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The Impact of Systemic BP on Coronary Blood Flow and Infarct Size During Reperfusion Therapy for Acute Myocardial Infarction : Refinements Beyond the “Plumbing” FREE TO VIEW

John E. Madias
Author and Funding Information

Affiliations: New York, NY
 ,  Dr. Madias is Professor of Medicine (Cardiology), Division of Cardiology, Elmhurst Hospital Center.

Correspondence to: John E. Madias, MD, Professor of Medicine (Cardiology), Division of Cardiology, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373; e-mail:madiasj@nychhc.org



Chest. 2004;125(4):1179-1181. doi:10.1378/chest.125.4.1179
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The levels of systemic arterial BP encountered in patients admitted for acute myocardial infarction (AMI) cover the gamut of values from hypertension (↑BP) to hypotension (↓BP). Also, the BP can either remain stable or show significant perturbations during the early phase of AMI. First, ↑BP can only be a manifestation of the clinical syndrome of AMI in patients without a history or evidence for ↑BP at subsequent follow-up. In this scenario, the patients are likely to have had an anterior AMI, have ↑BP, are sweating profusely, and manifest tachycardia, thus displaying the full complement of an autonomic hyperadrenergic state. These clinical features are transient, and BP in such patients is normal at follow-up. Second, BP can be high in patients with AMI and known or just-diagnosed ↑BP; often such a diagnosis can be made with certainty only at follow-up by documenting a persistently elevated BP. Third, BP in patients with an AMI can remain normal throughout the hospitalization, and at follow-up. Fourth, ↓BP can be seen along with evidence of tachycardia, and hypoperfusion of peripheral tissues in patients with cardiogenic shock.12 Some of these patients have ↓BP on admission or their initial BP is normal, prior to the development of ↓BP. Fifth, ↓BP may be observed in patients with inferior AMI and associated right ventricular infarct. In these patients ↓BP is mostly transient if fluids are infused in appropriate amounts, and its occurrence can be even prevented by such action. ST-segment elevation in right-chest ECG leads in patients with an inferior AMI,34 history of ↑ BP, and normal BP early after admission can aid in anticipating impending ↓BP.

Guidelines1 and the literature56 consistently have expressed concern about delays in seeking medical attention, extending to ≥ 2 h after symptom onset, thus resulting in reperfusion therapies starting late. The preoccupation (and rightly so) among physicians caring for victims of heart attacks to implement thrombolysis or angioplasty as soon as possible has advanced the time to reperfusion to a status of a “critical modulator,”6 and the time early in the course of an AMI to a role of an “adjunctive agent.”5 In reference to IV nitroglycerin (NTG) and in the context of its angina-relieving and hypotensive effects, it has been emphasized that NTG has a place in the management of patients with an AMI in the first 24 to 48 h when there is ↑BP, or the AMI is anterior, or there is congestive heart failure, or persistent chest pain (class I indications). Also when BP is normal and there is no tachycardia or bradycardia, the drug can be employed in patients with AMI even without the above characteristics (class IIb indication). NTG can be infused beyond the 48 h if the AMI is large, or there is persistent pulmonary congestion, or chest pain recurs (class I and class IIb indications). When there is systolic BP < 90 mm Hg and heart rate < 50 beats/min, the use of the drug is contraindicated, particularly in the presence of an inferior AMI (class III indication).1,4,7 Although as per guidelines, “inadvertent systemic ↓BP with resulting worsening of myocardial ischemia is the most serious potential complication of NTG therapy,”1 there is no linking explicitly expressed there, or in the literature among the triad of “BP, NTG, and reperfusion,” or the dyad of “BP and reperfusion.”

