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Biomedical subjects

A Hjalmarson

Publications and source records attributed to A Hjalmarson.

At least 109 records · Page 6Linked to original sources
PubMed1994

Empiric therapy with beta-blockers.

The only class of drugs with significant effects on ventricular fibrillation and sudden death in humans is that of beta-blockers. The exact mechanisms for these prophylactic effects are not known but may be related to both antiischemic or antiarrhythmic influences. It seems reasonable to suggest that one should use a beta-blocker with proven effect on total mortality and sudden cardiac death after myocardial infarction as prophylaxis. Therefore, propranolol, timolol, or metoprolol, should be instituted in order to improve prognosis when there are no contraindications. In addition to possible effects on survival one would also expect to reduce the risk for new ischemic events with angina or reinfarction. In contrast, class I antiarrhythmic agents are useful for symptomatic ventricular arrhythmias but there is no proof for any effect on ventricular fibrillation and sudden cardiac death.

Adrenergic beta-Antagonists↗
PubMed1994

Gi-mediated muscarinic adenylyl cyclase inhibition in timolol-treated stunned porcine myocardium.

The Gi-mediated muscarinic receptor-adenylyl cyclase system was examined in stunned myocardium induced by either three or five brief ischaemic periods after beta-adrenoceptor blockade by timolol (0.1 mg kg-1). The mid-left anterior descending coronary artery was occluded for 2, 10 and 2 min in four pigs, and for 2, 2, 5, 10 and 2 min in four other pigs. All the ischaemic periods were separated by 30 min of reperfusion and the biopsies were obtained 60 min after the last ischaemic period. Segment length function was measured in the ischaemic region and in the control region supplied by the left circumflex artery. In the two groups, the percentage systolic shortening was reduced equally, to 59 +/- 9 and 58 +/- 10% of control in the region subjected to ischaemia and only minimally in the control region. The biopsies from the stunned region from both groups showed: (1) no change in either the affinity for carbachol or the number of binding sites of the muscarinic receptors; (2) no alterations in messenger RNA encoding for the alpha subunit-2 of the inhibitory guanine nucleotide binding protein, as demonstrated by northern blot and solution hybridization; (3) no change in membrane-bound inhibitory guanine nucleotide binding protein, as shown by enzyme immunoassay utilizing a specific anti-peptide antibody, and (4) unchanged inhibition of stimulated adenylyl cyclase activity. These results suggest that there is an intact inhibitory guanine nucleotide binding protein-mediated muscarinic receptor adenylyl cyclase system in the stunned porcine myocardium.

Adenylyl Cyclase Inhibitors↗
PubMed1994

Ten year mortality in relation to original size of myocardial infarct: results from the Gothenburg metoprolol study.

OBJECTIVE: To describe the relation between the extent of a myocardial infarct, measured according to maximum serum enzyme activity of lactate dehydrogenase, and mortality at 10 years. PATIENTS: In 759 patients with acute myocardial infarction in whom serum activity of heat stable lactate dehydrogenase had been determined every 12 hours for 108 hours after randomisation in an early intervention trial with metoprolol. MAIN OUTCOME MEASURE: Mortality at 10 years in relation to quartile of maximum serum lactate dehydrogenase activity and history of cardiovascular disease. RESULTS: Among all patients mortality at 10 years was 39% in the lowest quartile, 51% in the second quartile, 50% in the third, and 59% in the fourth (p < 0.001 for relation between infarct size and 10 year mortality). Among patients without a history of myocardial infarction, angina pectoris, diabetes mellitus, or hypertension the mortality in each quartile was 29%, 32%, 41%, and 56%, respectively (p < 0.001 for relation between infarct size and 10 year mortality). Among patients with any of these risk indicators the association between the estimated infarct size and mortality at 10 years was weak (p < 0.05). CONCLUSION: Estimated size of a myocardial infarct and mortality over 10 years seem to be related but mainly in patients without a history of cardiovascular disease.

Adult↗
PubMed1994

Ten-year mortality among patients with suspected acute myocardial infarction in relation to early diagnosis.

