[Evident placebo effect in refractory angina pectoris. Do refer to the placebo-controlled study at the Huddinge hospital!].
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Angina Pectoris↗
Biomedical subjects
C Sylvén
Publications and source records attributed to C Sylvén.
Oscillation of pain intensity during adenosine infusion. Relationship to beta-endorphin and sympathetic tone.
Adenosine is a neuromodulator with both excitatory and inhibitory effects dependent in part upon preconditions; it can act as an algesic or an analgesic agent. Previously we found variations of pain intensity during constant infusion of adenosine. We therefore quantified pain intensity during constant infusion of adenosine at a rate of 140 microg/kg/min intravenously in healthy volunteers, placebo controlled, double blind, and the relation to hemodynamic, vasomotor and sudomotor responses of the sympathetic nervous system and to the role of peripheral beta-endorphin response. The perceived chest pain during adenosine infusion showed an oscillatory pattern. Painful periods of about 30s were interrupted by painfree periods, and pain was always preceded by an increase in vasomotor sympathetic activity and by increased sudomotor activity. Plasma beta-endorphin values were heterogenous but exhibited an increase during infusion.
Adenosine↗
[Gene therapy and cell therapy can be revolutionary for cardiology. An alternative in threatening heart failure after myocardial infarction].
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Angiogenesis Inducing Agents↗
Recalibration of the point-of-care test for CARDIAC T Quantitative with Elecsys Troponin T 3rd generation.
The rapid troponin T assay CARDIAC T Quantitative was recalibrated using Elecsys Troponin T 3rd Generation as a new reference method. This paper presents the method comparisons at six centres using the new reference method. Method comparison between CARDIAC T Quantitative versus Elecsys Troponin T 3rd Generation were performed using 319 samples from patients with acute coronary syndromes. The quality of the CARDIAC T Quantitative was controlled by a daily single determination of CARDIAC Control Troponin T, and for the Elecsys Troponin T 3rd Generation, the Elecsys controls were included in each run. The results for the control materials for the CARDIAC T Quantitative were between 93% and 107% of the target values. The CV ranged from 7% to 16%. From the regression analysis, according to Bablok and Passing (y=1.07x) and the Bland and Altman plot, the bias between CARDIAC T Quantitative and Elecsys Troponin T 3rd Generation is from +6% to +7%. The correlation coefficient is 0.93, and a 3x3 comparison of the clinical efficiency yielded 92% clinical concordance between CARDIAC T Quantitative and Elecsys Troponin T 3rd Generation. In conclusion, CARDIAC T Quantitative was in good agreement with the reference and calibration method Elecsys Troponin T 3rd Generation.
Calibration↗
Comprehensive local muscle training increases aerobic working capacity and quality of life and decreases neurohormonal activation in patients with chronic heart failure.
BACKGROUND: Beneficial training outcomes have been reported in patients with chronic heart failure (CHF) following leg exercise training. However, data from more comprehensive training programs are limited. The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF. METHODS: Twenty-four men and women [age 63+/-9 years (mean+/-S.D.)] with stable, moderate chronic heart failure (left ventricular ejection fraction 30+/-10%), were investigated in a randomized controlled study with a training group of 16 patients and a control group of 8 patients. The training was performed as an aerobic resistance training by activating all the main muscle groups, one at a time. The patients exercised for 1 h, three times per week for 8 weeks. RESULTS: Patient groups did not differ at baseline. Peak oxygen uptake (8%, P<0.03), the distance walked in a 6-min walking test (11%, P<0.002), the health-related quality of life (P<0.001) and plasma norepinephrine levels at rest (32%, P<0.003) and at submaximal intensities (P<0.03) improved after training. No changes were found in the control group, except for decreased peak oxygen uptake (P<0.02) and quality of life scores (P<0.03). CONCLUSIONS: Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels, it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist.
Analysis of Variance↗
Protein and angiogenic dose-response expression of phVEGF-A(165) gene in rat myocardium.
Therapeutic myocardial angiogenesis by means of transient overexpression of angiogenic growth factors is a potential treatment modality for severe ischemic heart disease. This study was undertaken in the rat to examine effects of phVEGF-A(165) myocardial transfection in terms of dose-response as regards the number of hVEGF-A expressing cells on one hand and on the other angiogenesis. Non-surgical echocardiography-guided intramyocardial injection of phVEGF-A(165) was done into normoxic or hypoxic (10% O(2)) rats. Cardiomyocytes expressing VEGF-A protein, capillary morphology and density were determined after 5 days. VEGF protein expression was seen in rat cardiomyocytes located around the tip of the injection scar and increased dose-dependently (p<0.05). Microvessel density also increased dose-dependently with phVEGF(165) (p<0.05) and with hypoxia (p<0.05). No vascular tumours were observed. In conclusion, direct intramyocardial injection of phVEGF-A(165) in the rat results in a dose-dependent increase both in transfected hVEGF-A protein producing cells and in angiogenesis.
