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Ann Thorac Surg 2002;73:1522-1527
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury

^a Department of Cardiothoracic Surgery, Boston Medical Center and the Boston University School of Medicine, Boston, Massachusetts, USA

Accepted for publication January 22, 2002.

* Address reprint requests to Dr Lazar, Department of Cardiothoracic Surgery, Boston Medical Center, 88 E. Newton St, B404, Boston, MA 02118 USA
e-mail: harold.lazar{at}bmc.org

	Abstract

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Background. The Heart Outcomes Prevention Evaluation (HOPE) trial demonstrated that ischemic events are decreased in patients receiving angiotensin-converting enzyme (ACE) inhibitors. This study sought to determine whether pretreatment with ACE inhibitors would attentuate ischemic injury during surgical revascularization of ischemic myocardium.

Methods. In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest, and 180 minutes of reperfusion. Ten pigs received quinapril (20 mg PO q.d.) for 7 days prior to surgery; 10 others received no-ACE inhibitors.

Results. Quinapril-treated animals required less cardioversions for ventricular arrhythmias (1.58 ± 0.40 vs 2.77 ± 0.22; p < 0.05), had higher wall motion scores assessed by two-dimensional echocardiography (4 = normal to -1 = dyskinesia; 2.11 ± 0.10 vs 1.50 ± 0.07; p < 0.05), more complete coronary artery endothelial relaxation to bradykinin (45% ± 3% vs 7% ± 4%; p < 0.005), and lower infarct size (24.0% ± 3.0% vs 40.0% ± 1.7%; p < 0.0001).

Conclusions. ACE inhibition prior to coronary revascularization enhances myocardial protection by decreasing ventricular irritability, improving regional wall motion, lowering infarct size, and preserving endothelial function.

	Introduction

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There is growing evidence to suggest that patients with atherosclerosis involving the coronary, cerebrovascular, and peripheral vascular systems, as well as diabetic patients, should be receiving angiotensin-converting enzyme (ACE) inhibitor therapy in an attempt to minimize ischemic events [1, 2]. The Studies of Left Ventricular Dysfunction and Survival and Ventricular Enlargement trials demonstrated that ACE inhibitors prevented major ischemic events in patients with low ejection fractions following a myocardial infarction (MI) [3, 4]. Recently, the Heart Outcomes Prevention Evaluation (HOPE) trial showed that ACE inhibition prevented atherothrombotic complications in a wide range of patients at risk for cardiovascular events, independent of their ejection fraction or whether clinical manifestations of congestive heart failure were present [1]. As a result of these trials, a significant number of patients coming for coronary artery bypass graft (CABG) surgery are now receiving ACE inhibitor therapy.

Previous studies have shown that patients receiving long-term ACE inhibitor therapy following CABG had a significant reduction in ischemic events and cardiovascular deaths [5, 6]. Recently, in a porcine model involving the revascularization of acutely ischemic myocardium on cardiopulmonary bypass (CPB) with cardioplegic arrest, we showed that the use of intravenous ACE inhibitors resulted in less ventricular irritability, better recovery of regional wall motion, and reduced ischemic necrosis [7]. ACE inhibitors with higher tissue affinity for ACE, such as quinaprilat, resulted in better preservation of endothelial function, which led to reduced infarct size [7]. However, the effects of ACE inhibitors given for extended periods of time prior to CABG is unknown. There is some evidence to suggest that prolonged ACE inhibitor administration prior to CABG may result in hypotension and increase the need for vasoconstrictor support [8–10]. Furthermore, it is uncertain as to whether ACE inhibitor therapy prior to CABG will confer the same protective effects as seen when initiated during and following surgical revascularization. Since increasing numbers of patients are now coming to CABG surgery on ACE inhibitor therapy, this experimental study was undertaken to determine whether pretreatment with a high tissue-affinity ACE inhibitor, such as quinapril, would protect against ischemic injury during surgical revascularization of acutely ischemic myocardium.