Previous studies have compared the outcome between patients with and without a confirmed acute myocardial infarction (AMI) mainly during the first few years after its onset. Our aim was to compare the prognosis between patients with and without a confirmed AMI during 10 years of follow-up. Patients participating in an early intervention trial with metoprolol in suspected AMI between 1976 and 1981 took part in this evaluation. The total 10-year mortality rate including hospital mortality was 51% for patients with confirmed AMI as compared with 32% for patients with a possible AMI and 23% for patients in whom AMI was definitely ruled out (p < 0.001). The 10-year mortality after discharge from hospital was in AMI 46%, possible AMI 32% and in definitely ruled out AMI 23% (p < 0.001). When simultaneously considering age, sex, previous history of cardiovascular disease and smoking, the development of AMI appeared as an independent predictor of death (p < 0.001). Thus, among patients hospitalized due to suspected AMI, 10-year mortality after discharge from hospital was directly related to the diagnosis during the first 3 days in hospital.

Adult↗
PubMed1994

Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect.

BACKGROUND: Autoantibodies against the beta 1-adrenoceptor have been detected in the sera of patients with idiopathic dilated cardiomyopathy (DCM). The mechanisms by which these autoantibodies can alter normal receptor function are investigated, and the results are interpreted in the light of the beneficial effects of beta 1-blockade in some of these patients. METHODS AND RESULTS: Autoantibodies against the beta 1-adrenoceptor, affinity purified from sera of patients with idiopathic DCM, were analyzed in a functional test system of spontaneously beating neonatal rat heart myocytes. Antibodies from rabbits immunized with peptides derived from the amino acid sequence of this receptor were also analyzed. Autoantibodies, against the second extracellular loop increased the beating frequency of isolated myocytes in a concentration-dependent manner, to approximately 80% of maximal isoproterenol stimulation. Rabbit anti-peptide antibodies against the second extracellular loop increased the beating frequency correspondingly. Autoantibodies and rabbit anti-peptide antibodies against the second extracellular loop were able to immunoprecipitate the unliganded receptor but not the antagonist-occupied receptor. In contrast, rabbit antibodies against the extracellular N-terminal sequence 34-57 of the beta 1-adrenoceptor were able to immunoprecipitate both the unliganded and the antagonist-occupied receptor although with no effect on the beating frequency of myocytes. The positive chronotropic effect of the antibodies was completely neutralized both by the addition of increasing concentrations of the beta 1-selective antagonist bisoprolol and by preincubation with the peptide corresponding to the second extracellular loop. The antibody-induced increase in beating frequency remained unchanged for more than 6 hours. This should be compared with the isoproterenol-stimulated beating frequency, which undergoes desensitization within 60 minutes. Addition of isoproterenol to autoantibody-stimulated myocytes resulted in only a small increase in beating frequency and did not cause desensitization. Antibodies had only a marginal effect on cyclic AMP production of stimulated cardiomyocytes compared with the 10-fold increase obtained after stimulation with isoproterenol. CONCLUSIONS: The second extracellular loop of the beta 1-adrenoceptor is a specific target for antibodies with stimulatory activity detected in patients with idiopathic DCM. The antibodies have a positive chronotropic effect on isolated rat heart myocytes. Autoantibody stimulation does not cause the normal agonist-induced desensitization phenomena of the effector system. These findings could contribute to our understanding of the pathophysiological mechanisms of the autoantibodies and of the beneficial effect of beta 1-blocking agents in the treatment of patients with idiopathic DCM.

Aged↗
PubMed1994

Immunocytochemical localization of M2 muscarinic receptors in rat ventricles with anti-peptide antibodies.

We produced antibodies against a synthetic peptide corresponding to amino acids 168-192 of the second extracellular loop of the M2 human muscarinic receptor in rabbits. In immunoblot, affinity-purified antibodies specifically recognized a major band of rat ventricular muscarinic receptor protein with a molecular weight of about 80 KD. This recognition could be blocked by pre-incubation with peptide. Moreover, with both light (LM) and electron microscopic (EM) immunocytochemistry techniques, muscarinic receptors were detected on sarcolemma and T-tubules of rat cardiomyocytes. In addition, immunoreactions were localized in membranes of capillaries. Likewise, these reactivities were abolished by pre-incubation with peptide. These results suggest that the antibodies against the second extracellular loop of human M2 muscarinic receptor could specifically recognize rat ventricular muscarinic receptor protein and could be a powerful tool to study the fate of this receptor under different pathological or physiological conditions.

