ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Bradley L. Bufkin
Jakob Vinten-Johansen
Ignacio G. Duarte
Vinod H. Thourani
Masanori Nakamura
Robert A. Guyton
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bufkin, B. L.
Right arrow Articles by Guyton, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bufkin, B. L.
Right arrow Articles by Guyton, R. A.

Ann Thorac Surg 1998;66:726-732
© 1998 The Society of Thoracic Surgeons

Original articles: Cardiovascular

Preconditioning during simulated MIDCABG attenuates blood flow defects and neutrophil accumulation

Bradley L. Bufkin, MDa, Steven T. Shearer, BSa, Jakob Vinten-Johansen, PhDa, Ignacio G. Duarte, MDa, Vinod H. Thourani, MDa, Masanori Nakamura, MDa, Zhi-Qing Zhao, PhDa, Robert A. Guyton, MDa

a Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine, Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Crawford Long Hospital, Atlanta, Georgia, USA

Address reprint requests to Dr Vinten-Johansen, Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center, Crawford Long Hospital, 550 Peachtree St NE, Atlanta, GA 30365-2225

Presented at the Forty-fourth Annual Meeting of the Southern Thoracic Surgical Association, Naples, FL, Nov 6–8, 1997.


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Background. Ischemic preconditioning (IP) may be cardioprotective in minimally invasive direct coronary artery bypass where cardioplegia is not used. This study tested the hypothesis that IP of the area at risk (AAR) would attenuate postischemic injury from transient coronary artery occlusion.

Methods. In 19 anesthetized dogs, the left anterior descending coronary artery was occluded for 30 minutes (simulating coronary occlusion during anastomosis) followed by 3 hours of reperfusion. In 10 dogs, occlusion was preceded by 5 minutes of occlusion and 5 minutes of reperfusion (IP), whereas 9 other dogs had no IP (control, C).

Results. Thirty minutes of left anterior descending occlusion caused comparable dyskinesis (systolic shortening, sonomicrometry) in the AAR in C (baseline, 29% ± 3% to 3% ± 2%) and in IP (baseline, 29% ± 2% to -0.3% ± 2%). After 3 hours of reperfusion, systolic shortening was significantly depressed in C (20% ± 4%), and was not significantly improved by IP (24% ± 3%, p = 0.8 versus C). Postischemic diastolic stiffness in the AAR was not altered by IP versus C (0.60 ± 0.12 versus 0.41 ± 0.13). Plasma creatine kinase activity was similar between C and IP at the end of reperfusion (20 ± 11 versus 16 ± 5 U/g). Postischemic AAR blood flow (in milliliters per minute per gram of tissue) at 180 minutes of reperfusion decreased by 56% versus baseline in C (from 1.04 ± 0.4 to 0.46 ± 0.12; p < 0.05) compared with no change in IP (from 0.74 ± 0.23 to 0.60 ± 0.10), but there was no significant group difference at this time. Myeloperoxidase activity as an index of neutrophil accumulation in AAR was decreased in IP versus C (0.4 ± 0.09 versus 0.7 ± 0.04 U/µg tissue).

Conclusions. Ischemic preconditioning does not decrease postischemic wall motion and only modestly increases postischemic blood flow abnormalities in the AAR, but does significantly inhibit neutrophil accumulation.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Minimally invasive direct coronary artery bypass grafting (MIDCABG) requires an interval of regional myocardial ischemia during anastomosis of the vascular graft to the target vessel. This relatively short period of ischemia, although not precipitating necrosis, may cause injury to the myocardium subtended by the target vessel, manifest as contractile dysfunction and vascular endothelial injury (endothelial stunning) [1]. In the absence of cardioplegia and other modalities of cardioprotection requiring extracorporeal techniques, a myocardial protection strategy for this interval of regional ischemia is needed to limit the deleterious consequences of iatrogenic regional ischemia. Ischemic preconditioning (IP) is a highly effective method of protection in models of coronary occlusion [2]. Ischemic preconditioning is defined as a short period of ischemia (regional or global) imposed before a more prolonged period of ischemia, which increases the myocardium’s tolerance to ischemia by endogenous adaptive mechanisms [2]. Ischemic preconditioning has been reported to reduce infarct size [2, 3] and attenuate postischemic arrhythmias [4]. However, reduction in postischemic wall motion abnormalities is not universally observed [5].

