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(Chest. 2002;121:1183-1189.)
© 2002 American College of Chest Physicians

Regional Ischemic Preconditioning Enhances Myocardial Performance in Off-Pump Coronary Artery Bypass Grafting*

Jari Laurikka, MD; Zhong-Kai Wu, MD; Pekka Iisalo, MD; Liisa Kaukinen, MD; Eva L. Honkonen, MD; Seppo Kaukinen, MD and Matti R. Tarkka, MD

* From the Department of Surgery (Drs. Laurikka, Wu, Iisalo, and Tarkka), and the Department of Anesthesiology and Intensive Care (Drs. L. Kaukinen, Honkonen, and S. Kaukinen), Division of Cardiothoracic Surgery, Tampere University Hospital, Tampere, Finland.

Correspondence to: Matti Tarkka, MD, Department of Surgery, Division of Cardiothoracic Surgery, Tampere University Hospital, 33521 Tampere, Finland; e-mail: matti.tarkka{at}tays.fi


   Abstract
TOP
 Abstract
Materials and Methods
 Results
 Discussion
 References
 
Objectives: We intended to investigate whether ischemic preconditioning (IP) enhances myocardial performance in patients who undergo off-pump coronary artery bypass grafting (CABG).

Design: A controlled, randomized, prospective study.

Setting: A university hospital.

Patients: Thirty-two patients with left anterior descending coronary artery (LAD) or two-vessel heart disease (including LAD) who were to undergo off-pump CABG were randomized into an IP group and a control group.

Interventions: IP was induced by occluding the LAD twice for a 2-min period followed by 3-min LAD reperfusion before bypass grafting of the first coronary vessel.

Measurements and results: Registration included hemodynamic data from the peripheral artery and the pulmonary artery, and the measurement of cardiac troponin I (CTnI) and creatine kinase isoenzyme MB (CK-MB) values. IP resulted in a complete recovery of the mean stroke volume index (SVI) after the operation. In the control subjects, the mean SVI showed a significant reduction postoperatively (p = 0.039). On the first postoperative day, the increase in the mean heart rate (HR) was also significantly lower in the IP patients. The CTnI level was statistically significantly lower in the IP group (p = 0.043), and IP patients tended to have a smaller CK-MB release after surgery (not significant). The duration of mechanical ventilation, the length of stay in the ICU, and the use of inotropic medication did not increase after the IP protocol.

Conclusions: Two cycles of regional 2-min IP in the LAD, followed by 3 min of reperfusion, proved to be applicable and safe in patients undergoing off-pump myocardial revascularization, it tended to decrease the immediate myocardial enzyme release, it prohibited the postoperative increase in HR, and it enhanced the recovery of SVI.

Key Words: coronary artery bypass grafting • ischemic preconditioning • off-pump • myocardial protection

Cardiopulmonary bypass (CPB) and cardioplegic cardiac arrest with aortic cross-clamping are used mainly to achieve adequate exposure to target vessels, but they carry a risk for local myocardial injury and systemically detrimental inflammatory effects.1 2 These harmful effects may be mediated by the generation of free radicals during reperfusion.3 4 Conventional CPB surgery also predisposes the patient to postoperative neurologic impairments that range from cognitive deficits to strokes.5 6 This may be associated with the occurrence of cerebral microembolisms that are generated by CPB and cross-clamping, especially from the diseased ascending aorta.5 6

Myocardial revascularization on the beating heart without CPB has gained increasing popularity because it may avoid the damage induced by CPB with hypothermia, aortic cannulation, and cross-clamping.7 Surgical procedures on the beating heart require less blood to be transfused and afford shorter hospital stays, lower rates of organ dysfunction (including cerebrovascular complications), fewer hemorrhagic complications, and lower mortality rates in high-risk patients.8 9 Thus, surgical procedures on the beating heart reduce the cost of surgery.8 However, a less optimal operative field and limited access may result in incomplete procedures.9 The ischemic period during grafting may cause contractile dysfunction and vascular endothelial injury, and involves a risk of myocardial necrosis.10

