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Intestinal Angina
Intestinal Angina Prom the Department of Surgery, UniverSity of Southern California School of Medicine, Los Angeles, California
WILLIAM P. MIKKELSEN, M.D., F.A.C.S. Associate Clinical Professor of Surgery, University of Southern California School of Medicine; Senior Attending Surgeon, Los Angeles County H08pital
CLARENCE J. BERNE, M.D. Profe8sor of Surgery, University of Southern California School of Medicine; Attending Staffs, Good Samaritan, St. Vincent's and L08 Angeles General Hospital
of the complexities of arterial occlusive disease has been stimulated by recent improvement in angiographic and surgical techniques. This improvement has resulted in a clearer understanding of many basic physiopathologic mechanisms involved in certain vascular entities, treatment for which did not exist a few years ago. Into this latter category fall the syndromes produced by visceral arterial insufficiency. Those syndromes currently recognized are cerebral ischemia due to carotid and vertebral arterial disease, renal ischemia and hypertension due to renal arterial disease and intestinal ischemia due to mesenteric and celiac arterial disease. It is to the last of these that our discussion is devoted. Complete mesenteric vascular occlusion manifested by extensive infarction of bowel has long been recognized. The clinical and pathologic features as well as its lethality have been well documented.1-6 In contrast to this status gravis, little attention has been focused upon an. entity which is frequently its prodrome.6-16 This entity, intestinal angina, although uncommon, has been regularly overlooked. 17- 19 This is understandable since it has been only during the last four years that the clinical and pathological features as well as the potential for surgical cure have been adequately described.6-8 Only three years have elapsed since the first patient with this disease was treated successfully. 7 This syndrome may exist for weeks, months or years before complete, massive and usually irremediable mesenteric vascular occlusion occurs. GREATER APPRECIATION
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P.
MIKKELSEN, CLARENCE
J. BERNE
Its one consistent characteristic is postcibal abdominal discomfort or pain. This usually takes the form of cramping pain; occasionally, it occurs as a constant ache. Most commonly the pain is centered in the upper midabdomen but a generalized distribution of the pain may also occur, especially when it is severe. Concurrent back pain is not uncommon. Irrespective of its location, the pain is provoked only by the ingestion of food. If food is not ingested, pain does not occur. The greater the amount of food ingested, the greater is the intensity and duration of pain. Most commonly the distress develops 15 to 30 minutes after a meal, gradually increases in severity, reaches a plateau, and slowly abates, usually, in one to three hours. Initially, pain may occur only after the largest meal. Progressive increase in the severity of symptoms is steady as the weeks or months elapse. Vomiting and steatorrhea may occur, but have not been important or consistent features. The "food pain" or "ingestiondistress" relation is the dominant feature and leads to a reluctance on the part of the patient to eat. Undernutrition and weight loss inevitably follow. Physical examination, even in the presence of pain, is rather unrevealing. Weight loss is evident as is occasional mild abdominal distention. In some patients a systolic bruit is audible in the upper abdomen. Abdominal tenderness and findings of peritoneal irritation do not occur until bowel infarction develops. Laboratory studies and roentgenographic examination of the gastrointestinal tract, including motility studies of the small bowel, are consistently within normal limits. The pathologic process productive of intestinal angina h s been demonstrated to be atherosclerotic narrowing and obliteration of the ostia of the gastrointestinal branches of the abdominal aorta. 6 , 7,8,21,22 The rich collateral anastomoses among the three gastrointestinal aortic branches provide for maintenance of intestinal viability and function if one of these branches becomes completely occluded. 20 Although anatomic variations exist, the major avenue of communication from the celiac axis to the superior mesenteric artery is the anastomosis formed by the superior and inferior pancreaticoduodenal arteries. Inosculating the superior and inferior mesenteric arteries is the marginal artery of Drummond. Lesser collaterals among these three vessels probably exist. That these collaterals are adequate has been fully established. Celiac artery ligation is well tolerated as has been demonstrated in patients with cirrhosis. Excision of abdominal aortic aneurysms routinely sacrifices the inferior mesenteric artery. Instances of tolerated nonfatal occlusion of the superior mesenteric artery have been recorded. However, simultaneous complete occlusion of the super:ior mesenteric artery and one of the two other major aortic branches would, in all likelihood, prove fatal. The syndrome of intestinal angina requims preliminarily the complete occlusion of one of the three gastrointestinal aortic branches. In most patients this asymptomatic event takes place in the celiac axis. Subse-
1323
Intestinal Angina
quently, there develops gradual atherosclerotic ostial narrowing of one or perhaps both of the other major surviving vessels; that involving the superior mesenteric artery is dominant. When blood flow through one or both of these surviving vessels becomes sufficiently compromised, abdominal pain develops as digestion demands an increased blood supply that cannot be provided. Effort intestinal ischemia results. When the intestine is at rest, however, the blood flow remains sufficient to prevent ischemic intestinal muscle pain. It can be readily appreciated that the factors productive of intestinal angina are directly analogous to those productive of angina pectoris and lower extremity claudication. 23 Whereas the increased demand for blood flow in the latter instances is stimulated by physical exertion or walking, in the former it is induced by eating. In all three situations the etiologic factor is the failure of diseased arteries to provide for this increased demand. Pathologic studies of the superior mesenteric artery have proved to be notably significant, especially as they relate to the potential of surgical maneuvers for relief. Necropsy examination after fatal mesenteric arterial occlusion has disclosed that the smaller branches of the superior mesenteric artery are frequently collapsed and bloodless. The occluding thrombus is located at or near the ostium of this vessel and extension of this thrombus into the branches does not necessarily occur. Of particular significance has been the recognition that the wall of the superior mesenteric artery distal to its first few centimeters is invariably free of atherosclerotic disease. 24 . 26 Furthermore, this artery is of sufficient diameter to permit surgical instrumentation with facility.26 The offending atherosclerotic segment in disease of the superior mesenteric artery is limited to the ostium or to the first two or three centimeters of this vessel. The occluding mechanism may reside primarily in aortic atherosclerosis which envelopes the orifice of the superior mesenteric artery, or it may consist primarily of intimal proliferation of the first few centimeters of. this artery itself. A combination of the two mechanisms may exist. An additional mechanism of superior mesenteric artery narrowing was encountered in one of our cases. The process involved in this case was encasement and compression of this vessel by intense periaortic fibroplasia secondary to Leriche occlusive disease of the aorta. It is reasonable to believe that retroperitoneal neoplasia may at times act similarly and terminally result in intestinal angina. The visceral angiitides as typified by polyarteritis and postirradiation angiitis of the terminal branches of the superior mesenteric artery have not, in our experience, produced a clinical picture like that of intestinal angina, although the end result, intestinal ischemia, may be similar. Visceral angiitis is more likely to produce segmental bowel ischemia, rather than near40tal midgut involvement as seen. in intestinal angina. ','
".