This study tested the hypothesis that IP may be cardioprotective for a regional ischemic interval producing reversible ischemic injury. A canine model of a simulated MIDCABG procedure with 30 minutes of regional ischemia was used to compare an ischemic preconditioned group with a nonpreconditioned (control) group. Regional myocardial performance, regional myocardial blood flow, creatine kinase concentration, and neutrophil accumulation in the area placed at risk were used as end points.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
The dogs in this study 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 National Academy of Sciences and published by the National Institutes of Health (NIH publication 85-23, revised 1985).The experimental protocol was approved by the Institutional Animal Care and Use Committee of Emory University.

Surgical procedure
Nineteen animals weighing 20 to 35 kg underwent premedication with 4 mg/kg morphine sulfate. Endotracheal intubation was then performed after administration of 20 µg/kg of fentanyl and 0.25 mg/kg of diazepam, and anesthesia was maintained by continuous infusion of 0.3 µg · kg-1 · min-2 of fentanyl and 0.03 mg · kg-1 · min-2 of diazepam. Initial ventilator settings used tidal volume of 10 mL/kg and rate of 12 breaths per minute with adjustments dictated by periodic arterial blood gases to maintain pH at 7.35 to 7.45, partial pressure of oxygen at more than 100 mm Hg, and partial pressure of carbon dioxide at 35 to 45 mm Hg. The left femoral artery was cannulated for arterial blood gas sampling and for reference blood sampling during regional myocardial blood flow measurements. Limb leads and a precordial lead were placed for electrocardiographic monitoring.

A median sternotomy incision was used for exposure. The internal mammary vessels and phrenic nerves were divided. A high-fidelity micromanometer (Millar Inc, Houston, TX) was secured in the ascending aorta for systemic blood pressure monitoring and another micromanometer was inserted into the left ventricle through the apex. A 14-gauge catheter was placed in the left atrium for injection of dye-release colored microspheres during regional myocardial blood flow measurements. Pairs of segment length sonomicrometer transducers (Triton Technology, Inc, San Diego, CA) were inserted through epicardial stab wounds in the midmyocardium of the region subtended by the left anterior descending coronary artery and the circumflex coronary artery for measurement of regional myocardial systolic and diastolic function.

The left anterior descending coronary artery (LAD) was mobilized distal to the first diagonal branch, involving approximately 35% of the left ventricle. All animals were given an intravenous bolus of lidocaine (2 mg/kg) and maintained on a lidocaine drip (1 mg/min). All animals were given 3,000 units of heparin and were observed for 15 minutes to allow stabilization.

Experimental protocol
Dogs were randomly assigned to a control group (C) or an ischemic preconditioned group (IP). All animals underwent 30 minutes of LAD occlusion followed by 3 hours of reperfusion. The IP animals underwent 5 minutes of LAD occlusion followed by 5 minutes of reperfusion before the 30 minutes of LAD occlusion, whereas control animals were not preconditioned before the 30 minutes of LAD occlusion. After the 30-minute interval of LAD occlusion, the LAD occlusion was released and animals in both groups were monitored for 3 hours of reperfusion. Animals in which ventricular fibrillation developed received an additional lidocaine bolus (2 mg/kg) and direct-current countershocks to restore a stable cardiac rhythm. Animals not responsive to these therapeutic maneuvers were excluded from the study.

Data acquisition and analysis
Hemodynamic data, including left ventricular, systemic arterial, and sonomicrometer data, were gathered during a 12-second period of respiratory apnea. The data from each channel were digitized at 250 Hz using an analog-to-digital conversion board (Data Translation, Inc, Marlboro, MA) and microprocessor (model 486; Intel, Houston, TX) using interactive proprietary software (Spectrum, Winston-Salem, NC). Measurements were taken at baseline, after 30 minutes of LAD occlusion, and at 30, 60, 90, 120, 150, and 180 minutes of reperfusion. Hemodynamic and regional myocardial function data were averaged from eight to ten beats. Percent segmental shortening and the characteristics of segmental stiffness were determined as previously described [6].

