ST elevation myocardial infarction pathophysiology of reperfusion
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753
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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]
Reocclusion
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.
Treatment
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. 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]
See also
External links
Sources
- The 2004 ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction [91]
- The 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction [92]
References
- ↑ 1.0 1.1 1.2 (April 1985) "The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group". N. Engl. J. Med. 312 (14): 932–6. PMID 4038784.
- ↑ 2.0 2.1 Simes RJ, Topol EJ, Holmes DR, et al (April 1995). "Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators". Circulation 91 (7): 1923–8. PMID 7895348.
- ↑ 3.0 3.1 (November 1993) "The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. The GUSTO Angiographic Investigators". N. Engl. J. Med. 329 (22): 1615–22. PMID 8232430.
- ↑ 4.0 4.1 Vogt A, von Essen R, Tebbe U, Feuerer W, Appel KF, Neuhaus KL (May 1993). "Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies". J. Am. Coll. Cardiol. 21 (6): 1391–5. PMID 8473646.
- ↑ 5.0 5.1 Karagounis L, Sorensen SG, Menlove RL, Moreno F, Anderson JL (January 1992). "Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study. Second Multicenter Thrombolysis Trial of Eminase in Acute Myocardial Infarction". J. Am. Coll. Cardiol. 19 (1): 1–10. PMID 1729317.
- ↑ 6.0 6.1 Anderson JL, Karagounis LA, Becker LC, Sorensen SG, Menlove RL (June 1993). "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 87 (6): 1829–39. PMID 8504495.
- ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 Gibson CM, Cannon CP, Daley WL, et al (March 1996). "TIMI frame count: a quantitative method of assessing coronary artery flow". Circulation 93 (5): 879–88. PMID 8598078.
- ↑ 8.0 8.1 8.2 8.3 8.4 Gibson CM, Murphy SA, Rizzo MJ, et al (April 1999). "Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Thrombolysis In Myocardial Infarction (TIMI) Study Group". Circulation 99 (15): 1945–50. PMID 10208996.
- ↑ 9.0 9.1 Gibson CM, Cannon CP, Murphy SA, et al (January 2000). "Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs". Circulation 101 (2): 125–30. PMID 10637197.
- ↑ 10.0 10.1 10.2 10.3 Gibson CM, Cannon CP, Murphy SA, Marble SJ, Barron HV, Braunwald E (April 2002). "Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction". Circulation 105 (16): 1909–13. PMID 11997276.
- ↑ 11.0 11.1 Angeja BG, Gunda M, Murphy SA, et al (January 2002). "TIMI myocardial perfusion grade and ST segment resolution: association with infarct size as assessed by single photon emission computed tomography imaging". Circulation 105 (3): 282–5. PMID 11804979.
- ↑ 12.0 12.1 Ito H, Tomooka T, Sakai N, et al (May 1992). "Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction". Circulation 85 (5): 1699–705. PMID 1572028.
- ↑ 13.0 13.1 Ito H, Maruyama A, Iwakura K, et al (January 1996). "Clinical implications of the 'no reflow' phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction". Circulation 93 (2): 223–8. PMID 8548892.
- ↑ Topol EJ (June 2001). "Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial". Lancet 357 (9272): 1905–14. PMID 11425410.
- ↑ 15.0 15.1 Hudson MP, Granger CB, Topol EJ, et al (September 2001). "Early reinfarction after fibrinolysis: experience from the global utilization of streptokinase and tissue plasminogen activator (alteplase) for occluded coronary arteries (GUSTO I) and global use of strategies to open occluded coronary arteries (GUSTO III) trials". Circulation 104 (11): 1229–35. PMID 11551872.
- ↑ 16.0 16.1 Gibson CM, Karha J, Murphy SA, et al (July 2003). "Early and long-term clinical outcomes associated with reinfarction following fibrinolytic administration in the Thrombolysis in Myocardial Infarction trials". J. Am. Coll. Cardiol. 42 (1): 7–16. PMID 12849652.
- ↑ Gibson CM (November 2000). "A union in reperfusion: the concept of facilitated percutaneous coronary intervention". J. Am. Coll. Cardiol. 36 (5): 1497–9. PMID 11079648.
- ↑ Gibson CM, Cannon CP, Piana RN, et al (March 1995). "Angiographic predictors of reocclusion after thrombolysis: results from the Thrombolysis in Myocardial Infarction (TIMI) 4 trial". J. Am. Coll. Cardiol. 25 (3): 582–9. PMID 7860900.
- ↑ 19.0 19.1 Gibson CM, Dodge JT, Goel M, et al (December 1997). "Angioplasty guidewire velocity: a new simple method to calculate absolute coronary blood velocity and flow". Am. J. Cardiol. 80 (12): 1536–9. PMID 9416931.
