Fig. 1: AZD1656 treatment attenuates diastolic dysfunction and reduces infarct size in dbCM.
a, The AZD1656 treatment protocol. Mice were fed nutritionally standardized and matched Teklad Standard Base Diet (Envigo), with AZD1656 added to the diet used for the db/db treatment group (30 mg kg−1 body weight). b, In vivo echocardiography assessment of diastolic dysfunction: isovolumic relaxation time (IVRT) (control versus db/db P = 0.0001; control versus AZD P = 0.0002; db/db versus AZD P = 0.0015), mitral valve deceleration (MV decel) (control versus db/db P < 0.0001; control versus AZD P < 0.0036; db/db versus AZD P = 0.0397), myocardial performance index (MPI) (control versus db/db P = 0.0007; control versus AZD P = 0.811; db/db versus AZD P = 0.0521), mitral valve early versus late ratio (E/A) (control versus db/db P = 0.0003 by one-way ANOVA, AZD versus control P = 0.185 and AZD versus db/db P = 0.036 by Fischer’s exact test). The approach to statistical analysis for E/A is described in the Methods. Control n = 17, db/db n = 17, AZD n = 14. c, Representative Langendorff perfused heart. d, Langendorff perfused heart ex vivo function end diastolic pressure (control n = 9; db/db n = 9; AZD n = 6; control versus db/db P = 0.0001; control versus AZD P = 0.0001; db/db versus AZD P = 0.0344) by one-way ANOVA. e, Langendorff perfused heart ex vivo function systolic pressure (control n = 9; db/db n = 9; AZD n = 6; control versus db/db P = 0.0001; control versus AZD P = 0.0001; db/db versus AZD P = 0.0344) by one-way ANOVA. f, Representative TTC stained cardiac cross sections after 20 min of total global ischemia and 2 h reperfusion, used for quantification of the infarct size. g, Quantification of infarct size after ischemia–reperfusion injury (db/db, AZD n = 5 per group; control n = 3) by one-way ANOVA (control versus db/db P = 0.0005; control versus AZD P = 0.1372; db/db versus AZD P = 0.005). h, Improved left ventricular developed pressure (LVDP) recovery after ischemia in Langendorff perfused hearts (control n = 5; db/db n = 5; AZD n = 6; control versus db/db P = 0.0001; control versus AZD P = 0.0001; db/db versus AZD P = 0.034) by one-way ANOVA. n represents biological replicates (individual animals). Data are presented as mean ± s.e.m. NS, non-significant. Created with BioRender.com.