Plasma creatine kinase activity
Blood samples for measuring plasma creatine kinase activity were withdrawn from the femoral artery at baseline, after 30 minutes of LAD occlusion, and at 30, 60, 120, and 180 minutes of reperfusion. The plasma was analyzed spectrophotometrically for creatine kinase activity (CK-10 kit; Sigma Diagnostics, St. Louis, MO) and protein concentration (Sigma Diagnostics). Creatine kinase activity was expressed as international units per gram of protein.

Cardiac myeloperoxidase activity
After 180 minutes of reperfusion, the heart was arrested with bolus sodium pentobarbital and rapidly excised, and tissue samples weighing approximately 0.5 g were taken from the ischemic (LAD) region and nonischemic (left circumflex coronary artery [CX]) region for spectrophotometric analysis of myeloperoxidase activity as a measure of neutrophil accumulation in myocardium as described previously [7].

Regional myocardial blood flow
Regional myocardial blood flow measurements were obtained with use of dye-release colored microspheres. Left atrial injections and reference blood sampling was performed at baseline, preconditioning reperfusion, 30 minutes of LAD occlusion, and at 15 and 180 minutes of reperfusion. The reference blood samples and myocardial tissue samples from the ischemic (LAD) and nonischemic (CX) regions underwent spectrophotometric analysis as previously described [8].


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
Hemodynamic data for the IP and control groups are presented in Table 1. Mean arterial pressure, heart rate, and left ventricular end-diastolic pressure were not significantly different between the two groups at any time. Maximum rate of change of pressure was depressed during LAD occlusion in both groups, but it was significantly greater in the IP group than in the C group during 90 to 180 minutes of reperfusion.


View this table:
[in this window]
[in a new window]
  		Table 1. Hemodynamic Data During the Experiment

 
In the ischemic-reperfused LAD region, percent systolic shortening was significantly and comparably depressed in both groups during LAD occlusion; there was no significant difference between the groups at 180 minutes of reperfusion (Fig 1). In the nonischemic CX region, percent systolic shortening displayed no change within groups during LAD occlusion and reperfusion, and there was no difference between the groups at any time point (Fig 1). Diastolic stiffness as measured by the ß-coefficient was not significantly different between the IP and control groups with a trend toward elevation in the value at 180 minutes of reperfusion in both groups in the LAD region (Table 2). The ß-coefficient in the nonischemic CX region displayed a higher degree of variability with no significant difference between the groups (Table 2). A trend toward increased stiffness in the CX region in both groups was observed.



View larger version (28K):
[in this window]
[in a new window]
  		Fig 1. Percent systolic shortening for control and ischemic preconditioned (IP) groups. (A) Percent systolic shortening for the zone perfused by the left anterior descending coronary artery (LAD). (B) Percent systolic shortening for the zone perfused by the left circumflex coronary artery (CX). Bars represent mean values with standard error represented by error bars. (Base = baseline; Occ = left anterior descending coronary artery occlusion; 30r, 60r, 90r, 120r, 150r, 180r = minutes of reperfusion; *p < 0.05 compared with baseline.)

 

View this table:
[in this window]
[in a new window]
  		Table 2. Diastolic Stiffness for Ischemic (LAD Region) and Nonischemic (CX Region) Determined by Curvature (Unitless ß-Coefficient) of the Exponential Pressure-Segment Length Relationship

 
Plasma creatine kinase, a measure of myocardial injury, increased gradually throughout the reperfusion period in the IP and C groups with no significant difference between the groups (Fig 2). Tissue myeloperoxidase activity, a measure of neutrophil accumulation in the myocardium, was significantly lower in the ischemic-reperfused LAD region of the IP group compared to C (Fig 3). A decrease in tissue myeloperoxidase activity was also observed in the nonischemic CX region in the IP group compared to the C group, although the difference was not statistically significant (Fig 3).



