Kenichiro Okadome

Effect of wall shear stress on intimal thickening of arterially transplanted autogenous veins in dogs

To determine whether or not changes in wall shear stress play a determinant role in the induction of hyperplasia of intimal tissue of arterially transplanted vein grafts, we developed two models of canine femoral arteries. Wall shear stress was defined by variation of wall shear stress (tau-variation) in the cardiac cycle, with the use of a newly designed computational flow waveform analyzer. In the group I model autogenous vein grafts were implanted under flow conditions of 79.7 +/- 3.2 ml/min of the normally high flow rate with 33.1 +/- 1.9 dynes/cm2 of low tau-variation. In the group II model grafts were implanted under conditions of 2.9 +/- 1.8 ml/min of low flow rate with 178.8 +/- 11.0 dynes/cm2 of normally high value of tau-variation. The intimal thickness of 259 +/- 36 microns 4 weeks after implantation in group I was statistically significant compared with that of 31 +/- 14 microns in group II (p less than 0.005). Our study revealed that change in wall shear stress and not the rate of blood flow is the essential hemodynamic factor related to intimal hyperplasia.

Development and regression of intimal thickening of arterially transplanted autologous vein grafts in dogs.

To investigate the influence of hemodynamic conditions on intimal thickening of arterially transplanted autologous vein grafts, two experimental models of canine femoral arteries were prepared. In group I, in which an autologous vein graft was transplanted under abnormal flow conditions (distal poor runoff), intimal thickening gradually developed and reached 358 +/- 33 microns at 8 months, whereas no thickening was observed under normal flow conditions at any time throughout the observation period. In group II the thickened intima, which developed under abnormal flow conditions for 1 month, was reimplanted into the contralateral leg under normal flow conditions. The thickness of the intima markedly regressed to about 66% at 1 month, 50% at 3 months, and 25% at 8 months, respectively, whereas no regression of the thickened intima was observed under continued abnormal flow conditions. Electron microscopic studies revealed that the thickened intima in group I was composed of proliferation of transformed smooth muscle cells with a marked increase in the mitochondria, the rough endoplasmic reticulum, and an abundant fibrous matrix, whereas with the regressed thickness of the intima of group II, the smooth muscle cells were spindle-shaped with distinct myofibrillae. These results provide pertinent data on the process involved in the intimal thickening in cases of graft placement.

Detection of active cytomegalovirus infection in inflammatory aortic aneurysms with RNA polymerase chain reaction

PURPOSE We previously reported the possible role of human cytomegalovirus in the pathogenesis of inflammatory aortic diseases. To further analyze the viral cause of human aortic diseases, in this study we examined the presence and the replication of human Herpesviridae in 60 aortic tissues, including 7 inflammatory aneurysms, 37 atherosclerotic aneurysms, and 16 normal aortas. METHODS To detect the genome of herpes simplex virus (type 1, type 2), cytomegalovirus, and Epstein-Barr virus, DNA polymerase chain reaction for each virus was performed. To analyze these herpesviral replications, the viral transcript was detected with RNA polymerase chain reaction. RESULTS The DNA polymerase chain reaction showed that either herpes simplex virus or cytomegalovirus was present more frequently in inflammatory (29% or 86%, respectively) and atherosclerotic aneurysms (27% or 65%, respectively) than in normal aortic tissues (6% or 31%, respectively), whereas the Epstein-Barr viral genome was not detected in any aortic tissue specimens. By the use of RNA polymerase chain reaction, only the cytomegaloviral transcript was recognized in 71% of the inflammatory aneurysms but was not recognized in any other tissue specimens. No other herpesviral transcripts were detected in any tissue specimens examined in this study. CONCLUSIONS Our results thus suggest that the human herpesviruses may play various roles in the pathogenicity of aortic diseases, in particular the replicating infections of the cytomegalovirus might potentially cause the formation of inflammatory aneurysms.

Intimal hyperplasia of experimental autologous vein graft in hyperlipidemic rabbits with poor distal runoff.

