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Effects of methylprednisolone in cardioplegic solution during coronary bypass grafting
Effects of methylprednisolone in cardioplegic solution during coronary bypass grafting The effects of adding 500 mg. of methylprednisolone to each liter of cardioplegic solution were studied in patients undergoing coronary artery bypass grafts. Patients were randomly assigned 10 control (12 patients) or steroid-treated groups (10 patients). The cardioplegic solution was identical in the two groups except for the added methylprednisolone. Contractile element velocity (VeE and left ventricular end-diastolic pressure (LVEDP) were recorded immediately before and after perfusion in the operating room. There were no differences between the two groups with respect 10 these two variables or the postoperative courses. Thus this study fails to demonstrate a beneficial effect of methylprednisolone when added to cardioplegic solutions.
Marvin M. Kirsh, M.D.,* Douglas M. Behrendt, M.D.,* and Kenneth E. Jochim, M.D.,** Ann Arbor, Mich.
Limitations of previously used techniques of myocardial preservation have led to renewed interest in the use of cold cardioplegia as a means of providing myocardial protection during coronary revascularization. Potassium is the active ingredient common to most of the proposed solutions, but various other components have been used as well, usually with little experimental support. Since there is evidence that steroids may exert a protective effect on the ischemic myocardium, some workers have added them to cardioplegic solutions. The present study was undertaken to determine whether steroids do provide additional protection when added to a cardioplegic solution during ischemic cardiac arrest in patients undergoing coronary revascularization.
Methods Twenty-two patients undergoing elective coronary artery bypass grafting were randomly assigned by the perfusionist to one of two groups: In Group I, IO patients, 500 mg. of methylprednisolone was added to each liter of cardioplegic solution. These patients were compared to a control group of 12 patients (Group II), From the University of Michigan, Ann Arbor, Mich. Received for publication Oct. 30, 1978. Accepted for publication Jan. 30, 1979. Address for reprints: Marvin M. Kirsh, M.D .. The Section of Thoracic Surgery, University Hospital, C7079 Out-patient Building, Ann Arbor, Mich. 48109. *Section of Thoracic Surgery, Department of Surgery. **Department of Physiology.
896
in whom methylprednisolone was not added to the cardioplegic solution. No member of the surgical staff knew which patients had received steroids until the data had been analyzed. After institution of cardiopulmonary bypass, the left ventricle was vented through the right superior pulmonary vein and the patient's temperature was lowered to 28° C. The aorta was then clamped and I L. of 4° C. cardioplegic solution was infused into the aortic root proximal to the aortic cross-clamp (Table I). Thereafter, 500 C.c. of the solution was infused after 30 minutes, or earlier if electrical activity resumed prior to 30 minutes. All distal anastomoses were constructed during one continuous period of aortic cross-clamping. After completion of the distal anastomoses, the aortic clamp was removed and the heart defibrillated if necessary. While the patient was being rewarmed, the proximal anastomoses were performed with a partial occluding clamp on the aorta and the heart beating. Efficacy of the cardioplegic solutions in protecting the myocardium from ischemic damage was evaluated in the following manner. Myocardial contractility was assessed immediately before and after the period of perfusion by intraoperative measurement of contractile element velocity. A No.4 Fr. Millar transducer-tipped catheter was inserted into the left ventricle through an apical stab wound to provide a high-fidelity left ventricular pressure signal and its first derivative (dP/dt). Then loops of the quantity (dP/dt)/P versus P were recorded, P being the instantaneous total left ventricular pressure.
0022-5223179/060896+04$00040/0 © 1979 The C. V. Mosby Co.
