Delayed migration due to shortening of the lower part of AFX endograft's main body in angled fusiform abdominal aortic aneurysm.

We encountered two fusiform abdominal aortic aneurysm cases with delayed AFX endograft (Endologix Inc) migration >4 years after placement. These cases showed shortening and slight angulation of the main body in the anteroposterior direction. We speculate that the potential mechanism relates to the AFX portion that is easily shortened at the bifurcation of its stent structure. This portion might contribute to delayed migration after slight angulation of the main body. Preoperative three-dimensional computed tomography should be performed from the anteroposterior and lateral views. Although the AFX is useful for narrow bifurcations, one should consider the patient's anatomy before deciding to use an AFX endograft.

Intraoperative identification of major blood supply to Adamkiewicz artery after multistep surgeries in thoraco-abdominal aortic aneurysm repair.

Herein, we report a case of thoraco-abdominal aortic repair in a 55-year-old man with a multiple treatment history for aortic aneurysm and aortic dissection. A computed tomography scan revealed that the Adamkiewicz artery was connected to an occluded intercostal artery, suggesting that the left inferior epigastric artery was the key artery supplying the Adamkiewicz artery; the key artery was identified through direct monitoring of cerebrospinal fluid temperature and selective hypothermic perfusion. No spinal cord injury was detected during the postoperative period.

Temporary ventricular assist device implantation by sternotomy-avoiding technique for bridge-to-decision therapy: a comparison with conventional implantation.

OBJECTIVE: Temporary ventricular assist device (VAD) is a commonly used therapeutic option for cardiogenic shock. Patients requiring this treatment are often critical, and clinical outcomes remain unsatisfactory. This study evaluated the feasibility and efficacy of a sternotomy-avoiding technique for temporary VAD implantation to improve patient outcomes. METHODS: Between December 2012 and November 2018, seven patients underwent temporary VAD implantation by sternotomy-avoiding technique (SA group) and eight by median sternotomy technique (MS group). Pre- and intraoperative characteristics, postoperative 7-day hemodynamic parameters, 30-day mortality, and adverse events were compared between the groups. RESULTS: More than 50% of the patients were mechanically supported before temporary VAD implantation. Cardiopulmonary bypass time was significantly shorter in the SA than in the MS group (84 min vs 215 min; p = 0.011); surgical time tended to be shorter in the SA group (385 min vs 461 min; p = 0.064). Pump index, cardiac index, mixed venous oxygen saturation, and central venous pressure did not differ significantly during the first seven days of support. The 30-day incidence of any adverse event was not significantly different between the groups. No patients in the SA group needed re-exploration for surgical bleeding. Thirty-day all-cause mortality rates were 29% in the SA group and 0% in the MS group (p = 0.11). CONCLUSIONS: The sternotomy-avoiding and conventional techniques resulted in comparable short-term hemodynamic support. The sternotomy-avoiding technique was associated with a potential reduction in risk of re-exploration for bleeding. These results support the usefulness of the sternotomy-avoiding procedure for selected patients.

Differential selective hypothermic intercostal artery perfusion: a new method to probe spinal cord perfusion during thoracoabdominal aortic aneurysm repair.

OBJECTIVE: To prevent paraplegia in patients undergoing thoracoabdominal aortic aneurysm repair, the importance of preoperative identification of the Adamkiewicz artery and reconstruction of critical intercostal artery have been advocated. Conversely, significance of collateral network for spinal cord perfusion has been recognized. We invented a new system consisting of a direct monitoring of cerebrospinal fluid temperature (CSFT) and differential selective hypothermic intercostal artery perfusion (D-HIAP). METHODS: After exposing a critical intercostal artery, a 10-mm prosthetic graft was anastomosed in an end to side fashion. A balloon-tipped catheter was inserted into the graft to perfuse with 15 °C blood. Neighboring intercostal arteries were also perfused in the same fashion. Serial monitoring of CSFT was performed. Between January 2011 and January 2015, D-HIAP was employed in 50 patients with Adamkiewicz artery that located within a reconstructed area. RESULTS: Significant CSFT drop was recorded after initiation of D-HIAP in 42 (84%) patients. Of those, 34 (68%) patients showed significantly lowered CSFT with D-HIAP into a single critical intercostal artery. Perfusion into plural intercostal arteries was necessary for CSFT drop in 2 cases (4%), and plural intercostal artery perfusion further enhanced CSFT drop that had been modestly achieved by single intercostal artery perfusion in 6 cases (12%). Eight (16%) patients did not exhibit a significant drop in CSFT even when D-HIAP was employed for the critical and neighboring intercostal arteries. CONCLUSIONS: The detection of a disparity in temperature between the intrathecal space and blood generated by D-HIAP revealed individual variability in CSFT changes, which may imply a complexity in spinal cord perfusion. Intraoperative D-HIAP may help to identify a major blood supply for spinal cord perfusion and underlying collateral network.

