Lethal reperfusion injury is a paradoxical type of myocardial injury caused by the restoration of coronary blood flow after an ischemic episode. This review focuses on the mechanisms of the injury, on attempts to protect the heart against it, and on promising new approaches to cardioprotection during percutaneous coronary intervention.

Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI.

Background— Whether alterations in mitochondrial morphology affect the susceptibility of the heart to ischemia/reperfusion injury is unknown. We hypothesized that modulating mitochondrial morphology protects the heart against ischemia/reperfusion injury. Methods and Results— In response to ischemia, mitochondria in HL-1 cells (a cardiac-derived cell line) undergo fragmentation, a process that is dependent on the mitochondrial fission protein dynamin-related protein 1 (Drp1). Transfection of HL-1 cells with the mitochondrial fusion proteins mitofusin 1 or 2 or with Drp1 _K38A , a dominant-negative mutant form of Drp1, increased the percentage of cells containing elongated mitochondria (65±4%, 69±5%, and 63±6%, respectively, versus 46±6% in control: n=80 cells per group; P <0.05), decreased mitochondrial permeability transition pore sensitivity (by 2.4±0.5-, 2.3±0.7-, and 2.4±0.3-fold, respectively; n=80 cells per group; P <0.05), and reduced cell death after simulated ischemia/reperfusion injury (11.6±3.9%, 16.2±3.9%, and 12.1±2.9%, respectively, versus 41.8±4.1% in control: n=320 cells per group; P <0.05). Treatment of HL-1 cells with mitochondrial division inhibitor-1, a pharmacological inhibitor of Drp1, replicated these beneficial effects. Interestingly, elongated interfibrillar mitochondria were identified in the adult rodent heart with confocal and electron microscopy, and in vivo treatment with mitochondrial division inhibitor-1 increased the percentage of elongated mitochondria from 3.6±0.5% to 14.5±2.8% ( P =0.023). Finally, treatment of adult murine cardiomyocytes with mitochondrial division inhibitor-1 reduced cell death and inhibited mitochondrial permeability transition pore opening after simulated ischemia/reperfusion injury, and in vivo treatment with mitochondrial division inhibitor-1 reduced myocardial infarct size in mice subject to coronary artery occlusion and reperfusion (21.0±2.2% with mitochondrial division inhibitor-1 versus 48.0±4.5% in control; n=6 animals per group; P <0.05). Conclusion— Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury, suggesting a novel pharmacological strategy for cardioprotection.

The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.

Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today’s anthracycline-treated cancer patients may become tomorrow’s cardiac patient.

Acute myocardial infarction (AMI) and the heart failure that often follows, are major causes of death and disability worldwide. As such, new therapies are required to limit myocardial infarct (MI) size, prevent adverse left ventricular (LV) remodeling, and reduce the onset of heart failure following AMI. The inflammatory response to AMI, plays a critical role in determining MI size, and a persistent pro-inflammatory reaction can contribute to adverse post-MI LV remodeling, making inflammation an important therapeutic target for improving outcomes following AMI. In this article, we provide an overview of the multiple players (and their dynamic roles) involved in the complex inflammatory response to AMI and subsequent LV remodeling, and highlight future opportunities for targeting inflammation as a therapeutic strategy for limiting MI size, preventing adverse LV remodeling, and reducing heart failure in AMI patients.