ABSTRACTS

THE MECHANISM OF PLACEBO EFFECT ON EXERCISE TOLERANCE IN ANGINA PECTORIS. John B. KostbsMD FACC, S.Ksie8er RN, N.Cosgrove RN, A.E.Moreyra YD FACC, J.Burns MD, K.Reddy MD, P.T.Kuo MD FACC: CMDNJ--Rutgers Medical School, Pis- cataway, New Jersey.

Exercise tolerance is considered an objective measure of the severity of angina and of the efficacy of therapeutic interventions. In double blind studies of beta blockers (BB, oxprenolol, pindolol, propranolol), 78 patients (pt) with angina were given placebo (PL), 92 pt BB and 22 en- rolled in a 12 week exercise conditioning program (COXD).

All three groups showed a decrease in the frequency of angina (15.5 f 1.3 attacks per two weeks to 4.6 f 3.9 p( 0.05 for BB, 11.6 f 0.8 to 6.2 f 0.6 ~(0.05 for COND) and an increase in exercise tolerance (Bruce protocol, 293.3 f 23.2 set to 357.4 f 21.7 ~(0.01 for BB, 345.6 f 25.2 to 434.4 f 52.3 ~(0.05 for COND). Although the effects of DL on these variables were less (ptO.05) pronounced, they were significant (exercise tolerance 340.7 f 20.2 set to 396.1 i_ 18.4 p<O.Ol and angina frequency 15.3 f 1.6 at- tacks per two weeks to 6.9 f 0.8 ~(0.05). HOWWel-, in contrast to BB and COND that lowered submaxi-

mal (9?1ETS) double product and exercise induced ST depres- sion (0.12 * 0.02 mV to 0.10 f 0.01 p<O.O5 BB, 0.14 f 0.02 to 0.12 f 0.02 p<O.O5) and lowered (196.3 * 8.1 beats/min x mm Hg x 10-2 to 161.2 f 9.5 p<O.O5 BB) or did not affect (184.3 f 5.2 to 182.4 f 9.7 p=NS COND) double product at onset of angina, PL caused increase in ST depression (0.09 -10.03mVto 0.11 f 0.04 p<O.O5) and double product at onset of angina (186.7 f 6.0 to 202.6 f 5.3 pCO.02). The data indicate that (1) in patients with angina pla-

cebo exerts a powerful effect not only on symptomatology but also on exercise tolerance, and (2) this effect is due to increased motivation and higher perception threshold for angina and not to conditioning from repeated stress tests or altered hemodynamic response to exercise.

EFFECTS OF ORAL PIRBUTEROL ON HAEMODYNAMICS, DISTRIBUTION OF BLOOD FLOW AND LACTATE PRODUCTION DURING TREADMILL EXERCISE IN PATIENTS WITH CHRONIC HEART FAILURE Rudolph Canepa-Anson, MRCP; Charles Ilsley, MRCP; John Bayliss, MRCP, Stuart Reuben, MD: George Sutton, !4D, Philip Poole-Wilson, MD, The National Heart Hospital, London, U.K.

Vasodilator drugs increase cardiac output (CO) during treadmill exercise (TEx) in patients with chronic heart failure (CHF) but may not increase exercise capacity (ExC): possibly because non-selective vasodilatation of vascular beds causes maldistribution of blood flow, thus misdirecting the increased CO.

The effects of acute oral pirbuterol were investigated at rest and during progressive TEr. (2-10 METS) in 9 patients with CHF (NYHA class 3) using standard methods. The balance of tissue oxygen demand and blood flow was assessed by estimation of oxygen saturation in the hepatic vein (HVO) for the splanchnic circulation, the femoral vein for working muscle, and in mixed venous blood (PAO). Measurements were made after 2 mins. at each exercise level. Results are given as mean values + SEM.

After pirbuterol the following changes were observed. ExC increased by 34% from 24.9+3.6 to 33.4+3.9 mins. (PCO.01). CO was significantly increased at rest and during mild and peak TEx by 12 to 22% (P<O.O5-0.005). Similar changes occurred in systemic vascular resistance (-11 to -20X, PcO.05 -.O.Ol). Left ventricular filling pressure fell only at rest (-ll%, P<O.Ol). PAO, FVO and HVO were all increased both at rest and during TEx, but not significantly. Lactate production was unchanged. Throughout the recovery phase (2-15mins.) FVO was in- creased (PcO.05).

Oral pirbuterol increases CO and ExC in patients with CHF without causing maldistribution of blood flow. During recovery blood flow to working muscle is improved.