Animals↗
Deterioration in peak systolic velocity is closely related to ischaemia during angioplasty: a vectorcardiographic and tissue Doppler imaging study.
We tested the hypothesis that the extent of signs of ischaemia detected by vectorcardiography (VCG) during elective coronary angioplasty (percutaneous transluminal coronary angioplasty; PTCA) is related to systolic and diastolic myocardial velocities, as determined by tissue Doppler echocardiography. A total of 15 patients undergoing PTCA (12 men/three women; age 61+/-9 years), without prior myocardial infarction and with an ejection fraction of >50%, were included. The balloon inflation was repeated three times, with minimum intervals of 2 min between inflations. Tissue Doppler echocardiography was performed, in an apical two- or four-chamber view, before and at the end of each inflation. Peak systolic velocity, time-to-peak systolic velocity (TTP), peak early (E(m)) and late (A(m)) diastolic velocities, the E(m)/A(m) ratio and isovolumic relaxation time were measured in the basal segments of the left ventricle. VCG recordings were carried out during the whole procedure. ST vector magnitude (ST-VM) and ST change vector magnitude (STC-VM) were monitored. The total duration and area of each VCG change during inflation were calculated for each patient. Isovolumic relaxation time, peak E(m) and A(m) values and the E(m)/A(m) ratio did not change significantly during inflation. Peak systolic velocity decreased (6.7+/-2.0 to 5.3+/-1.9 cm/s; P<0.001) and TTP increased (157+/-60 to 192+/-60 ms; P<0.01) during inflation. Both STC-VM time (r=-0.68, P<0.01) and STC-VM area (r=-0.68, P<0.01) were related to peak systolic velocity during inflation. STC-VM time was also related (r=0.55, P<0.05) to the difference in peak systolic velocity during compared with before inflation. ST-VM was less closely related to peak systolic velocity. Thus the duration and degree of ischaemia, as measured by VCG, are related to peak systolic velocity in the basal segments of the left ventricle.
Aged↗
Increased expression of VEGF following exercise training in patients with heart failure.
BACKGROUND AND AIMS: During the last decades several angiogenic factors have been characterized but so far it is unknown whether local muscle exercise training increases the expression of these factors in patients with moderate heart failure. Expression of the major putative angiogenic factor vascular endothelial growth factor (VEGF) at the level of messenger RNA (mRNA) and/or protein was therefore studied before and after 8 weeks of training in patient with chronic heart failure. METHODS: VEGF mRNA and protein concentrations were determined in skeletal muscle biopsies before and after 8 weeks of one-legged knee extension training in patients with chronic heart failure (New York Heart Association II-III). RESULTS: Exercise training increased the citrate synthase activity and peripheral exercise capacity by 46% and 36%, respectively, in parallel with a two-fold increase in VEGF at both the mRNA (P = 0.03) and protein (P = 0.02) levels CONCLUSION: The increase in VEGF gene expression in response to exercise training indicates VEGF to be one possible mediator in exercise-induced angiogenesis and may therefore regulate an important and early step in adaptation to increased muscle activity in patient with chronic heart failure.
Aged↗
Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease--12-month follow-up: angiogenic gene therapy.
OBJECTIVE: To test the safety and bioactivity of phVEGF-A165 after intramyocardial injection during 12-month follow-up. DESIGN: Open-labelled study. SUBJECTS: Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III-IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included. INTERVENTION: Via a mini-thoracotomy under general anaesthesia. phVEGF-A165 was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle. RESULTS: Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P < 0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.3+/-0.2 to 1.9+/-0.3 (P < 0.01) and nitroglycerine intake decreased from 39+/-15 to 12+/-5 tablets week(-1) (P < 0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A165 injection region was documented in all patients (P < 0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography. CONCLUSION: Intramyocardial injection of phVEGF-A165 is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial.
Aged↗
Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A165 plasmid in patients with inoperable angina pectoris.
BACKGROUND: Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A165 via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. OBJECTIVE: To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A165 via thoracotomy. DESIGN: Open label, phase I/II. METHODS: Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional class III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer. RESULTS: Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients. CONCLUSIONS: Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A165 intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.
Aged↗
Muscarinic M3 receptor subtype gene expression in the human heart.
The heart is an important target organ for cholinergic function. In this study, muscarinic receptor subtype(s) in the human heart were determined using reverse transcription-polymerase chain reaction. Our results demonstrated muscarinic receptor M2 and M3 subtype RNA in left/right atria/ventricles of donor hearts. Receptor autoradiography analysis using selective muscarinic ligands indicated an absence of M1 receptor subtype in the human heart. The level of muscarinic receptor binding in atria was two to three times greater than in ventricles. Our results suggest that muscarinic receptors in the human heart are of the M2 and M3 subtypes. This is the first report of M3 receptors in the human myocardium.
