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Myocardial adenosine kinase activity decreases with age
J Mol Cell Cardiol 19 (Supplement III) (1987)
46~P~E~
INOSINE UPTAKE BY THE HU~kN HEART. J.W. de Jong*, W. Czarnecki ~, W. R u z y ~ o ~ T. Huizer*, K. Herbaczy~ska-Cedro +, *Cardiochem. Lab., Thoraxctr., Eras~us Univ. Rotterdam, NL; +Med. Res. Ctr., Inst. Animal Physiol., ~ Acad. Sci.; Grochowski Hosp., Cardiol., ~ Med. Sch., Warsaw, PL. Although inosine has already been used clinically as myocardium supporting agent, no data are available on the fate of exogenous inosine in man. We used BPLC to study the arteriovenous difference (AA-V) of inosine and its catabolites across the heart of 6 patients catheterized for coronary angiography, infused with inosine at a rate of 5 mg/kg/min iv for 6 min. Before infusion, the AA-V of inosine, hypoxanthine and xanthine was nil, whereas urate was produced by the heart. During infusion, arterial inosine increased, exceeding the coronary sinus concentration by a maximum of 200 • 53 ~M (mean • SEM, P = 0.02) at the 4th min, suggesting inosine uptake by t h e h e a r t . The AA-V of hypoxanthine, xanthine and urate amounted to 16 • 11, i0 • 3 (P = 0.04), 15 • 14 ~M, respectively, Dp/dt increased by 22 ~ 6% (P = 0.04) at the end of infusion. In conclusion, a part of exogenous inosine is converted to catabolites. There seems to be a substantial uptake of inosine by the human heart concomitant with improvement in hemodynamics.
47 REPERFUSION/REOXYGENATION- INTRODUCTION.J.W. de Jong. Cardiochemical Laboratory,
Thoraxcenter, Erasmus University Rotterdam, Rotterdam, The Netherlands. Myocardial ischemia is characterized by a disbalance of energy supply and energy demand. Suboptimal substrate and oxygen delivery, together with suboptimal catabolite removal, w i l l eventually lead to cell necrosis. Therefore tissue reperfusion is essential to prevent permanent ischemic damage. However, in recent years i t has become clear that reperfusion and reoxygenation of heart tissue is not necessarily beneficial. Hopefully we w i l l learn in this session how to sail between Scylla and Charybdis. Dr. D.J. Hearse w i l l set the stage with his view on free-radical-induced damage of the myocardium. Dr. L.H. Opie w i l l outline mechanisms other than free-radical mediated, including calcium-dependent delayed afterdepolarizations and the role of transient inward current. I t w i l l be clear from the debate that we know l i t t l e about the true origin of reperfusion arrhythmias. Finally Dr. H.M, Piper w i l l discuss the role of cytosolic free calcium during anoxia and reoxygenation in single cardiomyocytes.
48
MYOCARDIAL ADENOSINE KINASE ACTIVITY DECREASES WITH AGE. J.W, de Jong, B. Schoutsen, E. Keijzer. Cardiochem. Lab., Thoraxctr., Erasmus Univ. Rotterdam, The Netherlands. A number of enzymes, involved in cardiac adenine nucleotide breakdown, change in I activity during development. This phenomenon has been described for 5'-nucleotidase , AMP-deaminase and xanthine oxidoreductase . We studied one of the anabolic routes, phosphorylation of adenosine, in isolated neonatal and adult rat-heart myocytes, cultured for 1-3 d. Then they were homogenized and assayed. In addition, homogenates of neonatal an~ adult ventricles were analyzed. The table lists the adenosine kinase act., measured at 30 ~ (~ • SD (n), *P<0.O05 vs neonate). This study shows that i) rat-heart myocytes contain Prepn. Adenosine kinase act. (U/g protein) adenosine kinase activity; 2) myocardial adenosine kinase decreases Myocyte Ventricle twofold during maturation. We suggest that the aging heart looses Neonate 1.0 • 0.2 (6), 1.83 • 0.12 (3), part of its capacity to regenerate Adult 0.55 • 0.14 (6) 0.83 • 0.i0 (3) adenine nucleotides. i. 2. 3. 4.
A.B, Awad & J. Chattopadhyay, Mech. Ageing Dev. 22 (1983) 151, J. Purzycka-Preiss et al., Int. J. Biochem. 6 (1975) 885. B. Schoutsen et al., J. Mol. Cell. Cardiol. 18, Suppl. 3 (1986) 62. J.W. de Jong, Arch. Int. Physiol. Biochim. 85 (1977) 557.