Ischemic preconditioning (IP) is created by a brief period of myocardial ischemia followed by reperfusion, and it increases myocardial tolerance to subsequent long-term ischemic insult.11 IP has been widely studied and has proved to be one of the most potent endogenous myocardial mechanisms protecting against ischemia/reperfusion injury in experimental models as well as in humans.11 12 IP delays myocardial damage, preserves high-energy phosphates, suppresses arrhythmias, and improves postischemic functional recovery.11 12 IP also results in the depletion of myocardial glycogen, which, during the ischemia, finally results in reduced lactate production, and it potentially also protects endothelium in the coronary vessel.11 12

The procedure of off-pump myocardial revascularization requires a period of coronary artery occlusion, which results in regional ischemia. IP and intracoronary shunts have been used to limit ischemic injury, but the use of the shunt in a vulnerable coronary artery may damage the endothelium.13 IP has been considered to be a promising method for achieving myocardial protection, although controversial results concerning the effectiveness of IP also have been shown.10 11 14 15 Reports on IP in patients undergoing off-pump CBP surgery are still few in number, and not all of those studies are even randomized.16 17 18 19 Therefore, we aimed at investigating the IP effects in patients undergoing off-pump coronary artery bypass grafting (CABG) in a randomized controlled study.


   Materials and Methods
TOP
 Abstract
 Materials and Methods
Results
 Discussion
 References
 
The study design was accepted by the Ethical Committee of Tampere University Hospital, Finland, and informed consent was obtained from all patients.

Patients
Thirty-two CABG patients with single-vessel or two-vessel coronary artery disease involving the left anterior descending coronary artery (LAD) alone or in combination with the right coronary artery (RCA), or the diagonal branch (ie, left diagonal artery) were randomized into an IP group (n = 16) and a control group (n = 16). The randomization was carried out in the operating room by opening a sealed, nontransparent protocol envelope. The IP group received the IP treatment before the first graft anastomosis, while routine operative methods were used in the control subjects.

The preoperative characteristics of the patients in the respective groups were similar. There were no statistically significant differences between the two groups in terms of patient age, sex, New York Heart Association class, the location of the diseased vessel, the vessels that were bypassed, risk factors, type of incision, and time of vessel occlusion (Table 1 ). The groups did not differ significantly in medical history, and the number of patients receiving medication blocking the ß-adrenergic receptors was equal in both groups.


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  		Table 1.. Preoperative Data*

 
Preconditioning Protocol
The IP protocol was achieved by occluding the LAD with silicon tape. After identifying the LAD, two pieces of silicon tape were used proximal to and distal to the site of the anastomosis. The LAD was occluded for 2 min and then was released for 3 min. The procedure was repeated once. Other vessels were not used for IP.

Anesthesia and Surgical Technique
A standardized anesthetic technique was used with sufentanil (7.8 µg/kg), midazolam (0.10 to 0.125 mg/kg for induction and 0.20 mg/kg for maintenance), and pancuronium (0.22 mg/kg). Anesthetic depth was monitored by heart rate (HR) and systemic BP. In the event of sudden increase in HR, the depth of anesthesia was increased with isoflurane for a short period. Other inhalation anesthetics agents were not used, the temperature of the patient was monitored, so that excessive temperature shifts did not occur. Episodes of hypotension were treated with a bolus injection of norepinephrine.

After a patient underwent a median sternotomy or left anterior small thoracotomy, 1 mg/kg heparin was administered on the completion of left internal mammary artery harvesting. Two milliliters papaverine (10 mg/mL) was injected into the distal left internal mammary artery to prevent arterial spasm. The LAD was identified and exposed for a distance of 2 to 3 cm, and two silicon snares were applied proximally and distally to the selected site of the anastomosis. A stabilizer (Origin; Menlo Park, CA) was used at the anastomosis site to provide a relatively still operative field. A CO2 blower (Ernst Biegler; Mauerbach, Austria) was used to achieve a bloodless anastomosis site. The same procedure also was adopted for anastomosis in other vessels. If multiple grafts were considered, the first anastomosis after the IP protocol was always in the non-LAD vessel by means of a venous or radial artery graft. Intracoronary shunts were not used.

