TIMI classification in coronary perfusion

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-In-Chief: Priyantha Ranaweera [2]; Phone:6176327783


Introduction

Name “coronary” was coined in the mid 19th century on the belief that there were free arterial anastomoses resembling a corona – latin for crown.

Earliest description of mechanical relief of coronary thrombotic obstruction came form the work of Chazov in 1962 ref1.

Earliest report of intra-coronary drug administration came from Ganz et al when intra coronary (ic) streptokinase was successfully administered to a thrombosed artery ref2.

Thrombolysis in acute myocardial infarction has reduced mortality by 30%.

The main aim at that time was to restore mere luminal patency in the culprit coronary artery.

With the introduction of the “normal flow” which included the TIMI flow grade, the goal of reperfusion further refined to restoration of “normal or TIMI III’ epicardial blood flow.

TIMI group noted that there was no improvement in left ventricular function after successful thrombolysis. (3)Understanding of "downstream" coronary flow dynamics and its clinical implications followed.

TIMI flow grade was further refined to a corrected TIMI frame count (CTFC).

This was followed by the angiographic observation of a surrogate of tissue level function of the myocardium – the TIMI myocardial perfusion grade (TMPG or TIMI blush grade).

Emphasis thus changed to tissue level preservation of the myocardial milieu.

Many interventions – both pharmacological and mechanical- have been tested in prevention and treatment of this disturbed milieu in the myocardial microvasculature in the setting of ischemia and thromboembolism. What follows is an overview.

Pathophysiology and sequelae of coronary thrombosis

The process of coronary thrombosis starts at a ruptured or fissured plaque creating an in-situ platelet and fibrin aggregate which progresses to an occlusive thrombus.

There is also dissemination of platelet rich thrombi down stream which cause micro vascular obstruction and tissue level myocardial ischemia.

This leads to coronary microvascular dysfunction, ( ie: disordered function of the smaller coronary resistance vessels (< 100-200 µm) which are not seen on coronary angiography.

There are also multiple humoral factors which play a role in setting up the cascade of reversible and irreversible damage at cellular and ultra-structural level.

This leads to

At macrovascular level

Spasm

At microvascular level

  • vasoconstriction
  • Thromboembolism and distal ischemia

At cellular level

  • Neutrophil plugging
  • Swelling and edema of endothelial and myocardial cells
  • Capillary leak
  • In the setting of reperfusion – hemorrhage in the interstitium
  • myocytolysis (large vacuoles in cells) and cell death and removal of dead cells by macrophages, with the beginning of vascular granulation tissue formation followed by repair-granulation tissue, becoming more fibrous and less vascular over time

At ultra-structural level

  • dead cells develop contraction bands (hypercontraction of myocytes)


Reveresible and irreversible components of the microvascular dysfunction

Clinically TIMI flow rate, CTFC, TMPG, ECG, LVEF all complement each other in their reflection of the state of the affected myocardium.

In the acute setting, apart from the ECG, there are no indicators to differentiate myocardial reversibility from irreversibility.


Pathophysiology of reversible flow changes in the microvasculature

1.Heightened downstream microvascular obstruction

1.1.alpha adrenergic neural reflexes,

1.2.spasm due to other causes

1.3.thrombotic occlusion of microvessels.

Pathophysiology of irreversible changes in the microvasculature

1.capillary leak – advanced stages

2.interstitial hemorrhage

3.Cell death

4.Fibrosis

TIMI CLASSIFICATION AND OPEN MUSCLE HYPOTHESIS – AN OVERVIEW

THE OPEN ARTERY CONCEPT AND THE TIMI FLOW RATE

Patients with a patent infarct related artery 90 minutes after the start of thrombolytic therapy, there was a lower 6 month (5.6% vs. 12.5%) and 1 year mortality (8.1% vs. 14.8%). (4)

(Figure 1 Source : http://www.timi.org )(4)


Fig 1.jpg


For patients with both early and sustained patency through hospital discharge, the subsequent mortality was 3.8% at 1 year. (4)

More studies confirmed that early reperfusion decreased infarct size, improved left ventricular function and survival. (5,6)

TIMI FLOW GRADE

In order to evaluate the coronary reperfusion more accurately and in a reproducible manner, a grading system of was developed initially for use in the TIMI 1 trial. This has subsequently been adopted almost universally.

TIMI grade 0 - complete occlusion of the coronary artery

TIMI grade 1 - some penetration of the obstruction by contrast material, but no perfusion of the distal coronary bed.

TIMI grade 2 - perfusion of the entire coronary artery, but with delayed flow compared to a normal artery

TIMI grade 3 - flow denotes full perfusion with normal flow.

