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.
Objective To investigate the role of mitochondrial adenosine triphosphatesensitive potassium channel(mitoKATP) in immature myocardial ischemic preconditioning, and to provide evidence for immature myocardial protection. Methods Langendorff isolated heart infused model was used in the experiment. Twentyfour rabbits (aged from 14 to 21 days) were randomly divided into 4 groups：ischemiareperfusion group（I/R group）, myocardial ischemic preconditioning group(E1 group), 5hydroxydecanoate(5-HD) group (E2 group) and Diazoxide (Diaz) group(E3 group). Hemodynamics recovery rate, myocardial water content(MWC), the leakage rates of serum creatine kinase and lactate dehydrogenase, adenosine triphosphate content, superoxide dismutase activity, malondialdehyde content, myocardial cell Ca2+ content and myocardial mitochondrial Ca2+ content, myocardial mitochondrial Ca2+-ATPase activity, the adenosine triphosphate(ATP) synthesizing ability of myocardial mitochondria were tested, and myocardial ultrastructure was observed via electron microscopy. Results The hemodynamics recovery rate, myocardial water content(P＜0.05), adenosine triphosphate content, superoxide dismutase activity, myocardial mitochondrial Ca2+-adenosine triphosphyatase(ATPase) activity and the ATP synthesizing ability of myocardial mitochondria of the rabbits in E1 and E3 group were significantly better than that in I/R group and E2 group(P＜0.05). Malondialdehyde content, the leakage rates of serum creatine kinase and lactate dehydrogenase, myocardial cell Ca2+ content and myocardial mitochondrial Ca2+ content of the rabbits in E1 group and E3 group were significantly lower than that in I/R group and E2 group (P＜0.05). The myocardial ultrastructure injury in E1 and E3 group were significantly reduced compared with that in I/R and E2 group. Conclusion Myocardial ischemic preconditioning has significant protective effects on immature myocardium. Its mechanism may be related to the activation of mitoKATP.
Abstract： Objective To assess the effects of simultaneous antegrade/retrograde cardioplegia (SARC) on myocardial perfusion and energy metabolism in ischemic myocardium using magnetic resonance imaging (MRI). Methods After the hearts were harvested from 18 domestic pigs, left anterior descending artery, aorta, anterior ascending cardiac vein and coronary sinus were cannulated to establish the perfusion routes. 6 hearts were used to assess the effects of SARC on myocardial perfusion. Energy metabolism was observed in the other 12 pig hearts. MRI was used to monitor the distribution of contrast agent (gadoliniumdiethylenetriamine penlaacetic acid, Gd-DTPA) in the myocardium after its injection through arterial and retrograde perfusion routes. The efficacies in sustaining myocardial perfusion and energy metabolism were evaluated by using phosphorus-31 magnetic resonance spectroscopy (31P MRS) during antegrade cardioplegia (AC) and SARC respectively. Results It was found that injection of Gd-DTPA into the aorta during AC did not result in signal increase in the ischemic myocardium on MRI. During SARC, however, Gd-DTPA was found in the ischemic region as well as in the other regions, no matter if it was given into the aorta or into the coronary sinus. Moreover,31P spectra showed that occlusion of LAD during AC resulted in severe decrease of the levels of phosphocreatine (PCr) and adenosine triphosphate (ATP), while the level of inorganic phosphate (Pi) increased in LAD-support myocardium. The abnormal metabolic changes were completely abolished by use of SARC. Conclusion It is concluded that SARC can deliver cardioplegic solution to the myocardium distal to a coronary occlusion and can sustain normal energy metabolism in the jeopardized myocardium.
Objective To investigate the effects on myocardial perfusion of simultaneous antegrade/retrograde cardiopiegia （SARC） through a single coronary artery and coronary sinus （CS）. Methods SARC was conducted in isolated pig hearts through CS in conjunction with the left anterior descending （LAD）, the left circumflex （LCX）, or the right coronary artery （RCA） respectively. After injecting magnetic resonance （MR） contrast agent （gadolinium diethyienetriamine pentaacetic acid, Gd-DTPA） into arterial or venous route, the distribution of Gd-DTPA with magnetic resonance imaging（MRI） was monitored and the effluent from the venting coronary arteries to assess the efficacy of SARC for myocardial perfusion was measured. Results Injection of Gd-DTPA into a perfusing artery during SARC resulted in increased signal intensity not only in the territory of the perfusing artery but also in the areas normally served by the other two venting coronary arteries （including the right ventrieuiar free wall）. With Gd DTPA given into the CS during SARC, the myocardium in the territories of the two venting coronary arteries was lightened. Signal intensity of the myocardium in the perfusing artery territory and right ventricuiar free wall remained unchanged. Moreover, a significant amount of effluent was collected from the venting coronary arteries during SARC： the LAD 10.5-17.7 ml/min; LCX 9.7-15.2 ml/min, and RCA 4.7-7.8 ml/min. Conclusion SARC through a single coronary artery and CS can provide homogeneous perfusion to the entire heart and is sufficient to prevent ischemic injury in the myocardium normally supported by the venting coronary arteries.
