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Biomedical subjects

B Ablad

Publications and source records attributed to B Ablad.

At least 19 recordsLinked to original sources
PubMed2003

Effect of thyroid hormone supplementation on survival of euthyroid dogs with congestive heart failure due to systolic myocardial dysfunction: a double-blind, placebo-controlled trial.

Nineteen euthyroid dogs of 12 breeds with echocardiographic signs of dilated cardiomyopathy (DCM) and radiographic and clinical signs of congestive heart failure (CHF) were evaluated in a randomised, double-blind, and placebo-controlled study. The dogs received either thyroxine or placebo as an adjunct to digoxin, furosemide and propranolol. The group assignment of individual dogs and serum concentrations of thyroid hormones remained unknown to owners and investigators during the entire study period. Dogs were evaluated clinically and with electrocardiography (ECG), thoracic radiography, echocardiography and measurement of total thyroxine (tT4) and thyroid stimulating hormone (TSH) before beginning of the trial, and then one week, 2 months, 6 months and yearly after initial examination, and, when applicable, at the time of euthanasia. End-point of the study was euthanasia (n = 17) due to severe congestive heart failure or sudden death (n = 2). Survival times ranged from 17 to 1030 days (median 187 days) in the placebo group, and from 18 to 1000 days (median 73 days) in the treatment group. There was no statistically significant difference in survival times between the treatment group and the placebo group (p = 0.46). Post mortem and histopathologic examinations revealed the attenuated wavy fiber type of DCM in 11 dogs, and myocardial infarcts, arteriosclerosis and chronic valvular disease in one dog. In conclusion, there was a wide range in survival times of dogs treated with digoxin, furosemide and propranolol. Adding thyroid hormones to the treatment did not significantly influence survival.

Animals↗
PubMed2003

The effect of a neuropeptide Y Y1 receptor antagonist in patients with angina pectoris.

AIMS: Neuropeptide Y (NPY) is a potent vasoconstrictor released during sympathetic activation that may be involved in myocardial ischaemia. We examined the effect of a Y1 receptor antagonist on haemodynamic and ischaemic responses to exercise in patients with coronary artery disease. METHODS AND RESULTS: Eighty-two evaluable male patients were included in a randomized, double blind, two-way crossover study with a low dose (6.7 microg/kg/min; n=59)and a high dose (13.3 microg/kg/min; n=23) of the Y1 receptor antagonist AR-H040922 given as infusions for 2h or placebo. Myocardial ischaemia during a symptom-limited exercise test was monitored by conventional ST-segment analysis and heart rate (HR)-adjusted ST changes including the ST/HR slope and ST/HR recovery. Administration of the high dose AR-H040922 attenuated systolic blood pressure by 6-11 mmHg (p<0.05) during and after exercise without affecting HR. None of the two doses of AR-H040922 influenced any of the ischaemic parameters or duration of exercise, however. The maximal increase in NPY was higher during AR-H040922 (p<0.05) compared with placebo. CONCLUSIONS: Selective NPY Y1 receptor blockade attenuates the increase in blood pressure during exercise indicating a role for endogenous NPY in blood pressure regulation. Despite this effect, the Y1 receptor antagonist did not influence exercise-induced ischaemic parameters in patients with coronary artery disease.

Adult↗
PubMed2000

Postexercise ischemia is associated with increased neuropeptide Y in patients with coronary artery disease.

BACKGROUND: Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. METHODS AND RESULTS: Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE. CONCLUSIONS: The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Analysis of Variance↗
PubMed1991

Prostacyclin synthesis in relation to sympathoadrenal activation. Effects of beta-blockade.

Results from several studies suggest that beta-adrenoceptor blockade causes increased biosynthesis of the vasodilator prostanoid prostacyclin in the arterial wall. This effect may contribute to the clinical effects of beta-blockers in hypertension and coronary heart disease. Studies in hypertensive patients and in animals indicate that the arterial pressure reduction after beta-blockade is related to the associated increase of prostacyclin biosynthesis, regarding both magnitude and time of onset of effect. Some observations suggest that the effects of beta-blockers in myocardial ischemia may in part be due to an improvement of coronary blood flow caused by increased prostacyclin biosynthesis.

Adrenergic beta-Antagonists↗
PubMed1990

Long-term cardiovascular effects of metoprolol therapy: a review article.

