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Sildenafil Improves Coronary Artery Patency in a Canine Model of Platelet-Mediated Cyclic Coronary Occlusion After Thrombolysis

Gregory D. Lewis, MD^_*, Christian Witzke, MD^_*, Pedro Colon-Hernandez, MD^_*, J. Luis Guerrero^_*, Kenneth D. Bloch, MD^_*, and Marc J. Semigran, MD^_*,_*

^_* Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Cardiovascular Research Center of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

View larger version (25K): [in a new window]   Figure 1 Schematic representation of the coronary artery patency status of 12 dogs during two sequential observation periods. All dogs were observed during an initial 60-min period (period 1). During the second period (period 2), six animals received sildenafil (50 µg/kg bolus followed by 4 µg/kg/min), whereas six control animals received no further treatment. White areas represent coronary patency (flow >25% of baseline), and black areas represent occlusion.

View larger version (15K): [in a new window]   Figure 2 Coronary artery patency ratio (CAPR; fraction of an observed observation period during which the coronary flow was >25% of immediate postconstriction flow). Dogs in the control group (n = 6) were given no additional treatment in period 2. Dogs in the sildenafil group were given 100 µg/kg sildenafil bolus followed by an infusion of 4 µg/kg/min during period 2. *p = 0.008; #p = 0.007.

View larger version (14K): [in a new window]   Figure 3 Effects of aspirin and sildenafil on platelet aggregation. (A) Thrombin-induced platelet aggregation during the treatment period (+aspirin [ASA], at 30 min, and +sildenafil and aspirin [S+ASA] at 90 min) relative to baseline aggregation in the pretreatment period, as determined by whole blood aggregometry (n = 6 dogs). *p < 0.05, ASA versus baseline. *#p < 0.05, ASA+sildenafil versus each of the other groups. (B) Representative platelet aggregation recordings in dog 9.

View larger version (14K): [in a new window]   Figure 4 Effect of the bolus administration of sildenafil on mean arterial blood pressure (MAP). There was a transient fall in MAP within 1 min of the bolus administration of sildenafil that persisted for 3 min. The MAP 5 min after sildenafil administration did not differ from that at the end of period 1. *p < 0.05.