Objective To investigate the protective effects of metallothionein （MT） for immature myocardium and myocardial interstitium.Methods Twenty-four rabbits （aged 14-21 days） were divided into 4 groups with random number table, 6 each group. Distilled water was injected intraperitoneally in control group and 3.6% ZnSO4 （1.5 ml/kg） was injected intraperitoneally in group 1, group 2 and group 3. Control group, group 1, group 2 and group 3 isolated working rabbit heart model were used in 24h, 12h, 24h and 48h after intraperitoneally respectively. The MT content, recovery of hemodynamics, biochemistry and myocardial ultrastructure were tested. Results The MT content, hemodynamics recovery, adenosine triphosphate （ATP） content, superoxide dismutase activity, Ca2＋-ATPase activity, synthesizing ATP activity of mitochondria, hydroxyproline in group 2 and group 3 were higher than those in control group and group 1 （P 〈 0. 01）. The myocardial watery content, creatine kinase and dehydrogenase leakage, malondialdehyde content, endothelin, mitochondrial Ca2＋ content in group 2 and group 3 were lower than those in control group and group 1（P〈0.01）. The myocardial ultrastructure injuries were less in group 2 and group 3 than that in control group and group l. Conclusion This study demonstrates that myocardial MT prolonged expression can be induced by ZnSO4 and the ischemia-reperfusion injury of immature myocardium and myocardial interstitium could be reduced by MT.
Objective To investigate the protection effects of different pH N 2 hydroxyethyl piperazine N′ 2 ethanesulfonic acid (HEPES) Krebs Henseleit (KH) reperfusate solutions on immature myocardium and myocardial interstitium. Methods Isolated perfused Langendorff model from immature rabbit hearts were performed. Twenty four rabbits were divided into control group, ischemia reperfusion group and acidic reperfusate group. The left ventricular function recovery, myocardial water content(MWC), lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, malondialdehyde(MDA) and adenosine triphosphate (ATP) content, superoxide dismutase(SOD) activity , hydroxyproline(HP) and endothelin(ET) content were tested. Results The left ventricular functional recovery, ATP content, SOD activity and HP content in acidic reperfusate group were higher than those of ischemia reperfusion group( P lt;0.05).MWC, MDA content, CK and LDH leakage, and ET content in acidic reperfusate group were lower than those of ischemia reperfusion group( P lt;0.05). Conclusion These results suggest pH paradox might be one of important mechanisms for immature myocardium and myocardial interstitium ischemia reperfusion injury,and acidic perfusate, at the beginning of reperfusion ,might attenuate pH paradox and ameliorate functional recovery in isolated perfused immature rabbit hearts.
Objective\ In order to assess and evaluate the clinical results of cold blood cardioplegia and intermittent cross clamping as myocardial preservation in coronary artery bypass grafting(CABG).\ Methods\ According to the management methods, 2 013 cases for elective, isolated CABG were divided into two groups at St.George’s Hospital, London.Cold blood cardioplegia group: 596 patients treated with cold blood cardioplegia, and hypothermic ventricular fibrillation group: 1 417 patients treated with intermitt...
Objective To elucidate the protective effect of leukocyte depletion on the myocardium during the settings of myocardial reperfusion injury. Methods Twenty patients undergoing cardiopulmonary bypass with continuous infusion of blood cardioplegia were randomized into two groups:the control group (n=10) with no leukocyte depletion filter used, and the experimental group (n=10) with the use of leukocyte depletion filter on the bypass circuit. The blood cells count before and after the filtration were measure...
ObjectiveTo systematically evaluate the effect of leucocyte-depleted blood cardioplegia on myocardial protection in adult patients underwent cardiac surgery with extracorporeal circulation. MethodsWe searched PubMed, EMbase, The Cochrane Library (Issue 2, 2015), CBM, VIP, WanFang Data and CNKI databases from inception to March 1st 2015, to collect randomized controlled trials (RCTs) about leucocyte-depleted blood cardioplegia for adult patients underwent cardiac surgery. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was conducted by using RevMan 5.3 software. ResultsA total of 17 RCTs including 637 patients were included. The results of meta-analysis showed that: Compared with the control group, the leucocyte-depleted blood cardioplegia could significantly reduce the level of postoperative CK-MB peak value (SMD=-0.75, 95%CI -1.12 to -0.39, P<0.0001), the utilization of inotropic drugs after operation (OR=0.51, 95%CI 0.29 to 0.92, P=0.02), and perioperative incidence of arrhythmia (OR=0.51, 95%CI 0.31 to 0.84, P=0.009). However, no significant differences were found in the incidence of perioperative myocardial infarction (OR=1.0, 95%CI 0.20 to 5.13, P=1.00), peri-operative mortality (peto-OR=0.51, 95%CI 0.05 to 4.94, P=0.56) and ICU stay (SMD=-0.06, 95%CI -0.32 to 0.21, P=0.68) between the two groups. ConclusionCurrent evidence shows, leucocyte-depleted blood cardioplegia could effectively reduce the myocardial injury in adult patients underwent cardiac surgery with extracorporeal circulation, but in reducing perioperative severe complications and mortality, improving the long-term prognosis in patients, the protective effect of leucocyte-depleted blood cardioplegia is yet to be evaluated. In addition, due to the limitation of quality and quantity of included studies, the above conclusion still need to be verified by conducting larger sample, high quality, multi-central RCTs.