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Biomedical subjects

L Kaijser

Publications and source records attributed to L Kaijser.

At least 109 records · Page 6Linked to original sources

Myocardial metabolism during aortic valve replacement. III. Continuous infusion of cold blood for cardioplegia.

Myocardial energy metabolism during hypothermic potassium cardioplegia with blood as the cardioplegia vehicle was studied in eight patients undergoing aortic valve replacement. Cardiac arrest was induced with a single bolus infusion and maintained by continuous perfusion. Myocardial biopsies were taken from the left ventricle 10 min after aortic cross-clamping (a.c.) and immediately before declamping (d.c.) and were analyzed for ATP, creatine phosphate (CP), creatine (C) and lactate. The interindividual range of myocardial temperature was 15-21 degrees a.c. and 17-22 degrees C immediately before d.c. The ATP concentration decreased (12.7 +/- 3.9-10.4 +/- 3.5 mmol X kg-1 dry muscle), the lactate concentration increased (102 +/- 30-156 +/- 8 mmol X kg-1 d.m.), and the total creatine (CP + C) remained constant. Induction of cardioplegia by blood resulting in a mean myocardial temperature of 19 degrees C could not prevent anaerobic metabolism. The changes in ATP levels between 10 min after a.c. and just before d.c. were small, however, indicating that oxygen delivery during continuous blood cardioplegia at a myocardial temperature of c. 20 degrees C prevented further loss of ATP. The lactate concentration, however, increased markedly between 10 min after a.c. and d.c., demonstrating that a significant proportion of the total metabolism was anaerobic.

Adenosine Triphosphate↗

In vivo metabolism of leukotriene C4 in man: urinary excretion of leukotriene E4.

Five - 20 nmoles of [5,6,8,9,11,12,14,15-3H8]leukotriene C4 was injected into three male volunteers. Forty-eight percent of the administered 3H was recovered from urine and 8% from feces, within a 72 hr period. Of the total urinary radioactivity 44% was excreted during the first hour after injection. This activity was mainly found in one compound, designated "I". The radioactivity excreted into urine later than one hour after injection, consisted partly of Compound I and two additional components, and partly of polar, non-volatile material. Compound I was identified as leukotriene E4 by UV-spectroscopy and cochromatographies in three high performance liquid chromatography systems with synthetic reference compounds. A total of 13% of administered radioactivity was excreted in urine as leukotriene E4.

Adult↗

Effect of beta 1-selective and nonselective beta blockade on blood pressure relative to physical performance in men with systemic hypertension.

Eleven physically active men with systemic hypertension were studied after 5 weeks of treatment with placebo, atenolol or propranolol. A double-blind, crossover randomized design was used. Blood pressure (BP), heart rate (HR), physical performance capacity, rate of perceived exertion and blood lactate concentrations were measured during rest, exercise to exhaustion and postexercise, at 8 and 24 hours after intake of the last dose. Blood pressure at rest and during exercise was similarly decreased with both drugs (8 and 24 hours), and there was no difference between 8 and 24 hours with any of the treatments. Heart rate (8 hours) was decreased similarly by both drugs, but after 24 hours, HR at increased workloads (above 120 watts) was higher with atenolol compared with propranolol. Maximal HR was lower with propranolol than atenolol at both 8 and 24 hours. Maximal exercise loads (8 and 24 hours) were 231 and 232 watts with placebo, 211 and 212 with propranolol and 228 and 227 with atenolol. That is, maximal workload was decreased with propranolol compared with placebo and atenolol at both 8 and 24 hours. No difference was found between placebo and atenolol at either 8 or 24 hours. The rate of perceived exertion values were higher with propranolol than atenolol. Blood lactate concentrations did not differ according to treatments. The results indicate that atenolol, when given in a dose that decreases resting and exercise BP to the same extent as propranolol, limits physical performance less than propranolol.

Adult↗

Autonomic cardiovascular responses in old age.

The effect of age on autonomically mediated cardiovascular responses to certain manoeuvres was studied in 15, healthy, old men and women (60-80 years). The results were compared with groups of healthy young (about 25 years) and middle-aged (about 45 years) subjects. There was no significant reduction in cardiovascular responses between the young and middle-aged groups. Respiratory sinus arrhythmia, and heart rate, blood-pressure and contralateral forearm blood flow increases to isometric hand grip, as well as the heart rate decrease during a dive reflex test, were significantly attenuated in the old age group. The Valsalva ratio, and the heart rate and blood-pressure changes during an 8 min orthostatic test did not differ between the old and the two younger age groups. There seems to be only a moderate attenuation of autonomic cardiovascular responses to about 60 years, after which there is a more rapid decline. The difference in reduction between different responses, even those mediated by the same type of autonomic nerve, suggests that the decreased responses are not due to an isolated impaired function of the peripheral autonomic nerve. The impairment may be due to the receptor organ or a combination of defects in function of several parts of the autonomic nervous system in old age.

