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Ann Thorac Surg 2003;75:1246-1252
© 2003 The Society of Thoracic Surgeons

Original article: cardiovascular

Ischemic preconditioning does not improve myocardial preservation during off-pump multivessel coronary operation

Hannu J. Penttilä, MDa*, Martti V.K. Lepojärvi, MD, PhDb, Päivi K. Kaukoranta, MD, PhDa, Kai T. Kiviluoma, MD, PhDa, Kari V. Ylitalo, MD, PhDc, Keijo J. Peuhkurinen, MD, PhDd

a Department of Anesthesiology, Oulu University Hospital, Oulu, Finland
b Department of Cardio-Thoracic Surgery, Oulu University Hospital, Oulu, Finland
c Oulu, Department of Medical Biochemistry, Oulu University, Oulu, Finland
d Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland

Accepted for publication October 16, 2002.

* Address reprint requests to Dr Penttilä, Department of Anesthesiology, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland
e-mail: hannu.penttila{at}tyks.fi


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: The value of ischemic preconditioning during coronary operations has remained controversial. The aim of this study was to evaluate the effects of ischemic preconditioning on myocardial energy metabolism and tissue injury during off-pump multivessel coronary surgery.

METHODS: Eleven patients with preceding preconditioning were compared with 11 patients without it. The preconditioning group underwent a 5-minute period of ischemia followed by a 5-minute reperfusion period before coronary occlusion for each of the first two anastomoses.

RESULTS: The transmyocardial differences (coronary sinus – arterial) in inosine and the sum of adenine degradation products increased in both groups, but the differences in xanthine and hypoxanthine increased only in the preconditioning group. Myocardial lactate production increased to a maximum of 0.09 mmol/L with preconditioning and to a maximum of 0.17 mmol/L without it. Transmyocardial pH differences increased to 0.03 U in both groups. The maximum postoperative concentration of creatine kinase-MB mass was 14.8 µg/L with preconditioning and 6.3 µg/L without preconditioning, and that of troponin I 7.4 µg/L and 5.2 µg/L, respectively. There were no statistically significant differences between the groups, however.

CONCLUSIONS: Ischemic preconditioning of 5 minutes followed by reperfusion of 5 minutes during off-pump multivessel coronary artery surgery did not prevent myocardial metabolic derangement and tissue injury and thus cannot be routinely recommended.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Ischemic preconditioning (IPC), defined as protection of the myocardium by inducing a short ischemic period before a subsequent longer period of ischemia, was first described by Murry and colleagues [1]. Since then, the phenomenon has been confirmed in numerous animal studies, but despite intensive research, its basic cellular mechanisms are not yet fully understood [2, 3]. Preinfarction angina in humans has been found to act like IPC because it preserves left ventricular function, even without collateral coronary artery circulation [4]. Coronary artery angioplasty has been a popular model in studying IPC in human subjects, but the results are conflicting [5–7]. In coronary artery bypass grafting (CABG) performed with cardiopulmonary bypass, IPC has been found to be effective during intermittent aortic cross-clamping [8, 9] or with normothermic or mild hypothermic cardioplegia but not with cold cardioplegia [10–12], although several conflicting results also exist [13–16]. In a rat model, IPC alone had similar protective effects as cardioplegia [17] and also ensured optimal myocardial protection when the delivery of cardioplegic solution was impaired [18].

In CABG without cardiopulmonary bypass, the coronary artery to be grafted is usually occluded during the suturing of the distal anastomosis, and the ischemic periods are longer than those in coronary angioplasty, thus offering a model to study the effects of IPC in human subjects. The aim of this prospective, randomized study was to evaluate whether preconditioning has a protective effect against ischemia-induced derangement of myocardial energy metabolism and tissue injury during multivessel CABG on a beating heart.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
Patients
The study was approved by the Ethical Committee of Oulu University Hospital. Thirty-three patients with coronary artery disease considered suitable for CABG without cardiopulmonary bypass were included in the series after written informed consent had been obtained. The exclusion criteria were ongoing ischemia, acute myocardial infarction less than 1 month previously, poorly controlled diabetes, serum creatinine level higher than 150 µmol/L, chronic atrial fibrillation, and aortic or mitral valvular disease. The patients were randomly assigned to three study groups: 22 patients were operated on off pump, of which 11 (study group) were preconditioned with regional ischemia before the construction of each of the first two anastomoses, and 11 patients (control group) were operated on without preconditioning. The patients in the third group (11 patients) were operated conventionally on pump. This on-pump group previously has been compared with the off-pump group without IPC (control group of the present study) in order to evaluate the effects of cardiopulmonary bypass and cardioplegia on myocardial injury and energy preservation [19]. Only the off-pump patients, with or without IPC, were included in this study to evaluate the effects of IPC during off-pump operations.

