ObjectiveTo explore the differential expression of Sirtuin1 (SIRT1) in type A aortic dissection at diverse ages.MethodsThe expression of SIRT1 and monocyte chemoattractant protein-1 (MCP-1) in aortic tissue of the patients with type A aortic dissection (an aortic dissection group) and coronary heart disease (a control group) from 2019 to 2020 in the First Hospital of China Medical University was analyzed. In each group, the patients were divided into 3 subgroups according to the age (a younger subgroup, <45 years; a middle age subgroup, 45-60 years; an elderly subgroup, >60 years). The quantitative real-time PCR, Western blotting and immunochemical stainning were used to detect the mRNA or protein expression of SIRT1 and MCP-1. ResultsA total of 60 patients were included in each group, including 79 males and 41 females. There were 20 patients in the yonger, middle age and elderly subgroups for the two groups, respectively. Compared with the control group, the expression of SIRT1 mRNA decreased in the aortic dissection group (the younger subgroup: 4.54±1.52 vs. 8.78±2.57; the middle age group: 2.70±1.50 vs. 5.74±1.07; the elderly group: 1.41±1.33 vs. 3.09±1.14, P<0.001). Meanwhile, SIRT1 mRNA in the aortic dissection group declined with age (P<0.01). Compared with the control group, SIRT1 protein expression decreased significantly in the aortic dissection group (the younger group: 0.64±0.18 vs. 1.18±0.47; the middle age group: 0.43±0.26 vs. 0.69±0.32; the elderly group: 0.31±0.24 vs. 0.45±0.29, P<0.01). The Western blotting results showed that the expression of SIRT1 protein in the aortic dissection group decreased with age (P<0.01). The MCP-1 protein expression of younger and middle age patients in the aortic dissection group was increased compared with that in the control group (the younger group: 0.65±0.27 vs. 0.38±0.22; the middle age group: 1.08±0.30 vs. 0.46±0.36, P<0.001). MCP-1 expression increased with age (P<0.01). The result of immunohistochemical staining for SIRT1 protein was similar to that of Western blotting.ConclusionThe expression of SIRT1 decreases in patients with aortic dissection disease, and declines with age. SIRT1 may play an important role in the treatment and screening of type A aortic dissection.
Objective To investigate the effect of combined delivery of hepatocyte growth factor (HGF) and insulinlike growth factor-1 (IGF-1) on the development of bone mesenchymal stem cells (BMSCs) differentiation by expression of GATA-4，and to supply some evidence for clinical BMSCs transplantation therapy. Methods BMSCs were isolated from the femurs and tibias of the randomly assigned rabbits and cocultured with myocytes in a ratio of 1∶1. Myocytes were obtained from neonatal rabbits ventricles. 150 ng/ml HGF and 200 ng/ml IGF-1 were added into 4 culture bottles of 8 bottles and the other 4 bottles were not. After BMSCs were cocultured with myocytes for 1 day, 3 days, 1 week, and till 6 weeks， differentiated BMSCs were targeted and microdissected with a laser capture microdissection system, and then ribonucleic acid (RNA) was extracted and isolated. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcriptionpolymerase chain reaction (RT-PCR). And expression of GATA-4 in BMSCs was detected by semiquantitative RT-PCR. Results Before coculturing, the BMSCs were negative for α-actinin and exhibited a nucleus with many nucleoli. After coculture with myocytes, some BMSCs became αactininpositive and showed a cardiomyocytelike ultrastructure, including sarcomeres, endoplasmic reticulum, and mitochondria. BMSCs cocultured with myocytes expressed cardiac transcription factor GATA-4. IGF-1 and HGF delivery can significantly increased expression of GATA-4 for the differentiated BMSCs as compared with cells of no delivery of HGF and IGF-1. The expression level of GATA-4 in captured BMSCs began to increase at the 1st day, reach the peak at the 2nd week and kept high expression level after the 2nd week. Conclusion BMSCs can transdifferentiate into cells with a cardiac phenotype when cocultured with myocytes. Differentiated myocytes express cardiac transcription factors GATA-4. Administration of HGF and IGF-1 promoted the development of BMSCs transdifferentiate into cardiac phenotype, which is associated with the increase in expression level of GATA-4.
