I. Chemotherapeutic Agents
II. Cardiac Damage from Anthracyclines
III. Cyclophosphamide
IV. 5-Fluorouracil
GLOSSARY
afterload arterial impedance, restriction of blood flow delivered from the left ventricle; force against which the myocardium contracts in systole; a major determinant of wall stress.
endocardium internal lining of the heart.
heart failure a failure of the heart to pump sufficient blood from the chambers into the aorta; inadequate supply of blood reaches organs and tissues.
hypotension marked decrease in blood pressure, usually less than 95 mmHg.
ischemia temporary lack of blood and oxygen to an area of cells, for example, the heart muscle, usually due to severe obstruc¬tion of the artery supplying blood to this area of cells.
metastases distant spread of cancer to various organs.
myopericarditis specific or nonspecific infection of both the pericardium and the myocardium.
necrosis cell death.
DURING THE PAST DECADE THERE HAVE BEEN considerable advances in the use of chemotherapy for the treatment of the various cancers such as Hodgkin’s and non-Hodgkin’s lymphoma, acute leukemias, colorectal and lung cancer, and local tumor control particularly with breast cancer. Metastases to various organs causes untold suffering and pain. Chemotherapy is effective in many patients, but its toxic effects on the heart, particularly on the myocardium, often limit their use in patients who may need these agents the most. Most important, cardio-myopathy caused by chemotherapeutic agents causes death in a significant number of patients. Further research is required to provide new effective agents with less toxicity.

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• I. CHEMOTHERAPEUTIC AGENTS
  It is common for chemotherapeutic agents to be associated with myocardial damage reduction in ejection fraction and heart failure.
• II. CARDIAC DAMAGE FROM ANTHRACYCLINES
  Anthracyclines contain an aromatic ring structure that intercalates in between DNA base pairs. The mechanism of cardiotoxicity appears to be inhibition of the function of topoisomerase II. This enzyme is critical in allowing DNA to undergo efficient repair. Most important, these agents generate free radicals that can damage cell membranes partly by lipid peroxidation. Amsacrine and mitoxantrone produce lower quantities of free radicals and cause less cardiotoxicity and cardiomyopathy compared with the doxorubicin, daunorubicin, idarubicin, and epirubicin. Cardiac tissues possess a low ability to detoxify these free radicals because of the presence of only small amounts of catalase that converts hydrogen peroxide to water.
• III. CYCLOPHOSPHAMIDE
  Cyclophosphamide and ifosfamide high-dose therapy may cause severe cardiomyopathy and heart failure in patients undergoing stem cell transplantation. Acute myocyte necrosis, with damage to the endothelial lining of the heart, and hemorrhagic myopericarditis may occur with a 30% mortality rate. The ECG shows abnormal patterns and the chest x-ray is a good test for detecting heart failure. An echocardiogram is not a test used for the detection of heart failure, but it is useful in revealing weakness of the heart muscle, pericarditis, or pericardial effusions. Serious complications are more common in patients with pre¬existing heart disease, particularly in those with left ventricular dysfunction and an ejection fraction of less than 45%.
• IV. 5-FLUOROURACIL
  This is a frequently used agent and its associated cardio-toxicity may be more common than previously thought.
• BIBLIOGRAPHY
  Stone, R. M., Bridges, K. R., and Libby, P. Hematological-oncological disorders and cardiovascular disease. In Heart Disease, seventh edition. E. Braunwald, D. P. Zipes, and P. Libby, eds. W. B. Saunders, Philadelphia, 2005.