Adult↗

Effect of nicotine on coronary blood-flow in man.

The effect of 4 mg nicotine administered in a chewing gum on coronary haemodynamics and oxygen transport, was studied by coronary sinus catheterization in eight healthy non-smoking men. Measurements were made of coronary sinus blood-flow (CSF) by thermodilution and arterial-coronary sinus (a-cs) O2-difference together with heart rate and intra-arterial pressure both at rest, and during, atrial pacing with and without nicotine. Nicotine increased myocardial oxygen consumption (MVO2) more than expected from the increase in the rate-pressure product. The increased MVO2 was covered only partly by increased coronary blood-flow; especially during and after pacing an increased a-cs O2-difference contributed significantly. This differed from the response when MVO2 was increased by atrial pacing alone, in which case the whole increase in MVO2 was covered by increased flow. The results suggest that nicotine affects coronary vascular resistance and blood-flow indirectly through a vasodilatory effect, by mechanisms related to the increased cardiac work, and directly through a vasoconstrictory effect. The suggested vasoconstrictor component is moderate in the non-ischaemic human heart.

Adult↗

Cardiovascular responses and plasma catecholamines in old age.

Plasma catecholamines and haemodynamic responses to isometric handgrip, orthostatic body position and dynamic cycle exercise were studied in 10 healthy old men (mean age 71 years) and 10 healthy young men (mean age 26 years). At rest, plasma noradrenaline (NA) was significantly higher in the old age group. During handgrip there were greater increases in heart rate and blood-pressure in the young rather than in the old men, while forearm blood-flow increase was similar in the two age groups, and there was no increase in NA in either groups. In the orthostatic position heart rate increased in the young men only, and forearm blood-flow decreased more in the young than in the old men. NA concentration increased similarly in both age groups. During dynamic exercise the increases in both the heart rate and the blood-pressure, at similar relative submaximal as well as maximal loads, were smaller in the old men. At maximal work NA and adrenaline (A) concentrations were higher in the young men, while at the lowest load, NA concentration was higher in the old men. Similar increases in exercise heart rate, blood-pressure or rate of perceived exertion corresponded to lower increases in NA in the old men. It can be concluded that old men, compared with young men, have a reduced maximal capacity to release NA and A upon provocation. In addition, the sensitivity for catecholamines in the target organ is reduced with age, as suggested by the smaller increases in heart rate and blood-pressure for a given increase in NA during exercise. The higher basal NA level and the higher NA level, during moderate provocation, may suggest a compensatory increase in activity.

Adult↗

Autonomic cardiovascular responses in parkinsonism: effect of levodopa with dopa-decarboxylase inhibition.

Autonomically mediated cardiovascular responses to certain manoeuvres were studied in 20 parkinson patients, 24 h off levodopa-decarboxylase inhibitor medication and again one h after medication. Results were compared with 15 healthy control subjects. The heart rate at rest was higher in parkinson, the respiratory sinus arrhythmia was lower, while the Valsalva ratio, the heart rate and blood pressure responses during an orthostatic test and the heart rate response to a dive reflex test were normal. These findings indicate a normal function of peripheral autonomic nerves and a possible central parasympathetic dysfunction. There were significantly attenuated responses of heart rate, blood pressure and contralateral forearm blood flow to an isometric handgrip. Since the peripheral autonomic nerves seemed to be normal, these results could be related to a reduced central command and/or diminished stimulation of postulated peripheral ergoreceptors in parkinsonism. There was no major effect on the cardiovascular responses by the acutely administered medication.

Aged↗

Autonomic function in amyotrophic lateral sclerosis: a study of cardiovascular responses.

Autonomically mediated cardiovascular responses were evaluated in 15 ALS patients and compared with 15 healthy subjects. The respiratory sinus arrhythmia, the heart rate response to a Valsalva manoeuvre, to isometric handgrip and to a dive reflex test was normal, indicating a normal function of vagal nerves. The heart rate and blood pressure responses during an orthostatic test were normal, indicating a normal function of sympathetic nerves. The increase in blood pressure and blood flow in the contralateral forearm which occurs on handgrip in healthy subjects was reduced in the ALS patients. The cause of this is unclear, but could be related to decreased function of "ergoreceptors" or altered vascular reactivity in atrophic muscle.

