Various models of cardiac conditioning in single or sequential periods of ischemia: comparative effects on infarct size and intracellular signaling.

BACKGROUND: Preconditioning (PreC) and postconditioning (PostC) reduce infarct size. We sought to determine the effects of PreC and PostC, alone or in combination, on infarct size and expression of intracellular signals in different ischemia models. METHODS: Male rabbits were subjected to myocardial ischemia followed by 3-hour reperfusion. In a first series we applied 3 ischemia models [a 20-min period (20), a 40-min period (40), and two sequential 20-min periods (20-20)] and 3 types of interventions [no intervention (controls, C), 2 cycles of 5-min ischemia/10-min reperfusion before index ischemia (PreC) and 6 cycles of 10-s ischemia/10-s reperfusion after index ischemia and/or between the sequential ischemic periods (PostC)] (12 groups in total). Infarct size (I) and area at risk (R) were assessed (%I/R). In a second series, samples were taken for western blot analysis of Akt phosphorylation. RESULTS: Overall, %I/R differed significantly among groups (p<0.001). In control groups, C-40 had a greater %I/R than C-20 (p=0.006). In intervention groups, no differences were found in %I/R. All intervention groups had significantly lower %I/R compared to C-40 group (p<0.001), whereas, compared to C-20-20 group, PreC-20-20, 20-PostC-20, 20-PostC-20-PostC and PreC-20-20-PostC groups had lower %I/R (all p<0.05). Akt was increased in all groups in which a significant %I/R reduction was achieved (p<0.05 versus all other groups). CONCLUSIONS: PreC and PostC, alone or in combination, are effective when an ischemic insult of a given duration is applied either as a single or as sequential periods. Protection from either intervention is associated with an enhanced Akt activation.

Acute administration of vitamin C abrogates protection from ischemic preconditioning in rabbits.

Vitamin C is considered to be an antioxidant agent that is broadly used. Free radicals are involved in the protective mechanism of preconditioning (PC), but some antioxidant compounds abolish this benefit. The aim of the present study was to evaluate the effect of vitamin C on the protective effect of PC with respect to infarct size and oxidative stress in anesthetized rabbits. Male rabbits were randomly divided into six groups and subjected to 30 min of myocardial ischemia and 3h of reperfusion with the following interventions per group: (1) Control (no intervention), (2) Vit C 150 group (i.v. vitamin C at a total dose of 150 mg/kg for 75 min, starting 40 min before the onset of long ischemia and lasting up to the 5th min of reperfusion), (3) Vit C 300 group (i.v. vitamin C at a total dose of 300 mg/kg as previously described), (4) PC group (two cycles of 5 min ischemia and 10 min reperfusion), (5) combined PC-Vit C 150 group and (6) combined PC-Vit C 300 group. Blood samples were taken at different time points for malondialdehyde (MDA) assessment as a lipid peroxidation marker and for superoxide dismutase (SOD) activity. At the end of the experiment the infarct size was determined. Vitamin C, at both doses, did not reduce the infarct size (35.5+/-4.1%, 38.3+/-7.0% vs. 44.9+/-3.3% in the control group) and diminished the protection afforded by PC (32.0+/-2.7%, 43.8+/-3.3% vs. 15.7+/-2.9% in the PC group, P<0.05). At reperfusion there was an elevation of circulating MDA levels in the control and PC groups while in both vitamin C groups the levels were decreased. SOD activity was enhanced in the PC group compared to the controls; vitamin C did not change SOD activity during ischemia-reperfusion. Vitamin C abrogates the beneficial effect of ischemic PC on infarct size and elicits antioxidant properties during ischemia-reperfusion.