Myonephropathic Metabolic Syndrome Research Articles

A case of massive distal embolizations occluding every collateral network during percutaneous intervention for chronic iliac artery occlusion

We describe a patient with right common iliac artery occlusion who presented with intermittent claudication and underwent percutaneous transluminal angioplasty. The angiogram showed 100% occluded right common iliac artery with bridged collateral flow. After initial ballooning to the artery, the occluding plaque detached from the artery and resulted in multiple embolizations, not only to the distal external iliac artery, but also to the internal iliac artery and its branches, which supplied collateral flow to the right femoral artery. Circulation in the collateral networks from internal iliac artery and its branching to the right femoral artery diminished from the multiple embolizations. Repeat aspiration and stenting to the portion of dislodged plaque was attempted, but repeat ballooning to open the external iliac artery was unsuccessful because of decreased collateral flows and distal displacement of the embolus to the right femoral artery. Finally, all blood flow to the right femoral artery was occluded. Surgical embolectomy was successfully performed, but the patient succumbed to myonephropathic metabolic syndrome. Multiple embolizations occluding numerous collateral arteries caused acute fatal ischemia to the right limb. This case report highlights potentially fatal complication in the percutaneous intervention for chronic iliac artery occlusion.

Evaluation of Thrombogenicity by Indium-111 Platelet Scintigraphy in Endografting for Abdominal Aortic Aneurysms

Obstruction of the endograft limb by thrombosis has often been reported and may cause fatal complications such as leg necrosis or myonephropathic metabolic syndrome. The purpose of this study was to evaluate endograft antithrombogenicity by indium-111 platelet scintigraphy. Seventeen patients with abdominal aortic aneurysms were treated by endografting. Thirteen patients were treated with conventional open surgery using an artificial graft. The endograft was constructed from a self-expanding Z-shaped stent and woven polyester fabric. Autologous platelets labeled with indium-111 were injected at 2 weeks postoperatively. At 24 hours and 72 hours postinjection, the ratio of scintillation count of the endograft or graft to that of the native artery was calculated to assess platelet deposition. The normalization ratio was calculated as follows: (scintillation count per pixel of endograft or graft/circumference)/(scintillation count per pixel of the native femoral artery). Platelet factor 4 and beta-thromboglobulin were measured to evaluate the systemic platelets activity at 2 weeks postoperatively. There was no significant difference in platelet counts or labeling efficiency between the groups. The ratio was significantly higher in the endografting group than in the open surgery group at 72 hours postinjection (2.5-0.7 vs 3.9-1.1, P<.001). There was no significant difference in platelet factor 4 and beta-thromboglobulin between the groups. Although there was no difference in systemic platelet activity, endografting was associated with lower antithrombogenicity. It remains unclear whether lower antithrombogenicity causes thromboembolism as a complication of the procedure. The authors recommend the administration of antiplatelet drugs to prevent endograft obstruction in patients with very narrow iliac arteries.

A Case of Myonephropathic Metabolic Syndrome Caused by Aortic Saddle Embolus Originating from a Left Atrial Myxoma

A Case of Myonephropathic Metabolic Syndrome Caused by Aortic Saddle Embolus Originating from a Left Atrial Myxoma

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia

The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.

Effects of LTB4 receptor antagonist on myonephropathic metabolic syndrome: an experimental study.