View larger version (19K):
[in this window]
[in a new window]
  		Fig 2. Plasma creatine kinase activity for control and ischemic preconditioned (IP) groups. Bars represent mean values with standard error represented by error bars. There were no significant group differences at any time. (Base = baseline; Occ = left anterior descending coronary artery occlusion; PC = preconditioning reperfusion; U = international units; 30r, 60r, 90r, 120r, 150r, 180r = minutes of reperfusion.)

 


View larger version (14K):
[in this window]
[in a new window]
  		Fig 3. Tissue myeloperoxidase activity for control and ischemic preconditioned (IP) groups. Bars represent mean values with standard error represented by error bars. (CX region = zone perfused by the left circumflex coronary artery; LAD region = zone perfused by the left anterior descending coronary artery; U = international units; #p < 0.05 compared with control group.)

 
Blood flow to the LAD region was statistically comparable between the two groups at baseline. After the brief preconditioning period, a significant hyperemic blood flow was observed in the LAD region (Fig 4). Ischemic zone blood flow was significantly decreased during the prolonged LAD occlusion period, with no group differences. The control group displayed a significantly increased hyperemic response in the LAD region at 15 minutes of reperfusion as compared with the IP group. Compared with baseline values, blood flow in the LAD zone at 180 minutes of reperfusion was reduced by more than 50% in the C group (p < 0.05 versus baseline), but not in the IP group. However, there was no significant difference (p = 0.26) between the two groups at 180 minutes of reperfusion. In the nonischemic CX region, blood flow was comparable in both groups throughout the experimental protocol.



View larger version (17K):
[in this window]
[in a new window]
  		Fig 4. Regional myocardial blood flow (milliliters per minute per gram of myocardium blood flow) for control and ischemic preconditioned (IP) groups in. (A) Regional myocardial blood flow for the zone perfused by the left anterior descending coronary artery (LAD). (B) Regional myocardial blood flow for the zone perfused by the left circumflex coronary artery (CX). Bars represent mean values with standard error represented by error bars. (Base = baseline; PC = preconditioning reperfusion; Occ = left anterior descending coronary artery occlusion; 15r, 180r = minutes of reperfusion; *p < 0.05 compared with baseline; #p < 0.05 compared with ischemic preconditioned group.)

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
A brief period of ischemia and reperfusion antecedent to a sustained period of ischemia, termed preconditioning, was first reported by Murry and colleagues [2] in models of irreversible injury (ie, infarction). Ischemic preconditioning mobilizes intrinsic protective mechanisms that significantly reduce infarct size [2, 9]. Ischemic preconditioning is one of the most potent cardioprotective interventions on myocardial necrosis, and has been mimicked by various pharmacologic agents including adenosine [10], adrenergic stimulators, and adenosine triphosphate-sensitive potassium-channel openers [11]. In contrast to infarction, the effects of IP on postischemic contractile function have shown mixed results in models using reversible ("stunning") or irreversible ischemia. Likewise the effects of IP on the coronary vasculature have been mixed, with some studies reporting protection against vascular dysfunction [12, 13] and others showing no benefit on endothelial function [14].

The present study evaluated the effects of IP on a 30-minute interval of regional myocardial ischemia. This duration of regional ischemia produces no apparent infarction, and is only somewhat longer than may be encountered during anastomosis of a target vessel in a clinical MIDCABG procedure. The interval of regional ischemia in the largest reported series of MIDCABG procedures averaged 23 minutes [15]. We found that sustained occlusion of the LAD (without preconditioning) produced systolic dysfunction in the myocardium perfused by the occluded vessel, which persisted throughout the reperfusion period. Preconditioning did not significantly improve regional function, although a trend toward better function was observed. Neither group showed diastolic dysfunction in the area at risk. The sustained occlusion showed a significant decrease in postischemic blood flow, which was not evident in the preconditioned group, although group differences did not emerge. Finally, preconditioning significantly reduced neutrophil accumulation in the area at risk as indexed by tissue myeloperoxidase activity. Therefore, ischemic preconditioning had modest cardioprotective effects on postischemic blood flow, but significant benefits on neutrophil accumulation in this model.