Aged↗

Skeletal muscle glycolysis during submaximal exercise following acute beta-adrenergic blockade in man.

The present study describes the influence of beta-adrenergic blockade on glycogen utilization and lactate accumulation in skeletal muscle of exercising man. Twelve physically active men were examined during 25 min of continuous cycle exercise equivalent to 65% of their maximal oxygen uptake both with and without oral administration of 80 mg of propranolol (Inderal). Heart rate, oxygen uptake, rate of perceived exertion (RPE) and blood lactate concentration were measured during exercise. Muscle biopsies were obtained from m. vastus lateralis after 5 and 25 min of exercise. Beta-adrenergic blockade decreased steady state exercise heart rate by (mean +/- SD) 35 +/- 10 beats . min-1 (P less than 0.001) and oxygen uptake from 2.47 to 2.39 l . min-1 (P less than 0.01). Muscle glycogen decreased from the 5th to the 25th min of exercise, and beta-blockade had no significant effect on this decrease. In contrast to without drug, beta-blockade resulted in a decrease (P less than 0.05) in muscle lactate concentration from the 5th (6.9 mmol . kg-1 w./w.) to the 25th min (4.8 mmol . kg-1 w./w.). Similarly blood lactate levels were lower (P less than 0.05) with than without beta-blockade in the last but not the first 10 min of exercise. The alteration in muscle lactate concentration pattern following beta-blockade, may imply that adrenergic effects per se contribute to the stimulation of glycolysis during submaximal exercise, except in its earliest phase. Nevertheless, the effect is not great enough to produce substantial differences in glycogen utilization.

Adult↗

Coronary flow regulation in patients with ischemic heart disease: release of purines and prostacyclin and the effect of inhibitors of prostaglandin formation.

The present investigation was undertaken to study cardiac release of adenosine and prostacyclin (prostaglandin [PG] I2) in patients with ischemic heart disease (IHD), and to assess coronary vascular resistance before and after inhibition of synthesis in such patients. In 48 patients with IHD, arterial and coronary sinus blood samples were taken at rest, during atrial pacing to angina, and after pacing. Levels of purines were determined by high-performance liquid chromatography and the PGI2 metabolite 6-keto-PGF1 alpha was measured with radioimmunoassay. Coronary sinus blood flow was determined with retrograde continuous thermodilution before and after oral administration of indomethacin, aspirin, naproxen, or ibuprofen. Atrial pacing induced myocardial ischemia, as evidenced by typical chest pain and arrested lactate extraction. Adenosine was extracted at rest, but during ischemia there was a significant release of its metabolite hypoxanthine, indicating increased myocardial breakdown of high-energy adenine nucleotides. Arterial and coronary sinus concentrations of 6-keto-PGF1 alpha were low and no significant differences between them were found. After administration of the PG-synthesis inhibitor indomethacin, coronary vascular resistance was elevated, as was the cardiac oxygen extraction. The three other PG-synthesis inhibitors (aspirin, naproxen, and ibuprofen) did not, however, induce any change in coronary vascular resistance or in the cardiac extraction of oxygen. On the basis of these data we suggest that in patients with IHD cardiac ischemia results in increased myocardial production and release of purines, cardiac ischemia does not elicit any detectable increase in coronary production of prostacyclin, and the increased coronary resistance induced by indomethacin does not reflect the involvement of locally formed PG in the maintenance of coronary flow, but is rather a direct effect of the drug.

Adenosine↗

Myocardial energy depletion during profound hypothermic cardioplegia for cardiac operations.

Myocardial biopsy specimens were taken from 10 patients undergoing aortic valve replacement using extracorporeal circulation and continuous perfusion blood cardioplegia at extremely low myocardial temperature (10 degrees C). They were analyzed for adenosine triphosphate, creatine phosphate, creatine, and lactate before, after 10 minutes, and after 60 minutes of cardioplegia. Patient inclusion criteria were heart volume less than 700 ml/m2 body surface area and no significant coronary atherosclerosis as judged from preoperative angiograms. The profound hypothermic cardioplegia resulted in a smaller intramyocardial lactate accumulation but a greater decrease in adenosine triphosphate and creatine phosphate than a moderate reduction of myocardial temperature (15 degrees C) as previously reported in a similar patient group. This suggests that at the lower temperature energy-generating processes are thwarted more than energy consumption. In addition, the profound hypothermic cardioplegia led to a reduction of the myocardial pool of total creatine, which may delay restitution of myocardial high-energy phosphate and function after cardioplegia.

