Frank W. Sellke

By Sarah R. Aldosari, Maan A. Awad, Frank W. Sellke and Md. Ruhul Abid

For decades, elevated levels of reactive oxygen species (ROS) have been associated with the pathogenesis of cardiovascular diseases (CVD), including myocardial ischemia and infarction (MI). However, several large clinical trials failed to demonstrate beneficial outcomes in response to the global reduction of ROS in patients with underlying CVD. Recent studies from our and other labs showed that it is rather a critical balance between mitochondrial and cytosolic ROS than total ROS levels which determines resilience of coronary endothelial cells (EC). Here, we will discuss published and unpublished work that has helped elucidate the molecular mechanisms by which subcellular ROS levels, duration and localization modulate metabolic pathways, including glycolysis and oxidative phosphorylation, energy production and utilization, and dNTP synthesis in EC. These redox-regulated processes play critical roles in providing resilience to EC which in turn help protect existing coronary vessels and induce coronary angiogenesis to improve post-MI recovery of cardiac function.

Part of the book: Oxidoreductase

By Shawn Kant, Frank W. Sellke and Jun Feng

Potassium homeostasis affects cardiac rhythm and contractility, along with vascular reactivity and vascular smooth muscle proliferation. This chapter will focus on potassium dynamics during and after cardiac surgery involving cardioplegic arrest and cardiopulmonary bypass (CPB). Hyperkalemic, hypothermic solutions are frequently used to induce cardioplegic arrest and protect the heart during cardiac surgery involving CPB. Common consequences of hyperkalemic cardioplegic arrest and reperfusion include microvascular dysfunction involving several organ systems and myocardial dysfunction. Immediately after CPB, blood potassium levels often drop precipitously due to a variety of factors, including CPB -induced electrolyte depletion and frequent, long-term administration of insulin during and after surgery. Meanwhile, some patients with pre-existing kidney dysfunction may experience postoperative hyperkalemia following cardioplegia. Any degree of postoperative hyper/hypokalemia significantly elevates the risk of cardiac arrythmias and subsequent myocardial failure. Therefore, proper management of blood potassium levels during and after cardioplegia/CPB is crucial for optimizing patient outcomes following cardiac surgery.

Part of the book: Potassium in Human Health

By Katherine Zhong, Shawn Kant, Frank Sellke and Jun Feng

Extensive evidence indicates that small-conductance Ca2+-activated K+ channels (SK channels) help regulate cardiac rhythm and myocardial function in physiological and pathophysiological conditions. This chapter will begin by discussing the basic physiology of SK channel expression, localization, and activation under normal conditions, before proceeding to address the impact of SK channel dysfunction on a variety of cardiac pathologies including atrial fibrillation (AF), ventricular arrhythmias (VA), cardiac hypertrophy/heart failure (HF) and myocardial ischemia/reperfusion (IR) injury. The critical role of aberrant SK channel regulation will also be discussed to establish unifying mechanisms of SK channel pathology across these different conditions. Several animal model and human tissue experiments suggest that pharmacologic modulation of SK channel function may be beneficial in controlling AF, VA, cardiomyopathy and myocardial IR injury. Therefore, targeting SK channels may represent a promising new therapeutic avenue for treating a variety of cardiovascular disease states.

Part of the book: Ion Transporters