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Granstam, Sven-Olof
Publications (7 of 7) Show all publications
Henrohn, D., Björkstrand, K., Lundberg, J. O., Granstam, S.-O., Baron, T., Ingimarsdóttir, I. J., . . . Wikström, G. (2018). Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.. Journal of Cardiac Failure, 24(10), 640-653
Open this publication in new window or tab >>Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.
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2018 (English)In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 24, no 10, p. 640-653Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH.

METHODS AND RESULTS: We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders).

CONCLUSIONS: BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.

Keywords
Pulmonary arterial hypertension, beetroot juice, nitrate, nitric oxide, nitrite
National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-366975 (URN)10.1016/j.cardfail.2018.09.010 (DOI)000452812400004 ()30244181 (PubMedID)
Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2019-04-17Bibliographically approved
Leonard, D., Svenungsson, E., Sandling, J. K., Berggren, O., Jonsen, A., Bengtsson, C., . . . Ronnblom, L. (2013). Coronary Heart Disease in Systemic Lupus Erythematosus is Associated with Interferon Regulatory Factor 8 Gene Variants. Annals of the Rheumatic Diseases, 72(S3), 270-270
Open this publication in new window or tab >>Coronary Heart Disease in Systemic Lupus Erythematosus is Associated with Interferon Regulatory Factor 8 Gene Variants
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2013 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, no S3, p. 270-270Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-221194 (URN)10.1136/annrheumdis-2013-eular.837 (DOI)000331587902228 ()
Available from: 2014-03-27 Created: 2014-03-26 Last updated: 2017-12-05Bibliographically approved
Leonard, D., Svenungsson, E., Sandling, J. K., Berggren, O., Jönsen, A., Bengtsson, C., . . . Rönnblom, L. (2013). Coronary heart disease in systemic lupus erythematosus is associated with interferon regulatory factor-8 gene variants. Circulation: Cardiovascular Genetics, 6(3), 255-263
Open this publication in new window or tab >>Coronary heart disease in systemic lupus erythematosus is associated with interferon regulatory factor-8 gene variants
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2013 (English)In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 6, no 3, p. 255-263Article in journal (Refereed) Published
Abstract [en]

Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9×10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.

National Category
Medical and Health Sciences
Research subject
Molecular Medicine
Identifiers
urn:nbn:se:uu:diva-202415 (URN)10.1161/CIRCGENETICS.113.000044 (DOI)000320580700006 ()23661672 (PubMedID)
Available from: 2013-06-24 Created: 2013-06-24 Last updated: 2017-12-06Bibliographically approved
Granstam, S.-O., Rosengren, S., Vedin, O., Kero, T., Sörensen, J., Carlson, K., . . . Wikström, G. (2013). Evaluation of patients with cardiac amyloidosis using echocardiography, ECG and right heart catheterization. Amyloid: Journal of Protein Folding Disorders, 20(1), 27-33
Open this publication in new window or tab >>Evaluation of patients with cardiac amyloidosis using echocardiography, ECG and right heart catheterization
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2013 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 20, no 1, p. 27-33Article in journal (Refereed) Published
Abstract [en]

Aims:

To characterize patients with cardiac amyloidosis using echocardiography, electrocardiogram (ECG) and right heart catheterization (RHC).

Methods and results:

Fourteen patients with biopsy verified light chain or transthyretin cardiac amyloidosis were included. All patients had heart failure with markedly elevated NT-proBNP. Echocardiography demonstrated biventricular hypertrophy, left atrial enlargement and normal to slightly reduced left ventricular ejection fraction. Tissue Doppler septal e´ was low and median E/e´ was high. Within 6 months RHC was performed in eight of the patients. The restrictive filling pattern demonstrated by echocardiography corresponded well to median pulmonary wedge pressure (21 mmHg). Systolic pulmonary artery pressure (SPAP) was increased, whereas cardiac output and stroke volume were seen to be decreased with both methods. ECG demonstrated: low voltage (36%), abnormal R-progression (65%), ST-T abnormalities (71%) and high incidence of fibrillation (36%). In addition, a case report following the treatment of melphalan and dexamethasone is presented with improvement of hypertrophy, SPAP, left ventricular mass and e´.

Conclusion:

These findings should lead to a suspicion of cardiac amyloidosis and suggest further investigation.

National Category
Medical and Health Sciences
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-196246 (URN)10.3109/13506129.2012.761967 (DOI)000315187100005 ()23339421 (PubMedID)
Available from: 2013-03-06 Created: 2013-03-06 Last updated: 2017-12-06Bibliographically approved
Antoni, G., Lubberink, M., Estrada, S., Axelsson, J., Carlson, K., Lindsjö, L., . . . Sörensen, J. (2013). In Vivo Visualization of Amyloid Deposits in the Heart with 11C-PIB and PET. Journal of Nuclear Medicine, 54(2), 213-220
Open this publication in new window or tab >>In Vivo Visualization of Amyloid Deposits in the Heart with 11C-PIB and PET
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2013 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, no 2, p. 213-220Article in journal (Refereed) Published
Abstract [en]

Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-11C]2-(4′-methylamino-phenyl)-6-hydroxybenzothiazole (11C-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of 11C-PIB PET in systemic amyloidosis affecting the heart.

