Lysosomes in heart tissue

Romeo, Domenico; Stagni, N.; Sottocasa, Gian Luigi; Pugliarello, Maria Chiara; Bernard, B. de; Vittur, Franco

doi:10.1016/0304-4165(66)90009-2

Cited by 52 publications

(10 citation statements)

References 24 publications

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“…Lysosomes occur in myocardial cells (27)(28)(29)(30)(31) and it is possible that steroids protect the myocardium by their well-known stabilizing effect on lysosomal membranes (32)(33)(34). These organelles, which are disrupted by acidotic conditions in hypoxic cells, release acid hvdrolases which ma!…”

Section: Discussionmentioning

confidence: 99%

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Libby¹,

Maroko²,

Bloor³

et al. 1973

J. Clin. Invest.

268

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A B S T R A C T The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronarv occlusion. In the control g,-oup ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5±0.8 to 1.1+0.4 mV (P<0.01) and NST was reduced from 6.7±1.1 to 1.4±0.8 (P < 0.01).In order to study the influence of hydrocortisone on r. crosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N:= 102 specimens, r =-0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs).Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected A preliminary report Of this investigation appeared in Clin. Res. 1972. 20: 207. from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK =-0.0288ST + 1.26 (N = 48, r = -0.71) and log CPK = -0.0321ST + 1.31 (N = 48, r = -0.76) in the i h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion. INTRODUCTIONRecent investigations in our laboratory have begun to delineate factors determining the extent and severity of myocardial ischemic injury and subsequent necrosis after acute coronary occlusion. The possibility of modi-

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Section: Discussionmentioning

confidence: 99%

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Libby¹,

Maroko²,

Bloor³

et al. 1973

J. Clin. Invest.

268

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“…Heart muscle has been shown to contain lysosomes (39), and the number of autophagic vacuoles and the acid phosphatase activity increase during long-term perfusion of isolated rat hearts (40). Cathepsin activity in the supernatant fraction of heart muscle increases after 60 minutes of autolysis (38).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat Hearts

Rovetto

Whitmer

Neely

1973

Circulation Research

294

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The rates of utilization of glycogen and exogenous glucose by hearts perfused at low coronary flows and high perfusate oxygen tension (ischemia) and by hearts perfused at high coronary flows and low perfusate oxygen tension (anoxia) were studied in the isolated, working rat heart. Ischemic tissue had a glycolytic rate that was 25% of the anoxic rate and 50* of the control rate; Inhibition of carbohydrate utilization during ischemia was due to a lower flux through the glycolytic pathway and not to a lower rate of glucose transport or substrate availability. Insulin and elevated perfusate glucose increased glucose transport and caused accumulation of free intracellular glucose, but ischemia still inhibited glucose utilization. Insulin failed to maintain tissue levels of high-energy phosphates or to prevent mechanical failure in ischemic hearts. In the absence of insulin, tissue lactate increased tenfold during 20 minutes of ischemia, although it increased only threefold in anoxic tissue. The increased tissue lactate in ischemic hearts corresponded to the inhibition of glycolysis and to the failure of mechanical performance. Insulin caused a further increase in tissue lactate during ischemia. These findings illustrate several important differences between anoxia and ischemia and suggest that insulin may be more harmful than it is beneficial in severely ischemic tissue.KEY WORDS glycolysis lactate production tissue lactate insulin coronary flow glycogenolysis glucose-6-phosphate glucose transport energy production• Decreased oxygen supply has several effects on myocardial metabolism. Utilization of both exogenous glucose and tissue glycogen is accelerated (1-3), and oxidation of fatty acids is inhibited (4) during hypoxia or anoxia. Acceleration of glycolysis has been related to decreased tissue levels of creatine phosphate and adenosine triphosphate (ATP) and to increased tissue levels of inorganic phosphate (Pi), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) (3, 5, 6). The activity of phosphofructoldnase is inhibited by ATP and accelerated by P,, ADP, and AMP (7, 8). The supply of substrate for glycolysis is increased during anoxia through the activation of both glycogenolysis (9) and glucose transport across the cell membrane (10,11). Glycogenolysis is accelerated by increased activity of phosphorylase b due to decreased levels of ATP (an inhibitor) and increased levels of AMP (an activator) and Pi (a substrate) (3, 9). Acceleration of glucose transport also may be related to changes in the tissue levels of adenine nucleotides (11). Pyruvate produced by glycolysis is diverted from oxidation through the citrate cycle to the formation of lactate due to high levels of NADH (6), and lactate release from the tissue is increased severalfold.Oxygen deprivation through decreased coronary flow (ischemia) rather than decreased oxygen tension (Po2) (anoxia or hypoxia) leads to similar changes in the energy state of the tissue (12-15): the levels of creatine phosphate and ATP decrease and the levels ...

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“…This observed enzyme-specific depression of hydrolase activities may be a result of a selective effect of diabetes on a particular subpopulation of lysosomes. Populations of lysosomes have been identified in the heart that differ in enzyme content and morphology (17,23,25,26). Our results, therefore generally agree with previous reports of decreased lysosomal enzyme activities in the aorta (28), skeletal muscle (22) and heart homogenates (3, 21, 24) from diabetic animals.…”

Section: Discussionmentioning

confidence: 98%

Alterations in heart and serum lysosomal activities in streptozotocin-induced diabetes

1987

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Alterations in the cardiac tissue and serum acid hydrolase activities were studied in chronic streptozotocin-induced diabetes in rats. No changes were observed in total cardiac tissue homogenate lysosomal enzyme activities at 4 weeks of diabetes but there were significant alterations in the distribution of selected enzymes. Significant decreases in nonsedimentable beta-N-acetylglucosaminidase (NAG) and beta-galactosidase (Gal) activities were observed at 4 weeks of diabetes. At 8 weeks of the disease, decreased activities of NAG and Gal were observed in heart homogenates but no changes were apparent in alpha-mannosidase (Man) or acid phosphatase activities. Nonsedimentable activities of NAG and both sedimentable and nonsedimentable activities of Gal were decreased at 8 weeks. At 16 weeks of the diabetic condition, increased activities of NAG, Gal and acid phosphatase were observed. This increase at 16 weeks of the disease was due to an increase in sedimentable enzyme activity. At all times of diabetes, serum enzyme activities were significantly increased. Insulin treatment reversed all of the observed changes in tissue homogenates, but serum levels were not completely reversed. These results suggest that cardiac lysosomal hydrolases are probably only involved in the later stages of the diabetic cardiomyopathy when extensive ultrastructural derangements are evident. The present evidence also suggests that the heart may be a source of serum hydrolase activities.

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Lysosomes in heart tissue

Cited by 52 publications

References 24 publications

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat Hearts

Alterations in heart and serum lysosomal activities in streptozotocin-induced diabetes

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