Intracoronary Serotonin and Endothelin Release After PCI / Stenting Taylor AJ. Am Heart J Aug;148(2): e10 Leosco et al, AJC 1999;84:

Dose Side Effects Adenosine 100 micrograms IC to a total dose of 4,000 micrograms Half life is 6 seconds. Adenosine can be repeatedly administered when pulse and blood pressure normalize Bradycardia, hypotension, difficulty breathing Verapamil 200 micrograms IC as a single dose to a total of 1000 micrograms (1 mg) Bradycardia, hypotension Diltiazem 200 micrograms IC as a single dose to a total dose of 1000 micrograms (1 mg) IC Bradycardia, hypotension Nicardipine 200 micrograms IC as a single dose to a total dose of 1000 micrograms (1 mg) IC Lower incidence of bradycardia, hypotension with this vasoselective agent Nitroprusside 100 micrograms IC as a single dose to a total dose of 1000 micrograms (1 mg) IC Lower incidence of bradycardia, hypotension *Administration of these agents is not listed as an approved indication in the package insert (i.e., off label use). ¶ Median dose was 200 micrograms IC in the Hillegass study (20). *Administration of these agents is not listed as an approved indication in the package insert (i.e., off label use). ¶ Median dose was 200 micrograms IC in the Hillegass study (20). Pharmacologic Agents Used to Treat Impaired Myocardial Perfusion* Gibson CM, Circulation 2003, in press

Randomized Intragraft Verapamil Prior to PCI: VAPOR Trial 1 p=0.02 Pre Post % Change Improved Worse No-Reflow (Improvement) 1 Michaels, Gibson et al. J Inv Cardiol 2002;14:299 TIMI FRAME COUNT TIMI MYOCARDIAL REPERFUSION GRADE In % P=0.06

Pharmacologic Management of No Reflow: Nipride Nitroprusside (Nipride) –Direct donor of nitric oxide 19 patients with no-reflow during native and SVG PCI 50-1,000  g boluses of SNP (median 200  g) Rapid improvement in –TIMI flow (p<0.01) –TFC (p<0.01) Hillegass WB, et al. J Am Coll Cardiol 37: , 2001

Impact of IC Adenosine & GP 2b3a Inhibitor on TIMI Myocardial Perfusion Grade Post PTCA Post PTCA + Adenosine Distal LAD with no blush Distal LAD with no blush Distal LAD with TIMI 3 Grade Blush Distal LAD with TIMI 3 Grade Blush (DSA = 0.1 Gray) (DSA = 5.2 Gray) CM Gibson 2004

Impact of IC Adenosine on Flow and Echocardiographic Outcomes in the Setting Primary PTCA % With Improved Wall Motion at One Week % With Worsened Wall Motion at One Week p < 0.05 p < Marzilli et al, Circulation 2000; 101: N=27 Placebo N=27 Adenosine 4 mg in 2 ml via central lumen of PTCA balloon % of Patients

Impact of IC Adenosine on Clinical & Electrocardiographic Outcomes in the Setting Primary PTCA % Developing Q Waves % Death, MI, CHF, Recurrent Angina p < 0.02 p < 0.04 p < 0.03 Marzilli et al, Circulation 2000; 101: N=27 Placebo N=27 Adenosine 4 mg in 2 ml via central lumen of PTCA balloon % of Patients

Coronary Flow Reserve Antithrombin + Eptifibatide Antithrombin + Eptifibatide N=27 N=16 P=0.02 Gray per sec P=0.05 N=27 N=18 Coronary Flow Reserve Rate of Increase in DSA Brightness (Gray /sec) Rate of Increase in DSA Brightness (Gray /sec) Circumference (cm) N=24 N= P=0.18 Rate of Growth in Blush Circumference (cm / sec) Rate of Growth in Blush Circumference (cm / sec) ESPRIT Substudy: Results All Patients Have TIMI Grade 3 Flow at Completion of Stenting & Antithrombin Treatment Antithrombin + Eptifibatide Antithrombin + Eptifibatide Antithrombin + Eptifibatide Antithrombin + Eptifibatide Gibson CM et al, Am J Cardiol 2001;87(11):

Integrilin in PCI and Filling of Muscle with Dye (Myocardial Blush) Addition of an antiplatelet agent eptifibatide to an antithrombin makes the muscle fill Bigger Brighter Faster Bigger Brighter Faster Gibson CM et al, Am J Cardiol 2001;87(11): Eptifibatide + Heparin: Muscle Brightness rises at 7.30 Gray per second Eptifibatide + Heparin: Muscle Brightness rises at 7.30 Gray per second Heparin Alone: Muscle Brightness rises at 3.97 Gray per second Heparin Alone: Muscle Brightness rises at 3.97 Gray per second P=0.05