Association between the severity of acquired von Willebrand syndrome and gastrointestinal bleeding after continuous-flow left ventricular assist device implantation.

OBJECTIVES: Acquired von Willebrand syndrome, characterized by the reduction in von Willebrand factor (vWF) large multimers, has recently been considered as one of the causes of gastrointestinal bleeding (GIB). It remains unclear whether its haematological severity is linked with susceptibility to bleeding because the definition of the haematological severity of acquired von Willebrand syndrome has not been precisely determined. This study sought to establish a quantitative methodology to assess the haematological severity of acquired von Willebrand syndrome and to define the threshold for occurrence of GIB in patients implanted with left ventricular assist devices (LVADs). METHODS: In total, 41 patients treated with continuous-flow LVAD implanted between 2011 and 2017 at Tohoku University Hospital were investigated. vWF large multimers were quantitatively evaluated using the 'vWF large multimer index' defined as the ratio of a large multimer proportion in total vWF derived from a patient to that from a normal control. Using this index, the amount of vWF large multimers was expressed as a percentage of its normal control value obtained with a simultaneous analysis of each time measurement. RESULTS: Twelve (29%) patients developed GIB events during follow-up periods (median 591 days) after an LVAD implantation. The vWF large multimer index in patients with GIB was significantly lower than that in those without GIB (25.0 ± 10.3% vs 37.5 ± 17.8%, P = 0.008). Most importantly, all patients experiencing GIB exhibited a vWF large multimer index below 40%. CONCLUSIONS: Patients with GIB exhibited a more severe loss of vWF large multimers. The vWF large multimer index may dictate the risk of GIB after an LVAD implantation. Clinical trial registration number: UMIN000018135.

Predictors of Heparin Resistance Before Cardiovascular Operations in Adults.

BACKGROUND: Heparin resistance (HR) is often encountered during cardiovascular operations that require cardiopulmonary bypass. Clinical risk factors and the mechanism underlying heparin resistance are yet to be determined. The aim of this study was to elucidate the clinically valid preoperative predictors related to HR. METHODS: The study evaluated 489 patients undergoing cardiovascular operations. Of these, 25 patients presented with HR and received antithrombin III for the initiation of cardiopulmonary bypass with an effective activated coagulation time. The remaining 464 patients, who did not receive antithrombin III, served as controls (NHR). Preoperative patient demographic and laboratory data were analyzed to identify risk factors for HR. RESULTS: The preoperative laboratory data showed platelet count, fibrinogen, D-dimer, creatinine, and C-reactive protein were significantly higher in the HR group than in the NHR group. As expected, the antithrombin III level was significantly lower overall in the HR group (86.0% vs 95.5%, p = 0.009); however, 80% of the patients in the HR group showed normal antithrombin III levels preoperatively. Multivariable logistic regression analysis identified chronic aortic dissection, chronic obstructive pulmonary disease, smoking, and elevated fibrinogen levels as independent predictors for HR. CONCLUSIONS: HR was shown to be associated with preoperative high fibrinogen levels, a smoking habit, and a preoperative diagnosis of chronic, but not acute, aortic dissection, with chronic obstructive pulmonary disease as comorbidity. Administration of antithrombin III resolved HR in all of the affected patients, even when their preoperative antithrombin III level was within the normal limit.

Selective Cerebral Perfusion with the Open Proximal Technique during Descending Thoracic or Thoracoabdominal Aortic Repair: An Option of Choice to Reduce Neurologic Complications.

