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Electrophysiologic mechanism for the anitifibrillatory action of verapamil
ABSTRACTS
DELETERIOUS HEMODYNAMIC AND CLINICAL RESPONSES TO HYDRALAZINE IN PATIENTS WITH SEVERE SECONDARY PULMONARY HYPERTENSION. Milton Packer MD, FACC, Barry Greenberg MD, FACC, Barry Massie MD, FACC, Harold Dash MD, FACC. Mount Sinai Medical Center, New York, NY Although hydralazine (H) has been reported to be beneficial in primary and secondary pulmonary hypertension (SPHT), clinical experience is limited. We administered H to IO patients (pts) with SPHT due to diffuse lung disease (7 pts) or multiple Mean pulmonary artery pressures pulmonary emboli (3 pts). (PAP) ranged from 40-75 mm Hg and pulmonary arteriolar resistances (PAR) from 460- I3 I8 dyn-sec/cms. The daily doses of H used were 200 mg (7 pts), 300 mg (2 pts) and 600 mg (I pt). Cardiac output (CO, I/min), stroke volume (SV, cc/beat), heart rate (HR, min-‘1, mean arterial pressure (MAP, mm Hg), PAP, pulmonary capillary wedge (PCW) and mean right atrial pressures (RAP, mm Hg), systemic vascular resistance (dyn-set/cm’) and PAR were determined before (C) and after 24 hrs on H. Results: (where * I p< .O I, + = p< .05, C vs H) HR MAP PAP PCW RAP SVR -----CO sv -----PAR C 3.7 42 88 88 53 II I3 1690 945 H 4.4+ 45 lOO+ 661 51 9 I4 989’ 765* Although PAR decreased (C) modestly (19%) with H, PAP did not $. In contrast, SVR $ markedly (41%) associated with large C in MAP&22 mm Hg) and reflex tachycardia (HR 4 > 20 beatslmin in 4 pts). There were only mild increases (4) in CO (19%) and no significant 4 in SV. Right ventricular stroke work (23 g-m) did not change; left ventricular stroke work actually + (45 to 34 g-m, p< .05). Of the IO pts evaluated, 4 pts became symptomatically hypotensive within 24 hrs of starting H, all with 200 mg daily. One pt became acutely dyspneic at peak effect of the first H dose associated with a reversible f in arterial O2 saturation from 85% to 77%; one pt developed progressive azotemia after initiation of H. The remoining 4 pts showed no clinical change. In conclusion, H produces little hemodynamic improvement in pts with SPHT and frequently causes serious adverse reactions.
SAFETY AND EFFICACY OF INTRAVENOUS QUINIDINE. Charles D. Swerdlow, MD, Jeanette 0. Yu, Eric Jacobson, BS, Susan Mann, RN, Roger A. Winkle, MD, FACC, Jerry C. Griffin, MD, FACC, David L. Ross, MB, BS, FRACP, Jay W. Mason, MD, FACC, Stanford University, Stanford, California. The safety and antiarrhythmic efficacy of intravenous (IV) quinidine (Q, mea" dose 9.0 .? 1.5mg/kg) was tested during electrophysiologic study in 88 patients (pts) with spontaneous and inducible ventricular tachycardia (VT) or supraventricular tachyarrhythmias. Sixty-seven percent of pts had clinical heart failure (NYHA Class 2, 3, or 4). CI, LVEDP, and LV ejection fraction were abnormal in 42%, 58% and 50% respectively. Despite the high incidence of heart failure, Q was discontinued because of hypotension (after a mean dose of 6.1 5 l.Chng/kg) in only 10 pts (11%). Saline was infused to maintain preload during Q administration in 35%. Hypotension was not more commc~n in pts with more severe heart failure or LV dysfunction. Intraventricular conduction delay (QRS z 120 msec) was present in 26%. The HV interval was prolonged (> 55 msec) in 25%. Q caused increas,es in QRS duration (111 ? 30 vs 124 + 36 msec, p < .OOl), QT, interval (422 ? 55 vs 505 + 62 msec, p < .OOl), HV interval (51 + 13 "s 60 + 17 msec, p < .OOl) and right ventricular effective refractory period (250 5 36 vs 270 5 51 msec, p < .OOl), but no heart block OL- QRS widening > 50%. Q prevented arrhythmia induction in 23/78 pts who received full doses (29%). VT cycle length increased in all pts in whom identical morphologies were induced before and after (2 (310 2 67 vs 392 f 98 msec, p < .OOl). IV Q may be administered safely to pts with intraventricular conduction delays and moderate heart failure. When antiarrhythmic efficacy is assessed by electrophysiologic study, Q compares favorably with other agents. IV Q should be used when first-line, IV antiarrhythmic agents are ineffective 0~. contraindicated.
THURSDAY, APRIL 29, 7982 AM PHARMACOLOGY OF ANTIARRHYTHMIC AGENTS 10:30- 12:oo ZL!XTIIOPHYSIOLOGIC !lECHANIS'lF09 THE AIITIFIBRILLATORY ACTION OF VEXPAMIL George Bre", \I.').;P. Jacob Varghese, M.D., FACC; Roy Leiboff, X.D.; Allan Ross, ,1.D., FACC; George Washington University, liashington, D.C.
A COMPARISON OF THE ELECTROPHYSIOLOGICAL EFFECTS OF INTRAVENOUS AND ORAL AMIODARONE.
Verapamil (V) has been s'lown to prevent ischenia (I) induced Ventricular fibrillation (V?) in animals, but the mechanism for this is unknown. '$e studied 21 episodes of I hy transiently ligating coronary arteries for up to 10 minutes both before and after V, O.l-O.Zmg/kg in 5 acute open chested dogs. Sipolar plunge electrodes were inserted in 2 sites each in the ischemic zone (IZ) and "onischemic zone (NZ) for recording and stimulation. Conduction time (CT) relative to a reference electrogram was measured during atrial-His sequential pacing at a constant t-ate. During ventricular pacing, effective refractory period (R) at >lOx diastolic threshold was measured and strength interval curves (SI) to evaluate excitability (E) were obtained. Measurements were made in both the NZ and IZ pre and post V. VF occurred at 3-6min. of all I episodes pre V, but none occurred after 10 min. of I post v. Relative delay in CT (ACT), changes in ?(AR) and E (AE) in the IZ were: Pre v Post v I A~~(msec) AR(nsec) AE
(3-6min.) +25i17 +11+43 4
(3-6min.) +11?13* -42+18** +
(10min.) +46t38** +46+40 44
*p<.o2 **p<.o5
No significant changes were see" in the NZ. Thus V prevents VF by delaying the prolongation of CT until such time AR and AE do not sustain reentry. This study shows the critical time relationship of these parameters in the genesis of VF and serve as a model to evaluate antiarrhythmic drugs.
Hein J.J. Wellens MD, FACC, Pedro Brugada MD, Denis RoyMD, Bill Heddle MD. Frits W. Bit-MD. Dept. of Cardiol, Annadal Hosp., Maastricht, Netherlands. The electrophysiological (EPS) effects of iv (5 "g/kg body weight in I min) and oral (total dose 9,800 to 11,200 mg over 5-6 weeks) Amiodarone (Am) were compared in 5 patients (pts) with WPW syndrome and 3 pts with ventricular tachycardie (VT). In all 8 pts the maximal changes in EPS parameters and mechanisms of T were compared uing data before Am and after iv and oral Am. Extrastimuli were given using identical basic pacing cycle length and teststimulus intervals before and after Am. Iv Am was given during T. Results: Sinus rate increased after iv Am, but slowed after oral Am (P
March 1992
The American Journal of CARDIOLOGY
Volume 49
1043
DELETERIOUS HEMODYNAMIC AND CLINICAL RESPONSES TO HYDRALAZINE IN PATIENTS WITH SEVERE SECONDARY PULMONARY HYPERTENSION. Milton Packer MD, FACC, Barry Greenberg MD, FACC, Barry Massie MD, FACC, Harold Dash MD, FACC. Mount Sinai Medical Center, New York, NY Although hydralazine (H) has been reported to be beneficial in primary and secondary pulmonary hypertension (SPHT), clinical experience is limited. We administered H to IO patients (pts) with SPHT due to diffuse lung disease (7 pts) or multiple Mean pulmonary artery pressures pulmonary emboli (3 pts). (PAP) ranged from 40-75 mm Hg and pulmonary arteriolar resistances (PAR) from 460- I3 I8 dyn-sec/cms. The daily doses of H used were 200 mg (7 pts), 300 mg (2 pts) and 600 mg (I pt). Cardiac output (CO, I/min), stroke volume (SV, cc/beat), heart rate (HR, min-‘1, mean arterial pressure (MAP, mm Hg), PAP, pulmonary capillary wedge (PCW) and mean right atrial pressures (RAP, mm Hg), systemic vascular resistance (dyn-set/cm’) and PAR were determined before (C) and after 24 hrs on H. Results: (where * I p< .O I, + = p< .05, C vs H) HR MAP PAP PCW RAP SVR -----CO sv -----PAR C 3.7 42 88 88 53 II I3 1690 945 H 4.4+ 45 lOO+ 661 51 9 I4 989’ 765* Although PAR decreased (C) modestly (19%) with H, PAP did not $. In contrast, SVR $ markedly (41%) associated with large C in MAP&22 mm Hg) and reflex tachycardia (HR 4 > 20 beatslmin in 4 pts). There were only mild increases (4) in CO (19%) and no significant 4 in SV. Right ventricular stroke work (23 g-m) did not change; left ventricular stroke work actually + (45 to 34 g-m, p< .05). Of the IO pts evaluated, 4 pts became symptomatically hypotensive within 24 hrs of starting H, all with 200 mg daily. One pt became acutely dyspneic at peak effect of the first H dose associated with a reversible f in arterial O2 saturation from 85% to 77%; one pt developed progressive azotemia after initiation of H. The remoining 4 pts showed no clinical change. In conclusion, H produces little hemodynamic improvement in pts with SPHT and frequently causes serious adverse reactions.
SAFETY AND EFFICACY OF INTRAVENOUS QUINIDINE. Charles D. Swerdlow, MD, Jeanette 0. Yu, Eric Jacobson, BS, Susan Mann, RN, Roger A. Winkle, MD, FACC, Jerry C. Griffin, MD, FACC, David L. Ross, MB, BS, FRACP, Jay W. Mason, MD, FACC, Stanford University, Stanford, California. The safety and antiarrhythmic efficacy of intravenous (IV) quinidine (Q, mea" dose 9.0 .? 1.5mg/kg) was tested during electrophysiologic study in 88 patients (pts) with spontaneous and inducible ventricular tachycardia (VT) or supraventricular tachyarrhythmias. Sixty-seven percent of pts had clinical heart failure (NYHA Class 2, 3, or 4). CI, LVEDP, and LV ejection fraction were abnormal in 42%, 58% and 50% respectively. Despite the high incidence of heart failure, Q was discontinued because of hypotension (after a mean dose of 6.1 5 l.Chng/kg) in only 10 pts (11%). Saline was infused to maintain preload during Q administration in 35%. Hypotension was not more commc~n in pts with more severe heart failure or LV dysfunction. Intraventricular conduction delay (QRS z 120 msec) was present in 26%. The HV interval was prolonged (> 55 msec) in 25%. Q caused increas,es in QRS duration (111 ? 30 vs 124 + 36 msec, p < .OOl), QT, interval (422 ? 55 vs 505 + 62 msec, p < .OOl), HV interval (51 + 13 "s 60 + 17 msec, p < .OOl) and right ventricular effective refractory period (250 5 36 vs 270 5 51 msec, p < .OOl), but no heart block OL- QRS widening > 50%. Q prevented arrhythmia induction in 23/78 pts who received full doses (29%). VT cycle length increased in all pts in whom identical morphologies were induced before and after (2 (310 2 67 vs 392 f 98 msec, p < .OOl). IV Q may be administered safely to pts with intraventricular conduction delays and moderate heart failure. When antiarrhythmic efficacy is assessed by electrophysiologic study, Q compares favorably with other agents. IV Q should be used when first-line, IV antiarrhythmic agents are ineffective 0~. contraindicated.
THURSDAY, APRIL 29, 7982 AM PHARMACOLOGY OF ANTIARRHYTHMIC AGENTS 10:30- 12:oo ZL!XTIIOPHYSIOLOGIC !lECHANIS'lF09 THE AIITIFIBRILLATORY ACTION OF VEXPAMIL George Bre", \I.').;P. Jacob Varghese, M.D., FACC; Roy Leiboff, X.D.; Allan Ross, ,1.D., FACC; George Washington University, liashington, D.C.
A COMPARISON OF THE ELECTROPHYSIOLOGICAL EFFECTS OF INTRAVENOUS AND ORAL AMIODARONE.
Verapamil (V) has been s'lown to prevent ischenia (I) induced Ventricular fibrillation (V?) in animals, but the mechanism for this is unknown. '$e studied 21 episodes of I hy transiently ligating coronary arteries for up to 10 minutes both before and after V, O.l-O.Zmg/kg in 5 acute open chested dogs. Sipolar plunge electrodes were inserted in 2 sites each in the ischemic zone (IZ) and "onischemic zone (NZ) for recording and stimulation. Conduction time (CT) relative to a reference electrogram was measured during atrial-His sequential pacing at a constant t-ate. During ventricular pacing, effective refractory period (R) at >lOx diastolic threshold was measured and strength interval curves (SI) to evaluate excitability (E) were obtained. Measurements were made in both the NZ and IZ pre and post V. VF occurred at 3-6min. of all I episodes pre V, but none occurred after 10 min. of I post v. Relative delay in CT (ACT), changes in ?(AR) and E (AE) in the IZ were: Pre v Post v I A~~(msec) AR(nsec) AE
(3-6min.) +25i17 +11+43 4
(3-6min.) +11?13* -42+18** +
(10min.) +46t38** +46+40 44
*p<.o2 **p<.o5
No significant changes were see" in the NZ. Thus V prevents VF by delaying the prolongation of CT until such time AR and AE do not sustain reentry. This study shows the critical time relationship of these parameters in the genesis of VF and serve as a model to evaluate antiarrhythmic drugs.
Hein J.J. Wellens MD, FACC, Pedro Brugada MD, Denis RoyMD, Bill Heddle MD. Frits W. Bit-MD. Dept. of Cardiol, Annadal Hosp., Maastricht, Netherlands. The electrophysiological (EPS) effects of iv (5 "g/kg body weight in I min) and oral (total dose 9,800 to 11,200 mg over 5-6 weeks) Amiodarone (Am) were compared in 5 patients (pts) with WPW syndrome and 3 pts with ventricular tachycardie (VT). In all 8 pts the maximal changes in EPS parameters and mechanisms of T were compared uing data before Am and after iv and oral Am. Extrastimuli were given using identical basic pacing cycle length and teststimulus intervals before and after Am. Iv Am was given during T. Results: Sinus rate increased after iv Am, but slowed after oral Am (P
March 1992
The American Journal of CARDIOLOGY
Volume 49
1043