The aims of this study were to determine the involvement of leukocytes in reperfusion injury following acute arterial occlusion and to evaluate the effect of the leukotriene B4 (LTB4), which is a chemical mediator of inflammation, receptor antagonist. We examined the usefulness of LTB4 receptor antagonist, ONO-4057, as a preventative drug for myonephropathic metabolic syndrome (MNMS). The experimental leg ischemic model was developed using Wistar strain rats. The rats were divided into 4 groups. In Group R3, the infra-renal abdominal aorta was clamped for 3 hrs and the right femoral muscle tissue was cut to block the development of a collateral artery. In Group R6, the infra-renal abdominal aorta was clamped for 6 hrs and the right femoral muscle tissue was cut. In Group C, the controls, there was no clamping of the abdominal aorta and the right femoral muscle tissue was cut. In Group M, the medicated group, rats were pretreated with an LTB4 receptor antagonist, ONO-4057, just before reperfusion. Blood serum interleukin-1 (IL-1), interleukin-8 (IL-8), creatine phosphokinase (CPK), and aldolase were measured and compared in each of those 4 groups. We also examined the intercellular adhesion molecule-1 (ICAM-1) expression in various organs (liver, heart and kidney) by immunohistochemistry. We found that IL-1 beta levels were low in all groups. CPK, aldolase and IL-8 levels after reperfusion in Group R6 significantly high compared with the levels in Group C (P < 0.03 about CPK, P < 0.05 about aldolase, and P < 0.05 about IL-8). The levels of CPK, aldolase, and IL-8 in Group M were significantly lower than those in Group R6 (P < 0.02 about CPK, P < 0.04 about aldolase, and P < 0.03 about IL-8). We determined immunohistochemically that the expression of ICAM-1 was positive on endothelial cells at the coronary artery and the small vein in Group R6 and that the expression of ICAM-1 was negative on endothelial cells in Group C. Those data suggested that ICAM-1 may play an important role in the progression of reperfusion injury, and the adhesion of neutrophilic leukocytes on endothelial cells may play a significant role in MNMS. LTB4 receptor antagonist may be useful for preventing reperfusion injury following acute aortic occlusion.

Predictability of Dielectric Properties for Ischemic Injury of the Skeletal Muscle before Reperfusion

Objective. The purpose of this study is to assess whether or not dielectric properties could predict the severity of ischemic injury of the skeletal muscle before reperfusion to prevent the myonephropathic metabolic syndrome (MNMS).Methods. Japanese White rabbits were anesthetized and their hind limbs were subjected to 0, 2, 4, and 6 h of ischemia and then 10 h of reperfusion (n = 4, 5, 6, and 6). Dielectric properties of the gastrocnemius muscle were measured and tan δm and D were calculated from them. To assess ischemic injury, we also measured (a) creatine phosphate kinase (CPK) and aldolase, (b) spectrophotometric assay of triphenyltetrazolium chloride assay, and (c) histological evaluation by H & E staining, 10 h after reperfusion.Results. The tan δm increased and D decreased significantly compared with those in preischemia (P < 0.01). The tan δm value just before reperfusion significantly correlated positively with the maximum value of CPK (CPKmax) or the maximum value of aldolase (ALDmax) (r = 0.73, 0.69) and negatively with %TTC (r = 0.66). The D value just prior to reperfusion significantly correlated negatively with CPKmax and ALDmax (r = 0.81, 0.86) and positively with %TTC (r = 0.79) after reperfusion, respectively. Histologically, skeletal muscle necrosis was detected in 11 out of 12 skeletal muscles with tan δm values which were 3.70 or more and 11 out of 14 muscles with D values which were 1.47 or less.Conclusion. The severity of skeletal muscle ischemic injury can be evaluated before reperfusion by measuring the dielectric properties during ischemia.

Strategy for prevention of myonephropathic metabolic syndrome (MNMS): comparison of cooling and perfusion.

To evaluate the usefulness of cooling and perfusion methods for acute ischemic legs, we performed the experimental study using adult mongrel dogs. As creation of acute ischemic legs, the abdominal aorta was cross-clamped below the renal arteries, where all branches were ligated, for 6 hours. After release of clamp, the various parameters were examined for 18 hours. All dogs were divided into four groups according to the suppressive methods. cross-clamping for 6 hours with no suppressive method, Group 1: cooling legs using crushed ice during 6 hour-clamping, Group 2: perfusion by heparinized saline of 2.5-10.0 ml/kg before declamping, Group 3: cooling during latter half of 6-hour clamping and perfusion same as Group 2. The serum levels of metabolites and the tissue pressure of the thigh showed significantly lower in the suppression groups than CONTROL GROUP after declamping. In addition, GOT, CPK and aldolase revealed significantly lower values in Group 3 than Group 2. The tissue blood flow of the thigh recovered to the same extent as before ischemia in Groups 2 and 3, while it did not so in CONTROL GROUP and Group 1. Microscopic findings in hematoxylin and eosin (H-E) staining indicated a marked destruction of muscle fiber and interstitial edema in the striated muscle in CONTROL GROUP. These changes were not found so much in Group 2, and almost no changes in Group 1 and 3. The immunostaining for Mb in the striated muscle showed negative in CONTROL GROUP and Group 2, while it showed positive staining in Groups 1 and 3. The immunostaining for Mb in the kidneys showed the most dense deposits of Mb in the renal tubules in CONTROL GROUP. These changes were less in Group 2, little in Group 3, and no change in Group 1. In conclusions, cooling method revealed the minimal metabolic change, and combined method with perfusion was still more effective for prevention of MNMS.

