ST elevation myocardial infarction pathophysiology of reperfusion

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

Pathophysiology of Reperfusion

The Importance of Restoring and Sustaining Complete Epicardial and Myocardial Perfusion

Recently, it has become recognized that it is necessary but not sufficient to restore epicardial flow in ST elevation MI. Not all TIMI grade 3 flow is created equally. [1] In addition to epicardial flow, myocardial perfusion must be restored as well. This has been demonstrated in both myocardial contrast echo studies as well as angiographic studies[1] [2][3][4][5][6][7][8][9][10][11][12][13] As a result of this new understanding, the goal of reperfusion therapies has shifted to include reperfusion downstream at the level of capillary bed, and it might be more appropriate that the current reperfusion hypothesis now be termed "the time dependent open muscle hypothesis."

TIMI Flow Grades (TFGs)

The Thrombolysis In Myocardial Infarction (TIMI) flow grade classification scheme has been widely used to assess coronary blood flow in acute coronary syndromes.[1] TFG 0 means the artery is closed; TFG 1 means that dye penetrates the stenosis but does not reach the downstream bed; TFG 2 means that flow is slow down the artery and TFG 3 means that normal flow has been restored. The association of the TFGs with clinical outcomes (including mortality) has been well documented [2][3][4][5][6][7][8]

The association of the TFGs with mortality must be interpreted with caution as there are several confounders:

1. The majority of TIMI grade 2 flow is observed in the left anterior descending artery (LAD) territory, whereas the majority of TIMI grade 3 flow is observed in the right coronary artery (RCA)[7]. Thus, the improved mortality observed among patients with TIMI grade 3 flow may be explained at least in part by the fact that inferior myocardial infarction (MI) location is associated with a lower mortality rate [7]

2. The clinical improvement associated with TIMI grade 3 flow may have be nonlinear. For example, greater clinical benefits may be observed if a closed artery (TFG 0/1) is opened (TFG 2) compared with the improvement that might occur if an artery with TFG 2 is converted to TFG 3 flow.

3. As more arteries with TFG 2 flow are treated with adjunctive percutaneous coronary intervention (PCI), the prognosis associated with this flow grade may improve. The fact that patients who were treated with an inferior fibrinolytic monotherapy strategy faired so well in GUSTO V may be explained in part by the fact that these patients underwent PCI more often [14][15]. Two-year follow-up in more recent studies indicates that the survival advantage of TFG 3 flow over TFG 2 flow at 2 years may not be as great as it once was in the era before aggressive utilization of rescue and adjunctive PCI [10]


While PCI may obviously improve epicardial flow, another often unrecognized benefit is the fact that rescue PCI (dilating a closed artery) and adjunctive PCI (dilating an open artery) following fibrinolytic administration may reduce the risk of reocclusion. Reinfarction doubles early mortality by 30 days [15] [16]. Controversy has surrounded the use of PCI immediately following PCI, and for many years, immediate PCI was classified as a class III contraindication. These early trials preceded the use of stents, thienopyridines, platelet GP IIb/IIIa inhibitors, and the monitoring of activated clotting times. Among 20 101 patients enrolled in recent TIMI trials, Gibson et al have reported that the performance of PCI during the index hospitalization was associated with a lower rate of in-hospital recurrent MI (1.6% versus 4.5%, P<0.001) and a lower 2-year mortality (5.6% versus 11.6%, P<0.001)[16][17]. In addition to flow other nonangiographic findings and processes may also underlie the pathophysiology of reocclusion as well as other clinical outcomes[18].

The TIMI Frame Count: A More Precise Angiographic Index of Coronary Blood Flow

There are several limitations to the TFG classification scheme [7]. To overcome these limitations, Gibson developed a more objective and precise index of coronary blood flow called the corrected TIMI frame count (CTFC). In this method, the number of cineframes required for dye to reach standardized distal landmarks are counted. Each frame is 1/30th of a second, and the angiogram is therefore essentially a measure of the time for dye to go down the artery [7][8][10]. In the first frame used for TIMI frame counting, a column of dye touches both borders of the coronary artery and moves forward [7]. In the last frame, dye begins to enter (but does not necessarily fill) a standard distal landmark in the artery. These standard distal landmarks are as follows: in the RCA, the first branch of the posterolateral artery; in the circumflex system, the most distal branch of the obtuse marginal branch, which includes the culprit lesion in the dye path; and in the LAD, the distal bifurcation, which is also known as the "moustache," "pitchfork" or "whale’s tail". These frame counts are corrected for the longer length of the LAD by dividing by 1.7 to arrive at the CTFC [7]. Knowing the time for dye to go down the artery from the CTFC (CTFC/30=seconds), and length of the artery (either from an angioplasty guide wire or by planimetry), dye velocity (cm/s) can also be calculated in a more refined fashion.[19]. This refined measure allows calculation of the velocity proximal and distal to the lesion[19].

