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On-line residue detection of 201Tl in isolated dog hearts during control and after global ischemia
10EFFECT OF MOLSIDOMINE, NITROGLYCERIN AND ISOSORBIDE DINITRATE ON THE INDUCTION RONARY ARTERY THROMBOSIS IN THE DOG. P. A. Martorana, B. Kettenbach, H. G&be1 R.-E. Nitz. CaSSella AG, Frankfurt (M.), West Germany.
OF COand
Platelet activation and aggregation in the coronary circulation may be important in the :>athoge"esis of myocardial ischemia. Molsidomine (M), nitroglycerin (N) and isosorbide dinitrate (ISDN), have been found to inhibit platelet aggregation in vitro. 1n the present study the activity of these compounds was investigated in a model of coronary artery thrombosis in viva. Dogs were anesthetized, ventilated, thoracotomized and their heart exposed. A" electrode was inserted into the left circumflex coronary artery (LCX) and set to rest on the intima. Electrical stimulation (9 V, 150 pA) lasted 6 h. Compounds were given as a" i.v. infusion starting 30 min after the beginning of the stimulation and lasting for the duration of the experiment. All control (C; saline treated; n=14), N (0.5 pg/kg/min; n=6), and ISDN (10 pg/kg/min; n=6) dogs but only 4/8 (pc 0.05) M (1 pg/kg/min; n=8) animals underwent total thrombotic occlusion of the LCX as assessed by flow measurement. Thrombus wet weight (mg) was (2 ! SE) C: 74.4 + 11.3; M: 31.2 f 7.9 (pCO.051; N: 120.2 ? 18.5; ISDN: 90.8 + 12.9. Thrombotic occlusion resulted in myocardial infarction (assessed with nitroblue tetrazolium) in all C, N and ISDN dogs but only in S/8 M (~(0.05) animals. The hemodynamic changes induced by the 3 compounds were similar in magnitude. Thus M, but not N or ISDN, showed in this in viva study a" antithrombotic activity.
11 ON-LINE RESIDUE DETECTION OF 201Tl IN ISOLATED DOG HEARTS DURING CONTROL AND AFTER GLOBAL ISCHEMIA. B. Winkler, K.J. Henrichs, H. Matsuoka, G. StUmmler, W. Schaper, Max-Planck-Institute, Bad Nauheim, Federal Republic of Germany. Residue detection of 201~1 was performed on isolated dog hearts which were perfused with blood from a donor dog. The photons of 201~1, observed with a NaI(Tl)-detector facing directly the surface of the isolated hearts, were registered in a multichannel analyzer (MCA) in multiscaling mode. The MCA was directly connected to a computer system to accomplish a rapid data transmission. Beside the fast vascular component of 201Tl a slow washout rate from the cellular space was observed during control as well as after 60' of total global ischemia (k1/2=50min VS. k1/2=15min). The slow washout rate from the cellular space might be explained by assuming a" intracellular binding site for 201Tl. A large cellular permeability surface area product (PS,,Il) of 20'11 was observed with the multiple indicator dilution technique which was changed after 60' of global ischemia in the same order of magnitude as compared to its washout rates (PS,,ll - 8 ml/mi"/g-1 vs. 1.98 ml/min/g-1. Therefore, membrane changes and additional destruction of the internal cellular milieu, caused by the global ischemic intervention must be assumed for the changes of the washout rates.
12 COMPARISON OF MOCARDIAL ADENINE POOL CATABOLIS@ DmING GLOBAL ANOXIA AND ISCHAEMIA. Department of S.M. Humphrey, L.C. Armiger, D.G. Hollis. M.A. Morrison. R.N. Seelye. Pathology, University of Auckland School of Medicine, Auckland, New Zealand. Differences in coronary flow rates may alter the rate and extent of adenine pool decay in myocardium subsequent to severe oxygen deficierlcy. We compared metabolite changes in globally ischaemic (cross-clamped aorta) and iri globally arloxic (oxygenand nutrient-free perfusion at 10 KPa pressure) isolated rat hearts. At timed intervals, from O-60 minutes, hearts were snap-frozen at -19O'C and subsequelitly the perchloric acid extracts of tissue were subjected to reverse-phase high performance liquid chromatography. The coronary perfusate draining from anoxically perfused hearts was similarly treated. ATP, ADP, AMP, IMP, adenosirle, irlosine, hypoxanthine and uric acid were separated and quantitated. After 60 minutes' ischaemia AMP, inosine and hypoxanthine constituted 70% of the total pool (11, 7 and 4 pmoles/g dry wt respectively). However, after 00 minutes' anoxia, AMP, I,VP, adenosine, inosine, hypoxanthine and uric acid, in approximately equal proportions, made up 95% of the total pool. In these hearts approximately 50% of the total pool was rerovered from the coronary perfusate although nucleotides were not released into the perrusate. (Supported National
by Heart
grants from Foundation
the Medical Research of New Zealand).
