Abstract 21359: Stress Hormone CRH: New Role in Cardiac Dysfunction
Introduction: The myocardial response to stressful stimuli is influenced by many factors. We investigated the contribution of the stress hormone corticotropin (CRH) in cardiac function using a model of acute endotoxemia in transgenic mice with partial (Crh+/−) or total depletion (Crh−/−) of CRH compared to Crh+/+ mice (WT).
Methods: We performed echocardiographic analysis using a high frequency system (Vivid 7, GE, 13 MHz linear transducer) for the study of adult male (WT n=17, Crh+/− n=10, Crh−/− n=4) and female (WT n=10, Crh+/− n=6, Crh−/− n=8) hearts intraperitoneally (i.p.) injected with normal saline or LPS (120μg per animal). Two-D targeted M-mode imaging was obtained in anesthetized mice (i.p. ketamine 100mg/kg) from the short axis view at the level of greatest LV dimension. End diastole was determined at the maximal LV diastolic dimension, and end systole was taken at the peak of posterior wall motion. The Heart Rate (HR) and the percentage of LV fractional shortening FS (%) = [(EDD-ESD)/EDD] × 100 were calculated. Results are presented as means ± SEM.
Results: Under basal conditions FS of WT mice was higher by 14% compared to Crh+/− (P=0.02) and 20% compared to Crh−/− (P=0.01). LPS administration significantly reduced FS at 6 (23% P=0.001) and 20 (25%) hours, in WT, without significant difference between WT and Crh+/− mice. Crh−/− mice showed increased (33%, P=0.001 at 6h, and 47%, P=0.003 at 20h) reduction and unexpected elevated levels of mortality (90–100% after 16–28h post-LPS treatment), compared to no mortality observed among WT. No gender-related differences were observed. Crh−/− mice' HR was non-significantly lower at baseline conditions, decreasing with LPS; 30%, P=0. 0004 at 20h vs WT.
Conclusions: Experimental endotoxemia, through LPS administration, in mice causes significantly greater cardiac contractility and heart rate decrease in Crh−/− compared to WT mice. It is interesting that both Crh+/− and Crh−/− demonstrate decreased FS even at basal conditions before stress. Our results indicate a possible new action of CRH stress hormone in cardiac function and HR under both basal and stressful conditions such as Gram-negative infections.
- © 2010 by American Heart Association, Inc.