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Biomedical subjects

S Haunsø

Publications and source records attributed to S Haunsø.

At least 19 recordsLinked to original sources
PubMed2004

Pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions: no effect on myocardial ischaemia or function.

BACKGROUND: Repeated episodes of myocardial ischaemia may lead to ischaemic preconditioning. This is believed to be mediated by the ATP sensitive potassium channels. OBJECTIVE: To examine the effect of pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions. DESIGN: Double blind, double dummy study. METHODS: 38 patients with a proximal stenosis of the left anterior descending coronary artery and no visible coronary collateral vessels underwent three identical 90 second balloon occlusions, each followed by five minutes of reperfusion. The patients were randomised to pinacidil 25 mg, glibenclamide 10.5 mg, or matching placebo 90 minutes before the start of the procedure. Myocardial ischaemia was measured by continuous monitoring of ECG ST segment changes. Changes in left ventricular function were recorded with a miniature radionuclide detector, and angina was scored on the Borg scale. RESULTS: In all patients the first balloon occlusion led to significant ST segment elevation, a clear decrease in left ventricular ejection fraction, and angina pectoris. This response was not attenuated at the second or third balloon occlusion, either in the placebo group or in the patients pretreated with pinacidil or glibenclamide. CONCLUSIONS: Under the given experimental conditions, this randomised and double blind study did not support the view that the human myocardium has an intrinsic protective mechanism that is activated by short lasting episodes of ischaemia.

Adenosine Triphosphate↗
PubMed2003

Differential G protein receptor kinase 2 expression in compensated hypertrophy and heart failure after myocardial infarction in the rat.

The onset of heart failure is associated with characteristic changes in myocardial expression of G protein receptor kinase 2 (GRK2). Although, GRK2 significantly contributes to the regulation of myocardial function in the failing heart, the GRK2 expression during cardiac hypertrophy without heart failure remains to be explored. We here report a differential expression of GRK2 in cardiac hypertrophy with or without heart failure in response to a myocardial infarction in the rat. Postmyocardial infarction animals were divided into two groups depending on the absence or presence of pulmonary edema, which is a manifestation of heart failure. Remarkably, cardiac GRK2 expression and activity were inhibited in animals with cardiac hypertrophy without heart failure, whereas animals with heart failure had elevated GRK2. Thus, three weeks after the infarction cardiac GRK2 expression in animals with hypertrophy alone was decreased to 0.34 of control, whereas in the group of animals with heart failure GRK2 expression was 1.89-fold higher than in sham-operated animals. GRK2 activity was affected in a similar way, three and nine weeks after the infarction cardiac GRK2 activity was reduced to 0.58 and 0.62 in animals with hypertrophy without heart failure when compared to sham operated animals. By contrast, GRK2 activity was increased by 1.32- and 1.21-fold three and nine weeks postinfarction in animals with heart failure when compared to sham animals. These data suggest that GRK2 expression is differentially regulated in hypertrophic, non-failing and hypertrophic, failing hearts.

Animals↗
PubMed2001

[Acquired warfarin resistance in a patient with mechanical heart valve].

We present a case report of a 37-year-old man with a mechanical mitral valve, who, presumably because of malabsorption, developed resistance to oral anticoagulant therapy. The patient was then treated with a replacement of the mechanical valve to biological valves, thereby eliminating the need for anticoagulant therapy. Our case report summarises the diagnostic approach to elucidate apparent resistance to anticoagulant therapy.

Administration, Oral↗
PubMed2001

G protein-coupled receptor kinase 2--a feedback regulator of Gq pathway signalling.

G protein coupled receptors or serpentine receptors work as signalling switches that turn extracellular signals into activation of multiple molecules at the intracellular face of the plasma membrane. Serpentine receptors are the targets of around 70% of all current drugs in clinical medicine. We suggest that these receptors can be pharmacologically targeted by modification of their unique internal inhibitors the G protein coupled receptor kinases (GRKs). The GRKs constitute a family of serine/threonine kinases that specifically bind to and phosphorylate agonist-activated serpentine receptors. The phosphorylated receptors are recognized by arrestins that bind to the receptor and uncouple them from attached G proteins thereby terminating G protein signalling. This review focuses on a ubiquitously expressed GRK family member dubbed GRK2 (previously called beta-adrenergic receptor kinase 1) that regulates cellular signalling at multiple levels. In Gq-coupled signalling modules GRK2 may function as a feedback inhibitor molecule that monitors, inhibits and re-directs the information flow. GRK2 acts as a negative feedback protein by interacting with at least six key signalling molecules in the Gq pathway including; receptors, free G beta gamma subunits, activated G alpha q subunits, phosphatidylinositol-4, 5-bisphosphate (PIP2), protein kinase C (PKC) and calmodulin (CaM). GRK signalling is important for immune, endocrine and cardiovascular function manifesting itself in disorders such as heart failure and lymphocyte activation especially in chronic inflammation. This review summarizes the advances made in understanding the many actions of GRKs and addresses their potential as novel therapeutic targets.