PURPOSE: Selective cerebral perfusion with the open proximal technique for thoracoabdominal aortic repair has not been conclusively validated because of its procedural complexity and unreliability. We report the clinical outcomes, particularly the cerebroneurological complications, of an open proximal procedure using selective cerebral perfusion. METHODS: A retrospective chart review identified 30 patients between 2007 and 2015 who underwent aortic repair through left lateral thoracotomy with selective cerebral perfusion, established through endoluminal brachiocephalic and left carotid artery and retrograde left axillary artery. RESULTS: The mean durations of the open proximal procedure and cerebral ischemia (the duration of the open proximal procedure minus the duration of selective cerebral perfusion) were 110.3 ± 40.1 min and 24.8 ± 13.0 min, respectively. There were two cases (7%) of permanent neurologic dysfunction (PND) but no in-hospital deaths. Multivariate analysis identified the duration of cerebral ischemia as an independent risk factor for neurologic complications including temporary neurologic dysfunction (TND; odds ratio (OR): 1.13; p = 0.007), but no correlation was found between selective cerebral perfusion duration and neurologic complications. CONCLUSION: Despite the relatively long duration of the open proximal procedure, selective cerebral perfusion has a potential to protect against cerebral complications during thoracic aortic repair through a left lateral thoracotomy.

Predictors of the need for pacemaker implantation after the Cox maze IV procedure for atrial fibrillation.

PURPOSE: The Cox maze IV (CMIV) procedure is being used increasingly frequently for surgical ablation of atrial fibrillation (AF). This study aimed to identify the risk factors of the need for postoperative pacemaker implantation (PMI) after CMIV. METHODS: Preoperative, intraoperative, and postoperative data were retrospectively collected from 67 consecutive patients who underwent CMIV at our institution; 7 (10.4%) required PMI (as a treatment of brady AF or sick sinus syndrome). RESULTS: Patients who needed PMI tended to have lower preoperative heart rates than those who did not on a 12-lead electrocardiogram (ECG; 68.7 ± 11.6 vs. 79.1 ± 18.5 bpm, p = 0.07) and a 24-h ECG (94,772 ± 9800 vs. 109,854 ± 19,078 beats/day, p = 0.03). A multivariate analysis identified a low amplitude of the fibrillatory wave on preoperative ECG as a risk factor of PMI necessity after CMIV [odds ratio = 14.7; 95% confidence interval (CI) 1.9-324.7; p = 0.007] and internal use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) as a negative risk factor (odds ratio = 0.16; 95% CI 0.02-0.99; p = 0.049). CONCLUSIONS: A low amplitude of the fibrillatory wave was identified as a risk factor of PMI necessity, whereas the internal use of ACEIs/ARBs diminished the need for PMI. These factors should be considered before CMIV is performed.

Successful management of antibody-mediated rejection after cardiac transplantation in a patient supported by a left ventricular assist device for more than 3 years.

Due to donor shortage, patients with refractory heart failure need to be supported on mechanical circulatory support (MCS). Critically, patients undergo several deployments of MCS in stages inevitably requiring blood products transfusion. MCSs per se along with blood products can trigger immune allosensitization. Antibody-mediated rejection (AMR) is associated with significant mortality after heart transplantation. Here, we present the case with high panel-reactive antibody over 95% who developed AMR early after heart transplantation. This life-threatening complication was successfully treated with multi-modal treatment including anti-CD20 antibody, rituximab.

Oxygenation of the cerebrospinal fluid with artificial cerebrospinal fluid can ameliorate a spinal cord ischemic injury in a rabbit model.

