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Biomedical subjects

Jan Sundell

Publications and source records attributed to Jan Sundell.

At least 19 recordsLinked to original sources
PubMed2006

Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease.

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission-computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia (n = 26) using positron emission tomography and (15)O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.

Aged↗
PubMed2005

Positive family history of coronary artery disease is associated with reduced myocardial vasoreactivity in healthy men.

OBJECTIVE: Positive family history as a risk factor for coronary artery disease seems to be most important in subjects who otherwise are at low risk. We examined the association between family history of coronary artery disease and myocardial vasoreactivity in healthy men. METHODS: 35 non-smoking healthy men (age 35+/-7 years) were studied: 16 had positive family history of coronary artery disease and 19 had negative family history. The myocardial blood flow measurements were performed basally and during adenosine infusion (140 mug/kg/min) with and without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and O-15-water. RESULTS: Basal myocardial blood flow was similar between the subjects with positive and negative family history of coronary artery disease (0.79+/-0.19 and 0.79+/-0.21 mL g(-1) min(-1), NS). Adenosine stimulated flow was significantly reduced in subjects with positive family history (3.0+/-0.5 vs 4.0+/-1.2 mL g(-1) min(-1), respectively, p=0.003). During physiological hyperinsulinemia adenosine stimulated flow was further enhanced in both groups but significantly blunted in subjects with positive family history (3.7+/-0.9 vs 5.2+/-1.5 mL g(-1) min(-1), respectively, p=0.001). These differences remained significant after simultaneous controlling for age, BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure (p=0.002). CONCLUSIONS: Healthy non-smoking men with positive family history of coronary artery disease are characterized by impaired myocardial vasoreactivity.

Adult↗
PubMed2005

Quantitative determination of volatile organic compounds in indoor dust using gas chromatography-UV spectrometry.

A novel technique, gas chromatography-UV spectrometry (GC-UV), was used to quantify volatile organic compounds (VOCs) in settled dust from 389 residences in Sweden. The dust samples were thermally desorbed in an inert atmosphere and evaporated compounds were concentrated by solid phase micro extraction and separated by capillary GC. Eluting compounds were then detected, identified, and quantified using a diode array UV spectrophotometer. Altogether, 28 compounds were quantified in each sample; 24 of these were found in more than 50% of the samples. The compounds found in highest concentrations were saturated aldehydes (C5-C10), furfuryl alcohol, 2,6-di-tert-butyl-4-methylphenol (BHT), 2-furaldehyde, and benzaldehyde. Alkenals were also found, notably 2-butenal (crotonaldehyde), 2-methyl-propenal (methacrolein), hexenal, heptenal, octenal, and nonenal. The concentrations of each of the 28 compounds ranged between two to three orders of magnitude, or even more. These results demonstrate the presence of a number of VOCs in indoor dust, and provide, for the first time, a quantitative determination of these compounds in a larger number of dust samples from residents. The findings also illustrate the potential use of GC-UV for analysing volatile compounds in indoor dust, some of which are potential irritants (to the skin, eyes or respiratory system) if present at higher concentrations. The potential use of GC-UV for improving survey and control of the human exposure to particle-bound irritants and other chemicals is inferred.

Air Pollution, Indoor↗
PubMed2005

Phthalates in indoor dust and their association with building characteristics.

In a recent study of 198 Swedish children with persistent allergic symptoms and 202 controls without such symptoms, we reported associations between the symptoms and the concentrations of n-butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in dust taken from the childrens' bedrooms. In the present study we examined associations between the concentrations of different phthalate esters in the dust from these bedrooms and various characteristics of the home. The study focused on BBzP and DEHP because these were the phthalates associated with health complaints. Associations have been examined using parametric and nonparametric tests as well as multiple logistic regression. For both BBzP and DEHP, we found associations between their dust concentrations and the amount of polyvinyl chloride (PVC) used as flooring and wall material in the home. Furthermore, high concentrations of BBzP (above median) were associated with self-reported water leakage in the home, and high concentrations of DEHP were associated with buildings constructed before 1960. Other associations, as well as absence of associations, are reported. Both BBzP and DEHP were found in buildings with neither PVC flooring nor wall covering, consistent with the numerous additional plasticized materials that are anticipated to be present in a typical home. The building characteristics examined in this study cannot serve as complete proxies for these quite varied sources. However, the associations reported here can help identify homes where phthalate concentrations are likely to be elevated and can aid in developing mitigation strategies.

