Early Reperfusion Research Articles

A SURVIVAL STORY OF 47 YEARS OLD MALE WITH ACUTE TOTAL OCCLUSION OF LEFT MAIN AND COEXISTING OSTIAL RIGHT CORONARY ARTERY LESION

Left main coronary artery (LMCA) thrombus occlusion causing acute coronary syndrome is an uncommon event and associated with severe life-threatening presentations. The clinical outcome depends on the age of the patients, presence of cardiogenic shock and the presence of dominant Right Coronary Artery (RCA) Early reperfusion is associated with improved outcomes. A 47-years man presented with sudden substernal burning sensation and dry cough for 1 hour. Coronary angiography revealed an acute totally occlusion of ostial left main (LM) with TIMI flow grade 0 and dominant RCA with ostial 80% stenosis having TIMI flow grade 3 and Grade 1 contralateral collaterals from RCA to left system. Emergency percutaneous coronary intervention (PCI) was performed to ostial LMCA toward the proximal LAD to cover the whole LMCA and stage PCI was performed to ostial RCA. Patient was discharge on 7th day with good general condition. An electrocardiographic pattern is associated with collateral filling territories in unprotected left main (ULM) occlusion. In our case diagnosis was completely made after diagnostic coronary angiogram. Acute total occlusion of LMCA is associated with arrhythmias, cardiogenic shock and sudden death. However, Patient was hemodynamically stable that showed indubitably the importance of dominant RCA with TIMI 3 flow and Grade 1 contralateral collaterals to left coronary circulation. We perform successful primary PCI of acute total occluded LMCA which shortened the ischemic time to salvage the ischemic myocardium.

Myocardial oxidative stress is increased in early reperfusion, but systemic antioxidative therapy does not prevent ischemia-reperfusion arrhythmias in pigs.

Arrhythmias in the early phase of reperfusion after myocardial infarction (MI) are common, and can lead to hemodynamic instability or even cardiac arrest. Reactive oxygen species (ROS) are thought to play a key role in the underlying mechanisms, but evidence from large animal models is scarce, and effects of systemic antioxidative treatment remain contentious. MI was induced in 7 male and 7 female pigs (Norwegian landrace, 35-40 kg) by clamping of the left anterior descending artery (LAD) during open thorax surgery. Ischemia was maintained for 90 min, before observation for 1 h after reperfusion. Pigs were randomized 1:1 in an operator-blinded fashion to receive either i.v. N-acetylcysteine (NAC) from 70 min of ischemia and onwards, or 0.9% NaCl as a control. Blood samples and tissue biopsies were collected at baseline, 60 min of ischemia, and 5 and 60 min of reperfusion. ECG and invasive blood pressure were monitored throughout. The protocol was completed in 11 pigs. Oxidative stress, as indicated by immunoblotting for Malondialdehyde in myocardial biopsies, was increased at 5 min of reperfusion compared to baseline, but not at 60 min of reperfusion, and not reduced with NAC. We found no significant differences in circulating biomarkers of myocardial necrosis, nor in the incidence of idioventricular rhythm (IVR), non-sustained ventricular tachycardia (NSVT), ventricular tachycardia (VT) or ventricular fibrillation (VF) between NAC-treated and control pigs during reperfusion. Myocardial oxidation was increased early after reperfusion in a porcine model of MI, but systemic antioxidative treatment did not protect against reperfusion arrhythmias.

Remote ischemic preconditioning prevents sarcolemmal-associated proteolysis by MMP-2 inhibition.