OBJECTIVE: We evaluated the effect of cerebrospinal fluid oxygenation for the prevention of spinal cord ischemic injury after infrarenal aortic occlusion in a rabbit model. METHODS: Twenty white Japanese rabbits were categorized into the following 4 groups (5 in each): group S (sham), balloon catheter insertion on to the aorta; group C (control), spinal cord ischemic injury by infrarenal abdominal aortic balloon occlusion for 15 minutes; group N (nonoxygenated), spinal cord ischemic injury with cerebrospinal fluid replacement by nonoxygenated artificial cerebrospinal fluid; and group O (oxygenated), spinal cord ischemic injury with cerebrospinal fluid replacement by nanobubble-oxygenated artificial cerebrospinal fluid. The changes in cerebrospinal fluid partial pressure of oxygen during the peri-ischemic period, modified Tarlov score, and histopathology of the spinal cord 48 hours after aortic maneuvers were evaluated. RESULTS: Cerebrospinal fluid partial pressure of oxygen significantly increased in group O compared with group N after cerebrospinal fluid replacement (254.5 ± 54.8 mm Hg vs 136.1 ± 43.5 mm Hg, P = .02). After 15 minutes of spinal cord ischemic injury, cerebrospinal fluid partial pressure of oxygen in group C decreased to 65.8 ± 18.6 mm Hg compared with baseline (148.8 ± 20.6 mm Hg, P < .01), whereas cerebrospinal fluid partial pressure of oxygen in group O was maintained at remarkably high levels after spinal cord ischemic injury (291.9 ± 51.8 mm Hg), which was associated with improved neurologic function, with 20% of spinal cord ischemic injury having a Tarlov score less than 5 compared with 100% of spinal cord ischemic injury in group C. Preservation of anterior horn neurons in groups N and O was confirmed by histopathologic analysis with significant reduction of degenerated neurons compared with group C. CONCLUSIONS: Cerebrospinal fluid oxygenation with artificial cerebrospinal fluid can exert a protective effect against spinal cord ischemic injury in rabbits.

Modification of a Standard Thoracoabdominal Incision to Preserve Collaterals to Adamkiewicz Artery.

We report a case of a 35-year-old male who underwent thoracoabdominal aortic repair of a chronic dissecting aortic aneurysm, Crawford extent II. Preoperative computed tomography showed thrombosis of almost all intercostal arteries. Precise diagnostic assessment demonstrated the Adamkiewicz artery originating from the left lateral thoracic artery and subscapular artery, which would have been at risk after using a standard Stoney's incision, thus potentially causing paraplegia or paraparesis due to spinal cord ischemia. We modified the lateral thoracic incision anteriorly and successfully preserved the collateral arteries without impairing the spinal cord function.

Long-term results after physiologic repair for congenitally corrected transposition of the great arteries.

OBJECTIVE: We aimed to evaluate the long-term results of physiologic repair for associated lesions of congenitally corrected transposition of great arteries (ccTGA) and to provide a basis for comparison with anatomic repair for this entity. SUBJECTS AND METHODS: Sixteen ccTGA patients who underwent physiologic repair from 1970 to 2000 comprise this retrospective study. Conventional Rastelli procedure was performed in 12 patients with pulmonary stenosis or atresia (PS/PA). Ventricular septal defect closure was carried out in 2 patients, atrial septal closure in 1, and tricuspid valvuloplasty in 1 without PS/PA. Mean follow-up period was 19.4 years. Long-term survival rates were assessed with respect to the presence or the absence of preoperative PS/PA and specifically in relation with the magnitude of pre- and postoperative tricuspid regurgitation (TR). RESULTS: There has been no long-term mortality in the ccTGA patients without PS/PA. Twenty-year survival rate after conventional Rastelli was 71 %. Overall 20-year freedom from more than mild TR or tricuspid valve replacement was 44 %. The development of postoperative more than mild TR was significantly linked with pre-repair right ventricular enlargement (p = 0.019), but not with the magnitude of pre-repair TR (p = 0.85). CONCLUSION: Long-term outcomes of physiologic repair for ccTGA were equivalent to those of reported anatomic repair performed in several centers during the same era. Notably, significant TR was observed in more than half of physiologically repaired patients over the 20 years after repair. The degree of pre-repair TR cannot predict the long-term function of tricuspid valve after physiologic repair.

[Issues in Coronary Artery Bypass Grafting for Kawasaki Disease].