Adolescent↗
Highly efficient cell-mediated gene transfer using non-viral vectors and FuGene6: in vitro and in vivo studies.
The present study was undertaken to develop an efficient non-viral gene delivery system for cardiovascular gene therapy. We investigated transfection efficiency and toxic properties of the new transfection reagent, FuGene6, and compared it with two other transfection reagents, Tfx-50 and LipoTaxi. For in vivo experiments, the plasmid was delivered intramuscularly via transplantation of fibroblasts transfected with plasmid and FuGene6. Conditions for efficient gene delivery were initially studied in vitro. Human and rabbit fibroblasts were isolated from skin, cultured and transfected with phVEGF165 or pCMVbeta gal plasmids, coding for vascular endothelial growth factor (VEGF) or beta-galactosidase, respectively. The effect of the DNA amount and the DNA:transfection reagent ratio on plasmid uptake were studied. Of the transfection reagents tested, only FuGene6 provided high-efficiency and dose-dependent plasmid transfer both for cell-localised (beta-galactosidase) and secreted (VEGF) gene products. When analysed with an MTT assay, FuGene6 showed no toxicity at low doses. Optimised conditions were applied for in vivo reporter gene delivery. Rabbits were injected intramuscularly with ex vivo-transfected fibroblasts. As in in vitro studies, ex vivo-transfected fibroblasts showed highly efficient gene expression in vivo. Tissue sections were analysed with macrophage-specific immunostaining. No signs of inflammation were seen in the region of fibroblast injection. This study demonstrates that FuGene6 is a highly efficient transfection reagent that may be useful for in vitro non-viral transfection of primary human and rabbit fibroblasts and for in vivo therapeutic non-viral gene delivery.
Adult↗
Beat-to-beat QRS amplitude variability in elite endurance athletes.
Results from variance electrocardiography, displaying the wide-band, phase-locked electrical micro-variability during the depolarization phase, was analysed versus clinical data, echocardiographic structural and functional variables and myocardial scintigraphic findings in 174 elite orienteers compared with 37 age-matched elite endurance athletes and 50 age-matched, healthy medical students. PCA analysis identified a subgroup of five orienteers deviating from the rest of the study group and both control groups with regard to their QRS amplitude variability. No correlations were found between pathology by medical history or any of the echocardiographic and scintigraphic variables or by the variance electrocardiographic aberrations in any of the groups studied.
Adolescent↗
Insulin treatment increases skeletal muscle fibre area in patients with diabetes mellitus type 2.
The effects of insulin treatment on skeletal muscle characteristics were studied in 18 patients (62 +/- 11 years) with poorly controlled diabetes mellitus type 2 (mean duration 7.5 +/- 6 years). Skeletal muscle biopsy samples were taken from the lateral portion of the quadriceps muscle before and after a period of insulin treatment of 40 +/- 14 days. Enzyme activities (phosphofructokinase, 3-hydroxyacyl-CoA dehydrogenase, citrate synthase, lactate dehydrogenase and creatine kinase) and myoglobin content were assessed. In a subgroup of 11 patients (60 +/- 11 years), skeletal muscle fibre type composition (type I, IIA, IIB and IIC) and fibre type cross-sectional area were also analysed. Following insulin treatment there were 32 and 38% increases, respectively, in the cross-sectional areas of type IIA and IIB fast-twitch fibres (P<0. 02). The fibre type distribution did not change. The myoglobin content in muscle decreased by 20% (P<0.01). Of the enzymes tested, the 3-hydroxyacyl-CoA dehydrogenase activity decreased by 10% (P<0. 04). Serum glucose, HbA1C and serum triglyceride levels decreased (P<0.001) and body weight and arm muscle circumference increased (P<0.02). In conclusion, insulin treatment of patients with poorly controlled non-insulin-dependent diabetes mellitus increased the fast-twitch fibre area, reduced myoglobin levels and decreased muscle enzyme activity related to fatty acid oxidation.
3-Hydroxyacyl CoA Dehydrogenases↗
Tirofiban counteracts pending myocardial infarction.
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Aged↗
On-line vectorcardiography during elective coronary angioplasty indicates procedure-related myocardial infarction.