- ↑ 20.0 20.1 20.2 20.3 20.4 Abaci A, Oguzhan A, Eryol NK, Ergin A (November 1999). "Effect of potential confounding factors on the thrombolysis in myocardial infarction (TIMI) trial frame count and its reproducibility". Circulation 100 (22): 2219–23. PMID 10577994.
- ↑ 21.0 21.1 Manginas A, Gatzov P, Chasikidis C, Voudris V, Pavlides G, Cokkinos DV (June 1999). "Estimation of coronary flow reserve using the Thrombolysis In Myocardial Infarction (TIMI) frame count method". Am. J. Cardiol. 83 (11): 1562–5, A7. PMID 10363873.
- ↑ 22.0 22.1 Stankovic G, Manginas A, Voudris V, et al (March 2000). "Prediction of restenosis after coronary angioplasty by use of a new index: TIMI frame count/minimal luminal diameter ratio". Circulation 101 (9): 962–8. PMID 10704161.
- ↑ 23.0 23.1 Barcin C, Denktas AE, Garratt KN, Higano ST, Holmes DR, Lerman A (February 2003). "Relation of Thrombolysis in Myocardial Infarction (TIMI) frame count to coronary flow parameters". Am. J. Cardiol. 91 (4): 466–9. PMID 12586269.
- ↑ 24.0 24.1 Umman B, Nisanci Y, Sezer M, et al (March 2002). "The relationship between corrected TIMI frame count and myocardial fractional flow reserve". J Invasive Cardiol 14 (3): 125–8. PMID 11870267.
- ↑ 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.
- ↑ Straznicky IT, French JK, Webber BJ, et al. Corrected TIMI frame count at 90 minutes predicts left ventricular function at 48 hours following myocardial infarction treated with streptokinase and heparin or hirulog. Eur Heart J. 1998; 19: 285.
- ↑ 27.0 27.1 French JK, Ellis CJ, Webber BJ, et al (March 1998). "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. 81 (6): 665–71. PMID 9527071.
- ↑ 28.0 28.1 French JK, Straznicky IT, Webber BJ, et al (February 1999). "Angiographic frame counts 90 minutes after streptokinase predict left ventricular function at 48 hours following myocardial infarction". Heart 81 (2): 128–33. PMID 9922346.
- ↑ 29.0 29.1 French JK, Hyde TA, Straznicky IT, et al (May 2000). "Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction". J. Am. Coll. Cardiol. 35 (6): 1516–24. PMID 10807455.
- ↑ 30.0 30.1 Amos DJ, French JK, Andrews J, et al (April 2001). "Corrected TIMI frame counts correlate with stenosis severity and infarct zone wall motion after thrombolytic therapy". Am. Heart J. 141 (4): 586–91. doi:10.1067/mhj.2001.113393. PMID 11275924.
- ↑ Sahin M, Basoglu T, Canbaz F, Elcik M, Kosus A (December 2002). "The value of the TIMI frame count method in the diagnosis of coronary no-reflow: a comparison with myocardial perfusion SPECT in patients with acute myocardial infarction". Nucl Med Commun 23 (12): 1205–10. doi:10.1097/01.mnm.0000046213.83338.9e. PMID 12464786.
- ↑ Moliterno D, Antman EM, Ohman M, et al. Concordance between core labs in trial results using TIMI flow grades and frame counts. Circulation. 2000; 102 (suppl II): II–590.
- ↑ 33.0 33.1 Dodge JT, Rizzo M, Nykiel M, et al (May 1998). "Impact of injection rate on the Thrombolysis in Myocardial Infarction (TIMI) trial frame count". Am. J. Cardiol. 81 (10): 1268–70. PMID 9604968.
- ↑ Gibson CM, Anshelevich M, Murphy S, et al (December 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.
- ↑ Gibson CM, Kirtane AJ, Murphy SA, et al (May 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.
- ↑ Faile BA, Guzzo JA, Tate DA, Nichols TC, Smith SC, Dehmer GJ (August 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.
- ↑ 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.
- ↑ Straznicky IT, French JK, Webber BJ, et al. Corrected TIMI frame count at 90 minutes predicts left ventricular function at 48 hours following myocardial infarction treated with streptokinase and heparin or hirulog. Eur Heart J. 1998; 19: 285.
- ↑ 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.
- ↑ Gibson CM, Dotani MI, Murphy SA, et al (July 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.
- ↑ Edep ME, Guarneri EM, Teirstein PS, Phillips PS, Brown DL (May 1999). "Differences in TIMI frame count following successful reperfusion with stenting or percutaneous transluminal coronary angioplasty for acute myocardial infarction". Am. J. Cardiol. 83 (9): 1326–9. PMID 10235089.
