Effect of Chronic Oral Moricizine and Intravenous Epinephrine on Ventricular Fibrillation and Defibrillation Thresholds

The purpose: of this study was to determine the effects of chronic oral moricizine therapy and physiological doses of epinephrine on ventricular fibrillation and defibrillation thresholds using an implantable transvenous/subcutaneous defihrillation system in a pig model. Thirteen pigs completed the three phases of the study. After a baseline study on day 1, the animals were randomized to receive moricizine 10–15 mg/kg tid or placebo for seven doses, at which time the protocol was repeated on day 4. The same protocol was again repeated on the same day after infusion of physiological doses of epinephrine. Multiple ventricular fibrillation and defibrillation thresholds were measured during each study. Moricizine did not alter ventricular fibrillation nor defibrillation thresholds, whereas epinephrine increased the ventricular defibrillation threshold from 20.8 J to 23.7 J (P < 0.05). In addition, we observed an increase in both ventricular fibrillation (19.7 J vs 12.6 J; P < 0.05) and defibrillation (20.8 J vs 17.8 J; P < 0.05) thresholds over the 4 days of the study. These findings suggest that moricizine may be a safe antiarrhythmic agent to use in patients with implantable cardioverter defibrillators, and that elevated endogenous epinephrine may render defibrillation more difficult.     

Propafenone for the treatment of refractory complex ventricular ectopic activity

The results of therapy with propafenone were evaluated in 45 patients with complex ventricular ectopic activity that had been refractory to a mean of 3.8 antiarrhythmic drugs. The cardiac diagnoses were ischemic heart disease (in 16 patients), cardiomyopathy (in 7), mitral valve prolapse (in 7), mitral valve prolapse (in 7), idiopathic ventricular ectopic beats (in 6), valvular heart disease (in 5), and hypertension (in 4). The frequency of ventricular ectopic beats was established after therapy with antiarrhythmic agents had been discontinued. Patients then received propafenone during a dose-ranging protocol. An effective response was defined as a reduction in total ventricular ectopic beats of 80% or more. During dose ranging, therapy failed in four patients because of side effects, in eight because of a reduction in ventricular ectopic beats of less than 80%, and in three because of an aggravation of the arrhythmia. Thirty patients had a reduction in total ventricular ectopic beats of 80% or more. During a mean follow-up of 12.4 months, therapy failed in 1 patient because of sustained ventricular tachycardia and in 7 because of intolerable side effects; 22 patients continued to receive propafenone. PR and QRS intervals were significantly prolonged (P = 0.001), but the corrected QT interval and the heart rate were unchanged. The mean trough plasma level of propafenone associated with an effective response was 756 ng/ml, and that associated with intolerable side effects was 920 ng/ml. Thus, in patients with refractory complex ventricular ectopic beats, propafenone was effective and well tolerated initially in 67% of patients and during long-term administration in 49%, and toxicity was minor in most patients.     

Cardiovascular effects of doxepin in cardiac patients with ventricular arrhythmias

The effect of doxepin on ventricular arrhythmias, the ECG, and left ventricular function was evaluated in 10 cardiac patients with symptoms with frequent ventricular premature depolarizations in a dose-ranging protocol. Four patients (40%) had greater than or equal to 80% ventricular premature depolarization suppression; four of eight with pairs and four of six with ventricular tachycardia had greater than or equal to 90% suppression. The mean maximal doxepin dose was 115 +/- 41 mg/day; mean nadir total doxepin concentration was 61 +/- 48 ng/ml and mean nadir total desmethyldoxepin concentration was 51 +/- 42 ng/ml. Doxepin increased the heart rate and the PR, QRS, and QTc intervals of the surface ECG (P not significant). There was no significant change in resting mean left ventricular ejection fraction with doxepin: 41% +/- 15% vs. 43% +/- 19% (P not significant). Complaints of sedation (eight patients) limited dose ranging and tolerance to the drug. Although doxepin suppressed ventricular premature depolarizations in four patients, marked sedation limits its usefulness for primary treatment of arrhythmias in this population.     