TIMI FLOW IN ACUTE STE MI

In the TIMI 1 trail, patients with TIMI grade 3 flow at 90 minutes of thrombolytic therapy had the lowest mortality, 4.7%, compared to 7.0% and nearly11% for patients with TIMI grade 2 flow and TIMI grade 0 - 1 flow respectively. (8)


TIMI FLOW IN UNSTABLE ANGINA

Faster flow was shown to be associated with improved clinical outcomes both in the acute MI setting and in the setting of unstable angina following percutaneous coronary intervention. (9,10,11)


(Figure 2).

Fig 2.jpg

CORRECTED TIMI FRAME COUNT – CTFC

limitations with TIMI grading of coronary blood flow is the relative lack of reproducibility between angiographers with one study, showing an agreement of TIMI grade 3 flow of 71%. (12)

This was addressed with the development of a quantitative assessment – the TIMI frame count – which was based on the number of angiographic frames needed for dye to traverse the artery. (13)

This is a measure of time and it does not account for vessel length or volume, and is only an index of coronary velocity and flow.

CTFC has been shown to be reproducible, with a coefficient of correlation of .0.95 between observers and differences between observers of 2 frames . French et al. reported mean differences between observers of 0.75 frames. (14,15,16,17)


TIMI 4 FLOW

Within the group with TIMI III flow, there is a group of patients with even faster (a TIMI frame count < 14) than normal flow (hyperemic flow)

Patients with this flow have even better outcomes than those patients with slower TIMI grade 3 flow. In order to have hyperemic flow, the integrity of the microvasculature must be better preserved when compared to the rest of the patient cohort. (18)(Figure 2).

(Figure 3 – Even faster epicardial flow is related to better outcomes)


Fig 3.jpg

BLOOD FLOW IN NON CULPRIT ARTERIES DURING ACS

both in acute MI and in the setting of unstable angina epicardical coronary flow was abnormal also in the non culprit arteries (by 40% in the setting of acute MI). (normally 21 frames for dye to traverse an epicardial artery in the absence of acute MI, flow in uninvolved arteries is slowed to over 30 frames)

In a quarter of cases, flow in the uninvolved artery was actually slower than the culprit artery. (19, 20)

(Figure 4 Acute MI slows blood flow globally)

Fig 4.jpg

FLOW FOLLOWING PCI – ACUTE MI

The flow following PCI for acute MI was often the same as that in non-culprit arteries: over 30 frames13

PCI improved culprit TIMI frame count by 6 frames – 9 frames short of being normal – a consequence of a disturbed milieu at tissue level.

Slower global flow in all three arteries was also associated with a higher risk of adverse outcomes including mortality compared to those who had normal flow in non culprit arteries.

In one study, flow in the uninvolved artery improved following PCI of the culprit artery significantly (by nearly 10 frames) if it was abnormal to begin with.

After 15 minutes of observation, however, flow in both the culprit and non-culprit arteries again slowed back down to pre-intervention values which was re-restored after administration of α-blockers. - In this study patients initially received thrombolysis followed by angiography 24 hrs later. Also there was no use of glycoprotein inhibitors. (21,22)

STENTING AND CTFC

In the PAMI stent trial, compared with conventional primary angioplasty, stenting reduced restenosis. How ever one month and six-month mortality were higher among stented patients, (specially with a closed vessel preceding PCI). Suggesting the possibility that stenting may have irreversibly disturbed the distal vascular bed, probably by increasing downstream embolization of atheroembolic particles. Also the stenting process may have generated more humoral factors –some of which may have been reversible - producing undesirable effects. (23,24)


RESIDUAL STENOSIS AND MORTALTY

Even though the residual stenosis was only 16% following adjunctive stent placement, normal flow was still not restored in up to one-third of patients – a group with significantly higher mortality. This is highly unlikely to be due to the minimal residual stenosis. (25)

IV nitrates following thrombolytic administration was shown to slow the CTFC (increase transit time down the artery). How ever overall flow in was preserved. (26)


IS BIGGER THE BETTER WITH STENTING?

It has also been shown that larger stent sizes were associated with a higher risk of slower flow. (27 ref pending)

CTFC AND LONG TERM SURVIVAL=

French et al, reported CTFC after myocardial infarction was an independent predictor of 5-year survival, but was not superior to TIMI flow grading. Neither factor independently influenced 10-year survival. (28)

CTFC COMPARED TO OTHER PROGNOSTICATORS

CFR

Maginas et al, showed that the CTFC, could be used reliably in the catheterization laboratory to estimate CFR. (29)

CTFC used in the context of a ratio with minimal luminal diameter, before and after adenosine was shown to be highly correlated with coronary flow reserve (CFR) as assessed using a Doppler velocity wire (r=0.88). (30)


TIMI FRAME COUNT IN ESTIMATING CORONARY BLOOD FLOW

The combination of quantitative coronary angiography and the TIMI frame count could be used to integrate velocity and volume measurements to estimate coronary blood flow.