The death of myocytes occurs through different pathways, but the rupture of the plasma membrane is the key point in the transition from reversible to irreversible injury. In the myocytes, three major groups of structural proteins that link the extracellular and intracellular milieus and confer structural stability to the cell membrane: the dystrophin-associated protein complex, the vinculin-integrin link, and the spectrin-based submembranous cytoskeleton. The objective was to determine if remote ischemic preconditioning (rIPC) preserves membrane-associated cytoskeletal proteins (dystrophin and β-dystroglycan) through the inhibition of metalloproteinase type 2 (MMP-2) activity. A second objective was to describe some of the intracellular signals of the rIPC, that modify mitochondrial function at the early reperfusion. Isolated rat hearts were subjected to 30min of global ischemia and 120min of reperfusion (I/R). rIPC was performed by 3 cycles of ischemia/reperfusion in the lower limb (rIPC). rIPC significantly decreased the infarct size, induced Akt/GSK-3 β phosphorylation and inhibition of the MPTP opening. rIPC improved mitochondrial function, increasing membrane potential, ATP production and respiratory control. I/R increased ONOO- production, which activates MMP-2. This enzyme degrades β-dystroglycan and dystrophin and collaborates to sarcolemmal disruption. rIPC attenuates the breakdown of β-dystroglycan and dystrophin through the inhibition of MMP-2 activity. Furthermore, we confirm that rIPC activates different intracellular pathway that involves the an Akt/Gsk3β and MPTP pore with preservation of mitochondrial function.

In-hospital outcomes after acute myocardial infarction with obstructive coronary artery disease in critically ill patients hospitalized for non-cardiac disease

BackgroundAcute myocardial infarction (AMI) is one of the major cardiac complications in patients hospitalized in the intensive care unit (ICU) for non-cardiac disease. A better knowledge of ischemic and bleeding risks in these patients is needed to identify those most likely to benefit from specific cardiac management. We therefore assessed the incidence and predictors of a composite outcome of severe ischemic event (AMI recurrence, ischemic stroke), major bleeding, or all-cause death in this setting.MethodsIn this multicenter retrospective study, all consecutive adult patients admitted for non-cardiac disease to four French university hospital ICUs between January 2012 and December 2018 who had an AMI with obstructive coronary artery disease (OCAD) during the ICU stay were considered for inclusion. AMI with OCAD was defined as an elevated cardiac troponin value associated with at least one sign (clinical, electrocardiographic, or echocardiographic) suggestive of myocardial ischemia and presence of OCAD on coronary angiography. The primary endpoint was in-hospital occurrence of the composite outcome.ResultsNinety-six patients [median age 69 years, 22 women (23%), 59 with sepsis (61%), 35 with ST elevation (37%), median sequential organ failure assessment (SOFA) of 8 on the day of AMI] were included. The median peak cardiac troponin value was 131 (IQR 44–303) times the upper reference limit. Dual antiplatelet, therapeutic anticoagulation, and early mechanical reperfusion therapies were administered in 61 (64%), 68 (71%), and 47 (49%) patients, respectively. The composite outcome occurred in 48 (50%) patients. Severe ischemic events occurred in 17 (18%) patients and major bleeding in 26 (27%) patients; 26 patients (27%) died in the hospital. AMI management was not significantly different in patients with and without the composite outcome. A history of arterial hypertension (HR 2.05, 95% CI 1.01–4.16) and high SOFA score at the time of AMI (HR 1.07, 95% CI 1.00–1.15) were independent risk factors for the composite outcome.ConclusionsPatients who have an AMI with OCAD during an ICU stay for non-cardiac disease are at risk of a composite outcome of severe ischemia, major bleeding, and death. A history of arterial hypertension and high SOFA scores were independent hazards for poor prognosis.Graphical

Instantaneous detection of acute myocardial infarction and ischaemia from a single carotid pressure waveform in rats.

Myocardial infarction (MI) is one of the leading causes of death worldwide. It is well accepted that early diagnosis followed by early reperfusion therapy significantly increases the MI survival. Diagnosis of acute MI is traditionally based on the presence of chest pain and electrocardiogram (ECG) criteria. However, around 50% of the MIs are without chest pain, and ECG is neither completely specific nor definitive. Therefore, there is an unmet need for methods that allow detection of acute MI or ischaemia without using ECG. Our hypothesis is that a hybrid physics-based machine learning (ML) method can detect the occurrence of acute MI or ischaemia from a single carotid pressure waveform. We used a standard occlusion/reperfusion rat model. Physics-based ML classifiers were developed using intrinsic frequency parameters extracted from carotid pressure waveforms. ML models were trained, validated, and generalized using data from 32 rats. The final ML models were tested on an external stratified blind dataset from additional 13 rats. When tested on blind data, the best ML model showed specificity = 0.92 and sensitivity = 0.92 for detecting acute MI. The best model's specificity and sensitivity for ischaemia detection were 0.85 and 0.92, respectively. We demonstrated that a hybrid physics-based ML approach can detect the occurrence of acute MI and ischaemia from carotid pressure waveform in rats. Since carotid pressure waveforms can be measured non-invasively, this proof-of-concept pre-clinical study can potentially be expanded in future studies for non-invasive detection of MI or myocardial ischaemia.

