Figure 7.

Dose and delivery route dependence of ext-P188 in protecting mdx mice skeletal muscle from lengthening contraction-induced force loss in vivo. Mdx mice were administered either low dose (60 mg/kg) (gray symbols) or high dose (160 mg/kg) (black symbols) ext-P188 via intraperitoneal (a) (IP), (b) intravenous (IV)), or (c) subcutaneous (subQ) injection at least 30 minutes prior to the protocol and the anterior crural muscle group tested for lengthening contraction-induced force loss over the course of 50 contractions. Force loss is presented as a fraction of the initial maximal force ± standard error of the mean (SEM). Contractions #1–15 are graphically emphasized. (a) High-dose ext-P188 (160 mg/kg) had no protective effect against lengthening contraction-induced force loss. However, low dose ext-P188 (60 mg/kg) significantly improved resistance to injury from contraction #8 through #50 (*P < 0.05 via two-way analysis of variance compared to mdx saline). (b,c) Neither low-dose nor high-dose ext-P188 administered IV or subQ had any significant effects on force deficit. (d) Low dosage 60 mg/kg ext-P188 was injected into the tibialis anterior (TA) muscle of mdx mice intramuscularly (IM) directly prior to the protocol. Ext-P188-treated mice had a highly significant and sustained resistance to lengthening contraction injury loss (contractions 6–50, *P < 0.05 two-way analysis of variance compared to mdx saline). Contractions #1–15 are graphically emphasized, entire protocol shown in inset. Error bars shown as mean ± SEM (in some cases symbol size was larger than error bar).