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Cohort Studies Affecting The Prognosis Of Surgical Treatment Of Coronary Heart Disease And The Role Of New Conductive Biomaterials In Myocardial Infarction

Posted on:2020-11-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:S L ChenFull Text:PDF
GTID:1364330578983599Subject:Surgery
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Background:Decreased graft patency after off-pump coronary artery bypass surgery(OPCAB)are common and lead to substantial increases in cardiac events and clinical outcomes.However,there is paucity of data on the efficacy and safety of perioperative statin therapy for OPCAB populations.Objectives:To evaluate the efficacy of perioperative continuation of statin therapy on early graft patency and clinical outcomes among patients undergoing off-pump coronary artery bypass surgery(OPCAB).Methods:A total of 582 patients who were scheduled for first-time isolated OPCAB in a single-institution database(October 2009-September 2012)were stratified by perioperative continuation of statin therapy(CS group,n=398)or not(DS group,n=184).To account for non-random treatment assignment,inverse probability weighted(IPW)propensity adjustment across 20 preoperative and procedural characteristics was used,resulting in a well-matched cohort Primary outcomes were graft patency at an average of five days after operation and in-hospital mortality.Secondary outcomes included intraoperative blood loss,liver and renal functions.Results:No in-hospital death occurred in this study.Low-density lipoprotein levels of patients on continuous statin treatment were reduced to 65.35 mg/dL(pre-IPW adjustment)and 65.02 mg/dL(post-IPW adjustment).Early graft patency rates post OPCAB were 98.4%(1255 of 1275 grafts)in the CS group and 98.0%(583 of 595 grafts,P=0.486)in the DS group.This lack of significant difference in graft patency between groups also held true following IPW adjustment(98.5%versus 98.0%,P=0.224).Subgroup analyses suggested that graft occlusion was less common in CS than in DS group among smoking patients(odds ratio 0.41;95%confidence interval,0.20 to 0.86;P<0.05),a difference that was absent in the non-smokers(6.0%versus 4.6%,OR 1.34;95%CI,0.64 to 2.83),P-interaction=0.026.Secondary outcomes showed a reduction in blood loss during operation(438.53 mL versus 480.47 mL,P=0.010).There was no significant difference in serum creatinine(1.04 mg/dL versus 1.06 mg/dL,P=0.331)and estimated glomerular filtration rate(76.28 mL/min/1.73m2 versus 76.13 mL/min/1.73m2,P=0.90).In the entire cohort,following IPW adjustment,abnormal alanine transaminase elevation was observed in 8.9%of the CS group,and 3.1%in the DS group(odds ratio 3.06;95%confidence interval,1.77 to 5.29,P<0.001),indicating that elevated liver function was more prevalent in CS than in DS conditions.Conclusions:Perioperative continuation of statin therapy did not improve early graft patency among patients undergoing OPCAB.Smoking patients might benefit from perioperative continuation of statin therapy in terms of graft occlusion.Perioperative continuation of statin therapy tended to increase the risk of elevated liver function.Objectives:To evaluate the hemodynamics and biocompatibility of FW-2 left ventricular assist device(LVAD)in sheep model.Methods:The FW-2 LVAD,a miniaturized axial rotary blood pump with a diameter of 30 mm and a weight of 180 g,had been developed at Fuwai Hospital over years.We evaluate the short-term(7 days)efficacy and safety of FW-2 LVAD on seven healthy adult sheep by hemodynamic and biochemical tests at dayl,3,5,7,postoperatively.The level of plasma-free hemoglobin was measured by plasma hemoglobin measuring kits(Sigma,St.Louis,MO).Complete necropsy,histological examination and pump inspection were also performed in order to analyse the situation of thromboembolism in the heart,lung,kidney,liver,spleen and brain.Results:No sheep died during the scheduled study duration of 7 days.All the sheep lived for 8 and 21 days respectively without any major adverse events,such as anorexia,infection,or neurologic disorders,under the mechanical circulatory support of FW-2 LVAD.The devices functioned well without any technical problem in all sheep.An average pump speed of 7500 r/min provided the average flow of 2.5 L/min.The average plasma-free hemoglobin concentration was 70 mg/L at postoperative day 3 and then decreased to 30 mg/L at postoperative day 7.Histological examination showed no evidence of ischemia or infarction in hearts,lungs,kidneys,livers,spleens or brains.Conclusions:FW-2 LVAD functioned well in vivo.It might be a promising device for short-term mechanical circulatory support.Objectives:Myocardial infarction(MI)results in cardiomyocyte necrosis which is replaced by fibroblasts and collagen tissue.The nonconductive nature of the fibrotic tissue causes abnormal electric signal propagation and desynchronizes cardiac contraction,resulting in cardiac arrhythmia.Both stable and biodegradable biomaterials have been used to treat myocardial infarction.However,neither type of biomaterial can conduct electrical activity.An implantable conductive biomaterial scaffold may hold such a potential to rebuild electric signaling propagation through the infarct region to synchronize contraction and restore ventricular function.However,biocompatibility of such a tissue-engineered scaffold is the key factor for the successful resynchronization of contraction.Besides,we evaluated the conductivity and efficacy of the newly synthesized conductive polyAMBA(3-amino-4-methoxybenzoic acid)-gelfoam(PAMB-G)cardiac scaffold to support cardiomyocyte(CM)viability and function in vitro and to surgically treat MI in vivo.Methods and Results:AMBA(3-amino-4-methoxybenzoic acid)has a unique structure as a conductive polymer,but is non-biocompatible.We conjugated AMBA to sidechain of gelfoam,which was mainly composed of gelatin,creating a novel conductive scaffold(PAMB-G).Cyclic voltammetry measurement showed that PAMB-G scaffold was 11 times more conductive than gelfoam alone.PAMB-G scaffold did not show any cytotoxicity regarding rat neonatal cardiomyocyte survival and growth.Ca2+ imaging analysis showed that cardiomyocytes grown on PAMB-G had higher conductive velocity with synchronized contraction of distinct clusters of spontaneously-beating cardiomyocytes in comparison with gelfoam alone.The backbone of gelfoam made PAMB-G a 3-dimensional conductive scaffold thus in vitro construction of tissue-engineered PAMB-G cardiac scaffold was performed.64-electrode microelectrode array(64-MEA)measurement showed PAMB-G had higher field potential amplitude as well as better conductive velocity.Implantation of tissue-engineered PAMB-G scaffold onto the scar zone of rat hearts improved electrical impulse propagation across the scarred tissue whereas gelfoam-implanted hearts continued to have delayed propagation patterns and significantly reduced conduction velocity.Program electrical stimulation analysis demonstrated that the infarcted heart with PAMB-G scaffold had significantly less occurrence of cardiac arrhythmia than those hearts with gelfoam implantation.Conclusions:The PAMB-G scaffold was biocompatible and conductive,making it an attractive candidate for a new biomaterial platform for cardiac surgical treatment to preserve synchronous ventricular contraction and improve ventricular function post myocardial infarction.
Keywords/Search Tags:coronary artery disease, off-pump coronary artery bypass, graft patency, perioperative statin therapy, HMG-CoA reductase inhibitors, left ventricular assist device, FW-2, biocompatibility, mechanical circulate support, preclinical study
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