Abstract： Objective To explore clinical outcomes of nitroglycerin perfusion via the aortic root before heart re-beating for patients undergoing heart valve replacement. Methods A total of 254 patients with valvular heart diseases underwent heart valve replacement in Beijing Anzhen Hospital from January 2008 to December 2011. According to whether or not they received nitroglycerin perfusion via the aortic root before heart re-beating during cardiopulmonary bypass （CPB）， all the 254 patients were randomly divided into two groups， the nitroglycerin group and the control group. There were 134 patients in the nitroglycerin group including 57 males and 77 females with their average age of 58.47±12.34 years. They received aortic root perfusion of 5 mg nitroglycerin diluted into 20 ml after full de-airing of the heart， and repeated aspiration was performed 8 to 10 times before heart re-beating during CPB. Aortic cross-clamp was released after the heart showed signs of automatic re-beating， and the aortic root was squeezed in high frequency by hand to make sure that the aorta was squeezed to close each time. In the control group， there were 120 patients including 64 males and 56 females with their average age of 61.85±11.97 years. Patients in the control group received routine procedures of CPB except nitroglycerin perfusion before heart re-beating. Automatic heart re-beating rate， CPB supporting time after heart re-beating， postoperative usage of inotropic drugs， mechanical ventilation time， perioperative morbidity and length of hospital stay were compared between the 2 groups， and patients were followed up and further evaluated. Results There was no in-hospital death. CPB supporting time after heart re-beating（12.32±9.76 min vs. 23.43±10.33 min， t=-1.233， P=0.000）， dopamine usage［3.45±2.33 μg/ （kg?min） vs. 5.67±3.12 μg/ （kg?min） ， t=-0.943 ， P=0.034］ and epinephrine usage ［0.026±0.013 μg/ （kg?min） vs. 0.056±0.021 μg/ （kg?min） ， t=-0.822 ， P=0.027］ of the nitroglycerin group were significantly shorter or lower than those of the control group. Automatic heart re-beating rate of the nitroglycerin group was significantly higher than that of the control group ［97.01% vs. 66.67 % ， χ 2 =-2.115 ， P=0.000］. A total of 121 patients in the nitroglycerin group were followed up for 2-36 months， and 13 patients were lost during follow-up. There was no death during follow-up. Conclusion For patients undergoing heart valve replacement， some myocardial protection strategies including nitroglycerin perfusion via the aortic root before heart re-beating， use of norepinephrine， and aortic root squeezing in high frequency by hand can significantly increase the automatic heart re-beating rate， shorten the CPB supporting time after heart re-beating， and improve postoperative clinical outcomes.
Abstract： Objective To observe myocardial protective effect of sevoflurane used in the whole process of cardiopulmonary bypass（CPB）. Methods A total of 150 patients older than 18 years who underwent cardiac surgery under CPB in Fu wai Hospital from January 2010 to November 2011 were enrolled in this double-blind and randomized controlled study. All the patients were randomly divided into three groups：Sevoflurane pretreatment group （Group A，n=50），whole-process Sevoflurane group （Group B，n=50），and whole-process intravenous anesthesia group （Group C，n=50）. Radial artery pressure and other hemodynamic parameters were continuously measured for all the patients. At following time points: CPB beginning （T1），aortic declamping （T2），3 hours after aortic declamping （T3），and 24 hours after aortic declamping （T4），serum concentrations of cardiac troponin I （cTnI） and other parameters were measured by enzyme-linked immunosorbent assay （ELISA）. Results There were 31 males and 19 females at age of 60.43±3.24 years in group A，28 males and 22 females at age of 59.88±4.12 years in group B，31 males and 19 females at age of 58.76±3.87 years. There was no statistical difference in mean arterial pressure （MAP），central venous pressure （CVP），pulmonary artery wedge pressure （PAWP） and heart rate （HR） at respective time points among the 3 groups （P＞0.05）. At T1 and T2，there was no statistical difference in cardiac index （CI） among the 3 groups （P＞0.05）. At T3，there was no statistical difference in CI between Group A and Group C（F=3.382，P=0.845），but CI of Group B was significantly higher than that of Group A and C（F=3.382，3.382； P=0.033，0.020）. At T4，CI of Group B was significantly higher than that of Group A and C （F=13.324，13.324； P=0.005，P=0.000），and CI of Group A was significantly higher than that of Group C （F=13.324，P=0.024）. At T1 and T2，there was no statistical difference in serum concentrations of creatinine kinase MB （CK-MB），cTnI，interleukin-6 （IL-6） and tumor necrosis factor alpha （TNF-α） among the 3 groups （P＞0.05）. At T3 and T4，serum concentrations of CK-MB，TNF-α，IL-6 and cTnI of Group C were significantly higher than those of Group A，and serum concentrations of CK-MB，TNF-α，IL-6 and cTnI of Group A were significantly higher than those of Group B （F=531.616，5.410，3.5813，3.160，1.126，4.702，7.819，5.424，all P=0.000）. Conclusion Sevoflurane used in the whole process of CPB has definite myocardial protective effect which is ber than that of Sevoflurane pretreatment.
