Ann Thorac Surg 1996;62:1039-1044
© 1996 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Does the Internal Thoracic Artery Graft Delay the Recovery of Myocardial Metabolism?
Vivek Rao, MD,
George T. Christakis, MD,
Richard D. Weisel, MD,
Rajdeep Grewal, BSc,
Joan Ivanov, MSc,
Gideon Cohen, MD,
Susan M. Carson, Aht,
Donald A. G. Mickle, MD
Division of Cardiovascular Surgery and Centre for Cardiovascular Research, The Toronto Hospital and the University of Toronto, Toronto, Ontario, Canada
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Abstract
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Background. The left internal thoracic artery (LITA) bypass graft to the left anterior descending artery has greater long-term patency than a saphenous vein graft. However, surgeons may be reluctant to use the LITA graft in some patients because they are unable to deliver cardioplegia to the left anterior descending artery territory.
Methods. We compared the myocardial levels of high-energy phosphates and their metabolites in patients who received an LITA graft with those in patients who received a saphenous vein graft to the left anterior descending artery territory during elective coronary artery bypass grafting. Right and left ventricular biopsy specimens were obtained at three times: before aortic cross-clamping, after cross-clamp removal, and after 10 minutes of reperfusion.
Results. No differences were found between the LITA graft group and the saphenous vein graft group in any right ventricular metabolites. There was an improvement in myocardial protection over time and a higher proportion of LITA graft patients in the late time period (early group, 63% versus late group, 80%; p < 0.01). Within each time period, there were no differences between the LITA and saphenous vein graft groups. Among patients receiving cold antegrade cardioplegia, the myocardial levels of high-energy phosphates were better preserved in those receiving an LITA graft.
Conclusions. Advances in myocardial protection have led to improved preservation of high-energy phosphate levels after cardioplegic arrest. In patients undergoing elective coronary artery bypass grafting, the use of an LITA graft does not adversely affect myocardial metabolism. Further investigations are required to determine the effects of the use of the LITA during urgent or emergent procedures.
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Introduction
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The long-term patency of the left internal thoracic artery (LITA) graft has been shown to be superior to that of the saphenous vein graft (SVG) when used to bypass the left anterior descending coronary artery (LAD) [1, 2]. Despite its proven effectiveness, however, there are relative contraindications to its use. Some surgeons are reluctant to use the LITA when the LAD territory is at risk for perioperative injury because of inadequate cardioplegic delivery. Patients who require emergency coronary artery bypass grafting because of an acute myocardial infarction or failed angioplasty of the LAD or those with hemodynamic compromise may have inadequate collaterals to permit cardioplegic protection.
However, the superior long-term patency of the LITA graft has prompted several investigators to employ it even in high-risk situations [3–5]. The perioperative morbidity reported for these studies has been remarkably low. The purpose of the present study was to determine if the use of the LITA graft to the LAD adversely affected myocardial metabolic recovery after cardioplegic arrest. We compared the myocardial levels of high-energy phosphates measured in right and left ventricular biopsy specimens obtained intraoperatively in patients who received SVGs to their LAD versus the levels in those who received LITA grafts. We have previously shown that a 50% improvement in the preservation of high-energy phosphate levels results in improved ventricular function after elective coronary artery bypass grafting [6, 7]. We hypothesized that the collateral coronary circulation in low-risk elective patients would permit adequate cardioplegic perfusion. If the LITA graft resulted in poorer preservation of the high-energy phosphate levels in patients undergoing elective procedures, then this metabolic impairment may result in poorer clinical outcomes in high-risk patients undergoing urgent revascularization.
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Methods
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Patient Population
Between January 1982 and December 1995, 335 patients scheduled to undergo isolated coronary artery bypass grafting performed by one surgeon agreed to participate in clinical trials comparing myocardial protective strategies. All patients signed a consent form approved by our institutional Human Experimentation Committee. Five patients subsequently underwent nonelective procedures and were eliminated from further analysis. Among the remaining 330 patients, those who received retrograde (n = 47) or normothermic (n = 45) cardioplegia were analyzed separately. The remaining 238 patients received antegrade cold blood or crystalloid cardioplegia and form the basis of this report.