Some of the advantages of the TIMI frame count method are as follows. In contrast to the TFG classification scheme, the CTFC is quantitative rather than qualitative, it is objective rather than subjective, it is a continuous rather than a categorical variable, and it is reproducible [7]. The CTFC demonstrates that flow is not divided into arbitrary slow and fast categories, but rather coronary blood flow is unimodally distributed as a continuous variable [7]. The CTFC has been shown to be quite reproducible with a 1- to 2-frame difference between observers [20][21][22][23][24][25][26][27][28][29][30][31][32]. The CTFC is also highly correlated with other measures of flow such as Doppler velocity wire measures of coronary flow reserve, distal velocity, average peak velocity, and volumetric flow, [21][22][23] as well as fractional flow reserve (r=0.85)[24]

Several technical and physiological variables may impact the CTFC [20][33][34][35][36]:

1. Injection force: A power injector to change the force of injection (cc/sec) from the 10th to the 90th percentile of human injection rates lowers the CTFC by only 2 frames [33].

2. Nitrate administration significantly increases the CTFC by 6 frames (P<0.001)[20]

3. Dye injection at the beginning of diastole decreases the CTFC by 3 to 6 frames [20]

4. Increasing the heart rate by 20 beats per minute significantly decreases the CTFC by 5 frames (P<0.001)[20]

Association of the CTFC with clinical outcomes

Following fibrinolytic administration as well as PCI, the CTFC is related to a variety of clinical outcomes[7][8][9][37][38][39] [27][28][29][30] Flow in the infarct-related artery in survivors is significantly faster than in patients who die (49.5 versus 69.6 frames; P=0.0003)[8]. In NSTEMI and STEMI, the post-PCI culprit flow among survivors is significantly faster than among those patients who died (CTFCs 20.4 versus 33.4 frames, P=0.017)[40]. Among patients undergoing PCI, the CTFC has demonstrated greater sensitivity in detecting improvements in epicardial flow compared with the use of TIMI grade 3 flow among patients treated with new device interventions and in the detection of transplant rejection.[41][42][43][44][45][46]

The pathophysiology of STEMI and UA/NSTEMI based on measures of epicardial flow

One of the more interesting observations learned with the use of the CTFC is the fact that flow in nonculprit arteries in the setting of acute coronary syndromes is "abnormal." For instance, the CTFC in uninvolved arteries in acute STEMI (30.5 frames) is in fact 40% slower than normal (21 frames, P<0.001)[7][47][48][49] Adjunctive and rescue PCI following fibrinolysis restores flow in culprit vessels that is nearly identical to that of nonculprit arteries in the STEMI setting (30.5 versus 30.5 frames, p=NS)[47], but this flow remains slower than normal (21 frames). It is notable that PCI of the culprit lesion is also associated with improvements in the nonculprit artery after the intervention in both the STEMI and UA/NSTEMI settings [47][48]. Slower flow throughout all 3 arteries in STEMI is associated with a higher risk of adverse outcomes [47], poorer wall motion in remote territories[47], poorer tissue perfusion on digital subtraction angiography (DSA)[48], and a greater magnitude of ST depression in remote territories such as the anterior precordium in inferior MI [50]. The basis of slowed flow in non-culprit arteries is not clear. It has been speculated that the delayed flow in the non-culprit artery may be the result of spasm in shared territories of microvasculature, or a result of global vasoconstriction mediated through either a local neurohumoral or paracrine mechanism. Gregorini et al[51] have highlighted the importance of sympathetic storm. Consistent with this hypothesis, they have demonstrated that the CTFC and fractional wall shortening is improved in both the culprit and nonculprit arteries after administration of alpha-blockers. Willerson and others [52][53][54][55][56][57][58]have also demonstrated that a wide range of vasoconstrictors including thromboxane A2, serotonin, endothelin, oxygen-derived free radicals, and thrombin are all released in the setting of vessel injury, thrombosis and reperfusion. While a residual stenosis following PCI in the setting of STEMI may be responsible for the delay in flow, it is important to note that despite a minimal 13% residual stenosis and the relief of intraluminal obstruction with stent placement, flow remains persistently abnormal in 34% of stented vessels.[59]

