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

This Article Abstract 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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alhan, H. C. Articles by Yigiter, B. Search for Related Content PubMed PubMed Citation Articles by Alhan, H. C. Articles by Yigiter, B.

Ann Thorac Surg 1996;61:834-839
© 1996 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

Intermittent Aortic Cross-Clamping and Cold Crystalloid Cardioplegia for Low-Risk Coronary Patients

H. Cem Alhan, MD, Hasan Karabulut, MD, Remzi Tosun, MD, Fehime Karakoç, MD, mer Okar, MD, Erdoan Demiray, MD, Sümer Tarcan, MD, Besim Yiiter, MD

Siyami Ersek Thoracic and Cardiovascular Surgery Center and Department of Histology and Embryology, University of Marmara, Istanbul, Turkey

Accepted for publication November 2, 1995.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Background. Blood cardioplegic strategies have been shown to increase myocardial oxygen uptake, replenish depleted energy stores, and improve myocardial function and survival in the high-risk subset of patients. However, the superiority of these techniques over intermittent aortic cross-clamping and crystalloid cardioplegia in low-risk patients is still controversial.

Methods. This study consisted of two parts. In the first part, we assessed the results of a recent cohort of 399 consecutive low-risk patients undergoing their first coronary artery bypass grafting between 1993 and 1995 using cold crystalloid cardioplegia (n = 128) and intermittent aortic cross-clamping (n = 271). In the second part of the study, 40 consecutive low-risk patients undergoing elective first-time coronary artery bypass grafting were randomly divided into two equal groups. One group received cold crystalloid cardioplegia and the other group had myocardial management with intermittent aortic cross-clamping. The two groups were compared with respect to hemodynamic, biochemical, and ultrastructural changes.

Results. The overall mortality rate, the perioperative myocardial infarction rate, the need for intraaortic balloon pumps, and the need for inotropic agents were 0.25%, 1.5%, 1%, and 5.8%, respectively. No significant differences were observed between the groups with respect to these clinically defined end points.

Conclusions. Both intermittent aortic cross-clamping and cold crystalloid cardioplegia techniques may be used safely in low-risk patients undergoing first-time coronary artery bypass grafting.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Since the introduction of the cardioplegic principle by Melrose and associates [1] in 1955, numerous different cardioplegic solutions and methods of myocardial protection have been advocated [2]. However, a substantial minority of cardiac surgeons still use intermittent aortic cross-clamping (IAC) for myocardial protection during coronary artery bypass grafting (CABG), mainly because of the versatility and greater intraoperative flexibility offered by this technique [3–5]. On the other hand, cold crystalloid cardioplegia (CC), used extensively in the past, may still have a place for myocardial protection [6, 7].

For many years, cold CC and IAC techniques have been the standard methods of myocardial preservation during coronary revascularization at our institution. Because the risk profile of patients undergoing open heart operations has changed in recent years (ie, increased age, poor left ventricular function, increased numbers of emergency operations), we deviated from these techniques to antegrade plus retrograde intermittent cold blood cardioplegia with warm induction and terminal warm reperfusion in this subgroup of patients. However, this complex and expensive procedure seemed to us to be unnecessary in elective low-risk patients, and we wanted to determine whether a change was really necessary in our method of myocardial protection in low-risk patients. For this reason, we reviewed the results of CABG operations in terms of mortality and morbidity and also performed a prospective, randomized study in low-risk elective CABG operations to evaluate hemodynamic, biochemical, and ultrastructural changes that occur in human hearts after the ischemic period using CC or after application of the IAC procedure.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Charts of patients undergoing first-time, elective CABG at the Siyami Ersek Thoracic and Cardiovascular Surgery Center by three surgeons between January 1993 and January 1995 were reviewed retrospectively. Patient variables, procedures, and outcomes were recorded. The Parsonnet risk stratification scoring system was used to determine the approximate risk of death for each patient [8]. Patients were excluded from the study if they had an expected mortality rate of 5 or higher (other than low-risk patients), if they were undergoing reoperative CABG, or if they were having procedures in addition to CABG. An additional 40 consecutive patients meeting the same criteria were randomized into two groups. One group received crystalloid cardioplegia (CC group, n = 20) for myocardial protection, and in the second group, myocardial management was with intermittent aortic cross-clamping (IAC group, n = 20). Unless there was a contraindication, all patients received ß blockers, calcium antagonists, and nitrates until the date of the operation. The study was approved by the institutional review board, and all patients gave informed consent.

