Biomedical subjects
L Kaijser
Publications and source records attributed to L Kaijser.
Cardiac synthesis of prostaglandins from arachidonic acid in man.
The bioformation of PGs in the human heart was studied in 7 male volunteers by constant rate infusion of 14C-labelled arachidonic acid (AA) into the aortic root and simultaneous blood sampling from the coronary sinus. After conventional extraction of lipids from the plasma samples, the various 14C-PGs formed were separated and quantified by means of thin layer chromatography and fractionated liquid scintillation spectrometry. The infused arachidonic acid was metabolized and well defined chromatographic peaks of 14C-PGs were obtained. Apart from a chromatographic peak corresponding to 14C-PG metabolites, 6-keto-PGF1 alpha constituted the main 14C-PG formed (23 +/- 8%) reflecting a considerable synthesis of prostacyclin in the heart. 14C-PGs of the D, E and F series were formed in roughly equal amounts (14--19%). In a 54-year-old subject, 6-keto-PGF1 alpha constituted a greater proportion of 14C-PGs (60%) than in the other subjects. This can reflect a general effect of ageing or it can indicate the presence of ischemic heart disease in this subject.
Prevalence of ECG findings in 18-19 year old Swedish men.
2268 consecutive men, 18-19 years of age, were examined at an enlistment centre regarding their health, some anthropometric variables and electrocardiogram. ECG items according to the modified Minnesota code [1] were found in 230 subjects (10%). Most common ECG findings were T wave abnormalities (2.2%). Heart rate was higher in the groups with QRS axis deviation, T wave items, sinus tachycardia and supraventricular ectopic beats. Systolic and/or diastolic blood pressure was increased in the groups with T wave items, sinus tachycardia and ventricular ectopic beats. A dysfunction of the autonomic tone can often be suspected as a cause of the abnormality, especially in the groups with tachycardia, T wave changes, AV block grade I and AV junctional rhythm. An ECG recording during orthostasis was considered to be of value to clarify the nature of the ECG abnormality.
Autonomic control of cardiovascular reflexes in narcolepsy.
Six male patients with narcolepsy for several years, were studied without and with amphetamine in order to evaluate possible abnormalities in autonomic control of the cardiovascular system. Studies were made of (1) heart rate and blood flow in the resting forearm during contralateral isometric handgrip, (2) respiratory sinus arrhythmia and (3) heart rate response to the Valsalva manoeuvre. The patients had a slow heart rate, a reduced forearm blood flow increase on handgrip, and a subnormal sinus arrhythmia. Only two out of the six patients had an abnormal Valsalva ratio. Amphetamine did not alter the response to handgrip but increased the sinus arrhythmia in three patients and the Valsalva ratio in two. It is concluded that narcolepsy is accompanied by reduced vegetative reactivity in the cardiovascular system. Since this applies to functions mediated by both the sympathetic and parasympathetic systems, and since some parasympathetically-mediated functions are affected while others are not, the functional disturbance found probably is of central origin.
Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following hypothermic cardioplegia.
Cardiac metabolism following hypothermic potassium cardioplegia was studied in 23 patients undergoing isolated aortic valve replacement. All had normal coronary arteries. Cardioplegia was induced by infusing 700-1 000 ml of cold Ringer's acetate containing 20 mekv K+ selectively into the left coronary artery. Simultaneous blood samples were taken from the radial artery, a central vein and from the coronary sinus before and after cardioplegia. The PO2, O2-saturation and content, PCO2, pH, lactate, glucose, potassium, myoglobin, total creatine kinase (CK), its isoenzyme CK-MB, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were assessed. Before bypass lactate was extracted by the heart. During the initial 10 to 20 min after cardioplegia there was a marked release of lactate in the coronary sinus. Myoglobin concentration and CK-MB serum activity peaked during the first 4 hours after the release of the aortic cross-clamping. In order to determine the best indicator of myocardial damage after cardioplegia, duration of extracorporeal circulation (ECC-time), aortic occlusion time (AOT), mean myocardial temperature (MMT) and the product of AOT and MMT, referred to as time-temperature area (TTA), were related to possible indicators of myocardial injury, such as enzyme and myoglobin release. The TTA was the best way of expressing the degree of exposure of the heart to ischaemia. The CK-MB to peak area (CK-MB max area) was the best indicator of the degree of ischaemic injury sustained by the heart during operation.
