-
Journal of the American College of... Jul 2018Heart failure after an acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a transvalvular...
BACKGROUND
Heart failure after an acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a transvalvular axial-flow pump in the left ventricle and delaying myocardial reperfusion, known as primary unloading, limits infarct size after AMI. The mechanisms underlying the cardioprotective benefit of primary unloading and whether the acute decrease in infarct size results in a durable reduction in LV scar and improves cardiac function remain unknown.
OBJECTIVES
This study tested the importance of LV unloading before reperfusion, explored cardioprotective mechanisms, and determined the late-term impact of primary unloading on myocardial function.
METHODS
Adult male swine were subjected to primary reperfusion or primary unloading after 90 min of percutaneous left anterior descending artery occlusion.
RESULTS
Compared with primary reperfusion, 30 min of LV unloading was necessary and sufficient before reperfusion to limit infarct size 28 days after AMI. Compared with primary reperfusion, primary unloading increased expression of genes associated with cellular respiration and mitochondrial integrity within the infarct zone. Primary unloading for 30 min further reduced activity levels of proteases known to degrade the cardioprotective cytokine, stromal-derived factor (SDF)-1α, thereby increasing SDF-1α signaling via reperfusion injury salvage kinases, which limits apoptosis within the infarct zone. Inhibiting SDF-1α activity attenuated the cardioprotective effect of primary unloading. Twenty-eight days after AMI, primary unloading reduced LV scar size, improved cardiac function, and limited expression of biomarkers associated with heart failure and maladaptive remodeling.
CONCLUSIONS
The authors report for the first time that first mechanically reducing LV work before coronary reperfusion with a transvalvular pump is necessary and sufficient to reduce infarct size and to activate a cardioprotective program that includes enhanced SDF-1α activity. Primary unloading further improved LV scar size and cardiac function 28 days after AMI.
Topics: Animals; Male; Myocardial Infarction; Myocardial Reperfusion; Recovery of Function; Swine; Ventricular Function, Left
PubMed: 30049311
DOI: 10.1016/j.jacc.2018.05.034 -
Experimental Physiology Nov 2021What is the central question of this study? Can remote limb ischaemic conditioning produce cardioprotection in rats with testicular ischaemia-reperfusion injury? What is...
NEW FINDINGS
What is the central question of this study? Can remote limb ischaemic conditioning produce cardioprotection in rats with testicular ischaemia-reperfusion injury? What is the main finding and its importance? Testicular ischaemia-reperfusion (TI/R)-injured rats were predisposed to myocardial reperfusion-induced atrioventricular block. Remote limb ischaemia preconditioning and postconditioning protected TI/R hearts against ischaemia-provoked ventricular arrhythmia and ultimately reduced the incidence of sudden cardiac death, with a possible role of c-Jun N-terminal kinase inhibition and connexin 43 activation.
ABSTRACT
Remote ischaemic conditioning can protect hearts against arrhythmia. Testicular ischaemia-reperfusion (TI/R) injury is associated with electrocardiographic abnormalities. We investigated the effect of remote limb ischaemia preconditioning (RIPre) and postconditioning (RIPost) on arrhythmogenesis in TI/R rats, and determined the potential role of c-Jun N-terminal kinase (JNK)/connexin 43 (Cx43) signalling. Rats were randomized to sham-operated, control, TI/R, RIPre and RIPost groups. TI/R rats were more predisposed to myocardial reperfusion-induced atrioventricular block (AVB). RIPre and RIPost reduced the incidence of sudden cardiac death (SCD) or AVB, and duration of ventricular tachyarrhythmias during myocardial reperfusion. RIPre and RIPost decreased myocardial I/R-induced phosphorylation level of JNK, while preserving myocardial Cx43 expression in TI/R rats. Taken together, TI/R rats were predisposed to myocardial reperfusion-induced AVB. RIPre and RIPost protected TI/R hearts against ischaemia-provoked ventricular arrhythmia and ultimately reduced the incidence of SCD by suppressing JNK activation and restoring Cx43 expression.