Hemodynamic Measurements and Treatment
HR, central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), cardiac output, and right ventricular ejection fraction (RVEF) were monitored. Derived cardiovascular variables, namely, cardiac index, stroke volume index (SVI), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), and right ventricular end-diastolic volume index (RVEDVI), were calculated using standard formulas. Right ventricular (RV) function was measured using a fast-response volumetric thermister-tipped pulmonary artery catheter (93A-434 h, 7.5F; Baxter Health Care Corp; Irvine, CA) and a microprocessor (Explorer; Baxter Health Care Corp), which allowed the measurement of the diastolic washout plateaus of a thermodilution cardiac output curve using exponential curve analysis. All measurements based on the thermodilution technique were made at end expiration in triplicate using ice-cold saline solution. The mean value of three consecutive measurements was registered for analysis. Before each measurement of the RVEF, the correct position of the catheter and the right atrial delivery site were confirmed by analysis of the transduced pressure waveform. Hemodynamic data were collected at the following four time points: (1) baseline (ie, before the induction of anesthesia); (2) 1 h after revascularization; (3) 6 h after revascularization; and (4) first postoperative day (POD).

Perioperatively, volume infusion was designed to maintain filling pressures at least at the preoperative level and at an optimal level heart performance. Therapy with inotropes (dopexamine, < 1.5 µg/kg/min) or epinephrine (< 0.1 µg/kg/min) was administered to maintain the cardiac index at > 2.0 L/min/m2. Amrinone (< 10 µg/kg/min) or norepinephrine (< 0.2 µg/kg/min) was used when dopexamine or epinephrine was insufficient to maintain cardiac output. These infusions, when needed, were continued for at least 6 h. Inotropic therapy was not discontinued at the time points when the hemodynamic parameters were measured. Perioperative infarction was diagnosed if any new Q wave appeared (ie, ranging to one third of the QRS height and lasting for > 0.04 s) or when the level of creatine kinase isoenzyme MB (CK-MB) was > 100 µg/L. The team in the ICU was blinded from the study.

Biochemical Markers
Blood samples were collected from peripheral vessels in the following manner: (1) before IP or vessel occlusion; (2) after the IP protocol in the IP group; (3) 5 min after revascularization; (4) 10 min after revascularization; (5) 6 h after revascularization; (6) during the first POD; and (7) during the second POD. Samples were collected in heparin-coated plastic tubes and underwent centrifugation. Serum samples were measured with an analyzer (Chiron ACS180 Plus; Chiron Diagnostics Corporation; East Walpole, MA) using a direct chemiluminescence method.

Statistical Analysis
Statistical analyses were performed using a statistical software package (SPSS, version 9.0; SPSS Inc; Chicago, IL). An unpaired Student t test (two-tailed) was used for continuous data, and a {chi}2 test or Fisher’s Exact Test was used for categoric data when comparing variables between the groups. In the tests of hemodynamic and biochemical data, an analysis of variance was performed in the repeated-measures design with Bonferroni correction. Data are presented as the mean ± SD. Significance was assumed when p < 0.05.


   Results
TOP
 Abstract
 Materials and Methods
 Results
Discussion
 References
 
All but one patient fulfilled the terms of the study protocol. The treatment of this patient (from the IP group) had to be converted to the traditional CPB operation because of technical problems with the LAD anastomosis, and he was excluded from the study due to incomplete data collection. Consequently, one additional patient was recruited for randomization. None of the patients experienced perioperative myocardial infarctions based on our ECG and CK-MB level criteria. None of the patients required an intra-aortic balloon pump, and none presented with cerebral complications.

Hemodynamic Data
The mean HR increased in both groups, but the elevation was more significant among the control subjects, especially on the first POD (p = 0.035 [analysis of variance with repeated-measures design]). There were no significant differences between the groups in terms of mean arterial pressure, CVP, MPAP, PCWP, RVEDVI, SVRI, and PVRI (Table 2 ).


