HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Nobuhiko Hayashida Tadashi Isomura Shigeaki Aoyagi Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hayashida, N. Articles by Aoyagi, S. Search for Related Content PubMed PubMed Citation Articles by Hayashida, N. Articles by Aoyagi, S.

Ann Thorac Surg 1998;65:615-621
© 1998 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

Minimally Diluted Tepid Blood Cardioplegia

Second Department of Surgery, Kurume University, Fukuoka, Japan

Accepted for publication August 19, 1997.

Dr Hayashida, Second Department of Surgery, Kurume University, 67 Asahi-machi, Kurume, Fukuoka 830, Japan.

	Abstract

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. To evaluate the effects of minimally diluted tepid blood cardioplegia, a prospective, randomized study was undertaken.

Methods. Thirty-seven patients undergoing isolated primary coronary artery bypass grafting were randomized to receive standard 4:1 diluted tepid blood cardioplegia (4:1 group, n = 18) or minimally diluted tepid blood cardioplegia (Mini group, n = 19). Cardioplegic solution was delivered in an intermittent antegrade fashion in both groups. Myocardial oxygen and lactate metabolism, release of the MB isoenzyme of creatine kinase and thiobarbituric acid reactive substances, and cardiac function were measured during and after the operation.

Results. Myocardial oxygen consumption was significantly greater and lactate release was significantly lower in the Mini group than in the 4:1 group during cardioplegia. Minimally diluted blood cardioplegia resulted in more prompt resumption of lactate extraction, lower levels of release of the myocardial-specific isoenzyme of creatine kinase and thiobarbituric acid reactive substances during reperfusion, and better postoperative left ventricular function compared with the standard 4:1 cardioplegia.

Conclusions. Minimally diluted tepid blood cardioplegia may provide superior myocardial protection than the standard 4:1 dilution technique by optimizing the aerobic environment through an increase in oxygen supply during intermittent cardioplegia.

	Introduction

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Since the introduction of normothermic blood cardioplegia in 1991 [1], many studies [2][3][4] have shown its superior effects on myocardial protection compared with those of conventional cold blood cardioplegia. To meet an increased myocardial energy demand and avoid warm ischemic injury during normothermic cardioplegia, continuous and homogeneous delivery of cardioplegic solution has been suggested to be preferable [5][6][7]. During coronary artery bypass procedures, however, continuous infusion of cardioplegic solution must be interrupted to permit adequate visualization during the distal anastomosis. Moreover, the presence of critical coronary stenoses limits the delivery of cardioplegic solution to ischemic regions of the heart, particularly when revascularization with the internal mammary artery prevents vein graft infusions to the left anterior descending coronary artery. Interruptions or inadequate distribution of normothermic cardioplegia may induce anaerobic metabolism and warm ischemic injury [5][6][7]. To avoid this problem, tepid (29°C) blood cardioplegia was recently introduced [8][9]. The technique has been reported to reduce anaerobic myocardial lactate and acid release without inhibiting myocardial metabolic activity [8][9]. Decreasing the heart temperature from 37° to 29°C may provide a buffer to ischemic injury when cardioplegia delivery is interrupted or nonhomogeneous.

In recent reports [10][11][12], minimally diluted oxygenated blood with concentrated arresting agents as the cardioplegic vehicle was proposed as an alternative technique to the standard 4:1 dilution of blood to crystalloid solution. The technique was reported to increase oxygen-carrying capacity during cardioplegia and reduce postoperative systemic vasodilatation in comparison with the standard dilution technique. Although the technique has been reported to provide superior clinical results [10][12], the published data on its effects on myocardial metabolism and cardiac function are limited [10][13]. Therefore we investigated the effects of intermittent minimally diluted tepid blood cardioplegia on myocardial metabolism and cardiac function in low-risk patients undergoing coronary artery bypass grafting. If this cardioplegic technique provides a significant benefit, we anticipate performing a large, randomized clinical trial in high-risk patients to determine whether the technique will reduce morbidity and mortality.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Thirty-seven patients scheduled for isolated coronary artery bypass grafting by one of us (T.I.) comprised the study group. All patients signed a consent form approved by the human experimentation committee. The patients ranged in age from 44 to 75 years and had left main disease or double- or triple-vessel disease. The demographic data are shown in Table 1.

