chapter  2
40 Pages

Pathobiology of Myocardial Ischemic Injury—Implications for Pharmacology and Toxicology

ByL. Maximilian Buja

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