Acetylcholine↗
PubMed1994

The role of beta-blockers in the treatment of cardiomyopathy and ischaemic heart failure.

As first reported by our group in 1975, severe heart failure due to idiopathic dilated cardiomyopathy could be improved in patients receiving beta-blocker therapy starting at a very low dose and followed by a stepwise increase. Since then, these results have been confirmed by our own group and by others, and similar results were also obtained in patients with other forms of cardiomyopathy, including ischaemic cardiomyopathy. In 13 separate studies involving a total of 651 patients with idiopathic dilated cardiomyopathy, beta-blockade for 2 to 19 months (in addition to conventional treatment of heart failure, including angiotensin converting enzyme inhibitor therapy), significantly improved cardiac function. These studies were performed using metoprolol, bucindolol, labetalol and practolol. Eight studies investigated the effects of long term beta-blocker treatment in patients with heart failure and cardiomyopathy due to coronary artery disease, valvular heart disease, diabetes and doxorubicin therapy. A total of 128 patients were treated with metoprolol, carvedilol or bucindolol for periods of 2 to 12 months. All studies reported a significant improvement in cardiac function. Three studies reported results on survival and the need for cardiac transplantation. The first study published by our group reported improved survival in patients with idiopathic dilated cardiomyopathy treated with metoprolol plus digitalis and diuretics compared with a matched control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group.

Several small studies have suggested beneficial effects of long-term beta-blocker treatment in idiopathic dilated cardiomyopathy. Our large multicentre study aimed to find out whether metoprolol improves overall survival and morbidity in this disorder. 383 subjects with heart failure from idiopathic dilated cardiomyopathy (ejection fraction < 0.40) were randomly assigned placebo or metoprolol. 94% were in New York Heart Association functional classes II and III, and 80% were receiving background treatment. A test dose of metoprolol (5 mg twice daily) was given for 2-7 days; those tolerating this dose (96%) entered randomisation. Study medication was increased slowly from 10 mg to 100-150 mg daily. There were 34% (95% CI -6 to 62%, p = 0.058) fewer primary endpoints in the metoprolol than the placebo group; 2 and 19 patients, respectively, deteriorated to the point of needing transplantation and 23 and 19 died. The change in ejection fraction from baseline to 12 months was significantly greater with metoprolol than with placebo (0.13 vs 0.06, p < 0.0001). Pulmonary capillary wedge pressure decreased more from baseline to 12 months with metoprolol than with placebo (5 vs 2 mm Hg, p = 0.06). Exercise time at 12 months was significantly greater (p = 0.046) in metoprolol-treated than in placebo-treated patients. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol prevented clinical deterioration, improved symptoms and cardiac function, and was well tolerated.

Adolescent↗
PubMed1993

One-year prognosis in patients hospitalized with a history of unstable angina pectoris.

The prognosis during 1 year of follow-up in 715 patients admitted to one single hospital due to suspected acute myocardial infarction (AMI) with a history of unstable angina pectoris immediately preceding hospitalization is described. AMI developed in 192 patients (27%) during the first three days and in 255 patients (38%) during the first year. The mortality during hospitalization was 7% (50 patients) and during 1 year 19% (130 patients). Of the nonsurvivors, 54% died of AMI, 28% of congestive heart failure, and 20% of cardiogenic shock. Based on simple clinical parameters on admission to the emergency room, risk indicators for death during the following year could be identified as follows, in the order of significance: high age (p < 0.001), ST-segment depression on admission (p < 0.001), and a history of diabetes mellitus (p < 0.05). At admission to the emergency room, risk indicators for development of AMI during the following year were as follows: initial degree of suspicion of AMI (p < 0.001), electrocardiographic signs of acute ischemia on admission (p < 0.001), ST-segment elevation on admission (p < 0.01), age (p < 0.05), and lack of a previous history of chronic stable angina pectoris (p < 0.05). We conclude that, among patients admitted to hospital due to suspected AMI with a history of unstable angina pectoris immediately preceding hospitalization, 38% developed a confirmed infarction and 19% died during the following year.

Age Factors↗
PubMed1993

Hypersensitivity of Gi protein mediated muscarinic receptor adenylyl cyclase in chronic ischaemic heart failure in the rat.