Postischemic blood flow to the area at risk myocardium undergoes dynamic changes during the reperfusion period. A significant reactive hyperemia is observed during the initial moments of reperfusion, consistent with the observations in the present study, which then progressively deteriorate to below baseline levels, particularly in the endocardium. This postischemic regional blood flow defect, or "no-reflow" condition, is proportionally related to the severity and duration of ischemia. The mechanisms underlying postischemic blood flow defects include microvascular collapse secondary to extravascular compression and edema [16], neutrophil adherence and plugging of the microvasculature [17], and impaired release of endogenous vasodilators by the endothelium such as nitric oxide [18] and possibly adenosine. A study by Thourani and colleagues [12] suggests that blood flow defects in a similar MIDCABG model are related to defects in endothelial vasodilator function and a failure in the normal basal inhibitory mechanisms of neutrophil interactions caused by impaired nitric oxide release [1, 7, 18].

Neutrophils play an important role in ischemic-reperfusion injury [19]. In models of irreversible injury (ie, infarction), neutrophils accumulate in the area at risk during reperfusion [19]; during the early moments of reperfusion, adherence to the vascular endothelium is the initial step that precedes both endothelial damage and necrosis [20]. However, the role of neutrophils is not clear in shorter or less severe ischemia producing reversible injury, and their role specifically as an active participant in contractile "stunning" is unclear [21]. In the present study, there was a significant accumulation of neutrophils (vis-à-vis increased myeloperoxidase activity) in the area at risk after 30 minutes of ischemia and 3 hours of reperfusion. This reduction in neutrophil accumulation may be related to preservation of endothelial function with preconditioning [6] involving a greater basal release of the endogenous antineutrophil autacoids nitric oxide or adenosine [6]. Increased basal release of nitric oxide from the coronary vascular endothelium has been associated with less adherence of neutrophils to the endothelial surface [18] and, hence, less acumulation within the area at risk over the reperfusion period. Increased basal release of nitric oxide from the coronary vascular endothelium has been associated with less adherence of neutrophils to the endothelial surface [18] and, hence, less acumulation over the reperfusion period. Although preconditioning significantly reduced neutrophil accumulation in the area at risk, there was not a significant improvement in postischemic contractile dysfunction. In addition, postischemic systolic shortening was gradually improving in the area at risk at a time when neutrophils are progressively accumulating. The relationship between neutrophils and contractile dysfunction is not clear in the model used in the present study. However, there may be a correlation between postischemic coronary artery endothelial function and contractile function, as suggested by the study of Thourani and colleagues [12] and other investigators [22].

In summary, this investigation demonstrates that ischemic preconditioning does not prevent contractile dysfunction after 30 minutes of LAD occlusion, but does provide subtle improvement in blood flow to the ischemic-reperfused region. In addition, preconditioning reduces neutrophil accumulation in the ischemic-reperfused region. These findings suggest that ischemic preconditioning may provide cardioprotection during regional ischemic intervals experienced during MIDCABG surgical revascularization. Although the protective effect is not manifest by reduced contractile dysfunction, the most frequently evaluated clinical parameter, protection, most likely benefits the coronary vascular endothelium. This may have implications on short-term and long-term patency of the revascularized target vessel, as well as the myocardium distal to the grafted vessel, as the health of the endothelium influences distal myocardium through release of cardioprotective autacoids such as nitric oxide [23] and adenosine [24].