Long-term studies in primary and secondary prevention using metoprolol have showed improvement in prognosis. This review summarizes the clinical results of such studies, and puts these results into the perspective of findings in mechanistic and explanatory studies. Many possible factors may have contributed to explain the beneficial effects on prognosis. The antihypertensive action, cardiac anti-ischemic action, antifibrillatory action, antiatherogenic and antithrombotic actions of metoprolol are discussed. The additive effects of these actions may explain the clinically observed beneficial effects. In the evaluation of a specific intervention, it is important to realize the multiple actions that may contribute, and not only discuss single factors.

Animals↗
PubMed1990

Influence of metoprolol CR/ZOK on plasminogen activator inhibitor (PAI-1) in man: a pilot study.

Recent primary and secondary preventive trials have shown that long-term metoprolol therapy reduces the risk of acute cardiovascular complications. To test whether part of this beneficial long-term effect may be due to effects on the fibrinolytic system, three pilot studies were performed; two in healthy individuals, and one in patients with mild hypertension or uncomplicated atrial fibrillation. The effect of metoprolol CR/ZOK (controlled release) 100-200 mg daily, on plasminogen activator inhibitor activity (PAI-1) in plasma was measured. In addition serum triglycerides and orosomucoid were analyzed. All the individuals were included in double-blind placebo controlled cross-over trials with treatment periods ranging from 4 days to 3 weeks. During metoprolol therapy PAI-1 values were reduced, while orosomucoid and triglyceride levels were unchanged. A linear inverse correlation was found between fibrinolysis and PAI-1 activity in plasma, indicating that PAI-1 activity serves as an indicator of fibrinolysis. PAI-1 activity and triglycerides were significantly correlated during placebo and metoprolol therapy. In conclusion, our results in these pilot studies suggest that metoprolol enhances fibrinolytic activity as seen by reduced PAI-1 activity. These results should be further confirmed and put into relation of clinical effects of the therapy.

Adult↗
PubMed1988

The role of sympathetic activity in atherogenesis: effects of beta-blockade.

Clinical and experimental evidence points to potential antiatherosclerotic effects of certain beta-adrenoreceptor antagonists. Long-term treatment with metoprolol resulted in significant reductions of total and cardiovascular mortality or morbidity due to decreased incidence of coronary and cerebrovascular complications both in a primary prevention trial in hypertensive patients and in a secondary prevention trial in patients surviving myocardial infarction. The observations suggest that a retardation of atherosclerosis development might have contributed to the reduced incidence of cardiovascular complications. An antiatherosclerotic effect of beta-blockers has been directly demonstrated in animal studies. In cholesterol-fed rabbits, metoprolol significantly reduced the development of atherosclerotic plaques in the aortic intima in the absence of any changes in blood lipids. Similar findings were reported for propranolol, which prevented psychosocial stress-induced atherosclerosis of the coronary artery in monkeys. Furthermore, beta-blockers have been shown to prevent stress-induced endothelial injury and platelet accumulation to intima at atherosclerotic predilection sites in animal models. These antiatherogenic effects may be due to biochemical and hemodynamic factors. Two biochemical effects of beta-blockade may lead to reduced cholesterol accumulation in arterial intima at unchanged serum cholesterol levels. One is a beta-blocker-induced increase of prostacyclin biosynthesis, and the other a metabolic change of low-density lipoprotein, reducing its potential for deposition in the arterial wall. The antiatherogenic effect of these factors may be reinforced by beta-blocker-induced hemodynamic changes leading to reductions of arterial flow aberrations and pressure-related wall stress.

Adrenergic beta-Antagonists↗
PubMed1987

Prejunctional beta 2-adrenoreceptor blockade reduces nerve stimulation evoked release of endogenous noradrenaline in skeletal muscle in situ.

Prejunctional beta-adrenoceptor-mediated modulation of endogenous noradrenaline (NA) overflow elicited by sympathetic nerve stimulation was studied in blood-perfused canine gracilis muscle in situ. An attempt was made to subclassify these beta-adrenoceptors by comparing the effects of beta 1-selective (metoprolol) and non-selective (propranolol) beta-adrenoceptor blockade. Animals were pre-treated with desipramine and phenoxybenzamine in order to counteract possible influences of neuronal uptake and stimulation-evoked changes in vascular resistance on the diffusion of NA into the blood stream. Metoprolol did not decrease stimulation-evoked NA overflow, as compared with control experiments (-10 and -8%, respectively). However, propranolol reduced stimulation-evoked NA overflow by 30% in metoprolol pre-treated animals (P less than 0.05 vs. control experiments). Both antagonists elevated basal perfusion pressure, suggesting that vascular post-junctional beta 1- as well as beta 2-adrenoceptors are present. Propranolol increased stimulation-evoked vasoconstriction in metoprolol pre-treated animals, indicating that neuronally released NA may activate postjunctional beta 2-adrenoceptors under these experimental conditions. In conclusion, our findings suggest that NA release can be enhanced by activation of prejunctional beta 2-adrenoceptors in vivo.