Animals↗
PubMed2000

[DANAMI. A Danish study of invasive versus conservative treatment of patients with post-infarction ischemia who had received thrombolytic therapy].

INTRODUCTION: To compare an invasive strategy employing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass grafting (CABG) with a medical strategy in patients who had received thrombolytic treatment for first acute myocardial infarction (AMI), and with signs of inducible ischaemia. METHODS: In a prospective study 1008 patients were randomized, 503 to invasive treatment, of whom 266 (52.9%) had PTCA, and 147 (29.2%) CABG, 505 to conservative treatment, of whom eight (1.6%) were revascularized within two months. RESULTS: After a median follow-up of 2.4 years the mortality in the invasive group was 3.6% vs. 4.4% (p = 0.45) in the conservative group, re-infarction incidence was 5.6% vs. 10.5% (p = 0.0038) and percentage of admissions with unstable angina was 17.9% vs. 29.5% (p < 0.00001). DISCUSSION: We conclude that post-infarct patients with inducible ischaemia should be referred to coronary angiography and revascularised accordingly.

Adult↗
PubMed2000

Assessment of continuous skeletal muscle blood flow during exercise in humans.

The ability to measure regional blood flow from exercising skeletal muscles is of great interest. However, noninvasive techniques such as venous occlusion plethysmography and pulsed Doppler duplex ultrasonography only allow determination of blood flow at rest. The aim of our study was to investigate the influence of position on continuous measured skeletal muscle blood flow response in the upright and supine positions during graded maximal exercise by means of the local (133)Xenon washout technique with portable CdTe(Cl) detectors. Fifteen healthy subjects (8 women and 7 men, mean age 46 +/- 11 years) performed graded maximal bicycle exercise in both supine and upright positions in random order on 2 subsequent days. Blood flow in the musculus tibialis anterior was measured using the local (133)Xenon washout technique. A total of 55-110 MBq of (133)Xenon dissolved in isotonic saline was injected intramuscularly and the gamma emission was registered by light-weight portable CdTe(Cl) detectors. During supine exercise skeletal muscle blood flow increased continuously with increasing work load. However, during upright exercise blood flow increased only at the initial three work loads, then it decreased gradually. Immediately after exercise blood flow returned to preexercise values for both positions. The skeletal muscle blood flow at maximum work load for each subject was 74% (relative flow values) (P < 0.05) higher in the supine compared with the upright position. There was no significant difference in absolute or relative blood flow values at similar time points. Exercise time was longer in the supine (1345 +/- 548 s) compared with the upright position (1148 +/- 453 s) (P < 0.005). The local (133)Xenon washout technique with portable CdTe(Cl) detectors allows continuous determination of skeletal muscle blood flow during graded bicycle exercise in supine and upright positions. Furthermore, blood flow at maximum work load and exercise time was increased in supine compared with upright exercise.

Adult↗
PubMed2000

ACE-inhibition promotes apoptosis after balloon injury of rat carotid arteries.

OBJECTIVE: Angiotensin II stimulates vascular smooth muscle cell (VSMC) growth, and is considered to be an important mediator of intimal thickening after vascular injury. Recent evidence has indicated that VSMC apoptosis plays a major role in the response to balloon injury, and we therefore examined the effect of angiotensin converting enzyme (ACE)-inhibition on VSMC apoptosis and vascular lesion formation in the rat model of balloon injury. METHODS: Male Sprague-Dawley rats were subjected to carotid artery balloon injury and randomised to a standard diet or a diet supplemented with 1 mg/ml captopril in the drinking water. Animals were sacrificed 2 and 14 days after injury for assessment of apoptosis and proliferation by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) immunohistochemistry, respectively. At 14 days post injury, vessel cross-sections were subjected to microscopic morphometry and total cell numbers were determined. RESULTS: At 2 days after balloon injury, captopril-treated animals displayed a significant increase in the percentage of TUNEL-positive VSMCs in the medial area (12 +/- 4% vs. 1 +/- 1%; P < 0.05) as compared to controls. This increase in early apoptosis was associated with decreased intimal cellularity 14 days post injury (238 +/- 47 cells/cross-section vs. 449 +/- 75 cells/cross-section; P < 0.05), and a reduction of neointimal formation (0.13 +/- 0.02 mm2 vs. 0.23 +/- 0.04 mm2; P < 0.05). The fraction of PCNA-positive VSMCs per cross-section 2 or 14 days after injury was not significantly altered by captopril administration. CONCLUSION: Captopril inhibits neointimal formation in the rat model of arterial injury by mechanisms involving induction of VSMC apoptosis.