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
We thank L. Susan Schmarkey, Sara L. Katzmark, and Jill Robinson for their technical assistance. This study was supported in part by the Carlyle Fraser Heart Center Foundation, Crawford Long Hospital and Emory University School of Medicine.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Bolli R., Triana F., Jeroudi M.O. Postischemic mechanical and vascular dysfunction (myocardial "stunning" and microvascular "stunning") and the effects of calcium-channel blockers on ischemia/reperfusion injury. Clin Cardiol 1989;12(Suppl 3):16-25.
  2. Murry C.E., Jennings R.B., Reimer K.A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124-1136.[Abstract/Free Full Text]
  3. Liu Y., Downey J.M. Ischemic preconditioning protects against infarction in rat heart. Am J Physiol 1992;263:H1107-H1112.
  4. Lawson C.S., Hearse D.J. Ischemic preconditioning against arrhythmias: an anti-arrhythmic or an anti-ischemic phenomenon?. Ann NY Acad Sci 1994;723:138-157.[Medline]
  5. Ovize M., Przyklenk K., Hale S.L., Kloner R.A. Preconditioning does not attenuate myocardial stunning. Circulation 1992;85:2247-2254.[Abstract/Free Full Text]
  6. Sato H., Zhao Z.-Q., McGee D.S., Williams M.W., Hammon J.W., Jr, Vinten-Johansen J. Supplemental L-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury. J Thorac Cardiovasc Surg 1995;110:302-314.[Abstract/Free Full Text]
  7. Lefer D.J., Nakanishi K., Johnston W.E., Vinten-Johansen J. Antineutrophil and myocardial protection actions of a novel nitric oxide donor after acute myocardial ischemia and reperfusion in dogs. Circulation 1993;88:2337-2350.[Abstract/Free Full Text]
  8. Bufkin B.L., Mellitt R.J., Gott J.P., Huang A.H., Chih P., Guyton R.A. Aerobic blood cardioplegia for revascularization of acute infarct: effects of delivery temperature. Ann Thorac Surg 1994;58:953-960.
  9. Miura T., Iimura O. Infarct size limitation by preconditioning: its phenomenological features and the key role of adenosine. Cardiovasc Res 1993;27:36-42.[Free Full Text]
  10. Toombs C.F., McGee D.S., Johnston W.E., Vinten-Johansen J. Myocardial protective effects of adenosine. Infarct size reduction with pretreatment and continued receptor stimulation during ischemia. Circulation 1992;86:986-994.[Abstract/Free Full Text]
  11. Grover G.J., Sleph P.G., Dzwonczyk S. Role of myocardial ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A1-receptors. Circulation 1992;86:1310-1316.[Abstract/Free Full Text]
  12. Thourani VH, Nakamura M, Duarte IG, et al. Ischemic preconditioning attenuates postischemic coronary artery endothelial dysfunction in a model of minimally invasive direct coronary artery bypass (MIDCAB) [Abstract]. J Thorac Cardiovasc Surg (in press).
  13. DeFily D.V., Chilian W.M. Preconditioning protects coronary arteriolar endothelium from ischemia-reperfusion injury. Am J Physiol 1993;265:H700-H706.
  14. Bauer B., Simkhovisch B.Z., Kloner R.A., Przyklenk K. Does preconditioning protect the coronary vasculature from subsequent ischemia/reperfusion injury?. Circulation 1993;88:659-672.[Abstract/Free Full Text]
  15. Calafiore A.M., Di Giammarco G., Teodori G. Left anterior descending coronary artery grafting via left anterior small thoracotomy without cardiopulmonary bypass. Ann Thorac Surg 1996;61:1658-1665.[Abstract/Free Full Text]
  16. Manciet L.H., Poole D.C., McDonagh P.F., Copeland J.G., Mathieu-Costello O. Microvascular compression during myocardial ischemia: mechanistic basis for no-reflow phenomenon. Am J Physiol 1994;266:H1541-H1550.
  17. Schmid-Schönbein G.W. Capillary plugging by granulocytes and the no-reflow phenomenon in the microcirculation. Fed Proc 1987;46:2397-2401.[Medline]
  18. Ma X.-L., Weyrich A.S., Lefer D.J., Lefer A.M. Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Res 1993;72:403-412.[Abstract/Free Full Text]
  19. Dreyer W.J., Michael L.H., West M.W., et al. Neutrophil accumulation in ischemic canine myocardium: insights into time course, distribution, and mechanism of localization during early reperfusion. Circulation 1991;84:400-411.[Abstract/Free Full Text]
  20. Mullane K. Neutrophil and endothelial changes in reperfusion injury. Trends Cardiovasc Med 1991;1:282-289.
  21. Bolli R. Role of neutrophils in myocardial stunning after brief ischaemia: the end of a six year old controversy (1987–1993). Cardiovasc Res 1993;27:728-730.[Medline]
  22. Wallace A. Do deficiencies of endothelial derived relaxing factor contribute to myocardial stunning?. J Cardiol Surg 1993;8:325-328.
  23. Williams M.W., Taft C.S., Ramnauth S., Zhao Z.-Q., Vinten-Johansen J. Endogenous nitric oxide (NO) protects against ischaemia-reperfusion injury in the rabbit. Cardiovasc Res 1995;30:79-86.[Medline]
  24. Vinten-Johansen J., Zhao Z.-Q. Cardioprotection from ischemic-reperfusion injury by adenosine. In: Abd-Elfattah A.S., Wechsler A.S., eds. Purines and myocardial protection. Norwell: Kluwer Academic Publishers, 1995:315-344.