Objective To explore the impact of ischemic postconditioning on ischemia-reperfusion injury in isolatedelderly rat hearts and their relation with P-Akt. Methods A total of 30 healthy elderly SD rats (21-23 months old， male or female) with their body weight of 450-500 g were divided into 3 groups: control group， ischemia-reperfusion group， and postconditioning group， with 10 rats in each group. Coronary artery blood flow，myocardial infarction size， phosphorylatedAkt （p-Akt） expression， and changes in myocardium and mitochondria were detected. Results Coronary artery blood flow of the postconditioning group was significantly higher than that of the ischemia-reperfusion group （6.4±1.2 ml/min vs.3.1±1.2 ml/min， P＜0. 01）， and myocardial infarction size of the postconditioning group was significantly smaller thanthat of the ischemia-reperfusion group （35.0%±2.0% vs. 55.7%±3.6%， Plt;0. 05）. The expression of P-Akt was significantlyhigher， and myocardial fibers and mitochondria were preserved better in the postconditioning group than the ischemia-reperfusion group. Conclusion Ischemic postconditioning can protect isolated elderly rat hearts against ischemia-reperfusion injury， which may be related to P-Akt activation.
Abstract： Ischemia postconditioning is a new concept based on ischemic preconditioning. It has become a hot topic in protection of ischemic-reperfusion injury because of its effective protection, relative ease of application, and postconditioning. However, its precise mechanisms and most effective application methods are still unclear. This review covers recent progress in the understanding, developments (in remote postconditioning and pharmacological postconditioning), applications to the protection of heart, lung, liver, kidney, and brain, mechanisms and appropriate protocol of ischemic post-conditioning.
Abstract: Objective To evaluate myocardial protection effect of different myocardial protective strategies for patients undergoing double valve replacement （DVR） . Methods From Jun. 2005 to Dec. 2005, 32 patients with predominant aortic valve stenosis undergoing DVR in Xinqiao Hospital were included in this study. These patients were randomly divided into four groups with 8 patients in each group： （1） antegrade perfusion group：Cold-blood cardioplegia was delivered antegradely through aortic root, and mitral valve replacement （MVR）was performed. Then cold-blood cardioplegia was delivered antegradely through left and right coronary ostia, and aortic valve replacement （AVR） was performed； （2）retrograde perfusion group：Cold-blood cardioplegia was delivered retrogradely and intermittently through coronary sinus, and DVR was performed； （3）antegrade＋retrograde perfusion group：The route of cold-blood cardioplegic infusion was antegrade during MVR procedure first and then retrograde during AVR procedure；and （4）beating heart group：Oxygenated blood from cardiopulmonary bypass machine was delivered retrogradely and continuously through coronary sinus, and DVR was performed with beating heart. Early clinical outcomes were observed. Serum cardiac troponin I （cTnI） was measured by enzyme-linked immunosorbent assay（ELISA）. Serum creatine kinase-MB （CK-MB） and myocardial lactic acid release rate were measured by Hitachi7150 Automatic Chemistry Analyzer. Myocardial mitochondria malondialdehyde （MDA） level was measured through thiobarbituric acid reagent species analysis. Results All the 32 patients survived their surgery and were discharged successfully. Myocardial lactic acid release rate at 80 min after aortic cross-clamping, serum cTnI and CK-MB on the first postoperative day, myocardial mitochondria MDA levels of beating heart group were 13.59%±6.27%,（1.17±0.25） ng/ml, （56.43±16.50） U/L and（2.18±1.23） nmol/（ng.prot）respectively, all significantly lower than those of retrograde perfusion group ［（33.49%±8.29%, （1.82±0.58 ）ng/ml, （78.31±21.27） U/L （5.07±2.35） nmol/（ng.prot），P＜0.05］ and antegrade＋retrograde perfusion group［20.87%±7.22%, （1.49±0.23） ng/ml,（66.67±19.13） U/L,（4.34±1.73） nmol/（ng.prot），P＜0.05］, but not statistically different from those of antegrade perfusion group ［18.83%±5.97%, （1.41±0.32） ng/ml, （63.21±37.52） U/L, （3.46±1.62） nmol/ （ng.prot），P＞0.05］. Conclusion All the four myocardial protective strategies are effective myocardial protection methods for DVR patients. Continuous retrograde perfusion with beating heart and intermittent antegrade perfusion can provide better myocardial protection, and therefore are preferred for DVR patients. The combination of antegrade and retrograde perfusion is easy to administer and does not negatively influence surgical procedures. Retrograde perfusion is also effective as it takes only a short time.