1324
WILLIAM
P.
MIKKELSEN, CLARENCE
J.
BERNE
The term intestinal angina was selected by us in the belief that it most appropriately describes the actual nature of this disease. Other labels currently in use seem semantically to be less desirable. In this category are included "intestinal claudication," "abdominal angina," "intermittent mesenteric ischemia" and "malabsorption syndrome," and "mesenteric angina." Of these, that enjoying the greatest usage is abdominal angina. In addition to its semantic incorrectness, this term can be misinterpreted to mean abdominal pain of cardiac origin. Recognition and correlation of the clinical and pathologic features of intestinal angina were stimulated by two patients personally observed by us who served as the basis for our first report. 6 From information gained from these two patients, both of whom succumbed to massive intestinal infarction, it was apparent that the potential for surgical cure existed; such surgery should consist in restoring a normal lumen for blood flow in the superior mesenteric artery. Ideally restoration of blood flow through the celiac axis should also be accomplished. Since our report we have successfully, electively operated upon two patients with intestinal angina, one of whom has been previously reported. 7 Other reports of successful surgery for this disease have appeared. 27 • 28 It is now apparent that surgery not only provides symptomatic relief, but is the only means by which the unrelenting progression to massive intestinal infarction can be interrupted. CASE REPORTS
CASE I. H.D., a 47 year old Caucasian male, was hospitalized on October 19, 1953, for elective cholecystectomy. He complained of cramping pain in the upper abdomen and back of 5 months' duration. The pain developed approximately 30 minutes after meals, persisted for 2 or 3 hours and then subsided. The greater the amount of food ingested, the greater would be the intensity of pain. A 20 pound weight loss had occurred. Physical examination was essentially normal. Cholecystography disclosed failure of gallbladder visualization. Upper and lower gastrointestinal roentgenograms were normal. The patient's symptoms were considered to be due to cholelithiasis. On the second hospital day cholecystectomy was carried out uneventfully. The gallbladder contained 8 calculi. By the fourth postoperative day significant abdominal distention, jaundice and fever appeared. During the following 19 days before death occurred, celiotomy was performed twice but failed to control the continuing sepsis, jaundice and multiple intestinal fistulas which;developed. Necropsy revealed extensive visceral infarction which extended froml the stomach to the splenic flexure of the colon. Multiple infarcts were present in the liver and spleen. The aorta presented moderately severe atherosclerosis which had completely obliterated the orifice of the celiac axis. The ostium of the superior mesenteric artery was narrowed by atherosclerosis and a recent thrombus completely occluded this vessel for a distance of 4 cm. Distal to its atherosclerotic ostium, the superior mesenteric artery was free of atheromatous disease. CASE II. J.F.K., a 36 year old Caucasian male, was hospitalized on January 15,1956, because of cramping, generalized abdominal pain of 2 months' duration.
