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Abstract
BackgroundIschemic 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/DesignThis 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.DiscussionIschemic 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.
Highlights
Ischemic preconditioning is a powerful mechanism of myocardial protection and in humans it can be evaluated by sequential exercise tests
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
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
Summary
There is no study in humans so far which have assessed the differences in IP between patients with and without diabetes and chronic coronary artery disease. Differences between species in relation to coronary collaterals and in myocardial perfusion may contribute to the variability of the results These differences between clinical and experimental studies may be due to the contribution of other diseases in diabetic patients, such as hypertension, dislypidemia, microvascular dysfunction, neuropathy, nephropathy, as well as the use of antidiabetic drugs which may block IP by preventing the opening of K(ATP) channels in the myocardium [23,24]. The aim of the present study will be to analyze ischemic preconditioning in diabetic and nondiabetic patients with chronic, stable coronary artery disease by sequential treadmill exercise tests. All authors participated in drafting and revising the manuscript, and all authors have read and approved the final manuscript
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