T has been prevailing in coronary bypass surgery due. Exercise Coronary Flow Reserve of Bilateral Internal Thoracic Artery Bypass Grafts

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1 Exercise Coronary Flow Reserve of Bilateral nternal Thoracic Artery Bypass Grafts Ryuichi Morita, MD, Soichiro Kitamura, MD, Kanji Kawachi, MD, Tetsuji Kawata, MD, Kazumi Mizuguchi, MD, Yoichi Kameda, MD, Jyunichi Hasegawa, MD, and Yoshitsugu Yoshida, MD Department of Surgery 111, Nara Medical College, Nara, Japan We attempted to quantify the exercise coronary flow reserve in 20 patients with bilateral internal thoracic artery grafts to the left coronary arteries (group ) who had complete revascularization. The coronary sinus blood flow was measured by the continuous thermodilution method both at rest and during exercise (50 W for 8 to 9 minutes) approximately 1 month after the operation. These results were compared with 30 patients treated with an internal thoracic artery and saphenous vein grafts to the left coronary arteries (group 11) and 9 patients with saphenous vein grafts alone to the left coronary arteries (group 111). There were no differences among the three groups in age, sex, number of vessels involved, heart rate, double products, left ventricular (LV) end-diastolic pressure, LV ejection fraction, LV end-diastolic volume, or LV mass at the time of study. None of the 59 patients in the study had abnormally enlarged LV end-diastolic volume or increased LV mass. The postoperative coronary sinus blood flow per 100 grams of LV mass at rest was similar among the three groups (73.0 f 28.4 ml/min per 100 g LV mass in group, 73.4 f 31.1 ml/min per 100 g LV mass in group 11, and 75.9 f 28.5 mwmin per 100 g LV mass in group 11 [not significant]) and significantly (p < 0.01) increased by exercise, although the differences between groups during exercise were not significant (158.9 f 45.9, f 72.1, and f 60.0 mwmin per 100 g LV mass, respectively [not significant]). The incremental ratio of coronary sinus blood flow during exercise was similar for each of the three groups as well (2.20 f 0.60,2.14 f 0.52, and 2.11 f 0.44, respectively [not significant]). We conclude that the use of bilateral internal thoracic artery grafts to the left coronary arteries can provide sufficient coronary flow reserve even during exercise at 1 month postoperatively. This flow is enough to safely implement complete revascularization of the left coronary artery system, on the condition that the left ventricle is neither markedly enlarged nor hypertrophied. (Ann Thoruc Surg 1993;55:883-7) he use of internal thoracic artery (TA) bypass grafts T has been prevailing in coronary bypass surgery due to the excellent late patency rates. The grafting of TA to the left anterior descending artery (LAD) has become a routine procedure in our department as well. However, whether bilateral TAs can provide sufficient coronary blood flow to the left ventricle during exercise has not been answered by flow measurement, and some doubts about the use of TA for left main trunk disease remain [l, 21. The purpose of the present study, therefore, was to assess the flow capability of bilateral TA grafts to the left coronary arteries (LCAs). Patients and Methods Selected for the study were those patients who had met the following two criteria: (1) absence of previous myocardial infarctions, and (2) successful complete revascularization with patent bypass grafts, and no distal or anastomotic stenosis confirmed by angiography. Patients with major residual diffuse disease were excluded. Of Accepted for publication July 16, 1992 Address reprint requests to Dr Morita, Department of Surgery 111, Nara Medical College, 840 Shijo-cho, Kashihara, Nara, Japan 634. those selected, 59 patients evaluated by postoperative exercise coronary sinus blood flow (CSBF) measurements were divided into three groups, according to the method of coronary artery grafting. Group consisted of 20 patients with bilateral TA grafts to the LCA system, group 1 of 30 patients with a single TA graft to LAD and saphenous vein grafts (SVGs) to circumflex lesions, and group 11 of 9 patients with SVGs alone to the LCA system. n all 3 groups, SVG was used for revascularization of the right coronary artery. There were no differences among the three groups in age, sex, number of vessels involved, number of patients with left main trunk lesion, or dominance of the left or right coronary circulatory system. Mean age was years in group, 54 f 8 years in group 11, and 56 f 10 years in group 111. The male to female ratio was 19:l in group, 28:2 in group 11, and 9:O in group 111. The average number of vessels involved per patient was 2.8 * 0.4 in group, 2.5 f 0.7 in group 11, and 2.4 & 0.7 in group 111. The number of patients with left main trunk lesion was 7 (35%) in group, 12 (40%) in group, and 3 (33%) in group 111. The rate of right-dominant coronary circulatory system evaluated by cineangiogram was 85%, 83%, and 86%, respectively. Group had more bypass grafts overall by The Society of Thoracic Surgeons /93/$6.00

