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Biomedical subjects

K Komori

Publications and source records attributed to K Komori.

At least 109 records · Page 6Linked to original sources

The effect of probucol on intimal thickening of autologous vein grafts in hyperlipidemic rabbit.

Probucol is used to treat hypercholesterolemia and also has an anti-atherogenic effect. The effects of probucol on intimal thickening of autologous vein graft in hyperlipidemic rabbits with poor distal run-off were investigated. A poor distal run-off model was prepared in the right hindlimb of 18 rabbits allocated to four groups depending on diet: normolipidemic commercial diet, (NL group, n = 5); hyperlipidemic diet (HL group, n = 5); commercial diet with 1% probucol (NP group, n = 4); and hyperlipidemic diet with 1% probucol (HP group, n = 4). After 4 weeks the femoral vein grafts were implanted into normal (n = 18) or poor (n = 18) runoff limbs. Vein grafts were harvested 4 weeks after implantation. Intimal thickening of the graft was measured and macrophages therein examined immunohistochemically. The serum cholesterol level was not reduced by probucol treatment. The mean flow rate of the graft was significantly reduced in the poor run-off limb. On histological examination intimal thickening in the poor run-off limb was significantly greater than that of controls, while intimal thickening in the HL and HP groups was enhanced compared with that in the NL and NP groups, respectively. Mean intimal thickening in each limb in HP group rabbits was significantly lower than that in HL rabbits (microm): control (HL/HP): 99.4(7.4)/58.8(0.7) (P < 0.05); poor run-off (HL/HP): 155.3(9.6)/130.3(7.3) (P < 0.O5). There was no difference between NL and NP (microm): control (NL/NP): 44.6(24.7)/31.5(12.8); poor run-off (HL/HP): 115.3(13.8)/97.5(34.0). In addition, enhanced intimal thickening due to poor distal run-off was not suppressed. Immunohistochemical staining showed intimal macrophage infiltration in the HL and HP groups; however, macrophage infiltration in grafts in the HP group was less than in the HL group. In conclusion, under hyperlipidemic conditions, probucol decreased intimal thickening enhancement of the vein graft, and suppressed intimal macrophage infiltration. These findings were similar to the anti-atherogenic effect of probucol in the native artery. Hence, probucol administration after vascular reconstruction with vein grafts in patients with hyperlipidemia may be beneficial.

Animals↗

Acceleration of impairment of endothelium-dependent responses under poor runoff conditions in canine autogenous vein grafts.

OBJECTIVES: To assess the effects of changes in shear stress on endothelium-dependent responses. MATERIALS AND METHODS: Autologous vein grafts were implanted in poor or normal distal runoff limbs of 10 mongrel dogs. Six weeks after grafting the vein grafts were removed, cut into rings, and suspended in organ chambers for isometric tension recording. RESULTS: The average value of intimal thickening was 110.7 +/- 45.2 microns in poor runoff limbs and 65.5 +/- 27.9 microns in control limbs, respectively. There was a significant difference between the two groups. Acetylcholine caused comparable endothelium-independent contractions in both groups. In the control group, adenosine diphosphate, thrombin and A23187 caused endothelium-dependent relaxations. In the poor runoff group, the endothelium-dependent relaxations caused by adenosine diphosphate and thrombin were impaired, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxations in response to sodium nitroprusside were comparable between the two groups. CONCLUSIONS: This dysfunction of the endothelium under conditions of abnormal flow may accelerate intimal thickening of the vein graft and result in late graft failure.

Animals↗

Surgical strategy of abdominal aortic aneurysm with preoperative renal failure.

OBJECTIVES: To determine the effect of preoperative renal failure on the outcome of patients suffering from infrarenal abdominal aortic aneurysm (AAA). METHOD: During the period from January 1979 to August 1995, 364 patients with AAA were admitted to our hospital and 323 underwent elective repair. The patients were retrospectively analysed in three groups. Group I was composed of 273 patients with a normal renal function who underwent an aneurysm repair. Group II was composed of 50 patients who demonstrated a preoperative renal dysfunction (creatinine above 2.0 mg/dl or creatinine clearance below 40 ml/min) and underwent an operation, including three patients maintained on chronic haemodialysis. Group III was composed of 18 patients with a renal dysfunction who did not undergo repair, including one patients maintained on chronic haemodialysis. RESULTS: The operative mortality rate of groups I and II were 0.4% and 2.0%, respectively, although no significant difference was observed. The incidence of postoperative cardiac and pulmonary complications were also comparable in two groups. No patients required acute haemodialysis. The 5-year survival rate of group II (44%) was significantly higher than that of group III (20%), and seven of the 18 patients (39%) in group III ultimately died of a rupture of the AAA. CONCLUSIONS: Patients with chronic renal failure can undergo an abdominal aortic aneurysm repair based on the same indications as those without renal failure.

