Dataset Information

Physiology of endothelin in producing myocardial perfusion heterogeneity: a mechanistic study using darusentan and positron emission tomography.

ABSTRACT: Heterogeneity of resting perfusion may be due in part to up-regulation of coronary vasoconstriction via endothelin (ET) type A receptors, as homogeneity increases during subsequent vasodilatory hyperemia. Therefore, we conducted a mechanistic study using an ET receptor antagonist to determine if it could alter the homogeneity of myocardial perfusion.Included subjects demonstrated a low myocardial perfusion homogeneity index (HI) compared to normal volunteers. Four serial cardiac positron emission tomography Rb-82 scans were performed 2 weeks apart. Before the middle two scans, subjects were randomized to receive either darusentan first then placebo or visa versa. Absolute flow and coronary flow reserve were quantified for each study. Rest flow was adjusted for the pressure-rate product (PRP).We screened 37 subjects and randomized 20 who satisfied entry criteria. Rest HI increased significantly while taking darusentan (0.39 ± 0.10 vs 0.33 ± 0.04 on placebo, P = .030, compared to a normal range of 0.52 ± 0.10) without an increase in the PRP (6,859 ± 1,503 vs 6,976 ± 1,092, P = .79), leading to a higher adjusted flow at rest (0.69 ± 0.18 cc/minute/g at 7,000 PRP vs 0.59 ± 0.07 with placebo).Antagonism of the type A ET receptor increases homogeneity of resting myocardial perfusion. The mechanism appears to be increased absolute rest flow without an increase in either the PRP or myocardial perfusion during hyperemia. Our translational results are consistent with one mechanism for the observed heterogeneity of myocardial perfusion in humans.

SUBMITTER: Johnson NP

PROVIDER: S-EPMC3779022 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Physiology of endothelin in producing myocardial perfusion heterogeneity: a mechanistic study using darusentan and positron emission tomography.

Johnson Nils P NP Gould K Lance KL

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 20130711 5

<h4>Background</h4>Heterogeneity of resting perfusion may be due in part to up-regulation of coronary vasoconstriction via endothelin (ET) type A receptors, as homogeneity increases during subsequent vasodilatory hyperemia. Therefore, we conducted a mechanistic study using an ET receptor antagonist to determine if it could alter the homogeneity of myocardial perfusion.<h4>Methods</h4>Included subjects demonstrated a low myocardial perfusion homogeneity index (HI) compared to normal volunteers. F ...[more]

PMID: 23842710

Similar Datasets

Project description:AimsTo examine whether test utilization and prevalence of ischemia with positron emission tomography (PET) myocardial perfusion imaging (MPI) follow the previously described trends with single photon computed tomography (SPECT).Methods and resultsMPI studies performed between January 2003 and December 2017 were identified. Number of PET and SPECT MPI studies performed per year was determined. Trends in the proportion of studies showing any ischaemia (>0%) with both modalities were compared before and after adjusting for baseline differences in patient characteristics using propensity scores. Interaction between imaging modality and year of testing was examined using modified Poisson regression. A total of 156 244 MPI studies were performed (30% PET and 70% SPECT). Between 2003 and 2017, the number of PET studies increased from 18 to 61 studies/1000 patient encounters, while SPECT volumes declined from 169 to 34/1000 patient encounters (P < 0.001 for within-group comparisons). The prevalence of any ischaemia in SPECT-tested patients declined from 53.9% to 28.3% between 2003 and 2017, whereas ischaemia prevalence in PET-tested patients declined from 57.2% to 38.2% (P < 0.001 for within-modality comparisons), with more PET studies showing ischaemia compared to SPECT [relative risk (RR) 1.44, 95% confidence interval (CI) 1.42-1.47; P < 0.001]. After propensity score matching of 26 066 patients tested with SPECT with 26 066 patients tested with PET, the between-modality difference in ischaemia prevalence was significantly attenuated, with a slightly higher overall likelihood of detecting ischaemia with PET compared to SPECT (RR 1.08, 95% CI 1.05-1.11; P < 0.001).ConclusionsUtilization of PET MPI at a large-volume referral centre increased significantly between 2003 and 2017. Despite a significant decrease in the prevalence of ischaemia with SPECT and PET during the same period, the decline was less with PET, perhaps related to baseline risk of tested patients.

Dataset Information

Physiology of endothelin in producing myocardial perfusion heterogeneity: a mechanistic study using darusentan and positron emission tomography.

Publications

Physiology of endothelin in producing myocardial perfusion heterogeneity: a mechanistic study using darusentan and positron emission tomography.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets