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Use of phosphorus31 nuclear magnetic resonance to assess intracellular buffering during global ischemia
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MODIFICATION OF CARDIOVASCULAR RESPONSES TO INTRAVENOUS MOLSIDOMINE BY NOREPINEPHRINE AND DOPAMINE IN DOGS. V.B. Fiedler and R.-E. Nits. Medical Biological Res., Cassella AG, Frankfurt, F.R.G. Molsidomine(M) reduces heart preload (LVEDP,PAP,venous return) and afterload (AoP,BP,TPR).Both these effects lower the heart work and myocardial oxygen consumption (MV02).we tried to influence M effects on preand afterload with pharmacological interventions in dogs. 20 dogs were instrumented and hemodynamic parameters continuously recorded:BP,HR,LVEDP,LVP,PAP,SV,CO,dp/dt,AoP.M was administered in a high dose (-5 mg/kg iv) to cause clear effects on the parameters. After stabilization of M effects, norepinephrine (Nor)was permanently infused up to 180 min in cumulative doses from ,1 to .2 ug/kg/ml x min (6 animals). Dopamine (Dop) was infused for a twenty-min period with 3 and 6 ug/kg/ml x min (6 animals). Nor and Dop antagonized the M induced effects on afterload of the heart (AoP,BP and TPR).Both compounds did not influence M effects on LVEDP and PAP.SV and CO as heart performance indices increased. HR was reduced after Nor and Dop while dp/dt was significantly increased with both substances. It is therefore suggested that Nor and Dop influence predominantly afterload changes following M administration.Dop was found to be more effective than Nor. Contractility augmentation (dp/dt) after Nor and Dop shows increased heart performance.These results suggest a therapeutic role for the combination of M and Nor or Dop in cardiogenic shock.
USE OF PHOSPHORUS31 NUCLEAR MAGNETIC RESONANCE TO ASSESS INTRACELLULAR BUFFERING DURING GLOBAL ISCHEMIA. J.T. Flaherty, W.E. Jacobus, M.L. Weisfeldt, D.L. Hollis, T.J. Gardner, V.L. Gott. Divisions of Cardiology and Cardiac Surgery,Johns Hopkins Medical Institutions Baltimore, MD. Recent studies from this laboratory demonstrated that phosphorus 3fnuclearmagnetic resonance (NMR) can be used to assess myocardial protection during global ischemia. In the present study NMR was employed with an isolated isovolumic perfused rabbit heart preparation to monitor intracellular pH and tissue levels of phosphoryl-creatine (PCr) and adenosine triphosphate (ATP). Sixteen hearts were studied: Group I was maintained hypothermic (270C) and received a single dose of hyperkalemic (37 mEq/ L) cardioplegic solution, Group II received 3 doses of cardioplegic solution at 20 min intervals and Group III received 3 doses of a cardioplegic solution which hod bicarbonate added to increase pH from 7.4 to 7.8, maintaining osmolality constant. NMR results after 60 min of ischemia are expressed as mean + SEM (*=p 4 .05 vs I or II). ATP (% Control) PCr (% Control) Group I (n = 5) 6xl-F-w 31 4 5 1 75 : 20* 6:2 Group I I (n = 5) 6.79 T :03* 71 TlO 17 r4* Group III (n = 6) 6.99 T- .04* Administration of multiple doses of cardioplegic solution reduced the severity of intracellular acidosis and improved preservation of ATP, but not PCr. Increasing pH and buffering capacity of the cordioplegic solution further reduced the severity of acidosis and improved reservation of PCr during ischemia. These results suggest that increasing the pH and P or buffering capacity of the cardioplegic solution may be important for optimizing myocardial preservation.
MODIFICATION OF CARDIOVASCULAR RESPONSES TO INTRAVENOUS MOLSIDOMINE BY NOREPINEPHRINE AND DOPAMINE IN DOGS. V.B. Fiedler and R.-E. Nits. Medical Biological Res., Cassella AG, Frankfurt, F.R.G. Molsidomine(M) reduces heart preload (LVEDP,PAP,venous return) and afterload (AoP,BP,TPR).Both these effects lower the heart work and myocardial oxygen consumption (MV02).we tried to influence M effects on preand afterload with pharmacological interventions in dogs. 20 dogs were instrumented and hemodynamic parameters continuously recorded:BP,HR,LVEDP,LVP,PAP,SV,CO,dp/dt,AoP.M was administered in a high dose (-5 mg/kg iv) to cause clear effects on the parameters. After stabilization of M effects, norepinephrine (Nor)was permanently infused up to 180 min in cumulative doses from ,1 to .2 ug/kg/ml x min (6 animals). Dopamine (Dop) was infused for a twenty-min period with 3 and 6 ug/kg/ml x min (6 animals). Nor and Dop antagonized the M induced effects on afterload of the heart (AoP,BP and TPR).Both compounds did not influence M effects on LVEDP and PAP.SV and CO as heart performance indices increased. HR was reduced after Nor and Dop while dp/dt was significantly increased with both substances. It is therefore suggested that Nor and Dop influence predominantly afterload changes following M administration.Dop was found to be more effective than Nor. Contractility augmentation (dp/dt) after Nor and Dop shows increased heart performance.These results suggest a therapeutic role for the combination of M and Nor or Dop in cardiogenic shock.
USE OF PHOSPHORUS31 NUCLEAR MAGNETIC RESONANCE TO ASSESS INTRACELLULAR BUFFERING DURING GLOBAL ISCHEMIA. J.T. Flaherty, W.E. Jacobus, M.L. Weisfeldt, D.L. Hollis, T.J. Gardner, V.L. Gott. Divisions of Cardiology and Cardiac Surgery,Johns Hopkins Medical Institutions Baltimore, MD. Recent studies from this laboratory demonstrated that phosphorus 3fnuclearmagnetic resonance (NMR) can be used to assess myocardial protection during global ischemia. In the present study NMR was employed with an isolated isovolumic perfused rabbit heart preparation to monitor intracellular pH and tissue levels of phosphoryl-creatine (PCr) and adenosine triphosphate (ATP). Sixteen hearts were studied: Group I was maintained hypothermic (270C) and received a single dose of hyperkalemic (37 mEq/ L) cardioplegic solution, Group II received 3 doses of cardioplegic solution at 20 min intervals and Group III received 3 doses of a cardioplegic solution which hod bicarbonate added to increase pH from 7.4 to 7.8, maintaining osmolality constant. NMR results after 60 min of ischemia are expressed as mean + SEM (*=p 4 .05 vs I or II). ATP (% Control) PCr (% Control) Group I (n = 5) 6xl-F-w 31 4 5 1 75 : 20* 6:2 Group I I (n = 5) 6.79 T :03* 71 TlO 17 r4* Group III (n = 6) 6.99 T- .04* Administration of multiple doses of cardioplegic solution reduced the severity of intracellular acidosis and improved preservation of ATP, but not PCr. Increasing pH and buffering capacity of the cordioplegic solution further reduced the severity of acidosis and improved reservation of PCr during ischemia. These results suggest that increasing the pH and P or buffering capacity of the cardioplegic solution may be important for optimizing myocardial preservation.