early reperfusion
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2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ayesheh Enayati ◽  
Aref Salehi ◽  
Mostafa Alilou ◽  
Hermann Stuppner ◽  
Mirali Polshekan ◽  
...  

Abstract Background Our previous study indicated that Potentilla reptans root has a preconditioning effect by its antioxidant and anti-apoptotic effects in an isolated rat heart ischemia/reperfusion (IR) model. In the present study, we investigated the post-conditioning cardio-protective effects of Potentilla reptans and its active substances. Methods The ethyl acetate fraction of P. reptans root (Et) was subjected to an IR model under 30 min of ischemia and 100 min of reperfusion. To investigate the postconditioning effect, Et was perfused for 15 min at the early phase of reperfusion. RISK/SAFE pathway inhibitors, 5HD and L-NAME, were applied individually 10 min before the ischemia, either alone or in combination with Et during the early reperfusion phase. The hemodynamic factors and ventricular arrhythmia were calculated during the reperfusion. Oxidative stress, apoptosis markers, GSK-3β and SGK1 proteins were assessed at the end of experiments. Results Et postconditioning (Etpost) significantly reduced the infarct size, arrhythmia score, ventricular fibrillation incidence, and enhanced the hemodynamic parameters by decreasing the MDA level and increasing expression of Nrf2, SOD and CAT activities. Meanwhile, Etpost increased the BCl-2/BAX ratio and decreased Caspase-3 expression. The cardioprotective effect of Etpost was abrogated by L-NAME, Wortmannin (a PI3K/Akt inhibitor), and AG490 (a JAK/STAT3 inhibitor). Finally, Etpost reduced the expression of GSK-3β and SGK1 proteins pertaining to the IR group. Conclusion P. reptans reveals the post-conditioning effects via the Nrf2 pathway, NO release, and the RISK/SAFE pathway. Also, Etpost decreased apoptotic indexes by inhibiting GSK-3β and SGK1 expressions. Hence, our data suggest that Etpost can be a suitable natural candidate to protect cardiomyocytes during reperfusion injury.


2021 ◽  
Vol 17 ◽  
Author(s):  
Behnam N Tehrani ◽  
Abdulla A Damluji ◽  
Wayne B Batchelor

: Despite advances in early reperfusion and a technologic renaissance in the space of mechanical circulatory support (MCS), cardiogenic shock (CS) remains the leading cause of in-hospital mortality following acute myocardial infarction (AMI). Given the challenges inherent to conducting adequately powered randomized controlled trials in this time-sensitive, hemodynamically complex, and highly lethal syndrome, treatment recommendations have been derived from AMI patient without shock. In this review, we aimed to (1) examine the pathophysiology and the new classification system for CS; (2) provide a comprehensive evidence-based review for best practices for interventional management of AMI-CS in the cardiac catheterization laboratory; and (3) highlight the concept of how frailty and geriatric syndromes can be integrated in the decision process and where medical futility lies in the spectrum of AMI-CS care. Management strategies in the cardiac catheterization laboratory for CS include optimal vascular access, periprocedural antithrombotic therapy, culprit lesion versus multi-vessel revascularization, selective utilization of hemodynamic MCS tailored to individual shock hemometabolic profiles, and management of cardiac arrest. Efforts to advance clinical evidence for patients with CS should be concentrated on (1) the coordination of multi-center registries; (2) development of pragmatic clinical trial designed to evaluate innovative therapies; (3) establishment of multidisciplinary care models that will inform quality care and improve clinical outcomes.


Neurology ◽  
2021 ◽  
Vol 97 (20 Supplement 2) ◽  
pp. S115-S125
Author(s):  
Rashi Krishnan ◽  
William Mays ◽  
Lucas Elijovich

Multiple randomized clinical trials have supported the use of mechanical thrombectomy (MT) as standard of care in the treatment of large vessel occlusion acute ischemic stroke. Optimal outcomes depend not only on early reperfusion therapy but also on post thrombectomy care. Early recognition of post MT complications including reperfusion hemorrhage, cerebral edema and large space occupying infarcts, and access site complications can guide early initiation of lifesaving therapies that can improve neurologic outcomes. Knowledge of common complications and their management is essential for stroke neurologists and critical care providers to ensure optimal outcomes. We present a review of the available literature evaluating the common complications in patients undergoing MT with emphasis on early recognition and management.


