Elsevier

Atherosclerosis

Volume 188, Issue 2, October 2006, Pages 356-362
Atherosclerosis

The effectiveness of postconditioning and preconditioning on infarct size in hypercholesterolemic and normal anesthetized rabbits

https://doi.org/10.1016/j.atherosclerosis.2005.11.023Get rights and content

Abstract

Background

Postconditioning with multiple very short coronary occlusions immediately after prolonged ischemia is a new endogenous mechanism for protection of the ischemic heart. We tested whether postconditioning is effective in limiting infarct size in hypercholesterolemic rabbits.

Methods

Male rabbits were fed a cholesterol-enriched diet for 6 weeks. Animals were subjected to 30 min of regional ischemia of the heart and 3 h of reperfusion with the following additional interventions: Control group no additional intervention, ischemic preconditioning (IPC) group to two cycles of 5 min ischemia separated by 10 min reperfusion before the index ischemia, 6/10 IPostC group to six cycles of 10 s ischemia separated by 10 s reperfusion and 4/30 IPostC group to four cycles of 30 s ischemia separated by 30 s reperfusion immediately after the end of the index ischemia. In a second series of experiments the same interventions were applied to animals fed with a normal diet. Infarct size (I) was determined by triphenyltetrazolium chloride staining.

Results

The I/R in hypercholesterolemic rabbits was 55.2 ± 5.9% in Control, 17.9 ± 4.2% in IPC (P < 0.01 versus Control), 63.4 ± 4.8% in 6/10 IPostC and 55.6 ± 8.2% in 4/30 IPostC (P = NS between them and the Control group). In the normal diet rabbits, the I/R was 48.2 ± 4.3% in Control, 15.1 ± 2.1% in IPC, 20.4 ± 2.9% in 6/10 IPostC (P < 0.01 versus Control) and 45.1 ± 8.9% in 4/30 IPostC (P = NS versus Control). Blood cholesterol levels were increased and atheromatic lesions were present in the first series.

Conclusion

Postconditioning is ineffective in limiting the infarct size in rabbits with hypercholesterolemia and atherosclerosis while preconditioning continued to be effective under the same conditions.

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

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