Anesthesia
All patients were anesthetized by the same experienced cardiac anesthesiologist (H.J.P.). All medications except salicylates were allowed without interruption until the day of the operation. Salicylates were withdrawn 1 to 2 weeks before the operation, except in 4 patients, 1 in the control group and 3 in the IPC group. Premedication consisted of oral diazepam (10 to 20 mg), intramuscular morphine (7 to 10 mg), and oral dipyridamole (200 mg). The radial artery was cannulated, and a Swan-Ganz pulmonary artery catheter (Baxter Healthcare Corp, Santa Ana, CA) for continuous monitoring of cardiac output and mixed venous oxygen saturation was introduced. Anesthesia was induced with propofol (1.1 to 2.8 mg/kg) and fentanyl (3.2 to 6.2 µg/kg). Muscle relaxation was achieved with pancuronium (0.07 to 0.11 mg/kg). The patients’ lungs were ventilated with 30% to 50% oxygen in air, and anesthesia was maintained with propofol (1.3 to 5.2 mgkg-1h-1), alfentanil (21.2 to 45.5 µgkg-1 h-1), and sevoflurane (minimal alveolar concentration 0.7 to 1.9). All patients received 20 mg of intravenous dipyridamole before the beginning of the operation.

The patients were given heparin, 1 mg/kg, for anticoagulation, and additional heparin was given when needed to maintain the activated coagulation time above 300 seconds. Heparinization was reversed with protamine sulfate (50 to 100 mg). Intraoperative myocardial ischemia was evaluated by continuous automatic monitoring of the ST segment in the modified leads V5 and II and by observing the appearance of a V wave in the pulmonary artery wedge pressure curve. Ischemia, if present, was treated with intravenous nitroglycerine. If the patient did not respond to nitroglycerine, an intracoronary flow-through catheter was inserted. The mean arterial blood pressure was maintained above 50 mm Hg with phenylephrine hydrochloride and enhanced intravenous fluid infusion. After the vein grafts were harvested, the patient was actively heated by placing a thermoblanket over the lower body to raise the core temperature above 36°C.

Surgical technique
All operations were performed by the same experienced cardiac surgeon (M.V.K.L). A conventional midline sternum-splitting incision was used, and a coronary sinus catheter (Pediatric RCSP Cannula, Grand Rapids, MI) was introduced through the right atrial wall before suturing the anastomoses.

Pericardial traction sutures and elevating gauze pads were used to facilitate visibility and access to either the left or the right side of the heart. Hemostatic silicone loops (Retract-O-Tape, Quest Medical Inc, Allen, TX) were used to obstruct the coronary artery for IPC. The IPC consisted of an ischemic period of 5 minutes followed by a reperfusion period of 5 minutes. The first IPC was performed before the first coronary artery closure for suturing the distal anastomosis and the second before the second closure (Figure 1). The following coronary closures were performed without preceding preconditioning. A commercial mechanical suction stabilizer (Octopus, Medtronic, Medtronic Inc, Minneapolic, MN) and moist air blower were used to facilitate the construction of distal anastomoses, and coronary artery probes were used to diminish the bleeding of the target artery. The left internal thoracic artery was used as a bypass graft in every patient. The most severely diseased coronary artery was always grafted first. The grafted coronary arteries are shown in Table 1, and the first and the second bypass grafts in Figure 2. The proximal anastomoses of vein grafts were finished with the aid of a partially occluding aortic side clamp.



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  		Fig 1. Study design and blood sampling schedule. (IPC = ischemic preconditioning [an ischemic period of 5 minutes followed by reperfusion for 5 minutes]; Time [T]0 = before bypass grafting; T1–T2 = immediately after the completion of the first two distal anastomoses; T3–T4 = 5 and 15 minutes after the suturing of the last anastomosis; T5–T6 = 2 and 8 hours after the suturing of the last anastomosis; T7–T10 = first to fourth postoperative day.)

