68 Myocardial Apoptosis for the Nuclear Physician Gurusher S. Panjrath, Diwakar Jain Division of Cardiology, Drexel University College of Medicine, Philadelphia, PA, USA N uclear imaging provides a unique opportunity to image various biological processes, receptor functions and molecular interactions in various organ systems in intact animals and humans under various physiological conditions. These techniques have enhanced our understanding of pathophysiology of various disease processes. In the last few years, myocardial apoptosis has attracted a lot of interest by the clinician, biomedical researcher and imaging scientist, because of its potential for enhancing our understanding of congestive heart failure (CHF) and its role in acute ischemia/reperfusion injury, plaque rupture and acute coronary events and thus development of strategies for their prevention and possible reversal. Key words: apoptosis, nuclear imaging, annexin V Apoptosis: a constructive or destructive path? Apoptosis is an evolutionary conserved mechanism of genetically controlled cell suicide first described by Kerr et al in 1972 (1). Apoptosis is a form of cell death that involves discrete genetic and molecular programs. The cells undergoing apoptosis undergo a series of morphological changes. In adults this occurs in conjunction with physiologic events such as menstrual cycle, clearing activated immune cells after their role is over and shedding of epithelium in the gastrointestinal tract. Homeostasis is maintained through a delicate balance between cell proliferation and cell death. This type of balance allows for the elimination of cells that have been produced in excess, have sustained genetic damage or have served their purpose. Apoptosis has been implicated in the etiology and pathophysiology of a wide range of human diseases by virtue of its excess or its deficiency. Apoptosis plays a crucial role in the cardiovascular system. Among stimuli responsible for inducing apoptosis in myocytes are ischemia/reperfusion, pressure overload, neurohumoral factors (e.g. catecholamines), and toxins (e.g. TNF-a, chemotherapeutic drugs etc). Apoptosis plays a critical role during heart development including formation of septal, valvular and vascular structures (2). Abnormalities in the regulation of apoptosis during embryogenesis may result in congenital heart disease such as WPW syndrome (inadequate apoptosis of accessory muscle bands below atria and ventricle) (3), heart block (excessive apoptosis of cardiac conduction pathway) (3, 4). Apoptosis plays a role in wide range of heart diseases in adults including myocardial infarction, myocarditis, cardiomyopathies, transplant rejection and congestive heart failure. Apoptosis versus Necrosis Cell death can occur through two very distinctive processes: necrosis and apoptosis (Figure 1). Necrosis occurs in the setting of sudden uncontrolled injury such as direct tissue trauma, chemical and thermal injury. These result in loss of cell membrane integrity resulting in cell swelling. The intracellular proteins are denatured and DNA is damaged in a non-specific manner. Energy production stops. Intracellular proteins of small size can escape into the circulation. Eventually the cell bursts releasing a lot of debris in the intercellular compartment. This attracts leukocytes and macrophages and Correspondence to: Diwakar Jain, MD, Professor of Medicine, Director of Nuclear Cardiology 245 N.15 th Street, MS 470, Philadelphia, PA 19102-1192 Telephone: 215-762-4990 Fax: 215-762-1525 E-mail: diwakar.jain@drexel.edu IJNM, 19(3): 68-74, 2004