Chwan Yau Luo

Intramyocardial Peptide Nanofiber Injection Improves Postinfarction Ventricular Remodeling and Efficacy of Bone Marrow Cell Therapy in Pigs

Background— Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and Results— A total of 40 mature minipigs were divided into 5 groups: sham, MI+normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1×108 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and −dP/dt (1214.5±91.9 and −1109.7±91.2 mm Hg/s in MI+NS, 1693.7±84.7 and −1809.6±264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3±4.5 cells/mm2 in MI+MNCs and 229.4±41.4 cells/mm2 in MI+MNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions— We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future.

In situ reconstruction of septic aortic pseudoaneurysm due to Salmonella or Streptococcus microbial aortitis: long-term follow-up.

OBJECTIVE This study was undertaken to illustrate the safety of in situ reconstruction of septic aortic pseudoaneurysm (SAP) secondary to microbial aortitis, with or without long-term antibiotic treatment. METHODS Data for patients with SAP (11 abdominal, 4 thoracic) operated on between 1993 and 1999 were reviewed. Computed tomography and aortography showed septic pseudoaneurysm in all patients before surgery. After diagnosis of SAP, all patients underwent aneurysm resection and extensive debridement, with in situ prosthetic grafting or patch repair angioplasty. The graft in 10 of the 11 patients with abdominal SAP was also wrapped with an omental pedicle. In vitro active parenteral antibiotic therapy was prescribed for all patients for at least 2 to 8 weeks after surgery. RESULTS All 15 patients had positive preoperative blood cultures or intraoperative tissue cultures for Salmonella spp (n = 12), viridans Streptococcus (n = 1), group G Streptococcus (n = 1), or Streptococcus pneumoniae (n = 1). There were two perioperative deaths (13.3%), one 6 days after surgery and the other 19 days after surgery, and two late deaths, at 8 and 10 months after surgery, neither of which was related to aortic repair. One patient was unavailable for follow-up. The other 10 patients have been regularly followed up with abdominal ultrasound or computed tomography (mean, 84 months; range, 47-118 months). To date, there has been no graft infection, thrombosis, false aneurysm, or subsequent aortic surgery in these 10 patients. CONCLUSION SAP due to Salmonella and streptococcal microbial aortitis can be successfully treated with resection of the aneurysm and extensive debridement, followed by in situ prosthetic graft interposition or patch repair aortoplasty. This is a safe and effective treatment that may result in complete remission of SAP. Postoperative parenteral antibiotic therapy should be continued for 2 to 8 weeks. Although usually recommended, lifelong suppressive antibiotic therapy appears to be nonessential with this approach.

Instructive Nanofiber Scaffolds with VEGF Create a Microenvironment for Arteriogenesis and Cardiac Repair

An intramyocardial microenvironment was created using nanofibers and VEGF for endogenous cardiac repair after infarction. Nanomaterials Help the Heart to Heal Normally, the cure for a broken heart is time. After a heart attack, or myocardial infarction (MI), however, time can work against the heart, allowing tissue remodeling, scar formation, and overall heart failure. In an effort to speed up the healing process after MI, Lin and colleagues have created self-assembling peptide nanofibers (NFs) that, when injected into the heart tissue immediately after MI, lead to rapid repair and functional recovery. The authors first tested the NF with and without varying doses of vascular endothelial growth factor (VEGF) in a rat model. The material–growth factor combination was injected into the heart immediately after MI, and 28 days later had significantly improved cardiac function compared with NF or VEGF alone. The NF/VEGF treatment also prevented tissue remodeling and collagen deposition (which cause heart scarring) and reduced the infarct size. Moving to a large animal that more closely resembles human MI, Lin et al. injected the NF/VEGF combination material into heart tissue of pigs immediately after infarction and observed tissue repair and restored function, similar to the rat. The authors found that the NF created the optimal microenvironment for healing by promoting arteriogenesis (increased densities of arteries and arterioles) and by recruiting endogenous myofibroblasts and cardiomyocyte-like cells to the damaged tissue. Moreover, for translation, the authors showed that their NF material helps to heal the heart in both small and large animal models, without harmful effects to other tissues. Before moving to patients, the material will need to be tested at later time points to mimic the sequence of events after a heart attack. Also, rather than direct myocardial injection, the material will likely need to be delivered via a minimally invasive catheter. With these considerations in mind, this promising NF/VEGF combination is ready to take a shot at healing the human heart. Angiogenic therapy is a promising approach for tissue repair and regeneration. However, recent clinical trials with protein delivery or gene therapy to promote angiogenesis have failed to provide therapeutic effects. A key factor for achieving effective revascularization is the durability of the microvasculature and the formation of new arterial vessels. Accordingly, we carried out experiments to test whether intramyocardial injection of self-assembling peptide nanofibers (NFs) combined with vascular endothelial growth factor (VEGF) could create an intramyocardial microenvironment with prolonged VEGF release to improve post-infarct neovascularization in rats. Our data showed that when injected with NF, VEGF delivery was sustained within the myocardium for up to 14 days, and the side effects of systemic edema and proteinuria were significantly reduced to the same level as that of control. NF/VEGF injection significantly improved angiogenesis, arteriogenesis, and cardiac performance 28 days after myocardial infarction. NF/VEGF injection not only allowed controlled local delivery but also transformed the injected site into a favorable microenvironment that recruited endogenous myofibroblasts and helped achieve effective revascularization. The engineered vascular niche further attracted a new population of cardiomyocyte-like cells to home to the injected sites, suggesting cardiomyocyte regeneration. Follow-up studies in pigs also revealed healing benefits consistent with observations in rats. In summary, this study demonstrates a new strategy for cardiovascular repair with potential for future clinical translation.

