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| NEUE FORSCHUNGSERGEBNISSE | |
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DPP-4 Inhibition by Sitagliptin Improves the Myocardial Response to Dobutamine
Stress and Mitigates Stunning in a Pilot Study of Patients with Coronary Artery
Disease.
BACKGROUND: -Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted post-prandially that promotes myocardial glucose uptake. The active amide GLP-1 (7-36) is degraded by the enzyme DPP-4, and drugs that inhibit this enzyme (such as sitagliptin) have been introduced to treat type 2 diabetes. We assessed the hypothesis that increasing the plasma concentration of GLP-1 by DPP-4 inhibition would protect the heart from ischemic left ventricular (LV) dysfunction during dobutamine stress echocardiography (DSE) in patients with coronary artery disease (CAD) METHODS AND RESULTS: -Fourteen patients with CAD and preserved LV function awaiting revascularisation were studied. Following either a single dose of sitagliptin 100mg or placebo, 75g of glucose was given orally to promote GLP-1 secretion and DSE conducted with tissue Doppler imaging at rest, peak stress and 30 minutes. After sitagliptin, plasma GLP-1 (7-36) was increased at peak stress (16.5 +/-; 10.7 vs 9.7 +/- 8.7 pg/ml; p = 0.003) and in recovery (12.4 +/- 5.5 vs 9.0 +/- 5.5 pg/ml; p = 0.01), and the LV response to stress was enhanced (ejection fraction 72.6 +/- 7.2 vs 63.9 +/- 7.9 %, p = 0.0001; mitral annular systolic velocity 12.54 +/- 3.18 vs 11.49 +/- 2.52 cm/s; p = 0.0006). DPP-4 inhibition also improved LV regional function in the 12 paired non-apical segments assessed by peak systolic tissue Doppler (velocity 10.56 +/- 4.49 vs 9.81 +/- 4.26 cm/s, p = 0.002; strain -15.9 +/- 6.3 vs -14.6 +/- 6.6 %, p = 0.01 and strain rate -2.04 +/- 1.04 vs -1.75 +/- 0.98 s(-1), p = 0.0003). This was predominantly due to a cardioprotective effect on ischemic segments (velocity in ischemic segments 9.77 +/- 4.18 vs 8.74 +/- 3.87, p = 0.007; velocity in non-ischemic segments 11.51 +/- 4.70 vs 11.14 +/- 4.38, p = 0.14). In recovery, sitagliptin attenuated the post ischemic stunning seen after the control study. CONCLUSIONS: -The augmentation of GLP-1 (7-36) by inhibition of DPP-4 improves global and regional LV performance in response to stress and mitigates post ischemic stunning in humans with coronary artery disease. Clinical Trial Registration Information-URL: http://isrctn.org. Registration number: ISRCTN78649100. |
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Autoren:
Read PA
; Khan FZ
; Heck PM
; Hoole SP
; Dutka DP
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Quelle:
Circ Cardiovasc Imaging. 2010 Jan 14.
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| Literaturrecherche: U.S.National Library of Medicine's PubMed® | |
 
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