Volume 77 Number 6
Methylprednisolone in cardioplegic solution
897
June, 1979
During isovolumetric systole, the quantity (dP/dt)/P is equal to the velocity of contractile element shortening (VCE).' Also, the maximum observed value of VCE (Vpm) is a sensitive contractility index, not influenced by afterload but somewhat dependent upon preload and heart rate. 2. :l Thus, in the present study, Vpm was recorded in each patient before and after bypass at 37° C., with heart rate held constant by atrial pacing when necessary and with preload held constant by volume infusion or withdrawal from the pump oxygenator when necessary. The "before" and "after" values of Vpm for each group were compared by use of a t test for paired data to determine if a significant change in contractility had occurred during the operation. The patient's records also were retrospectively reviewed to determine if there were differences between the two groups with regard to mortality rate, use of inotropic agents or balloon pump, or electrocardiographic evidence of myocardial infarction or arrhythmias.
Results Myocardial contractility. In patients who received steroids there was a statistically insignificant (p > 0.05) reduction in Vpm from 30.6 (± 9.3 S.D.) sec.- t to 30.1 (± 8.2 S.D.) sec.-I and a statistically insignificant increase in left ventricular end-diastolic pressure (LVEDP) from 18.5 (± 7.7 S.D.) to 22.1 (± 8.1 S.D.) mm. Hg. Similarly, no significant changes were observed in the patients who did not receive steroids- Vpm changed from 35.2 (± 13.1 S.D.) to 33.8 (± 12.9 S.D.) sec.-I and LVEDP from 16.2 (± 10.3 S.D.) to 16.5 (± 9.5 S.D.) mm. Hg. The difference between the means of the Vpm and L VEDP values of the two groups also was statistically insignificant both preoperatively and postoperatively. Retrospective analysis of characteristics of the two groups of patients revealed that they were comparable with regard to age, sex, ejection fraction, cardiac output, number of bypass grafts performed, and duration of ischemia (Table 11). Hospital course. The groups which received steroids were in a slightly lower average New York Heart Association functional class. There were no hospital deaths in either group. Seven patients in the control group and six in the steroid-treated group were given inotropic support postoperatively. Three control patients and two steroid-treated patients received counterpulsation postoperatively. Loss of R waves or appearance of new Q waves was seen on the electrocardiogram in four control patients and three steroidtreated patients.
Table I. Composition of cardioplegic solution 147.5 25 4.5 156 12.5
Na" (mEq.lL.) K+ (mEq.) Ca " (mEq.) CI (mEq.) Mannitol (Gm.) pH 7.40 at 37° cOsmolarity 370 mOsm.lL.
'The pH was adjusted by addition of sodium bicarbonate as required to each liter bag of stock Ringers injection (usually 3 to 8 mEq.). This changes the above ionic composition slightly.
Table II. Patient data
Number Age (yr.) Percent males Functional class Previous MI Previous CHF Preoperative LVEDP (mm. Hg)t Preoperative EF (%) Cardiac output before bypass (L./min.) Ischemic time (min.) No. of grafts
Group II (no steroids)
Difference *
10 50.5 (±8.9) 90 2.2 (±0.4) 4 1 13.1 (±4.7)
12 56.0 (±6.9) 100 2.6 (±0.5) 5 0 11.3 (±4.6)
NS NS <0.05 NS NS NS
70.8 (±1O.7) 5.4 (±1.1)
72.5 (± 16.1) 5.0 (±1.6)
NS NS
55.3 (±19.5) 2.3 (± 1.1)
45.4 (± 14.4) 2.1 (±0.7)
NS NS
Legend: MI, Myocardial infarction. CHF, Congestive heart failure. LVEDP, Left ventricular end-diastolic pressure. EF, Ejection fraction. NS, No significant difference. 'Significance between data determined by Student's t test and expressed as p value.
t At cardiac catheterization.