 

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  		Table 1. Demographics and Perioperative Course

 


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  		Fig 2. Coronary occlusion times (means and 95% confidence intervals), ischemic preconditionings for the first two bypass grafts, and a list of the first two bypassed coronaries. (CI = confidence interval; Cx = circumflex coronary artery and its branches; Dg = diagonal coronary artery; IPC = ischemic preconditioning; LAD = left anterior descending coronary artery; RCA = right coronary artery and its branches; T0–T2 = sampling times [Fig 1].)

 
Laboratory data and electrocardiogram
Intraoperative blood samples were withdrawn simultaneously from the arterial catheter and the coronary sinus catheter (T0–T4 in Fig 1). Oxygen and carbon dioxide tensions and pH were determined with a 288 blood gas system (Ciba Corning Diagnostics Corp, Walpole, MA), and oxygen content was calculated as follows: 1.39 hemoglobin concentration x oxygen saturation + 0.003 oxygen tension. Transcardiac differences of pH and carbon dioxide tension were determined, and myocardial oxygen extraction was calculated from the oxygen content values. Lactate was assayed by using an electrode-based lactate analyzer (YSI model 1500; Yellow Springs Instrument Co, Inc, Yellow Springs, OH), and transcardiac differences were calculated. To measure the plasma levels of adenosine triphosphate (ATP) degradation products (adenosine, inosine, hypoxanthine, and xanthine), blood samples were drawn into a syringe containing dipyridamole solution. The samples were processed and the metabolites were assayed as described earlier [20], and the transcardiac concentration differences in the ATP degradation products were calculated.

After the operation, the electrocardiogram was recorded, and the mass of the isoenzyme MB of creatine kinase (CK-MBM) and cardiac troponin I (TnI) were measured (T0 and T5–T10 in Fig 1). CK-MBM and TnI were analyzed by using microparticle enzyme immunoassay technology (AxSYM, Abbott Laboratories, North Chicago, IL). The electrocardiograms were evaluated by the same experienced cardiologist (K.J.P.), who was blinded to the group assignment of the patients. Perioperative myocardial infarction was defined as either new Q waves or ischemic ST-segment changes with a concomitant elevation of CK-MBM above 30 µg/L or TnI levels above 15 µg/L [21].

Statistics
Statistical analyses were performed by using the Statistica package software, version 5.1 (StatSoft, Inc, Tulsa, OK). The t test for independent changes was used for single continuous variables, and a cross-table was used for single categoric variables to test the differences between the groups. Analysis of variance with contrast analysis was used to analyze the time-dependent variance within the groups and the differences between the groups when repeated measures were made. In the case of non-normal distribution, nonparametric Kruskal-Wallis test was used. The data are presented as means and 95% confidence intervals (CIs). Significance was assumed when the p value was less than 0.05.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
The two study groups had similar preoperative characteristics and operative courses. The total ischemia time was increased in the IPC group because of the two preconditioning periods. However, there were no differences between the groups in the total ischemia times or in the ischemic times during the suturing of the first two bypass grafts (Table 1 and Fig 2).

Myocardial energy metabolism
The transmyocardial differences in inosine and the sum of ATP degradation products increased significantly without IPC during the construction of the anastomoses (p = 0.01 and p = 0.04, respectively). In addition to inosine and the sum of ATP degradation products, the transcardiac differences in xanthine and hypoxanthine also increased significantly in the IPC group (p = 0.006, p = 0.004, p = 0.009, and p = 0.04, respectively). However, there were no statistically significant differences between the groups (Table 2).


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  		Table 2. Transcardiac Concentration Differences (Coronary Sinus–Artery) of Adenosine Triphosphate Degradation Productsa

 
The highest value of myocardial lactate production in the IPC group was 0.09 mmol/L (95% CI, 0.01 to 0.17 mmol/L) after the suturing of the first distal anastomosis, with the increase from the initial level being statistically significant (p = 0.05). Without IPC, the increase of myocardial net lactate production was statistically significant only after the suturing of the second distal anastomosis (p = 0.04), with the maximum value being 0.17 mmol/L (95% CI, 0.07 to 0.27 mmol/L; Fig 3). The transcardiac pH difference increased significantly in both groups (p = 0.002 with IPC, and p = 0.01 without it), with the highest value being 0.03 U (95% CI, 0.02 to 0.05 U) in both groups (Figure 3). There were no statistically significant differences between the groups in lactate production or transcardiac pH differences.



