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
Cardiovascular Research Center of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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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.
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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.
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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.
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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.
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