Myocardial hypothermia induced after reperfusion does not prevent adverse left ventricular remodeling nor improve cardiac function.

Aims: The purpose of the study was to determine whether late therapeutic hypothermia (LTH), administered after reperfusion, could prevent adverse left ventricular (LV) remodeling and improve cardiac function in the rat myocardial ischemia/reperfusion model.

Main Methods: Rats were randomized to normothermia (n = 10) or LTH (initiated at 1 min after coronary artery reperfusion, n = 10) and subjected to 30 min of coronary occlusion followed by 6 weeks of reperfusion. Hypothermia was induced by pumping cold saline over the anterior surface of the LV until the temperature cooled to <32 °C.

Improved Long-term Survival with Remote Limb Ischemic Preconditioning in a Rat Fixed-Pressure Hemorrhagic Shock Model.

Purpose: We investigated whether bilateral, lower limb remote ischemic preconditioning (RIPC) improved long-term survival using a rat model of hemorrhagic shock/resuscitation.

Methods: Rats were anesthetized, intubated and ventilated, and randomly assigned to RIPC, induced by inflating bilateral pressure cuffs around the femoral arteries to 200 mmHg for 5 min, followed by 5-min release of the cuffs (repeated for 4 cycles), or control group (cuffs were inflated to 30 mmHg). Hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure of 30 mmHg for 30 min, followed by 30 min of resuscitation with shed blood.

New and revisited approaches to preserving the reperfused myocardium.

Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium.

Cardioprotection: Where to from here?

The size of the myocardial infarction remains an important therapeutic target, because heart attack size correlates with mortality and heart failure. In this era, myocardial infarct size is reduced primarily by timely reperfusion of the infarct related coronary artery. Whereas numerous pre-clinical studies have shown that certain pharmacologic agents and therapeutic maneuvers reduce myocardial infarction size greater than reperfusion alone, very few of these therapies have translated to successful clinical trials or standard clinical use.

Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size.

Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart.

Aims: We have observed that Bendavia, a mitochondrial-targeting peptide that binds the phospholipid cardiolipin and stabilizes the components of electron transport and ATP generation, improves cardiac function and prevents left ventricular remodeling in a 6week rat myocardial infarction (MI) model. We hypothesized that Bendavia restores mitochondrial biogenesis and gene expression, suppresses cardiac fibrosis, and preserves sarco/endoplasmic reticulum (SERCA2a) level in the noninfarcted border zone of infarcted hearts.

Main Methods: Starting 2h after left coronary artery ligation, rats were randomized to receive Bendavia (3mg/kg/day), water or sham operation.

Rapid Surface Cooling by ThermoSuit System Dramatically Reduces Scar Size, Prevents Post-Infarction Adverse Left Ventricular Remodeling, and Improves Cardiac Function in Rats.

Background: The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model.

Methods And Results: Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes coronary artery occlusion and 6 weeks of reperfusion. For hypothermia therapy, rats were placed into the ThermoSuit apparatus at 2 minutes after the onset of coronary artery occlusion, were taken out of the apparatus when the core body temperature reached 32°C (in ≈8 minutes), and were then allowed to rewarm.

Does sex influence the incidence or severity of reperfusion-induced cardiac arrhythmias?

Unlabelled: Whether sex affects the acute phase of myocardial ischemia in experimental animal models is currently being debated. Our purpose was to determine if sex influences either the incidence or severity of reperfusion-induced arrhythmias resulting from a brief coronary occlusion. Male and female Sprague-Dawley rats were assigned to the study.

Hypothermia in the setting of experimental acute myocardial infarction: a comprehensive review.

A door-to-balloon time of less than 90 minutes is the gold standard for reperfusion therapy to treat acute myocardial infarction (MI). Because 30-day mortality remains ∼ 10%, new methods must be cultivated to limit myocardial injury. Therapeutic hypothermia has long been experimentally used to attenuate myocardial necrosis during MI with promising results, but the treatment has yet to gain popularity among most clinicians.

Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats.

AB We evaluated the post-myocardial infarction (MI) therapeutic effects of Bendavia. Two hours after coronary artery ligation, rats were randomized to receive chronic Bendavia treatment (n = 28) or water (n = 26). Six weeks later, Bendavia significantly reduced scar circumference (39.

Ranolazine treatment for myocardial infarction? Effects on the development of necrosis, left ventricular function and arrhythmias in experimental models.

Ranolazine, an inhibitor of the late current of the cardiac action potential (late I(Na)), is a well established clinical treatment for chronic angina. The late INa in cardiac myocytes also plays an important role in the pathophysiology of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic target to ameliorate consequences of myocardial infarction. In experimental animal models, ranolazine has been shown to reduce myocardial infarct size, improve left ventricular function, decrease ischemia/reperfusion-induced arrhythmias and improve outcome in heart failure.

Dabigatran treatment: effects on infarct size and the no-reflow phenomenon in a model of acute myocardial ischemia/reperfusion.

The no-reflow phenomenon occurs when an epicardial coronary artery is reopened following myocardial infarction, but portions of the intramural microvasculature fail to reperfuse. One potential mechanism for this is the presence of fibrin tactoids. In addition, some recent studies have suggested that dabigatran treatment may be associated with increased incidence of myocardial infarction.