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Mechanism of contraction induced by bradykinin in the rabbit saphenous vein.

1. By using fura-PE3 fluorometry and receptor-coupled permeabilization by alpha-toxin, the mechanism of the bradykinin (BK)-induced contraction was determined in the rabbit saphenous vein (RSV). The receptor subtype responsible for the BK-induced contraction of RSV was determined by means of a pharmacological blocker study and reverse transcription polymerase chain reaction (RT-PCR). 2. In the presence of extracellular Ca2+ (1.25 mM), BK (10(-11)-3 x 10(-7) M) induced increases in both the cytosolic Ca2+ concentration ([Ca2+]i) and force, in a concentration-dependent manner. Both the release of Ca2+ from the store site and the influx of extracellular Ca2+ contribute to an increase in [Ca2+]i induced by BK. 3. In the absence of extracellular Ca2+, the application of 10(-7) M BK induced transient elevations of [Ca2+]i and force, both of which thereafter declined to the levels observed before the application of BK. When extracellular Ca2+ was replenished (1.25 mM), [Ca2+]i and force increased to form a peak, followed by a sustained elevation in the presence of BK. When an RSV strip was pretreated with 10(-5) M thapsigargin for 20 min, the BK-induced transient increases in both [Ca2+]i and force were markedly inhibited. 4. These responses induced by BK were inhibited by Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8] bradykinin), a highly specific bradykinin B2 receptor antagonist, in a concentration-dependent manner. In RT-PCR, B2-receptor mRNA was expressed in the smooth muscle of RSV. 5. The [Ca2+]i-force relationships, which were determined by cumulative applications of extracellular Ca2+ (0-5 mM) during 118 mM K(+)-depolarization, shifted to the upper left in the presence of BK, thus indicating that BK induced a greater force than 118 mM K(+)-depolarization for a given level of [Ca2+]i. 6. In alpha-toxin-permeabilized preparations of RSV, application of 10(-7) M BK after a steady state contraction had been induced by a mixture of 5 x 10(-7) M Ca2+, 10(-6) M GTP and 10(-6) M captopril caused an additional force development at a constant [Ca2+]i. However, treatment with 1 mM guanosine-5'-O-(beta-thiodiphosphate) (GDP beta S) for 5 min before and during the application of BK (10(-7) M), abolished this BK-induced additional contraction. 7. These results indicated that in RSV: (1) BK elicits vasoconstriction by increasing the Ca2+ influx from the extracellular space, Ca2+ release from intracellular thapsigargin-sensitive storage sites and increasing the Ca2+ sensitivity of the contractile apparatus, (2) the BK-induced increase in Ca2+ sensitivity is mediated by G-protein, (3) the BK-induced contractions are mediated via B2-receptors and (4) the smooth muscle cells express B2-receptor mRNA.

Animals↗

Human desmocollin 1 (Dsc1) is an autoantigen for the subcorneal pustular dermatosis type of IgA pemphigus.

IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease.

Animals↗

The inhibition of canine vein graft intimal thickening using a newly developed antiplatelet agent.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of a newly developed antiplatelet agent, 4-cyano-5, 5-bis[methoxyphenyl]-4-pentenoic acid (E5510) on intimal hyperplasia of experimental autologous vein grafts in a distal poor runoff canine model. METHOD: The femoral vein was implanted into the femoral artery preparing a distal poor runoff model. These animals were divided into three groups consisting of the E5510 group, the Aspirin group, and the Control group. The vein grafts were harvested at either 1 or 4 weeks after implantation. RESULTS: At 4 weeks, the degree of intimal hyperplasia of the graft of E5510 group was significantly less than that of the Aspirin group and the Control group (p < 0.05). No significant difference was observed between the Aspirin group and the Control group. At 1 week, the degree of intimal cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation and was expressed as the BrdU labeling index. The BrdU labeling index of the E5510 group was also significantly lower than that of the Control group (p < 0.05). CONCLUSIONS: These data demonstrate the efficacy of E5510 in reducing intimal hyperplasia of vein grafts under distal poor runoff conditions by reducing the degree of smooth muscle cell proliferation.