Potentially these methods could be automated to provide estimates of absolute coronary blood flow in the cardiac catheterization laboratory. (31)


BEYOND THE EPICARDIAL VESSEL – REACHING FOR THE MICROVASCULATURE MILIEU

MICROEMBOLISATION IN TO THE DISTAL VASCULAR BED

Small areas of myocardial necrosis due to emboli likely from a ruptured plaque were first demonstrated on post mortem analysis Falk in a post mortem analysis, which was subsequently confirmed in-vivo by Gibson et al. (32)


MYOCARDIAL CONTRAST ECHOCARDIOGRPHY

With no reflow, microbubbles do not enter the myocardium where there is a higher risk of arrhythmia, congestive heart failure, or death.

This technique is limited for routine clinical application due to the need of additional equipment, personnel, time and expense. (33)


TIMI MYOCARDIAL PERFUSION GRADE / BLUSH GRADE (TMPG)=

A simple semi-quantitative technique that could be conveniently and reliably applied in the cardiac catheterization laboratory, enabling the angiographer to assess tissue level perfusion from the angiogram alone. (34)

Figure 4 : video demonstration can be seen at

http://www.perfuse.org

http://www.timi.org.


Fig 4.jpg

CORRELATION OF TMPG TO OTHER MODALITIES IN ASSESSING MICROVASCULATURE =

TMPG was strongly related to i.v. myocardial contrast echocardiography (MCE) and CFR using iv adenosine.

Patients with normal myocardial blush also have improved wall motion on echocardiography. (35)


TIMI MYOCARDIAL PERFUSION GRADES

=NORMAL MYOCARDIUM – GRADE 3

Normal ground glass appearance of myocardial blush diffusely, and at the end of the washout phase, dye is only mildly persistent or is gone.

MILDLY IMPAIRED TISSUE LEVEL PERFUSION – GRADE 2=

Dye enters the myocardium, but accumulates and exits more slowly. At the end of the washout phase, dye in the myocardium is strongly persistent.

MODERATELY IMPAIRED TISSUE LEVEL PERFUSION - GRADE 1

The dye does not leave the myocardium and there is a stain on the next injection.

SEVERELY IMPAIRED TISSUE LEVEL PERFUSION – GRADE 0=

Dye does not enter the myocardium and there is minimal or no blush apparent during the injection and washout phases.


TMPG - SHORT TERM OUTCOMES

In patients treated with thrombolysis, normal TIMI myocardial perfusion grade 3 flow was associated with improved mortality. (36) (Figure)

(Figure 5 TMP grades)


Fig 5.jpg

DOES TMPG GRADING ADD INFORMATION BEYOND TIMI FLOW GRADING ?

Patients with TIMI grade 3 flow in the epicardial artery who had a closed microvasculature (TMPG 0/1 flow) had a higher mortality (5.4%) than those with TMPG 2 (2.9%) or TMPG 3 flow (0.7%)(p=0.007)(Figure).

Even among patients with TIMI grade 3 flow, there was a 7-fold increase in mortality dictated independently by the extent of the TMP grading. TIMI myocardial perfusion grade was a predictor of 30-day mortality, independent of gender, age, admission pulse, anterior MI location, the TIMI frame count, and the TIMI flow grade. (37)


TMPG - LONG TERM OUTCOMS

For patients who had thrombolytic therapy for STEMI, at 2 years following thrombolytic therapy, the TMPG was a multivariate predictor of mortality, independent of flow in the epicardial artery. (36)


(Figure 6 TMPG and mortality)


Fig 6.jpg

TMPG IN THE SETTING OF EMERGENCT PCI

TMPG was a more potent and accurate predictor of survival than was TIMI flow alone after acute infarct PTCA

Interventions which normalize myocardial blush may in fact reduce mortality.

Interestingly only ~30% of pts undergoing PTCA had normal myocardial blush restored (38)


TMPG IN THE SETTING OF OTHER KNOWN PROGNOSTICATORS

ECG

Among patients with epicardial TIMI grade 3 flow, improved flow in the microvasculature by the TMPG method is also associated with improved EKG resolution by the Schroeder criteria. (39)

In acute STE MI, restoration of flow associated with TMPG 3 was shown to be associated with higher rates of complete ST resolution on the static ECG. It was also a predictor of rapidity of achieving the time to stable ST-segment resolution by a factor of two. (40)

Though the ECG and the TMBG are associated, they provide independent and complimentary prognostic information about infarct size (41)


LEUKOCYTOSIS DURING ACUTE MI

Leukocytosis may not only be an association but also portends a poorer prognosis.

Leucocytosis was associated with reduced epicardial blood flow, myocardial perfusion thromboresistance (arteries open later and have a greater thrombus burden),and a higher incidence of new congestive heart failure and death, the development of which was independent of coronary blood flow and other covariates. (42)


TMPG USING DSA

By using digital subtraction angiography (DSA) further refinement of the interpretation of TMPG is possible.