Cardioplegia Groups
Patients were randomized into two groups according to the cardioplegic strategy by means of a computer-generated randomization table. Cargioplegia was given in intermittent antegrade fashion, and temperature was maintained at 30° ± 1°C (tepid) by means of a heat exchanger in both groups.

Eighteen patients received diluted blood cardioplegia (4:1) prepared by mixing four parts of oxygenated blood with each part of crystalloid solution (4:1 group) [4]. The cardioplegic solution was delivered by means of the Buckberg-Shiley Plus system (Shiley, Irvine, CA). Cardiac arrest was achieved with an antegrade infusion of 600 mL of high-potassium cardioplegia (containing 27 mEq/L of potassium) delivered into the aortic root at a pressure of 50 to 60 mm Hg. Infusions of 400 mL of low-potassium cardioplegia (containing 13 mEq/L of potassium) were delivered through the aortic root as well as all completed vein grafts after the completion of each distal anastomosis.

Nineteen patients received minimally diluted tepid blood cardioplegia (Mini group). Oxygenated blood was taken directly from the oxygenator through -inch (0.625-cm) tubing and was infused into the aortic root by means of a roller pump. A syringe pump (STC-523; Terumo, Tokyo, Japan) was connected to the -inch tubing to deliver potassium solution in a concentration of 2 mEq/mL. Composition and delivery of the cardioplegic solution followed the protocol described by Calafiore and colleagues [12]. Cardiac arrest was achieved with an antegrade infusion of 600 mL of cardioplegia (containing 18 to 20 mEq/L of potassium). Infusions of 400 to 600 mL of cardioplegia (containing 6.3 to 20 mEq/L of potassium) were delivered through the aortic root as well as all completed vein grafts after each distal anastomosis.

Myocardial Oxygen and Lactate Metabolism
Arterial and coronary venous blood samples were obtained simultaneously on bypass before application of the cross-clamp, immediately after cross-clamp release, and 5 and 20 minutes after cross-clamp release. These blood samples were assayed for partial pressure of oxygen (PO₂), oxygen saturation (SO₂), and hemoglobin concentration (Hb) with a blood gas analyzer (288 Blood Gas System; Ciba Corning, Medfield, MA). Oxygen content (O₂Con) was calculated by the formula: Myocardial oxygen extraction was calculated by subtracting the coronary venous oxygen content from the arterial oxygen content. Blood samples for lactate concentration were mixed with a measured volume of 6% perchloric acid. Lactate concentration was measured in protein-free supernatant by an enzymatic method (7150 Automatic Analyzer; Hitachi, Tokyo, Japan). Myocardial lactate extraction was calculated in the same manner as oxygen extraction. Negative lactate extraction was expressed as lactate production. During cross-clamping, cardioplegia samples and coronary sinus venous blood samples were obtained during each cardioplegic infusion, and myocardial oxygen consumption and lactate release were calculated as cardioplegic flow multiplied by the difference between the cardioplegic and coronary venous content.

Myocardial Release of MB Isoenzyme of Creatine Kinase and Thiobarbituric Acid Reactive Substances
We employed a chemiluminescent immunoassay (Type II Chemilumi-Analyzer; Ciba Corning) to measure the MB isoenzyme of creatine kinase (CK-MB) and a thiobarbituric acid reaction (RF-5000; Shimadzu, Tokyo, Japan) to measure the thiobarbituric acid reactive substances (TBARS) as described previously [14]. Myocardial release of CK-MB and TBARS was calculated by subtracting the arterial levels from the coronary venous levels. Additional venous blood samples were taken to determine the peak level of CK-MB 1 hour, 3 hours, 24 hours, 48, and 72 hours after CPB.

