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T Hedner

Publications and source records attributed to T Hedner.

At least 55 records · Page 3Linked to original sources
PubMed1999

Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure.

We wanted to study the expression of P2-receptors at the mRNA-level in the heart and if it is affected by congestive heart failure (CHF). To quantify the P2 receptor mRNA-expression we used a competitive RT-PCR protocol which is based on an internal RNA standard. The P2 receptor mRNA-expression was quantified in hearts from CHF rats and compared to sham-operated rats. Furthermore, the presence of receptor mRNA was studied in the myocardium from patients with heart failure. In the sham operated rats the G-protein coupled P2Y-receptors were expressed at a higher level than the ligand gated ion-channel receptor (P2X1). Among the P2Y-receptors the P2Y6-receptor was most abundantly expressed (P2Y6 > P2Y1 > P2Y2 = P2Y4 > P2X1). A prominent change was seen for the P2X1- and P2Y2-receptor mRNA levels which were increased 2.7-fold and 4.7-fold respectively in the myocardium from the left ventricle of CHF-rats. In contrast, the P2Y1-, P2Y4- and P2Y6-receptor mRNA levels were not significantly altered in CHF rats. In human myocard the P2X1-, P2Y1-, P2Y2-, P2Y6- and P2Y11-receptors were detected by RT-PCR in both right and left atria and ventricles, while the P2Y4-receptor band was weak or absent. In conclusion, most of the studied P2-receptors were expressed in both rat and human hearts. Furthermore, the P2X1- and P2Y2-receptor mRNA were upregulated in CHF, suggesting a pathophysiological role for these receptors in the development of heart failure.

Adolescent↗
PubMed1999

A comparison of the angiotensin II antagonists valsartan and losartan in the treatment of essential hypertension.

We compared the angiotensin II receptor antagonist valsartan to losartan as an antihypertensive agent in an 8-week trial. Adults with uncomplicated essential hypertension (baseline seated diastolic blood pressure < 115 mm Hg and > or = 95 mm Hg) were randomized to receive 80 mg valsartan, 50 mg losartan, or placebo once daily. After 4 weeks doses of active medication and placebo were doubled. Seated systolic and diastolic blood pressures were measured and the response rate evaluated. Tolerability was assessed by the incidence of adverse events. Both angiotensin II receptor antagonists produced similar significant reductions in mean blood pressures at 4 and 8 weeks compared to placebo. Valsartan produced a significantly higher number of responders (62%) than losartan (55%, P = .02) at the 8 week treatment endpoint. The incidence of adverse experiences (AE) was similar in all three groups, with headache and dizziness reported most often. Valsartan (80/160 mg) monotherapy in this trial was as effective and well tolerated as 50/100 mg losartan in treating mild to moderate essential hypertension, and at 160 mg has a significantly higher responder rate than 100 mg losartan.

Adolescent↗
PubMed1999

Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat.

It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status, the basilar, mesenteric and renal arteries and the iliac vein were studied in vitro. Dilatory responses were determined in relation to pre-contraction by the thromboxane mimetic U46619. Sham-operated animals (Sham) served as controls. U46619 induced stronger contraction in CHF basilar and renal arteries compared with the corresponding segments in Sham. ACh induced concentration-dependent dilations in all vessels examined with no difference of maximum relaxation or potency between CHF and Sham. SP induced weak dilations in all arteries examined while the response was markedly attenuated in CHF iliac veins compared with Sham (Emax% 12.2 +/- 3.4 vs. 32.3 +/- 4.8, P = 0.01). The CGRP induced dilation in the CHF basilar artery was weaker (Emax% 18.6 +/- 6.5 vs. 66.9 +/- 5.0, P < 0.001) and less potent (pEC50: 8.2 +/- 0.2 vs. 9.0 +/- 0.2, P = 0.01) compared with Sham. Further, CGRP was less potent in the renal artery of CHF rats compared with Sham (pEC50: 8.1 +/- 0.2 vs. 9.5 +/- 0.3, P < 0.01). In the CHF iliac vein, CGRP was more potent compared with Sham (pEC50: 9.7 +/- 0.4 vs. 8.3 +/- 0.4, P < 0.05). It can be concluded CHF is accompanied by alterations in the vascular response to the dilatory substances studied. The changes differ between vascular beds and between the different substances.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Decreased responsiveness of vascular postjunctional alpha1-, alpha2-adrenoceptors and neuropeptide Y1 receptors in rats with heart failure.

