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Meobentine sulfate: Antiarrhythmic efficacy and mechanism of action in a chronic canine model of myocardial infarction susceptible to ventricular tachyarrhythmias
ELECTRICAL INSTABILITY AS A FUNCTION OF MYOCARDIAL INFARCTION SIZE Beverly A. Jones Collins, MD, Randolph E. Patterson, MD, FACC, Stephen E. Epstein, MD, FACC, NHLBI, Bethesda, Md. The predisposing factors for post-infarction ventricular arrhythmias are ill-defined, and although indirect evidence supports the possibility that size of acute myocardial infarction is an important determining factor, no direct evidence exists. We therefore studied 13 conscious dogs 3 to 4 days after acute myocardial infarction was produced by closed chest coronary artery occlusion. The right ventricle was stimulated by a series of single, followed by double extrastimuli, scanning from end-diastole toward the T wave during right ventricle pacing. Abnormal responses included: repetitive ventricular responses (RVR), short runs of ventricular tachycardia (VT), sustained VT (SVT) and ventricular fibrillation (VF). An index of electrical instability was determined for each dog by the type of responses produced (score for VF>SVT>VT>RVR), the nature of the stimuli required to produce the responses (score for single>double) and the time in diastole at which they could be elicited (score for late>early diastole). Myocardial infarction size was measured by post- mortem tetrazolium staining. Electrical instability correlated strongly with myocardial infarction size (r=.93). This is the first study utilizing direct measurement of myocardial infarction size to demonstrate that electrical instability several days post-AMI, as determined by electrical stimulation, is a function of myocardial infarction size.
MEOBENTINE SULFATE: ANTIARRHYTHMIC EFFICACY AND MECHANISM OF ACTION IN A CHRONIC CANINE MODEL OF MYOCARDIAL INFARC-
TION SUSCEPTIBLE TO VENTRICULAR TACHYARRHYTHMIAS Eric L. Michelson, MD, FACC, Masahito Naito, MD, Daniel David, MD, E. Neil Moore, DVM, PhD, FACC, Leonard S. Dreifus, MD, FACC. Lankena" Hospital, Philadelphia, PA The antiarrhythmic efficacy of meobentine s"lfate(MBS), a non-neuronal blocking bethanidine derivative was evaluated in 6 open-chest pentobarbital-anesthesized dogs studied 4-6 days after 2-stage left anterior descending coronary artery occlusion and reperfusion. Prior to MBS, each dog was reproducibly susceptible to pacing-induced sustained ventricular fibrillation(VF,N=5 dogs)or tachycardia(VT, 1 dog). After intravenous infusion of 20 mg/kg MBS over 30 min, MBS demonstrated marked antiarrhythmic activity in each dog. In the 5 dogs with VF prior to MBS, VFre-initiation was prevented for a range of 5-12 hrs. In the one dog with VT prior to MBS,re-initiation of VT was prevented for 2hrs;VT then recurred at a slower rate until 6 hrs after drug infusion. This time course of antiarrhythmic activity paralleled the left ventricular tissue kinetics of MBS(T$ elimination=3 hrs) rather than its plasma concentration (a T$ = 1.8 min, B T$ = 90 min). Of note, MBS had no effect on the diastolic excitability threshold of either normal(N infarct(I)tis at the time of its antiarrhythmic activity,but did prolong ventricular refractory periods(VRP)at both N(mean increase 25+ 7I(SD)msecat a paced cycle length of 300 msec,p< O.Ol)and I sitescby 69 + 23 msec,p
392
February 1981
The American Journal of CARDIOLOGY
MONDAY, AM
MARCH
16, 1961
CARDIAC PACING 10:30- 12:oo
