Postconditioning In Patients Research Articles

Intralipid postconditioning in patients of cardiac surgery undergoing cardiopulmonary bypass (iCPB): study protocol for a randomized controlled trial

BackgroundIntralipid is a necessary fatty acid carrier that has been safely used as an energy supplier in the clinic. It has played an important role in rescuing the cardiac arrest caused by local anesthetic toxicity. In recent years, experimental studies have shown that intralipid postconditioning (ILPC) could reduce myocardial ischemic/reperfusion (I/R) injuries. Our research group has innovatively conducted a pilot randomized controlled trial (RCT), and the results showed that ILPC could reduce the release of cTnT and CK-MB, biomarkers of myocardial I/R injury, in valve replacement surgery. However, the potential effects of ILPC on the clinical outcome of adult cardiac surgery patients are unclear. Intralipid postconditioning in patients of cardiac surgery undergoing cardiopulmonary bypass (iCPB) trial is aimed to further study whether ILPC could improve short-term and long-term clinical outcome, as well as cardiac function in adult cardiac surgery patients.MethodsThe iCPB trial is an ongoing, single-center, prospective, double-blinded, large sample RCT. In total, 1000 adults undergoing cardiac surgery will be randomly allocated to either the ILPC group or the control group. The intervention group received an intravenous infusion of 2 mL/kg of 20% intralipid (medium-chain and long-chain fat emulsion injection C6~C24, Pharmaceutical) within 10 min before aortic cross-unclamping, and the control group received an equivalent volume of normal saline. The primary endpoints are complex morbidity of major complications during hospitalization and all-cause mortality within 30 days after surgery. The secondary endpoints include (1) all-cause mortality 6 months and 1 year postoperatively; (2) the quality of life within 1 year after surgery, using the QoR-15 questionnaire; (3) the postoperative cardiac function evaluated by LVEF, LVEDS, and LVEDD, and the myocardial injury evaluated by CK-MB, cTnT, and BNP; and (4) short-term clinical outcomes during hospitalization and total cost are also detailed evaluated.DiscussionThe iCPB trial is the first to explore ILPC on the clinical outcome of adult cardiac surgery patients. The results are expected to provide potential evidences about whether ILPC could reduce the morbidity and mortality and improve the cardiac function and quality of life. Therefore, the results will provide a rationale for the evaluation of the potentially clinically relevant benefit of intralipid therapy.Trial registrationChictr.org.cn ChiCTR1900024387. Prospectively registered on 9 July 2019.

Renoprotective effect of remote ischemic postconditioning in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BackgroundWhether upper arm remote ischemic postconditioning (RIPostC) exerts protection to kidney in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remains unknown.MethodsSixty-four patients with STEMI were randomized to PPCI + RIPostC (n=29) and PPCI (n=35) groups. RIPostC consisting of 4 cycles of 5 minutes occlusion/reperfusion by cuff inflation/deflation of the upper arm was started within 1 minute after the first balloon dilatation. Peripheral venous blood samples were collected before PPCI and at 0.5, 8, 24, 48, and 72 hours after PPCI to detect serum creatinine (SCr) and creatine kinase-MB (CK-MB). Acute kidney injury (AKI) rate and estimated glomerular filtration rate (eGFR) were calculated. The transthoracic echocardiography was performed 7 days after PPCI to assess left ventricular ejection fraction (LVEF).ResultsThe patients in the PPCI + RIPostC group had a lower AKI rate compared with those in the PPCI group (P=0.04). The eGFR after PPCI increased in the PPCI + RIPostC group compared to the PPCI group (P<0.01). The peak of CK-MB concentration in the PPCI + RIPostC group was significantly lower than that in the PPCI group (P<0.01). The area under the curve of CK-MB decreased in the PPCI + RIPostC group compared with that in the PPCI group. LVEF in the PPCI + RIPostC group was significantly higher than that in the PPCI group (P=0.04).ConclusionUpper arm RIPostC exerts renal and cardiac protection following cardiac ischemia–reperfusion in patients with STEMI.

Ischemic Postconditioning: Not Giving Up Yet.

Ischemic postconditioning protects against reperfusion injury. Adjunctive use of manual thrombus aspiration improves reperfusion results in patients undergoing primary angioplasty. Combining both strategies (ischemic postconditioning and thrombus aspiration) may have additive effects in terms of myocardial salvage. The PORT trial will study the role of ischemic postconditioning in patients undergoing primary angioplasty with thrombus aspiration.