Hemodynamic Measurements
Heart rate (HR), mean arterial blood pressure (MAP), mean pulmonary artery pressure (MPA), mean right atrial pressure (RAP), and pulmonary capillary wedge pressure (PCWP) were measured. Cardiac output (CO) was measured in triplicate by the thermodilution technique (Swan-Ganz model 93A-831H-7.5F; Baxter Healthcare Corp, Irvine, CA). Derived hemodynamic indices were calculated as follows: These hemodynamic variables were measured before initiation of CPB and 1 hour, 6 hours, 12 hours, and 24 hours after cessation of CPB. Postoperative volume repletion followed a standard protocol and was accomplished by individuals who were unaware of the intraoperative cardioplegic technique employed.

Statistical Analysis
Statistical analysis was performed with SPSS statistical software (SPSS Inc, Chicago, IL). All data are expressed as the mean ± the standard error of the mean. One-way or two-way repeated-measures analysis of variance was used to test the effect of cardioplegia group and time on myocardial oxygen and lactate metabolism, CK-MB and TBARS release, and hemodynamic measurements. An analysis of covariance was employed to compare LVSWIs and right ventricular stroke work indices (the independent variables) between the two cardioplegia groups with preload (left and right atrial pressures) as the covariate. When analysis of variance indicated a significant effect of cardioplegia group or time (p < 0.05), the differences were specified with Scheffé’s test for within-group comparison and unpaired Student’s t test for between-group comparison. Unpaired Student’s t test was used to compare other continuous variables. Categoric data were analyzed using the ² test or Fisher’s exact test where appropriate. Significance was assumed at a probability level of less than 0.05.

	Results

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Frequency and Continuity of Infusion, and Volume of Cardioplegia
There were no significant differences in the frequency of cardioplegic infusion (4:1 group, 3.8 ± 0.3, and Mini group, 3.9 ± 0.4; p = 0.86), duration of cardioplegia delivery (percentage of cross-clamp time during which cardioplegia was delivered: 4:1, 13% ± 5%, and Mini, 15% ± 4%; p = 0.19), and mean duration of ischemia (4:1, 13.6 ± 2.3 minutes, and Mini, 13.3 ± 2.5 minutes; p = 0.71; range, 6 to 19 minutes). Total volume of crystalloid cardioplegia was significantly lower in the Mini group compared with the 4:1 group (14 ± 3 mL versus 380 ± 60 mL; p < 0.0001).

Hemoglobin Concentration and Oxygen Content of Cardioplegia
Mean hemoglobin concentration and oxygen content of cardioplegic solution were significantly greater in the Mini group than in the 4:1 group (hemoglobin, 7.5 ± 0.3 g/dL versus 6.1 ± 0.2 g/dL [p = 0.001]; oxygen content, 11.7 ± 0.4 mL/dL versus 8.3 ± 0.3 mL/dL [p = 0.001]).

Myocardial Oxygen and Lactate Metabolism
Myocardial oxygen and lactate metabolism during the first and the last cardioplegic infusions are depicted in Fig 1. There was no significant difference in the timing of the blood sample for the last cardioplegic infusion (4:1 group, 51 ± 4 minutes of cross-clamping, and Mini group, 53 ± 3 minutes of cross-clamping; p = 0.64). Myocardial oxygen consumption was significantly greater in the Mini group than in the 4:1 group during the first and last cardioplegic infusions. Although lactate release did not differ between the groups during the first cardioplegic infusion, it was significantly (p = 0.04) greater in the 4:1 group than in the Mini group during the last infusion.

View larger version (29K): [in this window] [in a new window]   Myocardial oxygen consumption (MVO2) and lactate release (LR) during first (1st dose) and last cardioplegia infusions (Last dose). Myocardial oxygen consumption was significantly greater in the minimal dilution group (MINI) than in the standard dilution group (4:1) during these two infusions. Lactate release was significantly greater in the standard dilution group than in the minimal dilution group during the last infusion.

