Curdioiovascrtlur Research, 1979, 13, 58-61
Effects of methylprednisolone on ventricular arrhythmias during acute myocardial ischaemia M Y U N G S. Y O O N , B R l J G . G O E L . A N D J A O K H A N ' From the Departmetit of Medicine (Cardiology), Albany Medical College of Union University, and the E1ectrocardioRraph.v Luhoratory, Albany Medical Center Hospital, Albany, New York
S U M M A R Y The effects of methylprednisolone (50 mg-kg I ) on the incidence of ventricular tachycardia and fibrillation and on ventricular fibrillation threshold were studied during acute coronary occlusion in anaesthetised dogs. Ventricular tachycardia and /or ventricular fibrillation occurred in I I of the 16 animals (69%) both before and after methylprednisolone pretreatment. The mean ventricular fibrillation threshold of 10 dogs was 10.1 f1.8 mA before methylprednisolone and it increased slightly - . to 13.3 12.3 mA after the drug. This difference was not statistically significant
(P> 0.2).
Many recent studies indicated that glucocorticoids show beneficial and protective effects in ischaemic hearts by decreasing the infarct size through haernodynamic improvement (Libby et al., 1973; Maroko and Braunwald, 1973; Morrison et al., 1975, 1976; Braunwald and Maroko, 1976). The steroid has also been used to treat various degrees of atrioventricular block accompanying myocardial infarction (Prinzmetal and Kennamer, 1954; Aber and Jones, 1960; Carameli and Tellini, 1960; Dall, 1964). However, very little information is available in the literature regarding the effect of glucocorticoids on the incidence of ventricular arrhythmias and vulnerability to fibrillation. One group reported that administration of the steroid appeared to have reduced the incidence of ventricular fibrillation (VF) in experimental animals with cardiogenic shock induced by coronary occlusion (Clement et nl., 1974). A more recent publication, however, reported deleterious effects of methylprednisolone on ventricular arrhythmias in patients with myocardial infarction (Roberts et a/., 1976). Another group observed the lack of a beneficial effect of glucocorticoids on the incidence of ventricular arrhythmias during the course of acute ischaemia in isolated perfused cat hearts (Beardsley et ul., 1976). To date, the direct electrophysiological effects of steroids in ischaemic hearts have not been systematically studied. We therefore studied the effect of the potent synthetic glucocorticoid, methylprednisolone, on the incidence of ventricular arrhythmias and ventricular fibrillation threshold ( V F T ) during acute coronary occlusion in animal experiments.
Methods Experiments were performed on mongrel dogs anaesthetised by an intravenous injection of sodium pentobarbital (30 to 35 mgskg-I). Under artificial respiration, the chest was opened at the midline and the heart was cradled in the opened pericardiurn. To permit pacing of the heart at a constant rate, the sinoatrial node was inactivated by crushing. For reversible occlusion of the anterior descending branch of the left coronary artery, the artery was dissected free just above the diagonal branch take-off and a snare was applied around the vessel. A femoral artery was cannulated to monitor the arterial pressure and a femoral vein for the administration of methylprednisolone. The bipolar stimulating and recording electrodes were small steel hooks with an interelectrode distance of 3 to 4 mm. The stimulating electrodes were attached to the anterior septa1 margin of the right ventricle about 10 mm away from the edge of the expected ischaemic area. One set of the recording electrodes was attached to a site close to the stirnulating electrodes in the right ventricle. The arterial pressure, a lead I 1 electrocardiogram, the local electrogram and the artifact of stimuli delivered to the stimulating electrodes were all monitored on a Grass polygraph. The stimuli were also displayed on an oscilloscope and calibrated by a Tektronix current probe amplifier. The patterns of pacing and test stimuli delivered to the ventricle were programmed by using a variable interval generator and a series of Tektronix waveforms and pulse generators. The output of the pulse generator triggered a Grass stimulator which, in turn, delivered 2 ms pulses to the stimulating electrodes.
'Address for reprints: Jaok Han, M.D., Dept. of Medicine, Alhany Medical College, Albany. New York 12208, USA. 58
59
Sixteen dogs were used to study the incidence o f ventricular arrhythmias. Immediately after occlusion o f the anterior descending artery, the recording of electrocardiograms was continuously made for 10 min. The arterial occlusion was then released, and at least 15 rnin were allowed for recovery before further observations were made. When VF occurred within 10 rnin of coronary occlusion, the occlusion was immediately released and defibrillation was accomplished by DC countershock, and about 15 min were allowed for recovery. Following the control observation. methylprednisolone was administered intravenously in a dose of 50 mg-kg I over a 2 rnin period. I 5 rnin after methylprednisolone pretreatment. the coronary artery was again occluded and the same procedure was repeated to study the drug effect. The effect o f methylprednisolone on VFT was studied in 10 dogs by delivering a train o f rapid pulses across the vulnerable period as described previously by one of us (Han, 1969a). I n each animal, VFT's were determined 3 to 5 rnin after occlusion of I he anterior descending artery before and after methylprednisolone pretreatment. The ventricle was paced by basic stimuli at a cycle length o f 400 msand a train of rapid pulses was delivered after every 10th basic ventricular response. The rapid pulses were 2 ms in duration and occurred at 10 ms intervals. The train was started 60 to 100 ms after the last basic response and its duration was 100 ms and did not extend the absolute refractory period o f the first premature response induced by the train. The intensity o f the rapid pulses was gradually increased until fibrillation resulted. The VFT was then defined as the minimum current in mA which induced fibrillation. When VF occurred, the coronary occlusion was immediately released and defibrillation was accomplished and at least 15 rnin were allowed for recovery.
Results INCIDENCE O F V E N T R I C U L A R ARRHYTHMIAS
The records were reviewed with regard to the incidence and onset of ventricular premature beats (VPB's). tachycardia ( V T ) and fibrillation (VF). The particular emphasis was given to more serious arrhythmias such as VT and VF. The chi-square test was used to determine the statistical significance o f differences in the incidence of arrhythmias before and after methylprednisolone. Ventricular arrhythmias were graded according to the criteria used by us (Yoon 1'1 d..1978) as follows: Grade 0: no VPB Grade I : occasional VPBs ( I to 2 VPB's per niin) Grade 2: frequent VPB's ( 3 or more VPB's per min) Grade 3 : VT (more than 3 VPB's in a run) Grade 4: VF Fig. I shows the results obtained from the 16 experiments. The frequencies of occurrence o f various ventricular arrhythmias were similar before and after methylprednisolone. When VT and VF were considered together, the incidence of these high grade arrhythmias was 69% ( I I /16) both before and after the drug. VF occurred in 56% (9/16) before and i n 502, (8 /16) after methylprednisolone pretreatment. and the difference was not statistically significant (P>0.5). As shown in Fig. 2. the average time of onset o f VF was 244 ? 23 s before and 266 28 s after the drug, and the difference was again statistically insignificant (P> 0.5). 4
VENTR IC UL A
K F IH K IL L A TI 0 N
THRESHOLD
Fig. 3 shows the results obtained from the 10 dogs. The mean VFT was 10.1 I 1.8 mA before methyl-
Fig. I
Di.s/rihicticiri I/' vuriiiits wntriculur urrhj,thnrius occurring clirring 10 niin OJ coronurj' occlitsiun brforc, untl ujier nieth~~lpreti~risol~it~r pretreuarrirent in 16 dog.^. GO -graclr 0, no VPB: G I grudc I , occusionul VPB's; G2 grutlc' 2. /rcquc*tit VPB's; G3 grade 3. VT: G4 xrarle 4. VF. ~~
Mj~rtiigS.
Yoorr, Brrj G . Goi4, airtl JaoX Hair
VT and VF are among the leading causes of death during the initial phase of acute myocardial infarction. Various steroid preparations have been used clinically for patients suffering from myocardial infarction and cardiogenic shock. However, the direct effects of steroids on ventricular arrhythmias have not been studied systematically and the few reports available are contradictory (Beardsley et a/., 1976; Roberts et a/., 1976). Our study demonstrated that methylprednisolone has no significant beneficial effects on the incidence of ventricular arrhythmias or on the VFT during the acute phase of coronary occlusion. The tendency of a slight delay in the onset of VF shown after the methylprednisolone pretreatment was not statistically significant. These results suggest that methylprednisolone per se did not change the electrophysiological properties significantly enough to alter the ventricular vulnerability to arrhythmias during acute myocardial ischaemia. The lack of a beneficial effect of methylprednisolone in the ventricles subjected to acute coronary occlusion in this study suggests that it is unlikely to be of benefit in the treatment of ventricular arrhythmias in the early phase of myocardial infarction in
Fig. 2 The tiine of onset of VF aJier coronary occlusion ( C O ) before and aJier trreth~~lprerlnisolone administration.
prednisolone, and it increased slightly to 13.3 1 2.3 mA after the drug. This difference, however, was not statistically significant ( P > 0.2).