2 884 MORTAETAL AM Thorac Surg 1993;55:883-7 Table 1. Hemodymmic Data of the Three Groups" Group, Group 11, Group, Bilateral Single TA SVGs TAs + SVGs Alone p Variable (n = 20) (n = 30) (n = 9) Value LVEDP (mm Hg) 9.4 f f f 2.0 NS LVEF 0.64 f ? f 0.09 NS LVEDV (ml/m2) 86 f f f 17 NS Lvbf~ (g/m2) 98 f 11 % f f 14 NS a All values are given as mean k standard deviation. TA = internal thoracic artery; LVEDP = left ventricular end-diastolic pressure; LVEDV = left ventricular end-diastok volume index; LVEF = left ventricular ejection fraction; LVM = left ventricular mass index; NS = not sigruficant; SVG = saphenous vein graft. (3.3 f 0.7 grafts per patient), but to the LCA system, group had 2.3 k 0.5 grafts per patient, not sigruficantly different from that of group 1 or 11 (2.8 k 0.9 grafts per patient overall and 2.1 k 0.7 grafts per patient to the LCA system in group 11, and 2.7 k 0.5 grafts per patient overall and 2.0 k 0.6 grafts per patient to the LCA system in group ). All of the patients in this study underwent elective operations. Group 111 underwent a somewhat early series of operations; however, there were no differences among the three groups in the protocol of exercise CSBF measurements in this study, as will be discussed. Table 1 shows the hemodynamic data of the three groups: the left ventricular end-diastolic pressure, left ventricular ejection fraction, left ventricular end-diastolic volume index, and left ventricular mass weight index at the time of study. The last three variables were calculated from cineangiograms by the methods of Kennedy and associates [3] and Rackley and colleagues [4]. No significant differences existed between the three groups in any of the variables assessed. The mean time of the postoper- ative study was at 1.2 months in group, 1.4 months in group 11, and 1.3 months in group. The patency rate of grafts to the LCAs was 100% in all groups. Additionally, the patency rate of all grafts including right coronary artery grafts was also 100% in all groups. All of the grafts were excellently patent without any angiographic abnormalities in this postoperative study. Exercise Protocol For 48 hours before the study, all medications were discontinued including sodium warfarin, dipyridamole, and isosorbide dinitrate. None of the patients received calcium antagonists or /%blockers postoperatively. The heart rate, blood pressure, cardiac index, and CSBF at rest were measured, and then a constant loading of 50 W using a bicycle ergometer was given in the supine position. Three minutes after the exercise loading became constant, individual variables were recorded again. The measurement of CSBF during exercise required the patient to give a constant load of 50 W continuously for 8 to 9 minutes. When a submaximal to maximal load was given to the patients, many could not tolerate it for this period of time because of leg fatigue, and data collection was not attained during exercise. For this reason, a constant load of 50 W for 8 to 9 minutes was used for the evaluation of exercise CSBF. Coronary Sinus Blood Flow Measurements At the time of the postoperative study by cardiac catheterization, an 8F catheter (Webster Co, Baldwin Park, CA) for CSBF determination was inserted through the cubital vein. The CSBF was measured by the continuous thermodilution method [5] (Fig l), both at rest and during exercise as described. The CSBF reflects the coronary flow of the left ventricle [6], and all of the patients in this series were judged to have complete revascularization of the left 13:47 ET 01UU 5EC 11/19 13:48 ET 187,q 5EC 11/19 13:58 - t Fig 7. Coronary sinus blood flow (CSBF) measurements at rest and during exercise in a patient with bilateral internal thoracic artery (TA) grafting to the left coronary arteries. (CABG = corona ry artery bypass grafting; CS = coronary sinus; CSBF = coronary sinus blood pow; GCV = great cardiac vein; GCVBF = great cardiac vein blood pow; M = male.)

