|Year : 2005 | Volume
| Issue : 2 | Page : 44-46
|Date of Web Publication||18-Jun-2010|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Cardiovascular News. Heart Views 2005;6:44-6
Increasing elastin within a myocardial scar can preserve ventricular function
After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. Investigators evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy.
After causing a myocardial infarction by ligation of the left anterior descending artery in rats, endothelial cells transfected with the rat elastin gene were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination.
Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller (P < 0.05) in the elastin group than in the control group.Cardiac function evaluated by echocardiography and during Langendorff perfusion was significantly better (P < 0.05) in the elastin group than in the control group.
The study concluded that expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months.
Cell transplantation improves ventricular function after a myocardial infarction
Cell transplantation offers the promise of restoring ventricular function after an extensive myocardial infarction, but the optimal cell type remains controversial. Human unrestricted somatic stem cells (USSCs) isolated from umbilical cord blood have great potential to differentiate into myogenic cells and induce angiogenesis. A study performed in pigs evaluated the effect of USSCs on myocardial regeneration and improvement of heart function after myocardial infarction in a porcine model.
The distal left anterior descending artery of Yorkshire pigs (30 to 35 kg) was occluded by endovascular implantation of a coil. Four weeks after infarction, single-photon emission computed tomography technetium 99m sestamibi scans (MIBI) and echocardiography were performed. USSCs (100x106) or culture media were then directly injected into the infarcted region (n=8 per group). Pigs were immunosuppressed by daily administration of cyclosporin A. At 4 weeks after transplantation, MIBI and echocardiography were repeated and heart function was also assessed with a pressure-volume catheter. The infarcted myocardium and implanted cells were studied histologically. MIBI showed improved regional perfusion (P < 0.05) and wall motion (P < 0.05) of the infarct region in the transplant group compared with the control. Ejection fraction evaluated by both MIBI and echocardiography decreased in the control group but increased in the transplant group (P < 0.01). Scar thickness of the transplant group was higher than the control. The grafted cells were detected 4 weeks after transplantation by both immunohistochemistry and in situ hybridization.
Engrafted USSCs were detected in the infarct region 4 weeks after cell transplantation, and the implanted cells improved regional and global function of the porcine heart after a myocardial infarction. This study suggests that the USSC implantation will be efficacious for cellular cardiomyoplasty.
Tissue-engineered myocardial patch derived from extracellular matrix provides regional mechanical function
Extracellular matrix (ECM), a tissue-engineered scaffold, recently demonstrated cardiomyocyte population after myocardial implantation. Surgical restoration of myocardium frequently uses Dacron as a myocardial patch. Scientists hypothesized that an ECM-derived myocardial patch would provide a mechanical benefit not seen with Dacron.
Using a canine model, a full thickness defect in the right ventricle was repaired with either Dacron or ECM. A third group had no surgery and determined baseline RV function. Eight weeks later, global systolic function was assessed by the preload recruitable stroke work relationship. Regional systolic function was measured by systolic area contraction (SAC), calculated by high density mechanical mapping. Tau was used to assess global diastolic function. Recoil rate and diastolic shear were used as measures of regional diastolic function. After functional data acquisition, tissue was fixed for histological evaluation. Global systolic and diastolic functions were similar at baseline and after ECM and Dacron implantation. Regional systolic function was greater in the ECM group compared with the Dacron group (SAC: 4.1-0.9% versus -1.8-1.1, P < 0.05). Regional diastolic function was also greater in the ECM group (recoil rate ( sec-1): -44-7 versus -17-2, ECM versus Dacron; P<0.05). Immunohistochemical analysis revealed cardiomyocytes in the ECM implant region, a finding not seen with Dacron.
At 8 weeks, an ECM-derived tissue-engineered myocardial patch provides regional mechanical function, likely related to cardiomyocyte population. These results are in sharp contrast to Dacron, a commonly used myocardial patch.
Patients with multivessel disease have better long-term survival with CABG compared to PCI
Randomized trials comparing coronary artery bypass graft surgery (CABG) with percutaneous coronary interventions (PCIs) for patients with multivessel coronary disease (MVD) report similar long-term survival for CABG and PCI. These studies used a highly selected population of patients and providers, and their results may not be applicable to actual care. A study compared long-term survival of MVD patients treated with CABG vs PCI in contemporary practice.
Data for the study was collected from northern New England registries of consecutive coronary revascularizations. 10,198 CABG and 4295 PCI patients with MVD who may have been eligible for either CABG or PCI between 1994 and 2001 were identified
Vital status was obtained by linkage to the National Death Index. Proportional-hazards regression was used to calculate hazard ratios (HRs) for survival in CABG vs PCI patients after adjustment for comorbidities and disease characteristics. CABG patients were older; had more comorbidities, more 3-vessel disease, and lower ejection fractions; and were more completely revascularized. Adjusted long-term survival for patients with 3-vessel disease was better after CABG than PCI (HR, 0.60; P < 0.01) but not for patients with 2-vessel disease (HR, 0.98; P = 0.77). The survival advantage of CABG for 3-vessel disease patients was present in all patient populations, including women, diabetics, and the elderly and in the era of high stent utilization.
In contemporary practice, survival for patients with 3-vessel coronary disease is better after CABG than PCI, an observation that patients and physicians should carefully consider when deciding on a revascularization strategy.