Animals↗

Effects of serotonin and endothelin on the smooth muscle cells of autogenous vein grafts.

BACKGROUND: The purpose of this study was to compare the effects of vasoconstrictor substances such as 5-hydroxytryptamine (5-HT) and endothelin on the smooth muscle of canine femoral veins and vein grafts. METHODS: The right canine femoral vein was grafted into the right femoral artery. The left femoral vein was used as a control. In other experiments to examine the effects of surgical procedures such as dissection of the adventitia and the effects of grafting (vein-to-vein bypass), the right femoral vein was dissected out but not removed for grafting and an autogenous vein bypass of the right femoral vein was made using the left femoral vein. In all experiments, the veins were removed 4 weeks after operation and suspended in organ chambers for isometric tension recording. RESULTS: Maximum contractions to endothelin were comparable in control vein and vein grafts. In control vein, the maximum contraction to 5-HT was small, and was inhibited by both methiothepin, a 5-HT, and 5-HT2 antagonist, and sarpogrelate hydrochloride, a 5-HT2 antagonist. In vein grafts 5-HT produced significantly larger contractions than in control veins, which were inhibited by methiothepin but not by the 5-HT2 antagonist. In veins with adventitial dissection alone and vein-to-vein grafts, 5-HT produced small contractions which were comparable to those in control vein. CONCLUSION: The larger contraction response to 5-HT in canine vein grafts may be due to an increased responsiveness of the 5-HT1 receptor caused by grafting into the arterial circulation.

Animals↗

Effects of lumbar sympathectomy on the properties of both endothelium and smooth muscle cells of the canine femoral artery and autogenous vein grafts under poor runoff conditions.

The purpose of this study was to determine whether or not a lumbar sympathectomy would modulate the functions of the endothelium, in terms of endothelium-derived relaxing factor (EDRF), under poor distal runoff conditions. First, a poor distal runoff model was developed in the canine right and left femoral arteries. After 5 weeks, a unilateral left sympathectomy was performed from L-3 to L-6. In experiment I, changes in blood flow and endothelium-dependent responses were examined in the canine femoral artery 5 weeks after the lumbar sympathectomy. In experiment II, 5 weeks after the development of a poor runoff model, a unilateral left sympathectomy was performed and both femoral veins were also grafted to the femoral arteries on both sides. Then after 4 weeks, endothelium-dependent responses and intimal thickening of both autogenous vein grafts were examined. The endothelium-dependent responses were examined by mechanical tension recording. In both experiments, the mean blood flow of the left femoral arteries (denervated, 92.2 +/- 47.1 ml/min) and vein grafts (denervated, 100.0 +/- 35.4 ml/min) was significantly higher than that of the right femoral arteries (innervated, 46.9 +/-25.7 ml/min) and vein grafts (innervated, 50.0 +/- 20.1 ml/min) (P < 0.01). In experiment I, the endothelium-dependent relaxations to acetylcholine, ADP, and A23187 were comparable between the right and left femoral arteries. In experiment II, the endothelium-independent contractions to acetylcholine and endothelium-dependent relaxations to ADP and A23187 were all comparable between the right and left vein grafts. In addition, the intimal thickening of the vein graft was comparable between the two groups (denervated, 95.6 +/- 10.8 microm; innervated, 105.0 +/- 15.0 microm). In both experiments, the NE-induced contractions and SNP-induced relaxations were closely similar between the two groups, irrespective of the flow change. These results suggest that lumbar sympathectomy does not alter endothelial function in terms of EDRF, although mean blood flow of the denervated femoral arteries and vein grafts was significantly higher than that of the innervated femoral arteries and vein grafts. These results suggest that continuous vasodilation following sympathectomy may be a more potent factor with respect to regulation of vascular tonus than physiologic regulation of EDRF.

