Key result
Hypotension increases coronary resistance ~2.2-fold in isolated hearts, reversed by NO or ET-1 blockade.
Why the study?
A paradoxical microcirculatory constriction occurs in ischemic hearts secondary to coronary stenosis, and the mechanisms involving nitric oxide and endothelin-1 systems require elucidation.
Population
Isolated mouse hearts (Langendorff preparation)
Comparison
Hypotension with or without NO synthesis inhibitor, ET(A) antagonist, ET(B) antagonist, or ROS scavengers versus normal perfusion pressure or untreated hearts
Design
Preclinical experimental study
Follow-up
70 minutes
Authors
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Hypothesis-generating for ET-1/ROS pathways in coronary resistance; leaves open translation to human ischemia management.
Paradoxical coronary microcirculatory constriction during ischemia is mediated by ET-1 activating ET(A) and ET(B2) receptors and reactive nitrogen oxide species originating from ROS-NO interaction.
Kusmic et al. (2006) studied Ischemia. Hypotension and pharmacological inhibitors (L-NAME, BQ-610, BQ-788, ROS scavengers) vs. Untreated hearts / normal perfusion pressure was evaluated on Coronary resistance. In isolated mouse hearts, hypotension raised coronary resistance by 2.2-fold, a response blunted by ROS scavengers and converted to vasodilation by NO or ET-1 inhibitors.
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