Author(s):  
Kishal Lukhna ◽  
Derek J. Hausenloy ◽  
Abdelbagi Sidahmed Ali ◽  
Abdullah Bajaber ◽  
Alistair Calver ◽  
...  

Abstract Purpose Despite evidence of myocardial infarct size reduction in animal studies, remote ischaemic conditioning (RIC) failed to improve clinical outcomes in the large CONDI-2/ERIC-PPCI trial. Potential reasons include that the predominantly low-risk study participants all received timely optimal reperfusion therapy by primary percutaneous coronary intervention (PPCI). Whether RIC can improve clinical outcomes in higher-risk STEMI patients in environments with poor access to early reperfusion or PPCI will be investigated in the RIC-AFRICA trial. Methods The RIC-AFRICA study is a sub-Saharan African multi-centre, randomized, double-blind, sham-controlled clinical trial designed to test the impact of RIC on the composite endpoint of 30-day mortality and heart failure in 1200 adult STEMI patients without access to PPCI. Randomized participants will be stratified by whether or not they receive thrombolytic therapy within 12 h or arrive outside the thrombolytic window (12–24 h). Participants will receive either RIC (four 5-min cycles of inflation [20 mmHg above systolic blood pressure] and deflation of an automated blood pressure cuff placed on the upper arm) or sham control (similar protocol but with low-pressure inflation of 20 mmHg and deflation) within 1 h of thrombolysis and applied daily for the next 2 days. STEMI patients arriving greater than 24 h after chest pain but within 72 h will be recruited to participate in a concurrently running independent observational arm. Conclusion The RIC-AFRICA trial will determine whether RIC can reduce rates of death and heart failure in higher-risk sub-optimally reperfused STEMI patients, thereby providing a low-cost, non-invasive therapy for improving health outcomes.


Author(s):  
Islam El Malky ◽  
Ali Hendi ◽  
Hazem Abdelkhalek

Introduction : BAO (basilar artery occlusion) is well known by catastrophic outcomes whether death or disability in approximately 70 %. 1 Thrombectomy as an intervention in large vessel occlusion of anterior proximal circulation was approved after multiple RCTs and meta‐analyses. 2 In spite of two RCTs that appeared lately, there is still uncertainty about the effect of thrombectomy in BAO. 9, 10 Our study aims to report the outcome of BAO, as a further clue of MT effectiveness in BAO and variables affecting good outcome and mortality rate. Methods : We retrospectively collected the clinical and radiological data of 30 BAO patients treated in our center between 2016 and 2020. There is no limitation as regard age or presenting NIHHS. Twenty‐two patients who came to the emergency within 4.5 hours had I.V. thrombolytic therapy (73.3%). A favorable clinical outcome was considered if mRS ≤ 2. Angioplasty, stenting, or I.A thrombolysis were used as a rescue treatment. Symptomatic intracranial hemorrhage within two days after the initiation of treatment and mortality at 90 days were reported. The radiological outcome was assessed by modified Thrombolysis in Cerebral Infarction (mTICI) score where mTICI ≥ 2b or 3 at the end of the intervention was considered a favorable radiological result. Multiple variables were tested for their effect on favorable clinical outcomes and mortality (Table 1). Results : Among 30 patients, the mean age was 61.23 ± 16.81 years; 20/30 (66.7%) male. A favorable functional outcome was achieved in (40.7%). Successful revascularization was achieved in 26 patients (86.7 %). Four patients had procedural complications (13.3%). Symptomatic intracranial hemorrhage occurred in three cases (11%) and mortality at 90 days was 11 patients (36.7 %). The presenting NIHSS is the only predictor of mortality and the optimal cut‐off value for death was 15 with AUC = 0.758 (sensitivity 91 % and specificity 59%) and p‐value = 0.02. TOR (time of onset to recanalization) had no effect on the clinical outcome which is controversy with the paradigm of early reperfusion leading to a good outcome Conclusions : In spite of two RCSs approved no statistical difference between medical treatment and thrombectomy, thrombectomy is still an effective procedure in real‐world practice in selected cases. The presenting NIHSS is the only predictor of mortality in our studies. More studies are warranted to discover other predictors of BAO thrombectomy outcome to improve case selection and avoid futile recanalization.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xinye Li ◽  
Ning Ma ◽  
Juping Xu ◽  
Yanchi Zhang ◽  
Pan Yang ◽  
...  