Beta-blocker therapy in patients with acute myocardial infarction: not all patients need it.

Most of the evidences for beneficial effects of beta-blockers in patients with acute myocardial infarction (AMI) were from the clinical studies published in the pre-reperfusion era when anti-platelet drugs, statins or inhibitors of renin-angiotensin-aldosterone system which are known to reduce cardiovascular mortality of patients with AMI were not introduced. In the reperfusion era, beta-blockers' benefit has not been clearly shown except in patients with reduced ejection fraction (EF; ≤40%). In the era of the early reperfusion therapy for AMI, a number of patients with mildly reduced EF (>40%, <50%) or preserved EF (≥50%) become increasing. However, because no randomized clinical trials are available until now, the benefit and the optimal duration of oral treatment with beta-blockers in patients with mildly reduced or preserved EF are questionable. Registry data have not showed the association of oral beta-blocker therapy with decreased mortality in survivors without heart failure or left ventricular systolic dysfunction after AMI. In the Korea Acute Myocardial Infarction Registry-National Institute of Health of in-hospital survivors after AMI, the benefit of beta-blocker therapy at discharge was shown in patients with reduced or mildly reduced EF, but not in those with preserved EF, which provides new information about beta-blocker therapy in patients without reduced EF. However, clinical practice can be changed when the results of appropriate randomized clinical trials are available. Ongoing clinical trials may help to answer the unresolved issues of beta-blocker therapy in patients with AMI.

The Effect of Nitroglycerine on Myocardial Injury Induced by Ischemia/Reperfusion in Adult Male Albino Rats

Abstract Background Despite, early reperfusion is the current optimal way to rescue the heart and salvage of greater amount myocardium, the process of reperfusion could induce myocardial injury and cardiomyocyte death, that result in heart failure and death. Several therapeutic medications such as nitroglycerine is currently under investigation for preventing myocardial reperfusion injury which has the potential to improve clinical outcomes in patients with acute myocardial infarction treated Aim of the Work To investigate the effect of nitroglycerin on myocardial ischemic reperfusion injury as regard histopathological changes. Materials and methods 30 Male adult albino rats were randomly divided into four groups (10 rats for each); Group I (2 subgroups: group 1A (control group) &amp; group 1B (sham group)). Group II (ischemia/reperfusion animal model). Group III (nitroglycerine 0.5 mg/kg BW 15 min before I/R). Tissue samples of heart ventricles of all animals were collected and processed for light microscopic examination. Results The ischemia /reperfusion group showed massive disruption of the normal histological cardiac muscle picture, interstitial hemorrhage, inflammatory cells infiltration, pyknotic changes in the nuclei and dark acidophilic contraction bands. Nitroglycerine treated group revealed disruption of cardiac muscle fibers and with minimal improvement in the histological appearance. Conclusion Nitroglycerine injection attributed to potential improvement for myocardial ischemia reperfusion injury which. Therefore, it might be assumed that nitroglycerine could be used as a safe drug before induction of reperfusion.

Sex Differences in Therapies against Myocardial Ischemia-Reperfusion Injury: From Basic Science to Clinical Perspectives.