Reperfusion management strategies for AMI have so far emphasized almost exclusively the importance of expeditious administration of thrombolysis and implementation of angioplasty. However, a search for the variables determining effective reperfusion is now underway; also, all the measures that were advocated for a favorable balance of myocardial oxygen supply and demand8and the “protection of ischemic myocardium” in the prethrombolytic era are being adopted as adjuvant therapies to our reperfusion protocols.9As a corollary of the above, serious consideration of the levels of BP during reperfusion therapy is in order. Although the diastolic BP constitutes a determinant of coronary perfusion, and ↓BP can have a deleterious effect, equally detrimental is the role of ↑BP and resultant left ventricular hypertrophy on the infarct size, as shown in canine coronary artery occlusion models.1011 This is consistent with the notion that increased determinants of myocardial oxygen demands8during the delicate period after the inception of AMI exert a deleterious effect on the progression of myocardial necrosis. Such idea had been at the center of efforts to reduce infarct size by normalizing BP, heart rate, and contractility using β-blockers during the prethrombolytic era.9 However during thrombolysis in patients with AMI, systolic BP > 160 mm Hg was not shown to be detrimental, but < 120 mm Hg proved to be so in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) cohort.12 This seemingly paradoxical response was probably the impetus for a study in this issue, for which this commentary is offered.

In this issue of CHEST (see page 1493), Nanas et al report on the impact of low BP on the coronary blood flow and infarct size employing a porcine left anterior descending coronary artery occlusion/reperfusion experimental model. The relevance of their findings for the clinical situation is enhanced by the following: (1) their use of pigs rather than dogs, considering the similarities in the coronary circulation between humans and the former13; (2) the implementation of “1 h occlusion/2 h reperfusion” model, which is representative of what is encountered in patients presenting after a heart attack, and consistent with the time window during which the outcomes of reperfusion are expected to be very significant for tissue preservation1; and (3) the use of NTG, a commonly employed drug in clinical AMI. The only differences between the two experimental groups were that fluids were infused in the animals of group I, designed to counteract the hypotensive effect of NTG, and to maintain a normal BP, and the dose of this drug was lower than the one used in the animals of group II. As a result, and although the two groups were comparable in every other way (including the myocardium at risk, approximately 27% in both groups), group I animals realized a higher coronary blood flow, peak hyperemia coronary blood flow during reperfusion, and a decreased infarct size adjusted for myocardial tissue at risk (approximately 28%) in comparison with the group II animals, despite an increased mean BP (approximately 30%), and double product (23%). The authors provide a convincing argument as to the possible mechanisms of the cardioprotective effect exerted by the maintenance of adequate perfusion pressure by referring to the work of others and presenting a comprehensive comparison of their data with information from the literature.

The findings of this study support the notion that maintenance of normal systemic BP during reperfusion, or avoidance of ↓BP, are crucial for the salvage of a sizeable proportion of the ischemic myocardium at risk. Obviously this is important for both the immediate and the long-term outcomes of patients who have had an AMI. Also, BP may be only one in a number of physiologic variables, which can be influential in boosting the therapeutic outcome of reperfusion; perhaps others will be identified in the future, and all of them when applied in concert, along with adjunctive therapies, would enhance what we are currently accomplishing. Advancements as the one commented on herein contribute to the host of parameters that the clinician could take into consideration to predict the impact of reperfusion in AMI. Thus, along with the time interval between onset of chest pain and initiation of reperfusion therapy,1 the BP level during reperfusion would now be of concern. These considerations constitute refinements to our current concepts for the management of patients with AMI.

Although the porcine model that the authors used offers a useful experimental tool for the simulation of human AMI, we should remember that the findings of this report may not translate directly to the clinical milieu. We would have been provided more information had the time of reperfusion been extended beyond the 2 h to evaluate its impact on the infarct size; however, the authors afforded convincing evidence that coronary blood flows were stable and differed decidedly between the two groups, and thus it is unlikely that a much different outcome would be seen with a longer reperfusion period. Since the dose of NTG was much lower in the animals of group I, one wonders what would have been observed if this drug was administered in the same dose in all animals, and the BP in those of group I was supported with larger amounts of fluids. This would provide for further comparability of the two groups, although NTG was used for its BP-lowering effect and no cytoprotection is implied here.1417 Finally the syndrome of inferior AMI in association with right ventricular involvement (a common encounter in the coronary care unit) was not simulated in the work of the authors. Patients as the above have ↓BP, require infusion of large volumes of fluid often resulting in “dilutional hypocarbonatemia,”18 and require discontinuation of NTG therapy.1,4,7 The author of this commentary advocates continuation of NTG with infusion of large amounts of fluid, and close monitoring of BP. Had these workers used a right coronary artery occlusion/reperfusion model in some swine, such issues could have been explored, although whether such a model could reproduce the human inferior/right ventricular AMI needs confirmation.