Studies on serum lipoproteins and lipid metabolism. Analysis of a random sample of 40 year old men.
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Cardiac prostaglandin formation in man.
The quantitative relationship between various prostaglandins (PGs) formed in the human heart was studied by constant-rate infusion of 14C-labeled arachidonic acid into the aortic root and simultaneous blood sampling from the coronary sinus in six healthy volunteers. After conventional extraction procedures, the various 14C-PGs formed were separated and quantitied by means of thin-layer chromatography and fractionated liquid scintillation spectrometry. Most of the arachidonic acid infused was metabolized, and well defined peaks of 14C-PG were obtained in the chromatograms. 6-keto-PGF 1 alpha constituted the main PG formed, reflecting a considerable synthesis of prostacyclin in the heart. PGs of the D, E, and F weries were formed in roughly equal amounts. In a 54-year-old subject, 6-keto-PGF 1 alpha constituted a greater proportion of PG than in the other subjects. This may reflect a general effect of aging or it may indicate the presence of ischemic heart disease in this subject.
Effect of metabolic intervention on substrate metabolism in the human heart.
Myocardial substrate uptake and utilization is dependent on substrate concentrations in blood. Thus glucose extraction increases with increased glucose and decreases with increased free fatty acid (FFA) concentration, the latter effect probably mediated by inhibition of pyruvatedehydrogenase and phosphofructokinase. Carbohydrate oxidation requires less oxygen than lipid oxidation. In a series of studies in healthy men, the effects on myocardial metabolism of procedures intended to increase carbohydrate utilization were evaluated by coronary sinus catheterization utilizing [14C]oleate to estimate extraction and oxidation of FFA. Plasma FFA lowering by nicotinic acid decreased myocardial extraction of FFA and increased that of glucose, lactate, and pyruvate with concomitant increase in myocardial respiratory quotient (RQ). The fractional oxidation of FFA remained essentially unchanged. Intravenous glucose infusion increased myocardial glucose extraction, partly as a direct effect of the increased arterial glucose concentration, but, also, secondarily to the induced decrease in plasma FFA concentration and FFA extraction. It is concluded that enzyme inhibition by accumulation of intermediary metabolites, such as citrate, is important in the regulation of carbohydrate versus lipid utilization in the heart.
Prostaglandins contribute to the vasodilation induced by nicotinic acid.
The significance of endogenously formed prostaglandins in the vasodilation induced by nicotinic acid (NIC) was investigated. The forearm venous plasma level of radioimmunoassayed PGE (R-PGE) and the forearm blood flow (FBF) were measured in 13 healthy male volunteers at rest and during infusion of NIC. Each subject was subsequently re-studied after pretreatment with the PG synthesis inhibitor, naproxen. In the absence of naproxen, NIC infusion resulted in an almost four-fold rise in the release of R-PGE and a 60% increase in FBF. Pretreatment with naproxen did not affect the basal release of R-PGE or the basal FBF but inhibited both the release of R-PGE and the increase in FBF following NIC. The data support the hypothesis that the vasodilating effect of NIC is largely dependent upon an increased vascular formation of PG.
Effect of plasma free fatty acid lowering on exercise tolerance and ST segment depression in patients with angina pectoris.