Adenosine Triphosphate↗

Somatostatin-induced apnea: interaction with hypoxia and hypercapnea in the rat.

The effects of hypoxia and hypercapnea in the production of somatostatin (SRIF)-induced apnea were studied during rebreathing experiments. Hypoxia and hypercapnea resulted in a shortening of the latency of SRIF-induced apnea. In order to exclude the effect of stimulation of central chemoreceptors by mock-CSF solution, control experiments using mock-CSF in combination with hypoxia and hypercapnea were done. No apnea could be produced by the mock-CSF in combination with hypoxia and hypercapnea. The shortening of apneic latency from 480 +/- 8 s (S.E.M.) to 148 +/- 30 s with the addition of a chemostimulus (hypoxia and hypercapnea) in SRIF-induced respiratory depression demonstrates that chemostimulation interacts with the centrally originating apnea to enhance its apneic response.

Animals↗

Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man.

The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.

Adult↗

Myoglobin release in patients with angina pectoris following short-term ischaemia by pacing to angina.

Thirteen patients with severe stable angina pectoris were studied by coronary sinus catheterization. In all patients, severe chest pains were produced by atrial pacing. The chest pains had disappeared within 10 min after pacing. Simultaneous arterial (a) and coronary sinus (cs) blood samples were taken before, during and after pacing and analyzed for myoglobin and lactate. The a-cs difference of myoglobin tended to become more negative after pacing, although the change was not significant. However, the change in negative direction post-pacing of the a-cs myoglobin difference was quantitatively correlated with the change in negative direction of the a-cs lactate difference during pacing in the individual patients. This suggests that short-term myocardial ischaemia without signs of established myocardial infarction may provoke myocardial myoglobin release.

Acute Disease↗

Isometric muscle endurance during acute beta-adrenergic blockade.

Isometric muscle endurance was measured in fourteen physically active men without (placebo) and after acute oral administration of 160 mg propranolol (Inderal). Quadriceps muscle contractions were sustained at 65% maximum voluntary contraction (MVC) to exhaustion. Muscle biopsies were obtained from m. vastus lateralis at rest for subsequent histochemical analysis for myofibrillar ATPase and amylase-PAS in order to determine fiber type composition and capillary density. The time to exhaustion was shorter (p less than 0.01) during beta-blockade (0.82 +/- 0.22) min than placebo (0.90 +/- 0.23) min. Changes in endurance time, induced by beta-blockade, were not correlated with any of the muscle morphological or histochemical variables examined. It is concluded that muscular performance is impaired as a result of beta-blockade on muscle tissue irrespective of any concomitant change in central circulation.

Adenosine Triphosphatases↗

Leg citrate metabolism at rest and during exercise in relation to diet and substrate utilization in man.

Previously we have demonstrated a lower rate of carbohydrate utilization in skeletal muscle after a fat than after a carbohydrate rich diet both at rest and during exercise. To test the hypothesis of citrate as a regulator of glycolysis (1) arterial-femoral venous (a-fv) differences for oxygen, citrate, pyruvate and lactate and (2) muscle citrate and glucose-6-phosphate (G-6-P) were determined at rest and after 5 and 25 min of submaximal bicycle exercise. Citrate release and muscle citrate concentration were higher after fat than after carbohydrate diet at rest and 5 min exercise, but did not differ between diets at 25 min exercise. Lactate release and muscle lactate concentration were lower after fat diet at 5 and 25 min exercise. Pyruvate release at 5 min exercise was higher after fat diet. The G-6-P concentration was higher at rest, insignificantly higher after 5 min exercise and lower at 25 min exercise after the fat diet. The findings support the notion that at rest and 5 min exercise fat diet induced inhibition of glycolysis might be mediated through increased intramuscular citrate acting on phosphofructokinase. In addition, the greater pyruvate release at 5 min exercise after fat diet in spite of a smaller lactate release, indicates a decreased pyruvate dehydrogenase activity and/or NADH to NAD ratio after fat diet. The inhibition of glycolysis at 25 min exercise after fat diet on the other hand does not seem to be citrate mediated.

Adult↗