Progressive narrowing at the entrance and exit of coronary artery aneurysm can develop at late phase of Kawasaki disease (KD). Evaluation and prediction of progressive coronary lesions remain a challenge in the treatment of post-KD coronary artery disease. We aimed to elucidate long-standing issues imposed on the patients who underwent coronary artry bypass grafting (CABG) for coronary artery lesions associated with KD. Between January, 2000 and December, 2013, CABG for coronary artery lesions associated with KD were performed in 6 patients (male/female: 5/1, mean age 14.5±10.0). There was no operative mortality. Follow-up for the 6 patients has been performed with the average period of 5 years (1~9 years). Cardiac events occurred in 2 patients during follow-up. In 1 patient, left internal thoracic artery (LITA) occluded due to flow competition between the native artery and LITA graft after LITA to LAD bypass grafting. The other patient required a re-do CABG using the free right internal thoracic artery to the circumflex branch because of occlusion at the coronary artery aneurysms after 4 years postoperatively. Meticulous preoperative diagnostic evaluations of coronary artery aneurysm may further improve the long-term outcome after surgical intervention for coronary lesions in conjunction with an aneurysm.

[Preoperative Use of Tolvaptan in a Patient with Constrictive Pericarditis].

Tolvaptan is a new selective vasopression V2-receptor antagonist. We report our experience with a use of tolvaptan for preoperative fluid management in a patient with severe constrictive pericarditis. A 66-year-old man presented with heart failure symptoms derived from constrictive pericarditis. Chest X-ray showed right pleural effusion and chest computed tomography demonstrated severe pericardial calcification. Despite that he received optimal conventional medical treatments, his hemodynamic condition further exacerbated during hospitalization. We administered tolvaptan in an attempt to optimize preoperative fluid management. Tolvaptan was found to be remarkably effective in that regard. The body weight decreased and the heart failure symptoms improved. Pericardiectomy was performed successfully, and he recovered uneventfully.

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery.

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.

[Early Postoperative Outcomes and Evaluation of Hemodynamics after Mitral Valve Replacement with Epic Mitral Bioprosthesis].

BACKGROUND: In Guideline for Surgical and Interventional Treatment of Valvular Heart Disease, revised by Japanese Circulation Society in 2012, mitral valve replacement (MVR) with bioprosthesis is class II b recommendation for patients aged 70 years or older who have no risk factors for thromboembolism. The aim of this study was to evaluate the early postoperative surgical outcomes and the hemodynamic performance with the Epic mitral bioprosthesis. METHODS: Twenty-six consecutive patients underwent MVR with Epic mitral bioprostesis at Tohoku University Hospital between April 2011 and July 2014. Twenty-five cases of 26 were evaluated their hemodynamics at discharge, and of which 19 cases of 26 were evaluated at the outpatient clinic during follow-up period. RESULTS: There was 1 hospital death. Long-term mortality or reoperation for any valve abnormality was not observed in the median follow-up of 23.9 ± 11.3 months. Hemodynamic date at discharge obtained by transthoracic echocardiography included mean hemodynamics of mitral valve bioprosthesis as below. Effective orifice area (EOA):2.44 ± 0.62 cm², peak mitral pressure gradient (pMPG):15.8 ± 5.3 mmHg, mean mitral pressure gradient(mMPG):7.2 ± 2.4 mmHg. Hemodynamic parameters at follow-up were found to be stable as EOA:2.25 ± 0.64 cm², pMPG:17.3 ± 5.7 mmHg, mMPG:6.2 ± 2.3 mmHg, respectively. CONCLUSION: We have attempted to elucidate our preliminary postoperative outcomes and hemodynamics after MVR with Epic mitral bioprosthesis. These in vivo hemodynamic data can serves a clinical reference.

[Two cases of fulminant myocarditis with mesenteric ischemia].

Fulminant myocarditis (FM) can lead to a refractory cardiogenic shock and multiple organ failure. Mechanical circulatory support (MCS) is not infrequency required to salvage patients in a profound shock. Advanced technology in MCS such as a temporary ventricular assist device can yield improved early outcome. However, incessant mesenteric ischemia remains a challenge to be resolved even with MCS. We here-in report 2 cases of FM associated with mesenteric ischemia that was extremely difficult to diagnose and treat. Therapeutic strategy for FM with mesenteric ischemia is discussed.

Total aortic arch replacement using hypothermic circulatory arrest with antegrade selective cerebral perfusion: are there cerebral deficits other than frank stroke?

