Tyramine kinetics and metabolism in cirrhosis.

Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injections of [3H]-tyramine (180--200 muCi 12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (alpha-phase) followed by a slower decline (beta-phase) with an average t 1/2 of 20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 microgram/min, respectively. In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent different in beta-t 1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 microgram/min) in these patients was significantly greater (P less than 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) as compared with normals. Although the tyramine clearance rates are similar in normals and cirrhotics, different mechanisms may be responsible for catabolism.

Accelerated fibrinogen and platelet destruction after peritoneovenous shunting.

Peritoneovenous shunting with the LeVeen valve is generally recognized as an effective procedure for the treatment of intractable ascites and renal failure associated with severe liver disease. We recently observed a generalized hemorrhagic diathesis in patients receiving these valves. To investigate the mechanism of this hemorrhagic complication, we prospectively performed kinetic studies with 51Cr-labelled platelets and 125I-labelled fibrinogen in ten patients. When results of studies before and after valve insertion were compared, the following reductions were noted: fibrinogen concentration, 55%; the fibrinogen survival, 49%; the platelet count, 55% and the platelet survival, 35%. No endotoxin was detectable in ascitic fluid preoperatively, and there was no apparent relationship between ascitic fluid cell counts and changes in fibrinogen and platelet survival. Until the component or components of ascitic fluid responsible for accelerated consumption can be identified and steps are taken to modify the rates of platelet and fibrinogen consumption, it would seem prudent to select patients for surgery conservatively.

Congenital abdominal aortic aneurysms: report of a case and review of the literature.

Congenital abdominal aortic aneurysms are medical curiosities because of their rare occurrence even in groups with hereditary derangements of connective tissue metabolism (e.g., Marfan's syndrome and Ehlers- Danlos syndrome). We present the case of a 2 1/2-year-old boy with a congenital aneurysm of the aortoiliac bifurcation managed by excision and graft replacement. No associated disorder of connective tissue or other pathogenetic mechanism was discovered in this patient. The authors have summarized the existing literature regarding these rare but potentially lethal aneurysms.

Reoperative abdominal arterial surgery--a ten-year experience.

The safety and durability of elective reconstructive procedures of the abdominal aorta and its major branches are universally accepted; however, late complications continue to threaten limbs and lives of a minority of patients. The strategy of managing such revascularization failures has received inadequate attention. Between February 1971 and July 1981, 76 patients underwent 83 remedial, transabdominal revascularization procedures because of failed reconstructions. Group I consisted of 34 patients with occlusive complications (0% remedial operative mortality rate); group II, 21 patients with prosthetic sepsis including graft-enteric fistula (14% operative mortality); group III, 11 patients with aneurysmal degeneration (36% operative mortality); and group IV, 10 patients with visceral ischemia (0% operative mortality). The remedial operative mortality rate for the combined groups was 7.9%. Limb preservation was the rule in group I (91%); however, 29% of limbs at risk in group II ultimately required major amputation (15% early, 14% late). All patients in group II without an established graft-enteric fistula were saved; however, three of ten with active hemorrhage died of the sequelae of hypovolemic shock. Progressive arteriosclerotic morbidity and massive intraoperative bleeding accounted for the high mortality rate in group III. Favorable results were obtained in reoperation for recurrent visceral ischemia (renal ischemia in five, mesenteric ischemia in five). On the basis of this experience, an aggressive surgical approach seems justified. First, complete bifemoral revascularization performed at the time of original operation should reduce the need for reoperation. Second, elective, transabdominal remedial arterial surgery can be done with acceptable morbidity and mortality rates. Third, graft-enteric erosions and periprosthetic sepsis must be treated aggressively to avoid life-threatening sepsis and hemorrhage. Finally, anatomic revascularization can be performed successfully after a suitable period following removal of an infected retroperitoneal prosthesis.

Does contralateral carotid occlusion influence neurologic fate of carotid endarterectomy?

