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Torsten Toftegaard Nielsen

Publications and source records attributed to Torsten Toftegaard Nielsen.

At least 37 records · Page 2Linked to original sources
PubMed2004

Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism.

Local and remote ischemic preconditioning (IPC) reduce ischemia-reperfusion (I/R) injury and preserve cardiac function. In this study, we tested the hypothesis that remote preconditioning is memorized by the explanted heart and yields protection from subsequent I/R injury and that the underlying mechanism involves sarcolemmal and mitochondrial ATP-sensitive K(+) (K(ATP)) channels. Male Wistar rats (300-350 g) were randomized to a control (n = 10), a remote IPC (n = 10), and a local IPC group (n = 10). Remote IPC was induced by four cycles of 5 min of limb ischemia, followed by 5 min of reperfusion. Local IPC was induced by four cycles of 2 min of regional myocardial ischemia, followed by 3 min of reperfusion. The heart was excised within 5 min after the final cycle of preconditioning, mounted in a perfused Langendorff preparation for 40 min of stabilization, and subjected to 45 min of sustained ischemia by occluding the left coronary artery and 120 min of reperfusion. I/R injury was assessed as infarct size by triphenyltetrazolium staining. The influence of sarcolemmal and mitochondrial K(ATP) channels on remote preconditioning was assessed by the addition of glibenclamide (10 microM, a nonselective K(ATP) blocker), 5-hydroxydecanoic acid (5-HD; 100 microM, a mitochondrial K(ATP) blocker), and HMR-1098 (30 microM, a sarcolemmal K(ATP) blocker) to the Langendorff preparation before I/R. The role of mitochondrial K(ATP) channels as an effector mechanism for memorizing remote preconditioning was further studied by the effect of the specific mitochondrial K(ATP) activator diaxozide (10 mg/kg) on myocardial infarct size. Remote preconditioning reduced I/R injury in the explanted heart (0.17 +/- 0.03 vs. 0.39 +/- 0.05, P < 0.05) and improved left ventricular function during reperfusion compared with control (P < 0.05). Similar effects were obtained with diazoxide. Remote preconditioning was abolished by the addition of 5-HD and glibenclamide but not by HMR-1098. In conclusion, the protective effect of remote preconditioning is memorized in the explanted heart by a mechanism that involves mitochondrial K(ATP) channels.

Adenosine Triphosphate↗
PubMed2004

Three-year outcome after coronary stenting versus bypass surgery for the treatment of multivessel disease.

BACKGROUND: The primary results of Arterial Revascularization Therapy Study reported a greater need for repeated revascularization after percutaneous coronary intervention with stenting (PCI). However, PCI was less expensive than coronary artery bypass grafting (CABG) and offered the same degree of protection against death, stroke, and myocardial infarction. METHODS AND RESULTS: Patients with multivessel disease (n=1205) were randomly assigned to either CABG or PCI and followed up for up to 3 years. Survival rates without stroke or myocardial infarction were similar in each group at 1 year and 3 years (90.5% versus 91.4% for PCI versus CABG at 1 year and 87.2% versus 88.4% for PCI versus CABG at 3 years). However, the respective repeat revascularization rates were 21.2% and 26.7% at 1 and 3 years in patients allocated to PCI, compared with 3.8% and 6.6% in patients allocated to CABG (P<0.0001). Diabetes (P<0.0009) and maximal pressure for stent deployment (P<0.002) are the strongest independent predictors of events at 3 years after PCI, whereas left anterior descending coronary artery grafting (P<0.006) is the best predictor of event-free survival at 3 years after CABG. The incremental cost of surgery compared with PCI for an event-free patient was 19 257 at 1 year but decreased to 10 492 at 3 years. It remained at 142 391 at 3 years when revascularization procedures were excluded in the efficacy end point, however. CONCLUSIONS: Three-year survival rates without stroke and myocardial infarction are identical in both groups, and the cost/benefit ratio of stenting is determined primarily by the increasing need for revascularization in the PCI group.

Coronary Artery Bypass↗
PubMed2004

Insulin-stimulated myocardial glucose uptake and the relation to perfusion and the nitric oxide system.