BACKGROUND: Increased creatine kinase concentrations after elective percutaneous transluminal coronary angioplasty (PTCA) have been shown to be associated with increased late cardiac mortality. OBJECTIVE: To evaluate the potential of continuous on-line vectorcardiography during elective PTCA to identify procedure-related myocardial infarction. METHODS: Patients (n = 192, ages 58 +/- 10 years), treated with elective and initially successful PTCA, were studied using vectorcardiogram (VCG) recordings. VCG monitoring was started 5 min before start of the PTCA and was carried out during the entire procedure, for at least 30 min after the first balloon inflation. ST-segment vector magnitude (ST-VM) and ST-segment change vector magnitude (STC-VM) were monitored. RESULTS: Fifteen (7.8%) procedure-related myocardial infarctions occurred. Indicators of procedure-related myocardial infarction were maximum value of ST-VM (P < 0.001) and STC-VM (P < 0.001), total ischemic time of all ST-VM episodes (P < 0.001) and STC-VM episodes (P < 0.001). The variable most closely related to a procedure-related myocardial infarction was the maximum STC-VM value during the procedure. With an optimized cutoff value, maximum STC-VM predicts a procedure-related myocardial infarction with a sensitivity of 93%, a specificity of 59% and a negative predictive value of 99%. Patients who had a stent implanted had significantly greater VCG values (P < 0.05-P < 0.001) than the group without a stent. There was a trend (P < 0.06) to a relation between increased creatine kinase concentration and stent implantation. In patients both with and without an implanted stent, greater STC-VM values were associated with procedure-related myocardial infarction (P < 0.01). CONCLUSION: Continuous VCG monitoring during elective PTCA is a promising method for immediate detection of patients at increased risk of procedure-related myocardial infarction.
Adult↗
Prognostic role of on-line vectorcardiography as regards repeat revascularization after successful coronary angioplasty.
This study evaluated the prognostic significance of continuous on-line vectorcardiography (VCG) during elective coronary angioplasty (percutaneous transluminal coronary angioplasty, PTCA). Patients (n = 192, mean age 58 +/- 10), treated with elective and initially successful PTCA, were included. VCG monitoring was started before start of the PTCA procedure and was carried out during the entire procedure. ST vector magnitude (ST-VM) was monitored. A 6-month follow-up was obtained. Main outcome measures were the frequency of cardiac events and revascularization during follow-up. During follow-up, 1 patient died, 6 suffered a nonfatal myocardial infarction and 50 were revascularized. Angiography revealed restenosis in 88% of the patients who had a revascularization. In the total patient group, the VCG predictor of revascularization was the total ischemic time of all ST-VM episodes (p = 0.05). Clinical predictors of revascularization were diabetes mellitus (p < 0.01), a more severe type of lesion (type B; p < 0.01), percent post-PTCA stenosis (p < 0.05), nominal balloon size (p < 0.01), maximum balloon pressure (p < 0.05) and no stent implanted (p < 0.001). In a multivariate analysis all the above significant univariate variables of revascularization were entered. Total ischemic time of ST-VM (p < 0.01) was the best variable giving independent prognostic information. In the nonstent group, total ischemic time of ST-VM (p < 0.01) was the only independent predictor of a further revascularization. In conclusion, VCG monitoring during elective PTCA gives on-line information that identifies patients at an increased risk of a revascularization during 6 months after the initial procedure.
Angioplasty, Balloon, Coronary↗
Subtype specific downregulation of thyroid hormone receptor mRNA by beta-adrenoreceptor blockade in the myocardium.
The beta-adrenergic system is very important in cardiovascular medicine. Thyroid hormone (T3) affects beta-adrenergic receptors. In cell culture, isoproterenol, a beta-adrenergic agonist, has been shown to upregulate thyroid hormone receptor (TR) mRNA, thus indicating a bi-directional regulation. The aim of this study was to evaluate if beta-adrenoreceptor blockade may affect subtype TR mRNA expression in vivo. Propranolol or vehicle was delivered by implanting an Alzet osmotic pump subcutaneously in mice for 14d. The concentration of TRalpha1, alpha2, beta1 and beta2 subtype mRNA concentrations were quantified by reverse transcription-polymerase chain reaction and ELISA. Propranolol downregulated the levels of TRalpha1 by 44% (p < 0.0005) and beta1 mRNA by 39% (p < 0.0005) in mouse heart, in comparison to the control, while no difference in the TRalpha2 or beta2 mRNA levels occurred. The heart rate was reduced by 10% (p < 0.05) in the propranolol group, whereas no reduction was detected in the control group. In mouse treated with propranolol serum, T3 levels were 21% lower, (p < 0.05) while serum T4 levels were 23% higher (p < 0.05) in comparison to the control. This is the first study suggesting that a beta-adrenoreceptor blockade subtype selectively regulates TR mRNA subtypes, thus giving us further knowledge about the interaction between the beta-adrenergic system and the thyroid hormone sytem.
Adrenergic beta-Antagonists↗