Reasons for reperfusion delay in ST-elevation myocardial infarction and their impact on mortality.

AIMS: The impact of reperfusion delay in ST-elevation myocardial infarction (STEMI) is well known. We aimed to describe the specific reasons for delay to primary percutaneous coronary intervention (pPCI), and their impact on mortality after adjusting for confounders, using the first-medical-contact-to-device (FMCTD) time to measure the delay. METHODS: Between January 2006 and December 2019, 2149 STEMI patients underwent pPCI at our centre. Delayed pPCI was defined as FMCTD > 90 min or > 120 min in the case of inter-hospital transfer. The causes of delay were classified as system-related (related to the network organization) or patient-related (related to the clinical condition of the patient). Primary outcome was 1-year all-cause mortality. RESULTS: The pPCI was timely in 69.9% of patients, delayed for system-related causes in 16.4% or for patient-related causes in 13.7%. Different patient-related causes induced variable median FMCTD time (from 114 min for technically difficult pPCI to 159 min for ECG and/or symptom resolution). By multivariable Cox-regression models, the main independent risk factors for mortality were delay due to comorbidities [hazard ratio (HR) 2.19 (1.22-3.91)], or hemodynamic instability [HR 2.05 (1.25-3.38)], after adjusting for Global Registry of Acute Coronary Events risk score tertiles and angiographic success. The difference in risk of mortality is maintained over the entire spectrum of time from symptom onset. CONCLUSIONS: Different causes of delay had different impacts on mortality, generally more important than the length of the delay. Causes of delay such as hemodynamic instability and comorbidities should prompt specific programs of performance improvement. Timely pPCI maintains prognostic advantages after several hours from symptom onset, mandating prompt reperfusion also in late-presenter patients.

Reperfusion Strategies in Acute Myocardial Infarction: State of the Art

Abstract ST elevation myocardial infarction (STEMI) is a highly prevalent condition worldwide. Reperfusion therapy is strongly associated with the prognosis of STEMI and must be performed with a high standard of quality and without delay. A systematic review of different reperfusion strategies for STEMI was conducted, including randomized controlled trials that included major cardiovascular events (MACE), and systematic reviews in the last 5 years through the PRISMA ( Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology. The research was done in the PubMed and Cochrane Central Register of Controlled Trials databases, in addition to a few manual searches. After the exclusion criteria were applied, 90 articles were selected for this review. Despite the reestablishment of IRA patency in PCI for STEMI, microvascular lesions occur in a significant proportion of these patients, which can compromise ventricular function and clinical course. Several therapeutic strategies - intracoronary administration of nicorandil, nitrates, melatonin, antioxidant drugs (quercetin, glutathione), anti-inflammatory substances (tocilizumab [an inhibitor of interleukin 6], inclacumab, P-selectin inhibitor), immunosuppressants (cyclosporine), erythropoietin and ischemic pre- and post-conditioning and stem cell therapy - have been tested to reduce reperfusion injury, ventricular remodeling and serious cardiovascular events, with heterogeneous results: These therapies need confirmation in larger studies to be implemented in clinical practice

Controlling Reperfusion Injury With Controlled Reperfusion: Historical Perspectives and New Paradigms.

Cardiac reperfusion injury is a well-established outcome following treatment of acute myocardial infarction and other types of ischemic heart conditions. Numerous cardioprotection protocols and therapies have been pursued with success in pre-clinical models. Unfortunately, there has been lack of successful large-scale clinical translation, perhaps in part due to the multiple pathways that reperfusion can contribute to cell death. The search continues for new cardioprotection protocols based on what has been learned from past results. One class of cardioprotection protocols that remain under active investigation is that of controlled reperfusion. This class consists of those approaches that modify, in a controlled manner, the content of the reperfusate or the mechanical properties of the reperfusate (e.g., pressure and flow). This review article first provides a basic overview of the primary pathways to cell death that have the potential to be addressed by various forms of controlled reperfusion, including no-reflow phenomenon, ion imbalances (particularly calcium overload), and oxidative stress. Descriptions of various controlled reperfusion approaches are described, along with summaries of both mechanistic and outcome-oriented studies at the pre-clinical and clinical phases. This review will constrain itself to approaches that modify endogenously-occurring blood components. These approaches include ischemic postconditioning, gentle reperfusion, controlled hypoxic reperfusion, controlled hyperoxic reperfusion, controlled acidotic reperfusion, and controlled ionic reperfusion. This review concludes with a discussion of the limitations of past approaches and how they point to potential directions of investigation for the future.