Case-Control Studies↗
PubMed2004

Increased lipoprotein(a) is associated with reduced myocardial vasoreactivity in young healthy men.

OBJECTIVES AND BACKGROUND: We examined the association between lipoprotein(a) and myocardial vasoreactivity in healthy men. METHODS: Thirty non-smoking healthy men (age 34+/-6 years) were studied: 9 had increased lipoprotein(a) (>200 mg/L) concentrations (lipoprotein(a) 317 (range 218-550) mg/L) and 21 had normal lipoprotein(a) (<200 mg/L) concentrations (lipoprotein(a) 57 (range 13-156) mg/L). The myocardial blood flow measurements were performed basally and during adenosine infusion (140 microg/kg/min) with or without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and [(15)O]H(2)O. RESULTS: Basal myocardial blood flow was similar between the subjects with increased and normal lipoprotein(a) (0.76+/-0.20 and 0.79+/-0.20 mLg(-1) min(-1), NS). Adenosine-stimulated flow tended to be reduced in subjects with increased lipoprotein(a) (3.1+/-0.7 mLg(-1) min(-1) versus 3.7+/-1.1 mLg(-1) min(-1), respectively, p=0.1). During physiological hyperinsulinemia adenosine-stimulated flow was further enhanced in both groups but significantly blunted in subjects with increased lipoprotein(a) (3.7+/-0.8 mLg(-1) min(-1) versus 4.8+/-1.4 mLg(-1) min(-1), respectively, p=0.03). This difference remained significant after simultaneous controlling for BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure (p=0.04). CONCLUSIONS: Already young healthy men with lipoprotein(a) concentrations greater than 200mg/L are characterized by impaired myocardial vasoreactivity.

Adenosine↗
PubMed2004

Assessment of right ventricular oxidative metabolism by PET in patients with idiopathic dilated cardiomyopathy undergoing cardiac resynchronization therapy.

PURPOSE: Right ventricular (RV) performance is known to have prognostic value in patients with congestive heart failure (CHF). Cardiac resynchronization therapy (CRT) has been found to enhance left ventricular (LV) energetics and metabolic reserve in patients with heart failure. The interplay between the LV and RV may play an important role in CRT response. The purpose of the study was to investigate RV oxidative metabolism, metabolic reserve and the effects of CRT in patients with CHF and left bundle brach block. In addition, the role of the RV in the response to CRT was evaluated. METHODS: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of a biventricular pacemaker 8+/-5 months earlier were studied under two conditions: CRT ON and after CRT had been switched OFF for 24 h. Oxidative metabolism was measured using [11C]acetate positron emission tomography (Kmono). The measurements were performed at rest and during dobutamine-induced stress (5 microg/kg per minute). LV performance and interventricular mechanical delay (interventricular asynchrony) were measured using echocardiography. RESULTS: CRT had no effect on RV Kmono at rest (ON: 0.052+/-0.014, OFF: 0.047+/-0.018, NS). Dobutamine-induced stress increased RV Kmono significantly under both conditions but oxidative metabolism was more enhanced when CRT was ON (0.076+/-0.026 vs 0.065+/-0.027, p=0.003). CRT shortened interventricular delay significantly (45+/-33 vs 19+/-35 ms, p=0.05). In five patients the response to CRT was striking (32% increase in mean LV stroke volume, range 18-36%), while in the other five patients no response was observed (mean change +2%, range -6% to +4%). RV Kmono and LV stroke volume response to CRT correlated inversely (r=-0.66, p=0.034). None of the other measured parameters, including all LV parameters and electromechanical parameters, were associated with the response to CRT. In responders, RV Kmono with CRT OFF was significantly lower than in non-responders (0.036+/-0.01 vs 0.058+/-0.02, p=0.047). CONCLUSION: CRT appears to enhance RV oxidative metabolism and metabolic reserve during stress. Patients responding to CRT appear to have lower RV oxidative metabolism at rest, suggesting that the RV plays a significant role in the response to CRT.

