Yuntai Yao

Stenting technique, gender, and age are associated with cardioprotection by ischaemic postconditioning in primary coronary intervention: a systematic review of 10 randomized trials

AIMS We sought to perform a systematic review and meta-analysis to evaluate the potential factors affecting ischaemic postconditioning (IPoC) for patients with ST-segment elevation acute myocardial infarction (STEMI) in primary percutaneous coronary intervention (PCI). METHODS AND RESULTS Ten randomized controlled trials (RCTs) on IPoC reporting myocardial enzyme levels or left ventricular ejection fraction (LVEF) in a total of 560 STEMI patients were identified in PubMed, EMBase, and Cochrane Library (up to February 2012). Compared with controls, IPoC significantly reduced elevated cardiac enzyme levels [standardized mean difference = -0.84; 95% confidential interval (CI): -1.26 to -0.43; P < 0.00001; heterogeneity test, I(2) = 81.0%] and improved LVEF [weighted mean difference (WMD) = 3.98%; 95% CI: 1.27-6.70%; P = 0.004; heterogeneity test, I(2) = 87.1%]. The effect on LVEF remained significant after 1 year (WMD = 5.04%; 95% CI: 4.20-5.88%; P < 0.00001; heterogeneity test, I(2) = 0.0%). Univariate meta-regression analysis suggested that the major sources of significant heterogeneity (P < 0.1) were the use of direct-stenting technique (%) (coefficient = -0.886; P = 0.069; adjusted R(2) = 0.34) and male proportion (%) (coefficient = -0.022; P = 0.098; adjusted R(2) = 0.28) for myocardial enzyme levels, and age (coefficient = -1.34; P = 0.025; adjusted R(2)= 0.55) for LVEF (%). Subsequent multivariate regression and subgroup analysis confirmed these results. CONCLUSION Available evidence from this systematic review and meta-analysis of 10 RCTs suggests that IPoC may confer cardioprotection in terms of myocardial enzyme levels and LVEF for STEMI during primary PCI. These effects are more pronounced among young and male patients, and those in whom direct-stenting techniques were used. Future studies should focus on the mortality in high-quality, large-scale clinical trials with long-term follow-up.

β-Blockers and Volatile Anesthetics May Attenuate Cardioprotection by Remote Preconditioning in Adult Cardiac Surgery: A Meta-analysis of 15 Randomized Trials

OBJECTIVE Clinical trials on cardioprotection by remote ischemic preconditioning (RIPC) for adult patients undergoing cardiac surgery revealed mixed results. Previous meta-analyses have been conducted and found marked heterogeneity among studies. The aim of this meta-analysis was to evaluate the factors affecting cardioprotection by remote preconditioning in adult cardiac surgery. DESIGN A meta-analysis of randomized controlled trials. SETTING University hospitals. PARTICIPANTS Adult subjects undergoing cardiac surgery. INTERVENTIONS RIPC. MEASUREMENTS AND MAIN RESULTS Fifteen trials with a total of 1,155 study patients reporting postoperative myocardial biomarker (CK-MB or troponin) levels were identified from PubMed, Embase, and the Cochrane Library (up to July 2012). Compared with controls, RIPC significantly reduced postoperative biomarkers of myocardial injury (standardized mean difference = -0.31, p = 0.041; heterogeneity test: I(2) = 83.5%). This effect seemed more significant in valve surgery (standardized mean difference = -0.74, p = 0.002) than in coronary artery surgery (standardized mean difference = -0.23; p = 0.17). Univariate meta-regression analyses suggested that the major sources of significant heterogeneity were β-blockers (%) (coefficient = 0.0161, p = 0.022, adjusted R(2) = 0.37) and volatile anesthetics (coefficient = 0.6617, p = 0.065, adjusted R(2) = 0.22). These results were further confirmed in multivariate regression and subgroup analyses. CONCLUSIONS Available data from this meta-analysis further confirmed the cardioprotection conferred by RIPC in adult cardiac surgery. Moreover, the cardioprotective effect may be attenuated when combined with β-blockers or volatile anesthetics.

Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats

Aim:Sevoflurane postconditioning (SpostC) has been shown to protect the heart from ischemia-reperfusion (I/R) injury. In this study, we examined whether SpostC affected autophagic flux in myocardial tissues that contributed to its cardioprotective effects in rats following acute I/R injury.Methods:SD rats underwent 30 min of left anterior descending coronary artery ligation followed by 120 min of reperfusion. The rats were subjected to inhalation of 2.4% (v/v) sevoflurane during the first 5 min of reperfusion, and chloroquine (10 mg/kg, ip) was injected 1 h before I/R. Myocardial infarct size was estimated using TTC staining. Autophagosomes in myocardial tissues were detected under TEM. Expression of LC3B-II, beclin-1, p62/SQSTM1, cathepsin B, caspase-3 and cleaved PARP was assessed using Western blot analysis. Plasma cardiac troponin I was measured using ELISA. Cardiomyocyte apoptosis was evaluated with TUNEL staining.Results:I/R procedure produced severe myocardium infarct and apoptosis accompanied by markedly increased number of autophagosomes, as well as increased levels of LC3B-II, beclin-1 and p62 in myocardial tissues. SpostC significantly reduced infarct size, attenuated myocardial apoptosis, restored intact autophagic flux and improved the lysosomal function in myocardial tissues. Administration of chloroquine that blocked autophagic flux abrogated the cardioprotective effects of SpostC.Conclusion:SpostC exerts its cardioprotective effects in rats following I/R injury via restoring autophagic flux in myocardial tissues.