In skeletal muscle, insulin increases glucose uptake through endothelium-derived nitric oxide (EDNO)-dependent vasodilation. Insulin also enhances myocardial glucose uptake, but it is unknown whether vasodilation participates in the underlying mechanism. We studied whether insulin-stimulated myocardial glucose uptake (MGU) is associated with perfusion changes and whether MGU is EDNO dependent. Myocardial perfusion (MBF) and MGU were measured three times with positron emission tomography in 8 healthy volunteers (56 +/- 6 years): (1). During a hyperinsulinemic euglycemic clamp (clamp), (2). during clamp and blockage of the nitric oxide synthesis by L-NMMA and (3). during clamp and nitric oxide stimulation with nitroglycerin. We measured MBF at rest before and during clamp utilizing (13)N-ammonia and (18)F-fluoro-deoxy-glucose as perfusion and glucose tracers, respectively. Hemodynamics were affected neither by insulin nor by L-NMMA. Nitroglycerin reduced rate-pressure product. Insulin did not affect MBF. L-NMMA reduced MBF (0.60 +/- 0.15 vs. 0.66 +/- 0.14 ml/g/min; p < 0.05), while MGU was unchanged. Nitroglycerin did not alter MBF, while MGU was reduced (0.44 +/- 0.11 vs. 0.52 +/- 0.13 micromol/g/min; p = 0.05). Insulin-stimulated MGU does not rely on a simultaneous increment of MBF. Myocardial glucose uptake can be stimulated even when MBF decreases, suggesting that autoregulation of MGU is preserved despite uncoupling of vascular autoregulation.

Aged↗
PubMed2004

Five-year cardiovascular and all-cause mortality, and myocardial infarction in all subjects referred for exercise testing in two Danish counties.

OBJECTIVE: To examine the association between exercise test results and the 5-year cardiovascular and all-cause mortality, and myocardial infarction, in patients referred for exercise testing because of known or suspected coronary heart disease. DESIGN: A study of all patients (N = 2763) who in 1996 had an exercise test in two Danish counties (900000 inhabitants). Data and follow-up were based on medical records and general administrative healthcare and population registries. RESULTS: Abnormal tests, compared with normal ones, were associated with an increased adjusted cardiovascular mortality ratio of 1.77 (95% confidence interval (CI): 1.19-2.63), all-cause mortality ratio of 1.46 (95% CI: 1.11-1.93), and myocardial infarction ratio of 1.71 (95% CI: 1.28-2.28). Inconclusive tests, compared with normal ones, were associated with an increased adjusted all-cause mortality ratio of 1.52 (95% CI: 1.05-2.20) and myocardial infarction ratio of 1.67 (95% CI: 1.12-2.56). A history of myocardial infarction increased the cardiovascular death ratio by 1.51 (95% CI: 1.05-2.16) and the myocardial infarction ratio by 2.39 (95% CI: 1.84-3.10). CONCLUSION: Over a 5-year period, the result of the bicycle exercise test was clearly associated with both mortality and risk of myocardial infarction. An inconclusive test may deserve special attention.

Aged↗
PubMed2004

Coronary artery bypass grafting within 30 days after treatment of acute myocardial infarctions with angioplasty or fibrinolysis - a surgical substudy of DANAMI-2.

OBJECTIVE: To calculate the incidence and analyse the indications and outcome after surgical revascularization within the first 30 days after randomization of 1572 patients with acute myocardial infarction (MI) associated with ST-segment elevation (STEMI). DESIGN: Data regarding the patients undergoing heart surgery within the first 30 days after randomization were collected. RESULTS: Three patients (0.2%) with acute STEMI and randomized to percutaneous coronary intervention (PCI) underwent emergent coronary artery bypass grafting (CABG). A total of 50 patients (3.2%), 30 in the PCI group and 20 in the fibrinolysis group were revascularized by surgery within the first 30 days after randomization. The most frequent indication for surgery in both groups was unstable angina pectoris, followed by left main stenosis. The incidence of postoperative complications was higher compared with the outcome after elective CABG. CONCLUSIONS: The incidence of emergency CABG in this study was low (0.2%) after treatment of acute MI with either PCI or fibrinolysis. The overall incidence within 30 days was 3.2%, however, the mortality is increased with a 30-day mortality of 10% in this high-risk patient group.

Acute Disease↗
PubMed2004

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion.

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.

Arteries↗
PubMed2003

[Percutaneous coronary intervention in patients with diabetes mellitus].