Discussion The ideal method for avoiding myocardial injury from ischemia during myocardial revascularization remains controversial. Although some surgeons use brief periods of hypothermic coronary perfusion between anastomoses, there is some evidence that this may be harmful," especially if the heart is allowed to fibrillate through the entire procedure. Others have used profound local hypothermia to protect the myocardium during one continuous period of aortic cross-clamping. However, there are data to suggest that profound hypothermia itself produces diminished left ventricular compliance and impairment of function." Also, with this technique the heart is allowed to fibrillate for long periods of time, which may be detrimental. 6. 7 That these methods provide incomplete protection is suggested by the occasional need for inotropic support postoperatively and by the fact that 5 to 20 percent of patients have had intraoperative myocardial infarction. Cold cardioplegia appears to improve clinical re-
898
The Journal of Thoracic and Cardiovascular Surgery
Kirsh, Behrendt, Jochim
suits. H-IO However, the composition of the solutions used varies widely and the ideal composition awaits definition. It has been suggested that corticosteroids be one component of cardioplegic solutions because of their general ability to localize in cell membranes and stabilize cell and lysosomal membranes during ischernia.!': 12 However, their effectiveness in actually protecting myocardial cells during ischemia is debatable. In isolated heart and papillary muscle preparations, conflicting results have been obtained. Functional recovery from hypoxic perfusion was improved and intracellular energy stores were conserved by methylprednisolone in some studies but not others. 13 - 15 In whole animal experiments, evidence that methylprednisolone protects the heart from ischemia is also conflicting. Following global cardiac ischemia produced by aortic occlusion, Krause;" Busuttil," Fey, 17 Hicks ," and their co-workers showed reduction in cardiac enzyme release accompanied by improvement in cardiac function in methylprednisolone-treated animals. Barner and associates," on the other hand, were unable to demonstrate any protective effect of methylprednisolone on cardiodynamics or ultrastructure after 60 minutes of profound topical hypothermia. Other whole animal experiments have assessed the value of methylprednisolone in reducing the extent of localized myocardial infarction produced by occlusion of individual coronary arteries. Vyden,'" Spath.P" and their co-workers demonstrated a protective effect in terms of reduction in creatine phosphokinase and lysosomal hydrolase release and improved cardiac performance. Conversely, Vogel and associates" could measure no improvement in infarct size or enzyme depletion in dogs receiving methylprednisolone prior to a 90 minute coronary occlusion. Little quantitative data are available in human beings concerning the possible protective effect of steroids during global cardiac ischemia. Codd.F Morton." and their associates found no improvement in postoperative serum enzymes, incidence of infarction, or need for postoperative support in patients receiving 2 Gm. of methylprednisolone prior to myocardial revascularization. These are only indirect indices of cardiac performance and provide little insight into how the myocardium itself may have been affected functionally. This study focused upon myocardial performance itself as measured immediately before and after a period of ischemia during which the myocardium was protected by a cold, hyperkalemic cardioplegic solution. The addition of methylprednisolone to this solution produced no apparent benefit. Neither steroid-treated nor control patients had a demonstrable alteration in
cardiac performance, and the postoperative courses of the two groups were similar. One might speculate that, had a greater ischemic insult been produced, methylpredinsolone might have exerted an observable protective effect. Because both groups were so well protected by the cardioplegic solution, the beneficial effects of the added steroids may not have been apparent. In any case, because of these data, we do not recommend including methylprednisolone in the cardioplegic solution. We would like to thank Mr. John Straker and Mr. Munier Jallad for their technical assistance in these studies.