METHOD

(Figure 7 Computerized DSA imaging of TMPG)

Fig 7.jpg

A background image is created by saving an image before dye fills the myocardium which contains an image of the ribs, spine, lung and the artery itself. An image is then stored from several heart beats later, at a time when dye has filled the myocardium - the “blush image.” The background image is then subtracted from the “blush image” to remove the unwanted obtrusive structures isolating a picture of the dye in the heart muscle. The brightness of the blush, the size of the blush and the time it took for the blush to attain that size and brightness is measured. ECG gating is used to minimize motion artefacts.

This technique showed glycoprotein IIb/IIIa inhibition with eptifibatide to be associated with more rapid filling of the myocardium with a larger blush with improved coronary flow reserve, in the setting of unstable angina and stenting. It was also shown that TMPG grades 0-2 were associated with increased CK release and higher clinical event rates. (43)


The five laws as suggested by Gibson, governing the time-dependent open vasculature hypothesis

1 Not all TIMI grade 3 flow is created equally

2. TIMI grade 3 flow is necessary but not sufficient

3. It is the restoration of normal tissue level reperfusion that optimized outcomes

4. Time is myocardium: faster restoration of flow is related to improved clinical outcomes (44)

5. Sustained flow and the absence of re-occlusion is related to improved outcomes(45)

Resource

  1. ref1 PMID 15541835

References

1. Chazov, Bulletin of Experimental Biology and Medicine, Vol 5, No 2, Feb 1962

2. Ganz et al; Circ 1979 Vol 60 Supp II – 845

3. Passamani E, on behalf of the TIMI study group. The Thrombolysis In Myocardial Infarction (TIMI) trial. N Engl J Med. 1985;312:932–936

4. Dalen JE, Gore JM, Braunwald E, Borer J, Goldberg RJ, Passamani ER, Forman S, Knatterud G, and the TIMI Investigators. Six- and twelve-month follow-up of the Phase I Thrombolysis in Myocardial Infarction (TIMI) Trial. Am J Cardiol 1988;62:179-85

5. Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival: Should the paradigm be expanded? Circulation 1989;79:441-4

6. Braunwald E. The open-artery theory is alive and well - again. N Engl J Med 1993;329:1650-2.

7. Cannon CP, Braunwald E. GUSTO, TIMI and the case for rapid reperfusion. Acta Cardiol 1994;49:1-8.

8. Flygenring BP, Sheehan FH, Kennedy JW, Dodge HT, Braunwald E, for the TIMI Investigators. Does arterial patency 90 minutes following thrombolytic therapy predict 42 day survival?(abstract) J Am Coll Cardiol 1991;17 (Suppl. A):275A

9. Anderson JL, Karagounis LA, Becker LC, Sorensen SG, Menlove RL for the TEAM-3 Investigators. TIMI perfusion grade 3 but not grade 2 results in improved outcome after thrombolysis for myocardial infarction. Ventriculographic, enzymatic, and electrocardiographic evidence from the TEAM-3 study. Circulation 1993;87:1829-1839.

10. The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615-1622

11. Gibson CM, Murphy SA, Rizzo MJ, et al. The relationship between the TIMI Frame Count and clinical outcomes after thrombolytic administration. Circulation 1999;99:1945-1950.

12. Ross AM, Neuhaus KL, Ellis SG. Frequent lack of concordance among core laboratories in assessing TIMI flow grade after reperfusion therapy. Circulation 1995; 92:I-345.

13. Gibson CM, Cannon CP, Daley WL, et al. The TIMI Frame Count: A Quantitative Method of Assessing Coronary Artery Flow. Circulation 1996; 93:879-888.

14. Ivanc TB, Crowe TD, Balazs EM, et al. Reproducibility of the corrected TIMI frame count in angiograms of MI patients receiving thrombolysis (abstr). J Am Coll Cardiol 1998;31:11A.

15. French JK, Ellis CJ, Webber BJ, et al. Abnormal coronary flow in infarct arteries 1 year after myocardial infarction is predicted at 4 weeks by corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and stenosis severity. Am J Cardiol 1998;81:665–71.

16. French JK, Ellis CJ, White HD. The corrected TIMI frame count: the new gold standard? Aust N Z J Med 1998;28:569 -73.

17. French JK, Straznicky IT, Webber BJ, et al., for the HERO 1 Investigators. Angiographic frame counts 90 minutes after streptokinase predict left ventricular function at 48 hours following myocardial infarction. Heart 1999;81:128 –33.

18. Gibson CM, Murphy SA, Rizzo MJ, et al. The relationship between the TIMI Frame Count and clinical outcomes after thrombolytic administration. Circulation 1999;99:1945-1950.