Poor distal runoff and hyperlipidemia are factors affecting the fate of an implanted graft. In the present study, combined effects of poor distal runoff and hyperlipidemia on intimal hyperplasia (IH) of the vein graft were examined in a newly developed poor distal runoff model in rabbits. A poor distal runoff model was prepared in the right hindlimb of 30 rabbits. These animals were divided into two groups, depending on the diet provided; normolipidemic diet group (Group NL, n = 14) and hyperlipidemic 1% cholesterol diet group (Group HL, n = 16). Four weeks after preparing the poor runoff model, the femoral vein was implanted into the ipsilateral femoral artery. At 2, 4 and 6 weeks, the grafts were harvested. IH of the graft was measured and macrophages in the IH were examined immunohistochemically. Intimal cell proliferation was also determined by bromodeoxyuridine (BrdU) incorporation. IH of the vein graft was significantly accelerated in cases of poor distal runoff and hyperlipidemia. There were no macrophages in the IH in the NL group. In the HL group, macrophages infiltrated the outer layer of IH, sometimes just above the internal elastic lamina, and increased with time. In the poor distal runoff limbs at 6 weeks, macrophages also appeared in the subendothelial layer but were absent in that layer in the controls. Intimal cell proliferation expressed as the BrdU labeling index (LI) was maximum at 2 weeks. In the HL group, BrdU LI of IH in the poor distal runoff limb was higher than in the control at 2 and 4 weeks. Throughout the experiments, BrdU LIs in the HL group were significantly higher than in the NL. Hyperlipidemia accelerates intimal cell proliferation to a greater extent, then does IH. In cases of a poor distal runoff, the enhancement of cell proliferation by hyperlipidemia is augmented. These responses, in the presence of a hyperlipidemia, may be closely related to the migration of macrophages.

Management of concomitant abdominal aortic aneurysm and gastrointestinal malignancy

Selecting the most appropriate surgical approach for patients with abdominal aortic aneurysm (AAA) and gastrointestinal malignancy remains controversial. In an attempt to develop guidelines for the management of patients with these two simultaneous lesions, a retrospective review of patients who had concomitant AAA and gastrointestinal malignancy was undertaken. During the period from January 1985 to February 1993, 229 patients with AAA were admitted to our hospital. Among these, 19 patients (8%) had a gastrointestinal malignancy together with AAA and were divided into 2 groups. Group I was composed of 11 patients who underwent either a 1- or a 2-stage operation for both lesions. Group II was composed of eight patients who either underwent an operation for one lesion (six patients) or did not have any operation (two patients). Among group I, six patients underwent the two-stage operation. In four of the six patients, the malignancy was resected first. In the remaining two patients, the aneurysmectomy was performed first, because, in one patient, the aneurysm was more than 6 cm in diameter, and, in the other patient, the aneurysm was a saccular type. Among group I, five patients (two patients with gastric cancer, and one patient each with esophageal cancer, rectal cancer, and malignant lymphoma of the stomach) underwent a one-stage operation. In three of the five patients (two patients with gastric cancer and one patient with esophageal cancer), simultaneous resection was carried out by using segregated approaches, namely, the retroperitoneal approach for AAA and the transperitoneal approach for malignancy. Although the clinical characteristics of the patients were different, 8 of the 11 patients (73%) in group I are still alive, whereas only 1 of the 8 patients (13%) in group II is still alive. The principles of our surgical approaches for concomitant AAA and gastrointestinal malignancy are as follows: (1) The lesion that absolutely indicated urgent surgery was resected first. (2) If both lesions were asymptomatic, the malignancy was resected first. (3) Simultaneous resection using different approaches was useful in some patients with concomitant upper early gastrointestinal malignancy. (4) Both lesions need to be resected eventually for better long-term survival.

Possible role of cytomegalovirus in the pathogenesis of inflammatory aortic diseases: A preliminary report

To search for possible evidence of a relationship between human cytomegalovirus and aortic diseases, we examined 41 aortic lesions excised at surgery and 16 aortic tissues obtained at autopsy for the presence of cytomegalovirus DNA, by use of polymerase chain reaction. Cytomegalovirus DNA was present in seven (88%) of eight lesions of inflammatory aortic diseases with periaortic fibrosis, five of six inflammatory aneurysms, and all of two aortic occlusive lesions with inflammation. Cytomegalovirus DNA was detected in 20 (61%) of 33 atherosclerotic aneurysms, whereas it was detected in only five (31%) of 16 autopsy samples that showed neither inflammation nor atherosclerosis. Thus the possibility that cytomegalovirus may play a role in the pathogenesis of inflammatory aortic diseases warrants further attention.

