Fetal mouse hearts: a model for studying ischemia.
A new experimental model for the study of two important aspects of ischemia, namely, oxygen and substrate deprivation, is proposed: the intact, beating fetal mouse heart in organ culture. This model offers long-term stability, ease and reproducibility of preparation, and the ability to manipulate experimental conditions. Hearts deprived of oxygen and glucose ceased beating immediately. After 3-4 hr of deprivation, biochemical and ultrastructural changes consistent with ischemic injury were evident. These include depletion of ATP and glycogen levels, loss of cytoplasmic enzymes, and extensive swelling and disruption of mitochondrial structure. Glucose and insulin partially protected against ATP depletion. Upon resupply of oxygen and glucose , beating resumed immediately, ATP levels rapidly increased to control levels and, consistent with this, mitochondrial structure returned toward normal. During the recovery phase autophagic vacuoles containing damaged mitochondria and myofibrils were seen, indicating that repair mechanisms were activated. Consistent with this, the proportion of lysosomal enzymes that were present in the nonsedimentable fraction of the tissue homogenate increased. We conclude that the cultured fetal mouse heart is a model useful for studying myocardial responses to anoxia and/or substrate deprivation and for assessing interventions designed to limit damage or to stimulate repair after ischemic injury.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005865:Gestational Age; D005947:Glucose / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010101:Oxygen Consumption; D011247:Pregnancy; D013997:Time Factors
D000255:Adenosine Triphosphate; D000135:Acid Phosphatase; D000118:Acetylglucosaminidase; D002403:Cathepsins; D005947:Glucose