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Cessation of platelet-mediated cyclic canine coronary occlusion after thrombolysis by combining nitric oxide inhalation with phosphodiesterase-5 inhibition

^a Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
^b Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
^c Cardiovascular Research Center of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

View larger version (45K): [in a new window]   Figure 1 Schematic representation of the coronary artery patency status in each of four dogs during three sequential 45-min observation periods (pre-treatment, intra-treatment and post-treatment). During the treatment period, the dogs were either untreated (control), breathed 20 ppm nitric oxide (NO), received zaprinast (1.0 mg/kg intravenously over 4 min, followed by a continuous infusion of 0.05 mg/kg per min), received dipyridamole (0.15 mg/kg intravenously over 4 min, followed by a continuous infusion of 0.004 mg/kg per min), received NO plus zaprinast or received NO plus dipyridamole. White areas of bars represent coronary patency (flow >25% of immediate post-constriction flow), and black areas represent occlusion.

View larger version (17K): [in a new window]   Figure 2 Coronary artery patency ratio (CAPR) (fraction of an observation period during which the coronary flow was >25% of immediate post-constriction flow) during the treatment period in dogs ventilated without (black bars) or with 20 ppm nitric oxide (NO) (white bars). The dogs were treated with intravenous zaprinast or dipyridamole or did not receive a phosphodiesterase (PDE) inhibitor (without a PDE inhibitor) (n = 4 dogs in each group). *p < 0.05 versus breathing 20 ppm NO without a PDE inhibitor. p < 0.05 versus treatment with a PDE inhibitor without breathing NO.

View larger version (15K): [in a new window]   Figure 3 Peak diastolic coronary artery blood flow rate (A) and coronary artery cross-sectional area (B) during intracoronary infusion of 10 nmol/min of U-46619 alone, combined breathing of 20 ppm nitric oxide (NO) with intravenous infusion of zaprinast (ZAP) (1.0 mg/kg over 4 min, followed by a continuous infusion of 0.05 mg/kg per min) and simultaneous breathing of 20 ppm NO with intravenous infusion of zaprinast or intravenous infusion of 1 µg/kg per min sodium nitroprusside (SNP). Data are mean ± SEM and expressed as percent coronary flow or area before administration of U-46619. *p < 0.05 versus U-46619 alone.

View larger version (16K): [in a new window]   Figure 4 Thrombin-induced platelet aggregation during the treatment period relative to the pre-treatment period, as determined by whole-blood aggregometry in control dogs and dogs treated with intravenous dipyridamole, inhaled nitric oxide (NO) and the combination of intravenous dipyridamole with inhaled NO (n = 4 dogs in each group). Data are expressed as the mean value ± SEM. *p < 0.05, NO plus dipyridamole versus each of the other groups.