The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure

Figure 1. Time Course of Left Ventricular Dilatation (Upper panel) Left ventricular (LV) diastolic, LV systolic diameter, and LV fractional shortening determined, before and 90 days after sham surgery, in untreated Wistar (open circles; n = 10) and 2, 7, and 90 days after 45-min transient ischemia in placebo-treated I/R Wistar (filled circles; n = 15), early long-term (down-triangles; n = 14) or delayed long-term gevokizumab-treated I/R Wistar (up-triangles; n = 15). (Lower panel) LV diastolic, LV systolic diameter, and LV fractional shortening determined, before and 90 days after sham surgery in untreated Goto-Kakisaki (open circles; n = 12) and 2, 7, and 90 days after 20-min transient ischemia in placebo-treated I/R Goto-Kakisaki (filled circles; n = 16), early long-term (down-triangles; n = 15) or delayed long-term gevokizumab-treated I/R Goto-Kakisaki (up-triangles; n = 15). *p < 0.05 versus untreated sham. †p < 0.05 versus untreated I/R.

Figure 2. Left Ventricular Hemodynamics (Upper panel) Left ventricular end-systolic pressure (LVESP), left ventricular end-systolic pressure-volume relation (LVESPVR), left ventricular end-diastolic pressure (LVEDP), and left ventricular end-diastolic pressure-volume relation (LVEDPVR) determined 90 days after sham surgery in untreated Wistar (white bars; n = 14) and 90 days after 45-min transient ischemia in placebo-treated I/R Wistar (black bars; n = 16), early long-term (up-hatched bars; n = 14) or delayed long-term gevokizumab-treated I/R Wistar (down-hatched bars; n = 15). (Lower panel) LVESP, LVESPVR, LVEDP, and LVEDPVR determined 90 days after sham-surgery in untreated Goto-Kakisaki (white bars; n = 10) and 90 days after 20-min transient ischemia in placebo-treated I/R Goto-Kakisaki (black bars; n = 15), early long-term (up-hatched bars; n = 15) or delayed long-term gevokizumab-treated I/R Goto-Kakisaki (down-hatched bars; n = 15). *p < 0.05 versus untreated sham. †p < 0.05 versus untreated I/R.

Figure 3. Left Ventricular Remodeling (Upper panel) Left ventricular (LV) weight, collagen density, infarct size, and tissue perfusion in the ‘viable’ part of the LV determined 90 days after sham surgery in untreated Wistar (white bars; n = 14) and 90 days after 45-min transient ischemia in placebo-treated I/R Wistar (black bars; n = 16), early long-term (up-hatched bars; n = 14) or delayed long-term gevokizumab-treated I/R Wistar (down-hatched bars; n = 15). (Lower panel) LV weight, collagen density, infarct size, and tissue perfusion in the ‘viable’ part of the LV determined 90 days after sham surgery in untreated Goto-Kakisaki (white bars; n = 10) and 90 days after 20-min transient ischemia in placebo-treated I/R Goto-Kakisaki (black bars; n = 15), early long-term (up-hatched bars; n = 15) or delayed long-term gevokizumab-treated I/R Goto-Kakisaki (down-hatched bars; n = 15). *p < 0.05 versus untreated sham. †p < 0.05 versus untreated I/R.

Figure 4. Coronary Relaxation in Wistar Rats (Upper panel) Coronary relaxation induced by acetylcholine 90 days after sham surgery in untreated Wistar (open circles; n = 5) or 90 days after 45-min transient ischemia in placebo-treated I/R Wistar (filled circles; n = 6), early long-term (down-triangles; n = 15) or delayed long-term gevokizumab-treated I/R Wistar (up-triangles; n = 5). *p < 0.05 versus untreated sham. †p < 0.05 versus untreated I/R. (Middle and lower panel) Coronary relaxation induced by acetylcholine 90 days after sham surgery in untreated Wistar or 90 days after 45-min transient ischemia in untreated I/R Wistar, early long-term or delayed long-term gevokizumab-treated I/R Wistar before (open circles) and after incubation with apocyin or SOD (filled circles). *p < 0.05 versus before incubation.

Figure 5. Coronary Relaxation in Gotokakisaki Rats (Upper panel) Coronary relaxation induced by acetylcholine 90 days after sham surgery in untreated Goto-Kakisaki (open circles; n = 5) or 90 days after 20-min transient ischemia in placebo-treated I/R Goto-Kakisaki (filled circles; n = 8), early long-term (down-triangles; n = 6) or delayed long-term gevokizumab-treated I/R Goto-Kakisaki (up-triangles; n = 6). *p < 0.05 versus untreated sham. †p < 0.05 versus placebo-treated I/R. (Middle and lower panels) Coronary relaxation induced by acetylcholine 90 days after sham-surgery in IgG-treated Goto-Kakisaki or 90 days after 20-min transient ischemia in placebo-treated I/R Goto-Kakisaki, early long-term or delayed long-term gevokizumab-treated I/R Goto-Kakisaki before (open circles) and after incubation with apocyin or SOD (filled circles). *p < 0.05 versus before incubation.