Lysosomes in myocardial infarction: studies by means of cytochemistry and subcellular fractionation, with observations on the effects of methylprednisolone.
To evaluate lysosomal involvement in myocardial infarction, coronary artery thrombosis was induced by ligation in 16 dogs. Biopsies of infarcted and normal left ventricles were studied by ultrastructural cytochemistry and subcellular fractionation (0.25 M sucrose) from 30 min to 96 hrs post injury. Normal myocardium contained few "classical" (residual body) lysosomes: instead, acid phosphatase and aryl sulfatase were localized to longitudinal and to lateral sac elements of the sarcoplasmic reticulum. In postnuclear (450 X gm, 10 min) supernates, lysosomal acid phosphatase and beta-glucuronidase were divided 60:40 between sedimentable (98,000 X gm, 15 min) and non-sedimentable fractions of normal endocardium and epicardium (studied separately). At 2 hrs post infarction, ischemic muscle showed: 1) loss of membrane-bound acid  phosphatase and aryl sulfatase; 2) mitochondrial damage; 3) loss of glycogen and disappearance of I but not A bands; and 4) entry into cells of colloidal lanthanum (= loss of plasma membrane integrity. Total lysosomal hydrolase did not increase until 6-5 hrs post infarct. At 2 hrs, significant increments (32 +/- 7%) were found in nonsedimentable acid phosphatase and beta-glucuronidase of endocardium (P less than 0.005 vs. normal) but the epicardium. In dogs given methylprednisolone (50 mg/k) 30 min post infarct, ultrastructural cytochemistry showed retention of lysosomal enzymes within endocardial sarcoplasmic reticulum and no significant redistribution of enzymes into non-sedimentable fractions (vs. eight paired, infarcted, untreated controls). Data show early disruption of lysosomes in myocardial infarction and their protection by steroid given after the acute insult.
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D004285:Dogs; D005966:Glucuronidase / Q000378:metabolism; D006651:Histocytochemistry; D008247:Lysosomes / Q000201:enzymology*; D008775:Methylprednisolone / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D012508:Sarcolemma / Q000648:ultrastructure; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
D000135:Acid Phosphatase; D001192:Arylsulfatases; D005966:Glucuronidase; D008775:Methylprednisolone