- Email: [email protected]
Manuscript reviewers' comment
The Journal of
5 9 8 Parker et al
9 Slogoff S, Keats AS, Ott E: Preoperative propranolol therapy and aortocoronary bypass operation. lAMA 240:1487-1490, 1978 10 Mohr R, Smolinsky A, Goor DA: Prevention of supraventricular tachyarrhythmia with low-dose propranolol after coronary bypass. 1 THORAC CARDIOVASC SURG 81:840845, 1981 11 Williams JB, Stephenson LW, Holford FD, Langer T, Dunkman WB, Josephson ME: Arrhythmia prophylaxis using propranolol after coronary artery surgery. Ann Thorac Surg 34:435-438, 1982 12 Ivey MF, Ivey TP, Bailey WW, Williams DB, Hessel EA, Miller DW Jr: Influence of propranolol on supraventricular tachycardia early after coronary artery revascularization. J THoRAc CARDIOVASC SURG 85:214-218, 1983 13 Roffman lA, Fieldman A: Digoxin and propranolol in the prophylaxis of supraventricular tachydysrhythmias after coronary artery bypass surgery. Ann Thorac Surg 31:496501, 1981
Manuscript reviewers' comment Approximately one fourth of all patients undergoing coronary revascularization may require pharmacologic intervention for the treatment of symptomatic atrial tachyarrhythmias during the early postoperative period. The incidence of atrial arrhythmias is similar whether the method of myocardial protection is cold potassium cardioplegia or moderate hypothermia with intermittent aortic cross-clamping.t' In the present study and in a previous study by Parker's co-workers, a significant decrease in the incidence of atrial tachyarrhythmias was observed with the use of prophylactic digitalization. However, there are potential disadvantages of using digitalis for prophylaxis of atrial arrhythmias besides the fact that it is not effective against ventricular arrhythmias that commonly occur postoperatively. There is a small but definite incidence of digitalis toxicity following cardiopulmonary bypass in patients receiving digoxin up to the time of operation." In addition, several factors tend to increase sensitivity to digitalis and lessen the threshold for toxicity in patients after the operation. These include hypocalcemia, hypomagnesemia, and reduced creatinine clearance. In addition, there is an increase in sympathetic tone because of both endogenous and exogenous catecholamines in patients during the operation and for a period postoperatively. These factors tend to counterbalance the vagomimetic properties of digitalis that are responsible for controlling ventricular response to atrial tachyarrhythmias. Thus higher levels of digitalis are required to control the ventricular response under these conditions, and this increased dosage in tum may be associated with digitalis-induced ventricular tachyarrhythmias. Despite the potential disadvantages of prophylactic digitalization, O'Kane and associates,' Shields and Ujiki," and the present authors have observed a decreased incidence of postoperative atrial tachyarrhythmias with prophylactic digitalization. Tyras and colleagues," however, have actually found an increased incidence of atrial tachyarrhythmias when prophylactic digitalization was used during coronary revascularization. They used doses of digoxin almost identical to those of
Thoracic and Cardiovascular Surgery
the present authors. In Tyras' study, 140 patients were randomized with a 27.8% (17/61) incidence of atrial tachyarrhythmias in the group treated with digoxin versus 11.4% (9/79) in the control group. Roffmann and Fieldman" randomized patients to one of three groups during coronary revascularization. The control group consisting of 63 patients had a 28.2% incidence of atrial tachyarrhythmias after revascularization. A second group of 59 patients receiving digoxin prophylactically had a 28.9% incidence of atrial tachyarrhythmias postoperatively, and .a third group receiving both digoxin and low-dose propranolol had a 2.2% incidence of postoperative atrial tachyarrhythmias. The incidence of 2.2% in Roffman's study is similar to that of 3.1% in Parker's second group, in which low-dose propranolol was used in addition to digoxin. However, in Parker's study low-dose propranolol was also used in the control group. In an earlier study by Parker's co-workers, II the incidence of atrial tachyarrhythmias was 26% in the control group and 6% in the group receiving digoxin. In that earlier study, propranolol was not used postoperatively in either group. The data from Roffman's study suggest that propranolol is more effective than digoxin in the prevention of postoperative supraventricular tachycardias, whereas that of the present authors implies the reverse. Propranolol in low doses has been used successfully to