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  		Table 2.. Hemodynamic Data*

 
The baseline of the cardiac index was 2.96 ± 0.74 L/min/m2 in the control group and 2.64 ± 0.45 L/min/m2 in the IP group (p = 0.175 [t test]). The cardiac index decreased slightly 1 h after reperfusion in the control group (2.54 ± 0.85 L/min/m2) and subsequently recovered (6 h after reperfusion, 3.62 ± 0.90 L/min/m2; first POD, 3.34 ± 0.78 L/min/m2). In the IP group, on the other hand, the cardiac index increased at all three time points after the operation (1 h after reperfusion, 2.74 ± 0.45 L/min/m2 [p = 0.666]; 6 h after reperfusion, 3.70 ± 1.41 L/min/m2 [p = 0.010]; and first POD, 3.69 ± 0.93 L/min/m2 [p = 0.001, t test]). A comparison between the two groups revealed no statistically significant differences in cardiac index after the operation (p = 0.262 [analysis of variance for repeated measures]) [Fig. 1 ].



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  		Figure 1.. Cardiac index (CI) is shown for patients undergoing off-pump CABG in the treatment group (ie, the IP group) and for control subjects. Values are given as mean ± SEM.

 
The baseline of the SVI was 49.4 ± 6.1 mL per beat per m2 in the IP group and 50.8 ± 8.1 mL per beat per m2 in the control group (p = 0.598 [t test]). The SVI decreased after the operation in the control group (1 h after vessel reperfusion, 38.3 ± 9.3 mL per beat per m2 [p = 0.001]; 6 h after vessel reperfusion, 41.4 ± 9.5 mL per beat per m2 [p = 0.008]; and first POD, 39.4 ± 8.9 mL per beat per m2 [p = 0.001, t test]). In the IP group, on the other hand, the SVI was slightly decreased at first and then recovered (1 h after vessel reperfusion, 43.8 ± 14.5 mL/beat/m2 [p = 0.174]; 6 h after vessel reperfusion, 46.2 ± 15.9 mL/beat/m2 [p = 0.465]; and first POD, 50.5 ± 11.8 mL/beat/m2 [p = 0.759, t test]). In a comparison between the two groups, the SVI was statistically significantly better in the IP group (p = 0.039 [analysis of variance for repeated measures]) [Fig. 2 ].



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  		Figure 2.. The SVI is shown for patients undergoing off-pump CABG in the treatment group (ie, the IP group) and for control subjects. ml/b/m2 = milliliters per beat per m2. Values are given as mean ± SEM. ** = p < 0.01 (unpaired t test at time point). {dagger} = p < 0.05 (significance between the groups by analysis of variance with repeated measures).

 
RVEF was measured in 13 IP patients and in 10 control subjects without RCA stenosis. There were no statistically significant differences in RVEF before (43.4 ± 7.5% vs 41.4 ± 5.8%, respectively; p = 0.499 [t test]) or after the operation (1 h after declamping, 45.1 ± 7.9% vs 40.8 ± 9.4%; 6 h after declamping, 44.1 ± 10.3% vs 46.3 ± 8.7%; and first POD, 41.0 ± 6.7 vs 37.6 ± 7.5% [p = 0.652, analysis of variance for repeated measures]) [Fig. 3 ].



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  		Figure 3.. The RVEF is shown for patients undergoing off-pump CABG in the treatment group (ie, the IP group) and for control subjects. Values are given as mean ± SEM.

 
Biochemical Markers
Between the IP patients and control subjects, there was no difference in the baseline level of cardiac troponin I (CTnI) (0.1 ± 0.1 vs 0.1 ± 0.1 µg/L, respectively; p = 0.461 [t test]) or of CK-MB (0.5 ± 0.3 vs 0.7 ± 0.7 µg/L, respectively; p = 0.196 [t test]). CTnI and CK-MB levels increased significantly after the operation, reaching peak values on the first POD (CTnI: IP patients, 1.8 ± 4.2 µg/L; control subjects, 4.6 ± 9.6 µg/L; CK-MB: IP patients, 7.8 ± 11.8 µg/L; control subjects, 11.0 ± 14.6 µg/L). IP resulted in lower values for CTnI release after the operation (p = 0.045 [analysis of variance for repeated measures]) [Fig.4 ]. IP patients also had a lower CK-MB release after the operation but without a statistically significant difference (p = 0.100 [analysis of variance for repeated measures]) [Fig. 5 ]. General linear model analysis showed that the levels of both CTnI and CK-MB after the operation were significantly associated with the total coronary artery occlusion time (p = 0.025 and p = 0.031, respectively).