Acetates↗
PubMed2004

Association between insulin resistance and reduced coronary vasoreactivity in healthy subjects.

BACKGROUND: Insulin resistance appears to be an important risk factor for coronary artery disease. OBJECTIVE: To examine the role of insulin resistance on coronary vasoreactivity in healthy subjects. PATIENTS AND METHODS: Myocardial blood flow was quantitated using positron emission tomography and oxygen-15-labelled water in 10 healthy, nonobese men. The perfusion measurements were performed basally and during adenosine infusion, which has been used as a measure of coronary vasoreactivity. After perfusion measurements were taken, whole-body glucose uptake was determined using the euglycemic hyperinsulinemic clamp technique. RESULTS: Basal myocardial blood flow was 0.89+/-0.21 mL.g(-1).min(-1); adenosine significantly increased the flow to 4.00+/-1.13 mL.g(-1).min(-1). Adenosine-stimulated myocardial blood flow was inversely associated with fasting serum insulin concentration (r=-0.69, P<0.05). Concordantly, hyperemic blood flow was associated with whole-body glucose uptake during euglycemic hyperinsulinemic conditions (r=0.64, P<0.05). Basal myocardial blood flow was not affected by insulin resistance. CONCLUSION: The results of the present study demonstrate the novel finding that insulin resistance is associated with reduced coronary vasoreactivity, even in healthy subjects.

Adenosine↗
PubMed2004

The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure.

OBJECTIVES: The effects of long-term cardiac resynchronization therapy (CRT) on left ventricular (LV) energetics and metabolic reserve were evaluated. BACKGROUND: Cardiac resynchronization therapy is a new therapy for patients with drug-refractory severe heart failure (HF). METHODS: Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of biventricular pacemaker 8 +/- 5 months earlier were studied during two conditions: CRT switched on, and after CRT was switched off for 24 h. Left ventricular function was measured using echocardiography and oxidative metabolism using [(11)C]acetate positron emission tomography. Both measurements were performed at rest and during dobutamine-induced stress (5 microg/kg/min). Basal- and adenosine-stimulated (140 microg/kg/min) myocardial blood flow were quantitated using [(15)O]water. RESULTS: During CRT off, LV stroke volume was significantly reduced at rest (72 +/- 18 ml vs. 63 +/- 15 ml, p < 0.05), but LV oxidative metabolism (K(mono)) remained unchanged (0.046 +/- 0.008 vs. 0.054 +/- 0.016 min(-1)) leading to a significant deterioration of myocardial efficiency of forward work (from 48.2 +/- 16.7 to 36.6 +/- 11.7 mm Hg.l/g, p < 0.05). During dobutamine-induced stress, stroke volume and K(mono) values were not different whether CRT was on or off. However, myocardial efficiency (56.1 +/- 16.1 vs. 49.8 +/- 18.0 mm Hg.ml.g(-1).min(-1), p = 0.099) and metabolic reserve, the response of K(mono) to dobutamine (0.023 +/- 0.014 vs. 0.013 +/- 0.014 min(-1), p = 0.09), tended to reduce when CRT was switched off. Cardiac resynchronization therapy had no effects on myocardial perfusion. Natriuretic peptides increased significantly during CRT-off period. CONCLUSIONS: Long-term CRT has beneficial effects on LV function and myocardial efficiency at rest in patients with HF. These effects are not associated with changes in myocardial perfusion or oxygen consumption. During dobutamine-induced stress, CRT does not affect functional parameters, but myocardial efficiency and metabolic reserve may be increased.

Carbon Radioisotopes↗
PubMed2004

The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case-control study.