Operative Procedure
After induction of anesthesia, the patients were intubated, and hemodynamic monitoring lines including a flow-directed thermodilution catheter were established. After internal thoracic artery and long saphenous veins were harvested and heparin was administered, the patients were placed on cardiopulmonary bypass (CPB) using aortic and two-stage venous cannulation. Centrifugal pumps and membrane oxygenators were used in all operations. Patients in the CC group received crystalloid cardioplegia antegrade through the aortic root for the induction of cardioplegia. St. Thomas' Hospital II cardioplegic solution was used (Plegisol [Abbott Laboratories, North Chicago, IL]; K⁺, 16 mEq/L; pH 7.8). Ten mililiters per kilogram of this cardioplegic solution at 4°C was administered as soon as the cross-clamp was applied. Moderate systemic hypothermia (32°C) and topical cold saline solution were also used. The heart was vented through the aortic root. After each distal anastomosis was completed, 100 mL of the solution was given through the saphenous vein graft to check the graft patency and to perfuse the myocardium distal to the occlusion. Systemic rewarming was initiated during the final distal anastomosis, which usually involved the internal thoracic artery to left anterior descending artery. After completion of the distal anastomoses, we removed the cross-clamp and made the proximal anastomoses.

In the IAC group, moderate systemic hypothermia (32°C) was used. Ventricular fibrillation was induced electrically and the aorta was cross-clamped. The heart was vented through the main pulmonary artery. Each distal anastomosis was constructed during a single period of aortic occlusion. At completion of the coronary anastomosis, the aortic cross-clamp was released and the heart was allowed to beat while the corresponding aortic anastomosis was constructed. Systemic rewarming was started during the final distal anastomosis.

The patients were weaned from CPB when the rectal temperature reached 37°C.

Definitions
Elective operation was defined as that performed on a stable patient 72 hours after cardiac catheterization. Inotropic support was defined as any inotropic infusion other than digoxin or calcium. Inotropic support was used in patients with unstable hemodynamic indices, and intraaortic balloon counterpulsation was used in patients who required increasing doses or more than two inotropic agents. Perioperative myocardial infarctions were diagnosed if the creatine kinase myocardial isoenzyme level was greater than 60 IU or electrocardiographic changes appeared, including new Q waves or loss of R waves (more than 25% reduction in at least two contiguous leads). Mortality includes all patients who died within 30 days of operation or during the same hospitalization.

Hemodynamic Measurements and Sample Collection
A flow-directed thermodilution catheter was introduced through the internal jugular vein of each patient using the Seldinger technique after induction of anesthesia. Cardiac output was measured in triplicate. Right atrial pressure, mean arterial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure were also recorded. These variables were measured before incision, 10 and 15 minutes after the termination of CPB, and at postoperative hours 1, 6, 12, and 24 in both groups. Cardiac index, systemic and pulmonary vascular resistance, and left and right ventricular stroke work indexes were calculated according to standard formulas.

A retrograde cardioplegia cannula (Retroplegia; Research Medical Inc, Salt Lake City, UT) was inserted to the coronary sinus using a closed right atrial technique. Blood samples were taken from the aorta and coronary sinus simultaneously before CPB and 5, 10, 15, and 20 minutes after the termination of CPB for measurement of myocardial lactate extraction. Enzyme assay was done every 6 hours for the first 36 hours postoperatively by determination of creatine kinase myocardial isoenzyme in the plasma.