OBJECTIVE: The aim was to study the Gi protein mediated muscarinic signalling system in the myocardium of rats with chronic ischaemic heart failure. METHODS: Chronic ischaemic heart failure was induced by myocardial ischaemia (four weeks after coronary artery ligation) in rats. The densities and agonist affinities of muscarinic receptors, and the functional activity and concentration of Gi proteins were studied. RESULTS: In failing hearts, the activity of adenylyl cyclase stimulated by guanyliminodiphosphate (Gpp(NH)p) was decreased by 46%. Stimulated activities of adenylyl cyclase by both sodium fluoride and forskolin, however, remained unchanged. Carbachol depressed forskolin stimulated adenylyl cyclase more in membranes from failing hearts than those from normal hearts. The functional level of Gs protein as measured by a reconstitution assay in sarcolemmal membrane did not differ between the two groups. Furthermore, muscarinic receptors exhibited superhigh and low affinities for agonist in failing hearts whereas those in control hearts displayed only high and low affinities. No significant difference in the peptide equivalent amount of membrane bound Gi protein was found in either group. CONCLUSIONS: The experimental chronic failing heart due to myocardial ischaemia showed a depressed myocardial adenylyl cyclase signalling system. This may be due to the hypersensitivity of the Gi protein mediated muscarinic receptor-adenylyl cyclase system as shown by the increased inhibition of Gpp(NH)p mediated adenylyl cyclase, more potent inhibition of stimulated adenylyl cyclase by carbachol, and the superhigh affinity of the muscarinic receptors for carbachol.

Adenylyl Cyclases↗
PubMed1993

Free radical scavenging enzymes and G protein mediated receptor signalling systems in ischaemically preconditioned porcine myocardium.

OBJECTIVE: Increased antioxidant defence and altered G protein mediated receptor signalling systems could be expected in myocardial preconditioning. The myocardial antioxidant defence and the integrity of the G protein mediated receptor signalling systems were therefore examined in normal and preconditioned myocardium. METHODS: Preconditioning in the porcine heart was induced by two occlusions of the mid left anterior descending coronary artery for 10 min, with a 30 min reperfusion interval. Left ventricular biopsies were obtained from control and preconditioned regions 30 min after the last occlusion. RESULTS: In biopsies from the preconditioning region, neither the activities of superoxide dismutase of glutathione peroxidase, nor the content of malondialdehyde were changed. There were no alterations in either the number of receptors (beta adrenergic, muscarinic and endothelin receptors) or the amount of G proteins. Furthermore, the activity of adenylyl cyclase remained unchanged. CONCLUSIONS: No change in the antioxidant defence was demonstrated in preconditioned myocardium. This finding does not support the hypothesis that increased antioxidant defence could contribute to the cardioprotection of preconditioning. Additionally, an intact G protein mediated receptor signalling system was found in preconditioned myocardium with regard to beta adrenergic, muscarinic, and endothelin receptors.

Animals↗
PubMed1993

Occurrence of angina pectoris prior to acute myocardial infarction and its relation to prognosis.

In 917 patients with acute myocardial infarction (AMI) we evaluated the impact of previous angina pectoris on the prognosis. Thirty-four percent of the patients had chronic angina prior to AMI, and 22% had angina pectoris of short duration. Patients with chronic angina pectoris differed from the remaining patients having a more frequent previous history of AMI, diabetes mellitus, hypertension, and congestive heart failure. They less frequently developed a Q-wave AMI, and had smaller infarcts according to maximum serum-enzyme activity as compared with the remaining patients. They had a higher one-year mortality rate (36%) as compared with those having angina pectoris of short duration (22%), and those with no angina pectoris (26%). Their reinfarction rate was also higher (26%) as compared with that in the other two groups (15% and 9% respectively). In a multivariate analysis considering age, sex, clinical history, initial symptoms, initial electrocardiogram and estimated infarct size, previous chronic angina pectoris was not an independent risk factor for death, but was independently associated with the risk of reinfarction (P < 0.001). Among patients with a history of angina pectoris the outcome was related to medication prior to onset of AMI and at discharge from hospital. Patients in whom beta-blockers were prescribed at discharge had a one-year mortality of 13% as compared with 30% in the remaining patients (P < 0.001).