View larger version (29K): [in this window] [in a new window]   Myocardial oxygen extraction (O2Ex) and lactate extraction (LEx) before and after cross-clamping. No significant differences were found in O2Ex between groups throughout reperfusion. The minimal dilution group (MINI) had more prompt resumption of LEx than the standard dilution group (4:1). (NS = not significant; off = immediately after cross-clamp release; pre = before application of cross-clamp; 5 min and 20 min = 5 minutes and 20 minutes, respectively, after cross-clamp release.)

View larger version (20K): [in this window] [in a new window]   Release of myocardial-specific isoenzyme of creatine kinase (CK-MB) and thiobarbituric acid–reactive substances (TBARS). Release of both markers was significantly greater in the standard dilution group (4:1) than in the minimal dilution group (MINI) immediately after cross-clamp release. Other abbreviations are the same as in Fig 2.

View larger version (15K): [in this window] [in a new window]   Relation between left ventricular stroke work index (LVSWI) and pulmonary capillary wedge pressure (PCWP) before cardiopulmonary bypass (pre) and 6 hours and 12 hours after cardiopulmonary bypass. The minimal dilution group (MINI) had a greater LVSWI than the standard dilution group (4:1) 6 and 12 hours after cardiopulmonary bypass despite similar filling pressure (PCWP).

	Comment

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Continuous warm blood cardioplegia recently has been proposed as an alternative strategy for myocardial protection [1][2][3][4]. The technique offers the possibility of enhanced resuscitation of the ischemic myocardium and reduction of the morbidity and mortality of coronary bypass operations [1][2][3][4]. However, in clinical practice, continuous infusion of warm blood cardioplegia must be discontinued to permit adequate visualization during the construction of the distal anastomoses. Experimental and clinical studies [1][14][15][16] have demonstrated that antegrade warm blood cardioplegia can be interrupted safely for up to 15 minutes. In contrast, Landymore and colleagues [6] showed that oxygen debt and lactate production were significantly greater during interruption of warm blood cardioplegia compared with interruption of cold blood cardioplegia. Matsuura and associates [5] also have demonstrated that a 7-minute interruption of retrograde warm blood cardioplegia resulted in more tissue acidosis and a decrease in left ventricular function. Therefore, the safe duration of cardioplegia interruptions is still controversial under normothermic (35° to 37°C) conditions. To avoid the problem, tepid (29°C) blood cardioplegia was introduced recently, and its superior effects on myocardial protection compared with those of warm blood cardioplegia have been reported [8][9]. Reducing the heart temperature from 37° to 29°C may provide a buffer against ischemic injury when delivery of cardioplegia is interrupted or nonhomogeneous.

In regard to the composition of the cardioplegic solution, minimally diluted blood with concentrated arresting agents has been proposed as an alternative technique to the standard 4:1 dilution [10][11]. In a previous study [17], blood cardioplegia was reported to provide superior myocardial protection than crystalloid cardioplegia by enhanced red blood cell–mediated oxygen delivery to the myocytes. Yau and colleagues [4] also have demonstrated that myocardial oxygen utilization during normothermic antegrade cardioplegia was improved by a revision of the ratio of blood to crystalloid component from 2:1 to 4:1. Therefore, further reduction in the crystalloid component of blood cardioplegia may theoretically optimize the aerobic environment during cardioplegic arrest through an increase in oxygen supply.

In the present study, we demonstrated that minimally diluted blood cardioplegia increased both the oxygen content of the cardioplegic solution and the oxygen consumption during cardioplegia compared with standard 4:1 diluted cardioplegia. The results may be attributed directly to the increase in hemoglobin concentration by the minimal dilution technique. The technique also reduced lactate release during cardioplegia followed by more prompt resumption of lactate extraction during reperfusion compared with the standard dilution technique. Our results suggest that the minimal dilution technique reduces anaerobic myocardial metabolism and preserves myocardial metabolic activity through the increase in oxygen supply during cardioplegic arrest. Thus, the theoretic advantages of the minimal dilution technique over the standard 4:1 dilution technique in regard to myocardial aerobic metabolism are confirmed by our results.