Pulmonary Protective Effects of Remote Ischaemic Preconditioning with Postconditioning in Patients Undergoing Cardiac Surgery Involving Cardiopulmonary Bypass: A Substudy of the Remote Ischaemic Preconditioning with Postconditioning Outcome trial

The RISPO (Remote Ischemic Preconditioning with Postconditioning Outcome) trial evaluated whether remote ischaemic preconditioning (RIPC) combined with remote ischaemic postconditioning (RIPostC) improves the clinical outcomes of patients undergoing cardiac surgery. This substudy of the RISPO trial aimed to evaluate the effect of RIPC with RIPostC on pulmonary function in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Sixty-five patients were enrolled (32: control and 33: RIPC-RIPostC). In the RIPC-RIPostC group, four cycles of 5min ischaemia and 5min reperfusion were administered before and after CPB to the upper limb. Peri-operative PaO2/FIO2 ratio, intra-operative pulmonary shunt, and dynamic and static lung compliance were determined. The mean PaO2/ FIO2 was significantly higher in the RIPC-RIPostC group at 24h after surgery [290 (96) vs. 387 (137), p=0.001]. The incidence of mechanical ventilation for longer than 48h was significantly higher in the control group (23% vs. 3%, p<0.05). However, there were no significant differences in other pulmonary profiles, post-operative mechanical ventilation time, and duration of intensive care unit stay. In our study, RIPC-RIPostC improved the post-operative 24h PaO2/FIO2 ratio. Remote ischaemic preconditioning-Remote ischaemic postconditioning has limited and delayed pulmonary protective effects in cardiac surgery patients with CPB.

Ischemic postconditioning altered microRNAs in human valve replacement

BackgroundAlthough the involvement of microRNAs (miRNAs) has been intensively studied in myocardial infarction, there is no report on the regulation of miRNAs by ischemic postconditioning in patients undergoing cardiac surgery. We aim to explore the regulation of miRNAs by ischemic postconditioning in double valve replacement. Materials and methodsIn this prospective, controlled clinical study, consecutive 30 patients undergoing double valve replacement were enrolled. The patients were randomized into two groups, namely an ischemic postconditioning (IPO) group (n = 15) and a control (CON) group (n = 15). For ethical considerations, samples of right atrial muscle were harvested, respectively, 10 min before cardiopulmonary bypass (pre-CPB) and 5 min after aortic declamping (post-CPB) for analysis of miRNAs, genes and apoptosis. ResultsCompared with the CON group, miR-1 was downregulated, whereas miR-21 was upregulated, and BCL2 messenger RNA (mRNA) was upregulated, whereas BAX mRNA and programmed cell death 4 mRNA remained unchanged in the IPO group. Likewise, a significant increase in BCL2 protein and a striking decrease in BAX protein were observed in the IPO group when compared with those in the CON group. The IPO group showed a significantly smaller increase of terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling-positive myocytes after CPB than CON group. ConclusionsIschemic postconditioning could regulate miR-1, miR-21, and downstream effectors and resulted in actual attenuation of apoptosis in patients undergoing valvular heart surgery.

The cardioprotection of ischemic postconditioning in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

a Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China b Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China c Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China d Department of Emergency, Qilu Hospital, Shandong University, Jinan, China

Effects of ischemic postconditioning in patients with acute myocardial infarction undergoing primary PCI: a review and meta-analysis

To evaluate the cardiac protective effects of ischemic postconditioning (IPC) in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Both foreign and Chinese databases including PubMed, EMbase, Cochrane library, and CNKI were searched to identify randomized controlled trials (RCTs) that reported the effects of IPC on the myocardial infarction size, myocardial blush grade (MBG), left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE). Two reviews assessed the quality of each trial and extracted data independently. The Cochrane Collaboration's RevMan 4.2.8 software was used for statistical analysis. Twelve studies were identified and the Meta-analysis included a total of 937 patients with AMI undergoing primary PCI with or without IPC. Pooled analysis of all studies demonstrated no significant reductions of peak CK and CK-MB with IPC relative to standard care. A secondary analysis of the studies didn't show improvements of left ventricular ejection fraction during hospitalization with IPC. However, the incidence of MACE within 3 month after primary PCI in IPC group was less than that in the control group (P = 0.04). No significant benefit of IPC for reduction of myocardial infarct size as determined by peak creatine kinase and CK-MB release, as well as LVEF. The incidence of MACE was improved in patients who received IPC.

