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Membrane phospholipid metabolism during myocardial ischemia: Mechanisms of accumulation of unesterified arachidonate in ischemic canine myocardium
3 MEMBRANE PHOSPHOLIPID METABOLISM DURING MYOCARDIAL ISCHEMIA: MECHANISMS OF ACCUMULATION OF UNESTERIFIED ARACHIDONATE IN ISCHEMIC CANINE MYOCARDIUM. K.R. Chien, MD, PhD. Denartment of Medicine, Universitv of Texas Health Science Center, Dallas, TX. . Studies in ischemic canine left ventricle (ILV) have shown that degradatio&of membrane phcepholipids (PL) is a critical event in the development of a sarcolemmal Ca permeability defect and essociated irreversible myocyte injury. Since arachidonic acid (A) is found entirely in membrane PL, increases in unesterified A provides evidence of increased PL degradation. After 10-20 minutes of I, there was no significant increase in A content versus sham levels as detected by HPLC analysis~ However, increasing I to 60 minutes resulted in over a 70% increase in A content. Myocardial membranes contain an A CoA synthetase (A CoASl and A CoA:lysolipid reacylase which results in preferential re-esterification of A into PL and maintains low-free A levels under normal conditions. The onset of increases in A in ILV correlate with the depletion of ATP to levels near the Km of A CoAS for ATP. There is no structural inhibition of A CoAS evident in membranes from ILV. It is postulated that the accumulation of A in ILV may be partially the result of ATP depletion and subsequent decreased A CoAS activity, resulting in membrane PL depletion during myocardial ischemia.
M3EUL4TIoN OF CYCLIC NUCLEJX'IDE ME'I'ABOLISM BY ms PHCSPHOLIPIDS IN-CELL C.Cl6,B.Tantini,*E.l'urchetto,S.Manfroni,*C.Pignatti. Istituto di Chimica mm. Biologica e *centro Ricerche sulla Nutrizione, Univarsiti di Bola~~ (Italy). It is considered that@MP and @ represent the final ccxmonmadiators of cardiac functions and that enqrnatic control play an essential role in maintaining cyclic nucleotide levels. The activity of both esne bound and soluble cyclic nucleotide en zymes are affected in vitro by lipids, including phospholipids (PL). This reprt deais with experimente perfom&onconfluentand eemn-starvedheart cell cultures frun chick anbryo. The addition of phosphatidylcholine (20 ug/rm of medium) or pixsphatidyL etharolamine (20 pg/ml) or phosphatidylserine (50 pg/ml) to the cells causes a net maxirmanwithin IO to 30 min. The increase increase inc3P andadscrease i.ncAMpwith in oXP appears to be mediated by a faster rate of synthesis rather than by a decreaseddegradation. Conversely the fall in CAMP by PLis relatedtob3th adecreased adenylate cyclase and an increassd CAMP-PDE activity. The capability of PL to differently affect cyclic nucleotide contents by modulating their specific metabolic enzymes underlines the biological iqortance of these ccanpounls, especially for heart cell, whose metabolic ard functional activities are closely dependent on exa~etxous lipids, and might be of particular relevance in the study of cardiac performance during corditions involving abnormal levels of circulating lipids. suppod by a grant of Minister0 Pubblica Istruzione, FKxne (Italy).
EFFECTS OF ISCHAEMIA AND REPERFUSION ON GLUTATHIONE METABOLISM. S. Curello, C. Ceconi, R. Ferrari, 0. Visioli, C.*Guamieri, C.M.*Caldarera Cattedra di Cardiologia, Universita di Brescia e "Centro Studi Ricerthe sul metabolismo de1 miocardio dell'Universit.8 di BolognaItaly. and Reperfusion We have investigated the effects of Ischaemia (I) metabolism in the isolated and perfused rabbit (R) on glutathione heart. I was induced reducing flow from 25 to 1 ml/min for 90' and Hearts were either unpaced or paced. In unpaced group R was for 30'. I reduced tissue GSH and no effect on GSSG. During R there was a slight increase of GSH and GSSG without a significant release of GSH + GSSG with a 50% recovery in function. In pace,' into the coronary effluent, hearts I induced results similar to those of the unpaced heart, but after R tissue GSH content was strongly reduced and GSSG was increased. This last event was accompanied with a marked release of GSH + GSSG These data into the coronary effluent and no recovery of function. suggest that profound alterations of glutathione in the myocardial cells are correlated with a poor recovery in function.
M3EUL4TIoN OF CYCLIC NUCLEJX'IDE ME'I'ABOLISM BY ms PHCSPHOLIPIDS IN-CELL C.Cl6,B.Tantini,*E.l'urchetto,S.Manfroni,*C.Pignatti. Istituto di Chimica mm. Biologica e *centro Ricerche sulla Nutrizione, Univarsiti di Bola~~ (Italy). It is considered that@MP and @ represent the final ccxmonmadiators of cardiac functions and that enqrnatic control play an essential role in maintaining cyclic nucleotide levels. The activity of both esne bound and soluble cyclic nucleotide en zymes are affected in vitro by lipids, including phospholipids (PL). This reprt deais with experimente perfom&onconfluentand eemn-starvedheart cell cultures frun chick anbryo. The addition of phosphatidylcholine (20 ug/rm of medium) or pixsphatidyL etharolamine (20 pg/ml) or phosphatidylserine (50 pg/ml) to the cells causes a net maxirmanwithin IO to 30 min. The increase increase inc3P andadscrease i.ncAMpwith in oXP appears to be mediated by a faster rate of synthesis rather than by a decreaseddegradation. Conversely the fall in CAMP by PLis relatedtob3th adecreased adenylate cyclase and an increassd CAMP-PDE activity. The capability of PL to differently affect cyclic nucleotide contents by modulating their specific metabolic enzymes underlines the biological iqortance of these ccanpounls, especially for heart cell, whose metabolic ard functional activities are closely dependent on exa~etxous lipids, and might be of particular relevance in the study of cardiac performance during corditions involving abnormal levels of circulating lipids. suppod by a grant of Minister0 Pubblica Istruzione, FKxne (Italy).
EFFECTS OF ISCHAEMIA AND REPERFUSION ON GLUTATHIONE METABOLISM. S. Curello, C. Ceconi, R. Ferrari, 0. Visioli, C.*Guamieri, C.M.*Caldarera Cattedra di Cardiologia, Universita di Brescia e "Centro Studi Ricerthe sul metabolismo de1 miocardio dell'Universit.8 di BolognaItaly. and Reperfusion We have investigated the effects of Ischaemia (I) metabolism in the isolated and perfused rabbit (R) on glutathione heart. I was induced reducing flow from 25 to 1 ml/min for 90' and Hearts were either unpaced or paced. In unpaced group R was for 30'. I reduced tissue GSH and no effect on GSSG. During R there was a slight increase of GSH and GSSG without a significant release of GSH + GSSG with a 50% recovery in function. In pace,' into the coronary effluent, hearts I induced results similar to those of the unpaced heart, but after R tissue GSH content was strongly reduced and GSSG was increased. This last event was accompanied with a marked release of GSH + GSSG These data into the coronary effluent and no recovery of function. suggest that profound alterations of glutathione in the myocardial cells are correlated with a poor recovery in function.