Acetylcholine↗

Primary structure of mannuronate lyases SP1 and SP2 from Turbo cornutus and involvement of the hydrophobic C-terminal residues in the protein stability.

The complete amino acid sequences of two isoforms, SP1 and SP2, of mannuronate lyase from a wreath shell, Turbo cornutus, were determined to elucidate amino acid residues responsible for causing the more stable protein conformation of SP2. The sequences of the two isoforms were identical except for two hydrophobic C-terminal amino acid residues of SP2, Ile and Leu, which were additionally attached to Thr of the C-terminal residue of SP1 (253 residues in total). The molecular weight of SP2 was calculated to be 28,912 from the amino acid sequence data. Two disulfide bond cross-linkages were found to be between 106 and 115 and between 145 and 150, and a partially buried single SH group was located at 236. A carbohydrate chain that consisted of 3 GlcNAc, 3 Fuc, and 1 Man was anchored on Asn-105 in a typical carbohydrate-binding motif of Asn-X-Ser. This is the first evidence of the primary structure of mannuronate lyase, and no significant homology of the amino acid sequence among other proteins was found. The C-terminal truncated SP2, which was produced by digestion with carboxypeptidase Y and corresponded structurally to SP1, showed a thermal stability identical to that of SP1. These results indicate that the higher stability of SP2 than SP1 arises from the presence of the C-terminal two hydrophobic amino acid residues.

Amino Acid Sequence↗

Uptake and intracellular activity of NM394, a new quinolone, in human polymorphonuclear leukocytes.

The uptake of NM394, a new quinolone, by and its subsequent elution from human polymorphonuclear leukocytes were studied and compared with those of ofloxacin and ciprofloxacin. The kinetics of the uptake of NM394 was similar to that of ciprofloxacin. The maximum intracellular-to-extracellular concentration ratio was 12.3, compared with 8.6 for ciprofloxacin and 4.9 for ofloxacin at the extracellular concentration of 20 micrograms/ml. The elution of NM394 from human polymorphonuclear leukocytes occurs relatively slowly; 5 min after the removal of extracellular NM394, nearly 100% still remained in polymorphonuclear leukocytes, compared with ofloxacin, which was so rapidly eluted that only 12% remained. The uptake of NM394 was significantly decreased at 4 degrees C and by the presence of NaCN but was not affected by the presence of L-glycine, L-leucine, L-serine, adenosine, or NaF. NM394 showed intracellular activity at a concentration of 0.1 microgram/ml that significantly reduced the number of phagocytosed Pseudomonas aeruginosa cells with 2 h of incubation. These results suggest that uptake of NM394 by human polymorphonuclear leukocytes occurs via an active transport system differing from that of ofloxacin, whose uptake is affected by the presence of L-glycine and L-leucine, and that once accumulated, NM394 remains intracellularly active and participates in protection against bacterial infection.

Amino Acids↗

Endothelium-dependent relaxation in response to adenosine diphosphate is impaired under poor runoff conditions in the canine femoral artery.

To examine whether poor distal runoff conditions of the canine femoral artery modulates endothelium-dependent relaxations, we developed a poor distal runoff limb in the canine right femoral artery (poor runoff group). The left femoral artery was used as a control. Endothelium-dependent responses were examined in vitro. The rings of femoral artery were obtained from dogs pretreated with 6 weeks of poor distal runoff. In the control, flow rate and tau-variation were 79.1 ml/min and 214.2 dynes/cm2, respectively. In the poor runoff group, the flow rate and tau-variation were 27.4 ml/min and 52.7 dynes/cm2. There were significant differences between the two groups. In the rings taken from the control group contracted with norepinephrine, adenosine diphosphate (ADP) and A23187 caused endothelium-dependent relaxations. In the poor runoff group, the endothelium-dependent relaxations in response to ADP were impaired, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxations in response to sodium nitroprusside were comparable between the two groups. These experiments indicate that under poor runoff conditions, the endothelium-dependent relaxations to ADP are impaired without changing the properties of the smooth muscle cells. This dysfunction of the endothelium under conditions of abnormal flow may accelerate a loss of late patency of the reconstructed arteries.