Remote Ischemic Perconditioning Ameliorates Myocardial Ischemia and Reperfusion-Induced Coronary Endothelial Dysfunction and Aortic Stiffness in Rats.

BACKGROUND: Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events. AIM: To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI. METHODS: Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc. Three groups: (1) sham operated (Sham, without LAD occlusion); (2) myocardial ischemia and reperfusion (MIR) and (3) MIR + RIPerc group with 3 cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia were used. Assessment of vascular reactivity in isolated septal coronary arteries (non-occluded) and aortic rings as well as aortic stiffness was assessed by wire myography either 3 or 28 days after AMI, respectively. Markers of pro-inflammatory cytokines, adhesion molecules were assessed by RT-qPCR and ELISA. RESULTS: MIR promotes impaired endothelial-dependent relaxation in septal coronary artery segments, increased aortic stiffness and adverse left ventricular remodeling. These changes were markedly attenuated in rats treated with RIPerc and associated with a significant decline in P-selectin, IL-6 and TNF-α expression either in infarcted or non-infarcted myocardial tissue samples. CONCLUSIONS: Our study for the first time demonstrated that RIPerc alleviates MIR-induced coronary artery endothelial dysfunction in non-occluded artery segments and attenuates aortic stiffness in rats. The vascular protective effects of RIPerc are associated with ameliorated inflammation and might therefore be caused by reduced inflammatory signaling.

Engineering extracellular vesicles with platelet membranes fusion enhanced targeted therapeutic angiogenesis in a mouse model of myocardial ischemia reperfusion.

Therapeutic angiogenesis is one promising strategy for the treatment of ischemic heart disease, which is the leading cause of death globally. In recent years, extracellular vesicles (EVs) have quickly gained much attention as a cell-free approach to stimulate angiogenesis. However, clinical applications of EVs are limited by their insufficient targeting capability. Herein, we introduce a method to enhance therapeutic angiogenesis based on platelet membrane-engineered EVs. METHODS: Platelet-mimetic EVs (P-EVs) were fabricated by fusing the membranes of EVs with platelet membranes by extrusion. A mouse model of myocardial ischemia reperfusion (MI/R) was established and injected with PBS, EVs, and P-EVs to evaluate their targeting ability and therapeutic angiogenesis efficacy. RESULTS: P-EVs inherited the adhesive proteins and natural targeting ability to injured vasculature of platelets and retained the pro-angiogenic potential of EVs. In the MI/R model, P-EVs preferentially accumulated in the injured endothelium of the ischemic hearts and enhanced the angiogenesis potency of EVs. CONCLUSIONS: This engineering strategy to modify pre-isolated EVs with platelet membranes by membrane fusion bestows EVs with the targeting ability of platelets and offers an exciting opportunity to design other targeted EVs fused with cell membranes from different sources for therapeutic angiogenesis.

Veno-occlusive unloading of the heart reduces infarct size in experimental ischemia-reperfusion.

Mechanical unloading of the left ventricle reduces infarct size after acute myocardial infarction by reducing cardiac work. Left ventricular veno-occlusive unloading reduces cardiac work and may reduce ischemia and reperfusion injury. In a porcine model of myocardial ischemia-reperfusion injury we randomized 18 pigs to either control or veno-occlusive unloading using a balloon engaged from the femoral vein into the inferior caval vein and inflated at onset of ischemia. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to determine the myocardial area at risk and infarct size, respectively. Pressure-volume loops were recorded to calculate cardiac work, left ventricular (LV) volumes and ejection fraction. Veno-occlusive unloading reduced infarct size compared with controls (Unloading 13.9 ± 8.2% versus Control 22.4 ± 6.6%; p = 0.04). Unloading increased myocardial salvage (54.8 ± 23.4% vs 28.5 ± 14.0%; p = 0.02), while the area at risk was similar (28.4 ± 6.7% vs 27.4 ± 5.8%; p = 0.74). LV ejection fraction was preserved in the unloaded group, while the control group showed a reduced LV ejection fraction. Veno-occlusive unloading reduced myocardial infarct size and preserved LV ejection fraction in an experimental acute ischemia-reperfusion model. This proof-of-concept study demonstrated the potential of veno-occlusive unloading as an adjunctive cardioprotective therapy in patients undergoing revascularization for acute myocardial infarction.