	Material and methods

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Randomization
Twenty pigs were entered into the study and none were excluded. Animals were fed a standard chow diet to which either quinapril (20 mg PO q.d.) or a placebo were added for 1 week. They were randomized by selecting a sealed envelope, which contained a 7-day supply of medication, such that the investigators were blinded to the identity of the medication.

Preparation
Adult pigs (35 to 38 kg) were premedicated with ketamine (15 mg/kg intramuscularly [IM]) and xylazine (0.5 mg/kg IM), anesthetized with -chloralose (75 mg/kg), and placed on positive-pressure endotracheal ventilation. Following a mediasternotomy and systemic heparinization (3 mg/kg), the second and third diagonal branches just distal to the takeoff of the left anterior descending artery were occluded with snares for 90 minutes. The pigs were then placed on CPB and the hearts were arrested with multidose, antegrade/retrograde, cold blood cardioplegia (potassium 25 mEq/L, hematocrit 18 to 20, pH 7.6, temperature 4°C) supplemented with topical hypothermia for 45 minutes. The aortic cross-clamp was then removed, the coronary snares were released, and all hearts were perfused in normal sinus rhythm for 180 minutes on CPB with a mean aortic pressure (MAP) of 60 mm Hg at 37°C.

Treatment groups
During the 7 days prior to surgery, animals were divided into 2 groups:

No-ACE inhibitor group
In 10 animals, no-ACE inhibitor was given. The animals were given a placebo tablet with their chow.

Quinapril group
In 10 animals, quinapril (20 mg) was given daily with the chow. We used doses of quinapril that have been shown to reduce ischemic events in clinical studies following CABG surgery [5].

Measurements and statistical analyses
Electrocardiographic leads were placed to measure heart rate and to monitor electrical activity during cardioplegic arrest. Left ventricular end-diastolic pressure (LVEDP) was recorded with a piezoelectric Mikro-Tip catheter pressure transducer (Millar Instruments Inc, Houston, TX) inserted through a stab wound in the left ventricular apex. Intravenous (IV) lidocaine was used to treat ventricular arrhythmias. Electrical cardioversion was used to treat ventricular fibrillation and ventricular tachycardia, which was either unresponsive to IV lidocaine or resulted in a significant (20 mm Hg) decrease in systolic blood pressure.

Echocardiographic short and long-axis sections obtained from transthoracic echocardiograms were used to define wall motion changes in the area of risk as previously described [11]. A wall motion score (WMS) was derived (4 = normal, 3 = mild hypokinesis, 2 = moderate hypokinesis, 1 = severe hypokinesis, 0 = akinesis, and -1 = dyskinesia) to indicate changes in wall motion. The sections were interpreted by an experienced echocardiographer (S.A.B.) in a blinded fashion, and the scores were averaged for the coronary occlusion and reperfusion periods for all experimental groups.

Infarct size was assessed by determining the areas of necrosis to areas of risk using histochemical staining techniques with triphenyltetrazolium chloride as previously described [11]. Stained myocardial slices were planimetered to obtain the area of risk compared with the total left ventricular mass and the percent area of infarct in that area of risk.

Epicardial vascular relaxation was assessed using standard organ chamber methodology. A segment of the second or third diagonal vessel in the area at risk was dissected, cut into rings, and suspended in organ chambers with oxygenated Krebs buffer at 37°C. Ring tension was determined using a force displacement transducer (Grass Instruments, Inc, West Warwick, RI) attached to each tensiometer apparatus and recorded on MacLab recording software. The rings were allowed to equilibrate at a passive tension of 2 g to 3 g for 60 minutes and then contracted with 1 µmol/L prostaglandin (PG) F_2x and allowed to stabilize. Once a stable contraction was obtained, coronary vasomotor function was assessed by generating dose-response curves to cumulative concentrations of nitroglycerin (NTG) (10^-9 to 10^-5 mol/L), an endothelial-independent coronary vasodilator, and the calcium ionophore A23187 and bradykinin, endothelial-dependent coronary vasodilators. Relaxation in response to each concentration of the agonist was calculated as the percent reduction in isometric tension from the tension produced by 1 µmol/L PGF_2x. Values were calculated for each experiment and mean values were computed for the various treatment groups.