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Six months earlier endarterectomy of the termal aorta and iliac arteries had been performed for Leriche occlusive disease. His present pain was always postcibal, developing usually 15 minutes after eating and disappearing in 1 to 3 hours. If he fasted at mealtime, pain would not develop. There had been a 30 pound weight loss. Physical examination was essentially negative. All peripheral arterial pulsations were normal. Laboratory and x-ray examinations of the stomach, small and large bowel were normaL A diagnosis of intestinal angina was strongly considered. This prompted aortography which, although it actually confirmed this suspicion, was at the time misinterpreted. The patient was discharged from the hospital only to return 172 months later when findings of advanced intestinal infarction developed. During the interval, postcibal pain had progressively become more intense and prolonged. At celiotomy extensive, spotty ischemic gangrene extended from the stomach to the sigmoid colon. The mesenteric veins were collapsed and contained no thrombi. Death occurred 5 hours after operation. Necropsy disclosed complete occlusion at the ostium of both the celiac axis and the inferior mesenteric artery. The first centimeter of the superior mesenteric artery was narrowed to a lumen of less than 1 mm. Distal to this segment of narrowing, the superior mesenteric artery was normaL There was no thrombus in this vesseL CASE III. I.F.H., a 62 year old Caucasian male, was hospitalized on August 20, 1958. For 3 years abdominal pain had occurred intermittently after meals, occasionally associated with and relieved by vomiting. Pain was of a squeezing, bloating character and centered in the upper and right portions of the abdomen. It developed only after meals, but did not occur after every meaL A heavy meal always precipitated pain. A steady increase in the frequency and severity of abdominal pain led to progressive reduction in the size of his meals. Originally weighing 175 pounds 3 years before, he now weighed but 122 pounds. Physical examination disclosed emaciation. A systolic bruit was audible over the epigastrium. Leriche occlusive disease of the abdominal aorta and iliacs was present. Extensive laboratory studies were normal except for moderate increase in the fat content of the stools. All of the usual x-ray studies were normaL At operation, on September 8, 1958, complete abdominal exploration was negative except for the vascular abnormalities. Aortic occlusion extended from immediately below the renal arteries to the external iliac arteries. The superior mesenteric artery and its mesenteric branches were pulseless. A thrill, without expansile pulsation, was palpable in both the hepatic and splenic arteries. The mechanism of superior mesenteric artery obstruction proved to be a combination of ostial atherosclerosis and encasement of the first 3 to 4 cm. of this artery by intense fibroplastic reaction from the occlusive disease of the aorta. Liberation of this segment and endarterectomy of the ostium restored excellent blood flow through this artery and its intestinal branches. Three and one-half years have elapsed since this patient's operation. He rapidly regained 30 pounds and has maintained his weight at 150 pounds. He continues to be completely free from symptoms. CASE IV. C.F.H., a 57 year old white man, was hospitalized on July 19, 1960, for abdominal pain believed due to peptic ulcer. Seven years previously he had weighed a "chunky" 180 pounds. By means of diet he reduced to 145 pounds where he remained until 4 years before his present hospitalization when his current abdominal complaints started. On 3 occasions during these 4 years he entered an eastern hospitaL On the first 2 hospital admissions he was studied extensively and told that he had a "nervous stomach." On the third hospitalization, in February 1960, an operation was performed for a presumed perforated
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P.
MIKKELSEN, CLARENCE
J.
BERNE
gastric ulcer. During the entire 4 years his complaints consisted of postcibal cramping, upper abdominal and back pain. The greater the amount of food ingested, the greater was the intensity of the pain. Various dietary regimens failed to provide relief. Only milk and baby food were ingested during the 6 months preceding the present admission; these substances, furthermore, were taken in small portions at frequent intervals. A progressive weight loss to 91 pounds had occurred. He denied dysphagia or vomiting. His stools had recently become more frequent and lighter in color. Physical examination disclosed severe emaciation with the vertebral column clearly seen, in the supine position, to be pushing the anterior abdominal wall 5 cm. above the level of the adjacent abdomen. A harsh, systolic bruit was audible in the central and upper abdomen. A provocative test was carried out which consisted in insisting that the patient eat a reasonably full meal. This he did with relish, but with apprehension. Thirty minutes after conclusion of this meal, he was found lying on his side in bed with knees drawn up, writhing in abdominal pain. Upper gastrointestinal roentgenograms were normal. On July 22,1960, exploratory celiotomy was carried out. The liver, gallbladder, pancreas, kidneys and intestines were grossly normal. The stomach and duodenum demonstrated no evidence of recent or old peptic ulcer disease. Examination of the vascular system revealed the following: The arteries in the small intestinal mesentery were pulseless. The hepatic, left gastric and splenic arteries were pulseless. A faint pulsation was palpable in the first three centimeters of the superior mesenteric artery, but the pulsation disappeared distal to this point which also was the site of origin of the inferior pancreaticoduodenal artery. The latter vessel was considerably enlarged. Intimal atherosclerosis had markedly narrowed the lumen of the first portion of the superior mesenteric artery and had completely occluded this artery at the level of its first branch. The celiac axis was completely occluded. Endarterectomy of both of these vessels restored excellent blood flow as determined by return of normal pulsation of all vessels involved, including the finer arcade arteries of the small bowel mesentery. Postoperatively, intense jaundice occurred which cleared within 2 weeks and was believed due to postoperative pancreatic inflammatory obstruction of the common bile duct. A steady gain in weight to 145 pounds has occurred during the 1}2 years since operation, and the patient remains symptom-free. COMMENT
The clinical diagnosis of intestinal angina must be primarily one of exclusion of other causes of postprandial pain. It would be unusual, however, to encounter an entity other than intestinal angina in which so distinct a "food-pain" relation is not accompanied by at least one positive finding in the physical, laboratory or roentgenographic examinations. Weight loss in the absence of positive findings would likely stimulate a suspicion of occult neoplasia. Perhaps this suspicion could never be eliminated without the information gained from celiotomy. A provocative test, such as was used in the fourth case, might prove valuable. We have recently employed such a loading test consisting in 1 liter of homogenized milk administered within one hour. A hypotension-inducing drug might increase the sensitivity of the loading test. We have not as yet utilized this latter adjunct. Aortography unquestion-
