Abstract

Abstract Background Based on differences in the timing of left ventricular (LV) peak systolic pressure, distinction between early from late LV systolic loading is made. Reduced ascending aortic compliance results with chronic early LV systolic loading. Chronic late LV systolic loading associates with end-systolic wave refection's and developing earlier heart failure. The LV remodeling in chronic late vs early systolic loading has not been studied previously in a porcine model. Objective To develop novel porcin model and to study the LV hypertrophic remodeling in chronic late vs early LV systolic loading, during thoracic aorta banding. Methods Domestic male pigs (28±3.4kg, n=14) underwent thoracic aorta banding. Ascending aorta banding (PB, n=6) induced chronic early LV systolic loading. Descending thoracic aorta banding (DB n=8) provoked chronic late LV systolic loading. 3T cMRI with T1 mapping was performed at baseline, 4 and 8 weeks. Hemodynamic measurements were obtained using 5Fr Millar P-V catheter in LabChart, after 4 and 8 weeks. ANOVA two-way for repeated measurements was performed (R studio 3.5.1). Leven and Shapiro-Wilk normality testing was done. Analysis of variance of aligned rank transformed data was performed. Linear regression showed correlation between relevant parameters. Results Hemodynamic measurements are presented as means±se and means±sd for cMRI, for significant p<0.05. After 8 weeks of thoracic aorta banding, the timing of peak systolic LV pressure was prolonged in DB (PB 159±6 msec; DB 329±16 msec; p<0.01), correlating with LV dPdtmax (p=0.017, r=−0.8), Ea (p=0.04, r=0.73), LVEF (p=0.035, r=−0.74) and native T1 (p=0.01, r=−0.83) in DB. Tau was not different (p=0.8), correlated with the timing of peak LV pressure in DB (p=0.015, r=0.81). The gradients were not different (PB 25±5mmHg; DB 16±1mmHg; p=0.88) and LV systolic pressure (p=0.61). The isovolumic contraction phase was prolonged in DB (PB 34±4msec; DB 56±4msec, p<0.01). LV mass index increased (p=0.013) and was not different between the groups (PB 95±14g/m2; DB 89±12g/m2; p=0.89). RWT was different within (p<0.01) and between the groups (p=0.02),correlating with LVEFas dPdtmax (p=0.013, r=−0.82), whilst with dPdtmin (p=0.018, r=0.8) in DB. There was an interaction for site of aortic constriction and LV remodeling (RWT 0.067±0.08 in PB; 0.45±0.04 in DB, p=0.004; posterior LV wall thickness (PWT) p=0.012). RWT correlated with native T1 in PB (p=0.04) and DB (p<0.01, r=−0.8). Des. aorta banding in late LV loadining Conclusion The LV hypertrophic remodeling, defined by RWT, PWT and hemodynamic correlates is different between chronic late and early LV systolic loading, in this novel porcine model. The timing of peak LV afterload associates with increased LV afterload and adverse LV remodeling in presence of chronic late LV systolic loading, in the porcin model of descending thoracic aorta banding. Increased RWT ratio associates with adverse LV remodeling in the porcine model of descending thoracic aortic constriction.

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