Abstract 13117: Impaired Diastolic Adaptation to Acute Volume Overload in the Hypertrophic Rat Heart
In the present study we investigated diastolic adaptation to stretch in the intact heart and if it is preserved in the hypertrophic heart. Seven week old Wistar-Han male rats underwent: moderate transverse aortic constriction (TAC) with a 21G needle (mTAC n=12); severe TAC with a 25G needle (sTAC, n=12); no constriction (Sham, n=12). After 21 weeks the animals underwent echocardiographic evaluation and were then randomly allocated to: In vivo experiments, which evaluated in open-chest animals, instrumented with left ventricular (LV) pressure-volume conductance catheters, the response to acute volume overload (VO, =15% increase of circulating volume with Voluven®) or In vitro experiments in LV papillary muscles, stretched from 92 to 100% Lmax. Measurements were made at baseline, immediately, 5min and 15min after VO or stretch. Western blot analysis was applied to evaluate levels of RAGE and AGEs in ventricular tissues and Red Sirius staining for evaluation of myocardial fibrosis. sTAC, but not mTAC, significantly increased LV mass, end-diastolic diameter and posterior wall thickness. In both TAC groups fractional shortening and ejection fraction remained unchanged and E/E' was higher than 15. The sTAc group presented significantly higher percentage area of fibrosis (5.5±0.7 vs 2.1±0.3 in mTAC and 1.8±0.2 in sham, p<0.05), AGEs levels (% of control, 151±20 vs 110±20 in mTAC and 100±8,8 in sham, p=0.05) and RAGEs (RAGEs/actin ration, 1.2±0.1 vs 0.9±0.02 in mTAC and 0.8±0.04 in sham, p<0.05). The response to VO and stretch were parallel, LV end-diastolic pressure (EDP) and PT increased immediately in all groups, and decreased thereafter. Such decrease was similar for all groups in the first 5 min (PT -17±2%; LVEDP -14±2%). In the subsequent interval 5-15 min PT and LVEDP further decreased in sham (PT -12±2%, LVEDP -24±7%) and mTAC (PT -11±2%; LVEDP -28±9%,), but remained in sTAC (PT -3±2%, LVEDP 2±9%), even if muscle length and end-diastolic volume remained unchanged in all groups over the same time period. This study demonstrates for the first time an adaptation to acute volume in the intact heart, allowing it to reach higher volumes with lower filling pressures, a mechanism that is lost in the hypertrophic heart when accompanied by fibrosis and AGEs accumulation.
- © 2011 by American Heart Association, Inc.