig Disc Sci 1995; 40:709-716 84:129-132 2. Simpson R, Alon R, Kobzik L, Valeri CR et al: Neutrophil and 26. Bateller J, Kieny R: Superior mesenteric artery embolism: Eighty non neutrophil-mediated injury in intestinal ischemia-reperfusion two cases. Ann Vasc Surg 1990; 4:112-116 Ann Surg. 1993; 218(4):444–454 27. Sze DY, O’Sullivan GJ, Johnson DL: Mesenteric and Portal 3. Brown RA, Chui C, Scott HJ et al: Ultrastructural changes in the Venous Thrombosis Treated by Transjugular Mechanical canine ileal mucosal cell after mesenteric artery occlusion. Arch Thrombolysis. AJR 2000; 175:732-734 Surg 1970; 101:290-297 4. Crissnger KD, Granger DN: Mucosal injury induced by ischemia and reperfusion in the pelvic intestine: influence of the age and feeding. Gastroenterology 1989; 98:920-926 5. Parks DA, Granger DN: Contributions of ischemia and reperfu- PRACTICAL GASTROENTEROLOGY sion to mucosal lesion formation. Am J Physiol 1979; 247:G167 6. Jacob H, Brandt LJ, Farkas P et al: Beta adrenergic blockade and REPRINTS the gastrointestinal system. Am J Med 1983; 74:1042-51 7. Bulkley GB, Womack WA, Downey JM et al: Collateral blood flow in segmental intestinal ischemia: effects of vasoactive Visit our website at www.practicalgastro.com agents. Surgery 1986; 100:57-165

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