Moricizine Induced Increase in Pacing Threshold

GIROD, J.P., et al. : Moricizine Induced Increase in Pacing Threshold. A 72-year-old woman who was experiencing incessant ventricular tachycardia and recurrent automatic implantable cardioverter defibrillator (AICD) firing despite amiodarone therapy was referred to the Cleveland Clinic Foundation. Myocardial ischemia and infarction were ruled out by standard means. Several antiarrhythmic medications were tried previously without success. Moricizine, 200 mg three times daily, was initiated and controlled the ventricular tachycardia. However, after the dose of moricizine was titrated upward, the patient became symptomatically bradycardic and the ECG exhibited 2:1 block of her paced rhythm and an increased ventricular pacing threshold. (PACE 2003; 26[Pt. I]:110–111)     

Suppression of ventricular arrhythmias in man by d-propranolol independent of beta-adrenergic receptor blockade.

To investigate the mechanisms of ventricular arrhythmia suppression by propranolol, we determined the antiarrhythmic efficacy of d-propranolol in 10 patients with frequent ventricular ectopic depolarizations (VEDs) and nonsustained ventricular tachycardia. After an initial placebo phase, 40 mg d-propranolol was administered orally every 6 h with dosage increased every 2 d until arrhythmia suppression (greater than or equal to 80% VED reduction), intolerable side effects, or a maximal dosage (1,280 mg/d) was reached. Response was verified by documenting return of arrhythmia during a final placebo phase. Arrhythmia suppression occurred in six patients while two more had partial responses. Effective dosages were 320-1,280 mg/d (mean 920 +/- 360, SD) of d-propranolol with corresponding plasma concentrations of 60-2,280 ng/ml (mean 858 +/- 681). For the entire group, the QTc interval shortened by 4 +/- 4% (P = 0.03). Arrhythmia suppression was accompanied by a reduction in peak heart rate during exercise of 0-29%. To determine whether arrhythmia suppression could be attributed to beta-blockade, racemic propranolol was then administered in dosages producing the same or greater depression of exercise heart rate. In 3/8 patients, arrhythmias were not suppressed by racemic propranolol indicating that d-propranolol was effective via a non-beta-mediated action. By contrast, in 5/8 patients racemic propranolol also suppressed VEDs. We conclude that propranolol suppresses ventricular arrhythmias by both beta- and non-beta-adrenergic receptor-mediated effects.     

Electrophysiological Evaluation of Moricizine in Patients with Sustained Ventricular Tachyarrhythmias: Low Efficacy and High Incidence of Proarrhythmia

In patients with history of sustained ventricuiar tachyarrhythmias, the efficacy and safety of moricizine have not been systematically evaluated by electrophysiological studies. We performed electrophysiological testing in these patients in the drug-free state and then after moricizine loading, and evaluated the safety profile of moricizine during in-hospital loading and follow-up. The study population comprised of 31 patients with clinically sustained ventricular tachyarrhythmia. The underlying heart disease was coronary in 25 patients, cardiomyopathy in 5 patients, and none in 1 patient. The left ventricular (LV) ejection fraction ranged from 15%-69% (mean 39 ± 15%). During the baseline drug-free electrophysiological testing, sustained ventricular tachycardia was inducibie in 27 patients, ventricuiar fibrillation in 1 patient, and reproducible, nonsustained ventricular tachycardia (15–25 sec) in 3 patients. All 31 patients received moricizine to the maximum tolerated dose (851 ± 185 mg) over a period of 2–7 days. Six patients developed ventricular proarrhythmia within the first 4 days. Proarrhythmia required multiple cardioversions in three patients, was not associated with QT prolongation, and spontaneously resolved 6–24 hours after withdrawal of moricizine. Of the remaining 25 patients, 24 underwent electrophysiological testing on moricizine and 4 patients (16%) were rendered noninducible. The VT cycle length in the other 20 patients slowed from 243 ± 30 msec to 299 ± 60 msec (P < 0.09). Four noninducibie patients, two patients with inducible but slowed VTand one patient who had refused further testing were discharged on moricizine. Among these seven patients, recurrent arrhythmic events occurred in two patients, ventricular proarrhythmia in one patient, complete AV block in one patient, and severe disabling headache in one patient. Only two patients have continued to take moricizine without side effects or recurrent arrhythmic events during a follow-up of 4 months and 9 months, respectively. Moricizine is only rarely effective for long-term treatment of patients with spontaneous sustained ventricular tachyarrhythmias, It renders ventricular tachyarrhythmias noninducible in a small minority (16%) and is associated with a high incidence (23%) of ventricular proarrhythmias.     

Mexiletine and Propafenone: A Comparative Study of Monotherapy, Low, and Full Dose Combination Therapy

The electrophysiological effects of combination therapy of mexiletine and propafenone were assessed using standard 12-Iead electrocardiogram (standard ECG), signal-averaged EGG (SAECG), and ambulatory ECG in 31 patients with ventricular arrhythmias. All patients underwent mexiletine monotherapy (M-mono), propafenone monotherapy (P-mono), low dose combination therapy (low M 4- P), and full dose combination therapy (full M + P). Full M + P increased the PQ interval and QRS duration to the same extent as P-mono did. Low M + P increased PQ interval and QRS duration to a lesser extent than P-mono and full M + P did. P-mono and full M + P significantly decreased root mean square (RMS) and increased f-QRS in SAECG, while M-mono and low M + P showed only a weak trend. SAECGs with late potentials increased in number with treatments; 9 in predrug control, 11 on M-mono, 15 on P-mono, 10 on low M + P, and 14 on full M + P. The percent suppression of frequent premature ventricular contractions (PVCs) (> 1,000/day) with M-mono, P-mono, low M + P, and full M + P were 46.4 ± 9.0,56.6 ± 10.4,64.4 ± 9.2, and 71.4 ± 7.1, respectively, and those of frequent couplets (> 10/day) were 58.3 ± 17.7, 62.6 ± 23.6, 87.5 ± 6.2, and 92.1 ± 4.0, respectively. Thus, full dose combination of mexiletine and propafenone exhibited the maximum antiarrhythmic efficacy without enhancement of effects on standard ECG and SAECG. Low dose combination therapy showed better antiarrhythmic efficacy in association with lesser effects on standard ECG and SAECG compared with propafenone monotherapy.     

Atenolol for ventricular ectopy: a dose-response study

The antiarrhythmic efficacy, safety, and tolerance of atenolol was evaluated in 32 patients with an average of at least 60 ventricular ectopic depolarizations/hr. Patients received, single-blind, the following treatments for 2 weeks each: placebo and atenolol, 50, 100, and 200 mg daily. A 24-hour ambulatory ECG recording was obtained each week. Reduction in ventricular ectopic frequency by at least 75% occurred in six of 32 patients receiving 50 mg daily, five of 30 patients receiving 100 mg daily, and three of 21 patients receiving 200 mg daily (P = not significant for any paired dose comparison). No patient who failed to respond to a lower dose responded to 200 mg daily. The frequency of ventricular tachycardia was reduced by at least 75% in eight of 17 patients receiving 50 mg daily, seven of 16 patients receiving 100 mg daily, and eight of 11 receiving 200 mg daily (P = not significant for any paired dose comparison). Atenolol was discontinued because of adverse effects in 12 patients. The results indicate that atenolol is more effective in suppressing ventricular tachycardia than in suppressing overall ventricular ectopy.     

The development and testing of intravenous dosing regimens: application to flecainide for the suppression of ventricular arrhythmias

A two-part pharmacokinetic approach was used to prospectively develop and test intravenous flecainide infusion regimens for the acute therapy for ventricular arrhythmias. Initially, each of nine known responders to oral flecainide was given a rapid flecainide infusion to characterize pharmacokinetic parameters and determine the minimum effective concentration for each patient. These data were used to calculate individually appropriate three-stage flecainide infusions of predetermined durations in eight patients. The three-stage infusions (0.15 +/- 0.02 mg flecainide acetate/kg/min for 5 minutes, 0.046 +/- 0.004 mg/kg/min for 60 minutes, and 0.31 +/- 0.05 mg/kg/hr for 5 to 47 hours; mean +/- SE) resulted in 95% +/- 0.1% suppression of ventricular ectopic depolarizations. Based on these results, six additional patients received a uniform infusion regimen (0.1 mg/kg/min for 5 minutes, 0.025 mg/kg/min for 2 hours, and 0.25 mg/kg/hr for 46 hours). Supplemental doses of 0.25 mg/kg were given (four doses per patient). With this protocol, ventricular ectopic depolarizations were 82.6% +/- 8.5% suppressed. Measured plasma flecainide concentrations were not significantly different from those predicted by pharmacokinetic models. A prompt and sustained antiarrhythmic effect was obtained with an intravenous regimen of flecainide determined by a prospective pharmacokinetic approach. However, the dosages developed in this study may have to be modified for patients with impaired cardiac or renal function.     

