Ischemia and reperfusion stun the myocardium and the coronary vasculature. We have previously shown that a short period (15 min) of global
ischemia in the isolated rat heart causes impaired coronary constriction in response to a
thromboxane analog
U46619 during reperfusion.
Sepsis has also been shown to affect myocardial and vascular function. In the present study, we determined whether Escherichia coli-induced
sepsis would exacerbate the effects of
ischemia on the coronary circulation.
Sepsis prolonged the impairment in the coronary constriction response to
U46619 following short term
ischemia. We hypothesized that
sepsis-induced increases in
nitric oxide (NO) production caused the delay in the recovery of the contractile response to
U46619. Perfusion with
NO synthase inhibitors however indicated that the impaired response was not due to NO. However, NO did appear to have a significant role in the development of myocardial
ischemic contracture and on the recovery of diastolic function after
ischemia. Inhibitors of
NO synthase also caused a significant increase in basal coronary perfusion pressure as well as in the maximum coronary pressure generated in response to
U46619, suggesting a role of NO in regulating basal coronary vascular resistance in the isolated rat heart. Some of these effects were more pronounced in septic rat hearts than in the
sham surgical rat hearts, consistent with altered
nitric oxide production in the septic rat hearts.