Angioplasty, Balloon↗
PubMed2000

Effects of L-arginine on vascular smooth muscle cell proliferation and apoptosis after balloon injury.

Nitric oxide (NO) inhibits neointimal formation in experimental models of restenosis, but the mechanisms have not been fully elucidated. This study examined whether the beneficial effect of L-arginine, the physiological NO precursor, was associated with alteration of the apoptotic and proliferative activities of vascular smooth muscle cells (VSMCs) in the vessel wall after arterial injury. Balloon injury was performed in the rat carotid-artery injury model. Rats were treated with L-arginine (2.25% in the drinking water) or normal drinking water, and sacrificed at 1, 2 and 14 days postinjury. Apoptosis was assessed by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL), and proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry. Treatment with L-arginine increased the luminal area at 14 days postinjury (0.26 +/- 0.03 mm2 vs 0.14 +/- 0.04 mm2; p < 0.05), and this effect was attributable to a reduction in neointimal formation (0.11 +/- 0.03 mm2 vs 0.23 +/- 0.04 mm2; p < 0.05), while L-arginine did not affect vascular remodeling, as indicated by the total vessel area. The decreased neointimal area at 14 days after balloon injury contained a reduced percentage of TUNEL positive (0.1 +/- 0.1% vs 2.0 +/- 0.6%; p < 0.05), and PCNA positive (13.0 +/- 2.6% vs 27.2 +/- 5.9%; p < 0.05) nuclei, respectively. L-arginine did not influence the apoptotic or proliferative activities of VSMCs at earlier time points postinjury. The favourable effect of L-arginine in the rat model of arterial injury is associated with inhibition of VSMC proliferative activity in the vessel wall and is not explained by increased VSMC apoptosis.

Angioplasty, Balloon↗
PubMed2000

Tissue temperatures and lesion size during irrigated tip catheter radiofrequency ablation: an in vitro comparison of temperature-controlled irrigated tip ablation, power-controlled irrigated tip ablation, and standard temperature-controlled ablation.

The limited success rate of radiofrequency catheter ablation in patients with ventricular tachycardias related to structural heart disease may be increased by enlarging the lesion size. Irrigated tip catheter ablation is a new method for enlarging the size of the lesion. It was introduced in the power-controlled mode with high power and high infusion rate, and is associated with an increased risk of crater formation, which is related to high tissue temperatures. The present study explored the tissue temperatures during temperature-controlled irrigated tip ablation, comparing it with standard temperature-controlled ablation and power-controlled irrigated tip ablation. In vitro strips of porcine left ventricular myocardium were ablated. Temperature-controlled irrigated tip ablation at target temperatures 60 degrees C, 70 degrees C, and 80 degrees C with infusion of 1 mL saline/min were compared with standard temperature-controlled ablation at 70 degrees C and power-controlled irrigated tip ablation at 40 W, and infusion of 20 mL/min. Lesion size and tissue temperatures were significantly higher during all modes of irrigated tip ablation compared with standard temperature-controlled ablation (P < 0.05). Lesion volume correlated positively with tissue temperature (r = 0.87). The maximum recorded tissue temperature was always 1 mm from the ablation electrode and was 67 +/- 4 degrees C for standard ablation and 93 +/- 6 degrees C, 99 +/- 6 degrees C, and 115 +/- 13 degrees C for temperature-controlled irrigated tip ablation at 60 degrees C, 70 degrees C, and 80 degrees C, respectively, and 112 +/- 12 degrees C for power-controlled irrigated tip ablation, which for irrigated tip ablation was significantly higher than tip temperature (P < 0.0001). Crater formation only occurred at tissue temperatures > 100 degrees C. We conclude that irrigated tip catheter ablation increases lesion size and tissue temperatures compared with standard ablation in the temperature-controlled mode at the same or higher target temperatures and in the power-controlled mode. Furthermore, tissue temperature and delivered power are the best indicators of lesion volume during temperature-controlled ablation.