Abstract: Objective To compare the effects of nitroglycerine (NTG)， Verapamil(VP), papaverine(PA) and the mixed solution of Verapamil and nitroglycerine (VG) on relaxing function of human radial arteries. Methods The radial arteries of thirty patients were used during the operation of coronary artery bypass grafting (CABG). A short segment (1.0-1.5cm) of radial arteris were taken from the distal end of radial arteries of each patient and were cut into vascular rings, which were mounted in the organ bath chamber and then subject to a series of tests for vascular smooth muscle viability and endothelial integrity. The effects of five storage solutions on the relaxing function were evaluated by “OrganBath” technique. The five solutions included: (1) Ringer’ s solution (control group); (2) VP solution (VP group); (3) NTG solution (NTG group); (4) PA solution (PA group); (5) VG solution (VG group). First, challenged with phenylephrine (10-5mol/L), vasorelaxant effect of these drugs (effect onset and efficacy) was observed at different time point and resting tension was recorded. Second, after 30min preincubation with either verapamil, papaverine, phenoxybenzamine or VG mixture, potassium chloride (final concentration of 60mmol/L) was added in the organ bath chamber and then vasoconstriction was observed subsequently. Finally, after 30min pretreatment of different antispasmodic agent in the same way as described above, the vascular rings were mounted in organ bath chamber and challenged with phenylephrine(10-5mol/L). Vascular spasticity and vosospasm duration were observed at different time point which might provide guidance for optimal timing of clinical application. Results The radial arteries in VG, VP, NTG and PA solutions were relaxed in 11 min after vasospasm and there was no difference between them (Pgt;0.05). But during the initial three minutes，the relaxation effect of VG and NTG was significantly better than other two groups. Relaxation curve showed that the ability of vasodilatation of VG, NTG, VP and PA decreased in order. In the experiment about antivasospasm pretreatment of radial arteries, there was no difference between VG and VP group (Pgt;0.05 ), whose effects were better than NTG and PA group(Plt;0.05 ). After cold storage for 24h, VG and VP still could prevent vasospasm. But NTG and PA hardly had any function and there was no difference compared with the control group (Pgt;0.05 ). Conclusion Although in the final all these drugs could prevent and relieve vasospasm of radial arteries in the different level, it appeared that a combination of verapamil and nitroglycenn is more fit for treating radial artery during CABG operation than other drugs.
Abstract: Objective To explore the inhospital mortalityrelated risk factors in the patients undergoing offpump coronary artery bypass grafting (OPCAB). Methods We retrospectively analyzed the clinical data of 215 patients undergoing OPCAB in our hospital from November 2007 to November 2008. There were 171 males and 44 females aged between 40 and 85 years old. Among them, there were 47 patients older than 70 years old. All of them were coronary artery disease (CAD) patients with triple vessel disease. We adopted univarialble analysis and logistic multivariable regression analysis to screen the risk factors for the mortality of OPCAB. Results Six patients died in hospital after OPCAB with a mortality rate of 2.79% (6/215). No renal dysfunction or respiratory failure occurred. The rate of reoperation for bleeding was 4.65% (10/215) and all the 10 patients having undergone reoperation were alive. A total of 209 patients were all alive after 1year follow-up. The results of logistic multivariable regression analysis showed that New York Heart Association (NYHA) Ⅲ and Ⅳ heart function (OR=42.116，95% CI 3.319 to 534.465，P=0.004) and mechanical ventilation duration (OR=1.007，95%CI 1.001 to 1.013，P=0.028) were independent risk factors for inhospital mortality of OPCAB. Conclusion OPCAB is an effective and safe treatment for CAD with triple vessel disease. NYHA Ⅲ and Ⅳ heart function and mechanical ventilation time after OPCAB are the risk factors for OPCAB inhospital mortality, yet, needs further study with large sample.
