Aortic Wall Extracellular Matrix Proteins Correlate with Syntax Score in Patients Undergoing Coronary Artery Bypass Surgery.

AIMS: The SYNTAX score correlate with major cardiovascular events post-revascularization, although the histopathological basis is unclear. We aim to evaluate the association between syntax score and extracellular matrix histological characteristics of aortic punch tissue obtained during coronary artery bypass surgery (CABG). This analysis compares coronary artery bypass surgery patients with High and Low syntax score which were followed up for one year period. METHODS AND RESULTS: Patients with High (score ≥ 33, (n=77)) and Low Syntax Scores (score ≤ 22, (n=71)) undergoing elective CABG were recruited prospectively. Baseline clinical characteristics and surgical risks were well matched. At 1 year, EMACCE (Sum of cardiovascular death, stroke, congestive cardiac failure, and limb, gut and myocardial ischemia) was significantly elevated in the High syntax group (P=0.022). Mass spectrometry (MS)-based quantitative iTRAQ proteomic results validated on independent cohort by immunohistochemistry (IHC) revealed that the High syntax group had significantly upraised Collagen I (P<0.0001) and Elastin (P<0.0001) content in ascending aortic wall. CONCLUSION: This study shows that aortic extracellular matrix (ECM) differ between High and Low syntax groups with up-regulation of Collagen I and Elastin level in High Syntax Score group. This identifies aortic punches collected during CABG as another biomarker source related with atherosclerosis severity and possible clinical outcome.

Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic spheroids induce post-ischemic myocardial revascularization and preserve cardiac function in failing rat hearts.

A crucial question in post-ischemic cell therapy refers to the ideal method of cell delivery to the heart. We hypothesized that epicardial implantation of subamnion-cord-lining mesenchymal stem cells (CL-MSC) angiogenic spheroids embedded within fibrin grafts (SASG) facilitates donor cell survival and enhances cardiac function in failing rat hearts. Furthermore, we compared the efficacy of this approach applied through two delivery methods. Spheroids made of 1.5×10(4) human CL-MSC coated with 2×10(3) human umbilical vein endothelial cells were self-assembled in hanging drops. SASG were constructed by embedding 150 spheroids in fibrin matrix. Except for untreated rats (MI, n=8), grafts were implanted 2 weeks after myocardial infarction upon confirmation of ensued heart failure through thoracotomy: SASG (n=8) and fibrin graft (FG, n=8); or video-assisted thoracoscopic surgery (VATS): SASG-VATS (n=8) and FG-VATS (n=7). In vivo CL-MSC survival was comparable between both SASG-treated groups throughout the study. SASG and SASG-VATS animals had decreased left ventricular end-diastolic pressure relative to untreated animals, and increased fractional shortening compared to MI and FG controls, 4 weeks after treatment. A 14.1% and 6.2% enhancement in ejection fraction from week 2 to 6 after injury was observed in SASG/SASG-VATS, paralleled by improvement in cardiac output. Treated hearts had smaller scar size, and more blood vessels than MI, while donor CL-MSC contributed to arteriogenesis within the graft and infarct areas. Taken together, our data suggest that SASG treatment has the potential to restore failing hearts by preserving cardiac function and inducing myocardial revascularization, while attenuating cardiac fibrosis. Furthermore, we introduce a method for minimally invasive in situ graft assembly.

Post-ischaemic angiogenic therapy using in vivo prevascularized ascorbic acid-enriched myocardial artificial grafts improves heart function in a rat model.

Angiogenesis plays a key role in post-ischaemic myocardial repair. We hypothesized that epicardial implantation of an ascorbic acid (AA)-enriched myocardial artificial graft (MAG), which has been prevascularized in the recipients' own body, promotes restoration of the ischaemic heart. Gelatin patches were seeded with GFP-luciferase-expressing rat cardiomyoblasts and enriched with 5 µm AA. Grafts were prevascularized in vivo for 3 days, using a renal pouch model in rats. The MAG patch was then implanted into the same rat's ischaemic heart following myocardial infarction (MI). MAG-treated animals (MAG group, n = 6) were compared to untreated infarcted animals as injury controls (MI group, n = 6) and sham-operated rats as healthy controls (healthy group, n = 7). In vivo bioluminescence imaging indicated a decrease in donor cell survival by 83% during the first week post-implantation. Echocardiographic and haemodynamic assessment 4 weeks after MI revealed that MAG treatment attenuated left ventricular (LV) remodelling (LV end-systolic volume, 0.31 ± 0.13 vs 0.81 ± 0.01 ml, p < 0.05; LV end-diastolic volume 0.79 ± 0.33 vs 1.83 ± 0.26 ml, p < 0.076) and preserved LV wall thickness (0.21 ± 0.03 vs 0.09 ± 0.005 cm, p < 0.05) compared to the MI group. Cardiac output was higher in MAG than MI (51.59 ± 6.5 vs 25.06 ± 4.24 ml/min, p < 0.01) and comparable to healthy rats (47.08 ± 1.9 ml/min). Histology showed decreased fibrosis, and a seven-fold increase in blood vessel density in the scar area of MAG compared to MI group (15.3 ± 1.1 vs 2.1 ± 0.3 blood vessels/hpf, p < 0.0001). Implantation of AA-enriched prevascularized grafts enhanced vascularity in ischaemic rat hearts, attenuated LV remodelling and preserved LV function.