Animals↗
PubMed2000

Health related quality of life after conservative or invasive treatment of inducible postinfarction ischaemia. DANAMI study group.

OBJECTIVE: To assess health related quality of life in patients with inducible postinfarction ischaemia. DESIGN: A questionnaire based follow up study on patients randomised to conservative or invasive treatment because of postinfarction ischaemia. SETTING: Seven county hospitals in eastern Denmark and the Heart Centre, National University Hospital, Copenhagen, Denmark. PATIENTS: 113 patients with inducible postinfarction ischaemia: 51 were randomised to conservative treatment and 62 to invasive treatment. Average follow up time was three years (19-57 months). MAIN OUTCOME MEASURES: SF-36, Rose angina and dyspnoea questionnaire, drug use, lifestyle, and cognitive function. RESULTS: Invasively treated patients scored better on the SF-36 scales of physical functioning (p = 0.03) and on role-physical (p = 0.04) and physical component scales (p = 0.05) and took significantly less anti-ischaemic drug treatment. Angina occurred in 18% of the invasively treated patients and 31% of the conservatively treated patients (p = 0.09). However, more invasively treated patients suffered from concentration difficulties (18% v 4%; p = 0.04). CONCLUSIONS: Patients who were treated invasively had better health related quality of life scores in the physical variables compared with conservatively treated patients. However, a larger proportion of invasively treated patients had concentration difficulties.

Adult↗
PubMed1999

Aminoguanidine induces constrictive vascular remodeling and inhibits smooth muscle cell death after balloon injury.

We examined the effects of aminoguanidine, an inhibitor of inducible nitric oxide synthase, in the rat model of balloon injury. Arteries were assessed by histomorphometry, and vascular smooth muscle cell death and proliferation were examined 24 h and 14 days after balloon injury by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA and expression of proliferating cell nuclear antigen, respectively. Aminoguanidine decreased the luminal area 14 days after balloon injury (0.19+/-0.04 mm2 vs. 0.35+/-0.02 mmr2; P < 0.005), and this effect was attributable to reduction of the total vessel area, i.e., constrictive vascular remodeling (0.42+/-0.03 mm2 vs. 0.55+/-0.03 mm2; P < 0.005). At 24 h after injury, the percentage of TUNEL-positive cells in the medial layer was reduced by aminoguanidine (2.0+/-1.0% vs. 17.3+/-5.4%; P < 0.05), and the percentage of proliferating cells was increased (18.4+/-5.5% vs. 4.9+/-2.2%; P < 0.05). Aminoguanidine did not influence the density of VSMC nuclei in the injured artery wall, systemic blood pressure or endothelium-dependent vasorelaxation. We conclude, that in the rat model of balloon injury, aminoguanidine induces luminal loss by constrictive vascular remodeling in association with reduced early VSMC death and increased proliferation.

Angioplasty, Balloon↗
PubMed1999

Lesion dimensions during temperature-controlled radiofrequency catheter ablation of left ventricular porcine myocardium: impact of ablation site, electrode size, and convective cooling.

BACKGROUND: It is important to increase lesion size to improve the success rate for radiofrequency ablation of ischemic ventricular tachycardia. This study of radiofrequency ablation, with adjustment of power to approach a preset target temperature, ie, temperature-controlled ablation, explores the effect of catheter-tip length, ablation site, and convective cooling on lesion dimensions. METHODS AND RESULTS: In vitro strips of porcine left ventricular myocardium during different levels of convective cooling and in vivo pig hearts at 2 or 3 left ventricular sites were ablated with 2- to 12-mm-tip catheters. We found increased lesion volume for increased catheter-tip length </=8 mm in vitro (P<0.05) and 6 mm in vivo (P<0. 0001), but no further increase was found for longer tips. For the 4- to 10-mm catheter tips, we found smaller lesion volume in low-flow areas (apex) than in high-flow areas (free wall and septum) (P<0.05). Increasing convective cooling of the catheter tip in vitro increased lesion volume (P<0.0005) for the 4- and 8-mm tips but not for the 12-mm tip as the generator reached maximum output. In contrast to power-controlled ablation, we found a negative correlation between tip temperature reached and lesion volume for applications in which maximum generator output was not achieved (P<0. 0001), whereas delivered power and lesion volume correlated positively (P<0.0001). CONCLUSIONS: Lesion size differs in different left ventricular target sites, which is probably related to convective cooling, as illustrated in vitro. Longer electrode tips increase lesion size for tip lengths </=6 to 8 mm. For temperature-controlled ablation, the tip temperature achieved is a poor predictor of lesion size.