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ably would be of value in delineating structural abnormalities of the aorta and the ostia of its branches. The use of this examination in our opinion is tempered by two features. One involves the time, expense and potential hazard of the procedure. The second is the almost urgent obligation for abdominal exploration in a patient with unexplained but progressive and unrelenting distress. Through a small abdominal incision the diagnosis of intestinal angina can be quickly established by detecting the presence or absence of small intestinal mesenteric arterial pulsations. A loop of small bowel delivered into the wound is all that is required. This procedure involves little more than would aortography and provides far more certainty in diagnosis. From an academic viewpoint, aortography performed both preoperatively and postoperatively would be valuable. Restoration of blood flow through the superior mesenteric artery and the celiac axis and its branches can be accomplished in one of two ways. For our two cases, we chose endarterectomy. In some cases, however, a bypass graft from the aorta may prove better. A combination of the two maneuvers may at times be advisable. As awareness of this disease increases, more cases will surely be recognized at a stage when surgical relief can be provided. Unfortunately, but two of the eight cases that we have identified were recognized before the onset of intestinal gangrene. Both of these patients, however, have regained their lost weight and have been completely relieved of their symptoms during the three and one-half and one and one-half years respectively since operation. SUMMARY
The designation "intestinal angina" most clearly identifies a syndrome of "effort" intestinal ischemia, which may, for months or years, precede total intestinal infarction. Its etiology has been shown to be atherosclerotic obliteration or narrowing of the ostia of the gastrointestinal branches of the abdominal aorta. Symptomatically, it is consistently characterized by postcibal, cramping, abdominal pain and weight loss. These features when added to negative investigative studies usually suffice to permit a presumptive diagnosis. At this stage surgical restoration of the gastrointestinal blood supply provides relief. REFERENCES 1. Sullivan, J. F., Ezzo, J. A., Fitzgerald, W. T. and Mack, R. E.: Mesenteric Vascular Inadequacy. Geriatrics 13: 97, 1958. 2. Morse, L. J., Krynsky, B. and Mulkeen, T. T.: Superior Mesenteric Vascular Occlusion. Am. J. Surg. 93: 788, 1957. 3. Moore, T.: Mesenteric Vascular Occlusion. Brit. J. Surg. 28: 347, 1941. 4. Musgrove, J. E. and Seybold, W. D.: Symposium on Abdominal Surgery: Mesenteric Vascular Occlusion. S. OLIN. NORTH AMERICA 30: 1063, 1950.
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J.
BERNE
5. De Muth, W. E. Jr., Fitts, W. T. and Patterson, L. T.: Mesenteric Vascular Occlusion. Internat. Obstr. Surg. 108: 209, 1959. 6. Mikkelsen, W. P.: Intestinal Angina: Its Surgical Significance. Am. J. Surg. 94: 262,1957. 7. Mikkelsen, W. P. and Zaro, J. A. Jr.: Intestinal Angina: Report of a Case with Preoperative Diagnosis and Surgical Relief. New England J. Med. 260: 912, 1959. 8. Shaw, R. S. and Maynard, E. P. III.: Acute and Chronic Thrombosis of Mesenteric Arteries Associated with Malabsorption: Report of Two Cases Successfully Treated by Thromboendarterectomy. New England J. Med. 258: 874, 1958. 9. Sedlacek, R. A. and Bean, W. B.: Abdominal "Angina": Syndrome of Intermittent Ischemia of Mesenteric Arteries. Ann. Int. Med. 46: 148, 1957. 10. Mandell, H. N.: Abdominal Angina: Report of Case and Review of the Literature. New England J. Med. 257: 1035, 1957. 11. Case Records of the Massachusetts General Hospital (Case 44332). New England J. Med. 259: 347-351, 1958. 12. Berman, L. G. and Russo, F. R.: Abdominal Angina. New England J. Med. 242: 611-613, 1950. 13. Klein, E.: Embolism and Thrombosis of Superior Mesenteric Artery. Surg. Gynec. & Obst. 33: 385-405, 1921. 14. Dunphy, J. E. and Whitfield, R. D.: Mesenteric Vascular Disease. Am. J. Surg. 47: 632-638, 1940. 15. Greenberg, G.: Peritonitis Following Abdominal Angina. M. Rec. 150: 129-133, 1939. 16. Keeley, F. X., Misanik, L. F. and Wirts, C. W.: Abdominal Angina Syndrome. Gasteroenterology 37: 480,1959. 17. Dunphy, J. E.: Abdominal Pain of Vascular Origin. Am. J. M. Sc. 192: 109-113, 1936. 18. Benjamin, D.: Mesenteric Thrombosis. Am. J. Surg. 76: 338-343, 1948. 19. McClenahan, J. E. and Fisher, B.: Mesenteric Thrombosis. Surgery 23: 778-785, 1948. 20. Reiner, L., Rodriguez, F. L., Platt, R. and Schlesinger"M. J.: Injection Studies on the Mesenteric Arterial Circulation. 1. Technique and Observations on Collaterals. Surgery 45: 820, 1959. 21. Case Records of the Massachusetts General Hospital (Case 35071). New England J. Med. 240: 262-267, 1949. 22. Berman, J. K. and Thornton, H. C.: Case Report: Occlusive Vascular Disease of Abdomen. J. Indiana M. A. 33: 138-142, 1940. 23. Leading Article. Intestinal Angina. Lancet 1: 1211, 1958. 24. Carucci, J. J.: Mesenteric Vascular Occlusion. Am. J. Surg. 85: 47-54, 1953. 25. Derrick, J. R. and Logan, W. D.: Mesenteric Arterial Insufficiency. Surgery 44: 823-827, 1958. 26. Eisenberg, A. A. and Schlink, H. A.: Mesenteric Vascular Occlusion. Surg. Gynec. & Obst. 27: 66-72, 1918. 27. Derrick, J. R., Pollard, H. S. and Moore, R. M.: The Pattern of Arteriosclerotic Narrowing of the Celiac and Superior Mesenteric Arteries. Ann. Surg. 149: 684,1959. 28. Morris, G. C. and DeBakey, M. E.: Abdominal Angina-Diagnosis and Surgical Treatment. J.A.M.A. 176: 89, 1961. 1930 Wilshire Boulevard Los Angeles 57, California
WILLIAM P. MIKKELSEN, M.D., F.A.C.S. Associate Clinical Professor of Surgery, University of Southern California School of Medicine; Senior Attending Surgeon, Los Angeles County H08pital
CLARENCE J. BERNE, M.D. Profe8sor of Surgery, University of Southern California School of Medicine; Attending Staffs, Good Samaritan, St. Vincent's and L08 Angeles General Hospital
