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Biomedical subjects

J Kjekshus

Publications and source records attributed to J Kjekshus.

At least 127 records · Page 7Linked to original sources
PubMed1989

Interaction of naloxone and timolol on maximal exercise capacity and the subjective perception of fatigue.

The effect on exercise performance and on the subjective perception of fatigue of the opioid receptor blocker naloxone, the nonselective beta-blocker timolol, and the combination of these two was studied in a double-blind randomized cycle ergometry test in healthy young men. Cumulative work at exhaustion was reduced by 25% after timolol (P less than 0.002) and by 34% after naloxone/timolol (P less than 0.02) but not after naloxone, compared with placebo. Naloxone alone had no influence on the subjective perception of fatigue (Borg scale rating), but significantly higher ratings were obtained by timolol and by naloxone/timolol. The present study does not support the hypothesis that opioid peptides are of importance for maximal exercise capacity and subjective perception of fatigue during short-term dynamic exercise in healthy young men.

Adult↗
PubMed1989

The importance of potassium and lactate for maximal exercise performance during beta blockade.

Changes in femoral vein pH, lactate, glucose and potassium were studied in a double-blind randomized, short-term, dynamic cycle ergometry exercise test on six healthy male subjects after administration of non-selective (timolol), beta-1-selective (atenolol) beta blocker or placebo. The exercise intensity was increased in steps of 200 kpm/min every 2 min until exhaustion. During submaximal exercise, potassium concentrations in blood from the exercising leg muscles increased progressively with increasing exercise intensity, and was significantly higher for any given exercise level following timolol as compared to placebo administration. The potassium concentrations following atenolol were in-between those of timolol and placebo. Despite reduced working capacity after non-selective beta blockade, almost identical potassium concentrations were reached at exhaustion irrespective of treatment regimens (placebo: 6.3, range 5.8-6.8 mmol/l; atenolol: 6.5, range 6.1-7.3 mmol/l and timolol: 6.4, range 6.2-6.8 mmol/l). The increase in s-lactate concentrations was similar across all treatments, and rose in proportion to the increase in the exercise intensity. A biphasic increase in lactate was observed with identical breaking points (anaerobic threshold) irrespective of treatment regimens. There was no difference in glucose concentrations between the treatment regimens. The marked increase in serum potassium during maximal exercise coincides with leg muscle fatigue and may, by its effect on the muscle cell membrane potential, limit the maximal working capacity following beta blockers. The rise in serum potassium may curtail the use of maximal exercise test as an index of cardiac performance in healthy young subjects.

Adrenergic beta-Antagonists↗
PubMed1988

Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).

To evaluate the influence of the angiotensin-converting enzyme inhibitor, enalapril (2.5 to 40 mg/day), on the prognosis of severe congestive heart failure, defined as New York Heart Association functional class IV, a double-blind study was undertaken in which 253 patients were randomized to receive either placebo (n = 126) or enalapril (n = 127) in addition to conventional treatment, including vasodilators. Follow-up averaged 188 days (range 1 day to 20 months). The reduction in crude mortality within 6 months (primary objective) was 40% in the enalapril-treated group (from 44 to 26%, p = 0.002) and within 1 year 31% (p = 0.001). By the end of the study, 68 subjects in the placebo group and 50 in the enalapril group had died--a reduction of 27% (p = 0.003). The entire reduction in total mortality (50%) was found in patients dying from progressive heart failure, whereas no difference was seen in the incidence of sudden cardiac death. There was a significant improvement in New York Heart Association classification in the enalapril group, together with a reduction in heart size and a reduced requirement for other heart failure medication. It is concluded that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms. The effect seems to be due to a reduction in death from progression of heart failure.

Aged↗
PubMed1988

Tolerability of enalapril in congestive heart failure.

In a double-blind, randomized trial, 253 patients with heart failure (New York Heart Association functional class IV) received either enalapril (n = 127) or placebo (n = 126) in addition to their conventional therapeutic regimens (digitalis, diuretics and vasodilators other than angiotensin-converting enzyme inhibitors). Enalapril was administered in a dose of 2.5 to 40 mg/day. The placebo group was administered placebo tablets in addition to their conventional therapeutic regimen. The study was discontinued prematurely for ethical reasons because of the highly significant (p = 0.003) difference in mortality between the enalapril (n = 50) and placebo groups (n = 68). The important reduction was observed among patients dying from progressive heart failure. Follow-up ranged from 1 day to 20 months (average 188 days). The reduction in mortality was associated with general improvements in symptoms and signs of left and right ventricular heart failure, reduction of heart size, improvements in New York Heart Association classification, reduction of concurrent cardiovascular medication, and reduction in the number of hospital admissions and duration of hospitalization. The overall rate of withdrawal from the study was low and was comparable in the 2 treatment groups (16%). Induced hypotension was an intentional part of the treatment, and symptomatic hypotension was observed in 17% of treated patients vs 0% of the placebo group. Hypotension was the reason for withdrawal in 7 patients. After the initial dose of enalapril was reduced to 2.5 mg in high-risk patients, hypotension was the reason for withdrawal in only 3% of all patients. Hyperkalemia was observed exclusively among patients concurrently using potassium-sparing agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1988