Heart failure is associated with increased sympathetic nerve activity. We hypothesized that chronic sympathetic stimulation in heart failure resulted in decreased vascular sympathetic responsiveness. A pithed rat model was employed to evaluate peripheral vascular alpha-adrenoceptor and neuropeptide Y (NPY) receptor responsiveness. Heart failure was induced in Sprague-Dawley rats by coronary artery ligation. Sham operated rats (Sham) served as controls. Two months after this surgical procedure, both heart failure (n = 30) and Sham (n = 30) rats underwent standard pithing procedure. Pressor responses to preganglionic sympathetic nerve stimulation (PNS) and activation of postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors were studied. In response to PNS, cardiac index was similar between heart failure and sham rats (P = n.s.). Mean arterial pressure (MAP) increased in a frequency-dependent fashion after PNS in heart failure rats as well as in control rats. All the agonists used, i.e. the alpha1-adrenoceptor agonist phenylephrine, the alpha2-adrenoceptor agonists clonidine and BHT933 as well as NPY, induced dose-dependent increases in MAP in heart failure and in sham rats. However, in rats with heart failure, the response to all the agonists studied was significantly decreased and the dose response curves were shifted to the right (P < 0.01). We conclude that in vivo vascular response to postjunctional alpha1- and alpha2-adrenoceptors as well as Y1 receptors are decreased in rats with heart failure.

Adrenergic alpha-Agonists↗
PubMed1999

A comparison of metoprolol and morphine in the treatment of chest pain in patients with suspected acute myocardial infarction--the MEMO study.

OBJECTIVES: To compare the analgesic effect of metoprolol and morphine in patients with chest pain due to suspected or definite acute myocardial infarction after initial treatment with intravenous metoprolol. DESIGN: All patients, regardless of age, admitted to the coronary care unit at Uddevalla Central Hospital due to suspected acute myocardial infarction were evaluated for inclusion in the MEMO study (metoprolol-morphine). The effects on chest pain and side-effects of the two treatments were followed during 24 h. Pain was assessed by a numerical rating scale. RESULTS: A total of 265 patients were randomized in this prospective double-blind study and 59% developed a confirmed acute myocardial infarction. In both treatment groups, there were rapid reductions of pain intensity. However, in the patient group treated with morphine, there was a more pronounced pain relief during the first 80 min after start of double-blind treatment. The side-effects were few and were those expected from each therapeutic regimen. During the first 24 h, nausea requiring anti-emetics was more common in the morphine-treated patients. CONCLUSION: In suspected acute myocardial infarction, if chest pain persists after intravenous beta-adrenergic blockade treatment, standard doses of an opioid analgesic such as morphine will offer better pain relief than increased dosages of metoprolol.

Adrenergic beta-Antagonists↗
PubMed1999

Plasma noradrenaline and neuropeptide-Y may not be of primary importance in the pathophysiology of cardiac involvement in systemic sclerosis.

OBJECTIVE: The present study was performed to measure concentrations of plasma noradrenaline and neuropeptide-Y-like immunoreactivity in relation to cardiac function in patients with systemic sclerosis (SSc). METHODS: Plasma noradrenaline was measured by high performance liquid chromatography and neuropeptide-Y by radioimmunoassay in 30 consecutive patients with SSc and 48 sex and age matched controls. Left ventricular (LV) function was evaluated by Echocardiography. RESULTS: There were no significant differences between patients and controls in either plasma noradrenaline or plasma neuropeptide-Y. LV dysfunction and hypertrophy were common among patients. Plasma Neuropeptide-Y was related only to systolic function, while noradrenaline was related to both systolic and diastolic function as well as to LV hypertrophy. CONCLUSION: Patients with SSc develop different forms of myocardial dysfunction without activation of the sympathetic nervous system as evaluated by plasma noradrenaline and neuropeptide-Y; leaving vascular disease of the heart to be a main candidate.