The electrogenic sodium bicarbonate cotransporter and its roles in the myocardial ischemia-reperfusion induced cardiac diseases.

Cardiac tissue ischemia/hypoxia increases glycolysis and lactic acid accumulation in cardiomyocytes, leading to intracellular metabolic acidosis. Sodium bicarbonate cotransporters (NBCs) play a vital role in modulating intracellular pH and maintaining sodium ion concentrations in cardiomyocytes. Cardiomyocytes mainly express electrogenic sodium bicarbonate cotransporter (NBCe1), which has been demonstrated to participate in myocardial ischemia/reperfusion (I/R) injury. This review outlines the structural and functional properties of NBCe1, summarizes the signaling pathways and factors that may regulate the activity of NBCe1, and reviews the roles of NBCe1 in the pathogenesis of I/R-induced cardiac diseases. Further studies revealing the regulatory mechanisms of NBCe1 activity should provide novel therapeutic targets for preventing I/R-induced cardiac diseases.

Ex vivo evaluation of the biventricular cardiac function for donation after circulatory death model: An experimental study.

Few reports on a biventricular working heart model with ex vivo perfusion exist owing to the complexity of establishing a circuit. Hence, we investigated it for donation after circulatory death. The heart in six juvenile pigs (~20 kg) was arrested by asphyxiation. After 30 minutes of global ischemia, the heart was harvested, reperfused with normoxemic blood cardioplegia for 20 minutes, and subsequently perfused with hyperxemic blood. After 70 minutes of controlled reperfusion, the system was switched to the biventricular working mode. Cardiac function was assessed before anoxia and during the biventricular mode. Left and right ventricular functions worsened during the biventricular mode, as compared to those before anoxia (dP/dtmax , 673 ± 120 vs. 283 ± 95 and 251 ± 35 vs. 141 ± 21 mm Hg/s, respectively; P < .001). Systemic (resistance/100 g net heart weight) and pulmonary vascular resistance indexes during the biventricular mode were similar to those before anoxia (829 ± 262 vs. 759 ± 359, P = .707, and 167 ± 57 vs. 158 ± 83 dynes·sec·cm-5 - l-100-g net heart weight, P = .859, respectively). The biventricular working heart model with ex vivo perfusion was feasible, exhibited stable hemodynamics, and has the potential to be a powerful tool for direct cardiac function assessment.

Towards medicine of excellence in Mexico: the "Código Infarto" protocol, a view from the perspective of translational bioethics.

INTRODUCTION: Mexico is the country with the highest mortality due to ST-elevation acute myocardial infarction (STEMI), and the IMSS has therefore developed the protocol of care for emergency departments called Código Infarto (Infarction Code). In this article, aspects of translational medicine are discussed with a bioethical and comprehensive perspective. OBJECTIVE: To analyze the Código Infarto protocol from the perspective of translational bioethics. METHOD: A problem-centered approach was carried out through reflective equilibrium (or Rawls' method), as well as by applying the integral method for ethical discernment. RESULTS: The protocol of care for emergency services Código Infarto is governed by evidence-based medicine and value-based medicine; it is guided by a principle of integrity that considers six dimensions of quality for the care of patients with STEMI. CONCLUSION: The protocol overcomes some adverse social determinants that affect STEMI medical care, reduces mortality and global economic disease burden, and develops medicine of excellence with high social reach.

INTRODUCCIÓN: México es el país con mayor mortalidad por infarto agudo de miocardio con elevación del segmento ST (IAM CEST), por lo que el Instituto Mexicano del Seguro Social desarrolló el protocolo de atención para los servicios de urgencias denominado Código Infarto. En este artículo se discuten aspectos de la medicina traslacional con una perspectiva bioética e integral. OBJETIVO: Analizar el protocolo Código Infarto desde la perspectiva de la bioética traslacional. MÉTODO: Se realizó una aproximación centrada en el problema a través del equilibrio reflexivo, así como la aplicación del método integral para el discernimiento ético. RESULTADOS: El protocolo de atención para los servicios de urgencias Código Infarto se rige por la medicina basada en la evidencia y la medicina basada en valores; se orienta por el principio de integridad que considera las seis dimensiones de la calidad para la atención de pacientes con IAM CEST. CONCLUSIÓN: El protocolo supera algunos determinantes sociales adversos que afectan la atención médica del IAM CEST, disminuye la mortalidad, la carga económica global de la enfermedad y desarrolla una medicina de excelencia de alto alcance social.

Guía práctica interinstitucional para el tratamiento del infarto agudo de miocardio / Interinstitutional clinical practice guidelines for the treatment of acute myocardial infarction

Resumen Introducción: México tiene la mortalidad más alta a 30 días por infarto agudo de miocardio (IAM), el cual constituye una de las principales causas de mortalidad en el país: 28 % versus 7.5 % del promedio de los países de la Organización para la Cooperación y el Desarrollo Económicos. Objetivo: Establecer las rutas críticas y las estrategias farmacológicas esenciales interinstitucionales para la atención de los pacientes con IAM en México, independientemente de su condición socioeconómica. Método: Se reunió a un grupo de expertos en diagnóstico y tratamiento de IAM, representantes de las principales instituciones públicas de salud de México, así como las sociedades cardiológicas mexicanas, Cruz Roja Mexicana y representantes de la Sociedad Española de Cardiología, con la finalidad de optimizar las estrategias con base en la mejor evidencia existente. Resultados: Se diseñó una guía de práctica clínica interinstitucional para el diagnóstico temprano y tratamiento oportuno del IAM con elevación del segmento ST, siguiendo el horizonte clínico de la enfermedad, con la propuesta de algoritmos que mejoren el pronóstico de los pacientes que acuden por IAM a los servicios de urgencias. Conclusión: Con la presente guía práctica, el grupo de expertos propone universalizar el diagnóstico y tratamiento en el IAM, independientemente de la condición socioeconómica del paciente.

Abstract Introduction: Mexico has the highest 30-day acute myocardial infarction (AMI) mortality rate: 28% versus 7.5% on average for the OECD countries, and it constitutes one of the main causes of mortality in the country. Objective: To establish critical pathways and essential interinstitutional pharmacological strategies for the care of patients with AMI in Mexico, regardless of their socioeconomic status. Method: A group of experts in AMI diagnosis and treatment, representatives of the main public health institutions in Mexico, as well as the Mexican cardiology societies, the Mexican Red Cross and representatives of the Spanish Society of Cardiology, were brought together in order to optimize strategies based on the best existing evidence. Results: An interinstitutional clinical practice guideline was designed for early diagnosis and timely treatment of AMI with ST elevation, following the clinical horizon of the disease, with the proposal of algorithms that improve the prognosis of patients who attend the emergency services due to an AMI. Conclusion: With these clinical practice guidelines, the group of experts proposes to universalize AMI diagnosis and treatment, regardless of patient socioeconomic status.

Comparative Effectiveness of Reperfusion Strategies in Patients with ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of the Acute Coronary Syndrome Quality Improvement in Kerala (ACS QUIK) Trial.

Introduction: Substantial heterogeneity exists in reperfusion strategies for patients with ST-segment myocardial infarction (STEMI) in low- and middle-income countries (LMICs). We sought to compare outcomes associated with primary percutaneous coronary intervention (PPCI) and non-primary percutaneous coronary intervention (nPPCI) reperfusion strategies in patients with STEMI in Kerala, India. Methods: We performed a retrospective analysis of patients with STEMI (n = 8665) from the Acute Coronary Syndrome Quality Improvement in Kerala (ACS QUIK) randomized trial receiving either PPCI (n = 6623) or nPPCI (n = 2042). nPPCI included all PCI strategies implemented when PPCI was not available including all post-fibrinolysis PCI strategies and PCI without fibrinolysis. Clinical outcomes among patients undergoing PPCI and nPPCI were compared after propensity-score matching. The main outcomes were the rates of in-hospital and 30-day major adverse cardiovascular events (MACE), defined as the composite of death, reinfarction, stroke, and major bleeding. Results: In the propensity-score matched cohort (n = 1266 in each group), nPPCI had longer symptom onset to hospital arrival time (347.5 vs. 195.0 minutes, p < 0.001), door to balloon time (108 minutes vs. 75 minutes, p < 0.001), and were less likely to receive a coronary stent (89.4% vs. 95%, p < 0.001), including drug-eluting stents (89.5% vs. 94.4%, p < 0.001). There were no clinically meaningful differences in discharge medical therapy. However, patients treated with nPPCI were less commonly referred for cardiac rehabilitation (20.2% vs. 24.2%; p = 0.019). In-hospital (3.6% vs. 3.3%, p = 0.74%) and 30-day (4.4% vs. 4.6%, p = 0.77) MACE did not differ between nPPCI and PPCI matched groups. Conclusion: In a large, contemporary population of STEMI patients from a LMIC, patients treated with a nPPCI reperfusion strategy had comparable short- and intermediate-term outcomes compared to PPCI despite differences in hospital presentation time and coronary stent use. These findings are reassuring but highlight the need for continued quality improvement in the delivery of STEMI care in resource-limited settings.

