Hans Åström

Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure

Seventy-nine patients with stable chronic congestive heart failure were randomized into a double-blind, crossover placebo controlled study with 3-month treatment periods, where either 100 mg coenzyme Q10 (CoQ10) or placebo was added to conventional therapy. Mean patient age was 61 +/- 10 years, ejection fraction at rest was 22% +/- 10%, and maximal exercise tolerance was 91 +/- 30 W. The follow-up examinations included ejection fraction (primary objective), exercise test, and quality of life questions. Ejection fraction at rest, during a slight volume load, and during a submaximal supine exercise increased slightly compared with placebo: 24% +/- 12% versus 23% +/- 12% (NS), 25% +/- 13% versus 23% +/- 12% (P < .05), and 23% +/- 11% versus 22% +/- 11% (NS). Maximal exercise capacity increased from 94 +/- 31 W during the placebo period to 100 +/- 34 W during the CoQ10 period (P < .05). Total score for the quality of life assessment increased significantly from 107 +/- 23 during the placebo period to 113 +/- 22 during the CoQ10 period (P < .05). The results indicate that oral long-term treatment with 100 mg CoQ10 in patients with congestive heart failure only slightly improves maximal exercise capacity and the quality of life and that the clinical importance of this needs to be further evaluated.

Diagnostic value of programmed ventricular stimulation in patients with bifascicular block: A prospective study of patients with and without syncope

OBJECTIVES The aim of this study was to examine the inducibility of ventricular arrhythmias in patients with bifascicular block both with and without a history of syncope and to relate the findings to clinical events during follow-up. BACKGROUND Patients with bifascicular block have an increased risk of sudden death that is not reduced by pacemaker treatment. This risk could be related to a high incidence of ventricular arrhythmias. METHOD Programmed ventricular stimulation was performed in 101 patients with bifascicular block: 41 had a history of unexplained syncope, and 60 were asymptomatic. RESULTS Programmed ventricular stimulation resulted in a sustained ventricular arrhythmia in 18 patients (18%), 8 in the syncope group and 10 in the nonsyncope group (p = NS). Three patients in each group had an inducible sustained monomorphic ventricular tachycardia. During a mean follow-up of 21 months, 10 patients experienced a clinical event defined as sudden death (n = 4), syncope (n = 5) or appropriate discharges from an implantable cardioverter-defibrillator (n = 1). Only one of these patients had an inducible ventricular arrhythmia at baseline. CONCLUSIONS The inducibility of ventricular arrhythmias is high in patients with bifascicular block and of the same magnitude in patients with and without a history of syncope. Clinical events during follow-up were not predicted by programmed ventricular stimulation in either of the two groups. The finding of inducible ventricular arrhythmia in patients with bifascicular block should therefore be interpreted with caution.

Monitoring of Pulmonary Arterial Diastolic Pressure Through a Right Ventricular Pressure Transducer

Pulmonary arterial diastolic pressure is an important parameter for hemodynamic monitoring in congestive heart failure. It is traditionally obtained through a pulmonary arterial catheter. If it could be obtained from a sensor in the right ventricle, chronic monitoring would be possible without the use of a pulmonary arterial catheter. This study is based on the hypothesis that pulmonary valve opening and pulmonary arterial diastolic pressure occur at the time of maximum positive rate of pressure development (dP/dt) in the right ventricle, when the pressures should be equal. Thus, right ventricular pressure at the time of maximum dP/dt (PAD index) should be a reasonable estimate of pulmonary arterial diastolic pressure. Eight patients with heart failure were catheterized and exposed to hemodynamic stress. Right ventricular and pulmonary arterial pressures were simultaneously recorded from a Millar (Houston, TX) catheter with two pressure transducers. The distal transducer was positioned in the bifurcation of the pulmonary artery and the proximal transducer was placed in the right ventricle. Pulmonary arterial diastolic pressure and PAD index were stored beat by beat on a bed-side computer. Acceptable recordings were obtained in all patients. Recordings from the individual patients showed a good covariation between PAD index and pulmonary arterial pressure during different hemodynamic manuevers, except during infusion of dobutamine, when the correlation was not as good. Pulmonary arterial diastolic pressure may be estimated from a transducer in the right ventricle, thus eliminating the need for a permanent pulmonary arterial catheter in an implantable hemodynamic monitoring system. Further studies are needed to verify the correlation on a long-term basis.