- ↑ Vrachatis AD, Alpert MA, Georgulas VP, et al (March 2001). "Comparative efficacy of primary angioplasty with stent implantation and thrombolysis in restoring basal coronary artery flow in acute ST segment elevation myocardial infarction: quantitative assessment using the corrected TIMI frame count". Angiology 52 (3): 161–6. PMID 11269778.
- ↑ Hamada S, Nishiue T, Nakamura S, et al (September 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.
- ↑ Capozzolo C, Piscione F, De Luca G, et al (August 2001). "Direct coronary stenting: effect on coronary blood flow, immediate and late clinical results". Catheter Cardiovasc Interv 53 (4): 464–73. PMID 11514995.
- ↑ Bickel C, Rupprecht HJ, Maimaitiming A, et al (October 2002). "The superiority of TIMI frame count in detecting coronary flow changes after coronary stenting compared to TIMI Flow Classification". J Invasive Cardiol 14 (10): 590–6. PMID 12368511.
- ↑ Fang JC, Kinlay S, Wexberg P, et al (October 2000). "Use of the thrombolysis in myocardial infarction frame count for the quantitative assessment of transplant-associated arteriosclerosis". Am. J. Cardiol. 86 (8): 890–2. PMID 11024410.
- ↑ 47.0 47.1 47.2 47.3 47.4 Gibson CM, Ryan KA, Murphy SA, et al (October 1999). "Impaired coronary blood flow in nonculprit arteries in the setting of acute myocardial infarction. The TIMI Study Group. Thrombolysis in myocardial infarction". J. Am. Coll. Cardiol. 34 (4): 974–82. PMID 10520778.
- ↑ 48.0 48.1 48.2 Gibson CM, Goel M, Murphy SA, et al (December 2000). "Global impairment of coronary blood flow in the setting of acute coronary syndromes (a RESTORE substudy). Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis". Am. J. Cardiol. 86 (12): 1375–7, A5. PMID 11113417.
- ↑ Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O'Neill WW (September 2000). "Multiple complex coronary plaques in patients with acute myocardial infarction". N. Engl. J. Med. 343 (13): 915–22. PMID 11006367.
- ↑ Gibson CM, Chen M, Angeja BG, et al (February 2002). "Precordial ST-segment depression in inferior myocardial infarction is associated with slow flow in the non-culprit left anterior descending artery". J. Thromb. Thrombolysis 13 (1): 9–12. PMID 11994554.
- ↑ Gregorini L, Marco J, Kozàkovà M, et al (February 1999). "Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction". Circulation 99 (4): 482–90. PMID 9927393.
- ↑ Hirsh PD, Hillis LD, Campbell WB, Firth BG, Willerson JT (March 1981). "Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease". N. Engl. J. Med. 304 (12): 685–91. PMID 6894016.
- ↑ Bush LR, Campbell WB, Kern K, et al (November 1984). "The effects of alpha 2-adrenergic and serotonergic receptor antagonists on cyclic blood flow alterations in stenosed canine coronary arteries". Circ. Res. 55 (5): 642–52. PMID 6488486.
- ↑ Willerson JT, Campbell WB, Winniford MD, et al (December 1984). "Conversion from chronic to acute coronary artery disease: speculation regarding mechanisms". Am. J. Cardiol. 54 (10): 1349–54. PMID 6391133.
- ↑ Apprill P, Schmitz JM, Campbell WB, et al (August 1985). "Cyclic blood flow variations induced by platelet-activating factor in stenosed canine coronary arteries despite inhibition of thromboxane synthetase, serotonin receptors, and alpha-adrenergic receptors". Circulation 72 (2): 397–405. PMID 2988822.
- ↑ Ashton JH, Golino P, McNatt JM, Buja LM, Willerson JT (March 1989). "Serotonin S2 and thromboxane A2-prostaglandin H2 receptor blockade provide protection against epinephrine-induced cyclic flow variations in severely narrowed canine coronary arteries". J. Am. Coll. Cardiol. 13 (3): 755–63. PMID 2521875.
- ↑ Eidt JF, Allison P, Noble S, et al (July 1989). "Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury". J. Clin. Invest. 84 (1): 18–27. doi:10.1172/JCI114138. PMID 2661588.
- ↑ Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM (July 1989). "Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications". Circulation 80 (1): 198–205. PMID 2661053.
- ↑ Gibson CM, Murphy S, Menown IB, et al (November 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.
- ↑ 60.0 60.1 van 't Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F (June 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.