The concentrations of C5b-9 were determined by a modification of a dual monoclonal antibody enzyme immunoassay [12]. The monoclonal antibodies are specific for human C9 neoantigen (clone aE11; Dako, Carpinteria, CA) and human C7 (Quidel, San Diego, CA) and were demonstrated to cross-react with components of activated porcine complement. Concentrations of C5b-9 are reported in arbitrary units per milliliter and directly reflect complement activation in vivo.

All values represent mean ± SE. Differences in measurements between the various groups and across time were assessed by repeated measurements of ANOVA. StatView 4.5 (Abacus Concepts, Inc, Berkeley, CA) was used to compute these analyses. Data were considered significant at p values less than 0.05.

All pigs received humane care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH publication 86-23, revised 1985).

	Results

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Hemodynamic parameters during coronary occlusion prior to CPB
Table 1 summarizes the changes in hemodynamics during the 90 minutes of coronary occlusion prior to CPB. There was no significant difference in heart rate, MAP, or LVEDP between quinapril and non-ACE inhibitor animals prior to coronary occlusion. Following 90 minutes of coronary occlusion, both groups showed small, but significant (p < 0.05) decreases in heart rate and MAP from preischemic values, although there was no difference between the quinapril and no-ACE inhibitor groups. LVEDP was significantly (p < 0.05) higher in both groups after 90 minutes of coronary occlusion compared with preocclusion values. However, at a comparable MAP (65 ± 6 mmHg quinapril vs 64 ± 5 mmHg no-ACE inhibitor), LVEDP was significantly lower in the quinapril-treated hearts (7.0 ± 0.5 mmHg quinapril vs 9.4 ± 0.8 mmHg no-ACE inhibitor; p < 0.05).

Coronary artery vasomotor function
Coronary artery vasomotor function as assessed by coronary artery relaxation is depicted in Figure 1. Endothelial-independent relaxation in response to NTG remained intact in both groups (93% ± 3% quinapril vs 82% ± 9% no-ACE inhibitors). Endothelial-dependent relaxation was markedly impaired to both A23187 and bradykinin in the no-ACE inhibitor animals (Fig 1). Quinapril resulted in better preservation of endothelial-dependent relaxation to both A23187 (54.0% ± 9.6% vs 20.0% ± 10.1%; p < 0.05) and bradykinin (45.0% ± 3% vs 7.7% ± 4.0%; p = 0.005).

View larger version (15K): [in this window] [in a new window]   Fig 1. Coronary artery relaxation. Endothelium-independent coronary vasodilatation in response to nitroglycerin (A) is preserved in both the quinapril and no-ACE inhibitor groups. Endothelium-dependent relaxation to A23187 (B) and bradykinin (C) is significantly greater in the quinapril-treated animals. (ACE = angiotensin-converting enzyme.)

View larger version (19K): [in this window] [in a new window]   Fig 2. C5b-9 levels are significantly lower in the quinapril-treated animals during reperfusion on cardiopulmonary bypass. (ACE = angiotensin-converting enzyme.)

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Previous studies have shown that ACE inhibitors may play an important role in minimizing ischemic events during and following CABG surgery [5–7]. The results of this study indicate that they may also play an important role in preventing myocardial injury when given prior to surgery.