Adult↗
PubMed1999

Progress report on the Nordic diltiazem study (NORDIL): an outcome study in hypertensive patients.

NORDIL--the Nordic Diltiazem Study (NORDIL)--is a prospective, randomized, open blinded-endpoint (PROBE), multicenter, parallel-group morbidity/mortality outcome study in hypertensive patients designed to compare an intervention strategy based on the calcium antagonist diltiazem with a strategy based on conventional antihypertensive drug treatment (diuretics or beta-adrenergic blockers). Patient recruitment was started in Norway and Sweden in September 1992, and ended on December 15, 1996, when 10.896 male and female patients, aged 50-74 years, with essential hypertension had been randomized. In this paper we describe the baseline data of the patient cohort and blood pressures achieved in the two treatment groups during the early part of the study. The patient cohort consists of 5294 males and 5602 females with a mean age of 59.6 and 60.3 years, respectively. Concomitant disorders and risk factors in the cohort are: smoking 22%, ischemic heart disease 3.0%, previous myocardial infarction (MI) 2.0%, previous stroke 1.5%, diabetes mellitus 7.0%, and renal impairment 0.3%. There were no differences between the treatment groups in these respects. The blood pressure treatment goal is a target diastolic blood pressure of < or =90 mmHg or a 10% diastolic blood pressure reduction from the inclusion pressure. In the treatment group randomized to a diltiazem-based treatment strategy, blood pressure was 174/106 mmHg at baseline and 156/90 mmHg after 12 months of follow-up on active treatment. In the group randomized to a conventional treatment strategy, baseline blood pressure at randomization was 173/106 mmHg and 153/90 mmHg after 12 months on active therapy. The NORDIL study will terminate on October 31, 1999 and the final results should be available by mid-2000.

Aged↗
PubMed1999

Acute ischemic chest pain is not associated with increased calcitonin gene-related peptide (CGRP) levels in peripheral plasma nor in the coronary circulation.

Calcitonin gene-related peptide (CGRP) and substance P co-exist in capsaicin-sensitive primary sensory neurons and are released from the myocardium after activation of sensory nerve fibres as well as by ischemia in animals. This study was undertaken to try to clarify the potential involvement of immunoreactive (ir) CGRP in anginal pain and myocardial ischemia in humans. One clinical group (n = 87) and one experimental group (n = 14) were studied. The clinical group was admitted to a coronary care unit with suspected or definite acute myocardial infarction (AMI). The experimental group consisted of patients with severe angina pectoris (NYHA III-IV). This group was subjected to atrial pacing up to the appearance of angina pectoris. Mean irCGRP levels at admission for the clinical group with and without AMI showed no significant difference. Neither were any significant differences found in irCGRP concentrations between patients with pain as compared to those without pain or in the group who had had chest pain >30 min before hospital admission as compared to those with chest pain <30 min. Extraction ratios for lactate and irCGRP was calculated in the experimental group. No statistically significant covariance was found between irCGRP extraction ratio and lactate extraction ratio (r(xy) = -0.006) at the time of appearance of angina during atrial pacing. Despite the facts that CGRP may be liberated by a variety of physiological stimuli and may act as a potent vasodilator in the human vasculature, no evidence has been found in this study that CGRP release is increased as a consequence of ischemia or ischemic pain.

Aged↗
PubMed1999

Atrial natriuretic peptide attenuates pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease.