Divergent opinions regarding operative risks and late prognosis of patients undergoing endarterectomy for carotid stenosis with contralateral carotid occlusion have prompted a review of the experience at Emory University Hospital from Jan. 1, 1978, through Dec. 31, 1982. Fifty-four patients (37 men, 17 women; mean age 63 years) who underwent carotid endarterectomy (CEA) with contralateral carotid occlusion (group I) were compared with 410 demographically similar patients without contralateral carotid occlusion (group II) who underwent 503 CEAs during the same interval. CEA indications in group I were the following and were proportionately similar to those of group II: hemispheric transient ischemic attacks, 22 patients; asymptomatic stenosis, 12 patients; nonhemispheric symptoms, 11 patients; previous cerebral infarction, eight patients; and vascular tinnitus, one patient. General anesthesia, routine intraluminal shunting, systemic heparinization, and arteriotomy closure without patch were routinely employed in both groups. Three patients in group I suffered permanent neurologic deficits after operation (5.6%) and two had transient postoperative deficits with complete recovery. Ten patients (2.0%) in group II suffered permanent neurologic deficits and 10 patients experienced transient neurologic events after operation. Neither the transient nor the permanent neurologic deficit rates were statistically different (p greater than 0.05; Fisher exact test) in the two groups. Operative mortality rates for group I and group II were 0% and 0.8%, respectively, and were not significantly different (p greater than 0.10; Fisher exact test). Late postoperative ischemic brain infarctions occurred in two patients in group I (3.8%) and in 13 patients (3.6%) in group II (p greater than 0.10; Fisher exact test). Kaplan-Meier survival analyses were virtually identical in both groups, with the majority of deaths caused by cardiac occlusion may undergo CEA with morbidity and mortality rates similar to those without contralateral occlusions. Contralateral carotid occlusion does not necessarily portend an unfavorable early or late prognosis after CEA.

LeVeen vs Denver peritoneovenous shunts for intractable ascites of cirrhosis. A randomized, prospective trial.

Peritoneovenous shunts (PVSs) have provided salutary effects on medically recalcitrant ascites, functional renal impairment, nutritional derangements, ventilatory embarrassment, and locomotion potential in patients with cirrhosis. While the LeVeen (LPVS) and Denver (DPVS) PVSs are most frequently implanted in such patients, postoperative complications of bleeding gastroesophageal varices, sepsis, and shunt occlusion occur with notable frequency. Addressing primarily the complication of PVS occlusion, a randomized prospective trial of LPVSs and DPVSs was conducted in cirrhotic patients with refractory ascites. From July 1, 1982 to July 1, 1984, 26 initial PVSs were implanted for hepatic-related intractable ascites. Twenty-two patients were eligible for randomization (cirrhosis, sterile ascites, initial PVS, total bilirubin level less than or equal to 6.0 mg/dL, prothrombin time less than or equal to 5-s prolongation, serum creatinine level less than or equal to 2.0 mg/dL [creatinine clearance rate greater than or equal to 20 mL/min], absence of recent [less than 30 days] bleeding gastroesophageal varices, or absent spontaneous encephalopathy). Twelve LPVSs and ten DPVSs were implanted; however, one patient with a DPVS was found to have hepatic polycystic disease and was excluded from analysis. All patients were followed up until death or Jan 1, 1985. The PVS patency determinations included contrast shuntography, technetium Tc 99m albumin scintigraphy, sequential manual compression (DPVS), and operative or autopsy observation. Using the Kaplan-Meier actuarial analysis, the LPVS patency proved to be highly superior to that of the DPVS, while survival was not significantly different. As LPVS and DPVS complications other than patency are comparable, the LPVS is preferred for its superior patency in cirrhotic patients with intractable ascites.

Peritoneovenous shunts. Lessons learned from an eight-year experience with 70 patients.