Difference between beta-1-selective and non-selective beta-blockade during continuous and intermittent exercise.

Limiting factors of maximal exercise performance are not clearly defined. In order to differentiate between various factors, maximal exercise was studied during continuous (n = 12) and intermittent (n = 9) exercise. The non-selective beta-blocker timolol (10 mg b.i.d. for 5 days) was compared double-blind and placebo controlled with the beta-1-selective beta-blocker metoprolol (100 mg b.i.d. for 5 days), with respect to effect on maximal exercise tolerance. Total cumulated work was comparable during continuous and intermittent exercise. Timolol and metoprolol reduced maximal exercise performance. No difference was observed between the two beta-blockers during intermittent exercise. The non-selective beta-blocker caused a greater reduction in exercise performance (10.4%) than the beta-1-selective beta-blocker (4.7%) (P less than 0.05) during continuous exercise. Maximal heart rate was higher with metoprolol than timolol during continuous exercise. The non-selective beta-blocker caused a slightly greater inhibition of lipolysis than the beta-1 selective one. No significant differences in glucose concentrations were observed between the treatment regimens. Exercise caused a marked increase in serum potassium concentrations. Beta-blockade caused further increase in potassium at any given workload. This study indicates that maximal working capacity is comparable during continuous and intermittent exercise. Beta-1-selective and non-selective beta-blockade reduce the maximal working capacity, non-selective more than beta-1-selective. Substrate availability was not responsible for the beta-blocker induced reduction of the working capacity. The rate of rise in serum potassium was significantly higher during beta-blockade and may, therefore, be a limiting factor for the maximal working capacity.

Administration, Oral↗
PubMed1988

Redistribution of peripheral blood flow during acute left ventricular failure in the dog.

Acute left ventricular failure was induced in anaesthetized dogs by repeated embolization of the left coronary artery with 57 micron microspheres. Tissue blood flow was measured with isotope-labelled microspheres in two stages of heart failure. With increasing doses of embolizing solution there was a progressive decline in systemic blood pressure and cardiac output. Failure was accompanied by a significant decrease in blood flow in all tissues examined except for intestine, adrenal gland, skin and right ventricle. Overall cardiac output distribution was estimated by combining flow data with data on relative tissue weights obtained from a dissection study in a separate group of dogs. A selective redistribution of cardiac output took place in the failure state. The blood flow was redirected away from the skeletal muscles and the spleen in favour of the intestines, kidneys, heart and brain.

Animals↗
PubMed1987

Effect of ACE-inhibition on tissue blood flow during acute left ventricular failure in the dog.

Anesthetized dogs in acute left ventricular failure were treated with the ACE-inhibitor enalaprilat (MK-422). ACE-inhibition produced a fall in the mean blood pressure and a redistribution of cardiac output to the brain, right ventricle, upper gastrointestinal tract, and the inner and middle part of the renal cortex. The flow to the spleen, adrenals, skin, muscle, fat, lower gastrointestinal tract, and outer renal cortex did not change significantly. The differential sensitivity of the tissues to ACE-inhibition is most likely due to differences in sensitivity to circulating angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Temporal pattern of enzyme changes in cerebrospinal fluid in patients with neurologic complications after open heart surgery.

We serially measured creatine kinase (CK), lactate dehydrogenase, aspartate aminotransferase (AST) and lactate from the lumbar cerebrospinal fluid in 14 patients with neurologic complications after open heart surgery with cardiopulmonary bypass (CPB). These analyses revealed a correlation between worsening neurologic deficit and the peak CK (r = .87, p less than .001), AST (r = .75, p less than .01), and lactate (r = .93, p less than .001) levels. Lactate increased before enzymes did. In 12 patients without complications, only lactate was significantly (p less than .005) elevated; however, within this group, CK but not lactate could be used to differentiate patients who later developed subtle mental changes. Although CPB appeared to induce metabolic changes in the brain that could possibly disturb function, severe cerebral damage appeared to require additional global or focal anoxic-ischemic factors. Short hypothermia during bypass did not influence CK, but it was falsely elevated after prolonged hypothermic periods. The testing of these enzymes may be a reliable indicator of the degree of brain damage and the prognosis.