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REFERENCES Mirsky I, Ellison RC. Hugenholtz PG: Assessment of myocardial contractility in man from ventricular pressure recordings. Clin Res 17:255. 1969 Quinones MA, Goasch WH, Alexander JK: Influence of acute changes in preload, afterload, contractile state and heart rate on ejection and isovolumic indices of myocardial contractility in man. Circulation 53:293, 1976 Behrendt OM, Kirsh MM, Jochim KE, et al: Effects of cardioplegic solution on human contractile element velocity. Ann Thorac Surg 26:201, 1978 Levitsky S. Wright RN, Rao KS, Holland C. Roper K. Engelman R, Feinberg H: Does intermittent coronary perfusion offer greater myocardial protection than continuous aortic cross-clamping? Surgery 82:51, 1977 Tyers GFO, Williams EH, Hughes HC, Todd GJ: Effeci of perfusate temperature on myocardial protection from ischemia. J THoRAc CARDIOVASC SURG 73:766, 1977 Hottenrott CE, Towers B, Kurkji HJ, Maloney JV, Buckberg G: The hazard of ventricular fibrillation in hypertrophied ventricles during cardiopulmonary bypass. J THORAC CARDIOVASC SURG 66:742, 1973 Grover LF, Fewel JG, Ghidoni JJ, et al: Effects of ventricular fibrillation on coronary blood flow and myocardial metabolism. Presented at the Twenty-fifth Scientific Session of the American College of Cardiology, New Orleans, La., February, 1976 Molina JE, Feiber W, Sisk A, Polen T, Collins B: Cardioplegia without fibrillation or defibrillation in cardiac surgery. Surgery 81:619, 1977 Bleese N, Doring V, Kalmar P, Pokar H, Polonius M-1, Steiner 0, Rodewald G: Intraoperative myocardial protection by cardioplegia in hypothermia. 1 THoRAc CARDlOVASC SURG 75:405, 1978 Roe BB, Hutchinson JC, Fishman NH, Ullyot 01, Smith DL: Myocardial protection with cold, ischemic, potassium-induced cardioplegia. 1 THoRAc CARDIOVASC SURG 73:366, 1977 Clermont HG, Williams 1S, Adams JT: Steroid effect on the release of the lysosomal enzyme acid phosphatase in shock. Ann Surg 179:917, 1974 Fewitt DE, Skelton CL, Sonnenblick EH: Salutary effect
Volume 77 Number 6 June, 1979
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Methylprednisolone in cardioplegic solution
of methylprednisolone on viability of heart muscle exposed to anoxia. Br Heart J 35:863, 1973 Nayler WG, Seabra, Gomez RS: Effect of methylprednisolone sodium succinate on hypoxic heart muscle. Cardiovasc Res 10:349, 1976 Vyden JK, Nagasawa K, Rabinowitz B, et al: Effects of methylprednisolone administration in aeute myocardial infarction. Am J Cardiol 34:677, 1974 Krause LB, Hassan MA, McMillan AB, et al: Protective effect of methylprednisolone on ischemic myocardium assessed by ventricular function. Thorax 32: IS5, 1977 Busuttil RW, George WJ, Hewitt RL: Protective effect of methylprednisolone on the heart during ischemic arrest. J THORAC CARDIOVASC SURG 70:955, 1975 Fey KH, Follette DM, Livesay Ll. et al: Effects of steroid pretreatment on L V blood flow, compliance, and performance after hypothermic ischemic arrest. Surg Forum 27:246, 1976 Hicks GL. Hill AA, DeWeese JA: Myocardial preserva-
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899
tion with glucose-insulin-potassium and steroids during anoxic arrest. Surg Forum 27:239, 1976 Barner HB, Standeven JW, Jellinek M, Menz LJ, Hahn JH: Topical cardiac hypothermia for myocardial preservation. J THORAC CARDIOVASC SURG 73:865, 1977 Spath JA, Lane OL, Lefer AM: Protective action of methylprednisolone on the myocardium during experimental myocardial ischemia in the cat. Circ Res 35:44, 1974 Vogel WM, Zannoni VG, Abrams GO, et al: Inability of methylprednisolone sodium succinate to decrease infarct size or preserve enzyme activity measured 24 hours after coronary occlusion in the dog. Circulation 55:588, 1977 Codd JE, Wiens RD, Barner HB, Kaiser GC, and Willman VL: Steroids and myocardial preservation. Circulation 74:418, 1977 Morton JR, Hiebert CA, Lutes CA, et al: Effect of methylprednisolone on myocardial preservation during coronary artery surgery. Am J Surg 131:419, 1976
Information for authors Most of the provisions of the Copyright Act of 1976 became effective on January I, 1978. Therefore, all manuscripts must be accompanied by the following written statement, signed by one author: "The undersigned author transfers all copyright ownership of the manuscript (title of article) to The C. V. Mosby Company in the event the work is published. The undersigned author warrants that the article is original, is not under consideration by another journal, and has not been previously published. I sign for and accept responsibility for releasing this material on behalf of any and all co-authors." Authors will be consulted, when possible, regarding republication of their material.