Global phthalate ester production has increased from very low levels at the end of World War II to approximately 3.5 million metric tons/year. The aim of the present study was to investigate potential associations between persistent allergic symptoms in children, which have increased markedly in developed countries over the past three decades, and the concentration of phthalates in dust collected from their homes. This investigation is a case-control study nested within a cohort of 10,852 children. From the cohort, we selected 198 cases with persistent allergic symptoms and 202 controls without allergic symptoms. A clinical and a technical team investigated each child and her or his environment. We found higher median concentrations of butyl benzyl phthalate (BBzP) in dust among cases than among controls (0.15 vs. 0.12 mg/g dust). Analyzing the case group by symptoms showed that BBzP was associated with rhinitis (p = 0.001) and eczema (p = 0.001), whereas di(2-ethylhexyl) phthalate (DEHP) was associated with asthma (p = 0.022). Furthermore, dose-response relationships for these associations are supported by trend analyses. This study shows that phthalates, within the range of what is normally found in indoor environments, are associated with allergic symptoms in children. We believe that the different associations of symptoms for the three major phthalates-BBzP, DEHP, and di-n-butyl phthalate-can be explained by a combination of chemical physical properties and toxicologic potential. Given the phthalate exposures of children worldwide, the results from this study of Swedish children have global implications.

Air Pollution, Indoor↗
PubMed2003

C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients.

Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol.kg-1.min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 microg.kg-1.min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower (P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion (P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.

Adenosine↗
PubMed2003

Insulin and myocardial blood flow.

The renaissance of glucose-insulin-potassium infusion (GIK) as a treatment of acute myocardial infarction both in diabetic and nondiabetic subjects has raised new interests to clarify the effects and mechanisms of insulin on myocardium. Although the action of insulin on substrate metabolism is quite well studied in heart, the cardiovascular effects were until recent years poorly known. Insulin induces skeletal muscle vasodilation mainly via the endothelium-dependent mechanism and appears to have an important role in normal vascular function. There is increasing amount of evidence that insulin acts as a vasodilatory hormone also in coronary arteries. Insulin enhances myocardial blood flow and decreases coronary vascular resistance in a dose-dependent manner in healthy subjects. Moreover, insulin is able to increase myocardial blood flow also in subjects who are characterized by coronary dysfunction such as subjects with obesity, type 1 diabetes and coronary artery disease. However, vasodilatory effect of insulin may be blunted in these patients. Since already very small increase in myocardial blood flow can reduce significantly myocardial ischemia, these vasodilatory actions of insulin in coronary arteries might partly contribute to beneficial effects of GIK therapy. On the other hand, in contrast to these acute beneficial effect of insulin, epidemiological studies have indentified chronic hyperinsulinemia, a common feature in subjects with insulin resistance to glucose uptake, as an independent risk factor for coronary artery disease. The present article review the physiological and pathophysiological role of insulin in cardiac vasculature and its clinical importance during myocardial ischemia and development of coronary artery disease.

Coronary Circulation↗
PubMed2003

High serum leptin is associated with attenuated coronary vasoreactivity.

OBJECTIVE: Hyperleptinemia, a hallmark of obesity, appears to be a risk factor for coronary artery disease. However, although leptin is a vasoactive hormone, no studies addressing leptin's effect on coronary perfusion have been performed. We examined the association between circulating leptin concentration and coronary vasoreactivity in young obese and nonobese males. RESEARCH METHODS AND PROCEDURES: Myocardial blood flow was quantitated in 10 obese men (age 31 +/- 7 years, BMI 34 +/- 2 kg/m(2)) and 10 healthy matched nonobese men (age 33 +/- 8 years, BMI 24 +/- 2 kg/m(2)) using positron emission tomography and O-15-water. The measurements were performed basally and during adenosine infusion (140 micro g/kg per minute). RESULTS: Serum leptin was significantly higher in obese than nonobese subjects (10.3 +/- 5.6 vs. 4.3 +/- 2.5 ng/mL, p < 0.01). Basal myocardial blood flow was not significantly different between obese and nonobese subjects. Adenosine-stimulated flow was blunted in obese (3.2 +/- 0.6 mL/g per minute) when compared with nonobese subjects (4.0 +/- 1.1 mL/g per minute, p < 0.05). Serum leptin concentration was inversely associated with adenosine-stimulated flow in study subjects (r = -0.50, p < 0.05). This association was no longer observed after adjustment for obesity and/or hyperinsulinemia. DISCUSSION: Hyperleptinemia and reduced coronary vasoreactivity occur concomitantly in young obese but otherwise healthy men. Moreover, the adenosine-stimulated myocardial flow is inversely related to prevailing concentration of serum leptin. Although this relationship appears to be explained by obesity and/or hyperinsulinemia, leptin might have a role in regulation of myocardial blood supply.

Adenosine↗