The peritoneovenous shunt (PVS) is preferred over other treatment modalities in the treatment of the cirrhotic patient who has intractable ascites. The favorable effects on nutrition, pulmonary, and renal function, in addition to prompt control of ascites, frequently overshadow potentially life-threatening complications. We summarized our experience with the PVS in 70 patients with portal hypertension at Emory University, Atlanta, and identified the perioperative complications and operative mortalities. Late complications of sepsis and variceal hemorrhage were frequent and often were fatal. Of the multiple preoperative clinical and laboratory determinants, only the serum bilirubin level (greater than or equal to 3 mg/dL) was predictive of the operative mortality and longevity of survivors. The PVS should be reserved for patients with disabling, truly refractory ascites.

Splenic artery ligation in distal splenorenal shunts.

Splenic artery ligation, a simple surgical procedure expected to decrease splenic flow and portal pressure in patients with cirrhosis of the liver, was performed concomitantly with a distal splenorenal shunt procedure in six patients and as the main surgical procedure in two patients. Immediate cessation of bleeding was achieved in the four patients in whom the splenic artery was ligated to reduce intraoperative bleeding. However, three of the seven patients with previous gastroesophageal hemorrhage rebled from various postoperatively. Symptoms of splenic infarction were observed in six patients, resulting in thrombosis of the splenic vein and/or of the distal splenorenal shunt in four patients and necessitating splenectomy in one. This incidence of thrombosis of the distal splenorenal shunt is much higher than the overall incidence of 5 per cent observed at our institution. It is thus concluded that the splenic artery should not be ligated in cirrhotic patients with patent distal splenorenal shunts, since splenic arterial collateral vessels have already been reduced by the gastric devascularization, an integral component of the distal splenorenal shunt.

Variceal hemorrhage in the veteran population. To shunt or not to shunt?

Portasystemic decompression remains the most definitive procedure in the control of portal hypertension (PHT) and bleeding gastroesophageal varices (BGEV). However, controversy prevails regarding shunt timing, type, and even propriety, especially in alcoholics. Analysis of a recent portal hypertension questionnaire submitted to 75 university-affiliated Veterans Administration Medical Centers (VAMC) reflected optimism regarding portasystemic shunts for the management of bleeding varices; disappointingly, however, on the average, only 20 to 25 per cent of variceal bleeders underwent definitive surgical management of any type. Ending in January 1980, a 14-year experience at the Atlanta VAMC with 72 portasystemic shunts was reviewed and demonstrates that shunt procedures may be extended to the veteran, predominantly alcoholic, population. Criteria for successful patient selection and operation are presented. While elective variceal decompression, preferably by the distal splenorenal shunt operation, may be performed with minimal morbidity and mortality, more efficient control of alcoholism is essential to prevent late deaths from hepatic failure.

Wringer arm injuries.

During a 20-yr period, 483 children 16 yr of age or under were hospitalized for management of a wringer arm injury. Although the majority were indigent, black males, such trauma was frequently sustained by all classes and races as well as by both sexes. Principles of treatment consisted of cleansing the abrasion wound, application of a pressure dressing from axilla to finger tips, elevation, and close observation. With the exception of a destroyed brachial vein in one patien, significant vascular injuries did not occur despite a "medical fixation" on evidences of impaired circulation. Likewise, no fractures were noted even though all patients had x-rays of the full extremity. However, there were six metacarpophalangeal dislocations, five instances of neuropathy, and one traumatic amputation. Major skin sloughs occurred in 18 children, yet only 11 of them required a skin graft.

Descending thoracic aortofemoral-femoral bypass: a remedial alternative for the failed aortobifemoral bypass.

The patient with densely scarred retroperitoneum, multiple previous celiotomies, failed remedial retroperitoneal aortobifemoral graft or multiple extra-anatomic graft failures presenting with limb-threatening ischemia taxes the ingenuity of the most experienced vascular surgeon. Lower extremity revascularization, in these situations, is dependent upon achieving adequate femoral arterial inflow. One remedial alternative method to achieve this goal is the descending thoracic aortofemoral-femoral bypass (DTAF-F). The authors' experience with three recent patients requiring DTAF-F is described, and literature of similar alternative techniques is reviewed.