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46~P~E~
INOSINE UPTAKE BY THE HU~kN HEART. J.W. de Jong*, W. Czarnecki ~, W. R u z y ~ o ~ T. Huizer*, K. Herbaczy~ska-Cedro +, *Cardiochem. Lab., Thoraxctr., Eras~us Univ. Rotterdam, NL; +Med. Res. Ctr., Inst. Animal Physiol., ~ Acad. Sci.; Grochowski Hosp., Cardiol., ~ Med. Sch., Warsaw, PL. Although inosine has already been used clinically as myocardium supporting agent, no data are available on the fate of exogenous inosine in man. We used BPLC to study the arteriovenous difference (AA-V) of inosine and its catabolites across the heart of 6 patients catheterized for coronary angiography, infused with inosine at a rate of 5 mg/kg/min iv for 6 min. Before infusion, the AA-V of inosine, hypoxanthine and xanthine was nil, whereas urate was produced by the heart. During infusion, arterial inosine increased, exceeding the coronary sinus concentration by a maximum of 200 • 53 ~M (mean • SEM, P = 0.02) at the 4th min, suggesting inosine uptake by t h e h e a r t . The AA-V of hypoxanthine, xanthine and urate amounted to 16 • 11, i0 • 3 (P = 0.04), 15 • 14 ~M, respectively, Dp/dt increased by 22 ~ 6% (P = 0.04) at the end of infusion. In conclusion, a part of exogenous inosine is converted to catabolites. There seems to be a substantial uptake of inosine by the human heart concomitant with improvement in hemodynamics.
47 REPERFUSION/REOXYGENATION- INTRODUCTION.J.W. de Jong. Cardiochemical Laboratory,
Thoraxcenter, Erasmus University Rotterdam, Rotterdam, The Netherlands. Myocardial ischemia is characterized by a disbalance of energy supply and energy demand. Suboptimal substrate and oxygen delivery, together with suboptimal catabolite removal, w i l l eventually lead to cell necrosis. Therefore tissue reperfusion is essential to prevent permanent ischemic damage. However, in recent years i t has become clear that reperfusion and reoxygenation of heart tissue is not necessarily beneficial. Hopefully we w i l l learn in this session how to sail between Scylla and Charybdis. Dr. D.J. Hearse w i l l set the stage with his view on free-radical-induced damage of the myocardium. Dr. L.H. Opie w i l l outline mechanisms other than free-radical mediated, including calcium-dependent delayed afterdepolarizations and the role of transient inward current. I t w i l l be clear from the debate that we know l i t t l e about the true origin of reperfusion arrhythmias. Finally Dr. H.M, Piper w i l l discuss the role of cytosolic free calcium during anoxia and reoxygenation in single cardiomyocytes.
48
MYOCARDIAL ADENOSINE KINASE ACTIVITY DECREASES WITH AGE. J.W, de Jong, B. Schoutsen, E. Keijzer. Cardiochem. Lab., Thoraxctr., Erasmus Univ. Rotterdam, The Netherlands. A number of enzymes, involved in cardiac adenine nucleotide breakdown, change in I activity during development. This phenomenon has been described for 5'-nucleotidase , AMP-deaminase and xanthine oxidoreductase . We studied one of the anabolic routes, phosphorylation of adenosine, in isolated neonatal and adult rat-heart myocytes, cultured for 1-3 d. Then they were homogenized and assayed. In addition, homogenates of neonatal an~ adult ventricles were analyzed. The table lists the adenosine kinase act., measured at 30 ~ (~ • SD (n), *P<0.O05 vs neonate). This study shows that i) rat-heart myocytes contain Prepn. Adenosine kinase act. (U/g protein) adenosine kinase activity; 2) myocardial adenosine kinase decreases Myocyte Ventricle twofold during maturation. We suggest that the aging heart looses Neonate 1.0 • 0.2 (6), 1.83 • 0.12 (3), part of its capacity to regenerate Adult 0.55 • 0.14 (6) 0.83 • 0.i0 (3) adenine nucleotides. i. 2. 3. 4.
A.B, Awad & J. Chattopadhyay, Mech. Ageing Dev. 22 (1983) 151, J. Purzycka-Preiss et al., Int. J. Biochem. 6 (1975) 885. B. Schoutsen et al., J. Mol. Cell. Cardiol. 18, Suppl. 3 (1986) 62. J.W. de Jong, Arch. Int. Physiol. Biochim. 85 (1977) 557.
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