Biomedical subjects
Publications and source records attributed to L Brorson.
An 81-year old man with third-degree AV block and weakness underwent an unsuccessful attempt to DDD pacemaker implant caused by hypothyroidism. Administration of thyroxin until he was euthyroid permitted implantation with normal stimulation thresholds.
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Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmacokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in anti-anginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.
Myocardial monophasic action potentials (MAP) can be recorded with the aid of suction or contact electrodes applied endocardially via a catheter. The technique necessitates high input impedance amplifiers with infinite time constant. A bipolar technique improves signal quality with regard to electrical contamination around the rapid upstroke of the MAP. Mechanical artefacts in the recordings are common and may be explained by catheter movement induced by atrial or ventricular contractions. The MAP signal can be used for a precise measurement of time of local excitation and for the study of atrial as well as ventricular repolarization. The technique has mostly been applied in the exploration of atrial and ventricular repolarization in healthy hearts and during different cardiac arrhythmias. Furthermore, several studies have documented the electrophysiological action of antiarrhythmic drugs upon the human heart. Concluding from 576 different investigations we consider the technique to have no serious side-effects.
The authors have previously shown that 40% of patients whose ventricular arrhythmias respond to propranolol require plasma concentrations in excess of those producing substantial beta-receptor blockade (greater than 150 ng/ml). However, the electrophysiologic actions of propranolol have only been examined in human beings after small intravenous doses achieving concentrations of less than 100 ng/ml. In this study, the electrophysiologic effects of a wider concentration range of propranolol was examined in nine patients. Using a series of loading and maintenance infusions, measurements were made at baseline, at low mean plasma propranolol concentrations (104 +/- 17 ng/ml) and at high concentrations (472 +/- 68 ng/ml). Significant (p less than 0.05) increases in AH interval and sinus cycle length were seen at low concentrations of propranolol, with no further prolongation at the high concentrations; these effects are typical of those produced by beta-blockade. However, progressive shortening of the endocardial monophasic action potential duration and QTc interval were seen over the entire concentration range tested (p less than 0.05). At high concentrations, there was significant (p less than 0.05) further shortening of both the QTc and monophasic action potential duration beyond that seen at low propranolol concentrations, along with a progressive increase in the ratio of the ventricular effective refractory period to monophasic action potential duration. No significant changes were seen in HV interval, QRS duration or ventricular effective refractory period. In summary, the concentration-response relations for atrioventricular conductivity and sinus node automaticity were flat above concentrations of 150 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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Radionuclide and contrast ventriculography were evaluated for their ability to estimate myocardial ischemia. In 14 closed-chest, sedated dogs, a small and larger region of ischemia were produced by inflating balloon occluders on the left anterior descending coronary artery. The systemic arterial pressure, atrial-paced heart rate, global ejection fraction by radionuclide and contrast ventriculography, regional wall-motion abnormalities (as the percentage of abnormally contracting segments), and regional myocardial blood flow (using the microsphere technique) were measured during an initial control period, two separate ischemic periods, and a final control period. The regional ischemic weights based on myocardial blood flow ranged from 0 to 38.5 g and were grouped as zero, small (range 0 to less than 10 g, mean 3.40 g), and large regions of ischemia (greater than 10 g, mean 24.8 g). Regional wall-motion abnormalities were sensitive qualitative indicators of ischemia. Receiver operating characteristic analysis showed that both ventriculographic methods were highly sensitive, specific, and accurate for detecting regional ischemia. Contrast ventriculography was slightly superior for detecting small regions less than 4 g, but the methods were equal for regions greater than 4 g. The arterial pressure and heart rate were unchanged during ischemia. For small regions of ischemia, the global ejection fraction did not fall using either the contrast or radionuclide technique, but it fell significantly when large regions were produced. There was a quantitative relationship between the percentage of abnormally contracting segments and the grams of myocardial ischemia (for radionuclide ventriculography, r = 0.65, P = 0.003, and for contrast ventriculography, r = 0.75, P less than 0.001), but for many small regions of ischemia, wall-motion changes were greater than anticipated, suggesting hypofunction of the continguous normal tissue. This study demonstrated that both radionuclide and contrast ventriculography were quite sensitive and specific for detecting measured amounts of regional ischemia. The functional changes resulting from ischemia are quantitatively related to the extent of regional ischemia, small areas resulting in regional wall motion abnormalities, and large areas producing both reduced global ejection fraction and wall motion changes.
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Sustained handgrip at 30% of the maximal strength and submaximal supine bicycle exercise elicited mean blood pressure increases of similar magnitude in healthy males and in men with essential hypertension WHO Stage 1 and 2, but with different contributions of systolic and diastolic blood pressure changes. While systolic blood pressure exceeded 22.7 kPa (170 mmHg) during static exercise in every hypertensive man, this did not occur in any of the control subjects. During dynamic exercise, the arterial blood pressure increase per litre increase in cardiac output was significantly less than during static exercise, indicating different patterns of circulatory adaptation to these two forms of stress. Combination of dynamic and static exercise tests might be of value for identifying subjects with a hypertensive pattern of circulatory regulation.