Mortality from myocardial infarction (MI) has declined over recent decades, which could be attributed in large part to improved treatment methods. Early reperfusion is the cornerstone of current MI treatment. However, reoxygenation via restored blood flow induces further damage to the myocardium, leading to ischemia-reperfusion injury (IRI). While experimental studies overwhelmingly demonstrate that females experience greater functional recovery from MI and decreased severity in the underlying pathophysiological mechanisms, the outcomes of MI with subsequent reperfusion therapy, which is the clinical correlate of myocardial IRI, are generally poorer for women compared with men. Distressingly, women are also reported to benefit less from current guideline-based therapies compared with men. These seemingly contradicting outcomes between experimental and clinical studies show a need for further investigation of sex-based differences in disease pathophysiology, treatment response, and a sex-specific approach in the development of novel therapeutic methods against myocardial IRI. In this literature review, we summarize the current knowledge on sex differences in the underlying pathophysiological mechanisms of myocardial IRI, including the roles of sex hormones and sex chromosomes. Furthermore, we address sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics of current drugs prescribed to limit myocardial IRI. Lastly, we highlight ongoing clinical trials assessing novel pharmacological treatments against myocardial IRI and sex differences that may underlie the efficacy of these new therapeutic approaches.

Impact of quercetin in patients with myocardial infarction. A multicenter, randomized, and open-label pilot study

ObjectiveMyocardial infarction (MI) is one of the leading causes of death in the world. Early myocardial reperfusion improves acute MI survival. Bioflavonoid quercetin is known to have antioxidant, anti-inflammatory, and anti-proliferative properties. The presented pilot study aims to investigate the cardioprotective effect of quercetin on infarct size limiting in patients with ST-segment elevation myocardial infarction (STEMI). MethodsPatients (n = 143) with first anterior STEMI within 6 hours from symptoms onset were included in this open-label multicenter pilot study. Patients were randomized either into quercetin group (n = 70) in addition to standard treatment or recommended therapy alone group (control group, n = 73). Quercetin infusions were initiated before reperfusion and repeated during the next 5 days. The infarct size assessed using creatine kinase-myocardial band area under curve (CK-MB AUC) was the primary study outcome. ResultsThe study arms did not differ in demographics, time to admission, and main clinical data. The median early CK-MB AUC was significantly lower in quercetin group than in controls (8036 ± 7594 vs 11219 ± 8146 U × 1 h/L, p = 0.015). Intravenous quercetin administration was associated with less reperfusion-induced intramyocardial hemorrhage by Cardiac Magnetic Resonance on Day 3 (11.1% of patients in quercetin group vs 53.3% of patients in control group, p < 0.024). There were no significant differences in left ventricle ejection fraction and LV remodeling indicators. ConclusionOur pilot study is the first to demonstrate novel insight into ischemia/reperfusion damage in STEMI patients. The addition of quercetin to standard STEMI therapy limits infarct size and prevents intramyocardial hemorrhage after the first anterior STEMI. Further research will be necessary to both validate and expand upon these findings.

Abstract P2121: Relative Importance Of Reactive Oxygen Species From Reverse Electron Transfer At Mitochondrial Complex I In Reperfusion Injury

The metabolite succinate accumulates during tissue ischemia. In early reperfusion, succinate is rapidly metabolized, driving a burst of mitochondrial reactive oxygen species (ROS) generation that triggers cell death. It is widely believed that the source of succinate-driven ROS in early reperfusion is reverse electron transfer (RET) at respiratory complex I (Cx-I). However, evidence for Cx-I RET ROS is largely based on experimental evidence from isolated mitochondria with succinate as the sole substrate. We hypothesized that numerous other conditions present during early reperfusion may impact Cx-I RET ROS. Thus, experimental perturbations were applied to mitochondria to model early reperfusion, with measurement of ROS via the fluorescent probe PHPA. These conditions included: (i) A high concentration of NADH; (ii) A high concentration of lactate; (iii) A mildly acidic pH; (iv) A non-zero concentration of ADP buffered by a creatine / creatine phosphate / creatine kinase system; (v) Presence of purine nucleotide breakdown products; (vi) Presence of calcium. These studies revealed that under early reperfusion-like conditions mitochondrial ROS generation still occurred via Cx-I RET, but at a magnitude only half that previously reported. Furthermore, residual ROS that was insensitive to a specific Cx-I RET inhibitor (S1QEL) was slightly elevated under early-reperfusion like conditions, and this residual ROS was mostly inhibited by S3QEL, a blocker of ROS from respiratory complex III (Cx-III). Together, these data suggest that the relative contribution of Cx-I RET ROS to reperfusion injury may be overestimated, and that of Cx-III ROS underestimated.