Animals↗
PubMed1999

Exercise skeletal muscle blood flow is related to peripheral microvascular stiffness in idiopathic dilated cardiomyopathy.

Peripheral microvascular function plays an important role in congestive heart failure (CHF). Decreased exercise blood flow and microvascular dysfunction have been described in CHF and both factors are regarded as parameters that might influence exercise capacity in these patients. Whether these factors are related to or can be characterized in clinical severity of CHF has not been elucidated in this population. Skeletal muscle blood flow (SMBF) was measured continuously noninvasively, by means of the local isotope washout technique using (133)Xenon, in musculus tibialis anterior during graded maximal supine bicycle exercise. The distensibility in skeletal muscle was measured in a papaverine-relaxed vascular bed using (99m)Tc-pertechnetate. The investigation included 20 patients with moderate CHF (NYHA II), 11 patients with severe CHF (NYHA III, IV) due to idiopathic dilated cardiomyopathy (IDCM), and 31 age-matched healthy subjects. The maximal SMBF level was significantly lower in severe CHF (3.6 +/- 2.5 (ml x (100 g x min)(-1))) compared with moderate CHF (8.6 +/- 5.1 (ml x (100 g x min)(-1)); P < 0.005) and controls (11.0 +/- 4.1 (ml x (100 g x min)(-1)); P < 0.0001), but similar between moderate CHF and controls. Distensibility in skeletal muscle was decreased in severe CHF (12 +/- 8%) compared with controls (44 +/- 17%; P < 0.0001 vs severe CHF) and decreased with increasing severity of CHF (moderate CHF, 23 +/- 14%; P < 0.0005 vs controls). In CHF patients, a relationship was demonstrated between skeletal muscle distensibility and the maximal SMBF (P < 0.0001; r = 0.70). Moreover, maximal SMBF correlated directly to exercise time (P < 0.005; r = 0.54). Patients with CHF have reduced exercise SMBF, which may be a limiting factor for the reduced maximal exercise capacity. Moreover, microvascular distensibility in skeletal muscle is reduced and correlates to maximal exercise SMBF. Furthermore, maximal SMBF correlates to exercise time. This implies that increased skeletal muscle microvascular stiffness may contribute to the reduced blood flow during exercise and SMBF may partly limit exercise performance in CHF patients due to IDCM.

Adult↗
PubMed1999

Reversal of peripheral microvascular dysfunction during long-term treatment with the angiotensin-converting enzyme inhibitor fosinopril in congestive heart failure.

BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF) improves cardiac and peripheral hemodynamic function and exercise performance. However, studies on the effects of long-term treatment with an ACE inhibitor on the neurogenic and nonneurogenic regulation and structural microangiopathy of the peripheral microvasculature in CHF are lacking. METHODS AND RESULTS: We investigated the effect of 12 weeks of treatment with the ACE inhibitor fosinopril on peripheral microvascular function in a double-blind, placebo-controlled study of 12 patients treated with fosinopril and 10 patients treated with placebo. All had moderate CHF. Microvascular blood flow and resistance were calculated after application of the local isotope washout method in relaxed and nonrelaxed calf vascular beds in the supine position and during head-up tilt. Skeletal muscle vascular resistance was reduced in the fosinopril group (46 +/- 6 to 30 +/- 1 mm Hg.mL-1.100 g.min +/- standard error; P < .05) and differed compared with the effect of placebo (P < .05) where no change was seen (37 +/- 11 to 55 +/- 13 mm Hg.mL-1.100 g.min; not significant [NS]). Also, skin minimal vascular resistance was reduced during fosinopril treatment (13 +/- 0.6 to 11 +/- 0.7 mm Hg.mL-1.100 g.min; P < .05) and differed compared with the effect of placebo (P < .05) with absence of change (12 +/- 1.6 to 14 +/- 1.4 mm Hg.mL-1.100 g.min; NS). CONCLUSIONS: These results suggest that long-term ACE inhibitor treatment with fosinopril in patients with CHF improves hemodynamic status to as far as the peripheral microvascular level in both the relaxed and nonrelaxed microcirculation of the lower leg.

Aged↗