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  		Fig 3. Myocardial lactate production (top) and transcardiac pH difference (bottom) (median, 25% and 75% percentiles, and non-outlier range) before grafting (T0), after the completion of the first (T1) and second (T2) distal anastomoses, and five (T3) and 15 (T4) minutes after the completion of all the anastomoses (Fig 1). The increase in myocardial lactate production was significant after the first anastomosis (p = 0.05) with ischemic preconditioning and after the second anastomosis without preconditioning (p = 0.04). The increase of the transcardiac pH difference was significant in both groups (p < 0.001). There were no differences between the groups. (IPC = ischemic preconditioning.)

 
Myocardial oxygen extraction decreased evenly during and after the construction of the anastomoses from 69.0 mL O2/L blood (95% CI, 58.6 to 79.4 mL O2/L blood) to 49.7 mL O2/L blood (95% CI, 39.7 to 59.8 mL O2/L blood) with preceding preconditioning, and from 66.6 (95% CI, 58.0 to 75.3 mL O2/L blood) to 43.5 mL O2/L blood (95% CI, 37.6 to 49.5 mL O2/L blood) without IPC (p < 0.001). The oxygen saturation of hemoglobin in coronary sinus blood did not differ between groups, ranging between 39.3% and 77.9%. The transmyocardial difference in blood carbon dioxide tension decreased (p < 0.001) from the initial value of 0.81 kPa (95% CI, 0.64 to 0.97 kPa) to 0.66 kPa (95% CI, 0.52 to 0.81 kPa) without IPC, and from 0.79 kPa (95% CI, 0.59 to 0.99 kPa) to 0.74 kPa (95% CI, 0.61 to 0.86 kPa) with IPC.

Creatine kinase-MB mass and troponin I
The maximum values of CK-MBM were 14.8 µg/L (95% CI, 4.9 to 24.7 µg/L) with IPC and 6.3 µg/L (95% CI, 5.0 to 7.6 µg/L) without it. Maximum serum TnI concentrations were 7.4 µg/L (95% CI, 3.7 to 11.2 µg/L) with IPC and 5.2 µg/L (95% CI, 2.6 to 7.8 µg/L) without it. The highest values of both myocardial injury markers in both groups were recorded at 8 hours after the construction of the last anastomosis, and there were no statistically significant differences between the groups (Figure 4). One patient without preconditioning was considered to have had perioperative myocardial infarction and was excluded from the analyses of CK-MBM and TnI.



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  		Fig 4. Plasma levels of creatine kinase-MB (CK-MB) mass (top) and cardiac troponin I (bottom) (median, 25% and 75% percentiles, and non-outlier range) before construction of the anastomoses (T0), at 2 (T5) and 8 (T6) hours after the suturing of the last anastomosis, and on the next 4 days (T7–T10) (Fig 1). There were no statistically significant differences between the groups. (IPC = ischemic preconditioning.)

 
Perioperative course
There were no differences between groups in ST-segment changes during construction of the anastomoses. Four patients in each group received intravenous nitroglycerine, and 2 of these patients (1 in each group) also had an intracoronary flow-through catheter inserted. One patient without preconditioning received nitroglycerine to decrease his modestly elevated pulmonary artery pressure, and the others were considered to be ischemic. All the patients received phenylephrine hydrochloride to maintain arterial pressure above 50 mm Hg. The lowest mean arterial blood pressure was 62 mm Hg (95% CI, 54 to 70 mm Hg) in the IPC group and 60 mm Hg (95% CI, 55 to 65 mm Hg) without IPC. The lowest cardiac index and mixed venous saturation were 1.9 L/m2 per minute (95% CI, 1.6 to 2.1 L/m2 per minute) and 1.6 L/m2 per minute (95% CI, 1.5 to 1.8 L/m2 per minute) and 69% (95% CI, 62% to 75%) and 67% (95% CI, 62% to 72%), respectively. One patient in each group required defibrillation to restore sinus rhythm.

One patient without preconditioning had new anterolateral Q waves in electrocardiogram with concomitant CK-MBM and TnI increases (273 µg/L and 277.5 µg/L, respectively) and was considered to have had a perioperative myocardial infarction. The hemodynamic recovery of this patient was uneventful, however. Four patients without IPC had nonspecific postoperative changes in electrocardiogram indicating pericardial irritation.

