Dose-response relationships of the protective and antiprotective effects of acute @entity1068 exposure in isolated XXXX hearts.

@entity5045 @entity63 @entity167 @entity95 @entity1188 @entity1068
In the @entity95 heart, acute @entity1068 exposure followed by washout before @entity63 exerts a preconditioninglike effect. However, if @entity167 is still present during @entity63 , all preconditioning-related cardioprotection is abolished. The present follow-up study investigated the dose-response relationships of both the beneficial and detrimental effects of acute @entity1068 exposure. In the isolated @entity95 heart either 2.5-, 5-, 10-, 20-, or 50-mmol/L @entity1068 was given as a 5-minute pulse followed by washout before 30 minutes of regional @entity63 and 2 hours of reperfusion. Isolated @entity95 hearts were also preconditioned with 5 minutes of global @entity63 followed by 10 minutes of reperfusion (PC) before onset of 30 minutes of regional @entity63 . This latter protocol was combined with a 35-minute infusion of @entity1068 at concentrations of either 5, 10, 20, or 50 mmol/L, starting 5 minutes before the onset of the 30-minute period of @entity63 . @entity1188 size was determined with @entity5045 staining. No protection was seen with a 5-minute infusion of 2.5-mmol/L @entity1068 (29.9 +/- 1.6% of risk zone infarcted), and minimal protection was evident with the 5-mmol/L dose (25.4 +/- 3.4% @entity1188 ). In all other groups @entity1188 size was significantly reduced (17.9 +/- 3.2, 18.4 +/- 3.5, and 16.8 +/- 3.4%, respectively, versus 33.0 +/- 3.0% in control group, P < 0.05). In the presence of 10-, 20-, or 50-mmol/L @entity1068 , @entity1188 size following PC was not different from control (24.3 +/- 2.5, 28.4 +/- 4.3, and 39.0 +/- 4.0%, respectively, versus 28.5 +/- 2.5%). Thus the presence of @entity167 during @entity63 inhibited protection induced by preceding preconditioning @entity63 . Only in the PC group exposed to 5-mmol/L @entity1068 was @entity1188 size significantly smaller than in the control group (6.4 +/- 2.5%, P < 0.005). Thus both protective and antiprotective effects of @entity167 were dose dependent with similarly low threshold doses in in vitro @entity95 hearts. Since it might be impossible to find a dose of @entity1068 that would be protective if administered shortly before @entity63 , @entity1068 should be removed before that @entity63 to protect myocardium.