of the complexities of arterial occlusive disease has been stimulated by recent improvement in angiographic and surgical techniques. This improvement has resulted in a clearer understanding of many basic physiopathologic mechanisms involved in certain vascular entities, treatment for which did not exist a few years ago. Into this latter category fall the syndromes produced by visceral arterial insufficiency. Those syndromes currently recognized are cerebral ischemia due to carotid and vertebral arterial disease, renal ischemia and hypertension due to renal arterial disease and intestinal ischemia due to mesenteric and celiac arterial disease. It is to the last of these that our discussion is devoted. Complete mesenteric vascular occlusion manifested by extensive infarction of bowel has long been recognized. The clinical and pathologic features as well as its lethality have been well documented.1-6 In contrast to this status gravis, little attention has been focused upon an. entity which is frequently its prodrome.6-16 This entity, intestinal angina, although uncommon, has been regularly overlooked. 17- 19 This is understandable since it has been only during the last four years that the clinical and pathological features as well as the potential for surgical cure have been adequately described.6-8 Only three years have elapsed since the first patient with this disease was treated successfully. 7 This syndrome may exist for weeks, months or years before complete, massive and usually irremediable mesenteric vascular occlusion occurs. GREATER APPRECIATION
1321
1322
WILLIAM
P.
MIKKELSEN, CLARENCE
J. BERNE
Its one consistent characteristic is postcibal abdominal discomfort or pain. This usually takes the form of cramping pain; occasionally, it occurs as a constant ache. Most commonly the pain is centered in the upper midabdomen but a generalized distribution of the pain may also occur, especially when it is severe. Concurrent back pain is not uncommon. Irrespective of its location, the pain is provoked only by the ingestion of food. If food is not ingested, pain does not occur. The greater the amount of food ingested, the greater is the intensity and duration of pain. Most commonly the distress develops 15 to 30 minutes after a meal, gradually increases in severity, reaches a plateau, and slowly abates, usually, in one to three hours. Initially, pain may occur only after the largest meal. Progressive increase in the severity of symptoms is steady as the weeks or months elapse. Vomiting and steatorrhea may occur, but have not been important or consistent features. The "food pain" or "ingestiondistress" relation is the dominant feature and leads to a reluctance on the part of the patient to eat. Undernutrition and weight loss inevitably follow. Physical examination, even in the presence of pain, is rather unrevealing. Weight loss is evident as is occasional mild abdominal distention. In some patients a systolic bruit is audible in the upper abdomen. Abdominal tenderness and findings of peritoneal irritation do not occur until bowel infarction develops. Laboratory studies and roentgenographic examination of the gastrointestinal tract, including motility studies of the small bowel, are consistently within normal limits. The pathologic process productive of intestinal angina h s been demonstrated to be atherosclerotic narrowing and obliteration of the ostia of the gastrointestinal branches of the abdominal aorta. 6 , 7,8,21,22 The rich collateral anastomoses among the three gastrointestinal aortic branches provide for maintenance of intestinal viability and function if one of these branches becomes completely occluded. 20 Although anatomic variations exist, the major avenue of communication from the celiac axis to the superior mesenteric artery is the anastomosis formed by the superior and inferior pancreaticoduodenal arteries. Inosculating the superior and inferior mesenteric arteries is the marginal artery of Drummond. Lesser collaterals among these three vessels probably exist. That these collaterals are adequate has been fully established. Celiac artery ligation is well tolerated as has been demonstrated in patients with cirrhosis. Excision of abdominal aortic aneurysms routinely sacrifices the inferior mesenteric artery. Instances of tolerated nonfatal occlusion of the superior mesenteric artery have been recorded. However, simultaneous complete occlusion of the super:ior mesenteric artery and one of the two other major aortic branches would, in all likelihood, prove fatal. The syndrome of intestinal angina requims preliminarily the complete occlusion of one of the three gastrointestinal aortic branches. In most patients this asymptomatic event takes place in the celiac axis. Subse-
1323
Intestinal Angina
quently, there develops gradual atherosclerotic ostial narrowing of one or perhaps both of the other major surviving vessels; that involving the superior mesenteric artery is dominant. When blood flow through one or both of these surviving vessels becomes sufficiently compromised, abdominal pain develops as digestion demands an increased blood supply that cannot be provided. Effort intestinal ischemia results. When the intestine is at rest, however, the blood flow remains sufficient to prevent ischemic intestinal muscle pain. It can be readily appreciated that the factors productive of intestinal angina are directly analogous to those productive of angina pectoris and lower extremity claudication. 23 Whereas the increased demand for blood flow in the latter instances is stimulated by physical exertion or walking, in the former it is induced by eating. In all three situations the etiologic factor is the failure of diseased arteries to provide for this increased demand. Pathologic studies of the superior mesenteric artery have proved to be notably significant, especially as they relate to the potential of surgical maneuvers for relief. Necropsy examination after fatal mesenteric arterial occlusion has disclosed that the smaller branches of the superior mesenteric artery are frequently collapsed and bloodless. The occluding thrombus is located at or near the ostium of this vessel and extension of this thrombus into the branches does not necessarily occur. Of particular significance has been the recognition that the wall of the superior mesenteric artery distal to its first few centimeters is invariably free of atherosclerotic disease. 24 . 26 Furthermore, this artery is of sufficient diameter to permit surgical instrumentation with facility.26 The offending atherosclerotic segment in disease of the superior mesenteric artery is limited to the ostium or to the first two or three centimeters of this vessel. The occluding mechanism may reside primarily in aortic atherosclerosis which envelopes the orifice of the superior mesenteric artery, or it may consist primarily of intimal proliferation of the first few centimeters of. this artery itself. A combination of the two mechanisms may exist. An additional mechanism of superior mesenteric artery narrowing was encountered in one of our cases. The process involved in this case was encasement and compression of this vessel by intense periaortic fibroplasia secondary to Leriche occlusive disease of the aorta. It is reasonable to believe that retroperitoneal neoplasia may at times act similarly and terminally result in intestinal angina. The visceral angiitides as typified by polyarteritis and postirradiation angiitis of the terminal branches of the superior mesenteric artery have not, in our experience, produced a clinical picture like that of intestinal angina, although the end result, intestinal ischemia, may be similar. Visceral angiitis is more likely to produce segmental bowel ischemia, rather than near40tal midgut involvement as seen. in intestinal angina. ','
".