Prognostic value of an exercise test one year after myocardial infarction

An exercise test was performed in 306 patients who had had acute myocardial infarction one year previously. The five year cumulative coronary heart disease mortality was 40.0%, when the test had to be discontinued because of ventricular arrhythmias but only 13.0% if discontinued because of fatigue (P less than 0.05). If the maximum work load was less than 80 W the mortality was 30.7% compared with 16.6% in patients who exercised at least 80 W (P less than 0.01). If maximum systolic blood pressure was less than or equal to 150 mmHg mortality was 40.3% compared with 8.5% in patients with greater than 200 mgHg (P less than 0.001). The mortality was 38.2% in patients having single monoform ventricular ectopic beats at a rate of three or more per minute or multiform, paired or early cycle ventricular ectopic beats or ventricular tachycardias: this compared with 14.1% (P less than 0.001) in patients having no or only single monoform ventricular ectopic beats at a rate of less than three per minute. ST-segment depression in univariate testing had no prognostic value. When both exercise test and clinical variables were used in survival analysis (Cox's regression) the most important variable was heart volume and after that ventricular arrhythmias. In multivariate regression analysis ST segment depression also had additional prognostic value. Thus ventricular arrhythmias turned out to be the most important prognostic factor measured during exercise test.     

Effects of slow-release bezafibrate on serum lipids, lipoproteins, apolipoproteins, and postheparin lipolytic activities in patients with type IV and type V hypertriglyceridemia

The effects of bezafibrate on serum lipids, lipoproteins, apolipoproteins, and post-heparin lipolytic activities were studied in 17 patients with hypertriglyceridemia. All patients received 400 mg of slow-release (SR) bezafibrate daily for four months. In the nine patients with type IV hypertriglyceridemia, mean serum triglyceride (TG) levels decreased significantly, by 53% (P less than 0.01) at two months and 50% (P less than 0.001) after four months of bezafibrate, while in the eight patients with type V, the levels decreased by 61% (P less than 0.001) and 51% (P less than 0.001), respectively. Total cholesterol levels decreased significantly (P less than 0.05) in type V patients at two and four months, by 19% and 18%, respectively, while low-density lipoprotein cholesterol levels increased significantly (P less than 0.05) in type IV patients at two and four months, by 63% and 62%, respectively. High-density lipoprotein (HDL) levels increased significantly (P less than 0.05) at two months in both patient groups. HDL subfraction analysis showed a significant (P less than 0.05) rise in HDL3-cholesterol levels in type V but not in type IV patients. Apolipoprotein (apo) A-I, A-II, and B levels increased, while apo C-II, C-III, and E levels decreased in both groups. The apo A-I/apo A-II ratio decreased significantly (P less than 0.05) at two and four months in type V patients, which also supports increased HDL3 fractions in that group. Lipoprotein lipase and hepatic TG lipase levels tended to rise, and the particle size of TG-rich lipoprotein (TGRL) and the TGRL-apo C-III/TGRL-apo C-II ratio decreased in both patient groups. These data indicate that bezafibrate-induced changes in lipoprotein profiles differed slightly in type IV and type V patients. The results confirm the usefulness of bezafibrate as a lipid-lowering agent.     

Effect of hemodialysis on left ventricular function. Dissociation of changes in filling volume and in contractile state

