100 Chapter 5 state insulin concentration during the HE-clamp, divided by body weight and time can be used to quantify the M-value (μmol/kg/min). The M-value represents the metabolic insulin-resistance.44, 46 The final MCE-measurement is performed during administration of dobutamine. Dobutamine is administered in incremental doses, and MCE is performed at a target dose of 40 μg/kg/min dobutamine, or at a lower dose if a diagnostic endpoint is reached or in case of undesired effects (Table 4). Table 4. Dobutamine echocardiography-protocol Incremental infused doses 5 minutes of 10 µg/kg/min 3 minutes of 20 µg/kg/min 3 minutes of 30 µg/kg/min 3 minutes of 40 µg/kg/min Diagnostic endpoints 1) Reaching maximal heart rate (i.e. ((220-age) x 0,85) 2) Systolic blood pressure decrease greater than 20 mmHg 3) Blood pressure above 220/120 mmHg 4) Progressive symptoms of angina pectoris 5) Dyspnea 6) Dizziness 7) Progressive arrhythmia 8) Development of wall motility disorders in more than 1 wall segment as in myocardial ischemia 9) Diagnostic relevant ST-T-segment changes Undesired effects 1) Unbearable angina pectoris 2) Ventricular tachycardia 3) Bradycardia 4) Myocardial ischemia 5) Myocardial infarction 6) Cardiac arrest 7) Ventricular fibrillation Cardiac Magnetic Resonance (CMR) All subjects undergo CMR using a 3 Tesla-scanner (Magnetom Vida, Siemens, Healthcare, Erlangen Germany) after abstaining from caffeine and xanthine for 24 h. Figure 4 shows an overview of the imaging sequence protocol. Myocardial perfusion imaging is performed during stress and rest, using a dual sequence technique optimized for quantification of absolute myocardial blood flow. For this purpose, three short axis images (base, mid-LV and apex) will be acquired during first-pass perfusion imaging, both during adenosine stress (adenosine infusion 140 μg/kg/min) and
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