BACKGROUND: It is controversial whether cerebral deficits other than frank stroke develop after total aortic arch replacement using hypothermic circulatory arrest (HCA) with antegrade selective cerebral perfusion (SCP). OBJECTIVES: We investigated neuropsychological functions in patients who received total aortic arch replacement using deep HCA with SCP. METHODS: Eleven patients who underwent elective total arch replacement using deep HCA with antegrade SCP were included. Cognitive functions of the patients were evaluated at baseline, and 3 weeks and 6 months after the aortic arch surgery. RESULTS: The performance of cognitive tests did not change 3 weeks after surgery, except for the attention/calculation task of the Mini-Mental State Examination (MMSE). Six months after surgery, the decline in score for the attention/calculation task in the MMSE had reversed and the score for this task as well as for all other tests had returned to baseline levels. CONCLUSION: Long-lasting cognitive deficits other than frank stroke may not develop after total arch replacement surgery using deep HCA with SCP.

Trial of new vascular clips for aortic anastomosis in a canine model.

OBJECTIVES: We created a new vascular clip designed for aortic surgery. The purposes of this investigation were to examine surgical applicability in a clinically relevant aortic replacement model and to assess biomechanical strength of the clipped anastomosis and serial histologic changes in the clipped anastomotic site. METHODS: Twenty-one beagles underwent descending thoracic aortic replacement. Distal anastomosis was performed with the new clips, mimicking the cuffed anastomosis technique, and proximal anastomosis was carried out by conventional suture anastomosis. Tissue specimens of the anastomotic sites were harvested at 1, 3, 6, and 12 months postoperatively for examination. RESULTS: There was no significant difference in the time required to carry out clip anastomosis (12.2 +/- 1.3 minutes) and suture anastomosis (13.7 +/- 0.9 minutes; P = .38). Neither type of anastomotic site was disrupted by raising the intraluminal pressure to 280 mm Hg. Microscopically, the areas of aortic wall compressed by vascular clips appeared as hyalinized areas adjacent to surrounding collagen fibers, with no significant infiltration of inflammatory cells. Identical histologic changes were observed at the site of the sutured anastomosis. The media at the clipped anastomosis site was significantly thinner than that at the sutured anastomosis site at 1 month after the operation. However, there was no significant difference in the thickness of the media at 3 months. CONCLUSIONS: The new vascular clips were effective in this clinically relevant model, with appropriate biomechanical strength, and the anastomotic sites underwent similar histologic changes to those observed after suture anastomosis.

External application of rapamycin-eluting film at anastomotic sites inhibits neointimal hyperplasia in a canine model.

BACKGROUND: Stenosis at a vascular anastomotic site has been a significant clinical issue. We tested the hypothesis that rapamycin-eluting biodegradable poly L-lactic acid and epsilon-caprolactone copolymer (PLA-CL) film applied externally can inhibit neointimal hyperplasia in a canine vascular anastomosis model. METHODS: Femoral artery graft interposition was performed in 25 beagles. Beagles were divided into five groups (five in each): graft interposition without PLA-CL film (control); with PLA-CL film only; and PLA-CL containing rapamycin 8 microg, 80 microg, and 800 microg. Orthotopic arterial graft interposition was performed on the left side and vein graft from the ipsilateral femoral vein was interposed on the right. Morphometric and immunochemical analyses were performed at four-week intervals. RESULTS: In arterial graft models, the ratio of intimal area (intimal area divided by the entire vessel area) was significantly reduced in all the three rapamycin-eluting film groups compared with control (0.19, 0.07, 0.05, and 0.38 in 8 microg, 80 microg, 800 microg groups and control, respectively, p < 0.05). In vein graft models, the ratio of intimal area was significantly decreased only in the 800 microg rapamycin group compared with control (0.33 vs 0.54, p < 0.05). Inhibition of neointimal growth was associated with reduced cell proliferation, as evidenced by proliferating cell nuclear antigen immunostaining and diminished alpha-actin positive vascular smooth muscle cells. CONCLUSIONS: Rapamycin-eluting biodegradable PLA-CL film applied externally can inhibit neointimal hyperplasia of arterial and vein grafts in a canine model. The inhibitory effect of rapamycin-eluting film against neointimal growth is more pronounced in the arterial graft than the vein graft.