Abstract: Objective To investigate the effect of liposomal prostaglandin E1 (LipoPGE1) on inflammatory reaction during cardiopulmonary bypass (CPB) coronary artery bypass grafting (CABG). Methods Between July 2006 and December 2008, a total of 32 patients undergoing CABG were randomly divided into two groups of 16 patients each using a random digits table. The experimental group had 9 male and 7female patients with a mean age of 54.4±18.1 years; each patient received 15.0ng/(kg·min) of LipoPGE1 by venous pump through the central vein throughouttheCPB procedure. The control group had 9 male and 7 female patients with a mean age of 54.8±20.4 years, who were treated identically to the experimental group except did not receive LipoPGE1. Arterial blood samples were taken before CPBand at the 1st, 2nd, 6th, and 24th hour after open aorta ascendens. The levels of interleukin6(IL6), tumor necrosis factorα (TNFα), and soluble intercellular adhesion molecule1 (sICAM1) were tested and compared. Results In both groups, levels of IL6, TNFα, and sICAM1 were all gradually increased after the ascending aorta was opened, and they reached their highest levels at the 6th hour after open aorta ascendens. In the experimental group, at every time point afterthe ascending aorta was open, levels of IL6 (24th hour after open aorta ascendens: 16.1±2.2 μg/L vs. 19.2±4.5 μg/L,Plt;0.05), TNFα (24th hour after open aorta ascendens: 1.8±04 μg/L vs. 2.2±0.5 μg/L,Plt;0.05), and sICAM1 (24th hour after open aorta ascendens: 233.6±36.6 μg/L vs. 294.2±55.7 μg/L,Plt;0.05) were significantly lower than those of the control group. 〖WTHZ〗Conclusion LipoPGE1 effectively reduces the aggregation of polymorphonuclear neutrophilic leukocytes, inhibits activation of vascular endothelialcells, and decreases systemic inflammatorome during CPB.
Abstract:Objective To investigate the expression and significance of Voltage-gated Cl channel-3 （ClC-3） in acute cardiac allograft rejection in rats. Methods The model of heterotopic cardiac allograft of SD to Wistar rats was established. The rats were divided into two groups： control group and cyclosporin A（CsA） treated group （CsA group）. Living span of the transplants in eight rats of each group were observed. Allograft samples were harvested separately on the day 1, 3, 5, 7 after operation （n = 6）. The rejection was evaluated by routine pathological examinations. The myocardial apoptosis by terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling （TUNEL） method and the local expression of ClC-3 were detected by reverse transcriptase polymerase chain reaction （RT-PCR）. Results The allografts survival time was significantly longer in CsA group compared with that in control group （15.4±5.1dvs. 7.6±1.5d, P〈0.05）. There was lesser pathological changes in CsA group than that in control group. The apoptosis index were significantly higher in control group and the expression of ClC-3 was significantly lower（P〈0.05）. CsA could inhibit the rise of apoptosis index and the decrease of the ClC-3 expression. Conclusion The ClC-3 expression is closely related with the severity of myocardial necrosis and apoptosis index, which indicates that ClC-3 plays a very important role in the necrosis and apoptosis during acute cardiac allograft rejection of rat.
Objective To investigate the incidence of perioperative stroke in elderly patients (≥65 years) undergoing offpump coronary artery bypass grafting (OPCAB) versus onpump coronary artery bypass grafting (CABG). Methods WTBZ]We electronically searched PubMed (from 1966 to 2010), Cochrane Library (Issue 12, 2010), EMbase (from 1974 to 2010), CNKI (Chinese, from 1997 to 2010), CBM (Chinese, from 1989 to 2010), and manually searched some journals to collect published or grey literatures of clinical researches on comparison between OPCAB and CABG for elderly patients in the incidence of perioperative strokes. We assessed the methodology quality of included researches and extracted data to conduct metaanalysis by RevMan 5.0 software. Four subgroups (aged 65 to 70 years, 70 to 75 years, 75 to 80 years, and older than 80 years) according to the age of the patients, and subgroups according to the study design were analyzed respectively. Sensitivity analysis was conducted by deleting the studies of low quality. Results We finally identified 17 studies including 5 historical cohort studies and 12 case control studies. No randomized controlled trial was searched. A total of 7 275 patients including 2 521 (34.65%) in the OPCAB group and 4 754 (65.35%) in the CABG group were identified. The metaanalyses of historical cohort study subgroup and case control study subgroup showed statistical difference in stroke incidence between the OPCABG and CABG groups with OR 0.25 and 95%CI 0.10 to 0.62,and with OR 0.25 and 95%CI 0.15 to 0.41,respectively. Statistical difference was tested in three age subgroups (70 to 75 years, 75 to 80 years, and elder than 80 years) and the OR (95%CI) value was 0.35 (0.21, 0.59), 0.14 (0.04, 0.54), and 0.09 (0.02, 0.38),respectively. The difference of stroke incidence between OPCAB and CABG patients in all the three subgroups was significant, while there was no statistical difference in the subgroup aged 65 to 70 years with OR 0.10 and 95%CI 0.01 to 1.68. The sensitvity analysis showed that metaanalysis was stable in case control study subgroup, was not stable in historical cohort study subgroup. Conclusions OPCAB may reduce incidence of perioperative stroke in elderly patients. However, it still needs to be confirmed by more multicenter, largesample, and randomized doubleblind controlled trials in the future.