Areas/questions that need to be delineated/ answered in the future are as follows. (1) What is the level of the lowest BP that needs to be maintained to protect the ischemic myocardium during reperfusion, and up to what level of BP is there safety provided by not increasing myocardial oxygen demands? It should be assumed that beyond a particular level, BP may be acting as a factor augmenting infarct size (ie, window of BP benefit). Of course, these BP ranges may be different for the animal and the patient, and in different individuals, and may have a bearing on preexisting hypertension and/or left ventricular hypertrophy.1011 (2) Findings of this study refer to situations where reopening of the culprit vessel is accomplished at a 100% level, something that cannot be guaranteed in the human condition when thrombolysis is used; however, when reperfusion is based on successful angioplasty/stenting, this study may fit entirely. Consequently, levels of safe lowest BP may differ depending on the method used for reperfusion. (3) ↓BP is more common with inferior myocardial infarction, particularly in association with right ventricular infarction, while this study employed left anterior descending coronary artery occlusion. Future work may delineate the role of maintenance of the BP during reperfusion in inferior AMI and its impact on the infarct size and on the recovery of right ventricle. One can even envision that a range of BP levels could be induced in patients with an AMI for maximal benefit, by employing a feedback online index of coronary perfusion. All of these need to be defined, and this can be accomplished only through randomized clinical trials, as the authors conclude. Nevertheless and for the time being, these workers have provided us with additional knowledge, and stimulation to abandon our complacent preoccupation with only the reperfusion aspect of management of our patients with AMI and to look beyond the “plumbing.”

References

Ryan TJ, Antman EM, Brooks NH, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction,1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). Available at: http//:www.acc.org. Accessed March 1, 2004.
 
Hochman, JS, Sleeper, LA, Webb, JB, for the SHOCK Investigators. et al Early revascularization in acute myocardial infarction complicated by cardiogenic shock.N Engl J Med1999;341,625-634. [CrossRef] [PubMed]
 
Robalino, BD, Whitlow, PL, Underwood, DA, et al Electrocardiographic manifestations of right ventricular infarction.Am Heart J1989;118,138-144. [CrossRef] [PubMed]
 
Kinch, JW, Ryan, TJ Right ventricular infarction.N Engl J Med1994;330,1211-1217. [CrossRef] [PubMed]
 
Cannon, CP, Antman, EM, Walls, R, et al Time as an adjunctive agent to thrombolytic therapy.J Thromb Thrombolysis1994;1,27-34. [CrossRef] [PubMed]
 
Cannon, CP, Braunwald, E Time to reperfusion: the critical modulator in thrombolysis and primary angioplasty.J Thromb Thrombolysis1996;3,117-125. [PubMed]
 
Come, PC, Pitt, B Nitroglycerin-induced severe hypotension and bradycardia in patients with acute myocardial infarction.Circulation1976;54,624-628. [CrossRef] [PubMed]
 
Braunwald, E Myocardial oxygen consumption: the quest for its determinants and some clinical fallout.J Am Coll Cardiol2000;35(Suppl B),44B-48B
 
Braunwald, E Personal reflections on efforts to reduce ischemic myocardial damage.Cardiovasc Res2002;56,332-338. [CrossRef] [PubMed]
 
Inou, T, Lamberth, WC, Jr, Koyanagi, S, et al Relative importance of hypertension after coronary occlusion in chronic hypertensive dogs with LVH.Am J Physiol1987;253,H1148-H1158. [PubMed]
 
Dellsperger, KC, Clothier, JL, Hartnett, JA, et al Acceleration of the wavefront of myocardial necrosis by chronic hypertension and left ventricular hypertrophy in dogs.Circ Res1988;63,87-96. [CrossRef] [PubMed]
 
Lee, KL, Woodlief, LH, Topol, EJ, for the GUSTO-I Investigators. et al Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41021 patients.Circulation1995;91,1659-1668. [CrossRef] [PubMed]
 
Pantely, GA, Ladley, HD, Bristow, JD Low zero-flow pressure and minimal capacitance effect on diastolic coronary arterial pressure-flow relationships during maximum vasodilation in swine.Circulation1984;70,485-494. [CrossRef] [PubMed]
 