Surgical Technique
The surgical technique and management of cardiopulmonary bypass employed have been described previously [6, 7]. After the institution of cardiopulmonary bypass, distal and proximal anastomoses were performed during a prolonged cross-clamp period [8]. The patients who received SVGs to their LAD (n = 72) were compared with those who received LITA grafts (n = 166). The LAD anastomosis was the first to be completed in the SVG group, whereas in the LITA graft group, the LAD anastomosis was performed last before construction of the proximal anastomoses. In patients who received an SVG to the LAD, cardioplegia was delivered directly into the vein graft after the distal anastomosis and into the aortic root and each completed vein graft after each proximal anastomosis. Patients who received SVGs were more likely to be female (p = 0.01) and were more likely to have single-vessel coronary artery disease (p < 0.01). There were no differences between groups in age, left ventricular function, or the presence of left main coronary artery disease (Table 1
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Table 2 shows the methods of myocardial protection employed. To examine differences stemming from an improved surgical technique over the study period, we compared patients who underwent operation between 1982 and 1988 (early group, n = 142) with those who underwent operation between 1989 and 1995 (late group, n = 96). The number of patients in the SVG and LITA graft groups for each time period is shown in Figure 1. There were no demographic differences between the LITA graft and SVG groups within each time period.
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Fig 1. . Type of conduit employed to bypass the left anterior descending artery. Patients in the late group (1989–1995) were more likely to receive a left internal thoracic artery (LITA) graft than patients in the early group (1982–1988). The number of patients in each group is shown above the bars. (SVG = saphenous vein graft).
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Adenine Nucleotides and Degradation Products
Transmural right and left ventricular biopsy specimens were obtained from all patients with a Tru-Cut biopsy needle (Travenol Laboratories, Deerfield, IL). Left ventricular biopsy specimens were taken from the territory of the LAD before aortic cross-clamping, immediately after cross-clamp removal, and after 10 minutes of reperfusion. The specimens were flash-frozen in liquid nitrogen and then freeze-dried. Specimens were analyzed by high-performance liquid chromatography using the modifications described by Weisel and associates [9] of the step-gradient technique developed by Hull-Ryde and colleagues [10]. Using this method, we determined the myocardial concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). We also measured the creatine phosphate level and the levels of the metabolites adenosine, inosine, hypoxanthine, and xanthine. High-energy phosphate levels were determined as the sum of the ATP and creatine phosphate levels. The levels of the total degradation products were calculated as the sum of the adenosine, inosine, hypoxanthine, and xanthine levels.
The energy charge (EC) represents the utilizable high-energy phosphate pool and was calculated as follows:
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Statistical Analysis
Statistical analysis was performed with the Statistical Analysis System programs (SAS Institute, Cary, NC). Categorical data are expressed as the absolute and percentage frequency. Continuous data are expressed as the mean ± standard error of mean, unless otherwise specified. A repeated-measures analysis of variance was employed to evaluate the biopsy findings between groups. Because changes in the myocardial levels of adenine nucleotides and their degradation products may be related to their initial baseline concentrations, we report the change in concentration, the change as a percentage of the baseline values, and the absolute levels of each metabolite. Student's t test was employed to compare the change in the concentrations of adenine nucleotides and their degradation products in each group.
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Results
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Clinical Outcomes
Table 2
displays the clinical outcomes for 238 of the study patients. Among all 330 patients, 6 (1.8%) died and 16 (4.8%) had development of low-output syndrome (ie, the requirement for postoperative intraaortic balloon pump or high-dose inotropic support in the intensive care unit to maintain a systolic blood pressure of more than 90 mm Hg and a cardiac index of more than 2.1 L • min-1 • m-2). There were no significant differences between groups in these clinical outcomes.
Early Versus Late Period
Figure 1 shows the type of conduit employed in each time period. There was a significant increase in arterial revascularization with time (p < 0.01). Advances in surgical technique and perioperative myocardial protection resulted in improved preservation of the ATP level, energy charge, and high-energy phosphate levels after cardioplegic arrest and reperfusion (Fig 2). Within each time period, there were no differences between the SVG and LITA graft groups.