Renal decapsulation in the prevention of post-ischemic oliguria.

The delayed onset of anuria/oliguria in acute tubular necrosis has been theorized to represent a complicating compartment syndrome, i.e., parenchymal swelling within an unyielding capsule. To test this proposition, 12 monkeys had suprarenal aortic cross-clamping, followed by unilateral renal decapsulation to create an experimental as well as a control kidney unit in the same animal. Histologic examination uniformly confirmed tubular necrosis at death or sacrifice. Subsequent split renal function studies (creatinine, urea, and free water clearances) indicated significantly greater maintenance of renal function by the decapsulated kidney than by its paired control. Clinical evaluation in 21 hemorrhagic shock patients, with the capsule of one kidney stripped, revealed on follow-up that 15 developed a renal failure consistent with acute tubular necrosis. Although three patients with polyuric failure died before split studies could be run and two others have been too recent for computer analysis to have been completed, nine of the remaining ten had significantly greater renal plasma flows (194 versus 121 ml/min M(2), p < .01) and significantly greater urine flows (.99 versus .18 ml/min M(2), p < .01) on the decapsulated side than on the control, as determined by differential renal scans. No significant difference in these same lateralized renal functions was noted in the tenth patient with renal failure and in the six survivors without renal failure. Renal decapsulation as prophylaxis reduced the anticipated incidence of oliguria/anuria from an expected 75% to 7% (p < .01) in these 21 shock patients. Such data suggest that delayed renal ischemia, possibly based on a compartment syndrome, may be the cause for a progression of acute tubular necrosis from polyuria to oliguria and then to anuria.

Open treatment of pancreatic abscess.

Twenty-one consecutive patients with pancreatic abscess were managed by an open packing technique. Despite an anticipated mortality of less than 65 per cent predicted by Ranson's prognostic signs, the mortality in this group of patients was only 14 per cent. The marked improvement in results was attributed to several factors: earlier diagnosis and surgical intervention based upon serial abdominal tomography; prevention of persistent or recurrent sepsis by frequent scheduled dressing changes, and prevention of frequently related complications. Seven patients were found to have significant anaerobic involvement. All wounds were permitted to heal by secondary intention, and each patient received intravenous hyperalimentation. The average duration of hospitalization was 76 days, a period not differing significantly from that required by conventional closed methods of drainage. Open packing of pancreatic abscesses appears to represent a significant advance in the management of these difficult patients.

Transcatheter carotid occlusion: an alternative to the surgical treatment of cervical carotid aneurysms.

The treatment of choice for various aneurysms of the common and internal carotid arteries may involve carotid artery occlusion rather than a reconstructive approach. Carotid occlusion may be accomplished either surgically or via an endovascular method. We present two cases of patients with cervical carotid artery aneurysms in which the endovascular method was used for carotid occlusion, describe our rationale for using this approach rather than surgical intervention, and discuss the role of this method of treatment for this condition.

Poststenotic flow disturbance in the dog aorta as measured with pulsed Doppler ultrasound.

Blood flow velocity was measured in the dog aorta distal to mechanically induced constrictions of various degrees of severity employing an 8-MHz pulsed Doppler ultrasound velocimeter and a phase-lock loop frequency tracking method for extracting velocity from the Doppler quadrature signals. The data were analyzed to construct ensemble average velocity waveforms and random velocity disturbances. In any individual animal the effect of increasing the degree of stenosis beyond approximately 25 percent area reduction was to produce increasing levels of random velocity disturbance. However, variability among animals was such that the sensitivity of random behavior to the degree of stenosis was degraded to the point that it appears difficult to employ Doppler ultrasound measurements of random disturbances to discriminate among stenoses with area reductions less than approximately 75 percent. On the other hand, coherent vortex structures in velocity waveforms consistently occurred distal to mild constrictions (25-50 percent area reduction). Comparison of the phase-lock loop Doppler ultrasound data with simultaneous measurements using invasive hot-film anemometry, which possesses excellent frequency response, demonstrates that the ultrasound method can reliably detect those flow phenomena in such cases. Thus, the identification of coherent, rather than random, flow disturbances may offer improved diagnostic capability for noninvasively detecting arteriosclerotic plaques at relatively early stages of development.