Influence of β-adrenoceptor blockade on leg blood flow and lactate release in man

Nine healthy male volunteers were studied at rest and during exercise before and after acute local beta-blockade in one leg. Oxygen uptake, arterial pressure, heart rate, leg blood flow and arterial-femoral venous differences for oxygen and lactate were determined. In addition, five subjects were studied at rest during adrenaline infusion to test the blockade; in this situation the increase in leg blood flow and decrease in resistance seen in the control leg were prevented in the blocked leg. During exercise, the beta-blockade did not influence leg blood flow. At rest, lactate release was abolished from the blocked leg, and during exercise the release was reduced by 50%. These findings demonstrate that acute betareceptor blockade does not interfere with the exercise-induced vasadilation but has metabolic consequences reflected by a reduction in the release of lactate from the leg.

Is DDD pacing superior to VVI,R? A study on cardiac sympathetic nerve activity and myocardial oxygen consumption at rest and during exercise.

Rate responsive ventricular pacing (VVI,R) has been demonstrated to equal atrial synchronous ventricular pacing (DDD) with regard to hemodynamics and exercise tolerance. Whether the two modes are also comparable, with regard to cardiac metabolic effects, is not yet dear. We assessed central hemodynamics, cardiac sympathetic nerve activity fcardiac norepinephrine overflow), and myocardial oxygen consumption in 16 patients treated with rate responsive atrial synchronous ventricular pacemakers (DDD,R), due to high degree AV block. The study was performed at rest and during supine exercise at two workloads (30 ± 12 and 68 ± 24 watts, respectively) during VDD and rate matched VVI pacing (VVIm). Ventricular rates at rest and during both workloads were almost identical. Cardiac output at rest tended to be higher in the VDD mode, due to a slightly higher stroke volume. Central pressures including right atrial pressure and pulmonary capillary wedge pressure were similar in the pacing modes. The coronary sinus blood flow, the coronary sinus arteriovenous oxygen difference, and the myocardial oxygen consumption did not differ between the two pacing modes. Cardiac norepinephrine overflow was similar in the two pacing modes, at rest or during exercise. Thus, we found no significant differences between VDD and VVIm pacing with regard to central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), or myocardial oxygen consumption either at rest or during moderate exercise.

Myocardial Demands of Atrial‐Triggered Versus Fixed‐Rate Ventricular Pacing in Patients with Complete Heart Block

Hemodynamics, myocardial oxygen consumption, and lactate concentration were determined by cardiac catheterization at rest and during exercise in eight patients treated with AV universal pacemakers (DDD) for high degree AV block. The pulse generator was alternately programmed in ventricular inhibited (VVI) or atrial synchronous (VAT) mode. During VVI pacing, the cardiac output rose between rest and exercise (4.3–7.6 L/min) due to increased stroke volume. VAT pacing gave significantly greater increase (4.5–8.8 L/min) which, as the stroke volume was unchanged, resulted from acceleroted heart rate. The myocardial oxygen consumption and the coronary blood flow did not differ between VVI and VAT mode at rest or during exercise, nor did the modes make a difference in arterial systolic and pulmonary wedge pressures. These observations suggested that VAT pacing offers higher cardiac output than VVI pacing, but with similar demands on myocardial oxygen consumption.

A method for synthesis of an artificial ribonuclease.

5-Amino-2,9-dimethyl-1,10-phenanthroline-oligonucleotide conjugates have been synthesized. A 2′-O-methyl octaribonucleotide carrying a 2′-aminoethoxymethyl linker in a central position was produced. Reaction of the aminoneocuproine phenyl carbamate with the fully deprotected oligonucleotide in aqueous solution gave virtually quantitative conversion into the conjugate. Preliminary cleavage studies in presence of zinc ions show nuclease activity towards RNA targets.