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Fig 2. . Myocardial levels of high-energy phosphates before and after cardioplegic arrest. Patients in the late group (1989–1995) had improved preservation of high-energy phosphates compared with patients in the early group (1982–1988). (XCL = aortic cross-clamp).
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Adenine Nucleotides
We found no differences in the levels of any of the right ventricular metabolites between groups. In patients who received retrograde cardioplegia, there were no differences between groups. Patients in the LITA graft group had less of a decrease in the left ventricular ATP and high-energy phosphate levels after hypothermic cardioplegia (p < 0.05 versus SVG group), but there were no significant differences for the patients who received normothermic cardioplegia (Fig 3).
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Fig 3. . Hypothermic cardioplegia versus normothermic cardioplegia in preservation of adenosine triphosphate (ATP) and total high-energy phosphate (HEP) levels. Patients who received hypothermic cardioplegia and a left internal thoracic artery (LITA) graft had improved preservation of both ATP and HEP. (SVG = saphenous vein graft).
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Table 3 shows the absolute levels of myocardial ATP, ADP, and AMP and their metabolites adenosine, inosine, hypoxanthine, and xanthine for patients who received hypothermic, antegrade cardioplegia. Figure 4 shows the change in the ATP, ADP, and AMP concentrations after cardioplegic arrest. The myocardial ATP level was decreased in both groups at the time of cross-clamp removal (p < 0.001), but there were no differences between the groups (p = 0.0872). The myocardial levels of ADP and AMP had risen slightly (p < 0.05) at the time of cross-clamp removal, but there were no significant differences between the groups. Figure 5 shows the change in the myocardial levels of adenosine, inosine, hypoxanthine, and xanthine after cardioplegic arrest. There was a significant increase in the levels of each of these degradation products at this time (p < 0.05), but there were no differences between groups. Patients in the LITA graft group had lower levels of total degradation products at the time of cross-clamp removal and after 10 minutes of reperfusion (p < 0.05; Fig 6). Figure 7 shows the energy charge in both groups at all three time points. The energy charge was higher in the LITA graft group at the end of the cross-clamp period and also after 10 minutes of reperfusion (p < 0.05).
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Fig 4. . The change in adenine nucleotides after cardioplegic arrest. There was a significant drop in the adenosine triphosphate (ATP) level in both groups (p < 0.001 by paired t test), but there were no differences between groups. Myocardial levels of adenosine diphosphate (ADP) and adenosine monophosphate (AMP) rose slightly after cross-clamp removal (p < 0.05), with no differences between groups. (LITA = left internal thoracic artery; NS = not significant; SVG = saphenous vein graft).
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Fig 5. . The change in degradation products after cardioplegic arrest. The myocardial levels of all degradation products rose after cross-clamp removal (p < 0.05). There were no differences between groups. (ADO = adenosine; HXN = hypoxanthine; INO = inosine; LITA = left internal thoracic artery; NS = not significant; SVG = saphenous vein graft; XAN = xanthine).
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Fig 6. . The myocardial levels of total degradation products. Patients in the left internal thoracic artery (LITA) graft group had lower levels of total degradation products at cross-clamp removal and after 10 minutes of reperfusion (p < 0.05). (SVG = saphenous vein graft; XCL = aortic cross-clamp).
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Fig 7. . The myocardial energy charge (see text for definition) before and after cardioplegic arrest. Patients in the left internal thoracic artery (LITA) graft group had a higher energy charge at cross-clamp removal and after 10 minutes of reperfusion. (SVG = saphenous vein graft; XCL = aortic cross-clamp).
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Comment
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The LITA graft to the LAD has a better long-term patency and its use is associated with better patient survival than SVGs to the LAD [1, 2]. As a result, surgeons are now employing multiple arterial grafts for coronary artery bypass grafting [11–13].
Despite the proven benefits of an LITA graft, there are some concerns about its use in certain high-risk situations [14–17]. The inability to deliver cardioplegia through a completed vein graft may impair myocardial protection of the LAD territory and potentially augment the perioperative ischemic injury. In elective patients, inadequate cardioplegic perfusion may induce incomplete myocardial metabolic preservation and a decrease in the high-energy phosphate levels.