Marvin M. Kirsh, M.D.,* Douglas M. Behrendt, M.D.,* and Kenneth E. Jochim, M.D.,** Ann Arbor, Mich.
Limitations of previously used techniques of myocardial preservation have led to renewed interest in the use of cold cardioplegia as a means of providing myocardial protection during coronary revascularization. Potassium is the active ingredient common to most of the proposed solutions, but various other components have been used as well, usually with little experimental support. Since there is evidence that steroids may exert a protective effect on the ischemic myocardium, some workers have added them to cardioplegic solutions. The present study was undertaken to determine whether steroids do provide additional protection when added to a cardioplegic solution during ischemic cardiac arrest in patients undergoing coronary revascularization.
Methods Twenty-two patients undergoing elective coronary artery bypass grafting were randomly assigned by the perfusionist to one of two groups: In Group I, IO patients, 500 mg. of methylprednisolone was added to each liter of cardioplegic solution. These patients were compared to a control group of 12 patients (Group II), From the University of Michigan, Ann Arbor, Mich. Received for publication Oct. 30, 1978. Accepted for publication Jan. 30, 1979. Address for reprints: Marvin M. Kirsh, M.D .. The Section of Thoracic Surgery, University Hospital, C7079 Out-patient Building, Ann Arbor, Mich. 48109. *Section of Thoracic Surgery, Department of Surgery. **Department of Physiology.
896
in whom methylprednisolone was not added to the cardioplegic solution. No member of the surgical staff knew which patients had received steroids until the data had been analyzed. After institution of cardiopulmonary bypass, the left ventricle was vented through the right superior pulmonary vein and the patient's temperature was lowered to 28° C. The aorta was then clamped and I L. of 4° C. cardioplegic solution was infused into the aortic root proximal to the aortic cross-clamp (Table I). Thereafter, 500 C.c. of the solution was infused after 30 minutes, or earlier if electrical activity resumed prior to 30 minutes. All distal anastomoses were constructed during one continuous period of aortic cross-clamping. After completion of the distal anastomoses, the aortic clamp was removed and the heart defibrillated if necessary. While the patient was being rewarmed, the proximal anastomoses were performed with a partial occluding clamp on the aorta and the heart beating. Efficacy of the cardioplegic solutions in protecting the myocardium from ischemic damage was evaluated in the following manner. Myocardial contractility was assessed immediately before and after the period of perfusion by intraoperative measurement of contractile element velocity. A No.4 Fr. Millar transducer-tipped catheter was inserted into the left ventricle through an apical stab wound to provide a high-fidelity left ventricular pressure signal and its first derivative (dP/dt). Then loops of the quantity (dP/dt)/P versus P were recorded, P being the instantaneous total left ventricular pressure.
0022-5223179/060896+04$00040/0 © 1979 The C. V. Mosby Co.
Volume 77 Number 6
Methylprednisolone in cardioplegic solution
897
June, 1979
During isovolumetric systole, the quantity (dP/dt)/P is equal to the velocity of contractile element shortening (VCE).' Also, the maximum observed value of VCE (Vpm) is a sensitive contractility index, not influenced by afterload but somewhat dependent upon preload and heart rate. 2. :l Thus, in the present study, Vpm was recorded in each patient before and after bypass at 37° C., with heart rate held constant by atrial pacing when necessary and with preload held constant by volume infusion or withdrawal from the pump oxygenator when necessary. The "before" and "after" values of Vpm for each group were compared by use of a t test for paired data to determine if a significant change in contractility had occurred during the operation. The patient's records also were retrospectively reviewed to determine if there were differences between the two groups with regard to mortality rate, use of inotropic agents or balloon pump, or electrocardiographic evidence of myocardial infarction or arrhythmias.