1324
WILLIAM
P.
MIKKELSEN, CLARENCE
J.
BERNE
The term intestinal angina was selected by us in the belief that it most appropriately describes the actual nature of this disease. Other labels currently in use seem semantically to be less desirable. In this category are included "intestinal claudication," "abdominal angina," "intermittent mesenteric ischemia" and "malabsorption syndrome," and "mesenteric angina." Of these, that enjoying the greatest usage is abdominal angina. In addition to its semantic incorrectness, this term can be misinterpreted to mean abdominal pain of cardiac origin. Recognition and correlation of the clinical and pathologic features of intestinal angina were stimulated by two patients personally observed by us who served as the basis for our first report. 6 From information gained from these two patients, both of whom succumbed to massive intestinal infarction, it was apparent that the potential for surgical cure existed; such surgery should consist in restoring a normal lumen for blood flow in the superior mesenteric artery. Ideally restoration of blood flow through the celiac axis should also be accomplished. Since our report we have successfully, electively operated upon two patients with intestinal angina, one of whom has been previously reported. 7 Other reports of successful surgery for this disease have appeared. 27 • 28 It is now apparent that surgery not only provides symptomatic relief, but is the only means by which the unrelenting progression to massive intestinal infarction can be interrupted. CASE REPORTS
CASE I. H.D., a 47 year old Caucasian male, was hospitalized on October 19, 1953, for elective cholecystectomy. He complained of cramping pain in the upper abdomen and back of 5 months' duration. The pain developed approximately 30 minutes after meals, persisted for 2 or 3 hours and then subsided. The greater the amount of food ingested, the greater would be the intensity of pain. A 20 pound weight loss had occurred. Physical examination was essentially normal. Cholecystography disclosed failure of gallbladder visualization. Upper and lower gastrointestinal roentgenograms were normal. The patient's symptoms were considered to be due to cholelithiasis. On the second hospital day cholecystectomy was carried out uneventfully. The gallbladder contained 8 calculi. By the fourth postoperative day significant abdominal distention, jaundice and fever appeared. During the following 19 days before death occurred, celiotomy was performed twice but failed to control the continuing sepsis, jaundice and multiple intestinal fistulas which;developed. Necropsy revealed extensive visceral infarction which extended froml the stomach to the splenic flexure of the colon. Multiple infarcts were present in the liver and spleen. The aorta presented moderately severe atherosclerosis which had completely obliterated the orifice of the celiac axis. The ostium of the superior mesenteric artery was narrowed by atherosclerosis and a recent thrombus completely occluded this vessel for a distance of 4 cm. Distal to its atherosclerotic ostium, the superior mesenteric artery was free of atheromatous disease. CASE II. J.F.K., a 36 year old Caucasian male, was hospitalized on January 15,1956, because of cramping, generalized abdominal pain of 2 months' duration.
