Adaptation to myocardial stress in disease states: is preconditioning a healthy heart phenomenon?

https://doi.org/10.1016/S0165-6147(98)01212-7Get rights and content

Abstract

Effective therapeutic strategies for protecting the ischaemic myocardium are much sought after. Ischaemic heart disease in humans is a complex disorder, often associated with other systemic diseases such as dyslipidaemia, hypertension and diabetes that exert multiple biochemical effects on the heart, independently of ischaemia. Ischaemic preconditioning of myocardium is a well-described adaptive response in which brief exposure to ischaemia markedly enhances the ability of the heart to withstand a subsequent ischaemic insult. The underlying molecular mechanisms of this phenomenon have been extensively investigated in the hope of identifying new rational approaches to therapeutic protection of the ischaemic myocardium. However, most studies have been undertaken in animal models in which ischaemia is imposed in the absence of other disease processes. In this article, Peter Ferdinandy, Zoltan Szilvassy and Gary Baxter review the ways in which systemic diseases might modify the preconditioning response and they emphasize the importance of further preclinical studies that specifically examine preconditioning in relation to complicating disease states.

Section snippets

Interactions between hypercholesterolaemia and atherosclerosis and preconditioning

Hyperlipidaemia, atherosclerosis and their major clinical sequel, ischaemic heart disease, constitute the leading cause of death in industrialized societies. Moreover, several studies suggest that patients with coronary artery disease who experience frequent ischaemic episodes related to either exercise[9] or mental stress[10] have a worse prognosis than those without such episodes. On the other hand, in clinical practice, the terms `warm-up angina' or `walk-through angina' have been used to

Preconditioning and nitrate therapy

Organic nitrates have constituted the main therapy for angina pectoris for more than a century. One of the fascinating aspects of the pharmacology of nitrates, especially in the context of endogenous cardioprotection, is that these agents for the most part elicit their cardiovascular effects by releasing NO ([29]). Because NO might be a key trigger and/or mediator of ischaemic preconditioning, nitrate therapy is a plausible means of pharmacologically exploiting ischaemic preconditioning[2].

Preconditioning in diabetes

Epidemiological studies have clearly shown that patients with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) are more prone to develop myocardial infarction and post-infarction complications than patients without these disorders, independently of whether or not they display coronary atherosclerosis[37]. Although it has been known for a long time that diabetes is a risk factor for ischaemic heart disease, the literature is inconsistent with

Preconditioning in the hypertrophied and failing myocardium

Systemic arterial hypertension is a recognized risk factor for the development of ischaemic heart disease. Long-standing hypertension might also be associated with the development of left ventricular hypertrophy (LVH). Although LVH can be regarded as a structural adaptive response to a sustained overload of pressure, this condition has grave prognostic implications, independent of all other risk factors. Large cohort studies such as the Framingham study show that hypertensives with LVH have a

Preconditioning and aging

The developing heart undergoes a remarkable metabolic transformation as it adjusts to the rise in oxygen content in the environment outside the uterus[68]. Although protection of the immature heart against ischaemia is an important consideration in corrective surgery for congenital heart diseases[69], the susceptibility of the immature heart to ischaemiaā€“reperfusion under experimental conditions remains a matter of controversy70, 71. There has been very little investigation of preconditioning

Concluding remarks

It seems likely that the development of new therapeutic agents to protect the ischaemic myocardium will continue to be a major area of cardiovascular research. The mechanisms of classical and delayed preconditioning mechanisms might be feasible paradigms for the development of new pharmacological approaches. However, ischaemic heart disease is a clinically heterogeneous condition. The coexistence of other diseases and risk factors, as we have seen in some experimental models, could impair the

Acknowledgements

P.F. thanks the National Scientific Research Fund (OTKA F6396, F19946, D23736), the National Technical Development Committee (OMFB 05201950616), the Ministry of Education (FKFP 1284/1997) and the Hungarian Space Research Office. G.F.B. thanks the British Heart Foundation for a personal fellowship (FS 97/001) and the Hatter Foundation for its continuing generosity.

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