Age Factors↗
PubMed1993

Decreased density of mesenteric arteries but not of myocardial endothelin receptors and function in rats with chronic ischemic heart failure.

Mesenteric artery and cardiac ventricular endothelin receptors and endothelin-1-induced pressor responses were studied in normal rats and rats with chronic congestive heart failure induced by myocardial ischemia (4 weeks after coronary artery ligation). In mesenteric arteries of rats with chronic ischemic heart failure, endothelin receptor density was significantly decreased by 59%, whereas the dissociation constant was increased 2.8-fold, as compared with controls. There were, however, no changes in endothelin-receptor density or the dissociation constant in cardiac ventricular membrane preparations from rats with congestive heart failure as compared with controls. In pithed rats with congestive heart failure there was a reduced pressor response to a bolus injection of endothelin-1 (800 pmole/kg body weight), while the vasodilatory response was unaltered as compared with sham-operated controls. These results demonstrate that there is a decreased vascular endothelin-receptor function due to a down-regulated endothelin receptor. The in vivo data indicate that this is due to impaired endothelin A but not endothelin B receptor function. Thus, there is an impaired arterial but not cardiac ventricular endothelin receptor-mediated signalling system in the rat with chronic ischemic heart failure.

5'-Nucleotidase↗
PubMed1993

Prognosis in men and women coming to the emergency room with chest pain or other symptoms suggestive of acute myocardial infarction.

BACKGROUND: Previous studies suggest a gender-related difference in prognosis among patients with ischaemic heart disease. In the present study, we aimed to describe the characteristics and prognosis among patients with suspected ischaemic heart disease in relation to gender. METHODS: During the 21 months of the study, all patients who came to the medical emergency room of one single hospital as a result of chest pain or other symptoms suggestive of acute myocardial infarction were prospectively followed for 1 year. RESULTS: A total of 5362 patients were admitted on 7157 occasions; men accounted for 55% of the admissions. The 1-year mortality rate was 11% for men compared with 10% for women. The women were older and had a higher prevalence of known congestive heart failure and hypertension, whereas the prevalence of previous myocardial infarction was higher in men. When correcting for the dissimilarities in age and history of cardiovascular diseases, male gender appeared as an independent predictor of death. Development of myocardial infarction occurred in 25% of the men and 16% of the women (P < 0.001) during 1 year. The symptoms that brought patients to the emergency room were interpreted as being caused by myocardial infarction or myocardial ischemia in 29% of men compared with 21% of women (P < 0.001). CONCLUSIONS: In a consecutive series of patients with chest pain or other symptoms suggesting acute myocardial infarction in the emergency room, male gender was an independent risk indicator for death during 1 year. This might be explained by a higher occurrence of coronary artery disease in men than in women in this patient population.

Aged↗
PubMed1993

Ten-year mortality rate after development of acute myocardial infarction in relation to clinical history and observations during hospital stay: experience from the Göteborg metoprolol trial.

BACKGROUND: Previous studies on the prognosis after acute myocardial infarction (AMI) have mainly focused on the first few years. In this study, we aimed to describe the mortality rate during 10 years of follow-up after development of AMI in relation to clinical history and observations during the hospital stay. METHODS: We prospectively followed for 10 years all patients with suspected AMI, enrolled between 1976 and 1981, participating in an early intervention trial with metoprolol who fulfilled given criteria for AMI. RESULTS: A total of 809 patients developed AMI during the first 3 days in hospital, of whom 399 were randomly assigned to receive metoprolol and 410 to receive placebo. The overall 10-year mortality rate, including initial in-hospital mortality, was 51%. In a multivariate analysis considering age, sex, history of cardiovascular diseases, estimated infarct size, and the occurrence of various complications during initial hospitalization (i.e. congestive heart failure, severe ventricular arrhythmias, tachycardia, hypotension, high-degree atrioventricular block and severity of pain) the following appeared as independent predictors of death: a history of diabetes mellitus (P < 0.001), congestive heart failure during hospitalization (P < 0.001), age (P < 0.001), and a history of previous myocardial infarction (P < 0.001). CONCLUSION: Independent predictors of death during the first 10 years after AMI were a history of diabetes mellitus, congestive heart failure during hospitalization, age, and previous myocardial infarction.

Adult↗