Hypoxemia-induced modification of troponin I and T in canine diaphragm

Impaired muscle function (fatigue) may result, in part, from modification o f contractile proteins due to inadequate O-2 delivery. We hypothesized that severe hypoxemia would modify skeletal troponin I (TnI) and T (TnT), two r egulatory contractile proteins, in respiratory muscles. Severe isocapnic hy poxemia (arterial partial pressure of O-2 Of similar to 25 Torr) in six pen tobarbital sodium-anesthetized spontaneously breathing dogs increased respi ratory frequency and electromyographic activity of the diaphragm and intern al and external obliques, with death occurring after 131-285 min. Western b lot analysis revealed proteolyis of TnI and TnT, 17.5- and 28-kDa fragments , respectively, and higher molecular mass covalent complexes, one of which (42 kDa) contained TnI (or some fragment of it) and probably TnT in the cos tal and crural diaphragms but not the intercostal or abdominal muscles. The se modifications of myofibrillar proteins may provide a molecular basis for contractile dysfunction, including respiratory failure, under conditions o f limited O-2 delivery.