Cun Long

Expression of MicroRNA-1 and MicroRNA-21 in Different Protocols of Ischemic Conditioning in an Isolated Rat Heart Model

Background: ‘Conditioning’ [ischemic preconditioning (IPC), ischemic postconditioning (IPO) and remote ischemic preconditioning (RIPC)] the heart to render it more resistant to an episode of acute myocardial ischemia-reperfusion (I/R) injury is an endogenous cardioprotective strategy. There are several mechanisms proposed for ‘conditioning’, such as endogenous mediators or cytoprotective proteins. In recent reports, microRNAs (miRNAs) were involved in controlling the expression of myocardial ischemia-related genes. Some studies have demonstrated that cardiac miRNA-1 and miRNA-21 were significantly increased by late IPC with an increase in their target proteins [endothelial nitric oxide synthase and heat shock protein 70 (HSP70)], but their expression levels in ‘conditioning’ strategies are currently unknown. Methods: In the current study, Langendorff-perfused Sprague-Dawley rat hearts were randomly assigned to one of four groups [control group (CON group, n = 12), IPC group (n = 12), IPO group (n = 12) and RIPC group (n = 12)]. Cardiac function was digitalized and analyzed. The expression of miRNA-1 and miRNA-21 was detected by real-time reverse transcription polymerase chain reaction. The expression of HSP70, programmed cell death protein 4 (PDCD4), B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2-associated X protein (Bax) was detected by Western blot. Cardiac infarct size and myocardial apoptosis were determined using the 2,3,5-triphenyltetrazolium chloride assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively. Results: The results revealed that miRNA-1 (233 ± 45%) and miRNA-21 (356 ± 33%) expression was up-regulated in the IPC group, but the expression of miRNA-1 was down-regulated in the RIPC (61 ± 16%) group and IPO group (61 ± 13%). The expression of PDCD4 [IPC (74 ± 11%), RIPC (81 ± 16%), IPO (83 ± 12%)], HSP70 [IPC (74 ± 5%), RIPC (81 ± 6%), IPO (67 ± 11%)] and Bax [IPC (27 ± 6%), RIPC (21 ± 3%), IPO (27 ± 4%)] was down-regulated in the conditioning groups compared with the CON group [PDCD4 (130 ± 11%), HSP70 (121 ± 11%) and Bax (63 ± 8%)]. In the conditioning hearts, infarct size [IPC (31.7 ± 4.1%), RIPC (29.6 ± 6.19%) and IPO (32.8 ± 4.71%)] and myocardial apoptosis [IPC (15.2 ± 4.21%), RIPC (17.2 ± 1.92%) and IPO (15.6 ± 4.04%)] were significantly decreased compared with the CON group (infarct size: 51.77 ± 4.3%, myocardial apoptosis: 32.8 ± 3.96%). Conclusion: We concluded that miRNA-1 and miRNA-21 expression differed in IPC, RIPC and IPO groups, and their target proteins were not inversely correlated with the miRNAs in all the conditioning groups, which revealed that the miRNAs were regulated but complicated by the different conditioning protocols.

Perioperative Monitoring of Thromboelastograph on Blood Protection and Recovery for Severely Cyanotic Patients Undergoing Complex Cardiac Surgery