Ultrastructural Study
Three transmural myocardial tissue samples were taken from all 40 patients included in the study. The first biopsy specimens were obtained just before application of the aortic cross-clamp and constituted the control samples. The second biopsy specimens were taken just before release of the aortic cross-clamp (after the completion of the last distal anastomosis for the IAC group), and the third samples were gathered 25 minutes after release of the aortic cross-clamp. All samples were obtained from the interventricular septum with 14-gauge Tru-cut biopsy needles (Travenol Laboratories, Deerfield, IL) and were fixed with 4% phosphate-buffered glutaraldehyde solution. After fixation, the tissue samples were rinsed separately in Sorenson's phosphate buffer and postfixed in a 1% osmium tetroxide solution for 1 hour. Postfixation was followed by dehydration in graded ethanol. The specimens were blocked in Epon 812. Sections were contrast-stained with lead citrate and uranyl acetate.

The ultrastructural analysis was done with transmission electron microscopy (Jeol TEM 1200 EX II; Tokyo, Japan). The person doing the electron microscopic study was blinded as to the group of each patient. All tissue samples were graded on the variables listed in Table 1. With this grading, a total score was obtained for every tissue sample. In this scoring system [9], the minimum obtainable score was 0 and the maximum obtainable score was 25. The scores were then classified as follows: 0 to 5 = negligible ultrastructural changes; 6 to 15 = noticeable but reversible ultrastructural changes; 16 to 25 = irreversible ultrastructural changes.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Patient variables for the retrospective and prospective study groups are summarized in Tables 2 and 3, respectively. From a total of 657 CABG operations performed by three surgeons during the 2-year interval, 439 (66.8%) were found to be low-risk operations with predicted and observed mortality rates of 3.4% and 0.23%, respectively. The only death observed in the IAC group resulted from a massive intracerebral hemorrhage on the third postoperative day in a patient with severe hypertension who was sent to the ward after an unremarkable stay in the intensive care unit. Various myocardial protection methods including IAC, antegrade plus retrograde intermittent cold blood cardioplegia with warm induction and terminal warm reperfusion, and beating heart (with or without CPB) were used in the remaining higher-risk patients, who were excluded from the study. No patient in the high-risk group was operated on with CC. In these patients, the mean predicted and observed mortality rates were 11.2% and 3.67% (8 of 218), respectively.

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Blood cardioplegic strategies have been shown to increase myocardial oxygen uptake, replenish depleted energy stores, and improve myocardial function and survival in high-risk patients (ie, those with cardiogenic shock, extending myocardial infarction, and hemodynamic instability) undergoing cardiac operations [10]. However, the superiority of blood cardioplegic techniques over IAC and CC in low-risk patients is still controversial [6, 11, 12]. Using hemodynamic data only, it may be difficult to demonstrate a difference with any of these techniques in low-risk patients. As Chiu [13] mentioned, it is more relevant to use clinical end points including morbidity, mortality, and cost to determine the efficacy of myocardial preservation.

In this study, we reviewed our recent experience with cold CC and IAC in low-risk patients. The overall mortality rate seen in these groups of patients was 0.25%. In terms of postoperative complications, the perioperative myocardial infarction rate was 1.5%. The incidence of low cardiac output may be judged by the rates of use of inotropic agents and intraaortic balloon pumps. In this study, inotropic agents were used in 5.8% and intraaortic balloon pumps were used in 1% of patients. These results compare favorably with other published series using IAC and CC [4, 5, 14]. Bonchek and Burlingame [4] reported their experience with 500 patients operated on for coronary artery disease with IAC. They reported low mortality (1%) and morbidity rates, including patients with severe left ventricular dysfunction. All of the operative deaths occurred in high-risk patients. In 229 consecutive patients operated on with IAC, Antunes and associates [14] reported a mortality rate of 0.9% and a perioperative myocardial infarction rate of 1.7%; again, all operative deaths involved high-risk patients. In a recent randomized comparative study [5] using creatine kinase myocardial isoenzyme isoforms and troponin T assays, IAC was shown to be as effective as (or even superior to) blood cardioplegia for elective CABG as a strategy to manage the myocardium. In addition, blood cardioplegia with warm reperfusion enriched with aspartate-glutamate solution could not be found superior to IAC for patients having elective operations [11].