Topics: Animals; Heart; Ischemia; Ischemic Preconditioning, Myocardial; Myocardial Reperfusion; Myocardium; Rats; Reperfusion Injury
PubMed: 34487401
DOI: 10.1113/EP089289 -
Journal of the American College of... Mar 1991Indications for coronary angioplasty have expanded to include patients with unstable acute ischemic syndromes, severe multivessel coronary artery disease and impaired... (Review)
Review
Indications for coronary angioplasty have expanded to include patients with unstable acute ischemic syndromes, severe multivessel coronary artery disease and impaired left ventricular function. Several mechanical approaches have been developed as adjuncts to high risk coronary angioplasty to improve patient tolerance of coronary balloon occlusion and maintain hemodynamic stability in the event of complications. These percutaneous techniques include intraaortic balloon counterpulsation, anterograde transcatheter coronary perfusion, coronary sinus retroperfusion, cardiopulmonary bypass, Hemopump left ventricular assistance and partial left heart bypass. The intraaortic balloon pump provides hemodynamic support and ameliorates ischemia by decreasing myocardial work; it may be inserted for periprocedural complications or before angioplasty in patients with ischemia or hypotension. Anterograde distal coronary artery perfusion may be accomplished passively through an autoperfusion catheter or by active pumping of oxygenated blood or fluorocarbons through the central lumen of an angioplasty catheter. Synchronized coronary sinus retroperfusion produces pulsatile blood flow via the cardiac veins to the coronary bed distal to a stenosis. Both perfusion techniques limit development of ischemic chest pain and myocardial dysfunction in patients undergoing prolonged balloon inflations. Percutaneous cardiopulmonary bypass provides complete systemic hemodynamic support which is independent of intrinsic cardiac function or rhythm and has been employed prophylactically in very high risk patients before coronary angioplasty or emergently for abrupt closure. These and newer support devices, while associated with significant complications, may ultimately improve the safety of coronary angioplasty and allow its application to those who would otherwise not be candidates for revascularization.
Topics: Angioplasty, Balloon, Coronary; Cardiopulmonary Bypass; Coronary Disease; Emergencies; Equipment Design; Equipment Safety; Heart-Assist Devices; Humans; Myocardial Reperfusion
PubMed: 1993799
DOI: 10.1016/s0735-1097(10)80197-4 -
Current Heart Failure Reports Aug 2018Hibernation is an important and reversible cause of myocardial dysfunction in ischaemic heart failure. (Review)
Review
PURPOSE OF REVIEW
Hibernation is an important and reversible cause of myocardial dysfunction in ischaemic heart failure.
RECENT FINDINGS
Hibernation is an adaptive process that promotes myocyte survival over maintaining contractile function. It is innate to mammalian physiology, sharing features with physiological hibernation in other species. Advanced imaging methods have reasonable accuracy in identifying hibernating myocardium. Novel superior hybrid methods may provide diagnostic potential. New evidence supports the role of surgical revascularisation in ischaemic heart failure, but the role of viability tests in planning such procedures remains unclear. Research to date has exclusively involved patients with ambulatory heart failure: Investigating the role of hibernation in ADHF is a key avenue for the future. Whilst our understanding of hibernation pathophysiology has improved dramatically, the clinical utility of identifying and targeting hibernation remains unclear.
