Akie Shimada

Short-term 20-mg atorvastatin therapy reduces key inflammatory factors including c-Jun N-terminal kinase and dendritic cells and matrix metalloproteinase expression in human abdominal aortic aneurysmal wall.

BACKGROUND Abdominal aortic aneurysm (AAA) accumulates features of a chronic inflammatory disorder and irreversible destruction of connective tissue. A recent experimental study identified c-Jun N terminal kinase (JNK) as a proximal signaling molecule in the pathogenesis of AAA and vascular dendritic cells as key players in the inflammatory reaction and degradation of the extracellular matrix. Statins can inhibit cell proliferation and vascular inflammation, which might help prevent AAA progression. However, supporting clinical data from human studies are lacking. We hypothesized that atorvastatin might inhibit JNK and dendritic cells, resulting in suppression of inflammatory cells and matrix metalloproteinases (MMPs) in human tissue of AAA. METHODS Patients with AAA were randomized to atorvastatin (20mg/day, n=10) and non-treated (n=10) groups. After treatment for 4 weeks, patients underwent abdominal aorta replacement, tissue specimens were obtained, and tissue composition was assessed using immunohistochemistry with quantitative image analysis. RESULTS Atorvastatin significantly reduced expression of JNK (1.1% vs. 8.1%, P=0.0002) and dendritic cells (3.2 vs. 7.2, P=0.003) compared to controls. T cells (142 vs. 315, P=0.008), macrophages (13 vs. 24, P=0.048) and immunoreactivity to MMP-2 (7.8% vs. 21%, P=0.049) and MMP-9 (13% vs. 24%, P=0.028) were also suppressed in the atorvastatin group. Serum low-density lipoprotein cholesterol level was decreased by 40% in the atorvastatin group. CONCLUSIONS Atorvastatin treatment acutely reduces JNK expression and dendritic cells, resulting in reduced inflammatory cell content and expression of MMPs in the AAA wall.

Relationship between exercise tolerance and muscle strength following cardiac rehabilitation: Comparison of patients after cardiac surgery and patients with myocardial infarction

BACKGROUND AND PURPOSE Previous studies have demonstrated that cardiac rehabilitation (CR) improves exercise tolerance and muscle strength in patients with myocardial infarction (MI) and in patients after cardiac surgery. However, the association between exercise tolerance and muscular strength following CR and the comparison of relationships among various disease categories has not been fully examined. The purpose of the present study was to assess the relationship between exercise tolerance and muscle strength following CR in patients after cardiac surgery and patients with MI. METHODS AND RESULTS One hundred and four patients who participated in CR for 6 months were enrolled [post-cardiac valve surgery (VALVE), n=28; post-coronary artery bypass grafting (CABG), n=42; post-acute MI, n=34]. The exercise tolerance, thigh/calf circumferences, and muscle strength were measured before and after CR. At the baseline, the thigh circumference was significantly smaller in the VALVE group than in the MI group. There were significant positive correlations between peak VO(2) and muscle torques of the lower muscles in all groups. After 6 months, peak VO(2) and muscle torque were significantly increased in all groups (p<0.001). A positive significant correlation between percent increases in peak VO(2) and muscular strength was observed in the VALVE group (r=0.51, p<0.01), but not in the other groups. In addition, the changes in peak VO(2) and calf circumference after CR were significantly higher in the VALVE group than in the MI group. CONCLUSIONS These data suggest that exercise intolerance in patients after heart valve surgery may in part depend on decreased muscular strength. Further studies are needed to assess whether the strategy of increasing muscular strength of lower limb by programmed resistance training could be effective for improving exercise intolerance in patients after heart valve surgery and symptomatic patients with heart failure.

Impact of diabetes on muscle mass, muscle strength, and exercise tolerance in patients after coronary artery bypass grafting

BACKGROUND The impact of diabetes mellitus (DM) on muscle mass, muscle strength, and exercise tolerance in patients who had undergone coronary artery bypass grafting (CABG) has not been fully elucidated. METHODS We enrolled 329 consecutive patients who received cardiac rehabilitation (CR) after CABG (DM group, n=178; non-DM group, n=151) and measured lean body weight, mid-upper arm muscle area (MAMA), and handgrip power (HGP) at the beginning of CR. We also performed an isokinetic strength test of the knee extensor (Ext) and flexor (Flex) muscles and a cardiopulmonary exercise testing at the same time. RESULTS No significant differences in risk factors, including age, gender, number of diseased vessels, or ejection fraction were observed between the 2 groups. The levels of Ext muscle strength, peak oxygen uptake, and anaerobic threshold were significantly lower in the DM group than in the non-DM group (all p<0.05). Both peak oxygen uptake and MAMA correlated with Ext and Flex muscle strength as well as HGP (all p<0.005). The MAMA, HGP, and Ext muscle strength were lower in patients who received insulin therapy than in those who did not. Interestingly, fasting glucose levels significantly and negatively correlated with Ext muscle strength. CONCLUSIONS These data suggest that DM patients had a lower muscle strength and exercise tolerance than non-DM patients. Moreover, a high glucose level may affect these deteriorations in DM patients after CABG.