Fibrinolysis is a reasonable alternative for STEMI care during the COVID-19 pandemic.

OBJECTIVE: No data are available to develop uniform recommendations for reperfusion therapies in ST-segment elevation myocardial infarction (STEMI) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to fill the evidence gap regarding STEMI reperfusion strategy during the COVID-19 era. METHODS: Clinical characteristics and outcomes for 17 patients with STEMI who received fibrinolysis during the COVID-19 pandemic were compared with 20 patients who received primary percutaneous coronary intervention (PPCI), and were further compared with another 41 patients who received PPCI in the pre-COVID-19 period. RESULTS: In patients with STEMI, fibrinolysis achieved a comparable in-hospital and 30-day primary composite end point, as compared with those who received PPCI during the COVID-19 pandemic. No major bleeding was detected in either group. Compared patients with STEMI who received PPCI in the pre-COVID-19 period, we found a remarkable extension of chest pain onset-to-first medical contact (FMC) and FMC-to-wire crossing times, significantly increased number and length of stents, and much worse thrombolysis in myocardial infarction flow in patients with STEMI who received PPCI during the COVID-19 pandemic. CONCLUSION: Owing to its considerable efficacy and safety and advantages in conserving medical resources, we recommend fibrinolysis as a reasonable alternative for STEMI care during the COVID-19 pandemic.

Ambra1 Alleviates Hypoxia/Reoxygenation Injury in H9C2 Cells by Regulating Autophagy and Reactive Oxygen Species.

Reperfusion therapy is the most important method for treating acute myocardial infarction. However, myocardial ischemia reperfusion injury (MIRI) can offset the benefit of reperfusion therapy and worsen the outcome. In both ischemia and reperfusion, autophagy remains problematic. Activating molecule in Beclin1-regulated autophagy (Ambra1) is an important protein in autophagy regulation, and its function in MIRI remains unclear. Thus, we used H9C2 cells to investigate the function of Ambra1 in MIRI and the underlying mechanisms involved. Hypoxia and reoxygenation of H9C2 cells were used to mimic MIRI in vitro. During hypoxia, autophagy flux was blocked, then recovered in reoxygenation. Ambra1 overexpression increased autophagy in the H9C2 cells, as the LC3B II/I ratio increased, and alleviated cellular necrosis and apoptosis during hypoxia and reoxygenation. This effect was counteracted by an autophagy inhibitor. Knocking down Ambra1 can block autophagy which P62 sediment/supernatant ratio increased while the ratio of LC3B II/I decreased, and worsen outcomes. Ambra1 enhances autophagy in H9C2 cells by improving the stability and activity of the ULK1 complex. Reactive oxygen species (ROS) are an important cause of MIRI. ROS were reduced when Ambra1 was overexpressed and increased when Ambra1 was knocked down, indicating that Ambra1 can protect against hypoxia and reoxygenation injury in H9C2 cells by promoting autophagy and reducing ROS.

Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts.