Three patients with and 1 patient without IPC developed atrial fibrillation after the operation and were converted to sinus rhythm with the ß-blocking agents amiodarone hydrochloride or ibutilide fumarate. One patient with IPC and 2 patients without IPC received dopamine after the operation, mainly as a treatment for modest hypotension. Only one patient (without IPC) had a cardiac index below 2.2 L/m2. The mean time to tracheal extubation after the operation was 4.3 hours (95% CI, 3.3 to 5.4 hours) in the IPC group and 4.1 hours (95% CI, 3.4 to 4.9 hours) in the control group. One patient with IPC had mild weakness in the right arm because of a small hemorrhagic brain infarction, which was confirmed with computed tomography. All patients were moved from the intensive care unit to the ward on the first postoperative day, and there were no other major complications during the 5- to 7-day in-hospital period.


   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
Off-pump coronary operations offer some advantages over operations with cardiopulmonary bypass and are gaining popularity. The promising results of IPC attempt to predispose the beating myocardium to regional short-term ischemia before occluding the coronary artery in order to use the benefits of IPC. We evaluated the effects of IPC on myocardial energy metabolism and tissue injury during off-pump coronary operations. The two study groups were comparable with respect to demographics, perioperative courses, and the ischemic burden for the first two bypass grafts (Figure 2). The transcardiac differences in serum ATP degradation products increased only slightly, with the increases being equal in the two groups. This demonstrates that the overall energy state of the myocardium was relatively well maintained during the suturing of the first two bypass grafts.

Lactate and acid production are well-accepted indicators of ischemic metabolism. The overall increases in myocardial lactate production and the transcardiac pH differences were slight, and there were no statistically significant differences between the groups. The highest lactate production level occurred after the suturing of the first distal anastomosis in the IPC group and after the second one in the control group (Figure 3). It seems that a 5-minute ischemia period followed by a 5-minute reperfusion period is not enough to provide protection, although a tendency of lower lactate peaking was seen in the IPC group.

Iliodromitis and colleagues [22] showed that preconditioning reduces infarct size in rabbits when IPC was repeated up to four times, after which the infarct size increased. The IPC response, however, is species dependent, and the strength of the stimulus and the number of IPC repetitions needed to initiate the preconditioning in human subjects is largely unknown. One IPC cycle of 5 plus 5 minutes was chosen, because this cycle is most often used in studies of ischemic preconditioning. In off-pump operations, it also acts as a test occlusion for ischemic changes before the final coronary occlusion for suturing of the distal anastomosis. Multiple repetitions of the IPC cycle would have significantly increased the operation time, which we regarded as unethical for the patients. In our study, there were no statistically significant differences between groups in the postoperative levels of CK-MBM and TnI, although there was a slight tendency for higher levels of both markers and larger variations in the IPC group. There were 2.8 distal anastomoses and coronary artery occlusions without IPC and 3.1 distal anastomoses and 5.1 coronary occlusions with IPC, including the two occlusions for preconditioning. Thus, the slightly higher level and larger variation of CK-MBM and TnI with IPC can be explained by the larger number of coronary occlusions and the longer cumulative ischemic time. We conclude that IPC, as done in our study, was not beneficial when the operation was done on a beating heart.

The results of our study do not exclude the possibility of IPC counteracting impaired myocardial function during ischemia or postoperative stunning, although both seem unlikely in the light of the data on tissue injury markers. Also, cardiac output and mixed venous oxygen saturation were measured continuously during the operations, and they did not show any significant decrease. In this context it is interesting that Malkowski and colleagues [23] did not detect functional improvement in left ventricular wall motion after IPC performed during minimally invasive CABG. Bufkin and colleagues [24] also did not find any improvements in left ventricular function in a canine model. Conversely, the same group found that an IPC period of 5 minutes followed by a reperfusion period of 5 minutes decreased neutrophil accumulation, endothelial dysfunction, and apoptosis [24–26].

Continuous intravenous infusion of hypnotics, analgesics, and phenylephrine hydrochloride during the operations might have induced pharmacologic preconditioning [2, 3]. In addition, use of dipyridamole may recruit endogenous protective mechanisms through increased extracellular adenosine levels and specific receptor occupation. Whether any pharmacologic preconditioning occurred in our patients is impossible to say. Moreover, it is an essential status of the clinical practice in which IPC does not seem to offer any benefits in light of this study. The use of potential preconditioning mimicking agents, as well as the blood sampling protocol, was similar in both study groups, however.

