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We demonstrate that viscoelastic mechanics of striated muscle, measured as elastic and viscous moduli, emerge directly from the myosin crossbridge attachment time, 𝑡att, also called time-on. The distribution of 𝑡att was modeled using a gamma distribution with shape parameter, 𝑝, and scale parameter, 𝛽. At 5 mM MgATP, 𝛽 was similar between mouse 𝛼-MyHC (16.0±3.7 ms) and 𝛽-MyHC (17.9±2.0 ms), and 𝑝 was higher (𝑃<0.05) for 𝛽-MyHC (5.6±0.4 no units) compared to 𝛼-MyHC (3.2±0.9). At 1 mM MgATP, 𝑝 approached a value of 10 in both isoforms, but 𝛽 rose only in the 𝛽-MyHC (34.8±5.8 ms). The estimated mean 𝑡att (i.e., 𝑝𝛽 product) was longer in the 𝛽-MyHC compared to 𝛼-MyHC, and became prolonged in both isoforms as MgATP was reduced as expected. The application of our viscoelastic model to these isoforms and varying MgATP conditions suggest that 𝑡att is better modeled as a gamma distribution due to its representing multiple temporal events occurring within 𝑡att compared to a single exponential distribution which assumes only one temporal event within 𝑡att.

Nitric oxide has enigmatic qualities in inflammation. In order to appreciate the precise contributions of nitric oxide to a pathophysiological process, one must account for enzyme source, coproduction of oxidants and antioxidant defences, time, rate of nitric oxide production, cellular source, peroxynitrite formation and effects on DNA (mutagenesis/apoptosis). We contend that there is ample evidence to consider nitric oxide as a molecular aggressor in inflammation, particularly chronic inflammation. Therapeutic benefit can be achieved by inhibition of inducible nitric oxide synthase and not the donation of additional nitric oxide. Furthermore, there is growing appreciation that nitric oxide and products derived thereof, are critical components linking the increased incidence of cancer in states of chronic inflammation.