Discussion The glucocorticoid has been shown to be beneficial in ischaemic ventricles by reducing the infarct size (Maroko and Braunwald, 1973; Libby ef a/., 1973; Morrison et a/., 1975 1976; Braunwald and Maroko, 1976). The mechanism of the protective effect of the glucocorticoid is not clear. The coronary vasodilatory effect (Vyden et a/., 1971; Libby et a/., 1973) and the lysosomal stabilising effect (Clement e t a / . , 1974; Vaisrub, 1974; Lefer, 1974; Spath et a/., 1974) of the steroid were cited for the protective effect on the ischaemic ventricles. A well known anti-inflammatory effect of the steroid might also explain the beneficial effect through the stabilisation of the phagocytic vacuoles of the infiltrating inflammatory cells (Maroko and Braunwald, 1973). The glucocorticoid has also been used to reverse or improve the impaired atriOVentriCUhr conduction often accompanying acute myocardial infarction (Prinzmetal and Kannamer, 1954; Aber and Jones, 1960; Carameli and Tellini, 1960; Dall, 1964).
Fig. 3 ConIparison of v n s obtaine(/ before and after methylprednisolone pretreatment in I0 dogs during acute coronary occlusion (CO). The values are expressed as mean _t SE.
61
clinical situations. Marked depression in excitability and conductivity produced by myocardial ischaemia in the affected area are believed to be, in part, responsible for the mechanism of ventricular arrhythmias associated with myocardial infarction (Han, 1969a,b). Therefore, methylprednisolone seemingly failed to counteract such deleterious effects of myocardial ischaemia. It should be noted that our study was intended to test the direct effect of methylprednisolone on ventricular arrhythmias in acutely ischaemic hearts 15 min after a single dose of methylprednisolone. The deleterious effects of methylprednisolone reported in patients with acute myocardial infarction (Roberts et ul., 19’76)do not necessarily contradict our animal experimental results. The adverse effects reported in their study were observed only in patients treated by multiple doses of methylprednisolone (30 mg-kg-’ i.v. every 6 h for 48 h). A slight reduction in the incidence of ventricular arrhythmias after a single intravenous dose of methylprednisolone in their study agrees with our experimental observation. Based on the results of our animal experiments, it is suggested that the use of methylprednisolone might not be justified for the purpose of suppressing ventricular arrhythmias accompanying acute myocardial infarction. Supported by Grant HL-18796 from the National Institutes of Health, and a grant from the Upjohn Company. The authors are grateful to Susan Jones and Rosalyn Rogers for their technical assistance and to Oksana Ciupka for the preparation of this manusciipt. References Aher. C. P., and Jones, E. (1960). Complete heart block treated with corticotropin and corticosteroid. llrirish Hcwrr Jorirnal, 22,723-728, Beardsley. A. C., Okuda, M., and Lefer, A. M. (1976). Absence of a cardiodynamic action of glucocorticoids in acute myocardial ischaemia. Journal of Surgical Rrsrarclr, 20, 17-24. Braunwald, E. (1973). Reduction of experimental myocardial infarct size by corticosteroid administration. Clinical Invcsrigarion, 53, 599-607.