Sinus Node Recovery Time Assessment Revisited: Role of Pharmacologic Blockade of the Autonomic Nervous System

Sinus Node Recovery and Autonomic Blockade. Sinus node recovery time assessment is used to diagnose clinically significant sinus node dysfunction (SND) when Holter has failed to prove a relationship between sinus bradyarrhythmias and symptoms, but consensus has not been reached as to the value of including assessment after pharmacologic blockade of the autonomic nervous system. This issue was addressed in the present study performed on 52 patients with syncope or presyncope/dizziness (n = 48), sinus bradyarrhythmias (n = 45), or both (n = 41). Group 1 consisted of 13 patients with a proven relationship between symptoms and sinus bradyarrhythmias. Group 2 consisted of 39 patients with suspected SND. The protocol included three pacing periods at two pacing rates and was performed at baseline (n = 52), after single doses of atropine and propranolol (0.02 mg/kg and 0.1 mg/kg, respectively) (n = 41), and again after a second dose (n = 29). The sensitivity of prolonged recovery times was 77% in group 1. Among group 2 patients, 56% had prolonged recovery times at baseline (79% when including the results after the first dose of drugs). The second dose did not contribute diagnostic information, but it caused significant adverse reactions in 7 of 29 patients (P < 0.001). These 7 patients were all older than 60 years. Assessment of sinus node recovery time after pharmacologic blockade of the autonomic nervous system thus increases the sensitivity of the method in patients with suspected SND and normal baseline results. However, only 50% of the initially suggested doses of atropine and propranolol is sufficient and eliminates the risk for significant adverse reactions.

Contribution of 4‐hydroxy‐alprenolol to adrenergic beta receptor blockade of alprenolol

Alprenolol, like propranolol, is metabolized to a 4‐hydroxy derivative. This study was performed in 6 human volunteers to determine the potency of the metabolite in relation to that of alprenolol with respect to reduction of exercise‐induced tachycardia. The metabolite reached higher plasma levels than alprenolol during the first hours after both single and repetitive oral doses of alprenolol but was not detected in plasma after an intravenous dose. The plasma elimination half‐life for 4‐hydroxy‐alprenolol was one‐third that for alprenolol (0.8 hr and 2.5 hr, p < 0.01). Percentage reduction of exercise heart rate and total plasma levels of alprenolol after a 10‐mg intravenous dose correlated (r = 0.56, p < 0.01). This was generally higher within individuals, since the responsiveness to unchanged alprenolol differs among subjects. The effect‐concentration relationship was slightly higher (r = 0.67) when non‐protein‐bound alprenolol was substituted for total alprenolol. 4‐Hydroxy‐alprenolol contributed to the effect after oral administration of alprenolol; total plasma levels were equipotent with alprenolol. It is concluded that the contribution of the metabolite to effect varied among individuals and was dependent on mode of administration (intravenous or oral), dose, and time after dosage. We also introduce an approach to the evaluation of the activity of drug metabolites in the presence of the parent compound.

Screening for sinus node dysfunction by analysis of short-term sinus cycle variations on the surface electrocardiogram

A new noninvasive screening method for diagnosing sinus node dysfunction (SND) was evaluated. Sinus cycle variations from 1-minute electrocardiograms (ECG) were described by two variables: the variation range around the mean cycle length (percentage) and the maximal change between any two consecutive cycles (milliseconds). SND was diagnosed when both variables were increased. Part 1: Validation of this method against Holter and sinus node recovery time assessment in 69 patients with proven or possible sick sinus syndrome (SSS). Part 2: Application of the method to 60 patients with clinically significant cardiovascular and pulmonary disorders (group 3), but without any pretest suspicion of SND. Part 1: Sinus cycle variations and sinus node recovery times were abnormal in similar proportions, 55% and 63%, respectively. The sensitivities in proven SSS were 72% and 71%, respectively. Sinus node function was concordantly classified in 80% of 64 patients undergoing both tests. When sinus cycle variations were abnormal the probability of a prolonged recovery time was 89%. Part 2: Asymptomatic SND was found in 12% of patients in group 3. Thus, analysis of short-term beat-to-beat variations in the surface ECG has a sensitivity of approximately 70% and a specificity of 100% for diagnosing SND.