The beneficial effects of ACE inhibitors following CABG were reported in two clinical trials involving high tissue affinity ACE inhibitors [5, 6]. In the QUOVADIS (Quinapril on Vascular ACE and Determinants of Ischemia) study, 149 patients scheduled for elective CABG were randomized to receive quinapril 40 mg/day or a placebo for 3 to 4 weeks prior to CABG and for 1 year following surgery [5]. Quinapril-treated patients had an 80% reduction in ischemic events (MI, cerebrovascular accident [CVA], transient ischemic attack, or recurrence of angina) from 18% to 4%; p = 0.04. Blood pressure levels were similar in both groups suggesting that the cardioprotective effects of quinapril occurred through mechanisms other than antihypertensive effects. Furthermore, there were no untoward perioperative hemodynamic effects in the group pretreated with quinapril. The APRES (Angiotensin-Converting Enzyme Inhibition Post Revascularization Study) trial studied the effects of ramipril in 159 revascularized (130 CABG; 29 percutaneous transluminal coronary angioplasty) normotensive patients with moderately depressed (30% to 50%) ejection fractions [6]. The ramipril treated group had a significant reduction in the composite endpoint of cardiac death, MI, and congestive heart failure (a risk reduction of 58%; p = 0.03) after a median follow-up of 33 months. There was also a significant reduction in cardiac deaths (p = 0.03). No patient in the ramipril-treated group developed renal impairment or electrolyte derangements in doses as high as 10 mg. In a follow-up study, ramipril significantly reduced echo-derived end-diastolic and end-systolic volume indices suggesting that ramipril’s favorable effects in these patients may be due in part to a reduction in left ventricular volumes [13].

The results of the HOPE trial suggest that ACE inhibition may also prevent ischemic events in patients who ultimately may require CABG surgery [1]. In this study, patients with evidence of atherosclerotic vascular disease and diabetes were treated with ramipril for 5 years. Ramipril resulted in a significant reduction in the composite endpoint of MI, CVA, and death from cardiovascular disease as well as a significant reduction in the need for revascularization procedures. This was accomplished with a mean reduction in systolic and diastolic pressures of only 3.3 mmHg and 2 mmHg. The results strongly support the premise that all patients with atherosclerotic vascular disease should be treated with long-term ACE inhibitor therapy. This will undoubtedly increase the number of patients coming to CABG surgery on ACE inhibitors. The effects of ACE inhibitor therapy prior to CABG are, however, inconclusive.

Tuman and coworkers found that patients receiving ACE inhibitors for greater than 15 days prior to cardiac surgery had a significant increase in pressor utilization (7.7% vs 4.0%; p = 0.0001) at the termination of CPB [10]. However, 4 hours after CPB, there was no significant difference in pressor requirements between the groups. Although the ACE inhibitor patients required more pressor agents early after CPB, this occurred in the presence of normal cardiac outputs and indices and significantly lower systemic vascular resistance (SVR). Furthermore, the patients who received preoperative ACE inhibitor therapy were significantly older, had longer CPB and cross-clamp times, and a higher incidence of CHF, reoperative surgery, insulin-dependent diabetes, and valvular surgery. Pigott and coworkers noted similar findings in patients with pre-CPB ACE inhibitor therapy [9]. Although there was an increased requirement for pressor support to treat hypotension, it was transient and occurred in the setting of normal left ventricular function and adequate cardiac outputs and indices. Boldt and coworkers found that intravenous enalaprilat given as a bolus during induction prior to CPB decreased systolic blood pressure as a result of decreased SVR, but cardiac index was increased and heart rate unchanged [8]. Colson and coworkers found that captopril given in doses of 100 mg orally twice a day for 48 hours prior to CABG had no effect on blood pressure and attenuated the effects of transient renal dysfunction associated with CPB [14].