The Efficacy of Aortic Stent Grafts in the Management of Mycotic Abdominal Aortic Aneurysm-Institute Case Management with Systemic Literature Comparison

BACKGROUND Conventional surgery (CS) for treatment of mycotic aortic aneurysm has rather high surgical morbidity and mortality rates. The use of endovascular aortic repair (EVAR) might simplify the procedure and provide a good alternative for this critical condition, but this remains to be proved. We analyzed all mycotic abdominal aortic aneurysm (AAA) cases treated by CS or EVAR in our institute and the reported cases treated by EVAR from the literature to determine the risk factors for aneurysm-related mortality and morbidity and to clarify the efficacy of the EVAR technique. METHODS AND RESULTS All relevant literature reports of EVAR management of mycotic AAA and all cases treated in our institute, 41 cases, were included and analyzed. Of the 20 cases treated by EVAR, one had early mortality (1/20, 5%); of the remaining 21 cases that received CS, the early mortality rate was 4.8% (1/21). Patients in the CS group had a higher late mortality rate than those in the EVAR group (45% vs. 10.5%, p<0.05). However, the 24-month actual survival rate and actuarial aneurysm-related event-free rate were 83.9+/-8.6% and 78.3+/-9.7%, respectively, for the EVAR group and did not significantly differ from the CS group (70.4+/-10.2% and 80.1+/-8.9%). The significant predictors for aneurysm-related mortality and morbidity were age, Salmonella species infection, and leukocytosis, and possibly aortoenteric fistula and shock, but not the EVAR or CS procedures themselves. CONCLUSION Compared with CS, EVAR might be an alternative strategy for managing mycotic AAAs.

Systemic steroid pretreatment improves cerebral protection after circulatory arrest

BACKGROUND This study evaluates whether systemic steroid pretreatment enhances neuroprotection during deep hypothermic circulatory arrest (DHCA) compared with steroid in cardiopulmonary bypass (CPB) prime. METHODS Four-week-old piglets randomly placed into two groups (n = 5 per group) were given methylprednisolone (30 mg/kg) into the pump prime (group PP), or pretreated intravenously 4 hours before CPB (group PT). All animals underwent 100 minutes of DHCA (15 degrees C), were weaned off CPB, and were sacrificed 6 hours later. Postoperative changes in body weight, bioimpedance, and colloid oncotic pressure (COP) were measured. Cerebral trypan blue content, immunohistochemical evaluation of transforming growth factor-beta1 (TGF-beta1) expression, and caspase-3 activity were performed. RESULTS Percentage weight gain (group PP 25.0% +/- 10.4% versus group PT 12.5% +/- 4.0%; p = 0.036), and percentage decrease in bioimpedance (PP 37.2% +/- 14.5% versus PT 15.6% +/- 7.9%; p = 0.019) were significantly lower, whereas postoperative COP was significantly higher in group PT versus group PP (PT 15.3 +/- 1.8 mm Hg versus PP 11.6 +/- 0.8 mm Hg; p = 0.003). Cerebral trypan blue (ng/g dry tissue) was significantly lower in group PT (PT 5.6 x 10(-3) +/- 1.1 x 10(-3) versus PP 9.1 x 10(-3) +/- 5.7 x 10(-4); p = 0.001). Increased TGF-beta1 expression and decreased caspase-3 activity were shown in group PT. CONCLUSIONS Systemic steroid pretreatment significantly reduced total body edema and cerebral vascular leak and was associated with better immunohistochemical indices of neuroprotection after DHCA.

Circulating Cells Contribute to Cardiomyocyte Regeneration After Injury

Rationale: The contribution of bone marrow–borne hematopoietic cells to the ischemic myocardium has been documented. However, a pivotal study reported no evidence of myocardial regeneration from hematopoietic-derived cells. The study did not take into account the possible effect of early injury–induced signaling as the test mice were parabiotically paired to partners immediately after surgery-induced myocardial injury when cross-circulation has not yet developed. Objective: To re-evaluate the role of circulating cells in the injured myocardium. Methods and Results: By combining pulse-chase labeling and parabiosis model, we show that circulating cells derived from the parabiont expressed cardiac-specific markers in the injured myocardium. Genetic fate mapping also revealed that circulating hematopoietic cells acquired cardiac cell fate by means of cell fusion and transdifferentiation. Conclusions: These results suggest that circulating cells participate in cardiomyocyte regeneration in a mouse model of parabiosis when the circulatory system is fully developed before surgery-induced heart injury.