NON-INVASIVE SERIAL ELECTROPHYSIOLOGIC TESTING USING AN IMPLANTED PACEMAKER TO TRACK CHEST WALL STIMULI Ross Fletcher. MD. FACC; John Keimel, MSEE, Lou Larca, MD; James Cox, MEEE; Albert Del Negro, MD; Robert Di Bianco, MD, FACC; Steve Singh, MD; VA Medical Center, Georgetown University. Washington, D.C. A new technique for serial non-invasive electrophysiologic testing (EPT) was verified in 18 studies on 9 pts with an implanted multiprogrammable pacemaker * attached to ventricular (5pts) and atria1 (4pts) leads. After programming ** the pacemaker to a triggered mode at outputs 2 times threshold, an external stimulator delivered premature impulses to the chest wall at outputs below patient perception thru electrode patches. External leads (6) and an esophageal lead determined responses. The internal pacemaker tracked chest wall stimuli down to 22Gmsec (the refractory period of the pacemaker). The effective refractory period of the ventricles (250+24msec) and atria (270+34msec) was longer than 22Omsec. Two ventricular pacemaker pts with clinical ventricular tachycardia had tachycardia induced with premature stimuli of 32Chnsecand 33Omsec, and were reverted by tracking chest wall stimuli or programmed overdrive pacing. Three ventricular pacemaker pts without tachycardia had 5 2 repeti tive beats following 1, 2 or 3 premature stimuli. Four atria1 pacemaker pts had 6 supraventricular arrhythmias (4SVT, 2 atria1 flutter) induced which were reverted by tracking chest wall stimuli (4) or rapid pacing (2). Repeat testing verified antiarrhythmic control after drug intervention in the 5/6 pts with arrhythmia. Non-invasive serial EPT using permanent multipsogrammable pacemakers tracking chest wall stimuli is effective for inducing and reverting ventricular and atria1 arrhytmiss and in evaluating antiarrhythmic therapy. * Medtronic, Inc. Spectrax TM Model 5984/5885 ** Medtronic, Inc. Custom Model 9701-3231 Programmer
A FIFTEEN YEAR COMPARATIVE STUDY OF CARDIAC PACING COSTS Abe Lopman, BA; Clifford L. Langer, MBA; Seymour Furman, MD, FACC; Doris J.W. Escher, MD, FACC, Montefiore Hospital and Medical Center, Bronx, N.Y. The total cost of treating the pacemaker (PM) patient (PT) has decreased by 46% from 1965-1980. Figures are based upon: costs in dollars per PT day, costs of PM, PM longevity, PT longevity, follow-up care (i.e. clinic visits, trans telephone monitoring (TTM) calls), and personnel costs in constant 1980 dollars (U.S. Bureau of Labor Statistics). At Montefiore Hospital and Medical Center, 50% cumulative survival is 8 years after initial implant. The following table describes changing costs for treating the PM PT for 8 years of care from the point of initial implant in 1965, 1970, 1975, and 1980. 19ao* 1975* 2 #PM/8 Yrs 1 PM Life-Each (mos) 96 43,96 2,729 4,904 Tot PM Cost ($) Tot Days of Hosp 6.5 15 Tot Hasp $ 2,600 6,070 Tot Prof Fees ($1 1,710 2,067 Tot Staff ($) 249 406 6,348+ Tot Follow-up ($) 3,971+ 11,259+ 19,795+ 8 Yr CoSt/PT 2,474+ CoSt/Yr/PT 1,407+ * Year of implant; + Projected Cost
1970* 1965* 3 4 37,37,43 18,18,37,37 5,391 6,276 20 29 6,468 6,089 2,137 1,742 467 573 6,763 6,045 20,725 21,226 2,590 2,653
These data reflect the reduction in costs of contemporary cardiac pacing caused by the prolongation of the PM life span, transition from outpatient visits to the less expensive TTM follow-up and present TTM schedules, and to the reduction in hospital PT days, all producing a shift from a labor-intensive service, to a modern, costefficient, capital-intensive mode of care.
Volume 47
MEOBENTINE SULFATE: ANTIARRHYTHMIC EFFICACY AND MECHANISM OF ACTION IN A CHRONIC CANINE MODEL OF MYOCARDIAL INFARC-
TION SUSCEPTIBLE TO VENTRICULAR TACHYARRHYTHMIAS Eric L. Michelson, MD, FACC, Masahito Naito, MD, Daniel David, MD, E. Neil Moore, DVM, PhD, FACC, Leonard S. Dreifus, MD, FACC. Lankena" Hospital, Philadelphia, PA The antiarrhythmic efficacy of meobentine s"lfate(MBS), a non-neuronal blocking bethanidine derivative was evaluated in 6 open-chest pentobarbital-anesthesized dogs studied 4-6 days after 2-stage left anterior descending coronary artery occlusion and reperfusion. Prior to MBS, each dog was reproducibly susceptible to pacing-induced sustained ventricular fibrillation(VF,N=5 dogs)or tachycardia(VT, 1 dog). After intravenous infusion of 20 mg/kg MBS over 30 min, MBS demonstrated marked antiarrhythmic activity in each dog. In the 5 dogs with VF prior to MBS, VFre-initiation was prevented for a range of 5-12 hrs. In the one dog with VT prior to MBS,re-initiation of VT was prevented for 2hrs;VT then recurred at a slower rate until 6 hrs after drug infusion. This time course of antiarrhythmic activity paralleled the left ventricular tissue kinetics of MBS(T$ elimination=3 hrs) rather than its plasma concentration (a T$ = 1.8 min, B T$ = 90 min). Of note, MBS had no effect on the diastolic excitability threshold of either normal(N infarct(I)tis at the time of its antiarrhythmic activity,but did prolong ventricular refractory periods(VRP)at both N(mean increase 25+ 7I(SD)msecat a paced cycle length of 300 msec,p< O.Ol)and I sitescby 69 + 23 msec,p