Preoperative Aspirin Therapy is Associated With Improved Postoperative Outcomes in Patients Undergoing Coronary Artery Bypass Grafting
Aspirin is beneficial in the setting of atherosclerotic cardiovascular disease. There are limited data evaluating preoperative aspirin administration preceding coronary artery bypass grafting and associated postoperative outcomes.
Using prospectively collected data from 1636 consecutive patients undergoing first-time isolated coronary artery bypass surgery from January 2000 through December 2002, the association between aspirin usage within the 5 days preceding coronary bypass surgery and risk of adverse in-hospital postoperative events was evaluated. A logistic regression model, which included propensity scores, was used to adjust for remaining differences between groups.
Overall, there were 36 deaths (2.2%) and 48 adverse cerebrovascular events (2.9%) in the postoperative hospitalization period. Patients receiving preoperative aspirin (n=1316) had significantly lower postoperative in-hospital mortality compared with those not receiving preoperative aspirin [1.7% versus 4.4%; adjusted odds ratio (OR), 0.34; 95% CI, 0.15 to 0.75; P = 0.007]. Rates of postoperative cerebrovascular events were similar between groups (2.7% versus 3.8%; adjusted OR, 0.67; 95% CI, 0.32 to 1.50; P = 0.31). Preoperative aspirin therapy was not associated with an increased risk of reoperation for bleeding (3.5% versus 3.4%; P = 0.96) or requirement for postoperative blood product transfusion (adjusted OR, 1.17; 95% CI, 0.88 to 1.54; P = 0.28).
The use of aspirin within the 5 days preceding coronary artery bypass surgery is associated with a lower risk of postoperative in-hospital mortality and appears to be safe without an associated increased risk of reoperation for bleeding or need for blood product transfusion.
Aprotinin Decreases Postoperative Bleeding and Number of Transfusions in Patients on Clopidogrel Undergoing Coronary Artery Bypass Graft Surgery
Clopidogrel, an irreversible platelet inhibitor, is used to treat patients with unstable angina. These patients often present for coronary artery bypass graft surgery (CABG) and are at increased risk for perioperative bleeding. A study evaluated the impact of aprotinin on bleeding and transfusion requirements in clopidogrel-treated patients undergoing CABG.
Seventy-five consecutive patients with unstable angina, administered clopidogrel <5 days before CABG, were randomized. Using a double-blind design, patients received full-dose aprotinin (n =37) or saline (n =38). Elapsed times between the last dose of clopidogrel and start of the operation were similar between the 2 groups [aprotinin, 58-28 hour (mean- SD); control, 54-27 hour; P=0.86], as were age (aprotinin, 66.4-10 years; control, 68.3-10 years; P = 0.51), number of distal anastomoses (aprotinin, 3.6-1.0; control, 3.7-1.0; P = 0.79), operative times (aprotinin, 192-48 minutes; control, 200-53 minutes; P = 0.55), and lowest intraoperative hemoglobin level (aprotinin, 87-14 g/L; control, 88-14 g/L; P=0.60).
Postoperative bleeding was 760-350 mL in aprotinin-treated patients versus 1200-570 mL (P < 0.001) in control. During the hospital stay, patients in the aprotinin group received 1.2-1.5 and 0.1-0.4 U of erythrocytes and platelets, respectively, versus 2.8-3.2 (P = 0.02) and 0.9-1.4 (P = 0.002) units in the control. In the aprotinin group, 53% of patients received transfusions, whereas 79% of controls were exposed to blood products (P = 0.02).
In patients undergoing CABG and treated with clopidogrel <5 days before surgery, intraoperative aprotinin decreases postoperative bleeding and the number of transfusions.
Preoperative thrombolysis in CABG patients increase long-term survival
Coronary artery bypass grafting (CABG) is frequently used after thrombolytic therapy. However, there is little information regarding long-term survival in this setting. The purpose of the present study was to compare the long-term survival of patients subjected to CABG after thrombolysis to those without thrombolysis.
3760 consecutive patients with isolated CABG between 1992 and 2002 were studied. CABG patients without thrombolysis were compared with those who were treated with thrombolysis within 7 days before CABG. Groups were compared by Cox proportional hazard models and Kaplan-Meier survival plots. The propensity for thrombolysis was determined by logistic regression analysis, and each patient with thrombolysis was then matched to 5 patients without thrombolysis. One hundred ninety-six patients (5.2%) were treated with thrombolysis. Patients with thrombolysis were more likely to be male, younger, and with higher rates of unstable angina, emergency operation, recent or transmural myocardial infarction, preoperative intraaortic balloon pump, hemodynamic instability, shock, intravenous nitroglycerine, left-ventricular hypertrophy, sustained ventricular arrhythmia, and higher EuroSCORE. There were no differences in early outcome between matched groups, but the 5-year actuarial survival was higher in patients with thrombolysis (90.3-2.2% versus 78.5-1.6%; P=0.0007). After adjustment for all factors, the hazard ratio of long-term mortality for patients with thrombolysis was 0.54 (95% CI, 0.36 to 0.81; P = 0.003) and, if deaths during the first 12 months were excluded, 0.46 (95% CI, 0.27 to 0.76; P = 0.003).
Patients subjected to CABG within 7 days after thrombolysis demonstrated increased long-term survival.
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