Shannon R. Murphy, Lianguo Wang, Zhen Wang, Philip Domondon, Di Lang, Beth A. Habecker, Rachel C. Myles, Crystal M. Ripplinger
Abstract
β-adrenergic receptor (β-AR) blockers may be administered during acute myocardial infarction (MI), as they reduce energy demand through negative chronotropic and inotropic effects and prevent ischemia-induced arrhythmogenesis. However, the direct effects of β-AR blockers on ventricular electrophysiology and intracellular Ca(2+) handling during ischemia remain unknown. Using optical mapping of transmembrane potential (with RH237) and sarcoplasmic reticulum (SR) Ca(2+) (with the low-affinity indicator Fluo-5N AM), the effects of 15 min of regional ischemia were assessed in isolated rabbit hearts (n = 19). The impact of β-AR inhibition on isolated hearts was assessed by pre-treatment with 100 nM propranolol (Prop) prior to ischemia (n = 7). To control for chronotropy and inotropy, hearts were continuously paced at 3.3 Hz and contraction was inhibited with 20 μM blebbistatin. Untreated ischemic hearts displayed prototypical shortening of action potential duration (APD80) in the ischemic zone (IZ) compared to the non-ischemic zone (NI) at 10 and 15 min ischemia, whereas APD shortening was prevented with Prop. Untreated ischemic hearts also displayed significant changes in SR Ca(2+) handling in the IZ, including prolongation of SR Ca(2+) reuptake and SR Ca(2+) alternans, which were prevented with Prop pre-treatment. At 5 min ischemia, Prop pre-treated hearts also showed larger SR Ca(2+) release amplitude in the IZ compared to untreated hearts. These results suggest that even when controlling for chronotropic and inotropic effects, β-AR inhibition has a favorable effect during acute regional ischemia via direct effects on APD and Ca(2+) handling.
Pharmacology, Toxicology and Pharmaceutical Science
2
9%
Nursing and Health Professions
1
4%
Other
4
17%
Unknown
7
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 August 2017.
All research outputs
#17,913,495
of 22,999,744 outputs
Outputs from Frontiers in Physiology
#7,231
of 13,760 outputs
Outputs of similar age
#226,892
of 316,382 outputs
Outputs of similar age from Frontiers in Physiology
#166
of 291 outputs
Altmetric has tracked 22,999,744 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,760 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
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