Adrenergic beta-Antagonists↗
PubMed1987

Cardiac anti-ischemic effect of metoprolol: role of beta-blockade within the ischemic region.

The distribution of metoprolol and atenolol into ischemic and nonischemic myocardium was studied in anesthetized dogs, pigs, and cats. The beta-blockers were administered intravenously after coronary artery occlusion. Metoprolol was found to be significantly more efficiently distributed to the ischemic myocardium than atenolol in all three species. To investigate the functional implications of this difference in tissue distribution, the anti-ischemic effects of the two beta-blockers were studied in the 2-h period following coronary artery occlusion in anesthetized cats, in which heart rate was kept at a constant level. In this model, metoprolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) was found to attenuate or delay the developing ischemic process. This is shown by its significant reduction of (a) the decline of CK activity in ischemic myocardium, (b) the ST elevation in a precordial ECG lead, and (c) the decrease of arterial pressure and cardiac output. In contrast to metoprolol, atenolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) caused no significant anti-ischemic effect in this cat model. The difference in the effectiveness of the two drugs can most probably be explained by their differential distribution in the ischemic heart. Furthermore, the anti-ischemic effect of metoprolol shows that the presence of a beta-blocker in ischemic left ventricular myocardium can favorably affect the early phase of developing infarction.

Adrenergic beta-Antagonists↗
PubMed1986

Migraine and beta-blockade: modulation of sympathetic neurotransmission.

The pathophysiology of both classical and common migraine is still not understood, and there is controversy as to whether the origin is vascular, neuronal, or both. Although the mechanism for the prophylactic effect of beta-blockers in migraine has not been elucidated yet, the therapeutic action of beta 1-blockers and non-selective beta-blockers devoid of intrinsic activity is well established by many controlled trials. Mainly on the basis of data from animal experiments, the possible role of central beta-adrenoceptor-mediated mechanisms involved in the control of the activity of noradrenergic neurons will be discussed with reference to migraine.

Adrenergic beta-Antagonists↗
PubMed1981

The role of prostaglandins in the alpha- and beta-adrenoceptor mediated renin release response to graded renal nerve stimulation.

The role of prostaglandins in the renin release response to renal nerve stimulation (RNS) at different intensities was examined in the anaesthetized dog. The animals were divided into two groups receiving either low or high level RNS, defined by the frequencies of stimulation producing reduction in renal blood flow by 5% or less and 50%. Indomethacin or diclofenac sodium (5 mg/kg i.v.), prostaglandin synthesis inhibitors, did not affect the renin release response to low level RNS but decreased the renin release response to high level RNS by 31 +/- 8% (P less than 0.01). Addition of metoprolol, (0.5 mg/kg i.v.) beta-1-adrenoceptor antagonist, to indomethacin or diclofenac sodium resulted in a greater reduction (68 +/- 6% P less than 0.01) of the renin release response to high level RNS compared to that produced by either drug alone. Metoprolol, alone, reduced the renin release response to high level RNS by 37 +/- 14% (P less than 0.05). Phenoxybenzamine (0.6 microgram . kg-1 . min-1), alpha-adrenoceptor antagonist, into the renal artery practically abolished the renal vasoconstrictor response to high level RNS and reduced the renin release response by 50 +/- 7% (P less than 0.01). Addition of metoprolol to phenoxybenzamine practically abolished the renal vasoconstrictor response and the renin release response to high level RNS; 94 +/- 4% (P less than 0.01). Addition of phenoxybenzamine to indomethacin or diclofenac sodium practically abolished the renal vasoconstrictor response to high level RNS but did not produce any greater reduction of the renin release response than that produced by either drug alone. These findings suggest that low level RNS results in renin release which is not dependent on prostaglandins. High level RNS results in renin release which is partly mediated by beta-1-adrenoceptors and partly related to alpha-adrenoceptors mediated renal vasoconstriction. Prostaglandins are not involved in the renin release deriving from alpha-adrenoceptor mediated renal vasoconstriction.

Animals↗
PubMed1981

Effect of prenalterol, a beta-1-adrenoceptor agonist, on renin secretion rate in the anaesthetized dog.

