Intracoronary Serotonin and Endothelin Release After PCI / Stenting Taylor AJ. Am Heart J. 2004 Aug;148(2): e10 Leosco et al, AJC 1999;84:1317-1322.

Intracoronary Serotonin and Endothelin Release After PCI / StentingIntracoronary Serotonin and Endothelin Release After PCI / Stenting

Taylor AJ. Am Heart J. 2004 Aug;148(2): e10Taylor AJ. Am Heart J. 2004 Aug;148(2): e10

Leosco et al, AJC 1999;84:1317-1322 Leosco et al, AJC 1999;84:1317-1322

DoseDose Side EffectsSide Effects

AdenosineAdenosine 100 micrograms IC to a total dose of 4,000 micrograms100 micrograms IC to a total dose of 4,000 microgramsHalf life is 6 seconds. Adenosine can be repeatedly Half life is 6 seconds. Adenosine can be repeatedly administered when pulse and blood pressure administered when pulse and blood pressure normalizenormalize

Bradycardia, hypotension, Bradycardia, hypotension, difficulty breathingdifficulty breathing

VerapamilVerapamil 200 micrograms IC as a single dose to a total of 1000 200 micrograms IC as a single dose to a total of 1000 micrograms (1 mg)micrograms (1 mg)

Bradycardia, hypotensionBradycardia, hypotension

DiltiazemDiltiazem 200 micrograms IC as a single dose to a total dose of 200 micrograms IC as a single dose to a total dose of 1000 micrograms (1 mg) IC1000 micrograms (1 mg) IC

Bradycardia, hypotensionBradycardia, hypotension

NicardipineNicardipine 200 micrograms IC as a single dose to a total dose of 200 micrograms IC as a single dose to a total dose of 1000 micrograms (1 mg) IC 1000 micrograms (1 mg) IC

Lower incidence of bradycardia, Lower incidence of bradycardia, hypotension with this hypotension with this vasoselective agentvasoselective agent

NitroprussideNitroprusside 100 micrograms IC as a single dose to a total dose of 100 micrograms IC as a single dose to a total dose of 1000 micrograms (1 mg) IC 1000 micrograms (1 mg) IC

Lower incidence of bradycardia, Lower incidence of bradycardia, hypotensionhypotension

*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 pressGibson CM, Circulation 2003, in press

Randomized Intragraft Verapamil Prior to PCI: VAPOR Trial1

50 47

1217

8

33

79

35

53

37

0 00

10

20

30

40

50

60

70

80

90

100

No Verapamil (n=12)

Verapamil (n=10)p=0.02

Pre Post % Change Improved Worse No-Reflow (Improvement)

1Michaels, Gibson et al. J Inv Cardiol 2002;14:299

TIMI FRAME COUNT TIMI MYOCARDIALREPERFUSION GRADE In %

P=0.06

Pharmacologic Management of No Reflow: NipridePharmacologic 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 37:1335-43, 2001

Impact of IC Adenosine & GP 2b3a Inhibitor on TIMI Myocardial Perfusion Grade

Impact of IC Adenosine & GP 2b3a Inhibitor on TIMI Myocardial Perfusion Grade

Post PTCAPost PTCA Post PTCA + AdenosinePost PTCA + Adenosine

DistalLAD with no blush

DistalLAD with no blush

DistalLAD with

TIMI 3 Grade Blush

DistalLAD with

TIMI 3 Grade Blush

(DSA = 0.1 Gray)(DSA = 0.1 Gray) (DSA = 5.2 Gray)(DSA = 5.2 Gray)

CM Gibson 2004CM Gibson 2004

Impact of IC Adenosine on Flow and Echocardiographic Impact of IC Adenosine on Flow and Echocardiographic Outcomes in the Setting Primary PTCAOutcomes in the Setting Primary PTCA

Impact of IC Adenosine on Flow and Echocardiographic Impact of IC Adenosine on Flow and Echocardiographic Outcomes in the Setting Primary PTCAOutcomes in the Setting Primary PTCA