In this study, we assessed the clinical effect of a new transfusion therapy guided by thromboelastograph (TEG) on blood protection. Thirty-one children with severe cyanosis (hematocrit ≥54%), who were diagnosed as having transposition of the great arteries or double outlet right ventricle with or without pulmonary valve stenosis, and underwent arterial switch operation or double roots transplantation, were involved and were divided into two groups. In group F (n=17), the transfusion therapy after cardiopulmonary bypass was performed with fibrinogen administration combined with traditional transfusion, guided by TEG. In group C (n=14), traditional transfusion guided by clinical experiences only was performed. We observed the blood protection effects and recovery conditions of these patients. In surgery, compared with group C, the chest closure time, fresh-frozen plasma (FFP), and platelet (PLT) volume used at closure time had no significant reductions in group F (P>0.05, respectively), and the patients in group F had no significant reductions in the amount of chest drainage (P>0.05). The total PLT and total red blood cells usage were also the same (P>0.05). But during the first 24h, FFP usage in the intensive care unit (ICU) and total perioperative FFP usage had significantly dropped in group F (P<0.05); the mechanical ventilator time, ICU stay, and hospitalization time in group F were much shorter than those in group C (P<0.05). So, TEG was effective in perioperative blood protection. Fibrinogen could be a substitute for FFP to restore hemostasis and improve the prognosis for these patients.

The myocardial protection of HTK cardioplegic solution on the long-term ischemic period in pediatric heart surgery.

Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increase cellular edema due to repeated administration. We reviewed the clinical experiences on myocardial protection of one single perfusion with histidine-ketoglutarate-tryptophan (HTK) for infants. This retrospective study included 118 infants who underwent open-heart surgery between January 2004 and December 2007. We divided the entire cohort into two groups: In group H (n = 63), myocardial protection was carried out with one single perfusion with HTK solution, and in group S (n = 55) with conventional St. Thomas crystalloid cardioplegia. The duration of cardiopulmonary bypass (CPB) did not differ between these two groups, but the duration of aortic cross-clamping time in group H was significantly shorter than that in group S (p < 0.05). During reperfusion, the spontaneous re-beating rate was higher in group H (p < 0.05). There were no differences in doses of inotropic agent and creatinekinase (CK) values on postoperative day 1 between these two groups, but the level of CK in group H was significantly less than that in group S on postoperative day 2 (p < 0.01). The mortality in group H was lower than in group S (p < 0.05). The HTK group had shorter cross-clamping time and more frequent spontaneous defibrillation than St. Thomas group. We propose that HTK is valid for some complicated cardiac surgeries with long term cross-clamping time.

Clinical evaluation of two different extracorporeal membrane oxygenation systems: a single center report.

Refinements in extracorporeal membrane oxygenation (ECMO) equipment, including heparin-coated surfaces, centrifugal pump, membrane oxygenator, and more biocompatible pump-oxygenator circuits, have reduced procedure-related complications and have made ECMO a safe and effective therapy for critical patients. The aim of this study was to evaluate the performance of two different ECMO circuit systems in a clinical setting and compare their outcomes. From December 2004 to December 2009, 121 patients required ECMO for primary or postcardiotomy cardiogenic shock at our heart center. We used the Medtronic circuit system in our earlier series (Group M, n = 64), and from July 2007, ECMO was carried out mainly with the Quadrox D PLS circuit system (Group Q, n = 56). We retrospectively summarized and analyzed the data of these patients. The evaluation was based on the comparison between properties of the membrane oxygenators and pumps, anticoagulation therapy, circuit-related complications, and clinical outcomes. Support pump flow rates, platelet counts, and trans-membrane pressure drops (TMPDs) of preoxygenator and postoxygenator pressures were compared between two groups at the time of support established (T1) and support established for 24 h (T2). There were no significant differences between the two groups with regard to patient characteristics and pre-ECMO data. The support pump flow rates and platelet counts at different times were comparable in the two groups. The cannulation technique, ECMO duration, and mean heparin dosage were similar in both groups. There were also no significant differences between the groups in mortality or complications related to bleeding and organ dysfunction. Compared with the M group, the Q group experienced less mechanical failure of the ECMO circuit. The Quadrox PLS circuit system showed less circuit thrombus formation (P < 0.045), less plasma leakage (P < 0.001), and less need for replacement of oxygenators (P < 0.001). Furthermore, frequency of hemolysis during ECMO was significantly lower (P < 0.045). In addition, at T1 and T2, TMPDs were significantly lower in the Q group. Our results suggest that both ECMO circuit systems provide similar effects for safe clinical application, but the Quadrox PLS ECMO circuit system demonstrated partially improved biocompatibility in terms of improved cell preservation, lower TMPDs, less plasma leakage, and thrombus formation.

