The legacy of A. V. Hill's Nobel Prize winning work on muscle energetics.

A. V. Hill was awarded the 1922 Nobel Prize, jointly with Otto Meyerhof, for Physiology or Medicine for his work on energetic aspects of muscle contraction. Hill used his considerable mathematical and experimental skills to investigate the relationships among muscle mechanics, biochemistry and heat production. The main ideas of the work for which the Nobel Prize was awarded were superseded within a decade, and the legacy of Hill and Meyerhof's Nobel work was not a set of persistent, influential ideas but rather a prolonged period of extraordinary activity that advanced the understanding of how muscles work far beyond the concepts that led to the Nobel Prize. Hill pioneered the integration of mathematics into the study of physiology and pharmacology. Particular aspects of Hill's own work that remain in common use in muscle physiology include mathematical descriptions of the relationships between muscle force output and shortening velocity and between force output and calcium concentration, and the model of muscle as a contractile element in series with an elastic element. We describe some of the characteristics of Hill's broader scientific activities and then outline how Hill's work on muscle energetics was extended after 1922, as a result of Hill's own work and that of others, to the present day.

Contribution of stretch to the change of activation properties of muscle fibers in the diaphragm at the transition from fetal to neonatal life.

The transition from fetal to postnatal life involves clearance of liquid from the lung and airways, and rapid formation of a functional residual capacity. Despite the importance of the diaphragm in this process, the impact of birth on the mechanical and functional activity of its muscle fibers is not known. This study determined the contractile characteristics of individual "skinned" diaphragm fibers from 70 days (0.47) gestation to after birth in sheep. Based on differential sensitivity to the divalent ions calcium (Ca(2+)) and strontium (Sr(2+)), all fibers in the fetal diaphragm were classified as "fast," whereas fibers from the adult sheep diaphragm exhibited a "hybrid" phenotype where both "fast" and "slow" characteristics were present within each single fiber. Transition to the hybrid phenotype occurred at birth, was evident after only 40 min of spontaneous breathing, and could be induced by simple mechanical stretch of diaphragm fibers from near-term fetuses (∼147 days gestation). Both physical stretch of isolated fibers, and mechanical ventilation of the fetal diaphragm in situ, significantly increased sensitivity to Ca(2+) and Sr(2+), maximum force generating capacity, and decreased passive tension in near-term and preterm fetuses; however, only fibers from near-term fetuses showed a complete transition to a "hybrid" activation profile. These findings suggest that stretch associated with the transition from a liquid to air-filled lung at birth induces physical changes of proteins determining the activation and elastic properties of the diaphragm. These changes may allow the diaphragm to meet the increased mechanical demands of breathing immediately after birth.