This article has been cited by other articles:


Home page
 Asian Cardiovasc. Thorac. Ann.Home page
I. Karu, P. Tahepold, T. A. Sulling, M. Alver, M. Zilmer, and J. Starkopf
Off-Pump Coronary Surgery causes Immediate Release of Myocardial Damage Markers
Asian Cardiovasc Thorac Ann, October 1, 2009; 17(5): 494 - 499.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
R. S. Ronson, J. D. Puskas, V. H. Thourani, D. A. Velez, B. L. Bufkin, J. Glass, R. A. Guyton, and J. Vinten-Johansen
Controlled intermittent asystole cardiac therapy induced by pharmacologically potentiated vagus nerve stimulation in normal and hibernating myocardium
Ann. Thorac. Surg., June 1, 2003; 75(6): 1929 - 1936.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
H. J. Penttila, M. V.K. Lepojarvi, P. K. Kaukoranta, K. T. Kiviluoma, K. V. Ylitalo, and K. J. Peuhkurinen
Ischemic preconditioning does not improve myocardial preservation during off-pump multivessel coronary operation
Ann. Thorac. Surg., April 1, 2003; 75(4): 1246 - 1252.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. Laurikka, Z.-K. Wu, P. Iisalo, L. Kaukinen, E. L. Honkonen, S. Kaukinen, and M. R. Tarkka
Regional Ischemic Preconditioning Enhances Myocardial Performance in Off-Pump Coronary Artery Bypass Grafting*
Chest, April 1, 2002; 121(4): 1183 - 1189.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
S. Muraki, C. D. Morris, J. M. Budde, R. N. Otto, Z.-Q. Zhao, J. D. Puskas, R. A. Guyton, and J. Vinten-Johansen
Preserved myocardial blood flow and oxygen supply-demand balance with active coronary perfusion during simulated off-pump coronary artery bypass grafting
J. Thorac. Cardiovasc. Surg., January 1, 2002; 123(1): 53 - 62.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
E. E.H.L. van Aarnhem, A. P. Nierich, and E. W.L. Jansen
When and how to shunt the coronary circulation in off-pump coronary artery bypass grafting
Eur. J. Cardiothorac. Surg., November 1, 1999; 16(suppl_2): S2 - S6.
[Abstract] [Full Text] [PDF]

Home page
 SEMIN CARDIOTHORAC VASC ANESTHHome page
H.-S. V. Chen, S. C. Body, and S. K. Shernan
Myocardial Preconditioning: Characteristics, Mechanisms, and Clinical Applications
Seminars in Cardiothoracic and Vascular Anesthesia, July 1, 1999; 3(2): 85 - 97.
[Abstract] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
V. H. Thourani, M. Nakamura, I. G. Duarte, B. L. Bufkin, Z.-Q. Zhao, J. E. Jordan, S. T. Shearer, R. A. Guyton, and J. Vinten-Johansen
ISCHEMIC PRECONDITIONING ATTENUATES POSTISCHEMIC CORONARY ARTERY ENDOTHELIAL DYSFUNCTION IN A MODEL OF MINIMALLY INVASIVE DIRECT CORONARY ARTERY BYPASS GRAFTING
J. Thorac. Cardiovasc. Surg., February 1, 1999; 117(2): 383 - 389.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Bradley L. Bufkin
Jakob Vinten-Johansen
Ignacio G. Duarte
Vinod H. Thourani
Masanori Nakamura
Robert A. Guyton
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bufkin, B. L.
Right arrow Articles by Guyton, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bufkin, B. L.
Right arrow Articles by Guyton, R. A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS