| Recent data suggest that glucose-insuline-potassium infusion (GIK) in acute myocardial infarction results in an improved survival of patients, especially in patients undergoing reperfusion therapy. The mechanisms of improved survival by GIK infusion are not well defined but experimental data suggest that several mechanisms may play a role that limit infarct size. We have recently discovered by chance that GIK infusion in patients with an acute myocardial infarction resulted in improvement of regional and global left ventricular function. Furthermore, we found that only the non-contractile but viable segments in the infarct area showed improvement during GIK infusion. These data support the notion that GIK may reduce infarct size if reperfusion of the infarct related coronary artery is achieved. Thus, we hypothesize that myocardium at risk of necrosis in the infarct area may be preserved by GIK infusion and subsequent reperfusion therapy. Therefore, the aim of our study is to demonstrate that GIK infusion prior to a primary PTCA in the acute phase of infarction results in infarct size reduction which can be clinically observed as an improvement of left ventricular function. For this purpose 100 patients undergoing primary PTCA will be randomized to GIK infusion or to saline infusion. It is expected that the endsystolic volume (as a measure of global left ventricular function) after three months is significantly lower in the GIK treated PTCA group than in the saline treated PTCA group. The rationale for the choice of this patient group is that reperfusion can clearly be defined and is optimal compared to thrombolytic therapy. Using thrombolytic therapy reperfusion can be obtained but the moment of reperfusion may not be accurately assessed and often a severe residual stenosis is present. However, if the results of this study clearly demonstrate a benefit of GIK treatment, in later studies the use of GIK in patients undergoing thrombolytic therapy can be studied. The secondary endpoint will be other measures of infarct size based on a) the ventriculogram during catheterization, b) echocardiography and c) infarct enzymes. The tertiary endpoint in this study is the flow of the infarct related coronary artery and myocardial perfusion in the infarct territory. It has been observed that coronary flow immediately after opening of the vessel may not be normal (no reflow or slow reflow). This can be explained by microvascular injury due to infarction, thrombo-embolic plugging of the distal infarct-related coronary artery and release of vasoconstricting agents by the thrombotic material resident at the ruptured plaque. As we expect a reduction of infarct size by GIK, coronary flow and coronary flow reserve of the infarct-related artery may be higher directly after PTCA and after 3 months. More important than coronary flow is myocardial perfusion. Although we cannot measure myocardial perfusion, there are surrogates available, derived from coronary angiography: the so-called TIMI flow, the TIMI frame count and extent of myocardial blush. These parameters can routinely be obtained from the angiogram directly after PTCA. Another indirect measure of the success of reperfusion is the disappearance of the ST-segment elevation and depression on the ECG after PTCA: these parameters will also be compared between the GIK and saline treated group. It is expected that coronary flow reserve, myocardial perfusion and ST-segment resolution is higher in the GIK treated group than in the saline treated group. Finally, the activation of immunological processes after infarction will be measured in the study. Recent data suggest that reperfusion of ischemic myocardium itself may induce inflammatory reactions, which, among others, involve further activation of complement, neutrophils and oxygen radicals. These inflammatory reactions may damage the cardiac tissue and limit the beneficial effects of a restored circulation (reperfusion injury). Therefore we will measure inflammation markers to determine if these markers have independent influence on LV function and coronary flow and can be modified by GIK infusion. These markers can easily be determined by taken blood samples after infarction. |