The effect of a single oral dose of a plasma FFA-lowering drug (5-(3-pyridyl) tetrazole), which does not act by conversion into nicotinic acid, on exercise tolerance and ECG reaction was studied on a double-blind basis in 15 men with stable angina pectoris. Exercise was performed on a bicycle ergometer in the sitting position with a load increase of 10 W/min. In addition to ECG, time to onset of chest pains and to termination of exercise because of strong chest pains was recorded. 5-(3-pyridyl) tetrazole decreased plasma FFA during exercise from 523 to 299 mumol/l. It reduced significantly the ST depression at corresponding work loads and permitted the patients to exercise 0.6 min longer, corresponding to a 7% higher work load, before the onset of chest pain. However, absolute exercise time was not significantly increased. The most probable explanation of the improved performance is a decreased lipid and increased carbohydrate oxidation by the ischemic heart, although a contribution may have come from hemodynamic effects of the drug, unrelated to effects on myocardial metabolism but perhaps involving heart rate and BP. The lack of a significant effect on performance time may have been due to general fatigue.
Risk factors for ischaemic heart disease, with emphasis on nutrition and exercise.
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Insulin and substrate exchange in the forearm during prolonged forearm work.
Forearm exchange of insulin and uptake of oxygen, glucose and free fatty acids (FFA) were studied during 120 min forearm work in six healthy male volunteers. At rest the arterial-deep venous difference of insulin was zero. At the onset of work release of insulin occurred, which continued at constant rate throughout the work despite unaltered arterial insulin concentration. Extractions of oxygen, glucose and FFA were of similar magnitudes at 120 as at 15 min work, while lactate release decreased with time. It is concluded that (1) a significant insulin release from muscle tissue or its vascular bed occurs and continues at undiminished rate during prolonged work, (2) a substantial amount must be bound in the tissue, unless local synthesis takes place and (3) despite this loss of insulin from the forearm no major change in glucose and FFA extraction occurs with duration of work.
Dissociation of the effects of nicotinic acid on vasodilatation and lipolysis by a prostaglandin synthesis inhibitor, indomethacin, in man.
The effects of nicotinic acid on plasma free fatty acid (FFA) concentration and forearm blood flow were studied in seven healthy fasting volunteers with and without pretreatment by indomethacin to see if some effects of nicotinic acid are mediated by release of endogenous prostaglandin. 1 g of nicotinic acid per os decreased plasma FFA concentration to a lowest value of 1/4 of initial level and increased forearm blood flow four times. When the same dose of nicotinic acid was given after pretreatment with indomethacin, the blood flow increase was only 1/3 of that without indomethacin. Indomethacin did not alter the rapid initial decrease in plasma FFA, although the period of low FFA concentration was shortened and the rebound to supranormal concentration was abolished. Thus the vasodilatory effect of nicotinic acid seems to be mediated by release of endogenous prostaglandin while the inhibition of lipolysis by the drug is mainly produced by other mechanisms.
Change in myocardial metabolism in man by a new stimulator of carbohydrate oxidation.
The effect on human myocardial metabolism of (S)-4-hydroxyphenylglycine, a substance which in animal experiments has been shown to stimulate carbohydrate metabolism mainly by activation of pyruvate dehydrogenase was studied in five healthy volunteers by coronary sinus catheterization. 90 min after i.v. injection of the drug myocardial extraction of glucose and lactate was doubled, myocardial oxidation of plasma free fatty acids (FFA) significantly reduced and myocardial RQ increased accordingly. This a pronounce shift towards carbohydrate oxidation was achieved with a dose which gave no side effects.
Risk factors for ischaemic heart-disease in normal men aged 40. Edinburgh-Stockholm Study.
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The Edinburgh-Stockholm study of coronary heart disease risk factors: a summary.
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Capillary permeability in ALS, determined through transcapillary escape rate of 125I-albumin.
Since various macromolecules have experimentally been demonstrated to be taken up by the motor end-plates and subsequently transported through retrograde axoplasmic flow, noxious substances may gain entrance to the lower motorneurons through the same route. Consequently, the function of the capillary barrier in skeletal muscle is of interest in diseases of the lower motorneurons. The transcapillary escape of 125I-albumin was determined in six ALS patients. The values fell within the range earlier reported for normals.
Nicotinic acid stimulates prostaglandin synthesis in the rabbit heart without releasing noradrenaline.
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