Deleterious effects of hydrogen peroxide on the function and ultrastructure of cardiac muscle and the coronary vasculature of perfused rat hearts.

Objective: To examine the effect of hydrogen peroxide on the function and ultrastructure of cardiac muscle and the coronary vasculature in an isovolumic rat heart preparation perfused at constant flow.

Design: Ventricular function was monitored via a balloon placed in the left ventricle and the response of the coronary vessels to vasodilators was assessed in hearts arrested with 35 mM potassium and treated with 5 microM phenylephrine to contract the coronary resistance vessels. Changes in coronary perfusion pressure reflect changes in resistance vessel tone. SETTING/ANIMALS: This experimental study consisted of 14 heart preparations, six control and eight treated hearts.

Interventions: Hydrogen peroxide was included in the perfusate at a final concentration of 250 microM for 20 mins.

Main Results: Hydrogen peroxide reduced rate-pressure product by 42%, caused a fivefold increase in end-diastolic pressure and increased coronary perfusion pressure by 33%. Also, the response of the coronary vasculature to the endothelium-dependent vasodilator, histamine, and endothelium-independent vasodilator, sodium nitrite, was decreased by 55% and 53%, respectively. Electron microscopy of hydrogen peroxide-treated hearts showed damage to both capillaries and arterioles. Endothelial cells were distorted and contained pinocytotic vesicles, endothelial cell junctions were disrupted and blood vessels were detached from surrounding tissue. A comparatively small amount of injury was seen in the myocyte population.

Conclusions: The greater amount of ultrastructural damage seen in blood vessels compared with cardiac muscle suggests that the smooth muscle and endothelial cells of the vasculature are more susceptible to oxidant injury than the myocytes.