Prior studies of the effect of hemodialysis on left ventricular function have not distinguished between the removal of uremic toxins and the change in cardiac filling volume. To separate these effects, left ventricular function was examined by serial echocardiography in five stable hemodialysis patients before and after three different dialysis procedures: (a) hemodialysis with volume Loss, (b) ultrafiltration (volume loss only), and (c) hemodialysis without volume loss. The patients were similarly studied under control conditions and after increased (5 degrees of head-down tilt for 90 min) and decreased (lower body negative pressure) cardiac filling volume. After hemodialysis with volume loss, end-diastolic volume (EDV) decreased from 167 to 128 ml (P less than 0.001) and end-systolic volume (ESV) decreased from 97 to 51 ml (P less than 0.001) without a change in stroke volume (SV). Ejection fraction increased from 42 to 52% (P less than 0.001) and mean velocity of circumferential fiber shortening (VCF) increased from 0.61 to 1.04 circumferences (circ)/s (P less than 0.001). After ultrafiltration, EDV decreased from 167 ml to 124 ml (P less than 0.001) and SV from 73 ml to 39 ml (P less than 0.001), without significant changes in ESV or VCF. In contrast to the maneuvers in which volume loss occurred, after hemodialysis without volume loss ESV decreased from 95 to 66 ml (P less than 0.001) and SV increased from 74 ml to 97 ml (P less than 0.001) without changes in EDV. EF increased from 44 to 59% (P less than 0.001) and VCF increased from 0.64 to 1.26 circ/s (P less than 0.001). Ventricular function curves plotted from data obtained under conditions of altered cardiac filling volume before and after the three dialysis maneuvers demonstrate that ultrafiltration produced a pure Frank-Starling effect, while hemodialysis with or without volume loss produced a shift in the ventricular function curves, which demonstrated an increase in the contractile state of the left ventricle. The changes in left ventricular function produced by regular hemodialysis are the combined effects of a decrease in EDV and an increase in the contractile state of the left ventricle.     

Pharmacokinetic and electrophysiologic interactions of amiodarone and procainamide

The effects of amiodarone on the pharmacokinetic and electrophysiologic properties of procainamide were examined in eight patients treated for recurrent ventricular arrhythmias who received intravenous procainamide, 6 to 15 mg/kg, at control and after 1 to 2 weeks of oral amiodarone treatment. Compared with control, procainamide plasma clearance decreased from 0.43 +/- 0.12 L/kg-hr to 0.33 +/- 0.12 L/kg-hr (P less than 0.01), plasma elimination half-life increased from 3.77 +/- 0.64 hours to 5.21 +/- 0.42 hours (P less than 0.01), and volume of distribution was unchanged from 2.31 +/- 0.74 L/kg to 2.47 +/- 0.90 L/kg during amiodarone treatment. As single agents, intravenous procainamide and oral amiodarone produced equivalent increases in QRS duration, rate-corrected QT interval, right ventricular effective refractory period, and cycle length of induced ventricular tachycardia. After the addition of intravenous procainamide to amiodarone the QRS duration, rate-corrected QT interval, and, in six of eight patients, ventricular tachycardia cycle length were significantly increased compared with control or either drug alone, suggesting additive electrophysiologic effect. However, acceleration of induced ventricular tachycardia occurred in one patient with combined treatment, suggesting a potential for adverse electrophysiologic interactions. These findings indicate that amiodarone has pharmacokinetic and electrophysiologic interactions with procainamide and suggest that the intravenous dose of procainamide be reduced by 20% to 30% during concurrent drug administration.     

Variability in the Measurement of Human Ventricular Refractoriness

The degree of variability in ventricular refractoriness and factors potentially affecting this variability were evaluated in 80 patients undergoing an electrophysiological study. Each of seven variables (stimulation current, coupling interval of the basic drive train to spontaneous rhythm, pause between determinations, bipolar pacing configuration, bipolar vs unipolar pacing, atrioventricular synchrony, and autonomic tone) was evaluated in a group of ten patients to determine its effects on the reproducibility of refractoriness. Measurements were repeated ten times in every patient under each of two conditions. Five variables had significant effects on the reproducibility of measurements. Pacing at 10 mA was associated with less variability in the determination of ventricular refractoriness than pacing at twice threshold (within-subject variance component 4.5 vs 10.1 msec; P less than 0.001). The mean difference between the longest and shortest determinations of refractory periods (range) was 6.2 msec at 10 mA and 8.6 msec at twice threshold. The use of a conditioning period of pacing and continuous trains (eight beats with a 3-sec pause) rather than a variable pause between serial trials reduced the mean within-subject variance component from 16.5 to 3.3 (P less than 0.001) and the mean range of refractory period determinations from 10.8 to 4.8. The use of the distal rather than the proximal pole as the cathode decreased the mean within-subject variance component from 9.4 to 3.3 (P less than 0.001) and the range of determinations from 6.4 to 5.8 msec. Unipolar pacing was associated with less variability than bipolar pacing (mean within-subject variance component 4.6 vs 6.4; P less than 0.05, mean range 5.0 vs 7.6 msec).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of indecainide in patients with left ventricular dysfunction

Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had greater than or equal to 30 ventricular premature complexes/hour, moderate-to-marked left ventricular dysfunction, and mean ejection fraction 34% +/- 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until greater than or equal to 80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed greater than or equal to 80% in nine patients (p less than 0.05) and ventricular tachycardia episodes were completely suppressed in five of eight patients. The effective or maximal mean daily indecainide dose was 191 +/- 32 mg; half of the responders achieved achieved efficacy at serum drug concentration greater than or equal to 600 ng/ml. Serum drug concentration was directly related to gender (r = 0.78, p less than 0.04) and inversely related to creatinine clearance (r = 0.74, p less than 0.05) and ejection fraction (r = 0.71, p less than 0.02). Indecainide prolonged mean PR and QRS intervals (p less than 0.05) but not QT or QTc. There was a linear relation between percent change in PR (r = 0.80, p less than 0.001) and QRS (r = 0.66, p less than 0.001) intervals and serum drug concentration. After starting or increasing the dose, careful observation of patients with decreased renal function or reduced ejection fraction should be exercised because they attain higher drug concentration than normal subjects.     

Metabolic effects of dobutamine in normal man.

1. Dobutamine in 5% (w/v) D-glucose was infused at sequential doses of 2, 5 and 10 micrograms min-1 kg-1, 45 min at each dose, into eight healthy male subjects, and the effects were compared with those produced by infusion of the corresponding volumes of 5% (w/v) D-glucose alone. 2. The energy expenditure increased and was 33% higher than control (P less than 0.001) at 10 micrograms of dobutamine min-1 kg-1. The respiratory exchange ratio decreased from 0.85 (SEM 0.02) before infusion to 0.80 (SEM 0.01) at 10 micrograms of dobutamine min-1 kg-1, but did not alter during the placebo infusion (P less than 0.001). 3. Plasma noradrenaline concentrations were lower during the dobutamine infusion compared with during the infusion of D-glucose alone (P less than 0.025). Plasma dopamine concentrations remained below 0.1 nmol/l throughout both infusions. 4. Compared with during the placebo infusion, the blood glucose concentration decreased (P less than 0.001), the plasma glycerol and free fatty acid concentrations increased by 150 and 225%, respectively (both P less than 0.001), and the plasma potassium concentration decreased from 3.8 (SEM 0.07) to 3.6 (SEM 0.04) mmol/l (P less than 0.01) during dobutamine infusion. The plasma insulin concentration increased at 2 and 5 micrograms of dobutamine min-1 kg-1 (P less than 0.001) with no further rise at 10 micrograms of dobutamine min-1 kg-1. 5. Compared with during the placebo infusion, the systolic and diastolic blood pressures and the heart rate increased during dobutamine infusion (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of the parasympathetic and sympathetic nervous system on nocturnal bronchial obstruction

To determine whether an autonomic nervous system imbalance might underlie the nocturnal dyspnoea in patients with chronic airflow obstruction (CAO), we determined FEV1, sinus arrhythmia gap (SA gap), heart rate and urinary adrenaline and noradrenaline excretion every 4 h over 24 h. Measurements were performed in eight non-allergic patients with CAO and eight age- and sex-matched normal controls. The amplitude of the circadian changes in FEV1 in patients and controls was 27 +/- 2% and 7 +/- 1% respectively (P less than 0.001). Both an increased SA gap and a decreased heart rate are features of increased vagal activity. This vagal activity was significantly increased in patients, compared with normal controls (difference P less than 0.01), the difference being maximal at night. This increased activity might contribute to a bronchial obstruction in these patients. Urinary adrenaline excretion was significantly higher by day than by night in both patients and normal controls (P less than 0.01). The urinary levels of adrenaline in the patients were significantly decreased at all hours of observation as compared with levels in normal controls (P less than 0.05). Urinary noradrenaline levels were significantly lower in patients as compared with normal subjects (P less than 0.01), and lower by night than by day. Urinary histamine and Nt-methylhistamine excretion were in the normal range in each individual. Urinary levels, however, were significantly higher in patients at all hours of observation (P less than 0.05). No circadian rhythm was shown. Plasma cortisol levels showed a normal circadian variation, similar in patients and normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved left ventricular function after short-term treatment with fructose-1,6-diphosphate: echocardiographic study in chronic ischemic heart disease and idiopathic dilated cardiomyopathy