3 Ann Thorac Surg 1993;55:88?-7 MORTA ET AL 885 Table 2. Coronary Sinus Blood Flow Studf At Rest During Exercise Group Group 1 Group 11 Group Group 1 Group 111 Variable (n = 20) (n = 30) (n = 9) (n = 20) (n = 30) (n = 9) HR (beatdmin) 83 f f f f 16b 120 f 19b 123 f 24b Rate-pressure product 10.0 f f f f 3.5b 19.7 t 4.9b 21.4 f 6.8b ( x lo3 beats. mm Hg - min-') C (L. min-'. m-2) 3.14 t f f f 0.95b 5.36 f 1.20b 5.58 f 0.91b CSBG (ml/min) t t f f 73.4b f 84.6b f 77.8b CSBF/100 g LVM (mumin 73.0 t f f t 45.9b f 72.1b f 60.0b per 100 g LVM) a Values are shown as mean 5 standard deviation. There were no significant differences among the three groups in any variable at rest, or during exercise. Significantly different from value at rest, p < C = cardiac index; CSBF = coronary sinus blood flow; HR = heart rate; LVM = left ventricular mass. ventricle with no residual lesions. The location of the catheter tip was identified under fluoroscopy, and measurements were made at 15 to 30 seconds after the start of infusion to assure the stability of data. The mean value from three determinations was used for statistical analysis. Statistical Analysis The paired t test was employed to compare individual variables between resting and exercising states. The oneway analysis of variance was used to compare the data among the three groups. All values are given as mean f standard deviation, and changes were considered significant at the p less than 0.05 level. Results Exercise Stress Testing None of the patients complained of anginal pains or showed a significant electrocardiographic ST-T segment depression during exercise. The heart rate in group significantly (p < 0.01) increased from 83 f 13 beats/min at rest to 122 & 16 beats/min during exercise (Table 2). Similar significant (p < 0.01) increases were observed in group 1 from 78 f 12 beats/min to 120 f 19 beats/min and group 111 from 80 f 20 beats/min to 123 f 24 beatslmin. The rate-pressure product in group also significantly (p < 0.01) increased from x lo3 at rest to 19.0 & 3.5 x lo3 beats * mm Hg - min-' during exercise (see Table 2). Again, similar significant (p < 0.01) increases were produced by exercise load in group 1 from 9.2 f 1.8 x lo3 to 19.7 f 4.9 x lo3 and group 111 from 10.7 * 3.8 x 10" to 21.4 * 6.8 X lo3. Both the heart rate and the rate-pressure product during exercise showed no significant differences among the three groups; thus resting and exercise conditions were comparable among the three groups. The cardiac index measured by the thermodilution method significantly (p < 0.01) increased from 3.14 f 0.78 L - min-' - mp2 at rest to 5.38 f 0.95 L * min-' * m-2 during exercise in group ; similar significant (p < 0.01) increases were observed in group 1 from 3.17 f 0.68 to 5.36 f 1.20 L - min-' * m-2 and group 111 from to 5.58 f 0.91 L min-' - mp2 (see Table 2). Coronary Sinus Blood Flow Measurements The resting CSBF in individuals with no demonstrable cardiac disease was f 33.1 ml/min by our method. The postoperative CSBF at rest showed no significant differences among the three groups (116.2 f 25.8 mumin in group ; f 36.9 ml/min in group 11; ml/min in group 11 [not significant]) (see Table 2). Coronary sinus blood flow was significantly (p < 0.01) increased by exercise load in every group, although there were no significant differences among the three groups ( , f 84.6, and f 77.8 ml/min, respectively [not significant]). Furthermore, the CSBF per 100 g left ventricular (LV) mass was judged to be similar among the three groups both at rest and during exercise (73.0 f 28.4, 73.4 f 31.1, and 75.9 f 28.5 mwmin per 100 g LV mass at rest, respectively [not significant], and f 45.9, f 72.1, and f 60.0 ml/min per 100 g LV mass during exercise, respectively [not significant]) (Fig 2). mk?/min/loog LVM NS at rest ** T during exercise f Group f Group $ Group U Fig 2. Coronary sinus blood flow per 100 grams of left ventricular mass (LVM) after bypass grafting was similar for each of the three groups, both at rest and during exercise. (NS = not significant; ** values different from those at rest at p < 0.01 level.)