Delayed Remote Ischemic Preconditioning Produces an Additive Cardioprotection to Sevoflurane Postconditioning Through an Enhanced Heme Oxygenase 1 Level Partly Via Nuclear Factor Erythroid 2-Related Factor 2 Nuclear Translocation

Although both sevoflurane postconditioning (SPoC) and delayed remote ischemic preconditioning (DRIPC) have been proved effective in various animal and human studies, the combined effect of these 2 strategies remains unclear. Therefore, this study was designed to investigate this effect and elucidate the related signal mechanisms in a Langendorff perfused rat heart model. After 30-minute balanced perfusion, isolated hearts were subjected to 30-minute ischemia followed by 60-minute reperfusion except 90-minute perfusion for control. A synergic cardioprotective effect of SPoC (3% v/v) and DRIPC (4 cycles 5-minute occlusion/5-minute reflow at the unilateral hindlimb once per day for 3 days before heart isolation) was observed with facilitated cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect was more pronounced in the combined group (6.76% ± 2.18%) than in the SPoC group (16.50% ± 4.55%, P < .001) or in the DRIPC group (10.22% ± 2.57%, P = .047). Subsequent analysis revealed that an enhanced heme oxygenase 1 (HO-1) expression, but not protein kinase B/AKt or extracellular signal-regulated kinase 1 and 2 activation, was involved in the synergic cardioprotective effect, which was further confirmed in the messenger RNA level of HO-1. Such trend was also observed in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, an upstream regulation of HO-1. In addition, correlation analysis showed a significantly positive relationship between HO-1 expression and Nrf2 translocation (r = 0.729, P < .001). Hence, we conclude that DRIPC may produce an additive cardioprotection to SPoC through an enhanced HO-1 expression partly via Nrf2 translocation.

Failure to protect against myocardial ischemia-reperfusion injury with sevoflurane postconditioning in old rats in vivo.

Sevoflurane post‐conditioning (SpostC) protects young hearts against ischemia‐reperfusion injury. It is unknown whether the infarct‐limiting effect is also maintained in aged cohorts and whether there are age‐associated differences in the underlying mechanisms.

Age-associated differences in response to sevoflurane postconditioning in rats.

Abstract Background Experimental evidence suggests that anesthetic preconditioning and postconditioning could effectively attenuate myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed at investigating whether there are age-associated differences in response to sevoflurane postconditioning during myocardial I/R injury in young and old rats, and explore the underlying molecular mechanisms. Methods Young and old rats were subjected to 30 min myocardial ischemia, followed by 2 h of reperfusion, with or without sevoflurane postconditioning. Results Both 1 and 2 minimal aveolar concentration (MAC) sevoflurane postconditioning reduced infarct size (IS) (34 ± 3% and 32 ± 2% vs. 58 ± 5%, p < 0.05) and apoptotic index (8 ± 1% and 7 ± 1% vs. 15 ± 2%, p < 0.05) in young rats, compared to young control group. In contrast, they could not reduce IS (45 ± 3% and 43 ± 3% vs. 47 ± 3%, p > 0.05) and apoptotic index (28 ± 3% and 25 ± 2%, vs. 26 ± 2%, p > 0.05) in old rats, compared to old control group. Mechanistically, we found that the phosphorylation of both Akt and ERK1/2 but not STAT3 was substantially enhanced after sevoflurane postconditioning in young rats, compared to young control group, but not in old rats, relative to old control group. Conclusion There are age-related differences after exposure to sevoflurane postconditioning that protects young, but not old rat hearts against I/R injury, which may be at least associated with the inability to activate Akt and ERK1/2.

Downregulation of Na+/Ca2+ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats

Background: Calcium regulatory proteins-L-type Ca2+ channels (LTCCs), ryanodine receptor 2 (RyR2), and Na+/Ca2+ exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model. Methods: After 30-min balanced perfusion, isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion. Totally 40 isolated hearts were randomly assigned to four groups (n = 10/group): time control group, I/RI group, SevoPoC group, and DRIPC group. The effect of SevoPoC (3% v/v) and DRIPC were observed. Myocardial infarct size (IS), cardiac troponin I level, and heart function were measured. The protein and messenger RNA levels of LTCCs, RyR2, and NCX1 were determined. Results: Both SevoPoC and DRIPC improved the recovery of myocardial function, and reduced cardiac troponin I release after I/RI. The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group (16.50% ± 4.54% in the SevoPoC group [P = 0.0006], and 22.34% ± 4.02% in the DRIPC group [P = 0.0007] vs. 35.00% ± 5.24% in the I/RI group, respectively). SevoPoC, but not DRIPC significantly inhibited the activity of NCX1 (0.59 ± 0.09 in the I/RI group vs. 0.32 ± 0.16 in the SevoPoC group, P = 0.006; vs. 0.57 ± 0.14 in the DRIPC group, P = 0.072). No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC. In addition, subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin I level and the protein expression of NCX1 (r = 0.505, P = 0.023). Conclusion: SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.