Results Myocardial contractility. In patients who received steroids there was a statistically insignificant (p > 0.05) reduction in Vpm from 30.6 (± 9.3 S.D.) sec.- t to 30.1 (± 8.2 S.D.) sec.-I and a statistically insignificant increase in left ventricular end-diastolic pressure (LVEDP) from 18.5 (± 7.7 S.D.) to 22.1 (± 8.1 S.D.) mm. Hg. Similarly, no significant changes were observed in the patients who did not receive steroids- Vpm changed from 35.2 (± 13.1 S.D.) to 33.8 (± 12.9 S.D.) sec.-I and LVEDP from 16.2 (± 10.3 S.D.) to 16.5 (± 9.5 S.D.) mm. Hg. The difference between the means of the Vpm and L VEDP values of the two groups also was statistically insignificant both preoperatively and postoperatively. Retrospective analysis of characteristics of the two groups of patients revealed that they were comparable with regard to age, sex, ejection fraction, cardiac output, number of bypass grafts performed, and duration of ischemia (Table 11). Hospital course. The groups which received steroids were in a slightly lower average New York Heart Association functional class. There were no hospital deaths in either group. Seven patients in the control group and six in the steroid-treated group were given inotropic support postoperatively. Three control patients and two steroid-treated patients received counterpulsation postoperatively. Loss of R waves or appearance of new Q waves was seen on the electrocardiogram in four control patients and three steroidtreated patients.
Table I. Composition of cardioplegic solution 147.5 25 4.5 156 12.5
Na" (mEq.lL.) K+ (mEq.) Ca " (mEq.) CI (mEq.) Mannitol (Gm.) pH 7.40 at 37° cOsmolarity 370 mOsm.lL.
'The pH was adjusted by addition of sodium bicarbonate as required to each liter bag of stock Ringers injection (usually 3 to 8 mEq.). This changes the above ionic composition slightly.
Table II. Patient data
Number Age (yr.) Percent males Functional class Previous MI Previous CHF Preoperative LVEDP (mm. Hg)t Preoperative EF (%) Cardiac output before bypass (L./min.) Ischemic time (min.) No. of grafts
Group II (no steroids)
Difference *
10 50.5 (±8.9) 90 2.2 (±0.4) 4 1 13.1 (±4.7)
12 56.0 (±6.9) 100 2.6 (±0.5) 5 0 11.3 (±4.6)
NS NS <0.05 NS NS NS
70.8 (±1O.7) 5.4 (±1.1)
72.5 (± 16.1) 5.0 (±1.6)
NS NS
55.3 (±19.5) 2.3 (± 1.1)
45.4 (± 14.4) 2.1 (±0.7)
NS NS
Legend: MI, Myocardial infarction. CHF, Congestive heart failure. LVEDP, Left ventricular end-diastolic pressure. EF, Ejection fraction. NS, No significant difference. 'Significance between data determined by Student's t test and expressed as p value.
t At cardiac catheterization.