4 886 MORTAETAL AM Thorac Surg 1993:55:88%7 9 \!L m UY W 2.0 Y T 1- GROUP GROUP 11 GROUP Fig 3. Exercise coronay flow reserve: The incremental ratio of coronay sinus blood flow during exercise indicated no sign$cant differences among the three groups. Ex-CSBF = coronay sinus blood flow during exercise; NS = not significant; R-CSBF = coronay sinus blood flow at rest.) ncremental Ratio of Corona y Sinus Blood Flow During Exercise The response of CSBF to exercise was quantified as the incremental ratio between exercising and resting state CSBFs. The ratio of exercising CSBF to resting CSBF was calculated for comparisons among the three groups (Fig 3). The ratio was for group, 2.14 & 0.52 for group 11, and for group, indicating no significant differences among the three groups. Comment Although the TA graft has been demonstrated to have excellent long-term patency, some reports [l, 21 have raised questions concerning the ability of TA grafts to provide sufficient coronary blood flow. There have been other questions [, 7] as to whether the TA graft can cope with large perfusion areas postoperatively and whether it can match the increased myocardial oxygen demand seen during exercise. Furthermore, some reports [&lo] described that the intraoperative blood flow provided by TA grafts was smaller than that provided by SVGs when measured by means of an electromagnetic flow meter. Nevertheless, many investigators [8,11,12] have reported good clinical results in patients with TA bypass grafts. n patients with a single TA graft to LAD, the responsiveness of grafts to increased blood flow was reported to be similar between TA and SVG when tested by isoproterenol loading [13] and by atrial pacing [14]. We also previously reported that TA-to-LAD bypass grafting provided sufficient CSBF equivalent to that with an SVG to the LAD [8] at 1 month postoperatively. However, postoperative coronary blood flow reserve during exercise provided by bilateral TA grafts for the LCA system remained to be determined. There are many methods currently available for mea- suring CSBF. Direct CSBF measurement by the thermodilution method provides one of the most sensitive and useful determinations of regional LV coronary blood flow [15]. This method can be safely employed in humans and correlates well with electromagnetic flow measurements [5]. t can easily be performed for either prolonged or multiple serial measurements. One of the drawbacks of this method, however, is that complete left coronary venous drainage cannot be assessed, because the posterior interventricular vein enters the coronary sinus too close to the right atrial blood reflux [15]. Taking this drawback into consideration, we identified the location of the catheter tip in a secure position under fluoroscopy, both at rest and during exercise, and the mean of three determinations was adopted for statistical analysis to assure the stability of the data. The CSBF represents mainly an admixture of both LAD and circumflex coronary artery venous drainage [6]; however, it is somewhat influenced by the right coronary artery system. Moreover, the CSBF is affected by the presence or absence of diffuse disease, the dominance of the left or right coronary circulatory system, the variation in collaterals that different patients have, and the different sizes of the grafts. Therefore, the patients selected for this study were those who had successfully complete revascularization by coronary artery bypass grafting. That is, they had excellently patent grafts and had neither anastomotic stenosis nor residual lesions, including in the right coronary arterial system. The determination of CSBF by the thermodilution method requires a constant load to be given continuously for at least 8 to 9 minutes for correct data acquisition. Hence, a loading of 50 W was chosen, although the exercise load given may not have always reached a maximal load level. According to some investigations [6, 14, 161, as well as ours, normal adult human hearts gave a CSBF between 111 and 149 mumin when measured by the thermodilution method. The CSBF at rest in the three groups of our study showed normal values, because all 59 patients included in the present study had no enlarged LV end-diastolic volume or LV mass. The CSBF reflects the coronary blood flow of the left ventricle [6]. The CSBF per 100 g LV mass reported by Rowe [17] using the nitrous oxide method was 80.6 mumin per 100 g LV mass, which was similar to CSBF at rest using the thermodilution method. n the present study, the incremental ratio of CSBF during an exercise state of 50 W for 8 to 9 minutes showed similar figures (2.11 to 2.20) for the three groups. Therefore, the coronary flow reserve provided by bilateral TA grafts was quite comparable with that in the other two groups with this amount of exercise. Although blood flow measured intraoperatively by an electromagnetic flow meter is smaller in TA than in SVG [&lo], the viable TA graft appears to increase the capability of blood transportation in a relatively short period of time after operation [18, 191, as confirmed by experimental study [20] and by flow measurements during reoperation for hemostasis [lo]. t was confirmed by the present study that bilateral TA