Assessment of Myocardial Perfusion on the Angiogram: The TIMI Myocardial Perfusion Grade (TMPG)

Studies of myocardial constrast echocardiography (MCE) and angiography have demonstrated that restoration of epicardial flow does not necessarily lead to restoration of tissue level or microvascular perfusion.[11][12][13] Perfusion of the myocardium can also be assessed using the angiogram. In the TMPG system, TMPG 0 represents minimal or no myocardial blush; in TMPG 1, dye stains the myocardium, and this stain persists on the next injection; in TMPG 2, dye enters the myocardium but washes out slowly so that dye is strongly persistent at the end of the injection; and in TMPG 3, there is normal entrance and exit of dye in the myocardium. Another method of assessing myocardial perfusion on the angiogram is the myocardial blush grade (MBG) developed by van’t Hof et al.[60] A grade of 0 (no blush) and a grade of 3 (normal blush) are the same in the TMPG and MBG systems. An MBG grade 1 or 2 represents diminished intensity in the myocardium and corresponds to a value of 0.5 in the expanded TMPG grading system. A TMPG of 1 or a stain in the TIMI system is subsumed within the value of a 0 in the MBG system. Thus, normal perfusion in the myocardium carries a score of 3 in both the TMPG and MBG systems, and a closed muscle carries a score of 0 in both systems. Lepper et al.[61] have demonstrated that angiographic and echocardiographic myocardial perfusion are closely related, and among patients undergoing primary PCI for acute MI, impaired MBG was the best multivariate predictor of nonreperfusion on myocardial contrast echocardiography.

Independent of flow in the epicardial artery and other covariates such as age, blood pressure, and pulse, the TMPG has been shown to be multivariate predictors of mortality in acute STEMI at 2 years.[10] The TMPG permits risk stratification even within epicardial TIMI grade 3 flow. Despite achieving epicardial patency with normal TIMI grade 3 flow, those patients whose microvasculature fails to open (TMPG 0/1) have a 7-fold increase in mortality compared with those patients with both TIMI grade 3 flow in the epicardial artery. Achievement of both TIMI grade 3 flow in both the artery and the myocardium is associated with a mortality under 1%10. Likewise, in the setting of primary PCI, both van’t Hof et al.[60] and Haager et al.[61] have demonstrated an association between impaired myocardial perfusion and early and late mortality. These improvements in early and late mortality may be mediated by improvements in myocardial salvage.[62] As Dibra et al.[62] have demonstrated, restoration of TMPG 2/3 is associated with a higher salvage index (0.49±0.42 versus 0.34±0.49, P=0.01) and a smaller final infarct size (15.4±15.5% versus 22.1±16.2% of the left ventricle, P=0.001). Indeed, second only to stent placement, restoration of TMPG 2/3 was the next most powerful independent determinant of the myocardial salvage index, and was more closely associated with higher salvage indexes than the TFGs.[62][63][64][65][66][67][68][69][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86]

Reperfusion injury refers to damage to tissue caused when blood supply returns to the tissue after a period of ischemia. The absence of oxygen and nutrients from blood creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function.

Mechanisms of Reperfusion Injury

The damage of reperfusion injury is due in part to the inflammatory response of damaged tissues. White blood cells carried to the area by the newly returning blood release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage [87].The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane. Damage to the cell's membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling to turn on apoptosis. Leukocytes may also build up in small capillaries, obstructing them and leading to more ischemia[87].

Reperfusion injury plays a part in the brain's ischemic cascade, which is involved in stroke and brain trauma. Repeated bouts of ischemia and reperfusion injury also are thought to be a factor leading to the formation and failure to heal of chronic wounds such as pressure sores and diabetic foot ulcers[88]. Continuous pressure limits blood supply and causes ischemia, and the inflammation occurs during reperfusion. As this process is repeated, it eventually damages tissue enough to cause a wound[88].