Surgical strategy of concomitant abdominal aortic aneurysm and gastric cancer

PURPOSE Selecting the most appropriate surgical approach for patients with abdominal aortic aneurysm (AAA) and concurrent gastric cancer remains controversial. In an attempt to develop guidelines for the management of two concurrent lesions, a retrospective review of patients with concomitant AAA and gastric cancer was undertaken. METHODS During the period from January 1985 to December 1992, a total of 222 patients with AAA were admitted to our hospital. Among these, seven patients (3.2%) had gastric cancer and concurrent AAA. Six of the seven patients were treated surgically for both lesions with either a one- or two-stage operation. One patient underwent only an exploratory laparotomy because of the peritoneal dissemination of the gastric cancer. Four of the six patients underwent a two-stage operation. In three cases, the resection of the malignancy was performed first because the gastric cancer was diagnosed as advanced before operation. In one case, the aneurysmectomy was performed first because the aneurysm was more than 6 cm in diameter and the gastric cancer was in an early stage of development. Two of the six patients underwent a one-stage operation and a simultaneous resection was carried out by way of segregated approaches, such as the retroperitoneal approach for AAA and the transperitoneal approach for the malignant lesion. RESULTS Five of the seven patients (71.4%) are still alive. The length of follow-up for these patients ranged from 4 months to 4 years. CONCLUSIONS The principles of our surgical approaches for concomitant AAA and gastric cancer are as follows. (1) The lesion that absolutely indicates urgent operation should be operated on first. (2) If the malignant lesion is advanced, it is resected first. (3) If the malignancy is not advanced, the AAA should be resected first by the retroperitoneal approach. (4) Simultaneous resection by way of segregated approaches is useful in some patients with early gastric cancer. (5) Both lesions must be resected eventually for improvement of the long-term survival chances.

Natural course of endothelium-dependent and -independent responses in autogenous femoral veins grafted into the arterial circulation of the dog

We examined the natural course of endothelium-dependent and -independent responses in reversed autogenous vein grafts during regeneration and tissue repair processes after vein grafting in dogs. Vein grafts implanted in the canine femoral artery were removed, cut into rings, and suspended in organ chambers for isometric tension recording at 3 days and 1, 2, 4, and 6 weeks after implantation. Endothelial cells were denuded from some rings. Control veins were taken from nonsurgically treated femoral veins. Acetylcholine caused endothelium-dependent relaxations in the control veins, whereas in the vein grafts there was no evidence of endothelium-dependent relaxations to acetylcholine 3 days after the operation. Acetylcholine caused endothelium-independent contractions throughout the study. The endothelium-dependent responses to ADP and calcium ionophore A23187 were constantly maintained. Three days after the operation, the amplitude of norepinephrine-induced contractions of the vein grafts was impaired, and at 1 week the amplitude was recovered, although it was significantly smaller than the amplitude of contractions of the control veins at any postoperative period. Endothelium-independent relaxations to sodium nitroprusside were maintained throughout the study. Thus, there was a selective loss of acetylcholine-mediated relaxation in vein grafts in the early postoperative stage, a time when the intima is not thickened. These altered responses in vein grafts in the early postoperative period may have a role in graft failure.

A desktop computer to visualize the intraluminal velocity profile and its clinical application

Based on our previous study that the outcome of reconstructive surgery for lower limbs could well be predicted by flow waveforms and that this state was defined by variation of wall shear stress (tau) in a cardiac cycle, we set up a desktop computer that could calculate wall shear stress in a given patient. This work is based on a principle of a computational method for simulating pulsating blood flow. The flow data from the patient are sent to the waveform analyzer, where the intraluminal velocity profile as well as the shear stress variation is demonstrated. Our study revealed no late occlusion in patients with flow waveforms over 70 dynes/cm2 in tau-variation, early graft failure in those below 20 dynes/cm2, and late occlusion in considerable numbers of patients whose waveforms were between 70 and 20 dynes/cm2. Intraoperative use of the waveform analyzer disclosed the occult cause of obstruction, which would otherwise be overlooked, leading to a remarkable decrease in the rate of immediate graft failure. Follow-up of outpatients with this approach facilitated early detection of late failure, making it possible to repair the graft with minor surgery. Use of the waveform analyzer proved superior to ankle pressure index in predicting graft failure.

Combination of preoperative lymphangiography using lipiodcl and intraoperative lymphangiography using evans blue facilitates the accurate identification of postoperative chylous fistulas

In a 61-year-old woman who underwent extensive retroperitoneal lymph node dissection for rectal cancer, postoperative chylous ascites developed. The site of the lymphatic leak was evident on the lymphangiogram with lipiodol taken prior to the surgical repair of the leak, and another site seen on the intraoperative lymphangiogram using Evans Blue. A direct surgical repair led to good results. Therefore, the combination of pre- and intraoperative lymphangiography facilitates the successful surgical management of rare but alarmingly dangerous postoperative chylous ascites.