Left Atrial Appendage Closure Reduces the Incidence of Postoperative Cerebrovascular Accident in Patients Undergoing Cardiac Surgery

BACKGROUND Cerebrovascular accidents (CVA) are a major adverse event following cardiac surgery, for which atrial fibrillation (AF) is considered as a risk factor. We have recently performed left atrial appendage (LAA) surgical closure or amputation (LAAC/A), which is the main source of emboli, during open-heart surgery. METHODSANDRESULTS A prospective observational study of 1,831 consecutive patients (69.2% male, aged 66.8±12.2 years) undergoing cardiac surgery between 2009 and 2013 was performed. The incidence of postoperative CVA within 6 months in patients with and without LAAC/A was compared. We further stratified patients according to their risk of CVA using CHA2DS2-VASc score; dichotomizing low-risk (score <2) and high-risk groups (≥2). A total of 369 patients (20.2%) underwent LAAC/A. Although these patients had larger left atrial diameter preoperatively and developed postoperative AF more frequently than those without LAAC/A (45.4 vs. 41.1 mm, 49.3 vs. 39.1%, respectively, both P<0.001), the CVA incidence was not different between the groups (3.5 vs. 3.0%, P=0.612). Multivariate analysis revealed no association between LAAC/A and CVA in patients with CHA2DS2-VASc score ≥2, whereas in patients with CHA2DS2-VASc score <2, LAAC/A was the only and independent factor negatively associated with CVA development (odds ratio <10(-6); P=0.021). CONCLUSIONS Additional LAA procedure at the time of cardiac surgery reduces the incidence of early postoperative CVA in patients with low CHA2DS2-VASc score.

Reduction of c-kit positive cardiac stem cells in patients with atrial fibrillation

BACKGROUND We aimed to determine expression patterns of cardiac stem cells in the left atrium (LA) tissue from patients with atrial fibrillation. METHODS LA appendages were obtained during open-heart surgery and processed for explant cell culture and tissue analysis (n=319). The total number of grown cells and c-kit positive cells were analyzed by flow cytometry after 4 weeks of culture. The remaining tissue was used for Massons trichrome staining to determine the area of the fibrosis. RESULTS The diameter of the LA, as measured by echocardiography, was significantly larger in the AF group than in the sinus rhythm group. Reverse transcription polymerase chain reaction analysis revealed higher expression of collagen in the AF group and an increase in the expression of basic fibrosis growth factor and transforming growth factor-2 and -3. Massons trichrome staining showed progression of fibrosis in the AF tissue. In addition, the expression of apoptosis-related genes were significantly higher in AF group. There was no difference in the expression of connexin-40 between groups, while the expression of connexin-43 was decreased and that of connexin-45 was increased in the AF group. The total numbers of grown cells as well as c-kit positive cells after 4 weeks of cardiac tissue culture were significantly lower in the AF group. CONCLUSION Progression of remodeling in LA tissue was observed in AF patients. The number of c-kit positive cells cultured from LA appendages was reduced in AF patients, suggesting impairments in self-renewal.

Skeletonized Gastroepiploic Artery for Off-Pump Coronary Artery Bypass Grafting

BACKGROUND Skeletonized arterial grafting may reduce the risk of graft spasm and may improve graft patency. Previously we reported a pilot study of skeletonized gastroepiploic artery (GEA) grafting with favorable results. Skeletonized GEA harvesting with an ultrasonic scalpel has now become our routine procedure. In this report, we compare the early clinical outcomes of skeletonized versus pedicled GEA grafting to assess the safety and benefit of use of skeletonized GEA in coronary artery bypass grafting. METHODS Between July 2002 and October 2003, the GEA was used as a conduit for isolated off-pump coronary artery bypass grafting in 105 patients. Of these, 21 patients (group P) received pedicled GEA and 59 patients (group S) received skeletonized GEA grafts (excluding 25 patients whose results were reported in the pilot study). The perioperative and early follow-up data were prospectively collected and compared. RESULTS No graft injury was found in either group. The preoperative characteristics were similar in the two groups except that group S had a smaller body surface area (1.64 +/- 0.16 m 2 in group S versus 1.73 +/- 0.16 m 2 in group P, P <.05) and a significant number of patients with diabetes (36/59, 61.0% versus 7/21, 33.3%, P <.05). The number of distal anastomoses was 4.3 < 1.0 versus 3.9 +/- 0.9 ( P = not significant [NS]). An in situ GEA composite graft was constructed in 8 (13.6%) of the patients in group S and none of the patients in group P ( P = NS). There was one hospital death due to infection in group S. Otherwise, there were no cases of low output syndrome or postoperative myocardial infarction in either group. During early postoperative follow-up, no angina recurrence or myocardial infarction was found. CONCLUSION The GEA can be skeletonized safely with an ultrasonic scalpel. Skeletonization enables a wider variety of choices in the use of GEA grafting.