Myonephropathic Metabolic Syndrome After Bilateral Aortoiliac Bypass: A Pathogenic Role of Cholesterol Microemboli

A 72-year-old man was admitted to our hospital for management of intermittent claudication. A preoperative angiogram showed right common iliac artery occlusion with wellmaintained peripheral flow via collaterals and 50% stenosis of the aortic bifurcation through the left common iliac artery. The authors performed bilateral aortoiliac artery bypass surgery. Immediately following the operation, the left lower limb was cyanotic and cold despite a good pulse in the left dorsalis pedis artery. He suffered from severe pain throughout his entire left calf and part of his thigh. Thrombolytic therapy combined with anticoagulation therapy was started in an attempt to reduce limb ischemia. However, swelling of the left calf increased, and clinical and metabolic manifestations consistent with myonephropathic metabolic syndrome (MNMS) developed. Serum creatine kinase and creatinine rose to 21,600 u/L and 2.8 mg/dl, respectively. His toe became necrotic and a transmetatarsal amputation was done. A skin biopsy taken from the edge of the amputation revealed cholesterol crystals within the capillaries. This report suggests that massive cholesterol microemboli are responsible for MNMS in this patient.

A CASE OF ACUTE ARTERIAL OBSTRUCTION IN WHICH MNMS WAS SUCCESSFULLY PREVENTED BY HEMOFILTRATION THROUGH THE AFFECTED LIMB DURING OPERATION

Our experience with a case of acute arterial obstruction, in which myonephropathic metabolic syndrome (MNMS) was successfully prevented by hemofiltration which was done from a vein of the affected limb during operation, is repoted. An 80-year-old woman was referred to the hospital because of acute arterial obstruction of the left lower limb. On admission ecchymotic cyanosis and a partial swelling of the muscle were noted in the left leg, and the urine was port wine colored. Since we feared for a possible risk of causing MNMS after regaining blood flow when a thrombectomy was employed for the case, cannulation was conducted for the vein of the affected limb before restoring blood flow during operation, followed by thrombectomy. In addition, a cross-bypass of the right and left common femoral arteries was conducted for an insufficient central arterial blood supply. There was no postoperative complication. The life of the patient was saved and the affected limb was also salvaged. We think that the method of conducting hemofiltration from a vein of the affected limb before restoration of blood flow during operation is a useful adjuvant procedure to prevent MNMS.

THREE CASES OF TRAUMATIC POPLITEAL ARTERY INJURY

We have experienced three cases of traumatic popliteal artery injury in traffic accident. Of these three cases, one case was associated with a fracture of the tibia and two cases with an injury of the patellar ligament. All three limbs in them were successfully salvaged by reconstruction using autologous veins. Tension incision was conducted in two cases. Of the two cases one case was associated with postoperative myonephropathic metabolic syndrome (MNMS), but the life of the patient was saved by hemofiltration. As the disease often demands amputation in a high frequency compared with other injuries of the limb arteries, early diagnosis and prompt treatment are critical. We have to perform fascial incision aggressively as well as to be alert for the occurrence of MNMS even after revascularization. If any signs are seen, immediate therapeutic strategies including hemofiltration should be employed.