control supraventricular tachyarrhythmias and ventricular arrhythmias in patients receiving medical treatment only.":" In two randomized studies that we2 • 16 conducted in patients undergoing coronary revascularization, the incidence of symptomatic supraventricular tachyarrhythmias was 18% and 19% in the two control groups and 8% and 4% in the groups that had been treated with low-dose propranolol. The incidence of atrial tachyarrhythmias was not tabulated for the purposes of those studies until 4 hours after the patient had received the first dose of propranolol orally (same for control group), which was usually late on the first postoperative day. Nine patients also continued to receive digoxin postoperatively (four control and five propranolol) in our second study, and none of those had supraventricular arrhythmias. In another study, propranolol in small doses was initially given intravenously after operation, until the patients were able to take oral liquids, and then by mouth." In that study there was also a significant decrease in supraventricular arrhythmias in the propranolol over the control group. Mohr, Smolinsky, and Goor" studied a group of patients undergoing coronary revascularization who had all been receiving propranolol preoperatively. The patients who received low-dose propranolol after operation had a 5% incidence of atrial tachyarrhythmias, whereas those who did not had a 40% incidence. Mohr also studied an additional group of patients who had not been receiving propranolol preoperatively and found that postoperative propranolol was less effective in preventing supraventricular arrhythmias. The reason for this is not clear, although other authors have noted an increased incidence of postoperative arrhythmias, tachycardia, and hypertension in patients who had had their propranolol abruptly discontinued prior to operation."?" Abrupt discontinuance of propranolol may result in an increase of symptomatic activity, thus resulting in a greater incidence of
Volume 86 Number 4 October, 1983
Supraventricular arrhythmias 5 9 9
supraventricular arrhythmias. Preliminary data from our own laboratory have demonstrated that patients preoperatively treated with propranolol had a higher beta receptor density in atrial tissue removed at operation." They also had a higher incidence of postoperative atrial arrhythmias. This receptor regulation may provide a basis for some arrhythmias in the postoperative state, particularly those occurring in patients receiving beta blockers. The efficacy of propranolol in preventing the arrhythmia in such patients seems logical. A different mechanism, for example, atrial injury or pericarditis, may be operative in patients not receiving beta blockers prior to operation. In such instances the use of beta blockers may not be as efficacious. The incidence of ventricular arrhythmias postoperatively was 33% in the control group and 38% in the group that had been given digitalis in the earlier study by Parker's coworkers." In Parker's present study, in which both groups also received low-dose propranolol postoperatively, the incidence of ventricular arrhythmias was 17.9% for the control group and 21.8% for the group that received digitalis, almost a 50% reduction in ventricular arrhythmia rates. This may have been due to the concomitant use of beta blockers in the present study. In our two studies in which patients were randomized to low-dose propranolol or control after coronary revascularization, we observed fewer ventricular arrhythmias in the propranolol-treated patients. Despite these encouraging results with propranolol for postoperative prophylaxis of atrial arrhythmias, Ivey and associates" could find no difference (13.2% for propranolol and 16.1% for placebo) in atrial arrhythmia rates in a carefully controlled study comparing propranolol and placebo in patients undergoing coronary revascularization. No mention was made in that study of the incidence of ventricular arrhythmias in either group. In conclusion, seemingly well-eontrolled studies using either digoxin or propranolol for postoperative atrial arrhythmia prophylaxis have yielded conflicting results. Clearly, more information is needed to explain the differences in these results. The two studies (Roffman and Parker) in which propranolol and digoxin were given simultaneously have yielded as yet the lowest incidence of supraventricular arrhythmias (2.2% and 3.1%). Perhaps a tighter definition of "arrhythmias" and their timing, as well as related potential arrhythmogenic factors, need to 'be considered. The role of beta receptors in the genesis of these arrhythmias also requires further studies.
