WT, PARP1+/-, and PARP1-/- mice were monitored at 150 days’ post-infection. Shown are transthoracic echocardiography measurements of (A) stroke volume (SV), (B) cardiac output (CO), and (C) ejection fraction (EF). Pulse-wave doppler echocardiography was performed to measure (D) isovolumic contraction time (IVCT), (E) LV ejection time, mitral valve (F) early and (G) late peak velocities, and (H) isovolumic relaxation time (IVRT). The data presented in A-H were acquired from n = 8–12 mice/group with triplicate recordings per mouse. (I) Myocardial parasite burden was determined by qPCR amplification of Tc18SrDNA and normalized with GAPDH (n? 5 mice/group, three observations per mouse). Data in all bar graphs are plotted as mean value ± SEM. Statistical significance are marked as *WT.Tc vs. WT, &genetically modified/infected vs. matched controls, and #WT.Tc vs. genetically-modified/infected (*,&,#p<0.05, **,##p<0.01). Detailed LV function data are presented in S2 Table.
Finally, we obtained a quantitative measure of tissue parasite burden to confirm if the observed benefits of PARP1 depletion are delivered through its effects on parasite persistence. Myocardial level of Tc18SrDNA were similarly increased in chagasic WT, PARP1+/-, and PARP1-/- mice (Fig 7I). Together, the results presented in Fig 6 and Fig 7 suggest that changes in the LV walls’ thickness (and thereby contractile capacity) contributed to compromised systolic and diastolic performance of the heart in chagasic WT mice. The benefits of PARP1 depletion in preserving LV hemodynamics and myocardial performance were delivered via control of collagenosis and stiffness of IVS and LVPW in the myocardium of chagasic mice.