UNLABELLED: Atrial natriuretic peptide (ANP) exerts a dilatory effect on coronary arteries in humans. We investigated the effects of ANP on pacing-induced myocardial ischemia during enflurane anesthesia in patients with coronary artery disease (CAD). In 20 patients with CAD, myocardial ischemia was induced by atrial pacing before and after an i.v. infusion of ANP (50 mg x kg(-1) min(-1), n = 10) or placebo (n = 10). We studied the effects of ANP or placebo on pacing-induced changes in central hemodynamics, myocardial blood flow and regional myocardial indices of lactate uptake (RMLU), and oxygen consumption (RMVO2) and extraction (RMO2E). ST-segment depression was less pronounced during pacing with ANP compared with control pacing (-0.09 +/- 0.01 vs -0.24 +/- 0.02 mV; P < 0.001). RMLU decreased to -11.1 micromol/min during control pacing compared with -0.7 micromol/min during pacing with ANP (P < 0.01). ANP did not affect pacing-induced changes in RMVO2, RMO2E, or the rate pressure product. Placebo did not affect pacing-induced changes in ST-segment depression or RMLU. In conclusion, ANP attenuates ischemic ST-segment depression and lactate release during pacing-induced myocardial ischemia in patients with CAD. The antiischemic effect of ANP was not accompanied by any improvement in the regional myocardial oxygen supply/demand relationship. IMPLICATIONS: We evaluated the effects of i.v. atrial natriuretic peptide (50 ng x kg(-1) x min(-1)) on pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease. In contrast to placebo, atrial natriuretic peptide attenuated ST-segment depression and myocardial lactate production and improved left ventricular function during pacing-induced ischemia.

Adult↗
PubMed1999

The efficacy and tolerance of one or two daily doses of eprosartan in essential hypertension. The Eprosartan Multinational Study Group.

OBJECTIVE: The primary objective of this double-blind, parallel-group, placebo-controlled, multicentre study was to compare the antihypertensive efficacy of one versus two daily doses of eprosartan, a novel nonbiphenyl, nontetrazole angiotensin II receptor antagonist, in 243 patients with mild to moderate hypertension (sitting diastolic blood pressure > or = 95 to < or = 114 mmHg). PATIENTS AND METHODS: The patients were randomized to titrated doses of eprosartan at 400-800 mg once a day, eprosartan at 200-400 mg twice a day, or placebo, with the incremental dose titrated over a 9-week period. Patients reaching target blood pressure (sitting diastolic blood pressure of < or = 90 mmHg) continued the fixed-dose treatment for 4 weeks. The primary efficacy measure was the mean change in trough sitting diastolic blood pressure from baseline to the study endpoint, determined on an intent-to-treat basis. RESULTS: By the end of the study, eprosartan had significantly reduced mean trough sitting systolic and diastolic blood pressure relative to baseline and to placebo. The mean +/- SD change from baseline in diastolic pressure was -9 +/- 8.4 mmHg for the single daily dose, -9 +/- 8.5 mmHg for two doses a day and -4 +/- 8.1 mmHg for placebo (P < 0.0001 versus placebo for both eprosartan regimens). Similarly, both eprosartan regimens significantly reduced mean trough standing systolic and diastolic blood pressure. At the end of the study, the response rate in the single daily dose group (46.8%) was significantly higher than in the placebo group (25.6%). There were no significant differences between the treatment groups in the number of patients whose blood pressure responded to treatment; 41.7% of those taking eprosartan once a day and 44.4% of those taking eprosartan twice a day, and who responded to treatment, were maintained on their original starting doses. The total daily dose required to achieve target blood pressure was comparable, whether eprosartan was administered once or twice a day. Both eprosartan regimens were well tolerated and the incidence of adverse events with eprosartan was similar to that of placebo. CONCLUSIONS: These results demonstrate that there was no significant difference in antihypertensive efficacy or tolerance between eprosartan taken in one or in two daily doses. Both dosing regimens provided significant and clinically meaningful reductions in blood pressure that were superior to placebo. Eprosartan in a single daily dose was shown to be an effective antihypertensive agent. Because of the good adverse-effect profile and the simplicity of a single daily dose, eprosartan has the potential to improve patient compliance.

Acrylates↗
PubMed1999

Pain recollection after chest pain of cardiac origin.