On the other hand, in a recent report Hendry and colleagues [6] showed that cold CC may be administered at a very low cost with comparable mortality rates (0%), morbidity, and intensive care unit and hospital stays in patients undergoing elective CABG.

Loop and associates [12] have shown that, when compared with cold CC, antegrade plus retrograde blood cardioplegia combined with substrate-enriched warm reperfusion failed to improve mortality rates, but reduced the rates of stroke and wound infection and the length of hospital stay, yielding a decrease in hospital costs in low-risk patients. However, in this study we observed very low mortality and morbidity rates with an acceptable length of hospital stay that compare favorably with the results obtained by Loop and associates in low-risk patients. The different methods of myocardial protection show their benefits and advantages, especially in patients with severe left ventricular dysfunction. We share the idea that blood cardioplegic techniques, particularly antegrade plus retrograde cardioplegia, seem useful in high-risk patients.

Indeed, both IAC and CC have been shown to be safe and effective ways of managing the myocardium during CABG also in high-risk patients [15], and the results obtained in these series compare favorably with other published series using antegrade plus retrograde blood cardioplegia [16]. Recently, a randomized prospective clinical study comparing IAC and blood cardioplegia with normothermic substrate-enhanced reperfusion, performed in patients during acute myocardial infarction, also failed to find any statistically significant difference between the methods [17].

Clinical studies comparing cold CC with IAC failed to show any differences in the immediate postoperative period [15]. Cardiac troponin T release was also found to be similar after CC and IAC [18]. By comparing hemodynamic, biochemical, and ultrastructural changes and clinically defined end points, we also obtained similar results with the use of these techniques.

In this study, we did not intend to compare the blood cardioplegia technique with IAC and cold CC in low-risk patients, because we reserve blood cardioplegia for high-risk patients and for those undergoing reoperative CABG or additional procedures.

Another instance in which blood cardioplegia is considered for CABG in our practice is a severely calcified aorta. Repeated application of a partial occlusion clamp on such aortas can cause focal aortic injury and embolization. The use of CC with a single period of aortic cross-clamping unnecessarily extends the ischemic time, as anastomosis in such an aorta is time consuming. In such a situation, we do not hesitate to use antegrade plus retrograde blood cardioplegia, with all proximal and distal anastomoses done during a single period of aortic cross-clamping. This approach was used in 3 patients (1 in the IAC and 2 in the CC group) during this study.

Although there has been a trend in recent years toward fewer elective and more urgent operations, increasing age, and a decreasing ejection fraction in patients undergoing isolated CABG [19], a great majority of these patients are still in the low-risk group. The Society of Thoracic Surgeons National Database Status Report [20] stated that in 1992, more than 60% of the patients undergoing CABG were in the low-risk (0% to 5%) group. This figure points out the importance of reducing costs in low-risk patients.

Comparing the costs, the delivery system for CC is simple and inexpensive, whereas tubing for cold and warm blood increases the cost of each case by approximately $250. A considerable expense is incurred with the use of these delivery systems (ie, $250,000 per 1,000 cases per year). With similar mortality and morbidity rates and hospital stays between the techniques, this cost may be difficult to justify in the current climate of medical economic constraints.

The current study shows that in elective first-time CABG operations when overall ventricular function is good, CC and IAC techniques afford good myocardial protection, provide a quiet and bloodless operative field, and can be performed with very low mortality and morbidity rates and an acceptable length of hospital stay.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Address reprint requests to Dr Alhan, Acibadem, Sebboylu Sok, 2/8, Kadikoy, Istanbul, Turkey 81010.

