Resistance to ischemic damage in hearts of starved rabbits: Correlation with lysosomal alterations and delayed release of cathepsin D.

Prolonged starvation produces dramatic changes both in the lysosomal properties of the heart and in its energy stores and, therefore, might be expected to alter some of the characteristic cardiac responses to ischemia. To test this possibility we ligated the circumflex coronary artery of rabbits that had been fed normally or starved for 6 days. Ultrastructural evidence of myocytic damage following 30 to 120 minutes of ischemia was much less severe in the starved animals than in the normally fed group. The development of signs of irreversible injury (e.g., osmiophilic densities in mitochondria) was delayed for 1 hour or more by starvation. A similar delay occurred in the biochemical redistribution of cathepsin D activity and in the cytoplasmic release of acid hydrolases from lysosomes and sarcoplasmic reticulum. These results indicate a marked protective effect of starvation against myocardial ischemia. In addition, both in starved and in fed animals, ischemically induced release of lysosomal enzymes was closely linked temporally to the development of subcellular damage.