Larry w: Stephenson. M.D. Mark E. Josephson. M.D. Departments of Surgery and Medicine University of Pennsylvania School of Medicine Phi/adelphia. Pa. 19104
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3
4
5
6
7
8
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10
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16
REFERENCES Parker FB Jr, Greiner-Hayes C, Rove EL, Marvasti MA, Johnson LW, Eich RH: Supraventricular arrhythmias following coronary artery bypass. The effect of preopera-
17
tive digitalis. J THoRAc CARDIOVASC SURG 86: 594-600, 1983 Williams JB, Stephenson LW, Holford FD, Langer T, Dunkman WB, Josephson ME: Arrhythmia prophylaxis using propranolol after coronary artery surgery. Ann Thorac Surg 34:435-438, 1982 Rose M, Glassman E, Spencer FC: Arrhythmia following cardiac surgery. Relation to serum digoxin levels. Am Heart J 89:288-294, 1975 Johnson LW, Arahaki F, Kurmar MS, Deodhar SD: Digoxin level in digitalis intoxication and after surgery involving cardiopulmonary bypass. Cleve Clin Q 40:133, 1973 Krasula RW, Hastreiter AR, Levitsky S, Yanagi R, Soyka LF: Serum, atrial and urine digoxin levels during cardiopulmonary bypass in children. Circulation 49:10471052, 1974 Morrison J, Tallip PT: Serum digitalis and arrhythmia in patients undergoing cardiopulmonary bypass. Circulation 47:341-352, 1973 O'Kane H, Geha A, Baue A, Klerger R, Krone R, Oliver GC: Prophylactic digitalization in aortocoronary bypass patients. Circulation 45,46:Suppl 2:199, 1972 Shields TW, Ujiki GT: Digitalization for prevention of arrhythmias following pulmonary surgery. Surg Gynecol Obstet 126:743-746, 1968 Tyras DH, Stothert JC Jr, Kaiser GC, Barnes HB, Codd JE, Willman VL: Supraventricular tachyarrhythmias after myocardial revascularization. A randomized trial of prophylactic digitalization. J THoRAc CARDIOVASC SURG 77:310-314,1979 Roffman JA, Fieldman A: Digoxin and propranolol in the prophylaxis of supraventricular tachydysrhythmias after coronary artery bypass surgery. Ann Thorac Surg 31:496501,1981 Johnson LW, Dickstein RA, Fruehan CT, Kane P, Potts JL, Smulyan H, Webb WR, Eich RH: Prophylactic digitalization for coronary artery bypass surgery. Circulation 53:819-822, 1976 Gettes LS, Surawicz B: Long-term prevention of paroxysmal arrhythmias with propranolol therapy. Am J Med Sci 254:257-265, 1967 Gianelly R, Griffin JR, Harrison DC: Propranolol in the treatment and prevention of cardiac arrhythmias. Ann Intern Med 66:667-676, 1967 Harris A: Long-term treatment of paroxysmal cardiac arrhythmias with propranolol. Am J Cardiol 18:431-437, 1966 Walters L, Gettes LS, Noonan JA: Long-term management of chronic tachycardias with orally administered propranolol. Am J Cardiol 21:119, 1968 Stephenson LW, MacVaugh H III, Tomasello DN, Josephson ME: Propranolol for prevention of postoperative cardiac arrhythmias. A randomized study. Ann Thorac Surg 29: 113-116, 1980 Salazar C, Frishman W, Friedman S, Patel J, Lin YT, Oka Y, Frater RW, Becker RM: Beta-blockage therapy for supraventricular tachyarrhythmias after coronary sur-
6 00 Parker et al.
gery. A propranolol withdrawal syndrome? Angiology 30:816-819, 1979 18 Mohr R, Smolinsky A, Goor DA: Prevention of supraventricular tachyarrhythmia with low-dose propranolol after coronary bypass. J THORAC CARDIOVASC SURG 81:840845, 1981 19 Kirsh MM, Behrendt DM, Jackson AP, Dhadphale P, Alseri S, Brymer J, Orringer MB, Sloan H: Myocardial revascularization in patients receiving long-term propranolol therapy. Ann Thorac Surg 25: 117-121, 1978 20 Oka Y, Frishman W, Becker RM, Kadish A, Strom J, Matsumoto M, Oekin L, Frater R: Clinical pharmacology of the new beta-adrenergic blocking drugs: Part 10.