392
February 1981
The American Journal of CARDIOLOGY
MONDAY, AM
MARCH
16, 1961
CARDIAC PACING 10:30- 12:oo
NON-INVASIVE SERIAL ELECTROPHYSIOLOGIC TESTING USING AN IMPLANTED PACEMAKER TO TRACK CHEST WALL STIMULI Ross Fletcher. MD. FACC; John Keimel, MSEE, Lou Larca, MD; James Cox, MEEE; Albert Del Negro, MD; Robert Di Bianco, MD, FACC; Steve Singh, MD; VA Medical Center, Georgetown University. Washington, D.C. A new technique for serial non-invasive electrophysiologic testing (EPT) was verified in 18 studies on 9 pts with an implanted multiprogrammable pacemaker * attached to ventricular (5pts) and atria1 (4pts) leads. After programming ** the pacemaker to a triggered mode at outputs 2 times threshold, an external stimulator delivered premature impulses to the chest wall at outputs below patient perception thru electrode patches. External leads (6) and an esophageal lead determined responses. The internal pacemaker tracked chest wall stimuli down to 22Gmsec (the refractory period of the pacemaker). The effective refractory period of the ventricles (250+24msec) and atria (270+34msec) was longer than 22Omsec. Two ventricular pacemaker pts with clinical ventricular tachycardia had tachycardia induced with premature stimuli of 32Chnsecand 33Omsec, and were reverted by tracking chest wall stimuli or programmed overdrive pacing. Three ventricular pacemaker pts without tachycardia had 5 2 repeti tive beats following 1, 2 or 3 premature stimuli. Four atria1 pacemaker pts had 6 supraventricular arrhythmias (4SVT, 2 atria1 flutter) induced which were reverted by tracking chest wall stimuli (4) or rapid pacing (2). Repeat testing verified antiarrhythmic control after drug intervention in the 5/6 pts with arrhythmia. Non-invasive serial EPT using permanent multipsogrammable pacemakers tracking chest wall stimuli is effective for inducing and reverting ventricular and atria1 arrhytmiss and in evaluating antiarrhythmic therapy. * Medtronic, Inc. Spectrax TM Model 5984/5885 ** Medtronic, Inc. Custom Model 9701-3231 Programmer
A FIFTEEN YEAR COMPARATIVE STUDY OF CARDIAC PACING COSTS Abe Lopman, BA; Clifford L. Langer, MBA; Seymour Furman, MD, FACC; Doris J.W. Escher, MD, FACC, Montefiore Hospital and Medical Center, Bronx, N.Y. The total cost of treating the pacemaker (PM) patient (PT) has decreased by 46% from 1965-1980. Figures are based upon: costs in dollars per PT day, costs of PM, PM longevity, PT longevity, follow-up care (i.e. clinic visits, trans telephone monitoring (TTM) calls), and personnel costs in constant 1980 dollars (U.S. Bureau of Labor Statistics). At Montefiore Hospital and Medical Center, 50% cumulative survival is 8 years after initial implant. The following table describes changing costs for treating the PM PT for 8 years of care from the point of initial implant in 1965, 1970, 1975, and 1980. 19ao* 1975* 2 #PM/8 Yrs 1 PM Life-Each (mos) 96 43,96 2,729 4,904 Tot PM Cost ($) Tot Days of Hosp 6.5 15 Tot Hasp $ 2,600 6,070 Tot Prof Fees ($1 1,710 2,067 Tot Staff ($) 249 406 6,348+ Tot Follow-up ($) 3,971+ 11,259+ 19,795+ 8 Yr CoSt/PT 2,474+ CoSt/Yr/PT 1,407+ * Year of implant; + Projected Cost
1970* 1965* 3 4 37,37,43 18,18,37,37 5,391 6,276 20 29 6,468 6,089 2,137 1,742 467 573 6,763 6,045 20,725 21,226 2,590 2,653
These data reflect the reduction in costs of contemporary cardiac pacing caused by the prolongation of the PM life span, transition from outpatient visits to the less expensive TTM follow-up and present TTM schedules, and to the reduction in hospital PT days, all producing a shift from a labor-intensive service, to a modern, costefficient, capital-intensive mode of care.
Volume 47