The results of our experimental study strongly suggest that pretreatment with a high tissue affinity ACE inhibitor, such as quinapril, minimizes ischemic injury during surgical revascularization of acutely ischemic myocardium. Similar to the HOPE, QUOVADIS, and APRES trials, these beneficial effects occurred in doses that had no significant changes in blood pressure from the non-ACE inhibitor group. Quinapril-treated hearts had significantly lower end-diastolic pressures at comparable heart rates and mean aortic pressures suggesting lower end-diastolic volumes, similar to ramipril-treated hearts in the APRES trial [13]. Pretreatment with quinapril decreased ventricular irritability, attenuated the decrease in regional wall motion, and resulted in better recovery of coronary vasomotor function. As a result, quinapril-treated animals had significantly less tissue necrosis. Another interesting finding in this study is that quinapril significantly decreased C5b-9 production during CPB. C5b-9 is an important mediator of ischemic tissue injury and has been associated with altered endothelial function, impaired intracellular Ca⁺² metabolism, and increased transcellular migration of leukocytes by upregulation of P-selectin, all of which may contribute to cellular death [15]. Increased levels of C5b-9 have been observed in patients after an acute MI and have been deposited in ischemic myocardial endothelial cells [16]. In previous studies using a similar model of acute surgical revascularization, C5b-9 levels were highest after CPB and were associated with increased lung water accumulation, depressed regional wall motion, myocardial tissue acidosis, and larger infarct size [17]. Interventions, which lowered C5b-9 production resulted in significantly less ischemic damage [17]. It is unclear from our study whether the decreased levels of C5b-9 seen in the quinapril group were the result of decreased tissue necrosis or the direct effects of ACE inhibition.

Our experimental findings strongly support the use of ACE inhibitors prior to CABG surgery. In our study, we chose an ACE inhibitor with high tissue ACE affinity in doses that were successful in a previous clinical trial [5]. It is unknown whether other classes of ACE inhibitors at lower doses will also have protective effects. A major criticism of the QUOVADIS trial was that only elective patients receiving 3 to 4 weeks of ACE inhibitor therapy were studied. Our results suggest that shorter periods of treatment in hearts undergoing more urgent revascularization are also likely to benefit from ACE inhibitors. Concerns have been raised regarding the potential antagonism between ACE inhibition and aspirin (ASA). ACE inhibition increases prostaglandins, which are inhibited by ASA [18]. Some studies have suggested that ASA may reduce the benefits of ACE inhibitors in patients following an MI or with CHF [19, 20], whereas, others have exhibited no such effect [21]. It is important to remember that in the HOPE, QUOVADIS, and APRES trials, the beneficial effects of ACE inhibitors were seen despite the fact that 75% of patients were taking ASA [1, 5, 6]. It has been suggested by some that this problem may be avoided by giving ASA 8 to 12 hours prior to ACE inhibitors and reducing the ASA dose to 81 mg; thereby still obtaining the antiplatelet effects, while avoiding the problem of interference with prostaglandin synthesis [2].

Our own experience with ACE inhibitors prior to CABG surgery is similar to other studies [8–10]. The observed decrease in SVR is accompanied by a normal or increased cardiac output and index, and is easily reversed by short periods of low-dose pressor support. We have observed no adverse outcomes with ACE inhibitor therapy prior to CPB in our clinical practice.