The Journal of Thoracic and Cardiovascular Surgery
Beta-adrenoreceptor blockade and coronary artery surgery. Am Heart J 99:255-269, 1980 21 Slogoff S, Keats AS, Ott E: Preoperative propranolol therapy and aortocoronary bypass operations. JAMA 246:1487-1490,1978 22 Kempf FC, Hedberg A, Molioff P, Josephson ME: The effect of pharmacologic therapy on atrial beta receptor density and post-operative atrial arrhythmias. J Clin Res (in press) 23 Ivey MF, Ivey TP, Bailey WW, Williams DB, Hessel Ex II, Miller DW Jr: Influence of propranolol on supraventricular tachycardia early after coronary artery revascularization. J THoRAc CARDIOVASC SURG 85:214-218, 1983
5 9 8 Parker et al
9 Slogoff S, Keats AS, Ott E: Preoperative propranolol therapy and aortocoronary bypass operation. lAMA 240:1487-1490, 1978 10 Mohr R, Smolinsky A, Goor DA: Prevention of supraventricular tachyarrhythmia with low-dose propranolol after coronary bypass. 1 THORAC CARDIOVASC SURG 81:840845, 1981 11 Williams JB, Stephenson LW, Holford FD, Langer T, Dunkman WB, Josephson ME: Arrhythmia prophylaxis using propranolol after coronary artery surgery. Ann Thorac Surg 34:435-438, 1982 12 Ivey MF, Ivey TP, Bailey WW, Williams DB, Hessel EA, Miller DW Jr: Influence of propranolol on supraventricular tachycardia early after coronary artery revascularization. J THoRAc CARDIOVASC SURG 85:214-218, 1983 13 Roffman lA, Fieldman A: Digoxin and propranolol in the prophylaxis of supraventricular tachydysrhythmias after coronary artery bypass surgery. Ann Thorac Surg 31:496501, 1981
Manuscript reviewers' comment Approximately one fourth of all patients undergoing coronary revascularization may require pharmacologic intervention for the treatment of symptomatic atrial tachyarrhythmias during the early postoperative period. The incidence of atrial arrhythmias is similar whether the method of myocardial protection is cold potassium cardioplegia or moderate hypothermia with intermittent aortic cross-clamping.t' In the present study and in a previous study by Parker's co-workers, a significant decrease in the incidence of atrial tachyarrhythmias was observed with the use of prophylactic digitalization. However, there are potential disadvantages of using digitalis for prophylaxis of atrial arrhythmias besides the fact that it is not effective against ventricular arrhythmias that commonly occur postoperatively. There is a small but definite incidence of digitalis toxicity following cardiopulmonary bypass in patients receiving digoxin up to the time of operation." In addition, several factors tend to increase sensitivity to digitalis and lessen the threshold for toxicity in patients after the operation. These include hypocalcemia, hypomagnesemia, and reduced creatinine clearance. In addition, there is an increase in sympathetic tone because of both endogenous and exogenous catecholamines in patients during the operation and for a period postoperatively. These factors tend to counterbalance the vagomimetic properties of digitalis that are responsible for controlling ventricular response to atrial tachyarrhythmias. Thus higher levels of digitalis are required to control the ventricular response under these conditions, and this increased dosage in tum may be associated with digitalis-induced ventricular tachyarrhythmias. Despite the potential disadvantages of prophylactic digitalization, O'Kane and associates,' Shields and Ujiki," and the present authors have observed a decreased incidence of postoperative atrial tachyarrhythmias with prophylactic digitalization. Tyras and colleagues," however, have actually found an increased incidence of atrial tachyarrhythmias when prophylactic digitalization was used during coronary revascularization. They used doses of digoxin almost identical to those of
Thoracic and Cardiovascular Surgery
the present authors. In Tyras' study, 140 patients were randomized with a 27.8% (17/61) incidence of atrial tachyarrhythmias in the group treated with digoxin versus 11.4% (9/79) in the control group. Roffmann and Fieldman" randomized patients to one of three groups during coronary revascularization. The control group consisting of 63 patients had a 28.2% incidence of atrial tachyarrhythmias after revascularization. A second group of 59 patients receiving digoxin prophylactically had a 28.9% incidence of atrial tachyarrhythmias postoperatively, and .a third group receiving both digoxin and low-dose propranolol had a 2.2% incidence of postoperative atrial tachyarrhythmias. The incidence of 2.2% in Roffman's study is similar to that of 3.1% in Parker's second group, in which low-dose propranolol was used in addition to digoxin. However, in Parker's study low-dose propranolol was also used in the control group. In an earlier study by Parker's co-workers, II the incidence of atrial tachyarrhythmias was 26% in the control group and 6% in the group receiving digoxin. In that earlier study, propranolol was not used