The incidence of restenosis after percutaneous coronary intervention (PCI) in patients with ischemic heart disease and diabetes is increased compared to non-diabetics. The use of stents has reduced the incidence of restenosis significantly but the effect is not convincing, as restenosis in diabetics predominantly consists of intimal hyperplasia. Even with the use of stents, diabetics have increased morbidity and mortality compared to non-diabetics. The precise mechanism is unknown but may include the metabolic abnormalities characteristic of diabetes. No randomised prospective studies in diabetics compare coronary artery by-pass grafting (CABG) with optimal angioplastic therapy. We await such studies to clarify the conditions for diabetics. Retrospective subgroup analyses indicate a more favourable outcome in diabetics revascularised by CABG. Thus CABG is presumably the optimal revascularisation treatment for diabetics with three-vessel disease.

Angioplasty, Balloon, Coronary↗
PubMed2003

Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2).

BACKGROUND: Randomized trials have indicated that primary coronary angioplasty performed in patients admitted directly to highly-experienced angioplasty centers offers certain advantages over intravenous fibrinolytic therapy. However, the large majority of patients with acute myocardial infarction are submitted to hospitals without a catheterization laboratory. This means that additional transportation will be necessary for many patients if a strategy of acute coronary angioplasty is to be introduced as routine treatment. The delay of treatment caused by transportation might negate (part of) the benefits of primary angioplasty compared to fibrinolytic therapy given immediately at the local hospital. STUDY DESIGN: The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) is the first large-scale study to clarify, in a whole community, which of the 2 treatment strategies is best. A total of 1900 patients with ST-elevation myocardial infarction are to be randomized: 800 patients will be admitted to invasive hospitals and 1100 patients will be admitted to referral hospitals. Half of the 1100 patients admitted to referral hospitals will immediately be transferred to an invasive center to be treated with primary angioplasty. IMPLICATIONS: If acute transfer from a local hospital to an angioplasty center is the superior strategy, primary angioplasty should be offered to all patients as routine treatment on a community basis.

Angioplasty, Balloon, Coronary↗
PubMed2003

Regional myocardial perfusion during chronic biventricular pacing and after acute change of the pacing mode in patients with congestive heart failure and bundle branch block treated with an atrioventricular sequential biventricular pacemaker.

BACKGROUND: Biventricular (BiV) pacing has been found to improve systolic function and exercise tolerance in patients with severe congestive heart failure and bundle branch block. The mechanisms behind this beneficial effect is still not sufficiently clarified. AIM: To evaluate the regional myocardial perfusion (MP) during BiV pacing and after acute change of the pacing mode to conventional dual chamber (DDD) pacing, and single chamber atrial (AAI) pacing in patients with severe congestive heart failure and prolonged QRS width treated with chronic BiV pacing. METHODS AND RESULTS: Fourteen patients (age 63+/-7 years, 13 male) were evaluated 13+/-7 months after implantation of a triple-chamber biventricular pacemaker. MP was quantified with 13N-labeled ammonia positron emission tomography during BiV pacing, DDD pacing, and AAI pacing. MP was assessed in the anterior, lateral, inferior, and septal regions, and the global mean MP was calculated. Clinical assessment was performed before pacemaker implantation and after at least 3 months of BiV pacing including a 6-min walk test (WT), New York Heart Association (NYHA) class functional score and echocardiography. Global mean MP (BiV: 0.65+/-0.20 vs. DDD: 0.65+/-0.21 vs. AAI: 0.65+/-0.18 mlg(-1)min(-1)) and MP in each of the four regions did not differ between the three pacing modes. The patients improved clinically during BiV pacing; 6 min WT increased (338+/-59 vs. 415+/-73 m, P<0.001), NYHA class score improved (class I/II/III/IV: 0/0/11/3 vs. 1/9/2/0, P<0.001), and left ventricular ejection fraction increased (21+/-5 vs. 29+/-8%, P=0.004). CONCLUSION: No differences in regional MP are detectable after chronic BiV pacing when the pacing mode is changed acutely in patients with severe congestive heart failure and bundle branch block. This finding indicates, that the clinical improvement caused by BiV pacing is not associated with any increase in the MP and thereby oxygen demand.

Aged↗
PubMed2003

Revascularization in multivessel disease: comparison between two-year outcomes of coronary bypass surgery and stenting.