Time-based reperfusion in haemodynamically unstable pulmonary embolism patients: does early reperfusion therapy improve survival?

High-risk pulmonary embolism (PE) is associated with significant morbidity and mortality. Systemic thrombolysis remains the most evidenced-based treatment for haemodynamically unstable PE, but in daily clinical practice, it remains largely underused. In addition, unlike acute myocardial infarction or stroke, a clear time window for reperfusion therapy, including fibrinolysis, for high-risk PE has not been defined either for fibrinolysis or for the more recently incorporated options of catheter-based thrombolysis or thrombectomy. The aim of the present article is to review the current evidence supporting the potential benefit of earlier administration of reperfusion in haemodynamically unstable PE patients and suggest some potential strategies to further explore this issue.

Mechanisms regulating vascular and lymphatic regeneration in the heart after myocardial infarction.

Myocardial infarction, caused by a thrombus or coronary vascular occlusion, leads to irreversible ischaemic injury. Advances in early reperfusion strategies have significantly reduced short-term mortality after myocardial infarction. However, survivors have an increased risk of developing heart failure, which confers a high risk of death at 1 year. The capacity of the injured neonatal mammalian heart to regenerate has stimulated extensive research into whether recapitulation of developmental regeneration programmes may be beneficial in adult cardiovascular disease. Restoration of functional blood and lymphatic vascular networks in the infarct and border regions via neovascularisation and lymphangiogenesis, respectively, is a key requirement to facilitate myocardial regeneration. An improved understanding of the endogenous mechanisms regulating coronary vascular and lymphatic expansion and function in development and in adult patients after myocardial infarction may inform future therapeutic strategies and improve translation from pre-clinical studies. In this review, we explore the underpinning research and key findings in the field of cardiovascular regeneration, with a focus on neovascularisation and lymphangiogenesis, and discuss the outcomes of therapeutic strategies employed to date. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Reperfusion Delays and Outcomes Among Patients With ST-Segment-Elevation Myocardial Infarction With and Without Cardiogenic Shock.

Mortality remains high in patients with ST-segment-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS), and early reperfusion has been shown to improve outcomes. We analyzed the association between first medical contact (FMC)-to-percutaneous coronary angiography time with mortality and major adverse cardiovascular events among patients with STEMI with and without CS. We performed a retrospective analysis of the Vancouver Coastal Health Authority STEMI registry, including all patients with STEMI who received primary percutaneous coronary angiography between January 1, 2010, and December 31, 2020, and stratified them by presence or absence of CS at hospital arrival. The primary outcome was in-hospital mortality, the secondary outcome was in-hospital major adverse cardiovascular events, defined as a composite of the first occurrence of mortality, cardiac arrest, heart failure, intracerebral hemorrhage, cerebrovascular accident, or reinfarction. Mixed effects logistic regression with restricted cubic splines was used to estimate the relationships between FMC-to-device time and the outcomes in the CS and non-CS groups. 2929 patients were included, 9.4% (n=275) had CS. Median FMC-to-device time was 113.5 (interquartile range, 93.0-145.0) and 103.0 (interquartile range, 85.0-130.0) minutes for patients with CS and without CS, respectively. More patients with CS had FMC-to-device times above guideline recommendations (76.6% versus 54.1%, P<0.001). Between 60 and 90 minutes, for each 10-minute increase in FMC-to-device time, absolute mortality for patients with CS increased by 4% to 7%, whereas for patients without CS, it increased by <0.5%. Among patients with STEMI undergoing primary percutaneous coronary angiography, reperfusion delays among patients with CS are associated with significantly worse outcomes. Strategies to reduce FMC-to-device times for patients with STEMI presenting with CS are required.