19. Gibson CM, Ryan KA, Murphy SA, et al. Impaired coronary blood flow in non-culprit arteries in the setting of acute myocardial infarction. J Am Coll Cardiol 1999;34: 974-82.

20. Gibson CM, Goel, M, Rizzo M, et al for the RESTORE Investigators. Impaired Coronary Blood Flow in Non-Culprit Arteries in the Setting of Acute Coronary Syndromes:A RESTORE substudy. Am J Cardiol 2000,

21. Gibson CM, Ryan KA, Murphy SA, et al. Impaired coronary blood flow in non-culprit arteries in the setting of acute myocardial infarction. J Am Coll Cardiol 1999;34: 974-82.

22. Gregorini L, Marco J, Kozakova M, et al. Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction. Circulation 1999; 99:482-490.

23. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1999;341(26):1949-56.

24. Lansky AJ, Stone GW, Mehran R, et al. Impact of baseline TIMI flow on outcomes after primary stenting versus primary PTCA in acute myocardial infarction. Results from PAMI stent. J Am Coll Cardiol. 1999;33 (Suppl A):368A.

25. Gibson CM, Murphy SA, Menown I, et al for the TIMI Study Group. Determinants of Coronary Blood Flow Following Thrombolytic Administration. J Am Coll Cardiol 1999; 34:1403-12.

26. Rebecca Mesley, Martin Aldrich, Jill Swanson, Sabina Murphy, Colin Hynes, Timothy Saunders, Robert Zemble, Susan J. Marble, Carolyn H. McCabe, Christopher P. Cannon, C. Michael Gibson. For the T/Ml Study Group, University of California San Francisco, Brigham & Women’s Hospital, Boston, USA; Impact of Nitrate Administration on the TIMI Frame Count and TIMI Flow Grades in the Setting of Acute Myocardial Infarction.

27.

28. John K. French, Thomas A. Hyde, Ivan T. Straznicky, Jacquelin Andrews, Mayanna Lund, David J. Amos, Andrew Zambanini, Christopher J. Ellis, Bruce J. Webber, Stephanie C. McLaughlin, Ralph M.L. Whitlock, Hitesh Patel, Harvey D. White. Green Lane hospita/, Auckland, New Zealand; The Relationship Between Corrected Timi Frame Counts and Late Survival After Myocardial Infarction

29. Manginas A, Gatzov P, Chasikidis C, Voudris V, Pavlides G, Cokkinos DV. Estimation of coronary flow reserve using the Thrombolysis In Myocardial Infarction (TIMI) frame count method. Am J Cardiol 1999;83(11):1562-5.

30. Stankovic G, Manginas A, Voudris V, et al. Prediction of restenosis after coronary angioplasty by use of a new index: TIMI frame count/minimal luminal diameter ratio. Circulation 2000;101:962-8

31. Quantitative Angiographic Measurement of Absolute Coronary Blood Flow 81 Its Relation to Mortality in Acute Myocardial Infarction G. Michael Gibson, Rebecca Mesley, Timothy Saunders, Colin Hynes, Sabina Murphy, Robert Zemble, Susan J. Marble, Carolyn H. McCabe, Elliott M. Antman, Eugene Braunwald. for the T/M/ Study Group, University of California San Francisco, Brigham & Women’s Hospital Boston, USA

32. Falk, Circulation 71, No. 4, 699-708, 1985

33. Ito H, Tomooka T, Sakai N, et al. Lack of Myocardial Perfusion Immediately After Successful Thrombolysis. A Predictor of Poor Recovery of Left Ventricular Function in Anterior Myocardial Infarction. Circulation 1992; 85:1699-1705.

34. Gibson CM, Cannon CP, Murphy SA, et al for the TIMI Study Group. The Relationship of the TIMI Myocardial Perfusion Grade to Mortality Following Thrombolytic Administration. Circulation 2000;101:125-130

35. Lepper W, Hoffman R, Kamp O, et al. Angiographic myocardial blush grade relates to myocardial contrast echo and coronary flow reserve for assessment of reperfusion after myocardial infarction. J Am Coll Cardiol 2000; 35:397A

36. Gibson CM, Cannon CP, Murphy SA, et al for the TIMI Study Group. The Relationship of the TIMI Myocardial Perfusion Grade to Mortality Following Thrombolytic Administration. Circulation 2000;101:125-130.

37. Stone GW, Lansky AJ, Mehran R, et al. Beyond TIMI 3 Flow: The importance of restored myocardial perfusion for survival in high risk patients undergoing primary or rescue PTCA. J Am Coll Cardiol 2000; 35: 403A.