There was one small perioperative cerebral infarction in the IPC group and one myocardial infarction in the group without IPC. The patient with myocardial infarction was excluded from the analyses of CK-MBM and TnI because the purpose of this study was to evaluate overall myocardial preservation during operations with normal courses. Both patients with major complications recovered well, and there were no other major complications during the 1-week in-hospital period. Otherwise, the postoperative courses in the two groups were similar.

In conclusion, IPC of 5-minute regional ischemia followed by 5-minute reperfusion did not prevent metabolic perturbations, as evaluated by transcardiac differences of ATP degradation products, lactate, and pH. Neither did IPC reduce myocardial injury evaluated by serum levels of CK-MBM and TnI during multivessel CABG on a beating heart, and thus it cannot be routinely recommended.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
This study was supported by a grant from the Inari and Reijo Holopainen Foundation. We are grateful to Marja-Leena Lehtonen for her assistance in analyzing the ATP degradation products, and the staff of the operative and postoperative intensive care units of Oulu University Hospital.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

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Writing Committee Members, L. D. Hillis, P. K. Smith, J. L. Anderson, J. A. Bittl, C. R. Bridges, J. G. Byrne, J. E. Cigarroa, V. J. DiSesa, L. F. Hiratzka, et al.
2011 ACCF/AHA guideline for coronary artery bypass graft surgery: Executive summary A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
J. Thorac. Cardiovasc. Surg., January 1, 2012; 143(1): 4 - 34.
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 Anesth. Analg.Home page
L. D. Hillis, P. K. Smith, J. L. Anderson, J. A. Bittl, C. R. Bridges, J. G. Byrne, J. E. Cigarroa, V. J. DiSesa, L. F. Hiratzka, A. M. Hutter Jr, et al.
Special Article: 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Anesth. Analg., January 1, 2012; 114(1): 11 - 45.
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 J Am Coll CardiolHome page
L. D. Hillis, P. K. Smith, J. L. Anderson, J. A. Bittl, C. R. Bridges, J. G. Byrne, J. E. Cigarroa, V. J. DiSesa, L. F. Hiratzka, A. M. Hutter Jr, et al.
2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons
J. Am. Coll. Cardiol., December 6, 2011; 58(24): 2584 - 2614.
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 J Am Coll CardiolHome page
L. D. Hillis, P. K. Smith, J. L. Anderson, J. A. Bittl, C. R. Bridges, J. G. Byrne, J. E. Cigarroa, V. J. DiSesa, L. F. Hiratzka, A. M. Hutter Jr, et al.
2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons
J. Am. Coll. Cardiol., December 6, 2011; 58(24): e123 - e210.
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 CirculationHome page
Writing Committee Members, L. D. Hillis, P. K. Smith, J. L. Anderson, J. A. Bittl, C. R. Bridges, J. G. Byrne, J. E. Cigarroa, V. J. DiSesa, L. F. Hiratzka, et al.
2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Circulation, December 6, 2011; 124(23): e652 - e735.
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 CirculationHome page
Writing Committee Members, L. D. Hillis, P. K. Smith, J. L. Anderson, J. A. Bittl, C. R. Bridges, J. G. Byrne, J. E. Cigarroa, V. J. DiSesa, L. F. Hiratzka, et al.
2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Circulation, December 6, 2011; 124(23): 2610 - 2642.
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 Eur J Cardiothorac SurgHome page
S. R. Walsh, T. Y. Tang, P. Kullar, D. P. Jenkins, D. P. Dutka, and M. E. Gaunt
Ischaemic preconditioning during cardiac surgery: systematic review and meta-analysis of perioperative outcomes in randomised clinical trials
Eur J Cardiothorac Surg, November 1, 2008; 34(5): 985 - 994.
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 Ann. Thorac. Surg.Home page
M. E. Halkos, F. Kerendi, J. S. Corvera, N.-P. Wang, H. Kin, C. S. Payne, H.-Y. Sun, R. A. Guyton, J. Vinten-Johansen, and Z.-Q. Zhao
Myocardial protection with postconditioning is not enhanced by ischemic preconditioning
Ann. Thorac. Surg., September 1, 2004; 78(3): 961 - 969.
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 J. Thorac. Cardiovasc. Surg.Home page
B. Syeda, C. Schukro, G. Heinze, K. Modaressi, D. Glogar, G. Maurer, and W. Mohl
The salvage potential of coronary sinus interventions: Meta-analysis and pathophysiologic consequences
J. Thorac. Cardiovasc. Surg., June 1, 2004; 127(6): 1703 - 1712.
[Abstract] [Full Text] [PDF]

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