Using of supersaturated oxygen delivery (SSO2 therapy) in patients with acute myocardial ischemia

Oxygen is the main participant in redox reactions in the body and its deficiency can lead to organ dysfunction. Thus, a decrease in blood flow in a certain region of the myocardium in patients with coronary heart disease can cause a heart attack. According to experimental studies, early reperfusion reduces infarct size, and clinical studies have shown that early effective reperfusion of the affected artery and prevention of re-occlusion is the basis for minimizing infarct size and mortality.Timely performed percutaneous intervention in patients with acute myocardial infarction significantly reduced the mortality rate and the risk of heart failure. Despite the endovascular treatment effectiveness, there is still a need for additional methods of cardioprotection, reducing the area of myocardial infarction and preventing the development of heart failure and adverse left ventricular remodeling. Blood oxygen supersaturation (SSO2 therapy) is one of the adjuvant methods of cardioprotection in the treatment of patients with acute myocardial ischemia.This review describes possible mechanisms for implementing the cardioprotective effects of SSO2 therapy, technology and equipment necessary for the application of this technique. In addition, the results of experimental and clinical studies on SSO2 therapy are consecrated. Of note, only one multicentre prospective randomized controlled trial with uniform randomization was performed. Thus, the use of this technology is limited by the use a commercial equipment.

TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion.

Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion injury, including severe cerebral edema and hemorrhagic transformation. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve functional outcomes in animal models of early stroke reperfusion. In this study, we examined the role of M4P in a clinically relevant rat model of delayed stroke reperfusion in which the left middle cerebral artery was occluded for 7 h. To mimic the clinical scenario, M4P or control IgG was administered 1 h before recanalization. Immunostaining showed that M4P treatment improved vascular morphology after stroke. Evans blue extravasation demonstrated attenuated vascular leakage following M4P treatment. With better vascular integrity, cerebral perfusion was improved, leading to a reduction of infarct volume and animal mortality rate. Functional outcome was evaluated by the Rotarod test. As more animals with severe injuries died during the test in the control IgG group, we observed no difference in functional outcomes in the surviving animals. In conclusion, we identified the potential of TRPM4 blocking antibody M4P to ameliorate vascular injury during delayed stroke reperfusion. If combined with reperfusion therapy, M4P has the potential to improve current stroke management.

Protective role of chronic beta-blocker intake against the appearance of complex ventricular arrhythmias in acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Although the presence of ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) in the context of acute coronary syndromes (ACS) has decreased in the era of early reperfusion, their occurrence may lead to fatal consequences. However, clear predisposing or protective factors have not been identified yet. Purpose Our purpose is to describe the prevalence of ventricular arrhythmias before reperfusion treatment in a population of patients hospitalized due to ACS, as well as the possible protective role of chronic intake of beta-blockers, among other factors. Material and methods Retrospective, single-center and observational registry of patients admitted to a Coronary Care Unit from July 2011 to September 2022 with a diagnosis of ACS. The baseline characteristics were described, as well as factors related to diagnosis and treatment. A multivariate analysis was performed to study possible predictors of arrhythmic events. Results A total of 3123 patients diagnosed with ACS were included. 682 patients (21.8%) had beta- blockers as a chronic treatment and 201 patients (7.1%) presented ventricular arrhythmias. In Table 1 we can see the baseline characteristics of both groups, as well as the differences between them. Previous intake of beta-blockers was associated with a lower incidence of ventricular arrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) (11% vs 6%, p 0.002), while no differences were observed between patients without ST-segment elevation myocardial infarction (NSTEMI) (2.3% vs 1.6%, p = 0.435). As shown in the multivariate analysis (Table 2), prior intake of beta-blockers turned out to be a protective factor against the development of ventricular arrhythmias, while ST elevation and worse initial Killip were risk factors. Conclusion Chronic intake of beta-blockers could be a protective factor against the development of ventricular arrhythmias before revascularization in patients diagnosed with acute coronary syndrome, specially those with STEMI.

A case of early reperfusion of celiac artery for type A acute aortic dissection with malperfusion

Malperfusion of the celiac artery alone, with acute aortic dissection, rarely requires early intervention. A 57-year-old woman had thrombosed type A acute aortic dissection with celiac malperfusion, for which total arch replacement was performed after percutaneous balloon angioplasty of the celiac artery. The endovascular treatment minimized extensive hepatic infarction, which saved the patient's life.