In prolonged ischemia (60 minutes or more), hypoxanthine is formed as breakdown product of ATP metabolism. The enzyme xanthine dehydrogenase acts in reverse, that is as a xanthine oxidase as a result of the higher availability of oxygen. This oxidation results in molecular oxygen being converted into highly reactive superoxide and hydroxyl radicals. Xanthine oxidase also produces uric acid, which may act as both a prooxidant and as a scavenger of reactive species such as peroxinitrite. Excessive nitric oxide produced during reperfusion reacts with superoxide to produce the potent reactive species peroxynitrite. Such radicals and reactive oxygen species attack cell membrane lipids, proteins, and glycosaminoglycans, causing further damage. They may also initiate specific biological processes by redox signaling.


Superoxide dismutase (SOD) as well as a variety of other agents have been studied in an attempt to reduce reperfusion injury. These studies have not been successful in the entire populations studied. However, there are subpopulations in which promising results have been observed. One such subgorup includes patients with anterior myocardial infarction. High dose intravenous adenosine and hypothermia have been associated with improved outcomes in this subgorup of STEMI patients for instance.

Therapeutic hypothermia

An intriguing area of research demonstrates the ability of a reduction in body temperature to limit reperfusion injuries. This procedure is called therapeutic hypothermia (endovascular cooling). However, the therapeutic effect of hypothermia does not confine itself to metabolism and membrane stability. Another school of thought focuses on hypothermia’s ability to prevent the injuries that occur after circulation returns to the brain, or what is termed reperfusion injuries. In fact an individual suffering from an ischemic insult continues suffering injuries well after circulation is restored. In rats it has been shown that neurons often die a full 24 hours after blood flow returns. Some theorize that this delayed reaction derives from the various inflammatory immune responses that occur during reperfusion.[89] These inflammatory responses cause intracranial pressure, pressure which leads to cell injury and in some situations cell death. Hypothermia has been shown to help moderate intracranial pressure and therefore to minimize the harmful effect of a patient’s inflammatory immune responses during reperfusion. Beyond this, reperfusion also increases free radical production. Hypothermia too has been shown to minimize a patient’s production of deadly free radicals during reperfusion. Many now suspect it is because hypothermia reduces both intracranial pressure and free radical production that hypothermia improves patient outcome following a blockage of blood flow to the brain.[90]

Other Potential Therapies

Other potential therapies for reperfusion injury include:

  • Ischemic conditioning
  • Ischemic postconditioning involves repeated, brief balloon inflations at low pressure to temporarily occlude the infarct-related artery after stenting. Several small studies have reported conflicting results in patients with STEMI, while a larger study (DANAMI-3) of over 1230 patients found no reduction in the composite outcome of death from any cause and hospitalization for heart failure compared with conventional PCI.
  • Remote ischemic conditioning, which applies intermittent ischemia and reperfusion to an arm through automated cuff inflation and deflation, has been shown to reduce myocardial infarct size and improve myocardial salvage in a few small studies of STEMI patients treated before primary PCI. However, the large CONDI-2/ERIC-PPCI trial of 5401 patients eligible for primary PCI found no significant difference in the rate of the primary composite outcome of cardiac death or hospitalization for heart failure at 12 months.
  • Higher-risk patients with acute heart failure, cardiogenic shock, delayed reperfusion, or thrombolysis may benefit from remote ischemic conditioning. The RIC AFRICA study aims to investigate the effects of remote ischemic conditioning on clinical outcomes in patients with STEMI treated by thrombolysis, who are at high risk of complications due to suboptimal reperfusion, a high burden of cardiovascular risk factors, prolonged ischemic times, and poor compliance with secondary preventative therapies.
  • Glycoprotein IIb/IIIa inhibitors
  • Adenosine
  • Vasodilators
  • Ion channel modulation
  • Glucose-insulin-potassium solution
  • Antineutrophil and anti-complement therapy
  • Antioxidant therapy
  • Reperfusion injury is characterized by the involvement of oxygen radicals in its pathophysiology, leading to significant tissue damage. Antioxidant therapy has been proposed to mitigate the damage associated with reperfusion, and several studies have investigated its efficacy. However, results have been inconsistent, and research has primarily been conducted at the animal level. Erythropoietin, estrogen, heme oxygenase1, and hypoxia induced factor–1 have demonstrated promise in reducing reperfusion injury, and ongoing investigations are underway to further elucidate their therapeutic potential.
  • Magnesium
  • Cyclosporine
  • Intravenous MTP-131
  • Intravenous sodium nitrite
  • Losmapimod
  • Inhibitors of delta-protein kinase C