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Six months earlier endarterectomy of the termal aorta and iliac arteries had been performed for Leriche occlusive disease. His present pain was always postcibal, developing usually 15 minutes after eating and disappearing in 1 to 3 hours. If he fasted at mealtime, pain would not develop. There had been a 30 pound weight loss. Physical examination was essentially negative. All peripheral arterial pulsations were normal. Laboratory and x-ray examinations of the stomach, small and large bowel were normaL A diagnosis of intestinal angina was strongly considered. This prompted aortography which, although it actually confirmed this suspicion, was at the time misinterpreted. The patient was discharged from the hospital only to return 172 months later when findings of advanced intestinal infarction developed. During the interval, postcibal pain had progressively become more intense and prolonged. At celiotomy extensive, spotty ischemic gangrene extended from the stomach to the sigmoid colon. The mesenteric veins were collapsed and contained no thrombi. Death occurred 5 hours after operation. Necropsy disclosed complete occlusion at the ostium of both the celiac axis and the inferior mesenteric artery. The first centimeter of the superior mesenteric artery was narrowed to a lumen of less than 1 mm. Distal to this segment of narrowing, the superior mesenteric artery was normaL There was no thrombus in this vesseL CASE III. I.F.H., a 62 year old Caucasian male, was hospitalized on August 20, 1958. For 3 years abdominal pain had occurred intermittently after meals, occasionally associated with and relieved by vomiting. Pain was of a squeezing, bloating character and centered in the upper and right portions of the abdomen. It developed only after meals, but did not occur after every meaL A heavy meal always precipitated pain. A steady increase in the frequency and severity of abdominal pain led to progressive reduction in the size of his meals. Originally weighing 175 pounds 3 years before, he now weighed but 122 pounds. Physical examination disclosed emaciation. A systolic bruit was audible over the epigastrium. Leriche occlusive disease of the abdominal aorta and iliacs was present. Extensive laboratory studies were normal except for moderate increase in the fat content of the stools. All of the usual x-ray studies were normaL At operation, on September 8, 1958, complete abdominal exploration was negative except for the vascular abnormalities. Aortic occlusion extended from immediately below the renal arteries to the external iliac arteries. The superior mesenteric artery and its mesenteric branches were pulseless. A thrill, without expansile pulsation, was palpable in both the hepatic and splenic arteries. The mechanism of superior mesenteric artery obstruction proved to be a combination of ostial atherosclerosis and encasement of the first 3 to 4 cm. of this artery by intense fibroplastic reaction from the occlusive disease of the aorta. Liberation of this segment and endarterectomy of the ostium restored excellent blood flow through this artery and its intestinal branches. Three and one-half years have elapsed since this patient's operation. He rapidly regained 30 pounds and has maintained his weight at 150 pounds. He continues to be completely free from symptoms. CASE IV. C.F.H., a 57 year old white man, was hospitalized on July 19, 1960, for abdominal pain believed due to peptic ulcer. Seven years previously he had weighed a "chunky" 180 pounds. By means of diet he reduced to 145 pounds where he remained until 4 years before his present hospitalization when his current abdominal complaints started. On 3 occasions during these 4 years he entered an eastern hospitaL On the first 2 hospital admissions he was studied extensively and told that he had a "nervous stomach." On the third hospitalization, in February 1960, an operation was performed for a presumed perforated
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MIKKELSEN, CLARENCE
J.
BERNE
gastric ulcer. During the entire 4 years his complaints consisted of postcibal cramping, upper abdominal and back pain. The greater the amount of food ingested, the greater was the intensity of the pain. Various dietary regimens failed to provide relief. Only milk and baby food were ingested during the 6 months preceding the present admission; these substances, furthermore, were taken in small portions at frequent intervals. A progressive weight loss to 91 pounds had occurred. He denied dysphagia or vomiting. His stools had recently become more frequent and lighter in color. Physical examination disclosed severe emaciation with the vertebral column clearly seen, in the supine position, to be pushing the anterior abdominal wall 5 cm. above the level of the adjacent abdomen. A harsh, systolic bruit was audible in the central and upper abdomen. A provocative test was carried out which consisted in insisting that the patient eat a reasonably full meal. This he did with relish, but with apprehension. Thirty minutes after conclusion of this meal, he was found lying on his side in bed with knees drawn up, writhing in abdominal pain. Upper gastrointestinal roentgenograms were normal. On July 22,1960, exploratory celiotomy was carried out. The liver, gallbladder, pancreas, kidneys and intestines were grossly normal. The stomach and duodenum demonstrated no evidence of recent or old peptic ulcer disease. Examination of the vascular system revealed the following: The arteries in the small intestinal mesentery were pulseless. The hepatic, left gastric and splenic arteries were pulseless. A faint pulsation was palpable in the first three centimeters of the superior mesenteric artery, but the pulsation disappeared distal to this point which also was the site of origin of the inferior pancreaticoduodenal artery. The latter vessel was considerably enlarged. Intimal atherosclerosis had markedly narrowed the lumen of the first portion of the superior mesenteric artery and had completely occluded this artery at the level of its first branch. The celiac axis was completely occluded. Endarterectomy of both of these vessels restored excellent blood flow as determined by return of normal pulsation of all vessels involved, including the finer arcade arteries of the small bowel mesentery. Postoperatively, intense jaundice occurred which cleared within 2 weeks and was believed due to postoperative pancreatic inflammatory obstruction of the common bile duct. A steady gain in weight to 145 pounds has occurred during the 1}2 years since operation, and the patient remains symptom-free. COMMENT
