Type IV phosphodiesterase inhibition improves cardiac contractility in endotoxemic rats

Type IV phosphodiesterase inhibitors have a potential role in treating human sepsis. We examined the cardiac performance effects of type IV phosphodiesterase inhibition in vivo, in the absence and presence of catecholamines. Rats were randomized to receive either 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724) at 0 (vehicle), 2 or 10 mug/kg/min. Utilizing a left ventricular catheter to measure cardiac performance, each animal received each of the two catecholamines, epinephrine and norepinephrine, in randomized order. Rats then received intravenous endotoxin and additional infusions of catecholamines. Ro 20-1724 at 2 mug/kg/min protected cardiac contractility during endotoxemia, and at 10 mug/kg/min increased cardiac contractility and protected cardiac function during endotoxemia. Neither dose interfered with the maximal contractile response to catecholamines. Type IV phosphodiesterase inhibition with Ro 20-1724 exerts beneficial effects on cardiac performance during septicemia in an in vivo animal model. Clinical studies of type IV phosphodiesterase inhibitors in critically ill patients are indicated. (C) 2003 Elsevier Science B.V. All rights reserved.