Effects of retrograde autologous priming on blood transfusion and clinical outcomes in adults: a meta-analysis.

Objective: Reducing the priming volume is an effective means of decreasing hemodilution and blood transfusion during cardiopulmonary bypass (CPB). The patient’s own blood was used to replace the crystalloid in the CPB circuit by retrograde autologous priming (RAP) in order to decrease the priming volume. Therefore, we performed a meta-analysis to investigate whether RAP could reduce blood transfusion and improve clinical outcomes. Materials and Methods: A comprehensive search was conducted for randomized, controlled trials (RCTs) exploring RAP in PubMed, Embase, The Cochrane Library, Google Scholar and Chinese literature databases (WanFang, WeiPu and CNKI). Clinical parameters and outcomes were focused on the lowest hematocrit (Hct) during CPB, the number of patients transfused blood intraoperatively, the number of patients transfused blood perioperatively, the number of blood units transfused, 24-hour chest tube drainage, hours to extubation, length of ICU stay, and length of hospital stay. Results: Ten trials, with a total of 1123 patients, were included. The number of patients transfused blood intraoperatively (RR = 0.39, 95% CI = [0.29, 0.53], p<0.00001, I2 = 40%) and perioperatively (RR = 0.53, 95% CI = [0.43, 0.66], p<0.00001, I2 = 0%) and the number of blood units transfused (SMD = -0.53, 95% CI = [-0.73, -0.33], p<0.00001, I2 = 14%) were all significantly reduced in the RAP group. No differences in the hours to extubation (SMD = -0.11, 95% CI = [-0.33, 0.12], p=0.37, I2 = 0%) and the length of ICU stay (SMD = -0.17, 95% CI = [-0.41, 0.08], p=0.18, I2 = 0%) were observed between the two groups. Conclusion: Compared to conventional priming, RAP could reduce transfusion in adults significantly, but had no effect on clinical outcomes, comparing to conventional priming. Further studies involving RAP are expected to investigate if this technique is beneficial to the patient.

Effects of Pulsatile and Nonpulsatile Perfusion on Cerebral Regional Oxygen Saturation and Endothelin-1 in Tetralogy of Fallot Infants

Although benefits of pulsatile flow during cardiopulmonary bypass (CPB) in pediatric heart surgery remain controversial and nonpulsatile CPB is still widely used in clinical cardiac surgery, pulsatile CPB must be reconsidered due to its physiologic features. In this study, we aimed to evaluate the effects of pulsatile perfusion (PP) and nonpulsatile perfusion (NP) on cerebral regional oxygen saturation (rSO₂) and endothelin-1 (ET-1) in pediatric tetralogy of Fallot (TOF) patients undergoing open heart surgery with CPB. Forty pediatric patients were randomly divided into the PP group (n = 20) and the NP group (n = 20). Pulsatile patients used a modified roller pump during the cross-clamp period in CPB, while NP patients used a roller pump with continuous flat flow perfusion. The subjects were monitored for rSO₂ from the beginning of the operation until 6 h after returning to the intensive care unit (ICU). We also monitored the hemodynamic status and ET-1 concentration and plasma free hemoglobin (PFH) in blood samples of all patients over time. Effective PP was monitored in PP patients, and pulse pressure was significantly higher in the PP group than in the NP group (P < 0.01). rSO₂ of the PP group was higher than that of the NP group (P < 0.01) during the cross-clamp period, and this advantage of PP would be maintained until 2 h after patients returned to the ICU (P < 0.05). ET-1 level in blood samples was lower at clamping off and CPB weaning and early ICU period in the PP group than in the NP group (P < 0.01), and ET-1 concentration remained at a normal level after patients were transferred to the ICU 24 h in all patients. PFH levels in the PP group at pre-clamp off and CPB weaned off were higher than those of the NP group (P < 0.05) in these cyanotic patients. PP can increase rSO₂ and improve microcirculation during cross-clamping period in TOF pediatric patients, while PP resulted in more severe hemolysis in these cyanotic patients than NP.

