Original Article

Platelet Preservation During Simulated Cardiopulmonary Bypass Via Phosphodiesterase Inhibition

¹ University of Pennsylvania School of Medicine, Department of Surgery Division of Cardiothoracic Surgery, Philadelphia, PA
² PSICOR, Inc., San Diego, CA

^* Address correspondence to: V. Paul Addonizio, MD, Temple University School of Medicine, Department of Surgery, Broad and Ontario Streets, Philadelphia, PA 19140

Abstract

Inhibition of platelet function reduces adverse platelet alterations during cardiopulmonary bypass (CPB) but agents most efficacious must be given intravenously. Consequently, we evaluated a new type III phosphodiesterase inhibitor (PDEI), CK2130 (100 uM), comparing it with the most commonly prescribed oral PDEI, dipyridamole (100 uM). 450 ml of fresh heparinized (5U/ml) blood, drawn from aspirin-free volunteers, was recirculated for 2 hrs at 37°C in a polypropylene circuit (1.0m²) containing a spiral-coil membrane oxygenator. In control saline circuits (N=5), platelet counts fell to 10±3% (mean + standard error of the mean) of initial levels within 5 min and sensitivity to ADP disappeared. Plasma levels of a platelet-specific protein platelet factor 4 (PF4) rose from 2780±222 ng/ml at five minutes to 6338±767 ng/ml after 2 hrs (p < .05), indicating extensive platelet release. In contrast, with CK2130 (N=3), although platelets were similarly insensitive to ADP, platelet counts dropped to only 63±11% at five minutes and PF4 rose from 1012±510 ng/ml at five minutes to only 3689± 898 ng/ml after 2 hrs (p < .05). With dipyridamole (N=4) platelet counts fell to 66±7% and PF4 rose from 861±122 ng/ml at five minutes to only 2157±346 ng/ml after 2 hrs (p <.05) but platelets remained responsive to ADP. In conclusion, both CK2130 and dipyridamole significantly preserved the initial circulating platelet count and reduced release of PF4 with CK2130 producing more pronounced inhibition of function as well. Thus, PDEIs may play a promising role as platelet inhibitors during CPB.