postoperatively in either group. The data from Roffman's study suggest that propranolol is more effective than digoxin in the prevention of postoperative supraventricular tachycardias, whereas that of the present authors implies the reverse. Propranolol in low doses has been used successfully to control supraventricular tachyarrhythmias and ventricular arrhythmias in patients receiving medical treatment only.":" In two randomized studies that we2 • 16 conducted in patients undergoing coronary revascularization, the incidence of symptomatic supraventricular tachyarrhythmias was 18% and 19% in the two control groups and 8% and 4% in the groups that had been treated with low-dose propranolol. The incidence of atrial tachyarrhythmias was not tabulated for the purposes of those studies until 4 hours after the patient had received the first dose of propranolol orally (same for control group), which was usually late on the first postoperative day. Nine patients also continued to receive digoxin postoperatively (four control and five propranolol) in our second study, and none of those had supraventricular arrhythmias. In another study, propranolol in small doses was initially given intravenously after operation, until the patients were able to take oral liquids, and then by mouth." In that study there was also a significant decrease in supraventricular arrhythmias in the propranolol over the control group. Mohr, Smolinsky, and Goor" studied a group of patients undergoing coronary revascularization who had all been receiving propranolol preoperatively. The patients who received low-dose propranolol after operation had a 5% incidence of atrial tachyarrhythmias, whereas those who did not had a 40% incidence. Mohr also studied an additional group of patients who had not been receiving propranolol preoperatively and found that postoperative propranolol was less effective in preventing supraventricular arrhythmias. The reason for this is not clear, although other authors have noted an increased incidence of postoperative arrhythmias, tachycardia, and hypertension in patients who had had their propranolol abruptly discontinued prior to operation."?" Abrupt discontinuance of propranolol may result in an increase of symptomatic activity, thus resulting in a greater incidence of
Volume 86 Number 4 October, 1983
Supraventricular arrhythmias 5 9 9
supraventricular arrhythmias. Preliminary data from our own laboratory have demonstrated that patients preoperatively treated with propranolol had a higher beta receptor density in atrial tissue removed at operation." They also had a higher incidence of postoperative atrial arrhythmias. This receptor regulation may provide a basis for some arrhythmias in the postoperative state, particularly those occurring in patients receiving beta blockers. The efficacy of propranolol in preventing the arrhythmia in such patients seems logical. A different mechanism, for example, atrial injury or pericarditis, may be operative in patients not receiving beta blockers prior to operation. In such instances the use of beta blockers may not be as efficacious. The incidence of ventricular arrhythmias postoperatively was 33% in the control group and 38% in the group that had been given digitalis in the earlier study by Parker's coworkers." In Parker's present study, in which both groups also received low-dose propranolol postoperatively, the incidence of ventricular arrhythmias was 17.9% for the control group and 21.8% for the group that received digitalis, almost a 50% reduction in ventricular arrhythmia rates. This may have been due to the concomitant use of beta blockers in the present study. In our two studies in which patients were randomized to low-dose propranolol or control after coronary revascularization, we observed fewer ventricular arrhythmias in the propranolol-treated patients. Despite these encouraging results with propranolol for postoperative prophylaxis of atrial arrhythmias, Ivey and associates" could find no difference (13.2% for propranolol and 16.1% for placebo) in atrial arrhythmia rates in a carefully controlled study comparing propranolol and placebo in patients undergoing coronary revascularization. No mention was made in that study of the incidence of ventricular arrhythmias in either group. In conclusion, seemingly well-eontrolled studies using either digoxin or propranolol for postoperative atrial arrhythmia prophylaxis have yielded conflicting results. Clearly, more information is needed to explain the differences in these results. The two studies (Roffman and Parker) in which propranolol and digoxin were given simultaneously have yielded as yet the lowest incidence of supraventricular arrhythmias (2.2% and 3.1%). Perhaps a tighter definition of "arrhythmias" and their timing, as well as related potential arrhythmogenic factors, need to 'be considered. The role of beta receptors in the genesis of these arrhythmias also requires further studies.