In summary, this experimental study has found another potential indication for placing patients with atherosclerotic vascular disease on ACE inhibitor therapy. Should the need for surgical revascularization arise, ACE inhibition may confer added myocardial protection, and further limit ischemic damage. Prospective, randomized clinical trials will be necessary to better define the role of ACE inhibitors in improving outcomes when they are prescribed prior to CABG surgery.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
This work was supported in part by a grant from Pfizer Pharmaceuticals Inc, New York, NY.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. HOPE (Heart Outcomes Prevention Evaluation) Study Investigators. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-153.[Abstract/Free Full Text]
2. O’Keefe J.H., Wetzel M., Moe R.R., et al. Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic decrease?. J Am Coll Cardiol 2001;37:1-8.[Abstract/Free Full Text]
3. Yusuf S., Pepine C.J., Garces C., et al. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet 1992;340:1173-1178.[Medline]
4. Rutherford J.D., Pfeffer M.A., Moye L.A., et al. Effects of captopril on ischemic events after myocardial infarction: results of the Survival and Ventricular Enlargement trial. Circulation 1994;90:131-138.
5. Oosterga M., Voors A.A., Pinto Y.M., et al. Effects of quinapril on clinical outcome after coronary artery bypass grafting (the QUOVADIS study) Am J Cardiol 2001;87:542-546.
6. Kjoller-Hansen L., Steffensen R., Grande P. The angiotensin-converting enzyme inhibition post revascularization study (APRES). J Am Coll Cardiol 2000;35:881-888.[Abstract/Free Full Text]
7. Lazar H.L., Bao Y., Rivers S., Bernard S. High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial function and reduce infarct size. Ann Thorac Surg 2001;72:548-554.[Abstract/Free Full Text]
8. Boldt J., Schindler E., Harter K., et al. Influence of intravenous administration of angiotensin-converting enzyme inhibitor enalaprilat on cardiovascular mediators in cardiac surgery patients. Anesth Analg 1995;80:480-485.[Abstract]
9. Pigott D.N., Nagle C., Allman K., et al. Effect of omitting regular ACE inhibitor medication before cardiac surgery on haemodynamic variables and vasoactive drug requirements. Br J Anaesth 1999;83:715-720.[Abstract/Free Full Text]
10. Tuman K., McCarthy R.J., O’Connor C.J., et al. Angiotensin-converting enzyme inhibitors increase vasoconstrictor requirement after cardiopulmonary bypass. Anesth Analg 1995;80:473-479.[Abstract]
11. Lazar H.L., Yang X.M., Rivers S., et al. Role of percutaneous bypass in reducing infarct size after revascularization for acute coronary insufficiency. Circulation 1991;84:416-421.
12. Jansen J.G., Hogasen K., Mollnes T.E. Extensive complement activation in herediary porcine membranoproliferative glomerulonephritis type-II (porcine dense deposit disease). Am J Pathol 1993;143:1356-1365.[Abstract]
13. Kjoller-Hansen L.K., Steffensen R., Grande P. Beneficial effects of ramipril on left ventricular end-diastolic and end-systolic volume indexes after uncomplicated invasive revascularization are associated with a reduction in cardiac events in patients with moderately impaired left ventricular and no clinical heart failure. J Am Coll Cardiol 2001;37:1214-1220.[Abstract/Free Full Text]
14. Colson P., Ribstein J., Mimran A., et al. Effect of angiotensin-converting enzyme inhibition on blood pressure and renal function during open heart surgery. Anesthesiology 1990;72:23-27.[Medline]
15. Berger H.J., Taratuska A., Smith T.W., et al. Activated complement directly modifies the performance of isolated heart muscle cells from guinea pig and rat. Am J Physiol 1993;;265:H267-H272.[Abstract/Free Full Text]
16. Langlis P.F., Gawryl M.S. Detection of the terminal complement complex in patient plasma following acute myocardial infarction. Atherosclerosis 1988;70:95-105.[Medline]
17. Lazar H.L., Bao Y., Gaudiani J., et al. Total complement inhibition: an effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass. Circulation 1999;100:1438-1442.[Abstract/Free Full Text]
18. Maggioni A.P., Latini R. How to use ACE inhibitors, beta-blockers, and new therapies in AMI. Am Heart J 1999;138:183-187.
19. Bour L.M.B., Schipperleyn J.J., van der Laarse A., et al. Combining salicylate and enalapril in patients with coronary artery disease and heart failure. Br Heart J 1995;73:227-236.[Abstract/Free Full Text]
20. Hall D., Zeitler H., Rudolph W. Counteraction of the vasodilator effect of enalapril by aspirin in severe heart failure. J Am Coll Cardiol 1992;20:1549-1555.[Abstract]
21. Latini R., Tognoni G., Maggioni A.P., et al. Clinical effects of early angiotension-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin. J Am Coll Cardiol 2000;35:1801-1807.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Harold L. Lazar Yusheng Bao Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lazar, H. L. Articles by Bernard, S. A. Search for Related Content PubMed PubMed Citation Articles by Lazar, H. L. Articles by Bernard, S. A. Related Collections Myocardial protection