Discussion The ideal method for avoiding myocardial injury from ischemia during myocardial revascularization remains controversial. Although some surgeons use brief periods of hypothermic coronary perfusion between anastomoses, there is some evidence that this may be harmful," especially if the heart is allowed to fibrillate through the entire procedure. Others have used profound local hypothermia to protect the myocardium during one continuous period of aortic cross-clamping. However, there are data to suggest that profound hypothermia itself produces diminished left ventricular compliance and impairment of function." Also, with this technique the heart is allowed to fibrillate for long periods of time, which may be detrimental. 6. 7 That these methods provide incomplete protection is suggested by the occasional need for inotropic support postoperatively and by the fact that 5 to 20 percent of patients have had intraoperative myocardial infarction. Cold cardioplegia appears to improve clinical re-
898
The Journal of Thoracic and Cardiovascular Surgery
Kirsh, Behrendt, Jochim
suits. H-IO However, the composition of the solutions used varies widely and the ideal composition awaits definition. It has been suggested that corticosteroids be one component of cardioplegic solutions because of their general ability to localize in cell membranes and stabilize cell and lysosomal membranes during ischernia.!': 12 However, their effectiveness in actually protecting myocardial cells during ischemia is debatable. In isolated heart and papillary muscle preparations, conflicting results have been obtained. Functional recovery from hypoxic perfusion was improved and intracellular energy stores were conserved by methylprednisolone in some studies but not others. 13 - 15 In whole animal experiments, evidence that methylprednisolone protects the heart from ischemia is also conflicting. Following global cardiac ischemia produced by aortic occlusion, Krause;" Busuttil," Fey, 17 Hicks ," and their co-workers showed reduction in cardiac enzyme release accompanied by improvement in cardiac function in methylprednisolone-treated animals. Barner and associates," on the other hand, were unable to demonstrate any protective effect of methylprednisolone on cardiodynamics or ultrastructure after 60 minutes of profound topical hypothermia. Other whole animal experiments have assessed the value of methylprednisolone in reducing the extent of localized myocardial infarction produced by occlusion of individual coronary arteries. Vyden,'" Spath.P" and their co-workers demonstrated a protective effect in terms of reduction in creatine phosphokinase and lysosomal hydrolase release and improved cardiac performance. Conversely, Vogel and associates" could measure no improvement in infarct size or enzyme depletion in dogs receiving methylprednisolone prior to a 90 minute coronary occlusion. Little quantitative data are available in human beings concerning the possible protective effect of steroids during global cardiac ischemia. Codd.F Morton." and their associates found no improvement in postoperative serum enzymes, incidence of infarction, or need for postoperative support in patients receiving 2 Gm. of methylprednisolone prior to myocardial revascularization. These are only indirect indices of cardiac performance and provide little insight into how the myocardium itself may have been affected functionally. This study focused upon myocardial performance itself as measured immediately before and after a period of ischemia during which the myocardium was protected by a cold, hyperkalemic cardioplegic solution. The addition of methylprednisolone to this solution produced no apparent benefit. Neither steroid-treated nor control patients had a demonstrable alteration in
cardiac performance, and the postoperative courses of the two groups were similar. One might speculate that, had a greater ischemic insult been produced, methylpredinsolone might have exerted an observable protective effect. Because both groups were so well protected by the cardioplegic solution, the beneficial effects of the added steroids may not have been apparent. In any case, because of these data, we do not recommend including methylprednisolone in the cardioplegic solution. We would like to thank Mr. John Straker and Mr. Munier Jallad for their technical assistance in these studies.
