Open Access Highly Accessed Study protocol

Hypotheses, rationale, design, and methods for evaluation of ischemic preconditioning assessed by sequential exercise tests in diabetic and non-diabetic patients with stable coronary artery disease – a prospective study

Paulo Cury Rezende, Rosa Maria Rahmi Garcia, Augusto Hiroshi Uchida, Leandro Menezes Alves Costa, Thiago Luis Scudeler, Rodrigo Morel Vieira Melo, Fernando Teiichi Costa Oikawa, Cibele Larrosa Garzillo, Eduardo Gomes Lima, Carlos Alexandre Wainrober Segre, Desiderio Favarato, Priscyla Girardi, Myrthes Takiuti, Celia Cassaro Strunz, Whady Hueb*, José Antonio Franchini Ramires and Roberto Kalil Filho

Author Affiliations

Department of Atherosclerosis, Heart Institute of the University of Sao Paulo, Sao Paulo, Brazil

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BMC Cardiovascular Disorders 2013, 13:117  doi:10.1186/1471-2261-13-117

Published: 13 December 2013

Abstract

Background

Ischemic preconditioning is a powerful mechanism of myocardial protection and in humans it can be evaluated by sequential exercise tests. Coronary Artery Disease in the presence of diabetes mellitus may be associated with worse outcomes. In addition, some studies have shown that diabetes interferes negatively with the development of ischemic preconditioning. However, it is still unknown whether diabetes may influence the expression of ischemic preconditioning in patients with stable multivessel coronary artery disease.

Methods/Design

This study will include 140 diabetic and non-diabetic patients with chronic, stable coronary artery disease and preserved left ventricular systolic function. The patients will be submitted to two sequential exercise tests with 30-minutes interval between them. Ischemic parameters will be compared between diabetic and non-diabetic patients. Ischemic preconditioning will be considered present when time to 1.0 mm ST-segment deviation is greater in the second of two sequential exercise tests. Exercise tests will be analyzed by two independent cardiologists.

Discussion

Ischemic preconditioning was first demonstrated by Murry et al. in dog’s hearts. Its work was reproduced by other authors, clearly demonstrating that brief periods of myocardial ischemia followed by reperfusion triggers cardioprotective mechanisms against subsequent and severe ischemia. On the other hand, the demonstration of ischemic preconditioning in humans requires the presence of clinical symptoms or physiological changes difficult to be measured. One methodology largely accepted are the sequential exercise tests, in which, the improvement in the time to 1.0 mm ST depression in the second of two sequential tests is considered manifestation of ischemic preconditioning.

Diabetes is an important and independent determinant of clinical prognosis. It's a major risk factor for coronary artery disease. Furthermore, the association of diabetes with stable coronary artery disease imposes worse prognosis, irrespective of treatment strategy. It’s still not clearly known the mechanisms responsible by these worse outcomes. Impairment in the mechanisms of ischemic preconditioning may be one major cause of this worse prognosis, but, in the clinical setting, this is not known.

The present study aims to evaluate how diabetes mellitus interferes with ischemic preconditioning in patients with stable, multivessel coronary artery disease and preserved systolic ventricular function.

Keywords:
Ischemic preconditioning; Exercise test; Coronary heart disease; Angina; Myocardial ischemia