38. Gregg W. Stone, Alexandra J. Lansky, Roxana Mehran, Michael A. Peterson, Luis Gruberg, George Dangas, Kartik Eesai, Steven T. Slack, Renee Reed, Brian Proctor, Martin 8. Leon. Washington Hospital Center, Washington, DC, USA Myocardial perfusion may be impaired after PTCA in AMI despite restoration of normal epicardial (TIMI-3) blood flow, which may be partly responsible for mortality even after successful PTCA.

39. Barron HV, Cannon CP, Murphy SA, Braunwald E, Gibson CM. The association between white blood cell count, epicardial blood flow, myocardial perfusion and clinical outcomes in the setting of acute MI. A TIMI 10B substudy. Circulation 2000;102(19):2329-34.

40. de Lemos JA, Gibson CM, Antman EM, et al. Correlation between the TIMI myocardial perfusion grade and ST segment resolution among patients with normal epicardial flow after fibrinolysis. Circulation 2000:102: II-775.

41. Gibson CM, Giugliano RP, Roe MT, et al. Impaired TIMI epicardial flow and myocardial perfusion grades are associated with increased time to ST segment recovery in ST segment elevation MI: an INTEGRITI substudy. Circulation. 2002;106(suppl II):II-598.

42. Angeja BG, Gunda M, Murphy SA, et al. TIMI myocardial perfusion grade and ST segment resolution: association with infarct size as assessed by single photon emission computed tomography imaging. Circulation. 2002;105:282–285.

43. Gibson CM, Cohen DJ, Cohen E, et al for the ESPRIT study group. Eptifibatide improves tissue level perfusion: Results of the ESPRIT angiographic substudy. Circulation 2000, 102: II-366 (abstr).

44. Cannon CP, Gibson CM, Lambrew CT, et al for the NRMI-2 Investigators. Relationship of door-to-balloon time to mortality in patients with acute myocardial infarction treated with primary angioplasty. JAMA 2000; 283:2941-7.

45. Gibson CM, Cannon CP, Piana RN, et al. Angiographic predictors of early reocclusion in the TIMI 4 trial. J Am Coll Cardiol 1995; 25:582-589.

46. WILLIAM GANZ M.D.HAROLD S. MARCUS M.D. Failure of Intracoronary Nitroglycerin to Alleviate Pacing-Induced Angina ; Circulation. 1972;46:880;

47. Harrison DG, ET AL. The nitrovasodilators. New ideas about old drugs. Circulation 1993; 87:1461-1467

48. Garvan D Kane, Mayo clinic caridilogy concise text book 3rd ed, pp 1249

49. B. GREG BROWN, MD, PhD Response of Normal and Diseased Epicardial Coronary Arteries to Vasoactive Drugs: Quantitative Arteriographic Studies Am J Cardiol 1985;56:23E-29E

50. RL Feldman, JD Marx, CJ Pepine and CR Conti; Analysis of coronary responses to various doses of intracoronary nitroglycerin; Circulation, Vol 66, 321-32

51. Feldman RL, Pepine CJ, Conti CR: Magnitude of dilatation of large and small coronary arteries bv nitroglycerin. Circulation 64: 324, 1981


52. Hess OM, Bortone AS. Eid K, et al. Coronary vasomotor tone during static and dynamic exercise. Eur Heart J 1089:Ill;IllS-Ill.

53. CJ Pepine, RL Feldman and CR Conti; Action of intracoronary nitroglycerin in refractory coronary artery spasm; Circulation 1982;65;411-414

54. Richard M. Pomerantz, MD, Richard E. Kuntz, MD, Daniel J. Diver, MD, Robert D. Safian, MD, FSCAI, and Donald S. Baim, MD, FSCAl; lntracoronary Verapamil for the Treatment of Distal Microvascular Coronary Artery Spasm Following PTCA lntracoronary Verapamil for the Treatment of Distal Microvascular Coronary Artery Spasm Following PTCA

55. Richard M. Pomerantz, MD, Richard E. Kuntz, MD, Daniel J. Diver, MD, Robert D. Safian, MD, FSCAI, and Donald S. Baim, MD, FSCAl

56. Babbitt D, Perry J, Forman M.: Intracoronary verapamil for revera1 of refractory coronary vasospasm during percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 12: 1377-1381, 1988.

57. Walter A. Parham, MD; Andre Bouhasin, MD; Jeffrey P. Ciaramita, MD; Souheil Khoukaz, MD; Steven C. Herrmann, MD; Morton J. Kern, MD; Coronary Hyperemic Dose Responses of Intracoronary Sodium Nitroprusside; Circulation. 2004;109:1236-1243

58. William B. Hillegass, MD, MPH,* Neal A. Dean, BA,† Laurence Liao, MD, Rodney G. Rhinehart, MD,† Paul R. Myers, MD, PHD, FACC, FSCAI; Treatment of No-Reflow and Impaired Flow With the Nitric Oxide Donor Nitroprusside Following Percutaneous Coronary Interventions: Initial Human Clinical Experience; J Am Coll Cardiol 2001;37:1335– 43

59. Hillegass WB, Dean NA, Liao L, et al. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol. 2001;37:1335–1343.

60. Jose G. Diez’ , M.J. Lievano, Mihai Croitoru’ , James J. Ferguson’ Hospital Universitario San Rafael, Bogota, Colombia; ‘St. Luke’s Episcopal Hospital/The Texas Heart Institute, Houston, TX, USA

61. Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J 2001;22:729–39.