Abstract： Objective To investigate the effect of salvianolate on myocardium against ischemiareperfusion injury (IRI) in valve replacement with cardiopulmonary bypass (CPB), its outcome and mechanism, and the applicability and safety of salvianolate as a protection agent for CPB central muscles. Methods Thirty patients undergoing cardiac valve replacement were randomly divided into two groups by lot. In the control group, there were 15 patients including 5 males and 10 females, while in the 15 patients in the trial group, 7 were male and 8 were female. Salvianolate of 200 mg was given to the patients in the trial group intravenously. Hemodynamic parameters, blood gas analysis results, recovery of heartbeat, the dosage of dopamine used, and assisted ventilation time were recorded for both groups before aorta clamping, 2 h, 8 h, and 24 h after aorta declamping. Besides, ICU detention time, the amount of urine in 24 hours, and the amount of drainage in 24 hours after operation were also recorded. Blood samples were taken to determine serum cardial troponin I(cTnI), creatine kinase MB isoenzyme (CK-MB), malondialdehude (MDA), and superoxide dismutase (SOD) in both groups respectively at different times including after the induction of anesthesia, aorta opening, termination of CPB, end of operation, and one day after operation. Results There was no significant difference in hemodynamic parameters, the dosage of dopamine used, spontaneous recovery of heartbeat, and the amount of urine in 24 hours and drainage after operation for 24 hours between the two groups (Pgt;0.05). The rate of ventricular rhythm, blood lactic acid level, the time of assisted ventilation and ICU detention time for the trial group were significantly lower than those for the control group (Plt;0.05), while partial pressure of oxygen in artery(PaO2) was significantly lower in the trial group 8 h after aorta declamping (Plt;0.05). The levels of serum CK-MB, cTnI, and MDA after operation for both groups were higher than those before operation; and those levels for the trial group were significantly lower than the control group at various time points (Plt;0.05). The concentration of SOD decreased after operation in both groups (Plt;0.05), and it was higher in the trial group than the control group at different time points. The decrease of SOD level in the trial group was less than that in the control group. Conclusion Salvianolate can protect myocardium from ischemiareperfusion injury in cardiac valve replacement with CPB effectively, through promoting the activity of antioxidative enzymes and eliminating oxygen free radicals. Patients can be treated with salvianolate for antimyocardial ischemia reperfusion injury.
Objective To determine the protection effects and mechanisms for immature myocardium with limbs ischemic preconditioning (LIP). Methods Using the Langendorff perfusion apparatus to perfuse isolated hearts, we randomly divided 30 Japanese longeared white rabbits into 5 groups, each having 6 rabbits. For the I/R group，after the perfusion model was established, the isolated hearts underwent 15 min of perfusion with KH solution before working for another 15 min . Then perfusion was stopped to cause ischemia for 45 min before reperfusion for 15 min and working for another 30 min . For E1 group, the model was established by 3×LIP (double limbs obstructed for 5 min followed by 5 min reperfusion for 3 times) and then procedures of the I/R group were carried out. For E2 group, before procedures of the E1group were done, superoxide dismutase (SOD) was injected till LIP was completed. For E3 group, intravenous protein kinase C (PKC) polymyxin (PMB) was injected for 10 minutes before E1 procedures were repeated. For E4 group, intravenous mitochondrial ATPsensitive K+ channels (mitoKATP) blocker 5-hydroxydecanoate was injected for 10 min before E1 procedures were carried out. The left ventricular function recovery, myocardial water content (MWC), creatine kinase (CK) and lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) and ATP content, SOD activity and superoxygen negative ion (O2 ·-) content were tested. Results Left ventricular recovery in E1 group was better than other groups (Plt;0.05). ATP content and SOD activity in E1 group were also better than all other groups (Plt;0.05). MWC in E1 group was lower than other groups (Plt;0.05). MDA content, CK and LDH leakage in E1 group were also lower than other groups (Plt;0.05). There was no significant difference of the above indications among I/R,E2,E3 and E4 groups, while the difference of O2·- content in E1,E3 and E4 groups before and after preconditioning was significant. Conclusion LIP has obvious protective effects for immature myocardium and the mechanisms are probably through PKC stimulation and opening of mitoKATP.
Abstract： Objective To investigate the mechanism of protein kinase C(PKC) in immature myocardial ischemic preconditioning in order to further its clinical applicability. Methods Langendorff perfusion heart models of 24 rabbits were set up and they were randomly divided into 4 groups: ischemic reperfusion group (I/R group), myocardial ischemic preconditioning group (MIP group), chelerythrine group (CLT group) and protein kinase C group (PKC group). The emodynamics, biochemistry and myocardial ultrastructure were observed. Results The heart function recovery and myocardial water content in the MIP and the PKC groups were better than those of the I/R and the CLT groups (Plt;0.01). The adenosine triphosphate (ATP) content, superoxide dismutase activity, mitochondrial Ca2+-ATPase activity and synthesizing ATP activity of mitochondria in the MIP and the PKC groups were significantly higher than those of the I/R and the CLT groups (Plt;0.01). The dehydrogenase and creatine kinase leakage, malondialdehyde content, myocardial cell Ca2+ content and mitochondrial Ca2+ content in the MIP and the PKC groups were significantly lower than those of the I/R and the CLT groups (Plt;0.01). The myocardial ultrastructure injuries in the MIP and the PKC groups were less than that of the I/R and the CLT groups. Conclusion Myocardial ischemic preconditioning plays an important role in protecting immature myocardium, which is probably realized by the activation of PKC.