Ischemia-reperfusion (I/R) is a pathological process that occurs in many organs and diseases. Reperfusion, recovery of blood flow, and reoxygenation often lead to reperfusion injury. Drug therapy and early reperfusion therapy can reduce tissue injury and cell necrosis caused by ischemia, leading to irreversible I/R injury. Ferroptosis was clearly defined in 2012 as a newly discovered iron-dependent, peroxide-driven, nonapoptotic form of regulated cell death. Ferroptosis is considered the cause of reperfusion injury. This discovery provides new avenues for the recognition and treatment of diseases. Ferroptosis is a key factor that leads to I/R injury and organ failure. Given the important role of ferroptosis in I/R injury, there is considerable interest in the potential role of ferroptosis as a targeted treatment for a wide range of I/R injury-related diseases. Recently, substantial progress has been made in applying ferroptosis to I/R injury in various organs and diseases. The development of ferroptosis regulators is expected to provide new opportunities for the treatment of I/R injury. Herein, we analytically review the pathological mechanism and targeted treatment of ferroptosis in I/R and related diseases from the perspectives of myocardial I/R injury, cerebral I/R injury, and ischemic renal injury.


2021 ◽  
Author(s):  
Ruduwaan Salie ◽  
Erna Marais ◽  
Amanda Lochner

Abstract β3-AR activation contributes partly or may be solely responsible for ensuing cardiac damage in myocardial ischaemia or heart failure. This would largely depend on disease stage, severity, experimental model as well as drug specificities which should be considered when investigating β3-AR pharmacology for potential therapeutic applications. These conceptions largely contribute to the discrepancies of the subsequent role of β3-AR activation in the cardiovascular disease process. The β3-AR delivers a sustained intracellular signal because of its resistance to short term agonist promoted desensitization, making this receptor an ideal target for therapeutic intervention and in this manner protecting the heart from catecholamine overstimulation. The current communication highlights the importance of the cumulative effect of BRL (PerT) treatment, at the end stage of ischaemia as well as BRL (PostT) treatment, at the onset of reperfusion. This undoubtedly illustrate the significance of the end stage of ischaemia as well as the onset of reperfusion in the concept of ischaemia- reperfusion damage and the importance of the application of cardioprotective interventions at these time periods. Subsequently, if cardioprotective regimens are initiated during the late phase of ischaemia and continued into early reperfusion, it is likely that they will enhance protection, especially with longer durations of ischaemia.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Terenicheva ◽  
R M Shakhnovich ◽  
O V Stukalova ◽  
E A Butorova ◽  
S K Ternovoy

Abstract Purpose To investigate the impact of coronary anatomy and pPCI parameters on the most prognostically significant MRI measures of acute MI with ST segment elevation (MVO, infarct size). Methods The study included 52 patients with STEMI and primary percutaneous coronary intervention (pPCI) of infarct-related arteries (IRA). On Days 3–7 contrast-enhanced cardiac MRI was done. Tissue analysis of scans was performed evaluating infarct size, presence and size of MVO. Results The study included 52 patients with first STEMI within <48 hours of onset. All patients urgently underwent pPCI for reperfusion. Patients were divided into 2 groups separated by the median time to reperfusion treatment (3 hours). There were no significant differences between groups in MRI-measured EF (In the group with later pPCI (>3 hours of symptom onset EF was 49.0±11.0%, and in the comparator group – 45.7±10.5%, p=0,2). MRI-measured infarct size was significantly higher in the group where pPCI was done >3 hours of symptom onset: 18.1±1.7% of the LV mass, compared to the early reperfusion group – 10.9±1.9% (p=0.009). MVO magnitude was also higher in the later pPCI group (2.6±0.64% vs 0.03±0.3% in the comparator group), (p<0,027). Correlation analysis also revealed a reliable relationship between IS and time to reperfusion (R 0.381, p=0.006). LAD lesions were associated with higher infarct size values (p=0.02) and higher risk of MVO (odds ratio 2.9, CI 0.83–10.0, p=0.03). Complete occlusion of IRA was associated with higher IS (16,97±3.3 vs 12.05±1.4, p=0.02). There was no reliable correlations between IRA patientcy and MVO magnitude (p=0.7). Conclusions In this study pPCI timing, in groups of below and more than 3 hours after symptom onset, had no significant impact on EF, as determined by MRI. However, pPCI timing exceeding 3 hours significantly influenced infarct size, the occurrence and magnitude of microvascular obstruction. LAD being the IRA was associated with larger IS, higher risks of MVO development. Patient IRA was associated with smaller IS as determined by MRI. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Healthcare Russian Federation


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Toledo Aleman ◽  
H Gonzalez-Pacheco ◽  
J Sanchez-Nieto ◽  
R Gopar-Nieto ◽  
D Sierra-Lara ◽  
...  