Braunwald, E., and Maroko, P. R. (1976). Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion. Atwricon Joirrnal [I/ Carcliology, 37, 550-556. Carameli, Z., and Tellini, R. R. (1960). Treatment of atrioventricular block with prednisone. Anrrrican Journal of Cardiology, 5, 263-265. Clement, H. G.,Williams, J. S . . and Adanis. J. T. (1974). Steroid effect on the release of the lysosomal enzyme acid phosphatase in shock. Annals of Surgc*r.v, 179, 9 17-921. Dall, J. L. L. (1964). The effects of steroid therapy on normal and abnormal atrioventricular conduction. Brirish Hearf Joiimal, 26, 537-543. Han, J. (1969a). Ventricular vulnerability during coronary occlusion. American Juirrnal o/’ Cardiology, 24, 857-864. Han, J . (l969b). Mechanisms of ventricular arrhythmias associated with myocardial infarction. Anwrican Joiimal of Cardiology, 24, 800-8 13. Lefer, A. M. (1974). Toward a rational drug therapy in cardiogenic shock. Cirrrilation Shock, I, 165- 168. Libby, P., Maroko, R. R., Bloor, C. M.,Sobel. B. E. and Maroko, P. R., and Braunwald. E. (1973). Modification of myocardial infarction size after coronary occlusion. Annals o/lntcrnul Mrdicinc, 19, 720-733. Morrison, J., Reduto. L., Malley, T.. and Gulotta, S. (1975). Protection of ischaemic myocardium in man by methylprednisolone. Ant~ricaii Joiirnul (if Curcliolugg!., 35, 158 (abstract). Morrison, J.. Reduto, L.. Pizzarello. R., Geller. K., Malley, T., and Gulotta, S. (1976). Modification of myocardial injury in man by corticosteroid administration. Circularion 53, Supplement 1, 200-203. Prinzmetal, M., and Kennamer, R. (1954). Emergency P treatment of cardiac arrhythmias. Jorirnal of I ~ Anrrrican Mrrlical Association. 154, 1049- 1054. Roberts, R., De Mello. V., and Sobel, B. E. (1976). Deleterious effects of methylprednisolone in patients with myocardial infarction. Circiilariun, 53, Supplement 1. 204-206. Spath, J. A.. Lane, D. L., and Lefer, A. M. (1974). Preservation of cardiac cellular integrity by methylprednisolone in acute myocardial infarction. Anwricun Journal of Curtliokogy, 33, 171 (abstract). Vaisruh. A. (1974). Myocardial depression factor ( M D F ) in cardiogenic shock. Journal of /he Aiirc*riwn Met1ic.d Associurion. 228, 500 Vyden, J. K.. Tomoda, H.. Prakashi. R., Chuck. L., Parmley, W. W.. and Corday. E. (1971). Effect ofcorticosteroids in shock secondary to myocardial infarction. Circirlarion, 43/44, 11-237 (abstract). Yoon, M. S.. Fondacaro, J. D., and Han, J. (978). Effects of vagal stimilation and atropine on ventricular arrhythmias during acute coronary occlusion. Joirrnal of Elrcrrocardiography, I I, (I), 27-3 1.
Effects of methylprednisolone on ventricular arrhythmias during acute myocardial ischaemia M Y U N G S. Y O O N , B R l J G . G O E L . A N D J A O K H A N ' From the Departmetit of Medicine (Cardiology), Albany Medical College of Union University, and the E1ectrocardioRraph.v Luhoratory, Albany Medical Center Hospital, Albany, New York
S U M M A R Y The effects of methylprednisolone (50 mg-kg I ) on the incidence of ventricular tachycardia and fibrillation and on ventricular fibrillation threshold were studied during acute coronary occlusion in anaesthetised dogs. Ventricular tachycardia and /or ventricular fibrillation occurred in I I of the 16 animals (69%) both before and after methylprednisolone pretreatment. The mean ventricular fibrillation threshold of 10 dogs was 10.1 f1.8 mA before methylprednisolone and it increased slightly - . to 13.3 12.3 mA after the drug. This difference was not statistically significant
(P> 0.2).
Many recent studies indicated that glucocorticoids show beneficial and protective effects in ischaemic hearts by decreasing the infarct size through haernodynamic improvement (Libby et al., 1973; Maroko and Braunwald, 1973; Morrison et al., 1975, 1976; Braunwald and Maroko, 1976). The steroid has also been used to treat various degrees of atrioventricular block accompanying myocardial infarction (Prinzmetal and Kennamer, 1954; Aber and Jones, 1960; Carameli and Tellini, 1960; Dall, 1964). However, very little information is available in the literature regarding the effect of glucocorticoids on the incidence of ventricular arrhythmias and vulnerability to fibrillation. One group reported that administration of the steroid appeared to have reduced the incidence of ventricular fibrillation (VF) in experimental animals with cardiogenic shock induced by coronary occlusion (Clement et nl., 1974). A more recent publication, however, reported deleterious effects of methylprednisolone on ventricular arrhythmias in patients with myocardial infarction (Roberts et a/., 1976). Another group observed the lack of a beneficial effect of glucocorticoids on the incidence of ventricular arrhythmias during the course of acute ischaemia in isolated perfused cat hearts (Beardsley et ul., 1976). To date, the direct electrophysiological effects of steroids in ischaemic hearts have not been systematically studied. We therefore studied the effect of the potent synthetic glucocorticoid, methylprednisolone, on the incidence of ventricular arrhythmias and ventricular fibrillation threshold ( V F T ) during acute coronary occlusion in animal experiments.