TREATMENTS AND PROBLEMS IN CASES OF HIGH AORTIC OCCLUSION

Our experience with 10 cases of high aortic occlusion including 2 cases in an emergency phase during a recent 14-year period (1981-1995) are reviewed. Five cases including 1 case in an emergency phase were operated on in a fasion of anatomical bypass, and other 5 cases including 1 case in an emergency phase in a fasion of extra-anatomical bypass. Two cases in an emergency phase were lost in vain due to myonephropathic metabolic syndrome (MNMS). We discussed the patient's habitus, pre-operative, post-operative complications, changes in the renal function, operative procedures, and prognosis. Clinical signs seen in the two cases in an emergency phase are also presented.

Limb washout method: Management of acute arterial occlusion of the bilateral lower extremities complicated with myonephropathic metabolic syndrome (MNMS)

Limb washout method: Management of acute arterial occlusion of the bilateral lower extremities complicated with myonephropathic metabolic syndrome (MNMS)

Immediate Haemodialysis and staged fasciotomy in the treatment of reperfusion injury

A 67-year-old man was admitted with traumatic arterial occlusion in his leg 24 h after an accident. A double-lumen catheter was inserted into the left iliac vein, after revascularization, and haemodialysis started using a new membrane dialyser to remove myoglobin effectively. Intramuscular pressure of the limb was measured and, when it was 35 mmHg, staged fasciotomy was performed. A modification of the procedure used to prevent myonephropathic metabolic syndrome and compartment syndrome is described.

Involvement of calpain in myonephropathic metabolic syndrome (MNMS)

Myonephropathic metabolic syndrome (MNMS) is a serious muscle reperfusion injury associated with acute renal failure. The exact pathogenesis of MNMS has not been fully elucidated, nor effective treatment, through the renal failure is thought to be a consequence of rhabdomyolysis. In the present study, the possible involvement of calpain in the lysis was investigated in a MNMS animal model employing a cell permeable calpain antagonist calpeptin. Male rabbits were subjected to bilateral hind leg ischaemia for 5 hours by clamping the distal aorta, followed by reperfusion for 3 hours. Blood pressure, plasma N-acethyl-beta-D-glucosaminidase (NAG) and the presence of myoglobinuria were serially determined. Blood pressure remained constant during the ischemic period but dropped by about 25% immediately after reperfusion. This was significantly attenuated by intraaortic administration of calpeptin. NAG gradually increased during ischemia and during reperfusion and this was also significantly reduced by calpeptin. Myoglobinuria appeared immediately after reperfusion, and was also attenuated by calpeptin. Calpeptin prevented lytic and degenerative changes of the hind leg muscles, determined by light and electron microscopy. Thus it is concluded that activation of calpain in skeletal muscle is an important etiologic factor of MNMS and that the occurrence of MNMS may be prevented by administration of a calpain antagonist.

術前にＢｌｕｅ ｔｏｅ ｓｙｎｄｒｏｍｅ， Ｍｙｏｎｅｐｈｒｏｐａｔｈｉｃ ｍｅｔａｂｏｌｉｃ ｓｙｎｄｒｏｍｅ（ＭＮＭＳ）を併発したと考えられた腹部大動脈りゅう手術症例の１治験例

術前にＢｌｕｅ ｔｏｅ ｓｙｎｄｒｏｍｅ， Ｍｙｏｎｅｐｈｒｏｐａｔｈｉｃ ｍｅｔａｂｏｌｉｃ ｓｙｎｄｒｏｍｅ（ＭＮＭＳ）を併発したと考えられた腹部大動脈りゅう手術症例の１治験例

Extra-anatomic bypass for aorto-iliac occlusive disease in octogenarians

Fifteen patients over 80 years of age with aorto-iliac occlusive disease (AIOD) underwent surgical revascularization of an ischemic lower extremity by extra-anatomic bypasses. The mean age at operation was 81.7 years, ranging from 80 to 86 years. Surgical revascularization of the ischemic lower limbs could safely be performed with an extra-anatomic bypass in these patients without any major complications. The mean follow-up period was 32.7 months. Eight patients died during the follow-up, only one of them died from myo-nephropathic metabolic syndrome related to acute graft occlusion. As a long-term result, the cumulative survival after 37 months was only 23.9%, while the actual graft patency rate was 43.8% after 60 months in this series. The survival period with an improved quality of life after surgical intervention reached a level of approximately 40% of that for the general population. There should be no hesitation over whether to carry out surgical intervention for AIOD in patients over 80 years of age, because a reasonable extension of life can be obtained by an extra-anatomic bypass.