Council
of
New Zealand
a"d
the
OF COand
Platelet activation and aggregation in the coronary circulation may be important in the :>athoge"esis of myocardial ischemia. Molsidomine (M), nitroglycerin (N) and isosorbide dinitrate (ISDN), have been found to inhibit platelet aggregation in vitro. 1n the present study the activity of these compounds was investigated in a model of coronary artery thrombosis in viva. Dogs were anesthetized, ventilated, thoracotomized and their heart exposed. A" electrode was inserted into the left circumflex coronary artery (LCX) and set to rest on the intima. Electrical stimulation (9 V, 150 pA) lasted 6 h. Compounds were given as a" i.v. infusion starting 30 min after the beginning of the stimulation and lasting for the duration of the experiment. All control (C; saline treated; n=14), N (0.5 pg/kg/min; n=6), and ISDN (10 pg/kg/min; n=6) dogs but only 4/8 (pc 0.05) M (1 pg/kg/min; n=8) animals underwent total thrombotic occlusion of the LCX as assessed by flow measurement. Thrombus wet weight (mg) was (2 ! SE) C: 74.4 + 11.3; M: 31.2 f 7.9 (pCO.051; N: 120.2 ? 18.5; ISDN: 90.8 + 12.9. Thrombotic occlusion resulted in myocardial infarction (assessed with nitroblue tetrazolium) in all C, N and ISDN dogs but only in S/8 M (~(0.05) animals. The hemodynamic changes induced by the 3 compounds were similar in magnitude. Thus M, but not N or ISDN, showed in this in viva study a" antithrombotic activity.
11 ON-LINE RESIDUE DETECTION OF 201Tl IN ISOLATED DOG HEARTS DURING CONTROL AND AFTER GLOBAL ISCHEMIA. B. Winkler, K.J. Henrichs, H. Matsuoka, G. StUmmler, W. Schaper, Max-Planck-Institute, Bad Nauheim, Federal Republic of Germany. Residue detection of 201~1 was performed on isolated dog hearts which were perfused with blood from a donor dog. The photons of 201~1, observed with a NaI(Tl)-detector facing directly the surface of the isolated hearts, were registered in a multichannel analyzer (MCA) in multiscaling mode. The MCA was directly connected to a computer system to accomplish a rapid data transmission. Beside the fast vascular component of 201Tl a slow washout rate from the cellular space was observed during control as well as after 60' of total global ischemia (k1/2=50min VS. k1/2=15min). The slow washout rate from the cellular space might be explained by assuming a" intracellular binding site for 201Tl. A large cellular permeability surface area product (PS,,Il) of 20'11 was observed with the multiple indicator dilution technique which was changed after 60' of global ischemia in the same order of magnitude as compared to its washout rates (PS,,ll - 8 ml/mi"/g-1 vs. 1.98 ml/min/g-1. Therefore, membrane changes and additional destruction of the internal cellular milieu, caused by the global ischemic intervention must be assumed for the changes of the washout rates.
12 COMPARISON OF MOCARDIAL ADENINE POOL CATABOLIS@ DmING GLOBAL ANOXIA AND ISCHAEMIA. Department of S.M. Humphrey, L.C. Armiger, D.G. Hollis. M.A. Morrison. R.N. Seelye. Pathology, University of Auckland School of Medicine, Auckland, New Zealand. Differences in coronary flow rates may alter the rate and extent of adenine pool decay in myocardium subsequent to severe oxygen deficierlcy. We compared metabolite changes in globally ischaemic (cross-clamped aorta) and iri globally arloxic (oxygenand nutrient-free perfusion at 10 KPa pressure) isolated rat hearts. At timed intervals, from O-60 minutes, hearts were snap-frozen at -19O'C and subsequelitly the perchloric acid extracts of tissue were subjected to reverse-phase high performance liquid chromatography. The coronary perfusate draining from anoxically perfused hearts was similarly treated. ATP, ADP, AMP, IMP, adenosirle, irlosine, hypoxanthine and uric acid were separated and quantitated. After 60 minutes' ischaemia AMP, inosine and hypoxanthine constituted 70% of the total pool (11, 7 and 4 pmoles/g dry wt respectively). However, after 00 minutes' anoxia, AMP, I,VP, adenosine, inosine, hypoxanthine and uric acid, in approximately equal proportions, made up 95% of the total pool. In these hearts approximately 50% of the total pool was rerovered from the coronary perfusate although nucleotides were not released into the perrusate. (Supported National
by Heart
grants from Foundation
the Medical Research of New Zealand).
Council
of
New Zealand
a"d
the