Pathobiology of Myocardial Ischemic Injury—Implications for Pharmacology and Toxicology
Myocardial ischemia is a condition of myocardial impairment, which results
from inadequate delivery of oxygenated blood through the coronary arteries
relative to the metabolic demands of the myocardium (1-6). Thus, ischemic
heart disease, also known as coronary heart disease, involves an imbalance in the
normal integrated function of the coronary vasculature and the myocardium.
The major consequences of acute myocardial ischemia are depressed myocardial
contractile function, arrhythmias, and myocardial necrosis (infarction). The
multiple clinical manifestations of acute myocardial ischemia are referred to as
acute coronary syndrome (ACS), which includes unstable angina pectoris,
acute myocardial infarction (AMI), and sudden cardiac death. Ischemic heart
disease also encompasses stable angina pectoris and chronic ischemic heart dis-
ease. The myocardial response to ischemic injury can be modulated by a number
of biological processes, particularly preconditioning and reperfusion (Table 1).
Therapeutic approaches to ameliorate the natural progression of myocardial
ischemic injury include catheter-based interventions and surgical approaches as
well as pharmacological treatments, which may have toxicological complications.
ROLE OF CORONARY ALTERATIONS IN MYOCARDIAL ISCHEMIA