Off-pump coronary bypass surgery is safe in patients with a low ejection fraction (< or =25%).

BACKGROUND: A severely decreased ejection fraction (EF) of < or =25% is an established risk factor for a worse outcome after heart surgery and therefore has been incorporated into the EuroSCORE risk-stratification model. We compare clinical outcomes after off-pump coronary artery bypass grafting (OPCAB) and on-pump coronary artery bypass grafting in patients with a severely compromised EF. METHODS: We compared 112 patients with a low EF (< or =25%) who underwent myocardial revascularization between 2003 and 2008. Forty-four patients underwent OPCAB (group A), and 68 patients underwent on-pump surgery (group B). We compared demographics, intraoperative parameters, intraoperative outcomes, and the completeness of revascularization for the 2 groups. RESULTS: Demographic and EuroSCORE data were comparable for groups A and B. The 2 groups appeared to be similar with respect to mortality rate during the first 30 days (2.2% and 8.8%, respectively; P = .11) and the rate of major complications such as stroke (2.2% and 2.9%, respectively; P = 0.83). The patients in group A had fewer pulmonary complications (7% versus 25%, P < .01), received fewer blood transfusions (15.9% versus 47.0%, P < .01), required fewer postoperative pacing procedures (atrial, 11.4% versus 39.7%; ventricular, 13.6% versus 47.1%; P < .01), and had fewer wound infections (2.2% versus 16.1%, P = .02). The numbers of diseased vessels were comparable, and although the OPCAB patients received more arterial grafts (1.05 +/- 0.43 versus 0.84 +/- 0.37, P < .01), the total number of grafts per patient was lower among these patients (2.50 +/- 0.88 versus 3.53 +/- 0.92, P = .03). Similarly, complete revascularization was achieved less frequently within this group (80% versus 94%, P = .02). CONCLUSIONS: A standardized OPCAB approach in patients with a severely decreased EF is safe and may benefit this subset of patients with respect to fewer postoperative complications. Although complete revascularization is the optimal approach for these patients, they benefit from avoiding cardiopulmonary bypass.

Left ventricular shape-based contractility index.

This study develops contractility indices in terms of the left ventricular (LV) ellipsoidal geometrical shape-factor. The contractility index (CONT1) is given by the maximum value dsigma(*)/dt wherein sigma(*)=sigma/P, sigma is the wall stress, and sigma(*) is expressed in terms of the shape factor S (the ratio of the minor axis and major axis, B/A, of the instantaneous LV ellipsoidal model). Another contractility index (CONT2) is also developed based on how far apart the in vivo S at the start of ejection is from its optimized value, CONT2=(S(se)-S(se)(op))/S(se)(op), where S(se) refers to the value of S at the start of ejection, S(se)(op) is the derived optimal value of S(se) for which sigma* is maximum. The values of S(=B/A) were calculated from cineventriculographically monitored LV volume, myocardial volume and wall-thickness. Then both the contractility indices were evaluated in normal subjects, as well as in patients with mild heart failure and in patients with severe heart failure. The normal values of CONT1 and CONT2 are 8.75+/-2.30s(-1) and 0.09+/-0.07, respectively. CONT1 decreased in patients with mild and severe heart failures to 5.78+/-1.30 and 3.90+/-1.30, respectively. CONT2 increased in patients with mild and severe heart failures to 0.11+/-0.09 and 0.23+/-0.12, respectively. This implies that a non-optimal and less ellipsoidal shape is associated with decreased contractility (and poor systolic function) of the LV. CONT1 and CONT2 are useful as non-invasively determinable quantitative indices of LV contractility, to distinguish between normal and pathologic LVs.