Timing of steroid treatment is important for cerebral protection during cardiopulmonary bypass and circulatory arrest: minimal protection of pump prime methylprednisolone.

OBJECTIVES The contact of cardiopulmonary bypass surface and patients blood activates systemic inflammatory response which aggravates ischemia-reperfusion injury. This study evaluates the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on cerebral protection using different steroid administration protocols. METHODS Eighteen (n=6/group) 4 week-old piglets were divided in three groups. Methylprednisolone (30 mg/kg) was administered intravenously 4 h prior to CPB in Group I, or added in pump prime in group II. Group III received no steroid. All animals were cooled to 15 degrees C followed by 100 min of DHCA, then rewarmed over 40 min and sacrificed 6 h after CPB. Post-operative weight gain, bioelectrical impedance, colloid oncotic pressure (COP) and interleukin-6 (IL-6) were evaluated. Determination of cerebral trypan blue and immunohistochemical assays of transforming growth factor (TGF)-beta1 and caspase-3 activities were performed. RESULTS Post-operative % weight gain (13.0+/-3.8 (I) versus 26.4+/-9.9 (II) versus 22.6+/-6.4 (III), P=0.02); % bioimpedance reduction (14.5+/-8.0 (I) versus 38.3+/-13.3 (II) versus 30.5+/-8.0 (III), P=0.003); mean COP (mmHg) (14.9+/-1.8 (I) versus 10.9+/-2.0 (II) versus 6.5+/-1.8 (III), P=0.0001) and systemic IL-6 levels (pg/ml) (208.2+/-353.0 (I) versus 1562.1+/-1111.4 (II) versus 1712.3+/-533.2 (III), P=0.01) were significantly different between the groups. Spectrophotometric analysis of cerebral trypan blue (ng/g dry weight) was significantly different between the groups (0.0053+/-0.0010 (I) versus 0.0096+/-0.0026 (II) versus 0.0090+/-0.0019 (III), P=0.004). TGF-beta1 scores were 3.3+/-0.8 (I) versus 1.5+/-0.8 (II) versus 1.5+/-0.5 (III), P<0.05, groups I versus II and I versus III. Remarkable perivascular caspase-3 activity was observed in groups II and III. CONCLUSION Different timing of steroid administration results in different inflammatory mediator response. Steroid in CPB prime is not significantly better than no steroid treatment, while systemic steroid pre-treatment significantly decreases systemic manifestation of inflammatory response and brain damage.

Endoscopic saphenous vein harvest decreases leg wound complication in coronary artery bypass grafting patients

AbstractBackground: Coronary artery bypass grafting (CABG) is the most common procedure performed in adult cardiovascular surgery. The most frequently used conduit is the greater saphenous vein. Using traditional methods, the complication rate of the leg is relatively high (up to 24%). To decrease the complication rate, we used the Endo‐Path to harvest the greater saphenous vein. Methods and Results: From May 1997 through March 1999, a total of 135 patients received the CABG operation. We excluded the patients who died immediately postoperatively or had concomitant surgical procedures. Sixty patients received the endoscopic saphenous vein harvest procedure (group A), while another 59 patients (group B) did not. No important differences were noted between the two groups in respect to the number of distal anastomoses, length of harvested vein, total surgical time, and length of ICU stay. However, the leg wound complication rate decreased from 20.3% to 5.0% (p < 0.001). Conclusions: Although the long‐term patency rate needs time to be proven, the endoscopic greater saphenous vein harvest method is an attractive and effective method.

Extracorporeal membrane oxygenation as a bridge to definite surgery in recurrent postinfarction ventricular septal defect

A recurrent shunt after a postinfarction ventricular septal defect (PI-VSD) repair is common. We treated a case of cardiogenic shock caused by a large recurrent shunt after the patch repair of an apical PI-VSD with percutaneous extracorporeal membrane oxygenation (ECMO) for 4 days until a secondary definite repair. This suggests that percutaneous ECMO support is reliable before and after secondary definitive surgery in recurrent PI-VSD and may imply using a delayed surgical strategy with ECMO support to restore hemodynamic stability and avoid primary surgery on freshly fragile infarcted myocardium.

Bilateral Persistent Sciatic Arteries Complicated with Acute Left Lower Limb Ischemia

Persistent sciatic artery (PSA) is a rare congenital malformation. In the early embryonic stage, the sciatic artery is the major blood supply for the lower limb bulb and is later replaced by the iliofemoral artery as the limb develops. Its failure to regress, sometimes associated with femoral arterial hypoplasia, and therefore becoming the dominant inflow to the lower extremity is called PSA. This anomaly is often associated with a higher rate of aneurysm formation or thromboembolic complications causing lower extremity ischemia. Here, we describe a 79-year-old male patient who presented with acute left lower extremity ischemia. He was treated initially with conventional embolectomy through inguinal and popliteal incisions. The bilateral PSA with thrombosed aneurysms was not identified at first on computed tomographic angiography. It was later diagnosed intraoperatively due to the discontinuity of the superficial femoral artery and popliteal artery found with embolectomy catheter, and was managed successfully with ePTFE graft bypass. Careful interpretation of the imaging study may be helpful in preoperative diagnosis.