Objective To investigate whether the agonist of delta opoid receptor D-Ala(2),D-Leu(5) enkephalin (DADLE) has the effect of decreasing myocardial injury during ischemia-reperfusion of adult rabbits’ myocardium，so that a new mehanism and way to myocardial protection could be found. Methods Langendorff model was used during the experiment. Thirty rabbits were divided into three groups randomly (each group 10 rabbits). Control group: St.Thomas Ⅱ cardioplegic solution was used; group 1: St.Thomas Ⅱ cardioplegic solution and DADLE (1mg/kg) were used; group 2: St.Thomas Ⅱ cardioplegic solution and naloxone(3mg/kg) were used to induce the hearts to arrest respectively. After arrest the hearts were reperfused respectively. Data of left ventricle development pressure(LVDP) was recorded before and after ischemia. Biochemical indicators of myocardium, lactate dehydrogenase(LDH) were detected before and after ischemia. Some myocardial tissues were used to explore the changes of the tissue of ultrastructure with electron microscope，when the experiment was over. Still some myocardial tissues were to be detected by flow cytometer to evaluate the apoptosis of the myocardium. Results The LDH and LVDP showed significant difference among three groups after ischemia(Plt;0.05); LVDP in group 1 was higher than those in group 2 and control group(69.8±5.8 mmHg vs. 23.4±3.9 mmHg; 69.8±5.8 mmHg vs. 37.9±4.7 mmHg; Plt;0.05), the LDH in group 1 was lower than those in group 2 and control group(1 272.6±59.1 U/L vs. 2 764.4±27.7 U/L, 1 272.6±59.1 U/L vs. 1 884.4±37.5 U/L; Plt;0.05). The apoptosis rate in group 1 was lower than those in group 2 and control group. As could be shown from the ultrastructure: mitochondria structure was nearly normal in group 1; mitochondria structure was injuried severely in group 2; there was a minor injury in control group. Conclusion Agonist of δ opoid receptor DADLE in cardioplegic solution could induce hibernation, which has myocardial protection effect during ischemia-reperfusion injury.
Surgical Therapy for Valve Diseases Combined with Coronary Heart Diseases in Patients Over or Below 70 Years Old YU Lei, GU Tianxiang, SHI Enyi, XIU Zongyi, FANG Qin, ZHANG Yuhai. (Department of Cardiac Surgery, The No. 1 Hospital of China Medical University, Shenyang 110001, P.R. China)Corresponding author: GU Tianxiang, Email: cmugtx@sina.comAbstract： Objective To summarize the experiences of valve replacement combined with coronary artery bypass grafting (CABG) in senile patients by comparing clinical outcomes of valve diseases combined with coronary heart diseases in patients over or below 70 years old. Methods We retrospectively analyzed the clinical data of 49 patients who received valve replacement combined with CABG in our department from May 1999 to December 2007. Based on the age, the patients were divided into ≥70 years group (17 cases) with its patients at or above 70 years old and lt;70 years group (32 cases) with its patients younger than 70. The percentage of chronic obstructive pulmonary diseases (COPD) before surgery in ≥70 years group was higher than that in lt;70 years group(Plt;0.05). No significant difference was found in the other relevant factors between the two groups. The clinical index of patients in the two groups were compared and analyzed. Results There were significant differences between the two groups in such factors as the percentage of biovalve use (82.4% vs. 12.5%, χ2=23.311, P=0.000), the time of mechanic ventilation (34.5±29.3 h vs. 18.0±16.1 h, t=-2.542,P=0.014), the time of ICU stay (4.4±1.5 d vs. 3.3±0.7 d, t=-3.522, P=0.001), the time of hospital stay (21.4±7.7 d vs. 18.1±1.8 d, t=-2.319, P=0.025), the percentage of IABP use (29.4% vs. 6.3%, χ2=4.862, P=0.037), the percentage of pulmonary function failure (35.3% vs. 6.3%, χ2=6.859, P=0.009), the percentage of acute renal failure (23.5% vs. 