Abstract Background The current paradigm in the treatment of acute coronary syndromes classifies patients according to the presence of persistent ST-segment elevation as a potential marker of total coronary thrombosis, in whom immediate fibrinolysis or primary PCI is appropriate. However, patients with NSTEMI may present with a total acute thrombotic coronary occlusion and may not be detected by this approach, therefore precluding the benefits of early reperfusion strategies. Purpose To identify the prevalence of total thrombotic occlusion elicited by coronary angiography in patients with NSTEMI, and to analyze their baseline characteristics and in-hospital mortality. Methods Retrospective cohort study including consecutive patients admitted with NSTEMI in a single center over a 15-year period. Patients with coronary angiography were further classified in three groups: patients with a total angiographic coronary thrombotic occlusion (TIMI thrombus V), patients with subtotal coronary thrombus (TIMI thrombus I–IV) and patients without angiographic thrombus. Baseline characteristics and in-hospital outcomes were compared among the three groups. Results A total of 4216 of NSTEMI patients were admitted within the study period, of whom 3191 underwent coronary angiography and constituted in the final analytic sample. In 211 patients (6.6%) a TIMI thrombus V was found. Table 1 summarizes the main characteristics among the three groups. In the group of patients with total thrombotic occlussion, a higher proportion were male, were more prone to be current smokers, had a lower prevalence of major cardiovascular risk factors and had suffered less cardiovascular events at enrollment. During hospital follow-up, 15 (7.1%) patients within the total thrombus group, 14 (4.3%) patients within the subtotal thrombus group and 112 (4.2%) patients within the no-thrombus group died. No statistically significant differences in hospital mortality were noted when comparing total thrombotic occlusion vs. no thrombus (HR 1.69, 95% CI 0.94–3.01, p=0.07) (Figure 1). Conclusions In our study, 6.6% of the patients with NSTEMI presented an acute total thrombotic occlusion in coronary angiography. Patients with total thrombotic occlusion showed a different risk-factor profile and a similar in-hospital mortality when compared with non-total thrombus or no thrombus. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Ignacio Chavez National Heart Institute, Mexico City, Mexico Table 1. Baseline characteristics Figure 1. In-hospital mortality


2021 ◽  
Vol 50 (9) ◽  
pp. 671-678
Author(s):  
Zhenghong Liu ◽  
Mian Jie Lim ◽  
Pin Pin Pek ◽  
Aaron Sung Lung Wong ◽  
Kenneth Boon Kiat Tan ◽  
...  

ABSTRACT Introduction: Early reperfusion of ST-segment elevation myocardial infarction (STEMI) results in better outcomes. Interventions that have resulted in shorter door-to-balloon (DTB) time include prehospital cardiovascular laboratory activation and prehospital electrocardiogram (ECG) transmission, which are only available for patients who arrive via emergency ambulances. We assessed the impact of mode of transport on DTB time in a single tertiary institution and evaluated the factors that affected various components of DTB time. Methods: We conducted a retrospective cohort study using registry data of patients diagnosed with STEMI in the emergency department (ED) who underwent primary percutaneous coronary intervention. We compared patients who arrived by emergency ambulances with those who came via their own transport. The primary study end point was DTB, defined as the earliest time a patient arrived in the ED to balloon inflation. As deidentified data was used, ethics review was waived. Results: A total of 321 patients were included for analysis after excluding 7 with missing data. The mean age was 61.4±11.4 years old with 49 (15.3%) females. Ninety-nine (30.8%) patients arrived by emergency ambulance. The median DTB time was shorter for patients arriving by ambulance versus own transport (52min, interquartile range [IQR] 45–61 vs 67min, IQR 59–74; P<0.001), with shorter door-to-ECG and door-to-activation time. Conclusion: Arrival via emergency ambulance was associated with a decreased DTB for STEMI patients compared to arriving via own transport. There is a need for public education to increase the usage of emergency ambulances for suspected heart attacks to improve outcomes. Keywords: Cardiovascular lab activation, door-to-balloon time, emergency ambulance, primary PCI, STEMI


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