The impact of Joint Commission International accreditation on time periods in the operating room: A retrospective observational study

The Joint Commission International (JCI) is responsible for upholding standards in healthcare and organizations in compliance receive accreditation. JCI requires quality improvement on patient safety goals, but requirements may prolong the total procedure/surgery time and reduce efficiency. Here, we evaluate the impact of JCI requirements on time periods in the operating room. We included patients who received elective and emergency surgeries under general anesthesia at Juntendo University Hospital between December 2014 and June 2016. Patients were classified as before and after JCI accreditation on December 12, 2015. The primary outcome was total procedure/surgery time. Secondary outcomes include five time periods comprising the total procedure/surgery time: pre-anesthesia time, anesthesia induction time, procedure/surgery time, anesthesia awareness time and post-anesthesia time. We compared these time periods between patients before and after JCI accreditation and patients were matched for age, sex and the specific type of surgery. Although total procedure/surgery time did not change significantly, pre-anesthesia time significantly increased (8.2 ± 6.9 minutes vs. 8.5 ± 6.9 minutes, before vs. after JCI, respectively, p = 0.028) and anesthesia induction time significantly decreased (34.4 ± 16.1 minutes vs. 33.6 ± 15.4 minutes, before vs. after JCI, respectively, p = 0.037) after JCI accreditation. Other secondary study outcomes did not change significantly. Quality improvement initiatives associated with time periods in the operating room can be achieved without undermining efficiency.

Push-Up Technique and Anatomical Deployment With the Endurant Stent-Graft System for Severely Angulated Aneurysm Necks

Purpose: To describe a technique suitable for treating severely angulated (>75°) necks during endovascular aneurysm repair using the Endurant stent-graft. Technique: In the push-up technique, the suprarenal stent is released early to fix the proximal stent-graft in place so that each stent in the neck can be deployed individually without displacing the device upward. It is important to push the delivery system up after each stent deployment to allow the fabric between the stents to fold up circumferentially. By doing so, there is minimal upward force applied to the suprarenal stent. Because the stents expand along the angulated neck while catching blood flow, this anatomical deployment is feasible, with hardly any change to the proximal neck shape after stent-graft implantation. Conclusion: The push-up technique and anatomical deployment with the Endurant stent-graft system are effective and safe methods for treating aneurysms with severely angulated necks.

Factors for C-Kit Expression in Cardiac Outgrowth Cells and Human Heart Tissue

We determined the factors associated with the expression of c-kit in the heart and the proliferation of c-kit-positive (c-kitpos) cardiac stem cells among the outgrowth cells cultured from human cardiac explants.Samples of the right atrium (RA), left atrium (LA), and left ventricle obtained from patients during open-heart surgery were processed for cell culture of outgrowth cells and tissue analysis. The total number of growing cells and the population of c-kitpos cells were measured and compared with c-kit expression in native tissues and characteristics of the patients according to the region of the heart.We analyzed 452 samples from 334 patients. Atrial fibrillation (AF) in the patients reduced the number of outgrowth cells from the RA and LA, and aging was a co-factor for the LA. The c-kitpos population from the RA was associated with serum brain natriuretic peptide (BNP). C-kit expression in native tissue was also associated with BNP expression. However, we observed no relationship in expression between outgrowth cells and native tissue. In addition, the RA tissue provided the highest number of c-kitpos cells, and the left ventricle provided the lowest.C-kit was weakly expressed in response to damage. In addition, no correlation between outgrowth cells and native tissue was found for c-kit expression.

Vacuum-assisted closure with a portable system for treatment of poststernotomy mediastinitis

The patient was a 50-year-old man with diabetes who was on insulin. Complications of mediastinitis developed after coronary bypass surgery, which had been performed for unstable angina. Upon hospital admission, the patient was treated with antibiotics, and the wound was cleaned on a daily basis. However, because the patient’s fever persisted, the wound was completely opened surgically and found to be deep and large. Because the patient’s condition was relatively stable, minimally invasive vacuum-assisted closure was selected. We fabricated a portable vacuum-assisted closure system that imposed few limitations on individual movement. Vacuum-assisted closure treatment resulted in both rapid abatement of fever and improved granulation. Dressings were changed once a week; the wound was closed 4 weeks after vacuum-assisted closure and healed completely. Vacuum-assisted closure may be an effective therapy for postoperative mediastinitis, and our portable vacuum-assisted closure system may significantly reduce patient distress as well as direct medical care.