Larry w: Stephenson. M.D. Mark E. Josephson. M.D. Departments of Surgery and Medicine University of Pennsylvania School of Medicine Phi/adelphia. Pa. 19104
2
3
4
5
6
7
8
9
10
II
12
13
14
15
16
REFERENCES Parker FB Jr, Greiner-Hayes C, Rove EL, Marvasti MA, Johnson LW, Eich RH: Supraventricular arrhythmias following coronary artery bypass. The effect of preopera-
17
tive digitalis. J THoRAc CARDIOVASC SURG 86: 594-600, 1983 Williams JB, Stephenson LW, Holford FD, Langer T, Dunkman WB, Josephson ME: Arrhythmia prophylaxis using propranolol after coronary artery surgery. Ann Thorac Surg 34:435-438, 1982 Rose M, Glassman E, Spencer FC: Arrhythmia following cardiac surgery. Relation to serum digoxin levels. Am Heart J 89:288-294, 1975 Johnson LW, Arahaki F, Kurmar MS, Deodhar SD: Digoxin level in digitalis intoxication and after surgery involving cardiopulmonary bypass. Cleve Clin Q 40:133, 1973 Krasula RW, Hastreiter AR, Levitsky S, Yanagi R, Soyka LF: Serum, atrial and urine digoxin levels during cardiopulmonary bypass in children. Circulation 49:10471052, 1974 Morrison J, Tallip PT: Serum digitalis and arrhythmia in patients undergoing cardiopulmonary bypass. Circulation 47:341-352, 1973 O'Kane H, Geha A, Baue A, Klerger R, Krone R, Oliver GC: Prophylactic digitalization in aortocoronary bypass patients. Circulation 45,46:Suppl 2:199, 1972 Shields TW, Ujiki GT: Digitalization for prevention of arrhythmias following pulmonary surgery. Surg Gynecol Obstet 126:743-746, 1968 Tyras DH, Stothert JC Jr, Kaiser GC, Barnes HB, Codd JE, Willman VL: Supraventricular tachyarrhythmias after myocardial revascularization. A randomized trial of prophylactic digitalization. J THoRAc CARDIOVASC SURG 77:310-314,1979 Roffman JA, Fieldman A: Digoxin and propranolol in the prophylaxis of supraventricular tachydysrhythmias after coronary artery bypass surgery. Ann Thorac Surg 31:496501,1981 Johnson LW, Dickstein RA, Fruehan CT, Kane P, Potts JL, Smulyan H, Webb WR, Eich RH: Prophylactic digitalization for coronary artery bypass surgery. Circulation 53:819-822, 1976 Gettes LS, Surawicz B: Long-term prevention of paroxysmal arrhythmias with propranolol therapy. Am J Med Sci 254:257-265, 1967 Gianelly R, Griffin JR, Harrison DC: Propranolol in the treatment and prevention of cardiac arrhythmias. Ann Intern Med 66:667-676, 1967 Harris A: Long-term treatment of paroxysmal cardiac arrhythmias with propranolol. Am J Cardiol 18:431-437, 1966 Walters L, Gettes LS, Noonan JA: Long-term management of chronic tachycardias with orally administered propranolol. Am J Cardiol 21:119, 1968 Stephenson LW, MacVaugh H III, Tomasello DN, Josephson ME: Propranolol for prevention of postoperative cardiac arrhythmias. A randomized study. Ann Thorac Surg 29: 113-116, 1980 Salazar C, Frishman W, Friedman S, Patel J, Lin YT, Oka Y, Frater RW, Becker RM: Beta-blockage therapy for supraventricular tachyarrhythmias after coronary sur-
6 00 Parker et al.
gery. A propranolol withdrawal syndrome? Angiology 30:816-819, 1979 18 Mohr R, Smolinsky A, Goor DA: Prevention of supraventricular tachyarrhythmia with low-dose propranolol after coronary bypass. J THORAC CARDIOVASC SURG 81:840845, 1981 19 Kirsh MM, Behrendt DM, Jackson AP, Dhadphale P, Alseri S, Brymer J, Orringer MB, Sloan H: Myocardial revascularization in patients receiving long-term propranolol therapy. Ann Thorac Surg 25: 117-121, 1978 20 Oka Y, Frishman W, Becker RM, Kadish A, Strom J, Matsumoto M, Oekin L, Frater R: Clinical pharmacology of the new beta-adrenergic blocking drugs: Part 10.
The Journal of Thoracic and Cardiovascular Surgery
Beta-adrenoreceptor blockade and coronary artery surgery. Am Heart J 99:255-269, 1980 21 Slogoff S, Keats AS, Ott E: Preoperative propranolol therapy and aortocoronary bypass operations. JAMA 246:1487-1490,1978 22 Kempf FC, Hedberg A, Molioff P, Josephson ME: The effect of pharmacologic therapy on atrial beta receptor density and post-operative atrial arrhythmias. J Clin Res (in press) 23 Ivey MF, Ivey TP, Bailey WW, Williams DB, Hessel Ex II, Miller DW Jr: Influence of propranolol on supraventricular tachycardia early after coronary artery revascularization. J THoRAc CARDIOVASC SURG 85:214-218, 1983