5 Ann Thorac Surg 1993:55:8837 MORTA ET AL 887 grafts to the LCAs can provide sufficient coronary flow reserve during exercise approximately 1 month after the operation to safely implement complete revascularization, on the condition that the left ventricle is neither markedly enlarged nor hypertrophied. Therefore, the coronary flow reserves produced by these grafts are comparable with the coronary flow reserve capacity of a single TA graft plus SVGs, or SVGs alone, under these conditions. However, we will never support the indiscriminate use of bilateral TAs in any case as a conclusion of this study. Based on the present results, as well as the good long-term patency of the grafts, the use of bilateral TAs can be recommended to revascularize the entire LCA system unless the left ventricle is markedly enlarged or hypertrophied. This therapeutic modality can certainly be applicable to left main trunk disease, which was previously considered reluctantly for TA grafting [l, 21. References 1. Singh H, Flemma RJ, Tector A]. Direct myocardial revascularization. Determinants in the choice of vein graft or internal mammary artery. Arch Surg 1973; Flemma RJ, Singh Hh4, Tector A], Lepley D Jr, Frazier BL. Comparative hemodynamic properties of vein and mammary artery in coronary bypass operations. Ann Thorac Surg 1975;20: Kennedy JW, Trenholme SE, Kasser S. Left ventricular volume and mass from single plane cineangiocardiogram. A comparison of anteroposterior and right anterior oblique methods. Am Heart J 1970;80: Rackley CE, Dodge HT, Coble YD Jr, Hay RE. A method for determining left ventricular mass in man. Circulation 1964; 29: Ganz W, Tamura K, Marcus HS, Donoso R, Yoshida 5, Swan HJC. Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation 1971;54: Hood WB. Regional venous drainage of the human heart. Br Heart J 1968;30: Olearchyk AS, Magovern GJ. nternal mammary artery grafting. Clinical results, patency rates, and long-term survival in 833 patients. J Thorac Cardiovasc Surg 1986;92: Kitamura S, Kawachi K, Morita R, et al. Results of internal mammary artery-coronary artery bypass surgery and the characteristics of internal mammary artery grafts. Jpn Circ J 1987;51: Tyras DH, Barner HB, Kaiser GC, Codd JE, Pennington DG, Willman VL. Bypass grafts to the left anterior descending coronary artery. J Thorac Cardiovasc Surg 1980;80: Barner HB. Blood flow in the internal mammary artery. Am Heart J 1973;86: Vogel HK, McFadden RB, Spencer R, Jahnke EJ Jr, Love JW. Quantitative assessment of myocardial performance and graft patency following coronary bypass with the internal mammary artery. J Thorac Cardiovasc Surg 1978;75: Siege1 W, Loop FD. Comparison of internal mammary artery and saphenous vein bypass grafts for myocardial revascularization. Circulation 1976;54(Suppl 3):l Schmidt DH, Blau F, Hellman C, Grzelak L, Johnson WD. soproterenol-induced flow responses in mammary and vein bypass grafts. J Thorac Cardiovasc Surg 1980;80: Myojin K, Weiss G, Mee R, et al. Functional comparison of coronary bypass grafts of the saphenous vein and internal mammary artery. J Thorac Cardiovasc Surg 1980;79: Bradley AB, Baim DS. Measurement of coronary blood flow in man: methods and implications for clinical practice. Cardiovasc Clin 1985;15: Metha J, Pepine CJ. Effect of sublingual nitroglycerin on regional flow in patients with and without coronary disease. Circulation 1978;58: Rowe GG. The nitrous-oxide method for determining coronary blood flow in man. Am Heart J 1959;58: Singh RN, Beg RA, Kay EB. Physiological adaptability: the secret of success of the internal mammary artery grafts. Ann Thorac Surg 1986;41: Kitamura S, Seki T, Kawachi K, et al. Excellent patency and growth potential of internal mammary artery grafts in pediatric coronary artery bypass surgery. New evidence for a "live" conduit. Circulation 1988;78(Suppl 1): Lee CN, Orszulak TA, Schaff HV, Kaye MP. Flow capacity of the canine internal mammary artery. J Thorac Cardiovasc Surg 1986;9 1 :