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 

1. Melrose DG, Dreyer B, Bentall HH, Baker JBE. Elective cardiac arrest. Preliminary communication. Lancet 1955;2:21–2.[Medline]
2. Buckberg GD, Beyersdorf F, Allen BS, Robertson JM. Integrated myocardial management: background and initial application. J Cardiac Surg 1995;10:68–89.[Medline]
3. Akins CW. Noncardioplegic myocardial preservation for coronary revascularization. J Thorac Cardiovasc Surg 1984;88:174–81.[Abstract]
4. Bonchek LI, Burlingame MW. Coronary artery bypass without cardioplegia. J Thorac Cardiovasc Surg 1987;93:261–7.[Abstract]
5. Anderson JR, Hossein-Nia M, Kallis P, et al. Comparison of two strategies for myocardial management during coronary artery operations. Ann Thorac Surg 1994;58:768–73.[Abstract]
6. Hendry PJ, Masters RG, Haspect A. Is there a place for cold crystalloid cardioplegia in the 1990s? Ann Thorac Surg 1994;58:1690–4.[Abstract]
7. Robinson LA, Schwarz GD, Goddard DB, Fleming WH, Galbraith TA. Myocardial protection for acquired heart disease surgery: results of a national survey. Ann Thorac Surg 1995;59:361–72.[Abstract/Free Full Text]
8. Parsonnet V, Dean D, Bernstein AD. A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation 1987;79(Suppl 1): 3–12.[Medline]
9. Tademir O, Katircioglu SF, Küçükaksu DS, et al. Warm blood cardioplegia: ultrastructural and hemodynamic study. Ann Thorac Surg 1993;56:305–11.[Abstract]
10. Rosenkranz ER, Okamoto F, Buckberg GD, Robertson JM, Vinten-Johansen J, Bugyi HI. Safety of prolonged aortic clamping with blood cardioplegia. III. Aspartate enrichment of glutamate-blood cardioplegia in energy depleted hearts after ischemic and reperfusion injury. J Thorac Cardiovasc Surg 1986;91:428–35.[Abstract]
11. Gerola LR, Oliveira SA, Moreira LFP, et al. Blood cardioplegia with warm reperfusion versus intermittent aortic crossclamping in myocardial revascularization. J Thorac Cardiovasc Surg 1993;106:491–6.[Abstract]
12. Loop FD, Higgins TL, Panda R, Pearce G, Estafanous FG. Myocardial protection during cardiac operations. J Thorac Cardiovasc Surg 1992;104:608–18.[Abstract]
13. Chiu RC-J. Cardioplegia: from bedside to the laboratory and back again. Ann Thorac Surg 1991;52:1209–10.[Medline]
14. Antunes MJ, Bernardo JE, Oliveira JM, Fernandes LE, Andrade CM. Coronary artery bypass surgery with intermittent aortic cross-clamping. Eur J Cardiothorac Surg 1992;6: 189–94.[Abstract]
15. Elefteriades JA, Tolis G Jr, Levi E, Mills LK, Zaret BL. Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state. J Am Coll Cardiol 1993;22:1411–7.[Abstract]
16. Paolini G, Lucignani G, Zuccari M, et al. Identification and revascularization of hibernating myocardium in angina-free patients with left ventricular dysfunction. Eur J Cardiothorac Surg 1994;8:139–44.[Abstract]
17. Bonchek LI, Burlingame MW, Vazales BE, Ferdinand NJ. Coronary bypass with substrate-enhanced cardioplegia versus noncardioplegic technique for early revascularization in acute infarction. Eur J Cardiothorac Surg 1990;4:124–9.[Abstract]
18. Taggart DP, Bhusari S, Hopper J, et al. Intermittent ischaemic arrest and cardioplegia in coronary artery surgery: coming full circle? Br Heart J 1994;72:136–9.[Abstract/Free Full Text]
19. Disch DL, O'Connor GT, Birkmeyer JD, Olmstead EM, Levy DG, Plume SK. Changes in patients undergoing coronary artery bypass grafting: 1987–1990. Ann Thorac Surg 1994;57:416–23.[Abstract]
20. Clark RE. The Society of Thoracic Surgeons national database status report. Ann Thorac Surg 1994;57:20–6.[Abstract]

