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.


METHODS
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.


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


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.
Harrison
G J
GJ
Rotary Centre for Cardiovascular Research, Griffith University, Brisbane, Australia.
Jordan
L R
LR
Willis
R J
RJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006632:Histamine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D008297:Male; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D006632:Histamine; D006861:Hydrogen Peroxide; D012977:Sodium Nitrite