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  		Figure 4.. CTnI levels are shown for patients undergoing off-pump CABG in the treatment group (ie, the IP group) and for control subjects. Values are given as mean ± SEM. * = p < 0.05 (unpaired t test at time point). {dagger} = p < 0.05 (significance between the groups by analysis of variance with repeated measures).

 


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  		Figure 5.. CK-MB levels are shown for patients undergoing off-pump CABG in the treatment group (ie, the IP group) and for control subjects. Values are given as mean ± SEM.

 
Postoperative Care
Two patients in the control group experienced ventricular fibrillation after releasing a coronary artery occlusion. There were no statistically significant differences between the groups in the duration of mechanical ventilation and the length of stay in the ICU. Likewise, the use of inotropic or nitroglycerine infusions was similar in the two groups (Table 3 ).


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  		Table 3.. Postoperative Care*

 

   Discussion
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 Abstract
 Materials and Methods
 Results
 Discussion
References
 
Minimally invasive surgical techniques for CABG often lead to a beating, normothermic, but regionally ischemic heart. Ischemic injury is manifested as contractile dysfunction and vascular endothelial injury.10 Because of the limited tolerance of the working heart to ischemia under normothermia, the risk of irreversible myocardial damage becomes considerable in the absence of cardioplegia. IP has become a potential alternative method of myocardial protection since Przyklenk et al20 showed that brief episodes of ischemia in one vascular bed can protect even remote areas of the myocardium from subsequent sustained coronary artery occlusion.

Routine CABG, even with short periods of regional ischemia in a beating heart, results in myocardial ischemia/reperfusion injury, as also indicated in our patients by the significant release of CTnI and CK-MB after the operation and by temporary contractile dysfunction (stunning) as demonstrated by a higher HR and a reduced SVI. These findings, which reflect potential injury in cellular viability, were also closely associated with the target vessel occlusion times.

The RV myocardium has been recognized as being the most vulnerable during an on-pump CABG operation. The combined delivery of cardioplegia is insufficient to ensure myocardial protection to the posterior ventricular septum and the RV free wall.21 RV function, as measured by RVEF, has been reported21 to be decreased in patients after they undergo an on-pump bypass procedure, even when the RCA is open. In addition, experiments with induced anteroseptal myocardial infarction in pigs have shown systolic and diastolic dysfunction in the RV, as shown by decreased RVEF and increased RV end-diastolic pressure.22 In the present study, the change in RV function in patients after they have undergone an off-pump bypass procedure was not substantial, reflecting the presence of intact biventricular (and septal) myocardial function. Acute anterior/septal infarctions did not occur in either of the groups, despite the fact that the main target vessel was, most frequently, the LAD. All the patients in whom RVEF measurements were made had unobstructed RCAs, which favors better postoperative contractility in the RV and may also explain why patients in the IP group did not demonstrate changes in RVEF.

Despite abundant evidence showing that a short period of LAD occlusion protects the heart against subsequent sustained ischemia,11 12 15 there are reports indicating that IP does not improve short-term myocardial function in animals in simulated conditions resembling those of off-pump surgery.10 14 These reports, however, suggest that IP may provide longer term benefits such as improved endothelium-dependent relaxation, endothelial viability, improved ß-adrenergic regulation, better postischemic myocardial blood flow, and reduced neutrophil accumulation.10 14 When judging these results, it should be noted that they were performed on relatively healthy animal hearts, and the conclusions as such may not be applied to the human hearts undergoing off-pump surgery with obstructed coronary arteries and the potential for collateral circulation.

Even though reports exist showing that IP of 3 to 5 minutes’ duration in patients undergoing off-pump CABG protects the ischemic-endangered myocardium,17 18 controversial findings also have been reported.16 19 The results of our randomized, controlled study shows that IP decreases postoperative myocardial enzyme levels, especially that of CTnI, which remains detectable longer than CK-MB. The assumption that myocardial injury occurred less often in our IP patients also is supported by the tendency for a better recovery of mechanical function in the IP group than in the control subjects, as judged from the presence of a higher SVI and a smaller increase in the HR.