Related Chapters


  1. 1.0 1.1 1.2 "The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group". N. Engl. J. Med. 312 (14): 932–6. 1985. PMID 4038784. Unknown parameter |month= ignored (help)
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  34. Gibson CM, Anshelevich M, Murphy S; et al. (2000). "Impact of injections during diagnostic coronary arteriography on coronary patency in the setting of acute myocardial infarction from the TIMI trials. Thrombolysis In Myocardial Infarction". Am. J. Cardiol. 86 (12): 1378–9, A5. PMID 11113418. Unknown parameter |month= ignored (help)
  35. Gibson CM, Kirtane AJ, Murphy SA; et al. (2001). "Impact of contrast agent type (ionic versus nonionic) used for coronary angiography on angiographic, electrocardiographic, and clinical outcomes following thrombolytic administration in acute myocardial infarction". Catheter Cardiovasc Interv. 53 (1): 6–11. doi:10.1002/ccd.1121. PMID 11329210. Unknown parameter |month= ignored (help)
  36. Faile BA, Guzzo JA, Tate DA, Nichols TC, Smith SC, Dehmer GJ (2000). "Effect of sex, hemodynamics, body size, and other clinical variables on the corrected thrombolysis in myocardial infarction frame count used as an assessment of coronary blood flow". Am. Heart J. 140 (2): 308–14. doi:10.1067/mhj.2000.108003. PMID 10925348. Unknown parameter |month= ignored (help)
  37. French JK, Hyde TA, Amos DJ, et al. Corrected TIMI frame count at 3 weeks influences survival at 5 years but not 10 years after myocardial infarction. Eur Heart J. 1998; 19: 630.
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  39. 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: 665–671.
  40. Gibson CM, Dotani MI, Murphy SA; et al. (2002). "Correlates of coronary blood flow before and after percutaneous coronary intervention and their relationship to angiographic and clinical outcomes in the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis". Am. Heart J. 144 (1): 130–5. PMID 12094199. Unknown parameter |month= ignored (help)
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  43. Hamada S, Nishiue T, Nakamura S; et al. (2001). "TIMI frame count immediately after primary coronary angioplasty as a predictor of functional recovery in patients with TIMI 3 reperfused acute myocardial infarction". J. Am. Coll. Cardiol. 38 (3): 666–71. PMID 11527614. Unknown parameter |month= ignored (help)
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  50. Gibson CM, Chen M, Angeja BG; et al. (2002). "Precordial ST-segment depression in inferior myocardial infarction is associated with slow flow in the non-culprit left anterior descending artery" (PDF). J. Thromb. Thrombolysis. 13 (1): 9–12. PMID 11994554. Unknown parameter |month= ignored (help)
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  59. Gibson CM, Murphy S, Menown IB; et al. (1999). "Determinants of coronary blood flow after thrombolytic administration. TIMI Study Group. Thrombolysis in Myocardial Infarction". J. Am. Coll. Cardiol. 34 (5): 1403–12. PMID 10551685. Unknown parameter |month= ignored (help)
  60. 60.0 60.1 van 't Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F (1998). "Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group". Circulation. 97 (23): 2302–6. PMID 9639373. Unknown parameter |month= ignored (help)
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  63. Gibson CM, Murphy SA, Kirtane AJ; et al. (2004). "Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with ST-segment elevation myocardial infarction". J. Am. Coll. Cardiol. 44 (5): 980–7. doi:10.1016/j.jacc.2004.05.059. PMID 15337207. Unknown parameter |month= ignored (help)
  64. De Luca G, Suryapranata H, Zijlstra F; et al. (2003). "Symptom-onset-to-balloon time and mortality in patients with acute myocardial infarction treated by primary angioplasty". J. Am. Coll. Cardiol. 42 (6): 991–7. PMID 13678918. Unknown parameter |month= ignored (help)