Methods Experiments were performed on mongrel dogs anaesthetised by an intravenous injection of sodium pentobarbital (30 to 35 mgskg-I). Under artificial respiration, the chest was opened at the midline and the heart was cradled in the opened pericardiurn. To permit pacing of the heart at a constant rate, the sinoatrial node was inactivated by crushing. For reversible occlusion of the anterior descending branch of the left coronary artery, the artery was dissected free just above the diagonal branch take-off and a snare was applied around the vessel. A femoral artery was cannulated to monitor the arterial pressure and a femoral vein for the administration of methylprednisolone. The bipolar stimulating and recording electrodes were small steel hooks with an interelectrode distance of 3 to 4 mm. The stimulating electrodes were attached to the anterior septa1 margin of the right ventricle about 10 mm away from the edge of the expected ischaemic area. One set of the recording electrodes was attached to a site close to the stirnulating electrodes in the right ventricle. The arterial pressure, a lead I 1 electrocardiogram, the local electrogram and the artifact of stimuli delivered to the stimulating electrodes were all monitored on a Grass polygraph. The stimuli were also displayed on an oscilloscope and calibrated by a Tektronix current probe amplifier. The patterns of pacing and test stimuli delivered to the ventricle were programmed by using a variable interval generator and a series of Tektronix waveforms and pulse generators. The output of the pulse generator triggered a Grass stimulator which, in turn, delivered 2 ms pulses to the stimulating electrodes.
'Address for reprints: Jaok Han, M.D., Dept. of Medicine, Alhany Medical College, Albany. New York 12208, USA. 58
59
Sixteen dogs were used to study the incidence o f ventricular arrhythmias. Immediately after occlusion o f the anterior descending artery, the recording of electrocardiograms was continuously made for 10 min. The arterial occlusion was then released, and at least 15 rnin were allowed for recovery before further observations were made. When VF occurred within 10 rnin of coronary occlusion, the occlusion was immediately released and defibrillation was accomplished by DC countershock, and about 15 min were allowed for recovery. Following the control observation. methylprednisolone was administered intravenously in a dose of 50 mg-kg I over a 2 rnin period. I 5 rnin after methylprednisolone pretreatment. the coronary artery was again occluded and the same procedure was repeated to study the drug effect. The effect o f methylprednisolone on VFT was studied in 10 dogs by delivering a train o f rapid pulses across the vulnerable period as described previously by one of us (Han, 1969a). I n each animal, VFT's were determined 3 to 5 rnin after occlusion of I he anterior descending artery before and after methylprednisolone pretreatment. The ventricle was paced by basic stimuli at a cycle length o f 400 msand a train of rapid pulses was delivered after every 10th basic ventricular response. The rapid pulses were 2 ms in duration and occurred at 10 ms intervals. The train was started 60 to 100 ms after the last basic response and its duration was 100 ms and did not extend the absolute refractory period o f the first premature response induced by the train. The intensity o f the rapid pulses was gradually increased until fibrillation resulted. The VFT was then defined as the minimum current in mA which induced fibrillation. When VF occurred, the coronary occlusion was immediately released and defibrillation was accomplished and at least 15 rnin were allowed for recovery.