The clinical diagnosis of intestinal angina must be primarily one of exclusion of other causes of postprandial pain. It would be unusual, however, to encounter an entity other than intestinal angina in which so distinct a "food-pain" relation is not accompanied by at least one positive finding in the physical, laboratory or roentgenographic examinations. Weight loss in the absence of positive findings would likely stimulate a suspicion of occult neoplasia. Perhaps this suspicion could never be eliminated without the information gained from celiotomy. A provocative test, such as was used in the fourth case, might prove valuable. We have recently employed such a loading test consisting in 1 liter of homogenized milk administered within one hour. A hypotension-inducing drug might increase the sensitivity of the loading test. We have not as yet utilized this latter adjunct. Aortography unquestion-
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ably would be of value in delineating structural abnormalities of the aorta and the ostia of its branches. The use of this examination in our opinion is tempered by two features. One involves the time, expense and potential hazard of the procedure. The second is the almost urgent obligation for abdominal exploration in a patient with unexplained but progressive and unrelenting distress. Through a small abdominal incision the diagnosis of intestinal angina can be quickly established by detecting the presence or absence of small intestinal mesenteric arterial pulsations. A loop of small bowel delivered into the wound is all that is required. This procedure involves little more than would aortography and provides far more certainty in diagnosis. From an academic viewpoint, aortography performed both preoperatively and postoperatively would be valuable. Restoration of blood flow through the superior mesenteric artery and the celiac axis and its branches can be accomplished in one of two ways. For our two cases, we chose endarterectomy. In some cases, however, a bypass graft from the aorta may prove better. A combination of the two maneuvers may at times be advisable. As awareness of this disease increases, more cases will surely be recognized at a stage when surgical relief can be provided. Unfortunately, but two of the eight cases that we have identified were recognized before the onset of intestinal gangrene. Both of these patients, however, have regained their lost weight and have been completely relieved of their symptoms during the three and one-half and one and one-half years respectively since operation. SUMMARY
The designation "intestinal angina" most clearly identifies a syndrome of "effort" intestinal ischemia, which may, for months or years, precede total intestinal infarction. Its etiology has been shown to be atherosclerotic obliteration or narrowing of the ostia of the gastrointestinal branches of the abdominal aorta. Symptomatically, it is consistently characterized by postcibal, cramping, abdominal pain and weight loss. These features when added to negative investigative studies usually suffice to permit a presumptive diagnosis. At this stage surgical restoration of the gastrointestinal blood supply provides relief. REFERENCES 1. Sullivan, J. F., Ezzo, J. A., Fitzgerald, W. T. and Mack, R. E.: Mesenteric Vascular Inadequacy. Geriatrics 13: 97, 1958. 2. Morse, L. J., Krynsky, B. and Mulkeen, T. T.: Superior Mesenteric Vascular Occlusion. Am. J. Surg. 93: 788, 1957. 3. Moore, T.: Mesenteric Vascular Occlusion. Brit. J. Surg. 28: 347, 1941. 4. Musgrove, J. E. and Seybold, W. D.: Symposium on Abdominal Surgery: Mesenteric Vascular Occlusion. S. OLIN. NORTH AMERICA 30: 1063, 1950.
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5. De Muth, W. E. Jr., Fitts, W. T. and Patterson, L. T.: Mesenteric Vascular Occlusion. Internat. Obstr. Surg. 108: 209, 1959. 6. Mikkelsen, W. P.: Intestinal Angina: Its Surgical Significance. Am. J. Surg. 94: 262,1957. 7. Mikkelsen, W. P. and Zaro, J. A. Jr.: Intestinal Angina: Report of a Case with Preoperative Diagnosis and Surgical Relief. New England J. Med. 260: 912, 1959. 8. Shaw, R. S. and Maynard, E. P. III.: Acute and Chronic Thrombosis of Mesenteric Arteries Associated with Malabsorption: Report of Two Cases Successfully Treated by Thromboendarterectomy. New England J. Med. 258: 874, 1958. 9. Sedlacek, R. A. and Bean, W. B.: Abdominal "Angina": Syndrome of Intermittent Ischemia of Mesenteric Arteries. Ann. Int. Med. 46: 148, 1957. 10. Mandell, H. N.: Abdominal Angina: Report of Case and Review of the Literature. New England J. Med. 257: 1035, 1957. 11. Case Records of the Massachusetts General Hospital (Case 44332). New England J. Med. 259: 347-351, 1958. 12. Berman, L. G. and Russo, F. R.: Abdominal Angina. New England J. Med. 242: 611-613, 1950. 13. Klein, E.: Embolism and Thrombosis of Superior Mesenteric Artery. Surg. Gynec. & Obst. 33: 385-405, 1921. 14. Dunphy, J. E. and Whitfield, R. D.: Mesenteric Vascular Disease. Am. J. Surg. 47: 632-638, 1940. 15. Greenberg, G.: Peritonitis Following Abdominal Angina. M. Rec. 150: 129-133, 1939. 16. Keeley, F. X., Misanik, L. F. and Wirts, C. W.: Abdominal Angina Syndrome. Gasteroenterology 37: 480,1959. 17. Dunphy, J. E.: Abdominal Pain of Vascular Origin. Am. J. M. Sc. 192: 109-113, 1936. 18. Benjamin, D.: Mesenteric Thrombosis. Am. J. Surg. 76: 338-343, 1948. 19. McClenahan, J. E. and Fisher, B.: Mesenteric Thrombosis. Surgery 23: 778-785, 1948. 20. Reiner, L., Rodriguez, F. L., Platt, R. and Schlesinger"M. J.: Injection Studies on the Mesenteric Arterial Circulation. 1. Technique and Observations on Collaterals. Surgery 45: 820, 1959. 21. Case Records of the Massachusetts General Hospital (Case 35071). New England J. Med. 240: 262-267, 1949. 22. Berman, J. K. and Thornton, H. C.: Case Report: Occlusive Vascular Disease of Abdomen. J. Indiana M. A. 33: 138-142, 1940. 23. Leading Article. Intestinal Angina. Lancet 1: 1211, 1958. 24. Carucci, J. J.: Mesenteric Vascular Occlusion. Am. J. Surg. 85: 47-54, 1953. 25. Derrick, J. R. and Logan, W. D.: Mesenteric Arterial Insufficiency. Surgery 44: 823-827, 1958. 26. Eisenberg, A. A. and Schlink, H. A.: Mesenteric Vascular Occlusion. Surg. Gynec. & Obst. 27: 66-72, 1918. 27. Derrick, J. R., Pollard, H. S. and Moore, R. M.: The Pattern of Arteriosclerotic Narrowing of the Celiac and Superior Mesenteric Arteries. Ann. Surg. 149: 684,1959. 28. Morris, G. C. and DeBakey, M. E.: Abdominal Angina-Diagnosis and Surgical Treatment. J.A.M.A. 176: 89, 1961. 1930 Wilshire Boulevard Los Angeles 57, California