  65. De Luca G, van 't Hof AW, de Boer MJ; et al. (2004). "Time-to-treatment significantly affects the extent of ST-segment resolution and myocardial blush in patients with acute myocardial infarction treated by primary angioplasty". Eur. Heart J. 25 (12): 1009–13. doi:10.1016/j.ehj.2004.03.021. PMID 15191770. Unknown parameter |month= ignored (help)
  66. Kirtane AJ, Bui A, Murphy SA; et al. (2004). "Association of epicardial and tissue-level reperfusion with left ventricular end-diastolic pressures in ST-elevation myocardial infarction". J. Thromb. Thrombolysis. 17 (3): 177–84. doi:10.1023/B:THRO.0000040486.10549.f6. PMID 15353915. Unknown parameter |month= ignored (help)
  67. De Luca G, van 't Hof AW, de Boer MJ; et al. (2004). "Impaired myocardial perfusion is a major explanation of the poor outcome observed in patients undergoing primary angioplasty for ST-segment-elevation myocardial infarction and signs of heart failure". Circulation. 109 (8): 958–61. doi:10.1161/01.CIR.0000120504.31457.28. PMID 14981008. Unknown parameter |month= ignored (help)
  68. Tarantini G, Ramondo A, Napodano M; et al. (2004). "Myocardial perfusion grade and survival after percutaneous transluminal coronary angioplasty in patients with cardiogenic shock". Am. J. Cardiol. 93 (9): 1081–5. doi:10.1016/j.amjcard.2004.01.031. PMID 15110196. Unknown parameter |month= ignored (help)
  69. 69.0 69.1 Gibson CM (2003). "Has my patient achieved adequate myocardial reperfusion?". Circulation. 108 (5): 504–7. doi:10.1161/01.CIR.0000082932.69023.74. PMID 12900495. Unknown parameter |month= ignored (help)
  70. Poli A, Fetiveau R, Vandoni P; et al. (2002). "Integrated analysis of myocardial blush and ST-segment elevation recovery after successful primary angioplasty: Real-time grading of microvascular reperfusion and prediction of early and late recovery of left ventricular function". Circulation. 106 (3): 313–8. PMID 12119246. Unknown parameter |month= ignored (help)
  71. Gibson CM, Karha J, Giugliano RP; et al. (2004). "Association of the timing of ST-segment resolution with TIMI myocardial perfusion grade in acute myocardial infarction". Am. Heart J. 147 (5): 847–52. doi:10.1016/j.ahj.2003.11.015. PMID 15131541. Unknown parameter |month= ignored (help)
  72. Wong GC, Morrow DA, Murphy S; et al. (2002). "Elevations in troponin T and I are associated with abnormal tissue level perfusion: a TACTICS-TIMI 18 substudy. Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction". Circulation. 106 (2): 202–7. PMID 12105159. Unknown parameter |month= ignored (help)
  73. Gibson CM, Murphy SA, Marble SJ; et al. (2002). "Relationship of creatine kinase-myocardial band release to Thrombolysis in Myocardial Infarction perfusion grade after intracoronary stent placement: an ESPRIT substudy". Am. Heart J. 143 (1): 106–10. PMID 11773919. Unknown parameter |month= ignored (help)
  74. Gibson CM, de Lemos JA, Murphy SA; et al. (2002). "Methodologic and clinical validation of the TIMI myocardial perfusion grade in acute myocardial infarction" (PDF). J. Thromb. Thrombolysis. 14 (3): 233–7. PMID 12913404. Unknown parameter |month= ignored (help)
  75. Gibson CM, Cohen DJ, Cohen EA; et al. (2001). "Effect of eptifibatide on coronary flow reserve following coronary stent implantation (an ESPRIT substudy). Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy". Am. J. Cardiol. 87 (11): 1293–5. PMID 11377359. Unknown parameter |month= ignored (help)
  76. Murphy SA, Chen C, Gourlay SG, Gibbons RJ, Barron HV, Gibson CM (2003). "Impairment of myocardial perfusion in both culprit and nonculprit arteries in acute myocardial infarction: a LIMIT AMI substudy". Am. J. Cardiol. 91 (3): 325–8. PMID 12565089. Unknown parameter |month= ignored (help)
  77. Wong GC, Frisch D, Murphy SA; et al. (2003). "Time for contrast material to traverse the epicardial artery and the myocardium in ST-segment elevation acute myocardial infarction versus unstable angina pectoris/non-ST-elevation acute myocardial infarction". Am. J. Cardiol. 91 (10): 1163–7. PMID 12745096. Unknown parameter |month= ignored (help)
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