Venoarterial Extracorporeal Membrane Oxygenation in Adult Patients: Predictors of Mortality.

Background: Extracorporeal membrane oxygenation is a cardiopulmonary supportive therapy. In this study, we reviewed our experience with extracorporeal membrane oxygenation support and tried to identify measurable values which might predict in-hospital mortality. Methods: From January 2004 through December 2008, 50 of 21,298 adult patients received venoarterial extracorporeal membrane oxygenation. We retrospectively analyzed clinical records of these 50 consecutive patients. Details of demographics, preoperative measurements, clinical characteristics at the time of extracorporeal membrane oxygenation implantation, extracorporeal membrane oxygenation-related complications and in-hospital mortality were collected. Logistic regression analyses were performed to investigate predictors of mortality. A p-value ≤ 0.05 was accepted as significant. Results: Thirty-eight patients were weaned from extracorporeal membrane oxygenation and 33 patients survived to discharge. The overall survival rate was 66%. In a multiple logistic regression analysis, blood lactate level before initiation of extracorporeal membrane oxygenation was a risk factor associated with in-hospital mortality (OR 1.27 95% CI 1.042-1.542). To evaluate the utility of the lactate in predicting mortality, a conventional receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 12.6mmol/L, with an area under the curve of 0.752. The positive and negative predictive values were 73.3% and 83.9%, respectively. Conclusions: Extracorporeal membrane oxygenation is a justifiable alternative treatment for postoperative refractory cardiac and pulmonary dysfunction which could rescue more than sixty percent of otherwise fatal patients. Patients with pre-extracorporeal membrane oxygenation lactate levels above 12.6mmol/L are at higher risks for in-hospital death. Evidence-based therapy for this group of high risk patients is needed.BACKGROUND Extracorporeal membrane oxygenation is a cardiopulmonary supportive therapy. In this study, we reviewed our experience with extracorporeal membrane oxygenation support and tried to identify measurable values which might predict in-hospital mortality. METHODS From January 2004 through December 2008, 50 of 21,298 adult patients received venoarterial extracorporeal membrane oxygenation. We retrospectively analyzed clinical records of these 50 consecutive patients. Details of demographics, preoperative measurements, clinical characteristics at the time of extracorporeal membrane oxygenation implantation, extracorporeal membrane oxygenation-related complications and in-hospital mortality were collected. Logistic regression analyses were performed to investigate predictors of mortality. A p-value < or = 0.05 was accepted as significant. RESULTS Thirty-eight patients were weaned from extracorporeal membrane oxygenation and 33 patients survived to discharge. The overall survival rate was 66%. In a multiple logistic regression analysis, blood lactate level before initiation of extracorporeal membrane oxygenation was a risk factor associated with in-hospital mortality (OR 1.27 95% CI 1.042-1.542). To evaluate the utility of the lactate in predicting mortality, a conventional receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 12.6 mmol/L, with an area under the curve of 0.752. The positive and negative predictive values were 73.3% and 83.9%, respectively. CONCLUSIONS Extracorporeal membrane oxygenation is a justifiable alternative treatment for postoperative refractory cardiac and pulmonary dysfunction which could rescue more than sixty percent of otherwise fatal patients. Patients with pre-extracorporeal membrane oxygenation lactate levels above 12.6 mmol/L are at higher risks for in-hospital death. Evidence-based therapy for this group of high risk patients is needed.

Clinical outcomes and experience of 20 pediatric patients treated with extracorporeal membrane oxygenation in Fuwai Hospital.

