This study was undertaken to evaluate directly the relationship between evolution of irreversible myocardial injury induced by
hypoxia in an isolated papillary muscle preparation and the development of pathophysiological alterations related to severely impaired membrane function. An ionic
lanthanum probe technique was employed as a cytochemical marker to monitor the progression of cellular injury, and data from this cytologic technique were correlated with ultrastructure and measurements of contractile parameters in a total of 67 muscles subjected to control conditions or to graded intervals of
hypoxia with or without reoxygenation. Marked depression of developed tension and rate of tension development occurred after 30 min of
hypoxia. Contractile function showed significant recovery with reoxygenation after 1 h and 15 min of
hypoxia but remained depressed when reoxygenation was provided after 2 or 3 h of
hypoxia. Examination by transmission and analytical electron microscopy (energy dispersive X-ray microanalysis) revealed
lanthanum deposition only in extracellular regions of control muscles and muscles subjected to 30 min of
hypoxia. After hypoxic intervals of over 1 h, abnormal intracytoplasmic and intramitochondrial localization of
lanthanum were detected. After 1 h and 15 min of
hypoxia, abnormal intracellular
lanthanum accumulation was associated with only minimal ultrastructural evidence of injury; muscle provided reoxygenation after 1 h and 15 min of
hypoxia showed improved ultrastructure and did not exhibit intracellular
lanthanum deposits upon exposure to
lanthanum during the reoxygenation period. After 2 to 3 h of
hypoxia, abnormal intracellular
lanthanum accumulation was associated with ultrastructural evidence of severe muscle injury which persisted after reoxygenation. Thus, the data support the conclusion that cellular and membrane alterations responsible for abnormal intracellular
lanthanum deposition precede the development of irreversible injury but evolve at a transitional stage in the progression from reversible to irreversible injury induced by
hypoxia in isolated feline papillary muscles.