15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Escherichia-coli-Infections

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.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Disease Models, Animal; Escherichia coli Infections; Male; Myocardial Contraction; Myocardial Ischemia; Nitric Oxide; Rats; Rats, Sprague-Dawley; Sepsis; Time Factors; Vascular Resistance