Fukuyama, T, Schechtman, KB, Roberts, R The effects of intravenous nitroglycerin on hemodynamics, coronary blood flow and morphologically and enzymatically estimated infarct size in conscious dogs.Circulation1980;62,1227-1238. [CrossRef] [PubMed]
 
Jugdutt, BIM Myocardial salvage by intravenous nitroglycerin conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension.Circulation1983;68,673-684. [CrossRef] [PubMed]
 
GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction.Lancet1994;343,1115-1122. [PubMed]
 
ISIS-4: a randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial infarction.Lancet1995;345,669-685. [CrossRef] [PubMed]
 
Jaber, BL, Madias, NE Marked dilutional acidosis complicating management of right ventricular myocardial infarction.Am J Kidney Dis1997;30,561-567. [CrossRef] [PubMed]
 

Figures

Tables

References

Ryan TJ, Antman EM, Brooks NH, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction,1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). Available at: http//:www.acc.org. Accessed March 1, 2004.
 
Hochman, JS, Sleeper, LA, Webb, JB, for the SHOCK Investigators. et al Early revascularization in acute myocardial infarction complicated by cardiogenic shock.N Engl J Med1999;341,625-634. [CrossRef] [PubMed]
 
Robalino, BD, Whitlow, PL, Underwood, DA, et al Electrocardiographic manifestations of right ventricular infarction.Am Heart J1989;118,138-144. [CrossRef] [PubMed]
 
Kinch, JW, Ryan, TJ Right ventricular infarction.N Engl J Med1994;330,1211-1217. [CrossRef] [PubMed]
 
Cannon, CP, Antman, EM, Walls, R, et al Time as an adjunctive agent to thrombolytic therapy.J Thromb Thrombolysis1994;1,27-34. [CrossRef] [PubMed]
 
Cannon, CP, Braunwald, E Time to reperfusion: the critical modulator in thrombolysis and primary angioplasty.J Thromb Thrombolysis1996;3,117-125. [PubMed]
 
Come, PC, Pitt, B Nitroglycerin-induced severe hypotension and bradycardia in patients with acute myocardial infarction.Circulation1976;54,624-628. [CrossRef] [PubMed]
 
Braunwald, E Myocardial oxygen consumption: the quest for its determinants and some clinical fallout.J Am Coll Cardiol2000;35(Suppl B),44B-48B
 
Braunwald, E Personal reflections on efforts to reduce ischemic myocardial damage.Cardiovasc Res2002;56,332-338. [CrossRef] [PubMed]
 
Inou, T, Lamberth, WC, Jr, Koyanagi, S, et al Relative importance of hypertension after coronary occlusion in chronic hypertensive dogs with LVH.Am J Physiol1987;253,H1148-H1158. [PubMed]
 
Dellsperger, KC, Clothier, JL, Hartnett, JA, et al Acceleration of the wavefront of myocardial necrosis by chronic hypertension and left ventricular hypertrophy in dogs.Circ Res1988;63,87-96. [CrossRef] [PubMed]
 
Lee, KL, Woodlief, LH, Topol, EJ, for the GUSTO-I Investigators. et al Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41021 patients.Circulation1995;91,1659-1668. [CrossRef] [PubMed]
 
Pantely, GA, Ladley, HD, Bristow, JD Low zero-flow pressure and minimal capacitance effect on diastolic coronary arterial pressure-flow relationships during maximum vasodilation in swine.Circulation1984;70,485-494. [CrossRef] [PubMed]
 
Fukuyama, T, Schechtman, KB, Roberts, R The effects of intravenous nitroglycerin on hemodynamics, coronary blood flow and morphologically and enzymatically estimated infarct size in conscious dogs.Circulation1980;62,1227-1238. [CrossRef] [PubMed]
 
Jugdutt, BIM Myocardial salvage by intravenous nitroglycerin conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension.Circulation1983;68,673-684. [CrossRef] [PubMed]
 
GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction.Lancet1994;343,1115-1122. [PubMed]
 
ISIS-4: a randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial infarction.Lancet1995;345,669-685. [CrossRef] [PubMed]
 
Jaber, BL, Madias, NE Marked dilutional acidosis complicating management of right ventricular myocardial infarction.Am J Kidney Dis1997;30,561-567. [CrossRef] [PubMed]
 
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