Olof Nyquist

Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance

BACKGROUND Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance. AIM To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure. METHODS With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens. RESULTS Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05). CONCLUSIONS One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention.

Hemodynamic and antiarrhythmic effects of tocainide in patients with acute myocardial infarction

In order to evaluate the hemodynamic and antiarrhythmic efficacy of tocainide, studies were performed in patients suffering acute myocardial infarction. Intravenous tocainide was administered over a 15-minute period in order to determine its acute effects and subsequently, in a randomized double-blind study with placebo control, to determine its effects over a 24-hour period in acute myocardial infarction. Tocainide resulted in a significant decrease of frequent and complex ventricular arrhythmias acutely and had only minimal effects of hemodynamics in most patients. In the long-term studies, tocainide produced no adverse hemodynamic effects when compared with placebos.

Determination of (R)- and (S)-Disophyramide in human plasma using a chiral α1-acid glycoprotein column

Abstract The direct resolution and quantitation of (R)- and (S)-disopyramide, isolated from human plasma, was accomplished using a chiral α1-acid glycoprotein column. A LiChrosorb RP-2 column (50 × 3.0 mm I.D.) was used as a precolumn. Phosphate buffer, pH 6.20, containing 2-propanol and N,N-dimethyloctylamine was used as mobile phase, expressed as the relative standard deviation, was 1.8% and 3.3% for (R)- and (S)-disopyramide, respectively, at a drug level of 0.5 μg/ml. In two subjects who received a single capsule of racemic disopyramide (150 mg), the plasma levels of the (R) isomer were about half those of the (S) isomer. The half-lives of (R)- and (S)-disopyramide were similar.

Beat-to-beat QRS amplitude variability during dobutamine infusion in patients with coronary artery disease

The aim of this study was to investigate if provoked myocardial ischemia induces increased beat-to-beat QRS amplitude variability in patients with angiographically verified coronary artery disease. 15 patients (median age 62 years, range 46-73 years) and 10 healthy controls (median age 25 years, range 22-42 years) were studied. Dobutamine was infused intravenously at a low and at a high dose. The mean low dose of the drug was 10.0 micrograms/kg/min for both patients and controls, whereas the mean maximum dose was 31 +/- 2 for patients and 38 +/- 1 microgram/kg/min for controls. The total QRS amplitude beat-to-beat variance from 12 leads as well as individual variance scores in each single lead were evaluated. Before infusion, the total QRS variance did not differ between patients and controls, nor did the individual variance in 9 of the 12 ECG leads. Dobutamine elicited an increase (p < 0.01) in the total QRS variance, with significantly higher (p < 0.001) total variance in patients than in controls. At the high dose of the drug, the patients displayed significantly higher individual variance values in each ECG lead as well. During dobutamine infusion, 7 of 15 patients developed ST depressions (> or = 0.1 mV in > or = 2 leads) in 12-lead ECG readings. Eleven of 15 patients developed chest pain (grade > or = 3 at the Borgs CR-10 scale). In conclusion, in patients with ischemic heart disease, dobutamine-provoked stress gives rise to increased QRS amplitude beat-to-beat variability, as a sign of electrical instability of the myocardium.

Comparative bioavailability of disopyramide after multiple dosing with standard capsules and controlled-release tablets

SummaryPlasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.

Arterial Oxygen and Carbon-Dioxide Tension in Patients with Acute Myocardial Infarction

Over a 2-year period, 450 cases of acute myocardial infarction were treated in a coronary care unit. Arterial PO2 and PCO2, were routinely determined on the day of admission. In

Acute haemodynamic effects and pharmacokinetics of ramipril in patients with heart failure