Although a significant washout of lactate was observed immediately after cross-clamp removal in both groups (4:1, 0.71 ± 0.20 mmol/L, and Mini, 0.66 ± 0.49 mmol/L), the levels were virtually identical to those (0.69 ± 0.16 mmol/L) in our previous study [8] in which 4:1 diluted tepid blood cardioplegia was given in a relatively continuous manner (56% of cross-clamp time during which cardioplegia was delivered). In the present study, minimally diluted blood cardioplegia was delivered during 15% of cross-clamp time, and the mean interval of infusion was 13.3 minutes. Therefore, it appears that antegrade minimally diluted tepid blood cardioplegia can be safely interrupted for up to 13 minutes followed by a prompt recovery of myocardial lactate utilization. Although left ventricular function (LVSWI) was depressed similarly in both groups 1 hour after CPB, the recovery was significantly more prompt in the Mini group than in the 4:1 group. Previous studies [17][18] have suggested that enhanced red blood cell–mediated oxygen delivery during cardioplegic arrest provides a superior protective effect on cardiac function; hence, the increase in oxygen supply by the minimal dilution technique may have contributed to the preserved left ventricular function in the present study. However, because the left ventricular end-systolic volume was not evaluated in this study, the differences in LVSWI between the two groups could be explained by a difference in left ventricular end-diastolic compliance.

Although resumption of coronary flow to ischemic myocardium plays a central role in myocardial protection, it has been reported to be associated with a paradoxical extension of ischemic damage, the so-called ischemia-reperfusion injury [19][20][21][22]. Many studies [19][20][22] have demonstrated that free radicals and lipid peroxidation may play an important role in the pathophysiology of this injury. Weisel and colleagues [20] showed a significant release of myocardial conjugated dienes (chemical signatures of oxygen free-radical lipid peroxidation) 3 minutes after reperfusion and a delayed recovery of myocardial metabolism in patients receiving cold blood cardioplegia. Lazzarino and co-workers [22] also demonstrated that myocardial lipid peroxidation, estimated as malondialdehyde production, was commonly observed during and after cold blood cardioplegic arrest. Lapenna and associates [23], however, suggested that cold blood cardioplegia provided a lower oxidant burden mediated by the antioxidant capacity of the blood component, such as erythrocytes and specific plasma molecules, than cold crystalloid cardioplegia. Moreover, this phenomenon was reported to be enhanced by normothermic conditions in comparison with hypothermic conditions [13]. In the present study, a marked release of myocardial TBARS (as a marker of lipid peroxidation) was observed in the 4:1 group immediately after reperfusion, whereas the levels were quite constant in the mini group throughout the reperfusion period, a finding suggesting a reduction in lipid peroxidation by the minimal dilution technique. As previous studies [23][24] have suggested that the blood component may work as a free radical scavenger, the increase in the blood component by the minimal dilution technique may partly explain the decrease in lipid peroxidation. Radical-mediated lipid peroxidation also has been reported to alter fluidity and permeability of biomembranes [25]. Thus, the lower values of CK-MB release immediately after reperfusion in the Mini group can potentially be explained by the decrease in lipid peroxidation. However, antioxidant effects of erythrocytes and specific plasma molecules were not investigated in detail in this study; moreover, the specificity of TBARS as a marker of lipid peroxidation has been reported to be controversial [22]. Therefore, further studies are required for firm conclusions regarding the inhibitory effect of minimally diluted blood cardioplegia on reperfusion injury.

This study was designed to evaluate the myocardial metabolic and ventricular functional response to different cardioplegia techniques. In low-risk patients, no differences in clinical outcomes were anticipated, and none were found. Because there were differences in the metabolic and hemodynamic response, we plan to perform a prospective, randomized trial in high-risk patients.

In conclusion, during intermittent antegrade cardioplegia, minimally diluted tepid blood cardioplegia increased oxygen consumption and decreased lactate release followed by prompt recovery of lactate utilization during reperfusion. The technique also provided better postoperative left ventricular function compared with the standard 4:1 dilution technique. The results suggest that the minimal dilution technique may provide superior myocardial protection than the standard 4:1 dilution technique by optimizing the aerobic environment through an increase in oxygen supply during intermittent antegrade tepid blood cardioplegia.