Local IP in patients undergoing off-pump surgery favored myocardial functional recovery, but its effect was not as evident as in our on-pump patients who had undergone global IP.21 Obviously, aortic cross-clamping to generate global ischemia for IP renders more IP stimulus from the myocardium than does the local occlusion of the LAD (which only affects the septal and anterior left ventricle). On the other hand, the safety of our patients prevented us from endangering more of the myocardium. LAD occlusion also might have produced less of an IP effect due to the effects of potential collateral circulation in the distal LAD area. The detailed evaluation of the effects of existing collateral circulation is difficult. Since our patients had high-grade coronary artery stenoses, collateral circulation may have reduced the maximal myocardial area that was able to generate the IP effect. Collateral circulation may also directly prevent contractile dysfunction by reducing the size of the ischemic zone. On the other hand, the use of anesthetic agents and inotropic medications in the control group may produce effects resembling IP, thus diluting the studied effect.

In the present study, 2 min of ischemia was chosen for IP because the results of studies23 of patients undergoing coronary angioplasty have shown that IP effects are induced when the vessel is occluded for > 90 s. The use of IP with repeated cycles of ischemic stimuli has been proposed to ensure the protective effects.24 The ideal IP protocol should have a minimal permanent ischemic effect, and vessel occlusion should not be repeated many times to prevent inconvenience to the main bypass procedure, but should, on the other hand, induce the maximal myocardial protective effects. In conclusion, we have shown that two periods of 2 min of ischemia in the LAD area followed by 3 min of reperfusion has cardioprotective effects in patients undergoing off-pump CABG, as demonstrated by a smaller amount of specific enzyme release and a slightly better hemodynamic recovery.


   Footnotes
 
Abbreviations: CABG = coronary artery bypass grafting; CK-MB = creatine kinase isoenzyme MB; CPB = cardiopulmonary bypass; CTnI = cardiac troponin I; CVP = central venous pressure; HR = heart rate; POD = postoperative day; IP = ischemic preconditioning; LAD = left anterior descending artery; MPAP = mean pulmonary artery pressure; PCWP = pulmonary capillary wedge pressure; PVRI = pulmonary vascular resistance index; RCA = right coronary artery; RV = right ventricle, ventricular; RVEDVI = right ventricular end-diastolic volume index; RVEF = right ventricular ejection fraction; SVI = stroke volume index; SVRI = systemic vascular resistance index

The study was supported by the Research Foundation of Tampere University Hospital.

Received for publication January 4, 2001. Accepted for publication October 26, 2001.


   References
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 Abstract
 Materials and Methods
 Results
 Discussion
 References
 