S100-A8/A9 activated TLR4 in renal tubular cells to promote ischemia-reperfusion injury and fibrosis.

Renal ischemia/reperfusion injury (IRI) is a significant clinical problem without effective therapy. Unbiased omics approaches may reveal key renal mediators to initiate IRI. S100-A8/A9 was identified as the most significantly upregulated gene and protein base on proteomic analysis and RNA sequencing during the early reperfusion stage. S100-A8/A9 levels were significantly increased 1day after transplantation in patients with donation after brain death (DBD). S100-A8/A9 production was associated with CD11b+Ly6G+ CXCR2+ immunocytes infiltration. Administration of S100-A8/A9 blocker ABR238901 significantly alleviates renal tubular injury, inflammatory cell infiltration, and renal fibrosis after renal IRI. Mechanistically, S100-A8/A9 could promote renal tubular cell injury and profibrotic cytokine production via TLR4. In conclusion, our findings found that early activation of S100-A8/A9 in renal IRI and targeting S100-A8/A9 signaling alleviates tubular injury and inhibits inflammatory response and renal fibrosis, which may provide a novel target for the prevention and treatment of acute kidney injury.

Cardioprotective effects of shock wave therapy: A cardiac magnetic resonance imaging study on acute ischemia-reperfusion injury.

Cardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms. We evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing. During ischemia, LVEF decreased in both groups (25 ± 4.8% in controls (p = 0.031), 31.6 ± 3.2% in SW (p = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline (p = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR p = 0.05), close to baseline reference (LR vs. B p = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: ΔT1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while ΔT2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group. In conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50' LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up.

CHA2DS2 - Vasc Score Predict No Reflow Phenomenon in Primary Percutaneous Coronary Intervention

Purpose: ST-Elevation Myocardial Infarction is the most acute manifestation of Coronary artery disease, with substantial morbidity and mortality. Early reperfusion (re-establishing the blood flow in the occluded artery) is the most effective way to preserve the viability of the ischaemic myocardium and limit infarct size. Early diagnosis of STEMI is crucial to initiate appropriate treatment and should ideally be made within 10 minutes of first medical contact. This study aimed to evaluate the CHA2DS2-VASc score as a simple tool for predicting the no-reflow among patients with STEMI who underwent primary percutaneous coronary intervention.&#x0D; Methodology: This was a case-control study which was conducted on 100 patients, diagnosed with acute STEMI and underwent primary PCI, who was admitted to Cardiology Department, Benha University Hospital and National Heart Institute. Patients were classified into two groups, control and no-flow, according to their final angiographic TIMI flow rates resulting from primary PCI. The control group: 78 patients with TIMI flow rate &gt;2. The no-reflow group: 22 patients with TIMI flow rate ≤2, despite mechanical reopening of the infarct-related artery in patients without dissection of the coronary artery.&#x0D; Findings: In this study, LVEF was significantly lower in patients with no-reflow compared to patients with normal TIMI flow (p &lt;0.001), but LVEDV was significantly higher (p =0.01). There was no significant difference in LVESV between patients with no-reflow compared to patients with normal TIMI flow. CHA2DS2VASC score was significantly higher in patients with no-reflow compared to patients with normal TIMI flow (p &lt;0.001). CHA2DS2VASC score is a significant predictor of occurrence of no reflow phenomenon (AUC: 0.689, p =0.006). At a cut off value of ≥ 2it has a sensitivity of 68.2%, specificity of 58.9%, PPV of 31.9% and NPV of 86.8%.&#x0D; Recommendation: The study suggest that the CHA2DS2‑VASc score can be an independent predictor of no‑reflow phenomenon in patients undergoing primary PCI. As a simple and easy‑to‑calculate score, it might be a useful assessment tool to predict no‑reflow phenomenon before primary PCI interventions in patients with STEMI. Thus we recommend using CHA2DS2-VASc score as it is very simple and a quick tool to predict no-reflow before primary PCI