Lanthanum Probe Studies of Cellular Pathophysiology Induced by Hypoxia in Isolated Cardiac Muscle

Abstract

A B S T R A C T 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 Data from this study were presented at the 49th Scientific

Inhibition of the release of arachidonic acid prevents the development of sarcolemmal membrane defects in cultured rat myocardial cells during adenosine triphosphate depletion.

“…Using iodoacetate as a metabolic inhibitor, it has been demonstrated that myocardial cells can withstand large decreases in cellular ATP levels without developing sarcolemmal membrane defects. Since the development of these sarcolemmal defects is a hallmark ofirreversible injury (25,26), these results provide additional evidence that the release of arachidonic acid is linked to the onset of irreversible injury of cultured myocardial cells during ATP depletion. However, there are several reasons for interpreting the results of the present study with caution.…”

Release of arachidonate from membrane phospholipids in cultured neonatal rat myocardial cells during adenosine triphosphate depletion. Correlation with the progression of cell injury.

“…In intact ischemic heart models, previous studies have demonstrated the presence of sarcolemmal membrane defects by electron microscopy, which correlated with the time course of the onset of irreversible injury and the accumulation of tissue calcium (1,2). Previous studies in a perfused rabbit septal model related the decreases in myocardial contractile performance during ischemia with the development of increased sarcolemmal membrane cation permeability (3). Acute myoAddress reprint requests to Dr. Chien. Received for publication 8 May 1984 and in revised form 11 January 1985. cardial infarction in man is characterized by leakage of cytosolic enzymes across the sarcolemmal membrane into the vascular space (4).…”

Correlation of alterations in cation exchange and sarcolemmal ultrastructure produced by neuraminidase and phospholipases in cardiac cell tissue culture.

“…THERE is increasing evidence which indicates that surface structure of the myocardial cell is damaged by ischemia and anoxia (Jennings et al, 1975;Hearse et al, 1975;Frank et al, 1980) and that this damage leads to marked changes in cellular permeability to calcium (Ca) (Burton et al, 1977;Shen and Jennings, 1972). In addition, it is well known that exposure of the myocardium to solutions that contain no Ca produces major changes in membrane permeability upon reintroduction of Ca-the "Ca paradox" (Zimmerman and Hulsmann, 1966;Crevey et aL, 1978).…”