3.1%, χ2=5.051, P=0.025), and the percentage of cerebrovascular accident (11.8% vs. 0.0%, χ2=3.933, P=0.048). There was no significant difference between the two groups in factors like the anastomosis of distal graft (2.5±3.1 vs. 2.4±14, t=0.301, P=0.758), the time of aortic occlusion (89.3±25.4 min vs. 88.5±31.0 min, t=0.108,P=0.913), the time of cardiopulmonary bypass (144.6±44.8 min vs. 138.3±52.9 min, t=0.164, P=0.871) and the mortality (5.9% vs. 6.3%, χ2=0.002,P=0.959). The perioperative myocardial infarction rate was zero in both groups. ≥70 years group patients were followed up for 2 months to 9 years with only 1 case missing. One patient who had undergone mechanic valve replacement died of cerebral hemorrhage 1.5 years after operation. Two died of heart failure and lung cancer 3 months and 6 years after operation respectively. For all the others, the cardiac function was at class Ⅰ to Ⅱ and their life quality was significantly improved. The follow up time of lt;70 years group was 1 month to 6 years and 5 cases were missing. Four patients who had undergone mechanic valve replacement died of complications in relation to anticoagulation treatment. One died of severe low cardiac output. Another died of traffic accident. Conclusion Surgery operation and effective perioperative treatment are key elements in improving surgery successful rate and decreasing mortality in patients with valve and coronary artery diseases. Valve replacement combined with CABG is safe for patients older than 70 years old.
Objective To investigate the risk factors of acute kidney injury（AKI）after onpump coronary artery bypass grafting(on-pump CABG) and off-pump coronary artery bypass grafting (off-pump CABG) in order to provide superior renal protective measure after operation. Methods The clinical data of 849 consecutive patients undergone coronary artery bypass grafting（CABG） in a single institution between January 1990 and August 2006 were retrospectively analyzed. A simplex module and a multivariate logistic regression model were constructed to identify risk factors for the development of AKI. Results AKI were occurred in 61 patients （11.8%，61/518） undergone off-pump CABG and 63 patients （19.0%，63/331） undergone onpump CABG. Peak of serum creatinine (Scr) after operation arrived at the 12th hour and 24th hour in patients undergone off-pump CABG and patients undergone on-pump CABG respectively. The rapidly recovering period of Scr in patients undergone off-pump CABG and on-pump CABG were from the 24th hour to the 48th hour and from the 48th hour to the 72th hour respectively.The results of the multivariate forward stepwise logistic regression analysis found that risk factors for the development of postoperative AKI following isolated CABG were associated with heavy body mass index（OR=1.190，1.179）, emergent procedure（OR=2.737，3.678）, diabetes（OR=1.705，2.042）, peripheral vascular disease（OR=2.002，2.559）,ejection fraction≤30%（OR=2.267，4.606）, and New York Heart Association(NYHA) class Ⅲ and Ⅳ（OR=1.861，1.957） were risk factors for the development of postoperative AKI following offpump and on-pump CABG; pulse pressure≥60mmHg and triplevessel disease were risk factors for the development of postoperative AKI following off-pump CABG. But perioperative and postoperative intra aortic balloon pumping (IABP) could make protective effect on kidney for on-pump CABG （OR=0.146）which could lessen development of AKI. Conclusions It is critical period for AKI that renal protection strategies should be performed from general anesthesia until postoperative 48 hours (off-pump CABG) and 72 hours (on-pump CABG). AKI might be the most important stage in which a positive test should increase the physician’s awareness of the presence of risk for renal injury and then preventive or therapeutic intervention could be performed when the situation still is reversible.