70

100

0

20

40

60

80

100

TIMI 3

70

100

0

20

40

60

80

100

TIMI 3

36

64

0

20

40

60

80

100

36

64

0

20

40

60

80

100

% With Improved Wall Motion at

One Week

% With Improved Wall Motion at

One Week

29

20

20

40

60

80

100

29

20

20

40

60

80

100

% With Worsened Wall Motion at

One Week

% With Worsened Wall Motion at

One Week

p < 0.05p < 0.05 p < 0.0001p < 0.0001 p < 0.0001p < 0.0001

Marzilli et al, Circulation 2000; 101:2154-2159Marzilli et al, Circulation 2000; 101:2154-2159

N=27N=27 PlaceboPlacebo N=27N=27 Adenosine 4 mg in 2 ml via central lumen of PTCA balloonAdenosine 4 mg in 2 ml via central lumen of PTCA balloon

% o

f P

atie

nts

% o

f P

atie

nts

Impact of IC Adenosine on Clinical & Electrocardiographic Impact of IC Adenosine on Clinical & Electrocardiographic Outcomes in the Setting Primary PTCAOutcomes in the Setting Primary PTCA

Impact of IC Adenosine on Clinical & Electrocardiographic Impact of IC Adenosine on Clinical & Electrocardiographic Outcomes in the Setting Primary PTCAOutcomes in the Setting Primary PTCA

18

00

20

40

60

80

100

Death

18

00

20

40

60

80

100

Death

85

59

0

20

40

60

80

10085

59

0

20

40

60

80

100

% Developing Q Waves

% Developing Q Waves

48

18

0

20

40

60

80

100

48

18

0

20

40

60

80

100

% Death, MI, CHF, Recurrent Angina% Death, MI, CHF, Recurrent Angina

p < 0.02p < 0.02 p < 0.04p < 0.04p < 0.03p < 0.03

Marzilli et al, Circulation 2000; 101:2154-2159Marzilli et al, Circulation 2000; 101:2154-2159

N=27N=27 PlaceboPlacebo N=27N=27 Adenosine 4 mg in 2 ml via central lumen of PTCA balloonAdenosine 4 mg in 2 ml via central lumen of PTCA balloon

% o

f P

atie

nts

% o

f P

atie

nts

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

Co

ron

ary

Flo

w R

eser

veC

oro

nar

y F

low

Res

erve

AntithrombinAntithrombin Antithrombin

+ Eptifibatide

Antithrombin

+ Eptifibatide

1.28 + 0.41.28 + 0.4

1.78 + 0.951.78 + 0.95

N=27N=27 N=16N=16

P=0.02P=0.02

00

Gra

y p

er s

ecG

ray

per

sec

7.30 + 8.137.30 + 8.13

3.97 + 2.463.97 + 2.46

P=0.05P=0.05

N=27N=27 N=18N=18

Coronary Flow ReserveCoronary Flow Reserve Rate of Increase in DSA

Brightness (Gray /sec)

Rate of Increase in DSA

Brightness (Gray /sec)

5

10

5

10

Cir

cum

fere

nce

(cm

)C

ircu

mfe

ren

ce (

cm)

N=24N=24N=32N=32

7.2+ 3.27.2+ 3.2

8.5 + 4.08.5 + 4.0P=0.18P=0.18

Rate of Growth in

Blush Circumference

(cm / sec)

Rate of Growth in

Blush Circumference

(cm / sec)

ESPRIT Substudy: ResultsESPRIT Substudy: ResultsESPRIT Substudy: ResultsESPRIT Substudy: ResultsAll Patients Have TIMI Grade 3 Flow at Completion of Stenting & Antithrombin TreatmentAll Patients Have TIMI Grade 3 Flow at Completion of Stenting & Antithrombin Treatment

AntithrombinAntithrombin Antithrombin

+ Eptifibatide

Antithrombin

+ Eptifibatide

AntithrombinAntithrombin Antithrombin

+ Eptifibatide

Antithrombin

+ Eptifibatide

Gibson CM et al, Am J Cardiol 2001;87(11):1293-5.Gibson CM et al, Am J Cardiol 2001;87(11):1293-5.

Integrilin in PCI and Filling of Muscle with Dye (Myocardial Blush)

Integrilin in PCI and Filling of Muscle with Dye (Myocardial Blush)

Addition of an antiplatelet agent eptifibatide to an

antithrombin makes the muscle fill

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):1293-5.Gibson CM et al, Am J Cardiol 2001;87(11):1293-5.

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=0.05P=0.05