Topics: Echocardiography; Heart Failure; Humans; Magnetic Resonance Imaging, Cine; Myocardial Contraction; Myocardial Reperfusion; Myocardial Stunning; Myocardium
PubMed: 29959688
DOI: 10.1007/s11897-018-0396-6 -
Texas Heart Institute Journal 1994In some patients with acute myocardial infarction, thrombolytic therapy may be limited by its failure to reperfuse the occluded artery, by recurrent ischemia (despite... (Review)
Review
In some patients with acute myocardial infarction, thrombolytic therapy may be limited by its failure to reperfuse the occluded artery, by recurrent ischemia (despite initially successful reperfusion), and by major hemorrhagic complications. Primary coronary angioplasty may circumvent these limitations. This article reviews the results of primary angioplasty reported in patients with myocardial infarction and makes recommendations for its use. The review includes pertinent articles found in the English language literature from July 1987 to July 1993 on MEDLINE. Nonrandomized series of primary angioplasty in acute myocardial infarction have demonstrated high procedural success rates (86% to 99%) and infrequent recurrent ischemia (4%). Two randomized trials comparing primary angioplasty and thrombolytic therapy have shown that primary angioplasty results in lower mortality, less recurrent ischemia, shorter length of hospital stay, and improved left ventricular function. Two other randomized studies have shown little benefit from primary angioplasty on myocardial salvage, recurrent ischemia, or ventricular function. One major limitation of primary angioplasty is that it requires 24-hour availability of a catheterization laboratory and experienced surgical personnel. Primary angioplasty may be the preferred approach in patients with extensive myocardial infarction who have immediate (< 120 min) access to a cardiac catheterization laboratory with experienced personnel. Patients having 1) contraindications to thrombolytic therapy, 2) cardiogenic shock, 3) prior coronary bypass surgery, or 4) "stuttering" onset of pain may also benefit from primary angioplasty. Poor candidates for this procedure are those with a small myocardial infarction, those in whom undue delays in access to a cardiac catheterization facility would be expected, or those with complex coronary anatomy, including left main coronary artery disease.
Topics: Angioplasty, Balloon, Coronary; Cardiac Catheterization; Contraindications; Humans; Myocardial Infarction; Myocardial Reperfusion; Randomized Controlled Trials as Topic; Thrombolytic Therapy
PubMed: 8061539
DOI: No ID Found -
Arquivos Brasileiros de Cardiologia Jul 2021
Topics: Humans; Myocardial Infarction; Myocardial Reperfusion
PubMed: 34320063
DOI: 10.36660/abc.20210426 -
Critical Care (London, England) 2008Myocardial edema is a hallmark of ischemia-reperfusion-related cardiac injury. Ischemia-reperfusion has been shown to result in degradation of the endothelial...
Myocardial edema is a hallmark of ischemia-reperfusion-related cardiac injury. Ischemia-reperfusion has been shown to result in degradation of the endothelial glycocalyx. The glycocalyx is the gel-like mesh of polysaccharide structures and absorped plasma proteins on the luminal side of the vasculature, and in the past decade has been shown to play an important role in protection of the vessel wall, including its barrier properties. Prevention of glycocalyx loss or restoration of a damaged glycocalyx may be a promising therapeutic target during clinical procedures involving ischemia-reperfusion.
Topics: Capillary Leak Syndrome; Endothelium, Vascular; Fibrin Tissue Adhesive; Glycocalyx; Humans; Myocardial Reperfusion; Myocardial Reperfusion Injury
PubMed: 18638363
DOI: 10.1186/cc6939 -
The Journal of Extra-corporeal... Jun 2015Goal-directed therapy is a patient care strategy that has been implemented to improve patient outcomes. The strategy includes aggressive patient management and... (Review)
Review
Goal-directed therapy is a patient care strategy that has been implemented to improve patient outcomes. The strategy includes aggressive patient management and monitoring during a period of critical care. Goal-directed therapy has been adapted to perfusion and has been designated goal-directed perfusion (GDP). Since this is a new concept in perfusion, the purpose of this study is to review goal-directed therapy research in other areas of critical care management and compare that process to improving patient outcomes following cardiopulmonary bypass. Various areas of goaldirected therapy literature were reviewed, including fluid administration, neurologic injury, tissue perfusion, oxygenation, and inflammatory response. Data from these studies was compiled to document improvements in patient outcomes. Goal-directed therapy has been demonstrated to improve patient outcomes when performed within the optimal time frame resulting in decreased complications, reduction in hospital stay, and a decrease in morbidity. Based on the successes in other critical care areas, GDP during cardiopulmonary bypass would be expected to improve outcomes following cardiac surgery.
