Comparison between the effects of a novel Ca++ sensitizer and a phosphodiesterase inhibitor on stunned myocardium.
Inotropic agents are used widely for pharmacological bridging of the failing heart either until recovery after surgical intervention or until transplantation. EMD 57033 is a novel specific Ca++ sensitizing agent with purportedly minor phosphodiesterase (PDE) III-inhibiting properties. It acts as an inotropic agent without raising intracellular Ca++ levels. In turn, the PDE III-inhibitor enoximone has been used for several years to treat low cardiac output syndrome. However, little is known about its effects on postischemic reperfused (stunned) myocardium. We investigated the effects of EMD 57033 (EMD; 30 microM) and enoximone (E20 micrograms/ml) on stunned myocardium. The experiments were performed on 16 isolated rabbit hearts perfused with an erythrocyte suspension (hematocrit = 30%; [Ca++] = 2.5 mM). Hearts were reperfused after a 20 min no-flow ischemia. Measurements were performed at control, 30 min after the onset of reperfusion, and after administration of one of the drugs. Both agents significantly improved the depressed systolic function [left ventricular pressure (LVP)max from 61 +/- 12 to 93 +/- 18 mmHg, and its derived pressure (dP/dt)max from 860 +/- 220 to 1340 +/- 300 mmHg/s and LVPmax from 78 +/- 9 to 83 +/- 15 mmHg, and its derivative dP/dtmax from 1040 +/- 230 to 1385 +/- 300 mmHg/s, respectively] and early relaxation (dP/dtmin from 810 +/- 250 to 1260 +/- 345 mmHg/s and from 1000 +/- 200 to 1135 +/- 295 mmHg/s, respectively) that occurred during postischemic reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinic of Thoracic and Cardiovascular Surgery, University of Düsseldorf, Germany.
B
B
Korbmacher
U
U
Sunderdiek
H D
HD
Schulte
G
G
Arnold
J D
JD
Schipke
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D017335:Enoximone / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D013829:Thiadiazines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; D017335:Enoximone; D010100:Oxygen; D002118:Calcium