Results INCIDENCE O F V E N T R I C U L A R ARRHYTHMIAS
The records were reviewed with regard to the incidence and onset of ventricular premature beats (VPB's). tachycardia ( V T ) and fibrillation (VF). The particular emphasis was given to more serious arrhythmias such as VT and VF. The chi-square test was used to determine the statistical significance o f differences in the incidence of arrhythmias before and after methylprednisolone. Ventricular arrhythmias were graded according to the criteria used by us (Yoon 1'1 d..1978) as follows: Grade 0: no VPB Grade I : occasional VPBs ( I to 2 VPB's per niin) Grade 2: frequent VPB's ( 3 or more VPB's per min) Grade 3 : VT (more than 3 VPB's in a run) Grade 4: VF Fig. I shows the results obtained from the 16 experiments. The frequencies of occurrence o f various ventricular arrhythmias were similar before and after methylprednisolone. When VT and VF were considered together, the incidence of these high grade arrhythmias was 69% ( I I /16) both before and after the drug. VF occurred in 56% (9/16) before and i n 502, (8 /16) after methylprednisolone pretreatment. and the difference was not statistically significant (P>0.5). As shown in Fig. 2. the average time of onset o f VF was 244 ? 23 s before and 266 28 s after the drug, and the difference was again statistically insignificant (P> 0.5). 4
VENTR IC UL A
K F IH K IL L A TI 0 N
THRESHOLD
Fig. 3 shows the results obtained from the 10 dogs. The mean VFT was 10.1 I 1.8 mA before methyl-
Fig. I
Di.s/rihicticiri I/' vuriiiits wntriculur urrhj,thnrius occurring clirring 10 niin OJ coronurj' occlitsiun brforc, untl ujier nieth~~lpreti~risol~it~r pretreuarrirent in 16 dog.^. GO -graclr 0, no VPB: G I grudc I , occusionul VPB's; G2 grutlc' 2. /rcquc*tit VPB's; G3 grade 3. VT: G4 xrarle 4. VF. ~~
Mj~rtiigS.
Yoorr, Brrj G . Goi4, airtl JaoX Hair
VT and VF are among the leading causes of death during the initial phase of acute myocardial infarction. Various steroid preparations have been used clinically for patients suffering from myocardial infarction and cardiogenic shock. However, the direct effects of steroids on ventricular arrhythmias have not been studied systematically and the few reports available are contradictory (Beardsley et a/., 1976; Roberts et a/., 1976). Our study demonstrated that methylprednisolone has no significant beneficial effects on the incidence of ventricular arrhythmias or on the VFT during the acute phase of coronary occlusion. The tendency of a slight delay in the onset of VF shown after the methylprednisolone pretreatment was not statistically significant. These results suggest that methylprednisolone per se did not change the electrophysiological properties significantly enough to alter the ventricular vulnerability to arrhythmias during acute myocardial ischaemia. The lack of a beneficial effect of methylprednisolone in the ventricles subjected to acute coronary occlusion in this study suggests that it is unlikely to be of benefit in the treatment of ventricular arrhythmias in the early phase of myocardial infarction in
Fig. 2 The tiine of onset of VF aJier coronary occlusion ( C O ) before and aJier trreth~~lprerlnisolone administration.
prednisolone, and it increased slightly to 13.3 1 2.3 mA after the drug. This difference, however, was not statistically significant ( P > 0.2).
Discussion The glucocorticoid has been shown to be beneficial in ischaemic ventricles by reducing the infarct size (Maroko and Braunwald, 1973; Libby ef a/., 1973; Morrison et a/., 1975 1976; Braunwald and Maroko, 1976). The mechanism of the protective effect of the glucocorticoid is not clear. The coronary vasodilatory effect (Vyden et a/., 1971; Libby et a/., 1973) and the lysosomal stabilising effect (Clement e t a / . , 1974; Vaisrub, 1974; Lefer, 1974; Spath et a/., 1974) of the steroid were cited for the protective effect on the ischaemic ventricles. A well known anti-inflammatory effect of the steroid might also explain the beneficial effect through the stabilisation of the phagocytic vacuoles of the infiltrating inflammatory cells (Maroko and Braunwald, 1973). The glucocorticoid has also been used to reverse or improve the impaired atriOVentriCUhr conduction often accompanying acute myocardial infarction (Prinzmetal and Kannamer, 1954; Aber and Jones, 1960; Carameli and Tellini, 1960; Dall, 1964).
Fig. 3 ConIparison of v n s obtaine(/ before and after methylprednisolone pretreatment in I0 dogs during acute coronary occlusion (CO). The values are expressed as mean _t SE.