Topics: Cardiopulmonary Bypass; Delivery of Health Care; History, 20th Century; History, 21st Century; Humans; Myocardial Reperfusion; Treatment Outcome
PubMed: 26405356
DOI: No ID Found -
EuroIntervention : Journal of EuroPCR... Dec 2017Hypothermia reduces reperfusion injury and infarct size in animal models of acute myocardial infarction if started before reperfusion. Human studies have not confirmed... (Clinical Trial)
Clinical Trial
AIMS
Hypothermia reduces reperfusion injury and infarct size in animal models of acute myocardial infarction if started before reperfusion. Human studies have not confirmed benefit, probably due to insufficient myocardial cooling and adverse systemic effects. This study sought to assess the safety and feasibility of a novel method for selective, sensor-monitored intracoronary hypothermia.
METHODS AND RESULTS
Ten patients undergoing primary percutaneous coronary intervention (PPCI) were included. Saline at room temperature was administered distal to the culprit lesion through an inflated overthe- wire balloon (OTWB) in order to cool the endangered myocardium for 10 minutes (occlusion phase). Next, the OTWB was deflated and cooling continued with saline at 4°C for another 10 minutes (reperfusion phase). A sensor-tipped temperature wire in the distal coronary artery allowed titration of the infusion rate to achieve the desired coronary temperature (6°C below body temperature). Target coronary temperature was achieved within 27 seconds (median; IQR 21-46). Except for two patients with inferior wall infarction experiencing transient conduction disturbances, no side effects occurred. Systemic temperature remained unchanged. Finally, PPCI was performed as per routine.
CONCLUSIONS
Selective hypothermia of the infarct area by intracoronary infusion of saline provides a novel method to reduce coronary temperature quickly and guarantee local myocardial hypothermia. In anterior wall myocardial infarctions, the protocol appeared safe, without serious haemodynamic or systemic side effects. In inferior wall myocardial infarctions, transient conduction abnormalities of short duration occurred. Potentially, selective intracoronary delivery of hypothermia could attenuate reperfusion injury caused by traditional PPCI.
Topics: Aged; Feasibility Studies; Female; Humans; Hypothermia, Induced; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Pilot Projects; Sodium Chloride
PubMed: 28829744
DOI: 10.4244/EIJ-D-17-00240 -
International Journal of Cardiology Jan 2016Adenosine administered as an adjunct to reperfusion can reduce coronary no-reflow and limit myocardial infarct (MI) size in ST-segment elevation myocardial infarction... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adenosine administered as an adjunct to reperfusion can reduce coronary no-reflow and limit myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients. Whether adjunctive adenosine therapy can improve clinical outcomes in reperfused STEMI patients is not clear and is investigated in this meta-analysis of 13 randomized controlled trials (RCTs).
METHODS
We performed an up-to-date search for all RCTs investigating adenosine as an adjunct to reperfusion in STEMI patients. We calculated pooled relative risks using a fixed-effect meta-analysis assessing the impact of adjunctive adenosine therapy on major clinical endpoint including all-cause mortality, non-fatal myocardial infarction, and heart failure. Surrogate markers of reperfusion were also analyzed.
RESULTS
13 RCTs (4273 STEMI patients) were identified and divided into 2 subgroups: intracoronary adenosine versus control (8 RCTs) and intravenous adenosine versus control (5 RCTs). In patients administered intracoronary adenosine, the incidence of heart failure was significantly lower (risk ratio [RR] 0.44 [95% CI 0.25-0.78], P=0.005) and the incidence of coronary no-reflow was reduced (RR for TIMI flow<3 postreperfusion 0.68 [95% CI 0.47-0.99], P=0.04). There was no difference in heart failure incidence in the intravenous adenosine group but most RCTs in this subgroup were from the thrombolysis era. There was no difference in non-fatal MI or all-cause mortality in both subgroups.
CONCLUSION
We find evidence of improved clinical outcome in terms of less heart failure in STEMI patients administered intracoronary adenosine as an adjunct to reperfusion. This finding will need to be confirmed in a large adequately powered prospective RCT.
Topics: Adenosine; Electrocardiography; Humans; Myocardial Infarction; Myocardial Reperfusion; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 26402450
DOI: 10.1016/j.ijcard.2015.09.005