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Figure 4 Neuregulin-1 improves survival of rats subjected to myocardial infarction (a and b), doxorubicin-induced cardiomyopathy (c), or mice with Coxsackie B3 myocarditis (d). Treatments indicated were commenced 1 week (a; n = 51) or 2 months (b; n = 20) after LAD ligation or when doxorubicin (3.3 mg/kg, IV, once weekly for 4 weeks) (c; n = 20) or Coxsackie B3 (0.2 ml virus solution, IP, 50% tissue culture infectious dose = 10–4) (d; n = 20) was administered. The receptor-active 61-residue recombinant neuregulin-1 peptide (rhNRG-1) was given at 10 and 30 µg/kg/day IV for 5 days to rats and mice, respectively, except for the doxorubicin-treated rats that received 20 µg/kg/day for 7 days. Captopril (Capt.) was given at 2.5 mg/kg twice daily by gavage for the duration of the study. Cumulative survival curves of the sham-operated (SO) or untreated control subjects (black), rhNRG-1-treated (dark blue), rhNRG-1 + Capt.-treated (light blue), Capt.-treated (green), or vehicle-treated (red) animals, respectively, are shown. (a) rhNRG-1 versus vehicle, p < 0.028; rhNRG-1 versus Capt. p = ns; (b) rhNRG-1 or Capt. versus vehicle, p < 0.02; (c) rhNRG-1 versus vehicle, p < 0.0001; (d) rhNRG-1 versus vehicle, p < 0.02.
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