Methods:

Patients (n = 10) diagnosed with systemic amyloidosis—including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type—and healthy volunteers (n = 5) were investigated with PET/CT using 11C-PIB to study cardiac amyloid deposits and with 11C-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention.

Results:

Myocardial 11C-PIB uptake was visually evident in all patients 15–25 min after injection and was not seen in any volunteer. A significant difference in 11C-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with 11C-PIB. No correlation between 11C-PIB retention index and myocardial blood flow as measured with 11C-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient.

Conclusion:

11C-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-189479 (URN)10.2967/jnumed.111.102053 (DOI)000314691200021 ()23238792 (PubMedID)
Available from: 2013-01-02 Created: 2013-01-02 Last updated: 2017-12-06Bibliographically approved
Granstam, S.-O., Björklund, E., Wikström, G. & Roos, M. W. (2013). Use of echocardiographic pulmonary acceleration time and estimated vascular resistance for the evaluation of possible pulmonary hypertension. Cardiovascular Ultrasound, 11, 7
Open this publication in new window or tab >>Use of echocardiographic pulmonary acceleration time and estimated vascular resistance for the evaluation of possible pulmonary hypertension
2013 (English)In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 11, p. 7-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

During ultrasound examination, tricuspid regurgitation may be absent or gives a signal that is not reliable for the estimation of systolic pulmonary pressure. The aim of this study was to evaluate the usefulness of acceleration time (AT) from the right ventricular outflow tract (RVOT) as an estimation of the trans-tricuspid valve gradient (TTVG) and to investigate the correlation between estimated and invasive pulmonary vascular resistance (PVR).

METHODS:

The AT was correlated to the TTVG measured with routine standard echocardiography in 121 patients. In a subgroup of 29 patients, systolic pulmonary pressure (SPAP) and mean pulmonary arterial pressure (MPAP) were obtained from recent right heart catheterization (RHC).

RESULTS:

We found no significant correlation between the estimation of right atrial pressure (RAP) by echocardiography and the RAP obtained by RHC. Estimated SPAP (TTGV + RAP mean from RHC) showed a good linear relation to invasively measured SPAP. TTVG and AT showed a non-linear relation, similar to SPAP and MPAP measured by catheterization and AT. For detection of SPAP above 38 mmHg a cut-off for AT of 100 ms resulted in a sensitivity of 89% and a specificity of 84%. For detection of MPAP above 25 mmHg a cut-off for AT of 100 ms resulted in similar sensitivity and specificity. Invasive PVR and the ratio of TTVG and the time velocity integral of the RVOT (TVI RVOT ) had a strong linear relation.

CONCLUSIONS:

Our study confirms that AT appears to be useful for the evaluation of pulmonary hypertension. In high risk patients, an AT of less than 100 ms indicates a high probability of pulmonary hypertension. Furthermore, PVR estimation by ultrasound seems preferably be done by using the ratio of TTVG and TVI RVOT.

National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-196645 (URN)10.1186/1476-7120-11-7 (DOI)000316322400001 ()23445525 (PubMedID)
Available from: 2013-03-12 Created: 2013-03-12 Last updated: 2017-12-06Bibliographically approved
Granstam, S.-O. & Granstam, E. (2011). Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition. Journal of Physiological Sciences, 61(6), 497-505
Open this publication in new window or tab >>Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition
2011 (English)In: Journal of Physiological Sciences, ISSN 1880-6546, E-ISSN 1880-6562, Vol. 61, no 6, p. 497-505Article in journal (Refereed) Published
Abstract [en]

In this study, using the microsphere method, the hemodynamic response to endothelin-1 (ET-1) in healthy and streptozotocin (STZ)-diabetic rats was evaluated as well as the influences of inhibition of nitric oxide (NO)-synthase using L-NAME (N omega-nitro-l-arginine methyl ester) and the cyclooxygenase inhibitor indomethacin. Blood flow (Q) was measured in tissues of interest for vascular complications in diabetes such as kidney, eye, brain, heart and skeletal muscle with the main focus on ophthalmic circulation. Under resting conditions, evidence for renal vasoconstriction was found in diabetic animals. In both groups, administration of L-NAME reduced Q in all investigated tissues indicating a basal NO influence. In the normal rats, ET-1 induced a significant increase in blood pressure and intense vasoconstriction in all tissues except in the choroid of the eye and in the brain, where it induced an increased Q. In the STZ-diabetic rats, effects of ET-1 were less pronounced. Pretreatment with L-NAME, but not the cyclooxygenase inhibitor, abolished the ET-1-induced vasodilation in the choroid of both groups. Administration of ET A receptor antagonist BQ-123 reduced the ET-1-induced vasodilation in the choroid only in diabetic animals. In conclusion, evidence for altered vascular endothelial response to ET-1 in STZ-diabetic animals was found particularly in the ophthalmic circulation. The findings suggest differential involvement of receptors in the response to ET-1 in normal and STZ-diabetic animals.

Place, publisher, year, edition, pages
springer, 2011
Keywords
endothelin, nitric oxide, diabetes mellitus, rat, blood flow
National Category
Medical and Health Sciences
Research subject
Physiology; Ophtalmology; Cardiology
Identifiers
urn:nbn:se:uu:diva-160871 (URN)10.1007/s12576-011-0171-x (DOI)000296362700006 ()
Available from: 2011-11-02 Created: 2011-11-02 Last updated: 2017-12-08Bibliographically approved
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