The effects of the beta-1-adrenoceptor agonist, prenalterol, 20 microgram/kg intravenously on renin secretion rate (RSR), renal haemodynamics and sodium excretion were examined in anaesthetized dogs with innervated or denervated kidneys. In dogs with innervated kidneys, prenalterol increased RSR from 1.1 +/- 0.2 to 7.9 +/- 0.1 units X min.-1 X g-1 (P less than 0.01). Prenalterol did not affect mean arterial pressure, renal blood flow, glomerular filtration rate or sodium excretion. Heart rate was increased by 53 +/- 17 beats/min. (P less than 0.01). The increase in RSR produced by prenalterol was independent of intact renal innervation as RSR increased to the same extent in dogs with denervated kidneys. Pretreatment with the beta-1-adrenoceptor antagonist, metoprolol 0.5 mg/kg intravenously, abolished the increase in RSR produced by prenalterol. These findings suggest that prenalterol directly activates renal beta-1-adrenoceptors to increase RSR.

Adrenergic beta-Agonists↗
PubMed1980

The role of beta-1-adrenoceptors in the renin release response to graded renal sympathetic nerve stimulation.

The contribution of beta-adrenoceptor activation to renin release was examined in anaesthetized dogs using renal nerve stimulation (RNS) at different discharge rates in the presence of i.v. beta-adrenoceptor blockade. The animals were divided into 2 groups, which received either low or high level of RNS, defined by the frequency of stimulation producing decrease in renal blood flow of 5 and 50%, respectively. Low level RNS increased renin release tenfold. The renin release response was almost abolished by 0.5 mg/kg of metoprolol or dl-propranolol but unaffected by 0.5 mg/kg of d-propranolol. The increase in renin release to high level RNS was equally reduced by 33% by 0.5 mg/kg and 2.0 mg/kg of metoprolol. dl-propranolol, 0.5 mg/kg, reduced the renin release response to about the same extent, 44%, while 2.0 mg/kg reduced it somewhat more, 59%. This was probably due to its membrane stabilizing properties as d-propranolol, 2.0 mg/kg and lidocaine 2.0 mg/kg + 0.1 mg x kg-1 x min-1, also reduced the renin release response. These data suggest that the renin release response to low level RNS is almost completely mediated by beta-adrenoceptors which are of the beta-1 subtype. High level RNS results in a renin release, which is only partly mediated by beta-1-adrenoceptors. The remainder is apparently related to other mechanisms activated by high level RNS and is probably a consequence of the associated renal vasoconstriction.

Adrenergic beta-Antagonists↗
PubMed1980

Pre- and postjunctional beta-adrenoceptor mediated effects on transmitter release and effector response in the isolated rat portal vein.

Pre- and postjunctional control mechanisms of the portal vein of spontaneously hypertensive rats (SHR) were characterized. Emphasis was placed on the influence of the presynaptic beta-adrenoceptor mediated mechanism for regulation of neuronal noradrenaline (NA) release (studied as tritium overflow) and its consequences for the contractile response under in vitro conditions. It was found that isoprenaline increased, whereas dl-propranolol decreased the release of neuronal NA during transmural nerve stimulation, while effector responses remained unaltered. d-Propranolol and the beta-1 selective adrenoceptor antagonist, metoprolol, did not affect these two variables. It is concluded that the presynaptic beta-adrenoceptors in the rat portal vein are mainly of the beta-2 type and mediate facilitation of neuronal transmitter release and that concomitant changes of the effector responses of this tissue are below the level of detection under the present experimental conditions.

Animals↗
PubMed1978

Increased noradrenaline release in rat portal vein during sympathetic nerve stimulation due to activation of presynaptic beta-adrenoceptors by noradrenaline and adrenaline.

With the aim of investigating whether exogenous noradrenaline (NA) and adrenaline (A) can modulate transmitter release via the stimulation of presynaptic beta-adrenoceptors, 3H-release from isolated portal veins was studied after pretreatment with 3H-1-NA, phenoxybenzamine, desipramine and normetanephrine. NA (10 muM) and A (0.05 muM) increased the fractional 3H-release elicited by sympathetic nerve stimulation by 30%. This effect could be blocked by d, 1-propranolol which per se reduced the release by 10%. It is concluded that NA can facilitate its own release via a presynaptic beta-adrenoceptor-mediated positive feed-back mechanism and that adrenaline can stimulate this beta-adrenoceptor-mediated mechanism.

Animals↗