Use of the novel cardiotonic and vasodilator agent pimobendan in traumatic shock.
The effect of 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl- 3(2H)- pyridazinone (pimobendan, UD-CG 115 BS), a novel positive inotropic and vasodilator agent, was studied in a severe model of murine traumatic shock. Noble-Collip drum trauma produced a shock state characterized by a significantly reduced mean arterial blood pressure (MABP), a 5-fold increase in plasma cathepsin D and myocardial depressant factor (MDF) activities, and a survival time of 80 +/- 12 min. Administration of pimobendan (100 micrograms/kg, i.v. bolus) significantly prolonged the survival time to 175 +/- 24 min (p less than 0.01). Although plasma cathepsin D was not affected by pimobendan, this agent significantly attenuated the accumulation of MDF activity in the plasma when compared to animals receiving only its vehicle (37 +/- 6 vs 61 +/- 9 U/ml, p less than 0.05). Additionally, pimobendan inhibited platelet aggregation in cat platelet rich plasma, but failed to have an antiproteolytic effect in cat pancreatic homogenates. These results suggest that cardiotonic and vasodilator activities combined with inhibition of platelet aggregation could mediate the beneficial effects of pimobendan in traumatic shock.
Bitterman
H
H
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.
Smith
B A
BA
Lefer
A M
AM
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002402:Cathepsin D / Q000097:blood; D002415:Cats; D004195:Disease Models, Animal; D007511:Ischemia; D008297:Male; D009201:Myocardial Depressant Factor / Q000097:blood; D010179:Pancreas / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012774:Shock, Traumatic / Q000188:drug therapy*; D013152:Splanchnic Circulation; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D009201:Myocardial Depressant Factor; D011724:Pyridazines; D014665:Vasodilator Agents; C041648:pimobendan; D002402:Cathepsin D