  1. Krukenkamp, IB, Levitsky, S (1996) Physiology and cellular mechanism of myocardial protection. Am J Surg 172,79-84[CrossRef][ISI][Medline]
  2. Wan, S, DeSmet, JM, Barvais, L, et al (1996) Myocardium is a major source of proinflammatory cytokines in patients undergoing cardiopulmonary bypass. Thorac Cardiovasc Surg 112,806-811
  3. Wu, ZK, Tarkka, MR, Eloranta, J, et al (2000) Effect of ischemic preconditioning (IP) on myocardial protection in CABG patients: can the free radicals act as a trigger for IP? Chest 119,1061-1068[Abstract/Free Full Text]
  4. Bolli, R (1998) Basic and clinical aspects of myocardial stunning. Prog Cardiovasc Dis 40,477-516[CrossRef][ISI][Medline]
  5. BhaskerRao, B, VanHimbergen, D, Edmonds, HL, Jr, et al (1998) Evidence for improved cerebral function after minimally invasive bypass surgery. J Cardiol Surg 13,27-31
  6. Reichenspurner, H, Navia, JA, Berry, G, et al (2000) Particulate emboli capture by an intra-aortic filter device during cardiac surgery. Thorac Cardiovasc Surg 119,233-241
  7. Tasdemir, O, Vural, KM, Karagoz, H, et al (1998) Coronary artery bypass grafting on the beating heart without the use of extracorporeal circulation: review of 2052 cases. Thorac Cardiovasc Surg 116,68-73
  8. Magovern, JA, Benckart, DH, Landreneau, RJ, et al (1998) Morbidity, cost, and six-month outcome of minimally invasive direct coronary artery bypass grafting. Ann Thorac Surg 66,1224-1229[Abstract/Free Full Text]
  9. Matsuda, H, Sawa, Y, Takahashi, T, et al (1998) Minimally invasive cardiac surgery: current status and perspective. Artif Organs 22,759-764[CrossRef][ISI][Medline]
  10. Bufkin, BL, Shearer, ST, Vinten-Johansen, J, et al (1998) Preconditioning during simulated MIDCABG attenuates blood flow defects and neutrophil accumulation. Ann Thorac Surg 66,726-731[Abstract/Free Full Text]
  11. Murry, CE, Jennings, RB, Reimer, KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74,1124-1136[Abstract/Free Full Text]
  12. Przyklenk, K, Kloner, RA (1998) Ischemic preconditioning: exploring the paradox. Prog Cardiovasc Dis 40,517-547[CrossRef][ISI][Medline]
  13. Pavie, A, Lima, L, Bonnet, N, et al (1999) Perioperative management in minimally invasive coronary surgery. Eur J Cardiothorac Surg 16,S53-S57[Abstract/Free Full Text]
  14. Tofukuji, M, Metais, C, Li, J, et al (1998) Effects of ischemic preconditioning on myocardial perfusion, function, and microvascular regulation. Circulation 1998(suppl),II197-II204
  15. Thourani, VH, Nakamura, M, Duarte, IG, et al (1999) Ischemic preconditioning attenuates postischemic coronary artery endothelial dysfunction in a model of minimally invasive direct coronary artery bypass grafting. Thorac Cardiovasc Surg 117,383-389
  16. Lucchetti, V, Caputo, M, Suleiman, MS, et al (1998) Beating heart coronary revascularization without metabolic myocardial damage. Eur J Cardiothorac Surg 14,443-444
  17. Jacobsohn, E, Young, CJ, Aronson, S, et al (1997) Case 4–1997: the role of ischemic preconditioning during minimally invasive coronary artery bypass surgery. J Cardiothorac Vasc Anesth 11,787-792[CrossRef][ISI][Medline]
  18. Latham, P, Joshi, GP (1998) Coronary revascularization without cardiopulmonary bypass: use of ischemic preconditioning and adenosine. Anesthesiology 88,828-830[CrossRef][ISI][Medline]
  19. Malkowski, MJ, Kramer, CM, Parvizi, St, et al (1998) Transient ischemia does not limit subsequent ischemic regional dysfunction in humans: a transesophageal echocardiographic study during minimally invasive coronary artery bypass surgery. J Am Coll Cardiol 31,1035-1039[Abstract/Free Full Text]
  20. Przyklenk, K, Bauer, B, Ovize, M, et al (1993) Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87,893-899[Abstract/Free Full Text]
  21. Wu, ZK, Tarkka, MR, Pehkonen, E, et al (2000) Ischemic preconditioning has beneficial effects on right ventricular hemodynamic function during CABG operation. Ann Thorac Surg 70,1551-1557[Abstract/Free Full Text]
  22. Lancaster, LD, Kern, KB, Morrison, DA, et al (1989) Changes in right ventricular relaxation during acute anterior myocardial infarction in pigs. Cardiovasc Res 23,46-52[ISI][Medline]
  23. Airaksinen, KE, Huikuri, HV (1997) Antiarrhythmic effect of repeated coronary occlusion during balloon angioplasty. J Am Coll Cardiol 29,1035-1038[Abstract]
  24. Downey, JM, Cohen, MV (1997) Signal transduction in ischemic preconditioning. Adv Exp Med Biol 430,39-55[ISI][Medline]



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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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H. Yokoyama, S. Takase, Y. Misawa, K. Takahashi, Y. Sato, and H. Satokawa
A simple technique of introducing intracoronary shunts for off-pump coronary artery bypass surgery
Ann. Thorac. Surg., July 1, 2004; 78(1): 352 - 354.
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P.-G. Chassot, P. van der Linden, M. Zaugg, X. M. Mueller, and D. R. Spahn
Off-pump coronary artery bypass surgery: physiology and anaesthetic management{dagger}
Br. J. Anaesth., March 1, 2004; 92(3): 400 - 413.
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J. Vaage
Invited commentary
Ann. Thorac. Surg., April 1, 2003; 75(4): 1252 - 1252.
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