GW25-e4527 Dynamic variance of plasma superoxide dismutase (SOD) and malondialdehyde (MDA) after ischemic postconditioning in patients with acute ST-segment elevated myocardial infarction

GW25-e4527 Dynamic variance of plasma superoxide dismutase (SOD) and malondialdehyde (MDA) after ischemic postconditioning in patients with acute ST-segment elevated myocardial infarction

Protective effect of remote ischemic postconditioning in patients undergoing cardiac surgery with cardiopulmonary bypass: possible relation with the HIF-1α

Protective effect of remote ischemic postconditioning in patients undergoing cardiac surgery with cardiopulmonary bypass: possible relation with the HIF-1α

Remote Ischemic Post-Conditioning of the Lower Limb During Primary Percutaneous Coronary Intervention Safely Reduces Enzymatic Infarct Size in Anterior Myocardial Infarction: A Randomized Controlled Trial

This study sought to evaluate whether remote ischemic post-conditioning (RIPC) could reduce enzymatic infarct size in patients with anterior ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Myocardial reperfusion injury may attenuate the benefit of pPCI. In animal models, RIPC mitigates myocardial reperfusion injury. One hundred patients with anterior ST-segment elevation myocardial infarction and occluded left anterior descending artery were randomized to pPCI + RIPC (n = 50) or conventional pPCI (n = 50). RIPC consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower limb. The primary endpoint was infarct size assessed by the area under the curve of creatinine kinase-myocardial band release (CK-MB). Secondary endpoints included the following: infarct size assessed by cardiac magnetic resonance delayed enhancement volume; T2-weighted edema volume; ST-segment resolution >50%; TIMI (Thrombolysis In Myocardial Infarction) frame count; and myocardial blush grading. Four patients (2 RIPC, 2 controls) were excluded due to missing samples of CK-MB. A total of 96 patients were analyzed; median area under the curve CK-MB was 8,814 (interquartile range [IQR]: 5,567 to 11,325) arbitrary units in the RIPC group and 10,065 (IQR: 7,465 to 14,004) arbitrary units in control subjects (relative reduction: 20%, 95% confidence interval: 0.2% to 28.7%; p = 0.043). Seventy-seven patients underwent a cardiac magnetic resonance scan 3 to 5 days after randomization, and 66 patients repeated a second scan after 4 months. T2-weighted edema volume was 37 ± 16 cc in RIPC patients and 47 ± 22 cc in control subjects (p = 0.049). ST-segment resolution >50% was 66% in RIPC and 37% in control subjects (p = 0.015). We observed no significant differences in TIMI frame count, myocardial blush grading, and delayed enhancement volume. In patients with anterior ST-segment elevation myocardial infarction, RIPC at the time of pPCI reduced enzymatic infarct size and was also associated with an improvement of T2-weighted edema volume and ST-segment resolution >50%. (Remote Postconditioning in Patients With Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention [PCI] [RemPostCon]; NCT00865722).

Circulation: Cardiovascular Interventions Editors’ Picks

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Protection of Pharmacological Postconditioning in Liver Surgery

: To elucidate the possible organ-protective effect of pharmacological postconditioning in patients undergoing liver resection with inflow occlusion. : Inflow occlusion reduces blood loss during liver transection in selected patients but is potentially harmful due to ischemia-reperfusion injury. Preventive strategies include the use of repetitive short periods of ischemia interrupted by a reperfusion phase (intermittent clamping), application of a short period of ischemia before transection (ischemic preconditioning), or pharmacological preconditioning before transection. Whether intervention after resection (postconditioning) may confer protection is unknown. : A 3 arm, prospective, randomized trial was designed for patients undergoing liver resection with inflow occlusion to compare the effects of pharmacological postconditioning with the volatile anesthetic agent sevoflurane (n = 48), intermittent clamping (n = 50), or no protective intervention (continuous inflow occlusion, n = 17). Endpoints included peak serum aspartate transaminase level, postoperative complications, and hospital stay. All patients were intravenously anesthetized with propofol. In patients with postconditioning, propofol infusion was stopped upon reperfusion and replaced with sevoflurane for 10 minutes. : Compared with the control group, both postconditioning (P = 0.044) and intermittent clamping (P = 0.015) significantly reduced aspartate transaminase levels. The risk of complications was significantly decreased by postconditioning, odds ratio, 0.08 [95% confidence interval (CI), 0.02-0.36; P = 0.001]) and intermittent clamping, odds ratio, 0.50 [95% CI, 0.26-0.96; P = 0.038], compared with controls. Both interventions reduced length of hospital stay, postconditioning -4 days [95% CI, -6 to -1; P = 0.009], and intermittent clamping -2 days, [95% CI, -4 to 0; P = 0.019]. : Pharmacological postconditioning reduces organ injury and postoperative complications. This easily applicable strategy should be used in patients with prolonged continuous inflow occlusion.