The carotid sinus syndrome: a frequently overlooked cause of syncope in the elderly.

Exaggerated carotid sinus reflexes may account for alterations in consciousness responsible for significant disability and injury in elderly patients. Nonspecificity of symptoms and concomitant medical conditions frequently delay diagnosis and therapy. During a recent 9-year period, 82 patients were identified as having symptomatic carotid sinus hypersensitivity (CSH). Fifty-nine patients described complete syncope, 73 patients had multiple syncopal or near-syncopal episodes, and 40 patients related cervical pressure or motion as provocative events. Electrophysiologic testing demonstrated that 47% had cardioinhibitory CSH, 26% had vasodepressor CSH, and 27% had combined vasodepressor and cardioinhibitory CSH. The mean follow-up period of all patients was 36 months. Surgical therapy included ventricular demand pacemaker implantation in 33 patients and carotid sinus denervation in seven patients. Medical therapy was used in 32 patients, 11 mildly symptomatic patients were not treated, and 3 patients had carotid sinus irradiation. Pacemaker implantation relieved symptoms in 53%; however, 11 patients (33%) had significant postoperative complications. Carotid sinus denervation relieved symptoms in 86%, medical therapy in 54%, and carotid sinus irradiation in 33% of patients. Because of its demonstrated effectiveness in all variants of CSH and negligible perioperative morbidity, carotid sinus denervation should be offered to acceptable operative candidates when the diagnosis of CSH is confirmed.

Hyperalimentation in alcoholic hepatitis.

Enteral hyperalimentation in four patients with severe alcoholic hepatitis and anorexia increased spontaneous food intake, increased their nitrogen balance and the patients improved clinically. Seven patients with alcoholic hepatitis, who were clinically ill and able to eat only 410-1,100 calories per day, were given a 900 mosM/l. parenteral "hyperalimentation" solution by a peripheral vein (P-900). The intravenous nutrition provided daily 51.6-77.4 gm. amino acids in addition to oral intake. All patients improved. None developed detectable encephalopathy after 16-42 days of P-900 therapy. Five additional patients had ascites and alcoholic hepatitis. The daily infusion of 2,000 ml. P-900 was not associated with hyponatremia, renal failure or encephalopathy in four of these five patients who improved and continued their diuresis. P-900 therapy was discontinued in one because of progressive hyponatremia. The observations indicate that over and above the maximum tolerable oral nutrition, intravenous nutrition can be effectively utilized by clinically ill, jaundiced patients with alcoholic hepatitis without precipitating encephalopathy or interference with standard therapy of ascites.

Deranged tyrosine metabolism in cirrhosis.

In normal individuals, the main route for tyrosine degradation is the hepatic pathway tyrosine→4-hydroxyphenylpyruvic acid→homogentisic acid→CO(2). Quantitatively minor pathways, in large part extrahepatic, are: tyrosine→tyramine→octopamine and tyrosine→dopa→catecholamines.In cirrhosis, the main hepatic pathway is blocked to varying degrees at the first three stages. This appears to be due to lack of activity of the enzymes tyrosine transaminase, PHPA oxidase, and HGA oxidase, the first step being rate limiting. Hypertyrosinemia and tyrosine intolerance result.With the main hepatic pathway partially blocked, an abnormally large amount of tyrosine passes into the normally minor extrahepatic pathway leading to the false neurotransmitters tyramine and octopamine. Overproduction of these amines ensues and they accumulate in the body fluid.The false neurotransmitters can displace catecholamines from their storage sites in the peripheral and central nervous system, and thereby disrupt adrenergic processes in arterioles, kidneys, and brain. Their accumulation in cirrhotic patients may play a role in the pathogenesis of hepatic encephalopathy, hepatorenal syndrome, and hyperdynamic circulation.