Acute myocardial ischaemia and reperfusion (I-R) are major causes of ventricular arrhythmias in patients with a history of coronary artery disease. Ursodeoxycholic acid (UDCA) has previously been shown to be antiarrhythmic in fetal hearts. This study was performed to investigate if UDCA protects against ischaemia-induced and reperfusion-induced arrhythmias in the adult myocardium, and compares the effect of acute (perfusion only) versus prolonged (2 weeks pre-treatment plus perfusion) UDCA administration. Langendorff-perfused adult Sprague-Dawley rat hearts were subjected to acute regional ischaemia by ligation of the left anterior descending artery (10 min), followed by reperfusion (2 min), and arrhythmia incidence quantified. Prolonged UDCA administration reduced the incidence of acute ischaemia-induced arrhythmias (p = 0.028), with a reduction in number of ventricular ectopic beats during the ischaemic phase compared with acute treatment (10 ± 3 vs 58 ± 15, p = 0.036). No antiarrhythmic effect was observed in the acute UDCA administration group. Neither acute nor prolonged UDCA treatment altered the incidence of reperfusion arrhythmias. The antiarrhythmic effect of UDCA may be partially mediated by an increase in cardiac wavelength, due to the attenuation of conduction velocity slowing (p = 0.03), and the preservation of Connexin43 phosphorylation during acute ischaemia (p = 0.0027). The potential antiarrhythmic effects of prolonged UDCA administration merit further investigation.

Transvalvular Ventricular Unloading Before Reperfusion in Acute Myocardial Infarction.

BACKGROUND: Myocardial damage due to acute ST-segment elevation myocardial infarction (STEMI) remains a significant global health problem. New approaches to limit myocardial infarct size and reduce progression to heart failure after STEMI are needed. Mechanically reducing left ventricular (LV) workload (LV unloading) before coronary reperfusion is emerging as a potential approach to reduce infarct size. OBJECTIVES: Given the central importance of mitochondria in reperfusion injury, we hypothesized that compared with immediate reperfusion (IR), LV unloading before reperfusion improves myocardial energy substrate use and preserves mitochondrial structure and function. METHODS: To explore the effect of LV unloading duration on infarct size, we analyzed data from the STEMI-Door to Unload (STEMI-DTU) trial and then tested the effect of LV unloading on ischemia and reperfusion injury, cardiac metabolism, and mitochondrial function in swine models of acute myocardial infarction. RESULTS: The duration of LV unloading before reperfusion was inversely associated with infarct size in patients with large anterior STEMI. In preclinical models, LV unloading reduced the expression of hypoxia-sensitive proteins and myocardial damage due to ischemia alone. LV unloading with a transvalvular pump (TV-P) but not with venoarterial extracorporeal membrane oxygenation (ECMO) reduced infarct size. Using unbiased and blinded metabolic profiling, TV-P improved myocardial energy substrate use and preserved mitochondrial structure including cardiolipin content after reperfusion compared with IR or ECMO. Functional testing in mitochondria isolated from the infarct zone showed an intact mitochondrial structure including cardiolipin content, preserved activity of the electron transport chain including mitochondrial complex I, and reduced oxidative stress with TV-P-supported reperfusion but not with IR or ECMO. CONCLUSIONS: These novel findings identify that transvalvular unloading limits ischemic injury before reperfusion, improves myocardial energy substrate use, and preserves mitochondrial structure and function after reperfusion.

Dexmedetomidine pretreatment attenuates myocardial ischemia reperfusion induced acute kidney injury and endoplasmic reticulum stress in human and rat.

BACKGROUND: Patients undergoing cardiopulmonary bypass (CPB) often develop acute kidney injury (AKI) caused by myocardial ischemia reperfusion (MI/R), and this renal injury can be resolved notably by dexmedetomidine. Endoplasmic reticulum (ER) stress was reported to get involved in organ injury including AKI. OBJECTIVES: The current study aimed to address the correlation between MI/R induced AKI with ER stress and to assess the effects of dexmedetomidine pretreatment on AKI protection. METHOD: Patients selected for heart valve replacement surgery were randomly assigned to NS group (pre-anesthesia with 0.9% NaCl) and DEX group (pre-anesthesia with dexmedetomidine). Rat MI/R model was induced by occluding coronary artery for 30 min followed by 48-hour reperfusion. Rats were randomized into Sham (0.9% NaCl), I/R (MI/R + 0.9% NaCl) and I/R + DEX (MI/R + dexmedetomidine). Organ function and ER stress condition were evaluated by blood chemistry, pathology, and molecular test. RESULTS: Clinical data indicated dexmedetomidine pretreatment attenuated AKI and oxidative stress as well as postischemic myocardial injury in patients. Accordingly animal results suggested dexmedetomidine reduced cellular injury and improved postischemic myocardial and renal function. Dexmedetomidine also reduced myocardial and renal cells apoptosis and down-regulated ER stress. CONCLUSIONS: These results suggested that dexmedetomidine pretreatment attenuates MI/R injury-induced AKI by relieving the ER stress.