SummaryThe aim of the present study was primarily to evaluate the haemodynamic effects of the ACE-inhibitor ramipril which is active via its metabolite ramiprilat. Ramipril 1.25, 2.5 and 5 mg and placebo was administered orally to 4 groups of 12 patients with heart failure (NYHA III) in a double-blind randomised, parallel study. Haemodynamics were monitored for 24 h and blood was sampled and urine collected for up to 96 h.In the placebo-treated group the cardiac index (CI) was significantly increased (15.8%) and right atrial pressure decreased (26.6%). Ramipril 1.25 mg had insignificant haemodynamic effects compared to placebo and the 2.5 mg dose had significant effects on some haemodynamic variables. Ramipril 5 mg had pronounced and sustained effects on pulmonary artery pressure, which fell by 43.7%, and pulmonary capillary wedge pressure (PCWP; −59.1%); systemic vascular resistance was also decreased 21%. A significant effect on CI was only seen after 2.5 mg ramipril (+7.4%). The mean maximal degree of ACE inhibition was 73.2, 90.4 and 98.5%, respectively, after the three doses of ramipril. Complete inhibition of ACE-activity was seen at a mean plasma concentration of ramiprilat of 4.7 ng·ml−1. The degree of inhibition declined with a half life of about 75 h.There was a significant relation between the degree of ACE-inhibition and change in PCWP but not with the change in SVR. Ramipril was mainly eliminated in the form of ramiprilat and inactive metabolites.

A high risk subgroup of patients with unstable angina pectoris treated medically or surgically.

Among patients consecutively admitted to a coronary care unit (CCU) without a subsequent diagnosis of acute myocardial infarction (AMI), a subgroup fo unstable angina was selected, defined as continued episodes of angina at rest during a 48-hour period, despite medical treatment in the CCU. During a four-year period, 15 patients fulfilled these criteria. Eight patients were medically treated, seven of whom developed an AMI with three subsequent deaths. Six of the infarcts occurred within eight days of admission. In six patients, fulfilling the criteria, surgical treatment was performed. Angiography and surgery in this group were associated with low incidences of myocardial infarction, late infarction and death. In one patient, surgery was declined due to unfavourable anatomical conditions. This patient subsequently developed an AMI and died. It is concluded that the combination of recent onset of angina and continued episodes of angina at rest, despite medical treatment, selects a high risk subgroup of unstable angina. Acute coronary angiography and surgery ought to be considered in this subgroup.

The value of repeated echocardiographic evaluation in patients with idiopathic dilated cardiomyopathy during treatment with metoprolol or captopril

Serial echocardiographic investigations were carried out on patients with idiopathic dilated cardiomyopathy, to evaluate treatment effects on left ventricular (LV) performance during therapy with either metoprolol or captopril. Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of heart failure (NYHA II-III) and a mean age of 49 years were included in the investigation. The patients were investigated with Doppler echocardiography before treatment, after 3 and 6 months of treatment (either metoprolol or captopril) and 1 month after withdrawal of treatment. Intra- and inter-investigator reproducibility was acceptable, with a coefficient of variation of less than 5% for LV dimensions. A reduction in LV dimensions was seen in both treatment groups. In the metoprolol group there was also an increase in LV stroke volume and fractional shortening. The non-invasive data were in accordance with invasive measurements of stroke volume and LV filling pressure. In patients with idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure, echocardiography seemed to be sufficiently reproducible to be used for determination of treatment effects in a longitudinal heart failure study. Both metoprolol and captopril were well tolerated and had favourable effects on LV performance.

Hemodynamic effects of combined treatment with lignocaine, procainamide and practolol in acute myocardial infarction.

In the treatment of refractory ventricular tachyarrhythmias antiarrhythmic drugs must sometimes be combined. An electrophysiologically appropriate combination is lignocaine and procainamide and, when needed, a beta-blocking agent. The hemodynamic effects of this treatment were studied in 6 patients in the acute phase of myocardial infarction. After a control period, an infusion of lignocaine was started and 1 h later procainamide/placebo was added in a double-blind system and finally also practolol/placebo. The drugs were given intravenously in ordinary doses. Hemodynamics were studied by bedside catheterization. During triple treatment heart rate and aortic pressures fell significantly whereas right atrial mean pressure increased compared to the control period. Stroke volume, cardiac output and pulmonary artery pressures were unchanged. Most of the changes appeared when practolol was added. Following the procainamide injection a transient fall in aortic pressures was noted. Lignocaine gave no hemodynamic effects. The number of ventricular premature beats was reduced in all patients and no patient had ventricular tachycardia during treatment. In these patients it was possible to combine lignocaine, procainamide and practolol in the acute phase of myocardial infarction. However, 3 patients developed hypotension, 1 sinus bradycardia and 1 had a short run of nodal tachycardia. It is concluded that this kind of combined treatment, because of its potential risks, should be restricted to critical clinical situations and then it ought to be hemodynamically controlled.