Myocardial damage caused by free radicals in experimentally induced myonephropathic metabolic syndrome in dogs.

Myocardial damage was studied in the dog heart with experimentally induced myonephropathic metabolic syndrome (MNMS). The animals underwent a ligation of the infrarenal arteries with a re-establishment of arterial flow 5 hours after the operation (group 1) and all showed the typical phenomena of MNMS and revealed basophilic changes in the myocardial cells fixed with 4 per cent formalin in 2 per cent calcium acetate. These degenerated cells were distributed in either the left or right ventricle, or even in both as several foci composed of a considerable number of the myocardial cells. Most of these cells showed a significantly enhanced expression of immunoreactive copper-zinc superoxide dismutase in their sarcoplasm. With luxol fast blue staining, the basophilic myocardial cells appeared to be deep blue in color which indicated an accumulation of phospholipid. Such basophilic cells in the animals undergoing a sham operation (group 2) were only sporadically observed in the myocardium fixed with the same fixative. The present study including morphological procedures indicates that dog MNMS causes severe myocardial damage with superoxidation due to an excessive production of free radicals after the re-establishment of arterial flow.

Extracorporeal circulation for the removal of serum myoglobin in experimentally induced myonephropathic metabolic syndrome in dogs

The removal of serum myoglobin with extracorporeal circulation using a column filled with methylmethacrylate-divinylbenzene (MMA-DVB) was studied in experimentally induced myonephropathic metabolic syndrome in the dog. All animals showed marked edema in the hind limbs and degeneration or necrosis of the adductor muscle 5 hours after the reestablishment of arterial flow. The serum levels of myoglobin, creatinine phosphokinase, glutamic oxaloacetic transaminase and aldolase increased linearly after the reperfusion of blood in the group of animals which received no extracorporeal circulation (group 1). Sediments of numerous myoglobin casts in the renal tubules and immunoreactive myoglobin in the renal epithelium of almost all the tubules were seen in 4 out of 5 cases. In the group of animals reperfused with extracorporeal circulation using the MMA-DVB column, serum myoglobin was adsorbed selectively by the column and showed a significantly lower value at 0.5, 1, 2 and 3 hours than that of the group 1 animals. Concomitantly, the immunoreactive myoglobin was absent or scant in the renal epithelium of the proximal convoluted tubule. The present study therefore indicates that extracorporeal circulation using the MMA-DVB column is useful for the removal of serum myoglobin from experimentally induced myonephropathic metabolic syndrome.

急性動脈閉塞症治療上の工夫 簡便なＭＮＭＳ予防策の提唱

急性動脈閉塞症治療上の工夫 簡便なＭＮＭＳ予防策の提唱

Metabolic Complications of Acute Arterial Occlusions and Related Conditions (Myonephropathic-Metabolic Syndrome)

This volume culminates 29 years of interest by Dr Haimovici in the problems associated with rhabdomyolysis brought about by acute arterial occlusion. This work nicely summarizes the past and present status of the field. The reader is brought up to date on some of the newer approaches to the problem as it relates to reperfusion and the use of scavenging agents. The book begins with a review of the basic anatomy of the skeletal muscle unit and the biochemistry of contraction. There is a review of the biochemistry of myoglobin, how it is formed, and its role in the renal failure that accompanies advanced muscle ischemia. There is an important chapter on the pathology of rhabdomyolysis that reviews the histological changes that occur during the various stages of ischemic degeneration. This sets the stage for understanding the metabolic consequences of ischemic injury that can occur. All the possible causes for