OBJECTIVE: The recent appreciation that stenting has improved the short- and long-term outcomes of patients treated with coronary angioplasty has made it imperative to reconsider the comparison between surgery and percutaneous interventions in patients with multivessel disease. METHODS: One thousand two hundred five patients were randomly assigned to undergo bypass surgery or angioplasty with stent implantation when there was consensus between the cardiac surgeon and interventional cardiologist as to equivalent treatability. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at 1 year. Major adverse cardiac and cerebrovascular events at 2 years constituted a secondary end point. RESULTS: At 2 years, 89.6% of the surgical group and 89.2% of the stent group were free from death, stroke, and myocardial infarction (log-rank test P =.65). Among patients who survived without stroke or myocardial infarction, 19.7% in the stent group underwent a second revascularization, as compared with 4.8% in the surgical group (P <.001). At 2 years, 84.8% of the surgical group and 69.5% of the stent group were event-free survivors (log-rank test P <.001), and 87.2% in the surgical cohort and 79.6 % in the stent group were angina-free survivors (P =.001). In the diabetes subgroup, 82.3% of the surgical group and 56.3% of the stent group were free from any events after 2 years (log-rank test P <.001). CONCLUSION: The difference in outcome between surgery and stenting observed at 1 year in patients with multivessel disease remained essentially unchanged at 2 years. Stenting was associated with a greater need for repeat revascularization. In view of the relatively greater difference in outcome in patients with diabetes, surgery clearly seems to be the preferable form of treatment for these patients.

Coronary Artery Bypass↗
PubMed2003

Angiotensin II inhibition increases cellular glucose transport during reperfusion but not ischemia in pig hearts.

OBJECTIVE: To study whether ACE inhibition and AT-II receptor blockade modulates myocardial glucose uptake during ischemia and reperfusion. DESIGN: We developed a method for in vivo sampling of large trans-myocardial tissue samples from beating pig hearts and in vitro measurement of sarcolemmal glucose transport, in a series of experiments in which hearts were exposed to stimuli (glucose-insulin and pacing) known to promote cellular glucose transport. In the subsequent study we compared three experimental groups: (i) ACE inhibition (ACE-I, n = 6): increasing oral doses of benazepril up to 40 mg daily for 3 weeks, (ii) angiotensin II receptor antagonist (AT II-A, n = 7): increasing oral doses of valsartan up to 320 mg for 3 weeks, (iii) control (n = 7). Samples were harvested at baseline, following 20 min of regional ischemia, and following 5 and 15 min of reperfusion. The samples were incubated with 3-O-methylglucose (MeGlu), and cellular MeGlu uptake was measured. RESULTS: Insulin-glucose, pacing, and ischemia increased cellular MeGlu transport two- to fourfold (p < 0.001). Cellular MeGlu transport was increased in ACE-I and AT II-A animals during reperfusion (p < 0.001), but not at baseline or during ischemia, compared with controls. CONCLUSION: Enhanced capacity for glucose transport during reperfusion may be a mechanism underlying the beneficial effects of ACE inhibition and AT II-antagonism in ischemic heart disease.

Adenosine Triphosphate↗
PubMed2003

Glibenclamide blunts coronary flow reserve induced by adenosine and dipyridamole.

OBJECTIVE: A reduced coronary flow reserve is considered indicative of significant coronary stenosis. As experimental data suggest that adenosine and dipyridamole induce vasodilatation by opening of ATP-sensitive potassium channels, we sought to determine the effect of glibenclamide, an antidiabetic blocker of ATP-sensitive potassium channels, on adenosine- and dipyridamole-induced coronary flow reserve. DESIGN: Coronary flow velocities were measured in 15 pigs using a Doppler flow wire. The effect of increasing glibenclamide concentrations (0.1-10 microM) on adenosine-induced coronary flow reserve was examined in five animals. Ten pigs served as time controls. The time controls were subsequently treated by 3 microM glibenclamide (n = 5) or corresponding vehicle (n = 5) and the flow response to 0.56 mg/kg dipyridamole determined. RESULTS: Glibenclamide elicited a concentration-dependent inhibition of adenosine-induced coronary flow reserve, reaching significance at glibenclamide concentrations of 3 and 10 microM. The coronary flow reserve stimulated by dipyridamole was reduced significantly by 3 microM glibenclamide. CONCLUSION: Glibenclamide blunts coronary flow reserve stimulated by adenosine and dipyridamole. This interaction may have clinical implications in diabetics undergoing adenosine- or dipyridamole-dependent diagnostic procedures.

Adenosine↗