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In-vitro-studies on the influence of positive inotropic drugs on acute myocardial ischemia
J Mel Cell Cardiol 23 (SupplementV) (1991)
P88 INFLUENCE OF POSITIVE INOTROPIC INTERVENTIONS ON THE FORCE-FREQUENCY-RELATION IN
NONFAILING AND FAILING HUMAN MYOCARDIUM B.Pieske, G.Hasenfuss, Ch.Holubarsch, T.Walde*, H. Just. Dept. of Cardiology, University of Freiburg and *Dept. of Cardiology, University of Berlin, FRG. Recent experiments have shown that the force-frequency-relation (FFR) is altered in the failing human myocardium. The infl!Jence of inotropic interventions on FFR was investigated in isometrically contracting left ventricular papillar? muscle strips from failinq hearts with mitral valve requrqitation (NYHA II-III) and from hearts with normal left ventricular size and- function. FFR was investigated at 37'C from 30 beats per minute (bpm) in 15-beat-intervals up to 180 bpm under control conditions and with Isoproterenol (ISO;O.O3uM). In nonfailing myocardium peak twitch tension (PTT) at Ca2t 2.5mmol (n=ll) increased from 1.9t0.3mN at 30 bpm to [email protected] at 150 bpm. IS0 (n=6) increased PTT by lOO-120% throughout the whole frequency range. In the failing myocardium, PTT at Ca2+ 2.5mmol (nz8) was 1.8i0.2 mN at 30 bpm, increased to 2.1k0.3mN at 60 bpm and then declined to l.kO.1 mN at 180 bpm. With IS0 (n=5), PTT was significantly increased by 122% at 30 bpm, by 48% at 60 bpm and was no longer increased significantly above 120 bpm. Thus, in nonfailing myocardium, IS0 increases PTT frequency while in failing myocardium positive independently of stimulation rates. inotropic effects of IS0 are present only at low stimulation
p89 :~~~~~~~~~~~,ONI~~~~~CE
OF POSITIVE
INOTROPIC DRUGS ON
Renate R&en, Bjiirn Sigmund, Jens Fuchs, WolfAlexis F.E.Rump, Institut fiir Pharmakologie, Univ. Kdln, FRG. gang Klaus. The application of cardiac glycosides in the initial phase of controversial since myocardial infarction remains highly acute myocardial oxygen the positive inotropic effect might increase Therefore we have and thereby increase ischemic damage. demand Langenin isolated rabbit hearts perfused according to studied dorff the effect of g-strophantin or isoprenalin in non arrythmoquantitative concentrations after coronary ligation using genie increased conNADH-fluorescence photography . Both substances In the presence of isoprenalin the enhanced oxygentractility. coronary flow demand was compensated by an increase in global whereas in the presence of g-strophantin flow was diminished. In neither g-strophantin nor isoprenalin did change spite of this, NADH-fluorescence. the intensity or the distribution pattern of concluded that an increase in contractility and oxygenIt is demand would not automatically increase the ischemic area.
f'90
NONIONIC X-RAY CONTRAST MEDIA AND IONS: INOTROPIC EFFECTS OF CALCIUM ADDITION TO IODIXANOL. Per Jynge, Torunn Holten, Terje GrenBs, Audun N Oksendal*. Dept. of Pharmacology and Toxicology, University of Trondheim; * Nycomed A/S, Oslo, Norway. Iodixanol is-a recently developed nonionic,-dimeric agent (6 iodine atoms per molecule) which opens for a new class of low osmolar x-ray contrast media. The three formulations containina 150 (A). 200 (B), and 300 fC) maI/ml are hvootonic in the absence of additives and-have thus been supplemented with respectively 70, 53 and 24 mM of sodium chloride to obtain isotonicity. The intracoronary-application of these media may induce a negative inotropic effect in isolated hearts mainly due to the media content of sodium, an effect that may be counterbalanced bv a careful addition of calcium. In the present study isolated Langendorff-perfused rat hearts were subjected to rapid bolus infusions with A, B and C and left ventricular developed pressure (LVDP) was recorded during exposure and recovery. A concentration-response study of calcium addition revealed: initial depression of LVDP by 59% (A), 49% (B) and 31% (C) without calcium; and an optimal balance between negative and positive inotropy in the presence of calcium 0.6-0.9 mM (A), 0.4-0.6 mM (B) and 0.2-0.4 mM (Cl. S.86