Adenosine Diphosphate↗

Eicosapentanoic acid reduces the intimal thickening of autogenous vein grafts and enhances endothelium-derived relaxing factor.

The present study examined the effect of purified eicosapentanoic acid (EPA) on intimal thickening of an autogenous vein graft. In addition, experiments were performed to determine whether EPA supplementation would alter the endothelium-dependent responses of the reversed vein graft. Segments of femoral veins were grafted into the femoral arteries of dogs. Six dogs received regular chow (control group) and six other dogs regular chow with 1500 mg/day 90.0% pure EPA (EPA group). At 6 weeks after surgery, the vein grafts were removed from the dogs, cut into rings, and suspended in organ chambers for isometric tension recording. In some rings, the endothelial cells were removed. When the rings taken from the control group were contracted with norepinephrine, adenosine diphosphate (ADP) and A23187 caused endothelium-dependent relaxations. In the EPA group, the endothelium-dependent responses to ADP were significantly augmented, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxation in response to sodium nitroprusside was comparable between the two groups. Intimal thickening of the grafts in the control group (29.0 +/- 1.8 microns) was significantly (P < 0.05) greater than in the EPA group (12.5 +/- 1.8 microns). These results suggest that EPA enhances the release of endothelium-derived relaxing factor in autogenous vein grafts. This may be one of the effects of EPA in reducing the intimal thickening of autogenous vein grafts.

Animals↗

Late graft failure of autologous vein grafts for arterial occlusive disease: clinical and experimental studies.

Late graft failure following arterial reconstructive surgery, especially after infrainguinal reconstruction, remains a major concern for vascular surgeons. To more effectively predict the outcome of reconstructed arteries, we herein propose an intraoperative flow waveform analysis which correlates well with the long-term patency rate of grafts. According to this flow waveform analysis, late graft failure was occasionally seen in grafts with type II waveforms when poor distal runoff vessels had been shown by the preoperative arteriogram. Next, to investigate which events occurring in autologous vein grafts under abnormal hemodynamics may contribute to late graft failure, a distal poor-runoff model was made in the canine femoral artery. In this review, we present the results of our investigation on autologous vein grafts using this poor-runoff model. We also relate our recent findings on the function of regenerated endothelium in autologous vein grafts.

Animals↗

Comparison of endothelial function between in situ and reversed vein graft: differences in endothelium-dependent responses.

BACKGROUND: The endothelium releases endothelium-derived relaxing factors that are potent vasodilators and inhibitors of platelet aggregation. Experiments were performed to determine whether the endothelium-dependent responses differed between in situ and reversed vein grafts. The influence of valve disruption or of dissection of the adventitia was also examined. METHODS: Segments of canine jugular veins were grafted into the carotid arteries during procedures such as reversed grafting, in situ grafting with valve disruption, in situ grafting without valve disruption, and in situ grafting with dissection of adventitia. After 4 weeks the endothelium-dependent responses of the grafts were examined by isometric tension recording. RESULTS: In the reversed and in situ vein graft with valve disruption, acetylcholine caused endothelium-independent contractions, whereas in the in situ vein graft without valve disruption acetylcholine-induced endothelium-dependent relaxations were preserved. Adenosine diphosphate (ADP) caused comparable endothelium-dependent relaxations in the in situ vein graft irrespective of valve disruption. In the reversed vein graft ADP-induced relaxations were significantly impaired. In the in situ vein graft with dissection of the adventitia, relaxations in response to acetylcholine and ADP were significantly reduced. CONCLUSIONS: These results suggest that endothelial function, in terms of endothelium-derived relaxing factors in the in situ vein graft, can be preserved and that adventitial dissection in the in situ vein graft should be minimized to preserve endothelial function.

Acetylcholine↗

Successful simultaneous resection and reconstruction of abdominal aortic aneurysm and esophageal cancer.