This article has been cited by other articles:

				M. Scarci, H. B. Fallouh, C. P. Young, and D. J. Chambers Does intermittent cross-clamp fibrillation provide equivalent myocardial protection compared to cardioplegia in patients undergoing bypass graft revascularisation? Interactive CardioVascular and Thoracic Surgery, November 1, 2009; 9(5): 872 - 878. [Abstract] [Full Text] [PDF]

				V. Venugopal, A. Ludman, D. M. Yellon, and D. J. Hausenloy 'Conditioning' the heart during surgery Eur. J. Cardiothorac. Surg., June 1, 2009; 35(6): 977 - 987. [Abstract] [Full Text] [PDF]

				J. Dunning, J. R.L. Waller, B. Smith, S. Pitts, S. W.H. Kendall, and K. Khan Coronary Artery Bypass Grafting is Associated With Excellent Long-Term Survival and Quality of Life: A Prospective Cohort Study Ann. Thorac. Surg., June 1, 2008; 85(6): 1988 - 1993. [Abstract] [Full Text] [PDF]

				P. K. Mishra Fibrillatory arrest technique: is it worth tasting the old wine in new bottle? Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 860 - 860. [Full Text] [PDF]

				M. Fujii, M. Avkiran, and D. J Chambers Experimental studies on myocardial protection with intermittent cross-clamp fibrillation: additive effect of the sodium-hydrogen exchanger inhibitor, cariporide Ann. Thorac. Surg., April 1, 2004; 77(4): 1398 - 1407. [Abstract] [Full Text] [PDF]

				J. Alex, V. P. Rao, A. R.J. Cale, S. C. Griffin, M. E. Cowen, and L. Guvendik Surgical nurse assistants in cardiac surgery: a UK trainee's perspective Eur. J. Cardiothorac. Surg., January 1, 2004; 25(1): 111 - 115. [Abstract] [Full Text] [PDF]

				L. Raco, E. Mills, and R. J.W. Millner Isolated myocardial revascularization with intermittent aortic cross-clamping: experience with 800 cases Ann. Thorac. Surg., May 1, 2002; 73(5): 1436 - 1439. [Abstract] [Full Text] [PDF]

				U. Sunderdiek, P. Feindt, and E. Gams Aortocoronary bypass grafting: a comparison of HTK cardioplegia vs. intermittent aortic cross-clamping Eur. J. Cardiothorac. Surg., October 1, 2000; 18(4): 393 - 399. [Abstract] [Full Text] [PDF]

				R. Bessho and D. J. Chambers Experimental study of intermittent crossclamping with fibrillation and myocardial protection: Reduced injury from shorter cumulative ischemia or intrinsic protective effect? J. Thorac. Cardiovasc. Surg., September 1, 2000; 120(3): 528 - 537. [Abstract] [Full Text] [PDF]

				A. Borowski, M.R. Raji, H.C. Eichstaedt, S. Schickendantz, and H. Korb Myocardial protection by pressure- and volume-controlled continuous hypothermic coronary perfusion in combination with Esmolol and nitroglycerine for correction of congenital heart defects in pediatric risk patients Eur. J. Cardiothorac. Surg., September 1, 1999; 14(3): 243 - 249. [Abstract] [Full Text] [PDF]

				A. S. Koppula, B. R. Jagannath, K. R. Balakrishnan, and C. M. Gupta Noncardioplegic Myocardial Protection for CABG Deserves a Second Look Ann. Thorac. Surg., March 1, 1997; 63(3): 914 - 915. [Full Text]

This Article Abstract 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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alhan, H. C. Articles by Yigiter, B. Search for Related Content PubMed PubMed Citation Articles by Alhan, H. C. Articles by Yigiter, B.