Rapid Induction of Hypothermia by the ThermoSuit System Profoundly Reduces Infarct Size and Anatomic Zone of No Reflow Following Ischemia-Reperfusion in Rabbit and Rat Hearts.

Introduction: Although hypothermia reduces myocardial infarct size, noninvasive and rapid cooling methods are lacking. This study tests the effectiveness of a novel cooling apparatus on myocardial infarct size and no-reflow area in 2 models of coronary artery occlusion (CAO).

Methods And Results: Animals were randomized to normothermic (N) or hypothermic (H) groups after isolation of a proximal coronary artery.

Capsaicin-induced cardioprotection. Is hypothermia or the salvage kinase pathway involved?

Purpose: Topical capsaicin application was shown to reduce infarct size in experimental animal models. We hypothesized that cardioprotective properties of topical capsaicin application could be related to its hypothermic effect.

Methods: In the first arm of the study, anesthetized rats received capsaicin cream (Caps group) or vehicle (Control group, Ctrl) applied either 15 or 30 min prior to a 30-min coronary artery occlusion followed by 2-h reperfusion.

Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia.

We recently showed that Bendavia, a novel mitochondria-targeting peptide, reduced infarction and no-reflow across several experimental models. The purpose of this study was to determine the therapeutic timing and mechanism of action that underlie Bendavia's cytoprotective property. In rabbits exposed to in vivo ischemia/reperfusion (30/180 min), Bendavia administered 20 minutes prior to reperfusion (0.

Delayed treatment with hypothermia protects against the no-reflow phenomenon despite failure to reduce infarct size.

Background: Many studies have shown that when hypothermia is started after coronary artery reperfusion (CAR), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no-reflow. Our aim was to test the effects of hypothermia on no-reflow when initiated close to reperfusion and 30 minutes after reperfusion, times not associated with a protective effect on myocardial infarct size.

Continuous heliox breathing and the extent of anatomic zone of noreflow and necrosis following ischemia/reperfusion in the rabbit heart.

Background: Nitrogen may contribute to reperfusion injury. Some studies have shown that helium as a replacement for nitrogen in breathing gas (heliox) reduces cell necrosis after ischemia/reperfusion when used in a preconditioning fashion (intermittent heliox exposure). Our aim was to test whether heliox, breathed continuously throughout the ischemic and reperfusion periods, reduced necrosis and a marker of reperfusion injury, the no-reflow phenomenon.

The effect of acute versus delayed remote ischemic preconditioning on reperfusion induced ventricular arrhythmias.

Introduction: The effect of remote ischemic preconditioning (RIPC) on arrhythmias in in vivo models is unknown. Our purpose was to determine effects of both acute and delayed RIPC on arrhythmias.

Methods And Results: In the acute protocol anesthetized open chest rats were exposed to 5 minutes of proximal left coronary artery occlusion (CAO) and 10 minutes of reperfusion.

Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide.

Background: Manifestations of reperfusion injury include myocyte death leading to infarction, contractile dysfunction, and vascular injury characterized by the "no-reflow" phenomenon. Mitochondria-produced reactive oxygen species are believed to be centrally involved in each of these aspects of reperfusion injury, although currently no therapies reduce reperfusion injury by targeting mitochondria specifically.

Methods And Results: We investigated the cardioprotective effects of a mitochondria-targeted peptide, Bendavia (Stealth Peptides), across a spectrum of experimental cardiac ischemia/reperfusion models.

Absence of actions of commonly used Chinese herbal medicines and electroacupuncture on myocardial infarct size.

Background: Some studies have suggested that certain Chinese herbal remedies and acupuncture could limit ischemia/reperfusion damage. We sought to determine whether the commonly used single herb Danshen (DS), either alone or in combination with Jiang Xiang (JX), or electroacupuncture (EA) reduces myocardial infarct size.

Methods: An anesthetized rat model of proximal left coronary artery occlusion (30 minutes) and reperfusion (180 minutes) was used to measure infarct size (triphenyltetrazolium chloride) and ischemic risk zone (blue dye technique).

Therapeutic hypothermia for acute myocardial infarction and cardiac arrest.

This report focuses on cardioprotection and describes the advantages and disadvantages of various methods of inducing therapeutic hypothermia (TH) with regard to neuroprotection and cardioprotection for patients with cardiac arrest and ST-segment elevation myocardial infarction (STEMI). TH is recommended in cardiac arrest guidelines. For patients resuscitated after out-of-hospital cardiac arrest, improvements in survival and neurologic outcomes were observed with relatively slow induction of TH.

Mild hypothermia as a cardioprotective approach for acute myocardial infarction: laboratory to clinical application.

In many animal models, mild therapeutic hypothermia is a powerful intervention, reducing myocardial infarct size, reducing the no-reflow phenomenon, and improving healing after infarction. Cooling in these models has been produced by various means including whole-body hypothermia, synchronized hypothermic coronary venous retro-perfusion, heat exchangers, and regional hypothermia targeting the heart alone. However, in humans, the most widely used techniques are surface cooling and cooling by endovascular heat-exchange catheters.