The effectiveness of postconditioning and preconditioning on infarct size in hypercholesterolemic and normal anesthetized rabbits
Introduction
Ischemic preconditioning is a well-established endogenous mechanism of protection of the ischemic heart, which reduces the infarct size when brief periods of ischemia and reperfusion proceed to a more sustained episode of ischemia [1], [2]. The effectiveness of preconditioning is present under normal conditions in every species, but it remains in dispute under pathological conditions. Therefore, there is conflicting evidence in the literature regarding the beneficial effect of preconditioning in pathological conditions and in the aging heart [3], [4], [5], [6], [7], [8]. Recently, a novel endogenous mechanism of protection called postconditioning, has been described with very promising results [9], [10]. In brief, very short cycles of ischemia and reperfusion, 10–30 s duration, applied immediately after sustained ischemia – in the first minute of reperfusion – are capable of limiting the infarct size. Postconditioning has the advantage that it may be applied after sustained ischemia and therefore, it is clinically more relevant. This novel phenomenon has been studied only in species with normal hearts and under normal conditions.
However, the effectiveness of postconditioning has to be elucidated not only in normal but also in pathological conditions. In the present in vivo study, we chose hypercholesterolemia and atherosclerosis as pathological models, in order to test the effectiveness of postconditioning in limiting the infarct size after sustained ischemia and reperfusion in anesthetized rabbits.
Section snippets
Methods
New Zealand White male rabbits weighing between 2.4 and 3.4 kg were used in this study and received proper care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the National Institute of Health. The rabbits of the first series were fed for 6 weeks with cholesterol-enriched diet with 2 g of cholesterol (product
Animal exclusions
Seven animals were excluded from the first series of the study: two of them – one from the Control and one from the IPC group – were excluded for technical reasons; three animals – two from 6/10 IPostC and one from the Control group – were excluded for various hemodynamic reasons and two more animals were excluded because of normal cholesterol blood levels. Thus, 28 out of 35 rabbits completed the study. Three more animals were excluded from the second series of experiments: one from the 6/10
Discussion
The present study demonstrates that the endogenous mechanism of preconditioning preserves its power and reduces the infarct size in hypercholesterolemic and atheromatous hearts while the novel mechanism of postconditioning does not confer protection under the same pathological conditions. Postconditioning with six very short cycles of ischemia–reperfusion is equally effective as preconditioning in normal hearts under normal conditions. However, we found the effectiveness of postconditioning in
References (26)
- et al.
Failure, to precondition pathological human myocardium
J Am Coll Cardiol
(2001) - et al.
Preconditioning protects the severely atherosclerotic mouse heart
Ann Thorac Surg
(2001) - et al.
The loss of pacing-induced preconditioning in atherosclerotic rabbits: role of hypercholesterolemia
J Mol Cell Cardiol
(1995) - et al.
Improved myocardial tolerance to ischemia in the diabetic rabbit
J Mol Cell Cardiol
(1998) - et al.
No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits
J Am Coll Cardiol
(2001) - et al.
Preconditioning limits myocardial infarct size in hypercholesterolemic rabbits
Atherosclerosis
(2000) - et al.
Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction
J Am Coll Cardiol
(1999) - et al.
The PKC activator PMA preconditions rabbit heart in the presence of adenosine receptor blockade: is 5′-nucleotidase important?
J Mol Cell Cardiol
(1998) - et al.
Melatonin does not prevent the protection of ischemic preconditioning in vivo despite its antioxidant effect against oxidative stress
Free Radic Biol Med
(2004) - et al.
Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signalling pathways
J Am Coll Cardiol
(2004)