WEDNESDAY, APRIL 28, 1982 PM CLINICAL TRIAL OF NEWER DRWGS TO SUPPRESS VENTRICULAR ARRHYTHMIAS 2:00-3:30

ACUTE EFFECTS OF INTRAVENOUS AMIODARONE IN PATIENTS WITH COMPLEX VENTRICULAR DYSRHYTHMIAS.

Diederik v. Hooaenhuvze,MD; Pieter v.d.Burg,MD; Axe1 de Wilde, Willem 3.Remme.MD: X.Hanno Krauss,MD. Deot. of Cardiology, Zuiderziekenhuis, Rotterdam,'Thk Netherlands.

The effectiveness of oral Amiodarone(AM) in both supra- ventricular and ventricular dysrhythmias is well esta- blished, but its long onset of action, from 4 days to 3 weeks, limits its usefullness in acute cases. We in- vestigated the acute effect of intravenous(I in 17 patients(pts) with complex ventricular dysrhythmias(CVD). Nine of these pts suffered from coronary. heart disease but were not studied during acute myocardial infarction: 6 pts had dilated cardiomyopathy and 2 other cardiac disorders. CVD were documented on a baseline 24 hr ECG, and were defined as ventricular couplets(l5 pts), runs of ventricular tachycardia(VTj(12 pts) and ventricular bigeminy(7pts). AM was administered as an IV bolus of 5 mg/kg, followed by an infusion of 1500 mg in 24 hrs as the sole antiarrhytmic agent. 24 hr ECG monitoring was started 2 hrs before bolus injection. Changes in number of VT,couplets and periods of ventr. bigeminy were quantified, by comparing the treated and untreated periods. Results: Significant (>90 %) reduction occurred in 84 % (10/12) of pts with VT after a median interval (int) of 2 hrs; in 81 % (13/16) of pts with couplets (median int 4 hrs); and in 86 % (6/7) of pts with ventr. bigeminy (median int 2 hrs). Side effects were: transient fall in bloodpressure (t 15 mmlig) and heat sensation in all pts, phlebitis (in 5 pts) and heart failure(1 pt). Conclusion: Intravenous Amiodarone is highly effective and has a rapid onset of action in the acute treatment of complex ventricular dysrhythmias.

INTRAVENOUS AMIODARDNE; AN EFFECTIVE ANTI-ARRHYTHIIIC AGENT. Phyllis Holt,MRCP, Paul Curry,MD, Bernard Way,MRCP, David Holt,Ph D Cardiac Department, Guy's Hospital, London. Oral am;oAarone is successful in the therapy of supra vent- ricular and ventricular arrhythmias but may take 3-5 days to become effective. We investigated the acute anti- arrhythmic properties of the intravenous preparation. We studied 6 patients, 2 males, 4 females aged 32-66 Years. Five patients had paroxysmal V.T. and one paroxysmal A.F., resistant to conventional medication. Holter monitoring was performed for 24 hours prior to amiodarone therapy. Intravenous amiodarone 300mgs diluted with 20mls N.Saline was administered over 10 minutes, and blood collected for plasma amiodarone levels at 2,5,10,30 and 60 minutes after the onset of the infusion. ECG's were recorded at the same time intervals and analysed for rate, rhythm, PR, QRS and QTc values. Oral amiodarone was instituted immediately after the I.V.bolus. Plasma amiodarone levels and KG's were taken 1,4 and 12 weeks later, with further Holter monitoring at 3 months. During the amiodarone infusion, plasma levels rose to their maximum at 10 minutes,(e.g. 18.3mg/l). They then fell quickly reaching levels of l.l- 1.3mg/l at 60 minutes. Heart rate fell slightly but not significantly in all patients and there was no significant change in the B.P. or the PR and QRS values. The QTc was lengthened in all patients by S-20% of the resting values. The maximum QTc was achieved 2-5 minutes after the onset of the infusion and persisted until 10 minutes. Resting values were regained by 60 minutes. The anti-arrhythmic effect coincided with the maximum QTc, V.T. and V.P.B.'s being abolished between 2-5 minutes, and did not recur within the 60 minutes period. Thus I.V.amiodarone is an effective anti-arrhythmic agent and can be administered without significantly affecting the pulse rate or B.P. The QTc is prolonged in all patients, maximum values coincid- ing with the onset of its anti-arrhythmic action.

March 1982 The American Journal of CARDIOLOGY Volume 49 1001