Memory for pain is an important research and clinical issue since patients ability to accurately recall pain plays a prominent role in medical practice. The purpose of this prospective study was to find out if patients, with an episode of chest pain due to suspected acute myocardial infarction could accurately retrieve the pain initially experienced at home and during the first day of hospitalization after 6 months. A total of 177 patients were included in this analysis. The patients rated their experience of pain on a numerical rating scale. The maximal pain at home was retrospectively assessed, thereafter pain assessments were made at several points of time after admission. After 6 months they were asked to recall the intensity of pain and once again rate it on the numerical rating scale. The results from the initial and 6-month registrations were compared. In general, patients rated their maximal intensity of chest pain as being higher at the 6-month recollection as compared with the assessments made during the initial hospitalization. In particular, in patients with a high level of emotional distress, there was a systematic overestimation of the pain intensity at recall.

Age Factors↗
PubMed1999

Renal and cardiovascular role of the neuropeptide Y Y1 receptor in ischaemic heart failure rats.

The cardiovascular role of the neuropeptide Y Y1 receptors in-vivo and in-vitro in ischaemic heart failure was evaluated by using the novel neuropeptide Y Y1 selective antagonist BIBP 3226 (R-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amid e). In pithed rats, incremental doses of BIBP 3226 inhibited the exogenous neuropeptide Y induced pressor response in a dose-related fashion and a bolus injection of BIBP 3226 (0.5 mg kg(-1)) significantly shifted the pressor response curve of exogenous neuropeptide Y to the right. The potentiation effect to exogenous neuropeptide Y on the pressor response to preganglionic sympathetic nerve stimulation in ischaemic heart failure rats as well as on the contractile response to noradrenaline in renal arteries in sham-operated animals were also inhibited by the neuropeptide Y Y1 antagonist. In conscious ischaemic heart failure rats, incremental doses of BIBP 3226 (0.125-1 mg kg(-1)) significantly reduced basal blood pressure and heart rate. Compared with sham-operated rats, neuropeptide Y by itself induced no contraction and no potentiation on noradrenaline elicited contraction in renal artery of the ischaemic heart failure rat. Furthermore, under in-vivo conditions, BIBP 3226 did not influence basal renal function or the response to exogenous neuropeptide Y on urinary volume, urinary sodium and urinary potassium. Our results demonstrate that although there is a downregulation of the Y1 receptors by ischaemic heart failure, Y1 receptors are still mainly involved in cardiovascular actions of exogenous neuropeptide Y and play a role in maintaining basal blood pressure and heart rate in ischaemic heart failure. However, our data do not imply any significant role of Y1 receptors on basal renal function in the ischaemic heart failure rat model.

Animals↗
PubMed1999

Management of hypertension: the advent of a new angiotensin II receptor antagonist.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor antagonists have received increased therapeutic recognition in the treatment of hypertension. Although the overall effects of the ACE inhibitors and AT1 receptor antagonists may seem superficially similar, there are important differences between the two classes in terms of neurohumoral activation, concomitant bradykinin potentiation, and inhibition of angiotensin II, derived not only from the classical ACE pathway, but also from alternative pathways. The AT1 receptor antagonist eprosartan has been shown to lower blood pressure effectively in hypertensive patients. When taken in the recommended dose range, 600-800 mg once daily, eprosartan is effective in patients with all grades of hypertension, regardless of age, sex or race. In several clinical studies, the blood-pressure-lowering effect of eprosartan has been shown to be at least as great as that of the ACE inhibitor enalapril. With respect to tolerability, eprosartan is superior to ACE inhibitor therapy and comparable to placebo. The pharmacological and therapeutic profiles of the expanding array of AT1 receptor antagonists differ in a number of respects. Most of these agents are biphenyl tetrazole, non-competitive antagonists, and some have active metabolites. Eprosartan differs from other AT1 receptor antagonists in that it is a non-biphenyl, non-tetrazole competitive antagonist without active metabolites. Several large-scale, ongoing clinical research programmes (e.g. LIFE, SCOPE and VALUE) are expected to provide information on the extent to which AT1 receptor antagonists, in comparison with other therapeutic regimens, reduce cardiovascular morbidity and mortality in different groups of hypertensive subjects. Meanwhile, current evidence suggests that the AT1 receptor antagonists provide a new approach to the management of hypertension and that they merit a fuller assessment in other cardiovascular diseases.

Acrylates↗