The use of the LITA graft in emergent situations such as complications of cardiac catheterization, cardiogenic shock, or a recent anterior myocardial infarction has been reported by some authors to be associated with a relatively low morbidity [3–5]. Despite these encouraging results, there is still a concern that an LITA graft cannot provide adequate flow to an acutely occluded artery. Gurne and associates [18] recently reported the angiographic findings in the early and late postoperative periods in patients who received an LITA graft for coronary artery bypass grafting. These authors found that an increase in the myocardial blood flow induced by pacing resulted in vasodilatation of the LITA graft in the late, but not in the early, postoperative period. Thus, increased myocardial demand in the early postoperative period may result in ischemia to the LAD region. If the use of the LITA graft results in depleted myocardial high-energy phosphate stores, then these patients may be at increased risk for ischemic injury in the early postoperative period.
The purpose of this study was to determine if use of the LITA graft adversely affected early myocardial metabolic recovery in patients undergoing isolated coronary artery bypass grafting as a result of inadequate cardioplegic perfusion of the LAD territory. We previously found that subtle differences in perioperative myocardial metabolism can result in significant differences in the clinical outcomes in high-risk patients. For example, in a study comparing blood and crystalloid cardioplegia [19], we found that blood cardioplegia reduced ischemic injury and decreased anaerobic metabolism in elective patients. In high-risk patients undergoing urgent coronary artery bypass grafting for the treatment of unstable angina, the use of blood cardioplegia was found to lead to a significant reduction in mortality, perioperative myocardial infarction, and postoperative low-output syndrome [20].
In a previous study comparing alternative techniques of cardioplegia, we demonstrated better preservation of the myocardial high-energy phosphate levels with normothermic as opposed to hypothermic cardioplegia [6]. We found a greater decrease in ATP level with cold than warm cardioplegia with a sample size of 25 patients per group [6, 7]. In a subsequent study, we demonstrated that ventricular function recovered more rapidly after normothermic than after hypothermic blood cardioplegia [21]. Thus, subtle differences in perioperative myocardial metabolism correlated with recovery of left ventricular function in the early postoperative period.
In this study we found a significant improvement in the preservation of the ATP and high-energy phosphate levels over time. There were proportionately more patients in the late group who received LITA grafts. When the SVG and LITA graft groups were compared separately from the standpoint of each time period, no differences were found between the groups.
We hypothesized that significant collateral circulation to the left and right ventricles present in patients undergoing elective coronary artery bypass grafting would permit adequate cardioplegic perfusion. Using sonicated albumin and transesophageal echocardiography, we have previously demonstrated that antegrade cardioplegic perfusion is adequate to the left ventricular free wall, even in the presence of proximal LAD occlusions [22]. These findings are in contrast to those of Noyez and colleagues [23], who found that proximal coronary artery stenoses in the LAD limited antegrade cardioplegic perfusion. In our present study, we were unable to demonstrate a difference in the preservation of ATP or high-energy phosphate levels between those patients who had an occluded LAD (n = 28) and those with a patent but stenotic artery (n = 210). In patients who received LITA grafts to their LAD, the power of this observation was 99%. This observation supports our contention that patients presenting for elective procedures have adequate collateralization of their anterior wall and are sufficiently perfused with antegrade cardioplegia.
We conclude that, in low-risk, elective patients undergoing coronary artery bypass grafting, use of the LITA graft does not adversely affect myocardial metabolic recovery. Our results do not address the concern regarding use of the LITA graft during urgent or emergent operations. The metabolic consequences of employing an LITA graft in these circumstances requires further investigation.
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Acknowledgments
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Supported by the Medical Research Council of Canada (MRC grant MT 9829) and the Heart and Stroke Foundation of Ontario (Grant B2227). Doctor Rao is a Pharmaceutical Roundtable Research Fellow of the HSFO; Dr Christakis is a Research Scholar of the HSFO; Dr Weisel is a Career Investigator of the HSFO; and Dr Cohen is a surgical scientist at the Department of Surgery, University of Toronto.
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Footnotes
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Presented at the Poster Session of the Thirty-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29–31, 1996.
Address reprint requests to Dr Weisel, Division of Cardiovascular Surgery, The Toronto Hospital, EN 14-215, 200 Elizabeth St, Toronto, Ont, Canada M5G 2C4.
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References
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Abstract
Introduction