Aged↗
PubMed1987

Haemodynamics during repeated exercise tests with special reference to the 'warm-up' phenomenon in patients with angina pectoris.

The haemodynamic effect of two successive supine exercise tests 20 min apart was examined in 12 patients with angina pectoris. All the patients had coronary artery disease verified by angiography and were accepted for coronary bypass surgery. They exercised 20-40 W and all of them had angina during the first exercise test. Half the patients did not experience angina during the second of the two exercise tests ('warm-up' responders). In these patients left ventricular filling pressure (LVFP) was reduced by 40% (P less than 0.01) in the second compared to the first exercise test. The non-responders showed no significant change in LVFP. The heart rate pressure product (RPP) and thus myocardial oxygen demand were unchanged in responders and non-responders. In another 10 patients with angina and coronary artery disease, also accepted for coronary bypass surgery, atropine (1.5-2.0 mg) was given intravenously. Ten minutes after administration of atropine, these patients followed exactly the same investigation programme including two successive supine exercise tests as in the group not given atropine. In the group given atropine, four 'warm-up' responders and six non-responders showed the same pattern of response in LVFP as in the group not given atropine. In the 'warm-up' responders a smaller increase in RPP was observed during the second exercise test compared to the first. The present study indicates that cholinergic mechanisms are probably not involved in the 'warm-up' phenomenon. Due to the difference in haemodynamic response, the 'warm-up' phenomenon has to be taken into account when evaluating results from haemodynamic studies of cardiovascular drugs.

Adult↗
PubMed1987

Nitrates in acute myocardial infarction.

Nitrates relieve symptoms and improve left ventricular haemodynamics during acute myocardial ischaemia. The ability to increase cardiac output appears to be greatest in those patients with the most severe left ventricular failure. In humans and in animal experiments it has been demonstrated that indices of infarct evolution are reduced by early (less than 6 hours) administration of nitrate. Glyceryl trinitrate reduces myocardial oxygen consumption and improves delivery of oxygen to the ischaemic subendocardium. In addition, nitrates dilate epicardial coronary vessels with improvement of collateral flow Glyceryl trinitrate appears to have a more favourable effect on coronary collateral flow, pulmonary artery pressure, myocardial oxygen consumption and lactate production than other vasodilators. The effect of glyceryl trinitrate is dose dependent; doses larger than 100 micrograms/min may cause a paradoxical increase in the ischaemic condition. Hypovolaemic patients or patients with right heart infarction seem especially susceptible to hypotension. Nitrate-induced hypotension occurs in 15 to 20% of all patients with acute myocardial infarction. Administration of glyceryl trinitrate appears to offer most benefit in acute myocardial infarction complicated by significant left ventricular dysfunction. There is evidence that morbidity and mortality are reduced by early administration of nitrates; however, a properly conducted randomised double-blind trial remains to be performed.

Humans↗
PubMed1987

The effects of naloxone and timolol on plasma catecholamine levels during short-term dynamic exercise.

In order to study the role of opioid- and betareceptors on exercise-induced catecholamine responses, the effects of acute intravenous administration of 1 and 4 mg naloxone and of the non-selective betablocker timolol 2 mg of on circulating concentrations of adrenalin, noradrenaline and dopamine during exercise to exhaustion were examined in eight normal, healthy young men, using a double-blind, randomized, placebo-controlled design. During maximal exercise, adrenalin levels increased from 71 +/- 17 to 821 +/- 235 pg/ml (p less than 0.05), noradrenaline from 355 +/- 58 to 4235 +/- 1031 pg/ml (p less than 0.05), and dopamine from 72 +/- 20 to 178 +/- 44 pg/ml (p less than 0.05). Naloxone did not influence basal or exercise-induced noradrenaline responses. Timolol clearly augmented peak adrenalin concentration at maximal exercise capacity (1543 +/- 510 pg/ml, p less than 0.05). Basal noradrenaline level was increased (546 +/- 86 pg/ml, p less than 0.05), while exercise-induced noradrenaline level was reduced (2954 +/- 594 pg/ml, p less than 0.05) in proportion to the reduction in maximal exercise capacity during timolol treatment. Neither naloxone nor timolol affected dopamine levels. No additive effect was seen with the combination of naloxone and timolol. It is concluded that the opioid peptides are probably not involved in noradrenaline and dopamine responses, whereas betablockers change the catecholamine response to short-term maximal exercise.

Adrenergic beta-Antagonists↗