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. 2020 May 25;5(5):484–497. doi: 10.1016/j.jacbts.2020.03.007

Figure 2.

Figure 2

Long-Term Chemogenetic Activation of PVN Oxytocin Neurons Attenuates Cardiac Dysfunction Seen in Animals With Heart Failure

(A) The top panel depicts high-resolution 2D echocardiograms in parasternal longitudinal-axis B mode taken from 16-week post-Sham, TAC, early activation of DREADDs-expressing PVN oxytocin neurons (initiated at 4 weeks post-TAC), and late treatment (starting at 6 weeks post-TAC) animals showing left ventricle (LV) in mid-systole with directional vectors in green. Vertical scale bar represents 3 mm. The middle panel shows 2D echocardiograms in parasternal short-axis M-mode at 16 weeks post-Sham, TAC, early- and late-treatment animals, used to measure the LV posterior-wall thickness and interventricular septal-wall thickness, LV internal diameter, and percent fractional shortening. Vertical and horizontal scale bar represents 3 mm and 0.1 sec, respectively. The bottom panel displays pulsed Doppler measurements of descending aortic flow velocities taken immediately after TAC point in Sham, TAC, and treatment animals. (B) Quantitative longitudinal Doppler descending aortic flow velocities in Sham, TAC saline (expressing DREADDs), TAC CNO (not expressing DREADDs), early- and late-treatment animals taken biweekly from 2 to 16 weeks post-Sham/TAC surgery. The velocities were 3-fold greater in TAC and treatment animals compared with Sham animals. Graphs displaying longitudinal echocardiographic measurements of stroke volume (C), percent ejection fraction (D), cardiac output (CO) (E) from parasternal longitudinal axis B-mode and percent fractional shortening from parasternal short-axis M-mode measured biweekly from 2 to 16 weeks post-Sham, TAC saline (expressing DREADDs), TAC CNO (not expressing DREADDs), and early- and late- treatment animals. Data were analyzed using mixed-effects model with Tukey’s multiple comparison post-test. Sham (n = 6); TAC (n = 6); early treatment (n = 6); late treatment (n = 7); TAC CNO (n = 5);. ∗Sham vs. TAC; $TAC vs. early treatment; #TAC vs. late treatment; ∧Sham vs. early treatment; τSham vs. late treatment; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. CNO, clozapine-N-oxide; DREADDs, designer receptors exclusively activated by designer drugs; PVN, paraventricular nucleus of the hypothalamus; TAC, transascending aortic constriction.