Table 1.
Greater Systolic Dysfunction in sGCα1−/−CM than Wild-Type Mice After 12 Weeks of Doxorubicin Administration
| WT + saline (n = 6) | sGCα1−/−CM + saline (n = 5) | WT + DOX (n = 12) | sGCα1−/−CM + DOX (n = 9) | Adjusted p-value | |
|---|---|---|---|---|---|
| ESV (μl) | 19 ± 1 | 19 ± 1 | 26 ± 3 | 37 ± 3†,* | 0.01 |
| EDV (μl) | 43 ± 2 | 41 ± 2 | 51 ± 2 | 58 ± 2† | 0.07 |
| EF (%) | 60 ± 2 | 58 ± 3 | 55 ± 4 | 42 ± 4* | 0.03 |
| MAP (mmHg) | 104 ± 5 | 96 ± 6 | 105 ± 5 | 102 ± 4 | 0.94 |
| Ea (mmHg/μl) | 3.6 ± 0.3 | 3.6 ± 0.4 | 4.0 ± 0.4 | 3.9 ± 0.3 | 1.00 |
| PES (mmHg) | 91 ± 8 | 83 ± 4 | 97 ± 4 | 91 ± 5 | 0.67 |
| PED (mmHg) | 2.5 ± 0.5 | 2.6 ± 0.3 | 3.3 ± 0.6 | 4.5 ± 0.7† | 0.11 |
| dP/dtmax (mmHg/s) | 13,499 ± 1433 | 11,995 ± 601 | 13,503 ± 678 | 10,387 ± 922* | 0.03 |
| dP/dtmin (mmHg/s) | −12,054 ± 1809 | −11,420 ± 950 | −13,531 ± 846 | −10,943 ± 991 | 0.21 |
| Tau (ms) | 5.1 ± 0.1 | 4.9 ± 0.2 | 5.6 ± 0.2 | 6.3 ± 0.4†,* | 0.048 |
| PRSW | 83 ± 9 | 84 ± 6 | 70 ± 9 | 49 ± 7† | 0.22 |
| EES (mmHg/μl) | 7.4 ± 0.6 | 7.3 ± 1.4 | 4.0 ± 0.8 | 2.3 ± 0.3† | 0.73 |
| EDPVR (mmHg/μl) | 0.22 ± 0.03 | 0.18 ± 0.02 | 0.16 ± 0.02 | 0.19 ± 0.02 | 0.56 |
| HR (bpm) | 576 ± 8 | 614 ± 12 | 528 ± 9† | 530 ± 14† | 1.00 |
Invasive hemodynamic measurements revealed increased systolic dysfunction in sGCα1−/−CM compared with WT mice after 12 weeks of DOX administration.
Multiplicity-adjusted p-values for comparison between WT + DOX and sGCα1−/−CM + DOX are reported. †p < 0.05 versus saline and *p < 0.05 versus WT + doxorubicin.
bpm, beats per minute; DOX, doxorubicin; dP/dtmax, maximum first derivative of developed LV pressure; dP/dtmin, minimum first derivative of developed LV pressure; Ea, arterial elastance; EDPVR, end-diastolic pressure volume relationship; EDV, end-diastolic volume; EES, end-systolic elastance; EF, ejection fraction; ESV, end-systolic volume; HR, heart rate; LV, left ventricular; MAP, mean arterial pressure; PED, end-diastolic pressure; PES, end-systolic pressure; PRSW, preload recruitable stroke work; sGC, soluble guanylate cyclase; sGCα1−/−CM, mice with cardiomyocyte-specific deletion of exon 6 of the sGCα1 allele; Tau, time constant for isovolumic relaxation; WT, wild-type.