61
clinical situations. Marked depression in excitability and conductivity produced by myocardial ischaemia in the affected area are believed to be, in part, responsible for the mechanism of ventricular arrhythmias associated with myocardial infarction (Han, 1969a,b). Therefore, methylprednisolone seemingly failed to counteract such deleterious effects of myocardial ischaemia. It should be noted that our study was intended to test the direct effect of methylprednisolone on ventricular arrhythmias in acutely ischaemic hearts 15 min after a single dose of methylprednisolone. The deleterious effects of methylprednisolone reported in patients with acute myocardial infarction (Roberts et ul., 19’76)do not necessarily contradict our animal experimental results. The adverse effects reported in their study were observed only in patients treated by multiple doses of methylprednisolone (30 mg-kg-’ i.v. every 6 h for 48 h). A slight reduction in the incidence of ventricular arrhythmias after a single intravenous dose of methylprednisolone in their study agrees with our experimental observation. Based on the results of our animal experiments, it is suggested that the use of methylprednisolone might not be justified for the purpose of suppressing ventricular arrhythmias accompanying acute myocardial infarction. Supported by Grant HL-18796 from the National Institutes of Health, and a grant from the Upjohn Company. The authors are grateful to Susan Jones and Rosalyn Rogers for their technical assistance and to Oksana Ciupka for the preparation of this manusciipt. References Aher. C. P., and Jones, E. (1960). Complete heart block treated with corticotropin and corticosteroid. llrirish Hcwrr Jorirnal, 22,723-728, Beardsley. A. C., Okuda, M., and Lefer, A. M. (1976). Absence of a cardiodynamic action of glucocorticoids in acute myocardial ischaemia. Journal of Surgical Rrsrarclr, 20, 17-24. Braunwald, E. (1973). Reduction of experimental myocardial infarct size by corticosteroid administration. Clinical Invcsrigarion, 53, 599-607.
Braunwald, E., and Maroko, P. R. (1976). Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion. Atwricon Joirrnal [I/ Carcliology, 37, 550-556. Carameli, Z., and Tellini, R. R. (1960). Treatment of atrioventricular block with prednisone. Anrrrican Journal of Cardiology, 5, 263-265. Clement, H. G.,Williams, J. S . . and Adanis. J. T. (1974). Steroid effect on the release of the lysosomal enzyme acid phosphatase in shock. Annals of Surgc*r.v, 179, 9 17-921. Dall, J. L. L. (1964). The effects of steroid therapy on normal and abnormal atrioventricular conduction. Brirish Hearf Joiimal, 26, 537-543. Han, J. (1969a). Ventricular vulnerability during coronary occlusion. American Juirrnal o/’ Cardiology, 24, 857-864. Han, J . (l969b). Mechanisms of ventricular arrhythmias associated with myocardial infarction. Anwrican Joiimal of Cardiology, 24, 800-8 13. Lefer, A. M. (1974). Toward a rational drug therapy in cardiogenic shock. Cirrrilation Shock, I, 165- 168. Libby, P., Maroko, R. R., Bloor, C. M.,Sobel. B. E. and Maroko, P. R., and Braunwald. E. (1973). Modification of myocardial infarction size after coronary occlusion. Annals o/lntcrnul Mrdicinc, 19, 720-733. Morrison, J., Reduto. L., Malley, T.. and Gulotta, S. (1975). Protection of ischaemic myocardium in man by methylprednisolone. Ant~ricaii Joiirnul (if Curcliolugg!., 35, 158 (abstract). Morrison, J.. Reduto, L.. Pizzarello. R., Geller. K., Malley, T., and Gulotta, S. (1976). Modification of myocardial injury in man by corticosteroid administration. Circularion 53, Supplement 1, 200-203. Prinzmetal, M., and Kennamer, R. (1954). Emergency P treatment of cardiac arrhythmias. Jorirnal of I ~ Anrrrican Mrrlical Association. 154, 1049- 1054. Roberts, R., De Mello. V., and Sobel, B. E. (1976). Deleterious effects of methylprednisolone in patients with myocardial infarction. Circiilariun, 53, Supplement 1. 204-206. Spath, J. A.. Lane, D. L., and Lefer, A. M. (1974). Preservation of cardiac cellular integrity by methylprednisolone in acute myocardial infarction. Anwricun Journal of Curtliokogy, 33, 171 (abstract). Vaisruh. A. (1974). Myocardial depression factor ( M D F ) in cardiogenic shock. Journal of /he Aiirc*riwn Met1ic.d Associurion. 228, 500 Vyden, J. K.. Tomoda, H.. Prakashi. R., Chuck. L., Parmley, W. W.. and Corday. E. (1971). Effect ofcorticosteroids in shock secondary to myocardial infarction. Circirlarion, 43/44, 11-237 (abstract). Yoon, M. S.. Fondacaro, J. D., and Han, J. (978). Effects of vagal stimilation and atropine on ventricular arrhythmias during acute coronary occlusion. Joirrnal of Elrcrrocardiography, I I, (I), 27-3 1.