The effect of fructose-1,6-diphosphate (FDP) on left ventricular function was assessed in seven patients with chronic ischemic heart disease and eight patients with idiopathic dilated cardiomyopathy. In a crossover study design each patient received 10 gm of FDP or saline placebo intravenously for three days. An M-mode echocardiographic assessment of left ventricular (LV) function was made before and after each treatment period. After FDP treatment, LV end-diastolic and systolic dimensions showed a 6% reduction (P less than 0.01), while peak lengthening rate of LV dimension in diastole and peak shortening rate of LV dimension in systole increased 17% and 10%, respectively (P less than 0.05). There was evidence that FDP was more effective in the patients with ischemic heart disease than in the patients with cardiomyopathy.     

Diagnostic Value of Comparison of Ventriculoatrial Interval During Junctional Tachycardia and Right Ventricular Apical Pacing

We postulated that comparison of ventriculoatrial intervals during junctional tachycardia and during right ventricular apical pacing may provide similar diagnostic information to that obtained from the insertion of ventricular extrasystoles during tachycardia. We studied 39 patients with either atrioventricular reentrant tachycardia (AVRT) (23 patients) using a single atrioventricular accessory pathway or atrioventricular nodal reentrant tachycardia (AVNRT) (16 patients). Ventriculoatrial [VA] intervals were measured during tachycardia, during right ventricular apical pacing at the same rate as that of the tachycardia and following a ventricular extrasystole delivered at the minimum reset interval (minimum prematurity of a ventricular extrasystole required to advance the subsequent atrial complex by more than 10 msec). The difference between the minimum VA interval during tachycardia and during ventricular pacing was closely related to both the minimum reset interval (r = 0.92, P less than 0.001) and the difference between the minimum VA interval during tachycardia and following a ventricular extrasystole delivered at the minimum reset interval (r = 0.97, P less than 0.001) in the 23 patients in whom the minimum reset interval could be determined. The ratio between the minimum ventriculoatrial interval during tachycardia and ventricular pacing could be determined in all cases and was between 1.53 and 1.68 in AVRT with right free wall (two patients), 0.94 and 1.29 with anteroseptal (three patients), 0.91 and 1.08 with posteroseptal (five patients) and 0.48 and 0.71 with left free wall (13 patients) pathways, while it was between 0.32 and 0.27 in AVNRT (16 patients). The ratio was more discriminative when corrected for ventricular latency and was also useful when calculated from the high right atrial electrogram. We concluded that comparison of ventriculoatrial intervals during junctional tachycardia and during right ventricular apical pacing can discriminate between the mechanisms of tachycardia and the site of pathway. It provides similar information to that obtained from ventricular extrasystoles during tachycardia with the advantage that it can be determined in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of 1-epinephrine on hemodynamics and cardiac function in coronary disease: dose-response studies

To assess the effects of elevated epinephrine levels on cardiovascular performance in patients with coronary artery disease (CAD), epinephrine was infused intravenously into eight patients with normal coronary anatomy and 22 patients with CAD at dose rates of 0.06, 0.12, 0.18, and 0.24 micrograms/kg/min. Hemodynamic responses to epinephrine were not significantly different between the two groups. However, contractility increased significantly more (P less than 0.05) and end-systolic volume decreased significantly more (P less than 0.025) in normal subjects than in those with CAD. Plasma norepinephrine concentrations increased significantly (P less than 0.05) at 0.24 micrograms/kg/min epinephrine, indicating activation of sympathetic nervous system. Epinephrine ischemic thresholds ranged from 652 to 3362 pg/ml. Patients with CAD compared with normal subjects had more frequent ventricular arrhythmias (55% vs. 25%), chest pain (50% vs. 13%), and ischemic ECG changes (73% vs. 13%). These results indicate that although epinephrine induced myocardial ischemia in CAD, hemodynamics and ventricular pump function were maintained.