The tricyclic antidepressant agent imipramine was tested intravenously in 8 healthy individuals with respect to its effect on sinus recovery time, intervals in His bundle electrograms and the duration of the repolarization in the right atrium and ventricle judged from the refractoriness and monophasic action potential duration. Sinus recovery time was unchanged after the drug. The interval between the His bundle deflection and the start of the QRS complex in the standard lead showed no consistent changes but increased to pathological values in two individuals. The duration of the repolarization decreased in the atrium--an effect which could be arrhythmia-provoking or arrhythmia-protecting. The duration increased at the ventricular level. This effect could explain the antiarrhythmic effect on ventricular ectopics observed in other investigations.
The effective right ventricular refractory (EVRP) period was estimated in 24 patients using the extra stimulus technique. All patients were paced from the right ventricle at basic pacing intervals of 400, 500, 600 and 800 ms, respectively. In all patients the EVRP decreased when the basic pacing rate was increased. At the same basic pacing rate there was a wide variation in the EVRP between individual patients. Within an individual patient, however, providing the position of the pacing electrode remained stable, there was no significant variation in the EVRP when estimations were performed 15-30 min apart. Thus the technique can be used to assess the effect of a drug on the EVRP in an individual patient.
Thirteen patients with paroxysmal atrial tachyaarhthmias (six atrial supraventricular tachycardia, six atrial fibrillation, and one atrial flutter) have been investigated by recording of monophasic action potentials (MAP) during a period free from arrhythmias. None of the patients differed from healthy individuals with respect to any of the MAP variables. Occasional recordings showed values not found in healthy individuals, such as prolonged duration of the MAP or slow phase 4 depolarization. The atrial effective refractory period (AERP) was determined in two patients. One AERP was short compared with values found in healthy individuals. Thus some MAP recordings gave a possible explanation for the mechanism behind the arrhythmias, while other recordings showed no differences from results in healthy individuals.
Atrial conduction time (ACT) between a stimulating pacemaker electrode and an "impulse-detecting" monophasic action potential (MAP) electrode has been determined in 20 healthy males. A small increase in ACT was found with increasing paced heart rates. Using the extra stimulus technique, ACT was found to increase when the early ectopics approached the atrial effective refractory period (AERP). The degree of ACT prolongation was similar at long and short basic ACTs, indicating that the slowing of impulse propagation probably occurred near the simulating electrode and presumably within 1/2-1 cm from that electrode. The increase in ACT close to the AERP was of importance when determining the atrioventricular refractory period. In three recordings a supernormal phase of conduction was found. The small errors of the MAP recordings in detecting the time of excitation make the method sensitive enough to detect small differences in ACT.
The monophasic action potential (MAP) and the effective refractory period (ERP) of the right atrium were determined in eight healthy volunteers before and after hard physical training. The duration and amplitude of the MAP increased in seven individuals after training. ERP showed no consistent changes. One possible explanation of the findings is an accumulation of intracellular potassium. The duration of the MAP was well correlated to maximal heart rate.
Right atrial monophasic action potentials (MAP) have been recorded in 40 healthy males. At least one MAP recording was performed in each individual during spontaneous sinus rhythm. Right atrial pacing and simultaneous MAP recording were performed in 25 of the 40 individuals. The paced cycle length was successively decreased in steps of 100 msec between 800 and 400 msec. The durations of the MAP at 50 and 90% repolarization and the relative repolarization rate during phase 3 (RRR ph 3) were calculated and normal values for the variables are given. A correlation was demonstrated between the duration of the MAP and the cycle length-the longer the cycle length, the longer the duration of the MAP-both during sinus rhythm and during the atrial pacing. A significant correlation was also shown between the RRR ph 3 and the duration of the MAP at 90% repolarization-the shorter the MAP, the faster the RRR ph 3. One age group (45-54 years) deviated significantly from the rest in some respects, but in general there was no age trend in the whole material.
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Right atrial effective refractory periods (AERP) and monophasic action potentials (MAP) have been determined in 29 healthy males in four different age groups between 25 and 64 years. One age group (45-54 years) showed a significantly longer AERP than the others, with a mean of 283 msec compared with 230-238 msec in the other groups. However, no age trend was found in the total material. The AERP decreased at higher paced heart rates, the decrease between paced cycle lengths of 800 and 600 msec amounting to 13 msec. When the MAP and the AERP were determined in the same position of the atrium, they showed no statistically significant correlation. A possible explanation is that the cells contributing to the AERP and the MAP are not altogether the same. The MAP and the AERP determinations have a similar degree of reproducibility but possibly mirror different kinds of repolarization phenomenon.