Impairment of endothelial protection by ischemic postconditioning in patients with major depressive disorder

This study used a model of ischemia-reperfusion injury to the brachial artery endothelium to investigate whether the protective role of ischemic postconditioning (IPostC) is impaired in patients with major depressive episode. Flow-mediated dilation (FMD) was measured before and after ischemia-reperfusion in the absence or presence of IPostC in 24 patients with major depressive disorder and 20 healthy controls. In addition, the severity of the depression, as assessed by the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) scores, and plasma nitrogen dioxide (NO(x)) levels were also determined. Ischemia-reperfusion resulted in a significant decrease in FMD in both patients with a major depressive episode and healthy controls. IPostC effectively prevented this decrease in FMD in healthy controls, but not in patients with a major depressive episode. HDRS and BDI scores were markedly increased, but plasma NO(x) levels decreased, in patients with a major depressive episode compared with those in healthy controls. Correlation analysis showed that HDRS and BDI scores and plasma NO(x) levels were significantly associated with post-ischemia-reperfusion FMD. These results suggest that endothelial protection by IPostC is impaired in patients with major depressive disorder, which may be related to the decrease in endothelial nitric oxide production and the severity of the depression.

Cardioprotective Effects of Ischemic Postconditioning in Patients Treated With Primary Percutaneous Coronary Intervention, Evaluated by Magnetic Resonance

Postconditioning has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI) in patients with ST-segment-elevation myocardial infarction. However, because clinical experience is limited, we examined the cardioprotective effects of postconditioning, using cardiac MRI in patients treated with PPCI. One hundred eighteen patients with ST-segment-elevation myocardial infarction referred for PPCI were randomly assigned to have either conventional PPCI or PPCI with postconditioning. Postconditioning was performed immediately after obtained reperfusion with 4 balloon occlusions, each lasting 30 seconds, followed by 30 seconds of reperfusion. The primary end point was myocardial salvage after 3 months as judged by delayed enhancement cardiac MRI. We found a 19% relative reduction of infarct size in the postconditioning group (51+/-16% of total area at risk versus 63+/-17%, P<0.01), corresponding to a 31% increase in salvage ratio. The number of patients developing heart failure was significantly fewer in the postconditioning group (27% versus 46%, P=0.048). No significant evidence of interaction between the impact of postconditioning and the location of the culprit lesion or size of the myocardium at risk was detected (P=0.21 and P=0.71). Mechanical postconditioning reduces infarct size in patients with ST-segment-elevation myocardial infarction treated with PPCI. The impact of mechanical postconditioning seems to be independent of the size of myocardium at risk. http://www.clinicaltrials.gov. Unique Identifier: NCT00507156.

Postconditioning during primary percutaneous coronary intervention: A review and meta-analysis

BackgroundMyocardial postconditioning (POC), defined as intermittent interruptions of blood flow at the onset of reperfusion after sustained ischemia, may attenuate reperfusion injury. In order to weigh the current evidence linking POC to reduction of myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI), we performed a systematic review and meta-analysis of the available data from small randomised trials. MethodsA Web-based search was performed for relevant studies, and retrieved data were subjected to systematic review and meta-analysis. ResultsSix studies were identified and the meta-analysis included a total of 244 patients with STEMI undergoing pPCI with or without POC. Pooled analysis of all studies demonstrated a significant reduction of peak creatine kinase with POC relative to standard care (weighted mean peak creatine kinase difference −609.59 IU/L, 95% confidence interval [CI] −1030 to −189; p=0.005). A secondary analysis of 4 of the studies also showed an improvement of left ventricular ejection fraction with POC (weighted mean ejection fraction difference 4.2%, 95% CI 2.1% to 6.2%; p=0.0001). ConclusionThis first systematic review and meta-analysis of randomized trials of POC in patients with STEMI undergoing primary PCI, demonstrated a significant benefit of POC over standard care for reduction of myocardial infarct size as determined by peak creatine kinase release and left ventricular ejection fraction. The effects of POC on clinical outcomes remain to be determined.

Ischämische Prä- und Postkonditionierung

One or several short cycles of ischemia/reperfusion before (preconditioning) or after (postconditioning) a sustained coronary occlusion with subsequent reperfusion reduce the ultimate infarct size. The protection is potent, but limited to a narrow time frame. In animal experiments a complex signal transduction cascade was identified which results specifically in a reduction of reperfusion injury. There is evidence for both ischemic pre-and postconditioning in patients with coronary artery disease.