	Acknowledgments

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
This work was supported by the Scientific Research Fund of the Ministry of Education, Japan (grant A-08771046).

	References

Top Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Lichtenstein SV, Ashe KA, El Dalati H, Cushimano RJ, Panos A, Slutsky AS Warm heart surgery. J Thorac Cardiovasc Surg 1991;101:269-274.[Abstract]
2. The Warm Heart Investigators. Randomized trial of normothermic versus hypothermic coronary bypass surgery. Lancet 1994;343:559-563.[Medline]
3. Yau TM, Ikonomidis JS, Weisel RD, et al. Ventricular function after normothermic versus hypothermic cardioplegia. J Thorac Cardiovasc Surg 1993;105:833-844.[Abstract]
4. Yau TM, Weisel RD, Mickel DAG, et al. Optimal delivery of blood cardioplegia. Circulation 1991;84(Suppl 3):380-388.
5. Matsuura H, Lazar HL, Yang XM, River S, Treanor PR, Shemin RJ Detrimental effects of interrupting warm blood cardioplegia during coronary revascularization. J Thorac Cardiovasc Surg 1993;106:357-361.[Abstract]
6. Landymore RW, Marble AE, Eng P, MacAulay MA, Fris J Myocardial oxygen consumption and lactate production during antegrade warm blood cardioplegia. Eur J Cardiothorac Surg 1992;6:372-376.[Abstract/Free Full Text]
7. Hayashida N, Ikonomidis JS, Weisel RD, et al. Adequate distribution of warm cardioplegic solution. J Thorac Cardiovasc Surg 1995;110:800-812.[Abstract/Free Full Text]
8. Hayashida N, Ikonomidis JS, Weisel RD, et al. The optimal cardioplegic temperature. Ann Thorac Surg 1994;58:961-971.[Abstract/Free Full Text]
9. Hayashida N, Weisel RD, Shirai T, et al. Tepid antegrade and retrograde cardioplegia. Ann Thorac Surg 1995;59:723-729.[Abstract/Free Full Text]
10. Menasché P, Fleury J-P, Veyssié L, et al. Limitation of vasodilation associated with warm heart operation by a "mini-cardioplegia" delivery technique. Ann Thorac Surg 1993;56:1148-1153.[Abstract/Free Full Text]
11. Menasché P Blood cardioplegia: do we still need to dilute? [Editorial]. Ann Thorac Surg 1996;62:957-960.[Free Full Text]
12. Calafiore AM, Teodori G, Mezzetti A, et al. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg 1995;59:398-402.[Abstract/Free Full Text]
13. Mezzetti A, Calafiore AM, Lapenna D, et al. Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium. J Thorac Cardiovasc Surg 1995;109:787-795.[Abstract/Free Full Text]
14. Isomura T, Hisatomi K, Sato T, Hayashida N, Ohishi K Interrupted warm blood cardioplegia for coronary artery bypass grafting. Eur J Cardiothorac Surg 1995;9:133-138.[Abstract/Free Full Text]
15. Landymore RW, Marble AE, Fris J Effect of intermittent delivery of warm blood cardioplegia on myocardial recovery. Ann Thorac Surg 1994;57:1267-1272.[Abstract/Free Full Text]
16. Torracca L, Pasini E, Curello S, et al. Continuous versus intermittent warm blood cardioplegia: functional and energetics changes. Ann Thorac Surg 1996;62:1172-1179.[Abstract/Free Full Text]
17. Bing OHL, RaLaia PJ, Stoughton F, Weintraub RM Mechanism of myocardial protection during blood-potassium cardioplegia: a comparison of crystalloid red cell and methemoglobin solutions. Circulation 1984;70(Suppl 1):84-89.
18. Fremes SE, Christakis GT, Weisel RD, et al. A clinical trial of blood and crystalloid cardioplegia. J Thorac Cardiovasc Surg 1984;88:726-741.[Abstract]
19. Menasché P, Piwnica A Free radicals and myocardial protection: a surgical viewpoint. Ann Thorac Surg 1989;47:939-945.[Abstract/Free Full Text]
20. Weisel RD, Mickle DAG, Finkle CD, et al. Myocardial free-radical injury after cardioplegia. Circulation 1989;80(Suppl 3):14-18.
21. Ferrari R, Algieri O, Curello S, et al. Occurrence of oxidative stress during reperfusion of the human heart. Circulation 1990;81:201-211.[Abstract/Free Full Text]
22. Lazzarino G, Raatikainen P, Nuutinen M, et al. Myocardial release of malondialdehyde and purine compounds during coronary bypass surgery. Circulation 1994;90:291-297.[Abstract/Free Full Text]
23. Lapenna D, Mezzetti A, de Gioia S, et al. Blood cardioplegia reduces oxidant burden in the ischemic and reperfused human myocardium. Ann Thorac Surg 1994;57:1522-1525.[Abstract/Free Full Text]
24. Brown JM, Grosso MA, Terada LS, et al. Erythrocytes decrease myocardial hydrogen peroxide levels and reperfusion injury. Am J Physiol 1989;256:H584-H588.[Medline]
25. Freeman BA, Crapo JD Biology of disease. Free radicals and tissue injury. Lab Invest 1982;47:412-426.[Medline]