62. Mahaffey KW, Puma JA, Barbagelata NA, et al. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the acute myocardial infarction study of adenosine (AMISTAD) trial. J Am Coll Cardiol 1999;34:1711–20.

63. Ross AM, Gibbons RJ, Stone GW, et al. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol 2005;45:1775–80.

64. Increment in Coronarv Flow (TIMI Frame Count) in Men With Microvascuiar Angina Jose G. Diez’ , M.J. Lievano, Mihai Croitoru’ , James J. Ferguson’ Hospital Universitario San Rafael, Bogota, Colombia; ‘St. Luke’s Episcopal Hospital/The Texas Heart Institute, Houston, TX, USA, Abs JACC 2000=

65. Marzilli M, Orsini E, Marraccini P, et al. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000; 101:2154–2159.

66. Assali AR, Sdringola S, Ghani M, et al. Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of ‘‘no reflow’’ phenomenon. Catheter Cardiovasc Interv 2000;51:27–31.

67. Micari A, Belcik TA, Balcells EA, et al. Improvement in microvascular reflow and reduction of infarct size with adenosine in patients undergoing primary coronary stenting. Am J Cardiol 2005;96:1410–5.

68. K Vijayalakshmi, V J Whittaker, B Kunadian, J Graham, R A Wright, J A Hall, A Sutton, M A de Belder; Prospective, randomised, controlled trial to study the effect of intracoronary injection of verapamil and adenosine on coronary blood flow during percutaneous coronary intervention in patients with acute coronary syndromes, Heart 2006;92:1278–1284. doi: 10.1136/hrt.2005.075077

69. Rembert J, Boyd LM, Watkinson WP, Greenfield JC: Effect of adenosine on transmural myocardial blood flow distribution in the awake dog. Am J Physiol 1980;239(Heart Circ Physiol 8):H7-H13

70. Robert F. Wilson, MD, Keith Wyche, BS, Betsy V. Christensen, BSN,Steven Zimmer, MD, and David D. Laxson, MD;Effects of Adenosine on Human Coronary Arterial Circulation; Circulation 1990;82:1595-1606

71. Zijlstra F, Juilliere Y, Serruys PW, Roelandt JRTC: Value and limitations of intracoronary adenosine for the assessment of coronary flow reserve. Cathet Cardvasc Diagn 1988;15:76-80

72. Zijlstra F, Juilliere Y, Serruys PW, Roelandt JRTC: Value and limitations of intracoronary adenosine for the assessment of coronary flow reserve. Cathet Cardvasc Diagn 1988;15:76-80

73. RF Wilson, K Wyche, BV Christensen, S Zimmer and DD Laxson; Effects of adenosine on human coronary arterial circulation, Circulation 1990;82;1595-1606

74. Ross AM, Gibbons RJ, Stone GW, et al. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol 2005;45:1775–80.

75. Micari A, Belcik TA, Balcells EA, et al. Improvement in microvascular reflow and reduction of infarct size with adenosine in patients undergoing primary coronary stenting. Am J Cardiol 2005;96:1410–5.

76. Zijlstra F, Juilliere Y, Serruys PW, Roelandt JRTC: Value and limitations of intracoronary adenosine for the assessment of coronary flow reserve. Cathet Cardvasc Diagn 1988;15:76-80

77. Steven E. Reis, Richard Holubkov, Joon S. Lee, Barry Sharaf, Nathaniel Reichek, William J. Rogers, Edward G. Walsh, Anthon R. Fuisz, Richard Kerensky, Katherine M. Detre, et al.Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease : Results from the pilot phase of the Women’s Ischemia Syndrome Evaluation (WISE) Study Pages 1469-1475

78. ROGER L. WHITING, PhD Animal Pharmacology of Nicardipine and Its Clinical Relevance; Am J Cardiol 1987;59:3J-8J

79. Roussenu MF, Vincent MF. Van Hoof F. Van den Berghc G. Ch:wlicr AAPouleur H. Effects of nicardipine and nisoldipine on myocordiol metabolism, coronary blood flow and oxygen supply in angina pectoris. Am J Cardiol 1984;54:1189-1194.

80. Fugit MD, Rubal BJ, Donovan DJ. Effects of intracoronary nicardipine, diltiazem and verapamil on coronary blood flow. J Invas Cardiol 2000;12:80–85.

81. PHILIPP KAUFMANN, MD, GIUSEPPE VASSALLI, MD, URS UTZINGER, PHD, OTTO M. HESS, MDJ; Coronary Vasomotion During Dynamic Exercise: Influence Of Intravenous and Intracoronary Nicardipine Am Coil Cardiol 1995;26:624-31)

82. Gage JE. Hess OM. Murakami T. Rittcr M, Grimm J, Krayenbuchl HP. Vasoconstriction of stenotic coronary arteries during exercise in patients with classic angina pectoris: reversibiiity by nitroglycerin. Circulation 1986; 73:865-76.

83. CLAUDE HANET, MD, MICHEL F. ROUSSEAU, MD, MARIE-FRANCOISE VINCENT, MD, EDITH LAVENNE-PARDONGE, MD, and HUBERT POULEUR, MD; Myocardial Protection by lntracoronary Nicardipine Administration During Percutaneous Transluminal Coronary Angioplasty AmJ Cardiol 1987;59:1035-1040

84. CLAUDE HANET, MD, MICHEL F. ROUSSEAU, MD, MARIE-FRANCOISE VINCENT, MD, EDITH LAVENNE-PARDONGE, MD, and HUBERT POULEUR, MD; Myocardial Protection by lntracoronary Nicardipine Administration During Percutaneous Transluminal Coronary Angioplasty AmJ Cardiol 1987;59:1035-1040

85. Rousseau MF, Vincent MF, Cheron P, Van Den Berghe G, Charlier AA, Pouleur H. Effects of nicordipine on coronary blood flow, left ventricular inotropic state and myocurdial metabolism in patients with onginu pectoris. Br J Clin Phormocol 1985;20:147S-157s.

86. Nonogi H, Hess OM, Ritter M, et al. Prevention of coronary vasoconstriction by diltiazem during dynamic exercise in patients with coronary artery disease. J Am Coil Cardiol 1988;12:892-9.

87. Piana R, Paik G, Moscucci M, et al. Incidence and treatment of ‘no-reflow’ after percutaneous coronary intervention. Circulation 1994;89:2514–8.

88. Piana RN, Paik GY, Mosucci M, et al. Incidence and treatment of “no reflow” after percutaneous coronary intervention. Circulation 1994;89: 2514–8.

89. Werner GS, Lang K, Kuehnert H, et al. Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction. Catheter Cardiovasc Interv 2002;57:444–51.

90. Chi-Ling Hang, MD; Cha-Ping Wang, MD; Hon-Kan Yip, MD; Cheng-Hsu Yang, MD; G. Bih-Fang Guo, MD, PhD; Chiung-Jen Wu, MD; and Shyh-Ming Chen, MD; Early Administration of Intracoronary Verapamil Improves Myocardial Perfusion During Percutaneous Coronary Interventions for Acute Myocardial Infarction; CHEST 2005; 128:2593–2598

91. Michaels AM, Appleby M, Dauterman K, et al. Pretreatment with intragraft verapamil prior to percutaneous coronary intervention of saphenous vein graft lesions: results of the randomized, controlled vasodilator prevention of no-reflow (VAPOR) trial. J Invasive Cardiol. 2002;14:299–302.

92. YOSHIAKI TANIYAMA, MD, HIROSHI ITO, MD, KATSUOMI IWAKURA, MD, TOHRU MASUYAMA, MD,* MASATSUGU HORI, MD,* SHIN TAKIUCHI, MD, NAGAHIRO NISHIKAWA, MD, YORIHIKO HIGASHINO, MD, KENSHI FUJII, MD, TAKAZO MINAMINO, MD Beneficial Effect of Intracoronary Verapamil on Microvascular and Myocardial Salvage in Patients With Acute Myocardial Infarction JACC Vol. 30, No. 5 November 1, 1997:1193-9

93. Pomerantz R, Kuntz RE, Diver DJ, Safian RD, Baim DS. Intracoronary verapamil for the treatment of distal microvascular coronary artery spasm following PTCA. Cathet Cardiovasc Diagn 1991;24:283–5.

94. Intracoronary Verapamil Rapidly Terminates Reperfusion Tachyarrhythmias in Acute Myocardial Infarction; Masaya Kato, MD, PhD; Keigo Dote, MD, PhD; Shota Sasaki, MD, PhD; Hiroaki Takemoto, MD; Seiji Habara, MD; and Daiji Hasegawa, MD; CHEST 2004; 126:702–708

95. Gregorini L, Marco J, Farah B, et al. Effects of selective alpha1- and alpha2-adrenergic blockade on coronary flow reserve after coronary stenting. Circulation. 2002 3;106: 2901–2907.

96. Wilson RF, Laxson DD, Lesser JR, et al. Intense microvascular constriction after angioplasty of acute thrombotic coronary arterial lesions. Lancet 1989;i:807–11.




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