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REFERENCES Mirsky I, Ellison RC. Hugenholtz PG: Assessment of myocardial contractility in man from ventricular pressure recordings. Clin Res 17:255. 1969 Quinones MA, Goasch WH, Alexander JK: Influence of acute changes in preload, afterload, contractile state and heart rate on ejection and isovolumic indices of myocardial contractility in man. Circulation 53:293, 1976 Behrendt OM, Kirsh MM, Jochim KE, et al: Effects of cardioplegic solution on human contractile element velocity. Ann Thorac Surg 26:201, 1978 Levitsky S. Wright RN, Rao KS, Holland C. Roper K. Engelman R, Feinberg H: Does intermittent coronary perfusion offer greater myocardial protection than continuous aortic cross-clamping? Surgery 82:51, 1977 Tyers GFO, Williams EH, Hughes HC, Todd GJ: Effeci of perfusate temperature on myocardial protection from ischemia. J THoRAc CARDIOVASC SURG 73:766, 1977 Hottenrott CE, Towers B, Kurkji HJ, Maloney JV, Buckberg G: The hazard of ventricular fibrillation in hypertrophied ventricles during cardiopulmonary bypass. J THORAC CARDIOVASC SURG 66:742, 1973 Grover LF, Fewel JG, Ghidoni JJ, et al: Effects of ventricular fibrillation on coronary blood flow and myocardial metabolism. Presented at the Twenty-fifth Scientific Session of the American College of Cardiology, New Orleans, La., February, 1976 Molina JE, Feiber W, Sisk A, Polen T, Collins B: Cardioplegia without fibrillation or defibrillation in cardiac surgery. Surgery 81:619, 1977 Bleese N, Doring V, Kalmar P, Pokar H, Polonius M-1, Steiner 0, Rodewald G: Intraoperative myocardial protection by cardioplegia in hypothermia. 1 THoRAc CARDlOVASC SURG 75:405, 1978 Roe BB, Hutchinson JC, Fishman NH, Ullyot 01, Smith DL: Myocardial protection with cold, ischemic, potassium-induced cardioplegia. 1 THoRAc CARDIOVASC SURG 73:366, 1977 Clermont HG, Williams 1S, Adams JT: Steroid effect on the release of the lysosomal enzyme acid phosphatase in shock. Ann Surg 179:917, 1974 Fewitt DE, Skelton CL, Sonnenblick EH: Salutary effect
Volume 77 Number 6 June, 1979
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Methylprednisolone in cardioplegic solution
of methylprednisolone on viability of heart muscle exposed to anoxia. Br Heart J 35:863, 1973 Nayler WG, Seabra, Gomez RS: Effect of methylprednisolone sodium succinate on hypoxic heart muscle. Cardiovasc Res 10:349, 1976 Vyden JK, Nagasawa K, Rabinowitz B, et al: Effects of methylprednisolone administration in aeute myocardial infarction. Am J Cardiol 34:677, 1974 Krause LB, Hassan MA, McMillan AB, et al: Protective effect of methylprednisolone on ischemic myocardium assessed by ventricular function. Thorax 32: IS5, 1977 Busuttil RW, George WJ, Hewitt RL: Protective effect of methylprednisolone on the heart during ischemic arrest. J THORAC CARDIOVASC SURG 70:955, 1975 Fey KH, Follette DM, Livesay Ll. et al: Effects of steroid pretreatment on L V blood flow, compliance, and performance after hypothermic ischemic arrest. Surg Forum 27:246, 1976 Hicks GL. Hill AA, DeWeese JA: Myocardial preserva-
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tion with glucose-insulin-potassium and steroids during anoxic arrest. Surg Forum 27:239, 1976 Barner HB, Standeven JW, Jellinek M, Menz LJ, Hahn JH: Topical cardiac hypothermia for myocardial preservation. J THORAC CARDIOVASC SURG 73:865, 1977 Spath JA, Lane OL, Lefer AM: Protective action of methylprednisolone on the myocardium during experimental myocardial ischemia in the cat. Circ Res 35:44, 1974 Vogel WM, Zannoni VG, Abrams GO, et al: Inability of methylprednisolone sodium succinate to decrease infarct size or preserve enzyme activity measured 24 hours after coronary occlusion in the dog. Circulation 55:588, 1977 Codd JE, Wiens RD, Barner HB, Kaiser GC, and Willman VL: Steroids and myocardial preservation. Circulation 74:418, 1977 Morton JR, Hiebert CA, Lutes CA, et al: Effect of methylprednisolone on myocardial preservation during coronary artery surgery. Am J Surg 131:419, 1976
Information for authors Most of the provisions of the Copyright Act of 1976 became effective on January I, 1978. Therefore, all manuscripts must be accompanied by the following written statement, signed by one author: "The undersigned author transfers all copyright ownership of the manuscript (title of article) to The C. V. Mosby Company in the event the work is published. The undersigned author warrants that the article is original, is not under consideration by another journal, and has not been previously published. I sign for and accept responsibility for releasing this material on behalf of any and all co-authors." Authors will be consulted, when possible, regarding republication of their material.