This article has been cited by other articles:

				C. Rosu, M. Laflamme, C. Perrault-Hebert, M. Carrier, and L. P. Perrault Decreased incidence of low output syndrome with a switch from tepid to cold continuous minimally diluted blood cardioplegia in isolated coronary artery bypass grafting Interact CardioVasc Thorac Surg, October 1, 2012; 15(4): 655 - 660. [Abstract] [Full Text] [PDF]

				V. A. Ferraris, J. R. Brown, G. J. Despotis, J. W. Hammon, T. B. Reece, S. P. Saha, H. K. Song, E. R. Clough, L. J. Shore-Lesserson, L. T. Goodnough, et al. 2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines Ann. Thorac. Surg., March 1, 2011; 91(3): 944 - 982. [Abstract] [Full Text] [PDF]

				T. B. Albacker, R. Chaturvedi, A. H. Al Kindi, H. Al-Habib, T. Al-Atassi, B. de Varennes, and K. Lachapelle The effect of using microplegia on perioperative morbidity and mortality in elderly patients undergoing cardiac surgery Interact CardioVasc Thorac Surg, July 1, 2009; 9(1): 56 - 60. [Abstract] [Full Text] [PDF]

				R. M. Mentzer Jr, M. S. Jahania, and R. D. Lasley Myocardial Protection , January 1, 2008; 3(2008): 443 - 464. [Full Text]

				T. E. Tan, S. Ahmed, and H. S. Paterson Intermittent Tepid Blood Cardioplegia Improves Clinical Outcome Asian Cardiovascular and Thoracic Annals, June 1, 2003; 11(2): 116 - 121. [Abstract] [Full Text] [PDF]

				T. Isomura, H. Suma, A. Yamaguchi, T. Kobashi, and A. Yuda Left ventricular restoration for ischemic cardiomyopathy - comparison of presence and absence of mitral valve procedure Eur J Cardiothorac Surg, April 1, 2003; 23(4): 614 - 619. [Abstract] [Full Text] [PDF]

				R. M. Mentzer Jr., M. S. Jahania, and R. D. Lasley Myocardial Protection , January 1, 2003; 2(2003): 413 - 438. [Full Text]

				H. J. Penttila, M. V.K. Lepojarvi, K. T. Kiviluoma, P. K. Kaukoranta, I. E. Hassinen, and K. J. Peuhkurinen Myocardial preservation during coronary surgery with and without cardiopulmonary bypass Ann. Thorac. Surg., February 1, 2001; 71(2): 565 - 570. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Nobuhiko Hayashida Tadashi Isomura Shigeaki Aoyagi Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hayashida, N. Articles by Aoyagi, S. Search for Related Content PubMed PubMed Citation Articles by Hayashida, N. Articles by Aoyagi, S.