- ↑ 61.0 61.1 Lepper W, Sieswerda GT, Vanoverschelde JL, et al (December 2001). "Predictive value of markers of myocardial reperfusion in acute myocardial infarction for follow-up left ventricular function". Am. J. Cardiol. 88 (12): 1358–63. PMID 11741552.
- ↑ 62.0 62.1 62.2 Dibra A, Mehilli J, Dirschinger J, et al (March 2003). "Thrombolysis in myocardial infarction myocardial perfusion grade in angiography correlates with myocardial salvage in patients with acute myocardial infarction treated with stenting or thrombolysis". J. Am. Coll. Cardiol. 41 (6): 925–9. PMID 12651035.
- ↑ Gibson CM, Murphy SA, Kirtane AJ, et al (September 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.
- ↑ De Luca G, Suryapranata H, Zijlstra F, et al (September 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.
- ↑ De Luca G, van 't Hof AW, de Boer MJ, et al (June 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.
- ↑ Kirtane AJ, Bui A, Murphy SA, et al (June 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.
- ↑ De Luca G, van 't Hof AW, de Boer MJ, et al (March 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.
- ↑ Tarantini G, Ramondo A, Napodano M, et al (May 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.
- ↑ 69.0 69.1 Gibson CM (August 2003). "Has my patient achieved adequate myocardial reperfusion?". Circulation 108 (5): 504–7. doi:10.1161/01.CIR.0000082932.69023.74. PMID 12900495.
- ↑ Poli A, Fetiveau R, Vandoni P, et al (July 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.
- ↑ Gibson CM, Karha J, Giugliano RP, et al (May 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.
- ↑ Wong GC, Morrow DA, Murphy S, et al (July 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.
- ↑ Gibson CM, Murphy SA, Marble SJ, et al (January 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.
- ↑ Gibson CM, de Lemos JA, Murphy SA, et al (December 2002). "Methodologic and clinical validation of the TIMI myocardial perfusion grade in acute myocardial infarction". J. Thromb. Thrombolysis 14 (3): 233–7. PMID 12913404.
- ↑ Gibson CM, Cohen DJ, Cohen EA, et al (June 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.
- ↑ Murphy SA, Chen C, Gourlay SG, Gibbons RJ, Barron HV, Gibson CM (February 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.
- ↑ Wong GC, Frisch D, Murphy SA, et al (May 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.
- ↑ Gibson CM, Murphy SA, Morrow DA, et al (August 2004). "Angiographic perfusion score: an angiographic variable that integrates both epicardial and tissue level perfusion before and after facilitated percutaneous coronary intervention in acute myocardial infarction". Am. Heart J. 148 (2): 336–40. doi:10.1016/j.ahj.2003.12.044. PMID 15309006.
- ↑ Karha J, Murphy SA, Kirtane AJ, et al (October 2003). "Evaluation of the association of proximal coronary culprit artery lesion location with clinical outcomes in acute myocardial infarction". Am. J. Cardiol. 92 (8): 913–8. PMID 14556865.
- ↑ Gibson CM, Karha J, Murphy SA, et al (April 2004). "Association of a pulsatile blood flow pattern on coronary arteriography and short-term clinical outcomes in acute myocardial infarction". J. Am. Coll. Cardiol. 43 (7): 1170–6. doi:10.1016/j.jacc.2003.11.035. PMID 15063425.
- ↑ (August 1988) "Guidelines for percutaneous transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty)". J. Am. Coll. Cardiol. 12 (2): 529–45. PMID 2969021.
- ↑ Ellis SG, Vandormael MG, Cowley MJ, et al (October 1990). "Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Multivessel Angioplasty Prognosis Study Group". Circulation 82 (4): 1193–202. PMID 2401060.
- ↑ Myler RK, Shaw RE, Stertzer SH, et al (June 1992). "Lesion morphology and coronary angioplasty: current experience and analysis". J. Am. Coll. Cardiol. 19 (7): 1641–52. PMID 1593061.
- ↑ Krone RJ, Laskey WK, Johnson C, et al (May 2000). "A simplified lesion classification for predicting success and complications of coronary angioplasty. Registry Committee of the Society for Cardiac Angiography and Intervention". Am. J. Cardiol. 85 (10): 1179–84. PMID 10801997.
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- ↑ Gibson CM, Bigelow B, James D, et al (July 2004). "Association of lesion complexity following fibrinolytic administration with mortality in ST-elevation myocardial infarction". Am. J. Cardiol. 94 (1): 108–11. doi:10.1016/j.amjcard.2004.03.038. PMID 15219518.
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- ↑ Antman EM, Hand M, Armstrong PW, et al (January 2008). "2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee". Circulation 117 (2): 296–329. doi:10.1161/CIRCULATIONAHA.107.188209. PMID 18071078.
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