A simultaneous resection and reconstruction of abdominal aortic aneurysm (AAA) and esophageal cancer was performed on an eighty-year-old Japanese man. In spite of his advanced age, preoperative assessments revealed that the general functions of the patient were quite satisfactory. An esophagram, endoscopy and CT scan all demonstrated the esophageal cancer to be in a relatively early stage without any lymph node metastasis, while the CT scan demonstrated an infrarenal type of fusiform abdominal aortic aneurysm with a maximum transverse diameter of 7.0 cm. A simultaneous resection and reconstruction of both the AAA and esophageal cancer was performed on August 8, 1991. First, the operation for AAA was done through a retroperitoneal approach, and next, a resection and reconstruction of the esophageal cancer was performed with a right thoracotomy and laparotomy using the gastric tube as an esophageal substitute. The postoperative course was uneventful except for a temporary purulent discharge through the mediastinal drain. The patient was discharged on the 56th postoperative day. Therefore, when the general conditions are considered to be tolerable for operation, such a simultaneous operation may be indicated even inpatients of advanced age by utilizing isolated approaches and taking great care.

Aged↗

[Care for patients with Pick's disease--by using their preserved procedural memory].

Pick's disease are more often complicated than Alzheimer's disease by behavioral disturbances such as social misconduct and stereotypy, that are troublesome and clinically difficult to manage. The purpose of this study was to investigate the possibility of improvement in care for patients with Pick's disease by using their presumably preserved procedural memory. Four inpatients and two outpatients with Pick's disease were studied. Case 1: A 54-year-old right-handed retired clerk presented with a 3-year history of increasing restlessness, word-finding difficulty and impaired comprehension of nominal terms. He was forced to retire from his work because of his social misconduct and incommunicability. On admission he wandered about the ward irritably, did not enter into any conversation, and destroyed all keys in the ward by putting a pencil into keyholes. Neuroradiological examination revealed circumscribed bilateral frontotemporal atrophy which was more marked on the left side. However, he has become more adaptive to the life in the ward and his expression has become peaceful since he began to play othello games with other patients and his doctors. Case 2: A 71-year-old right-handed housewife had progressively altered in her personality and behavior over 4 years. She was restless and showed striking palilalia with marked right frontotemporal atrophy when initially evaluated 2 years after her initial symptoms. Subsequently, her verbal output decreased. She ate large amounts of food and her overweight became a serious problem in her care at home. On admission she wandered about the ward irritably, ate meals of other patients, and put on a quilt on their head. However, these troublesome behavior disappeared when she was bent on knitting that was her former hobby. Case 3: A 63-year-old right handed physician presented with a 5-year history of increasing word-finding difficulty and impaired comprehension of nominal terms. His conversation was limited to continuous repetition of a few phrases. He wandered into several hospitals around his house in fixed order every day. On examination, he was mildly disinhibited and distractible with circumscribed bilateral frontotemporal atrophy which was more marked on the left side. Wandering away from home overnight necessitated admission to the hospital. In the ward he wandered about and tried to open each door restlessly and irritably. However, he has become calm and his expression has become peaceful since he was conducted to measure blood pressures of his nurses. Case 4: A 65-year-old right-handed retired office worker.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Blood flow and kinetics of smooth muscle cell proliferation in canine autogenous vein grafts: in vivo BrdU incorporation.

The effects of blood flow on the kinetics of smooth muscle cell (SMC) proliferation were examined in canine autogenous vein grafts with a distal poor run-off model. The in vivo bromodeoxyuridine (BrdU, a thymidine analogue) incorporation method was used to label proliferating SMCs in each layer of the vein graft. The BrdU labeling index (LI) was defined as a percentage of labeled cells compared to the total number of SMCs, and BrdU LIs were measured in the media and the intima of the graft. The development of intimal thickening of grafts was accelerated at 2 to 4 weeks after implantation. In poor run-off limbs with an abnormal blood flow condition, as characterized by a low flow and a low shear stress variation, the intima of the graft thickened more progressively than that in control limbs with a normal blood flow. In both groups, the medial BrdU LIs reached a maximum 3 to 5 days after implantation and decreased thereafter. The peak of the intimal BrdU LIs occurred at 1 week in both groups. The intimal LIs of the grafts in poor run-off limbs (6.34% at 1 week and 2.97% at 2 weeks) were significantly higher than those in control limbs (5.34 and 1.98%) for 2 weeks after implantation (P < 0.05). The medial SMC proliferation and the following intimal SMC proliferation of vein grafts were accelerated prior to development of the intimal thickening. SMC proliferation in the intima was prominent in a poor run-off limb with a low flow and a low shear stress variation.

Animals↗