The purpose of this study was to report retrospectively the summarized clinical findings from 20 consecutive pediatric extracorporeal membrane oxygenation (ECMO) patients and to investigate the factors associated with mortality. The ECMO circuit system was completely covered using heparin-coating technique, and venoarterial ECMO was used in all patients. Heparin dosage was 4–20 U/kg/h and active clotting time was maintained between 146 and 360 seconds. ECMO was weaned off successfully in 15 patients (75%); 11 of 15 patients (73%) survived and were discharged from the hospital; 4 of 15 patients died of postoperative complications; 5 patients failed to be weaned off ECMO. The percentage of discharged patients was 55% (11 of 20) in this cohort study. Lactic acid concentration of artery blood before ECMO in survivor patients was significantly lower than in nonsurvivor patients (p = 0.009); patient weight between two groups also had statistical difference (p = 0.046). ECMO effectively treats cardiac and pulmonary failure secondary to cardiac surgeries for complicated congenital heart diseases. Early application of ECMO in patients with cardiac and respiratory failure is still the key point of success in preventing vital organs from irreversible damage.

The effect of preprocessing stored red blood cells on neonates undergoing corrective cardiac surgery.

This study compared the effect of unprocessed and processed packed red blood cells (PRBCs) with the continuous autotransfusion system (CATS) during neonate heart surgery. Sixteen neonatal patients undergoing cardiac surgery were randomly divided into two groups: unprocessed PRBC (C group, n = 8); processed PRBC (P group, n = 8). The CATS was employed perioperatively. Series laboratory and clinical parameters, including levels of hematocrit, blood potassium, blood glucose, blood lactate, acid-base, and total priming volume of PRBC, were used to compare the effect between the two groups. Before CPB, the hematocrit of processed PRBCs in P group was significantly higher than those in C group (p < 0.01), and the concentrations of potassium, blood glucose, and lactate of processed PRBCs in P group were significantly lower than those in C group (p < 0.01). At the beginning and the end of CPB, the hematocrit levels in P group were all higher than those in C group (p < 0.05); lactate levels in P group were significantly lower than those in C group at the beginning of CPB (p < 0.01), and lower than that of C group at the end of CPB (p < 0.05). The total priming of PRBCs in P group was significantly less than that in C group (p < 0.01). Perioperative processing with CATS provided a high-quality RBC concentration, decreased the total priming of PRBCs, providing increased high-quality blood salvage during neonatal CPB procedure.

Hyperoxia management during deep hypothermia for cerebral protection in circulatory arrest rabbit model.

As a brain protection strategy, antegrade selective cerebral perfusion (ASCP) is widely used in thoracic aorta surgery with deep hypothermic circulatory arrest (DHCA), yet the oxygen management for ASCP has never been standardized. The aim of this study was to investigate the possible neuroprotective effects of hyperoxia management during deep hyperthermia for ASCP combined with DHCA in a rabbit model. Rabbits were assigned into four groups: sham group, without cardiopulmonary bypass (CPB); DHCA group, DHCA for 80 minutes; ASCP group, ASCP combined with DHCA; and SH group, hyperoxia management combined with ASCP and DHCA. Hyperoxia management was performed when the nasopharyngeal temperature was below 22°C. Deep hypothermic circulatory arrest was initiated when nasopharyngeal temperature reached 16–18°C. Blood samples were withdrawn to determine blood gas indexes and neurobiochemical markers of damage, and brain tissues were stored for biochemical analysis. Cerebral oxygen balance was performed better in the SH group compared with the DHCA group and the ASCP group. Hyperoxia management did not increase lipid peroxidation with lower malondialdehyde levels in the SH group compared with the DHCA group and the ASCP group (p < 0.05). S100 calcium binding protein B in the SH group was lower compared with the DHCA group and the ASCP group (p < 0.05). There was no significant difference of neuron-specific enolase in the SH group compared with the sham group. Hyperoxia management during deep hypothermia provided substantial dissolved oxygen and demonstrated better cerebral protection over normoxia management.