P88 INFLUENCE OF POSITIVE INOTROPIC INTERVENTIONS ON THE FORCE-FREQUENCY-RELATION IN
NONFAILING AND FAILING HUMAN MYOCARDIUM B.Pieske, G.Hasenfuss, Ch.Holubarsch, T.Walde*, H. Just. Dept. of Cardiology, University of Freiburg and *Dept. of Cardiology, University of Berlin, FRG. Recent experiments have shown that the force-frequency-relation (FFR) is altered in the failing human myocardium. The infl!Jence of inotropic interventions on FFR was investigated in isometrically contracting left ventricular papillar? muscle strips from failinq hearts with mitral valve requrqitation (NYHA II-III) and from hearts with normal left ventricular size and- function. FFR was investigated at 37'C from 30 beats per minute (bpm) in 15-beat-intervals up to 180 bpm under control conditions and with Isoproterenol (ISO;O.O3uM). In nonfailing myocardium peak twitch tension (PTT) at Ca2t 2.5mmol (n=ll) increased from 1.9t0.3mN at 30 bpm to [email protected] at 150 bpm. IS0 (n=6) increased PTT by lOO-120% throughout the whole frequency range. In the failing myocardium, PTT at Ca2+ 2.5mmol (nz8) was 1.8i0.2 mN at 30 bpm, increased to 2.1k0.3mN at 60 bpm and then declined to l.kO.1 mN at 180 bpm. With IS0 (n=5), PTT was significantly increased by 122% at 30 bpm, by 48% at 60 bpm and was no longer increased significantly above 120 bpm. Thus, in nonfailing myocardium, IS0 increases PTT frequency while in failing myocardium positive independently of stimulation rates. inotropic effects of IS0 are present only at low stimulation
p89 :~~~~~~~~~~~,ONI~~~~~CE
OF POSITIVE
INOTROPIC DRUGS ON
Renate R&en, Bjiirn Sigmund, Jens Fuchs, WolfAlexis F.E.Rump, Institut fiir Pharmakologie, Univ. Kdln, FRG. gang Klaus. The application of cardiac glycosides in the initial phase of controversial since myocardial infarction remains highly acute myocardial oxygen the positive inotropic effect might increase Therefore we have and thereby increase ischemic damage. demand Langenin isolated rabbit hearts perfused according to studied dorff the effect of g-strophantin or isoprenalin in non arrythmoquantitative concentrations after coronary ligation using genie increased conNADH-fluorescence photography . Both substances In the presence of isoprenalin the enhanced oxygentractility. coronary flow demand was compensated by an increase in global whereas in the presence of g-strophantin flow was diminished. In neither g-strophantin nor isoprenalin did change spite of this, NADH-fluorescence. the intensity or the distribution pattern of concluded that an increase in contractility and oxygenIt is demand would not automatically increase the ischemic area.
f'90
NONIONIC X-RAY CONTRAST MEDIA AND IONS: INOTROPIC EFFECTS OF CALCIUM ADDITION TO IODIXANOL. Per Jynge, Torunn Holten, Terje GrenBs, Audun N Oksendal*. Dept. of Pharmacology and Toxicology, University of Trondheim; * Nycomed A/S, Oslo, Norway. Iodixanol is-a recently developed nonionic,-dimeric agent (6 iodine atoms per molecule) which opens for a new class of low osmolar x-ray contrast media. The three formulations containina 150 (A). 200 (B), and 300 fC) maI/ml are hvootonic in the absence of additives and-have thus been supplemented with respectively 70, 53 and 24 mM of sodium chloride to obtain isotonicity. The intracoronary-application of these media may induce a negative inotropic effect in isolated hearts mainly due to the media content of sodium, an effect that may be counterbalanced bv a careful addition of calcium. In the present study isolated Langendorff-perfused rat hearts were subjected to rapid bolus infusions with A, B and C and left ventricular developed pressure (LVDP) was recorded during exposure and recovery. A concentration-response study of calcium addition revealed: initial depression of LVDP by 59% (A), 49% (B) and 31% (C) without calcium; and an optimal balance between negative and positive inotropy in the presence of calcium 0.6-0.9 mM (A), 0.4-0.6 mM (B) and 0.2-0.4 mM (Cl. S.86