Mechanisms of electrical vasoconstriction
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RESEARCH
Open Access
Mechanisms of electrical vasoconstriction Mark Brinton1* , Yossi Mandel2, Ira Schachar3 and Daniel Palanker3,4
Abstract Background: Electrical vasoconstriction is a promising approach to control blood pressure or restrict bleeding in non-compressible wounds. We explore the neural and non-neural pathways of electrical vasoconstriction in-vivo. Methods: Charge-balanced, asymmetric pulses were delivered through a pair of metal disc electrodes. Vasoconstriction was assessed by measuring the diameter of rat saphenous vessels stimulated with low-voltage (20 V, 1 ms) and highvoltage (150 V, 10 μs) stimuli at 10 Hz for 5 min. Activation pathways were explored by topical application of a specific neural agonist (phenylephrine, alpha-1 receptor), a non-specific agonist (KCl) and neural inhibitors (phenoxybenzamine, 25 mg/ml; guanethidine, 1 mg/ml). Acute tissue damage was assessed with a membrane permeability (live-dead) fluorescent assay. The Joule heating in tissue was estimated using COMSOL Multiphysics modeling. Results: During stimulation, arteries constricted to 41 ± 8% and 37 ± 6% of their pre-stimulus diameter with low- and high-voltage stimuli, while veins constricted to 80 ± 18% and 40 ± 11%, respectively. In arteries, despite similar extent of constriction, the recovery time was very different: about 30 s for low-voltage and 10 min for high-voltage stimuli. Neural inhibitors significantly reduced low-voltage arterial constriction, but did not affect high-voltage arterial or venous constriction, indicating that high-voltage stimuli activate non-neural vasoconstriction pathways. Adrenergic pathways predominantly controlled low-voltage arterial but not venous constriction, which may involve a purinergic pathway. Viability staining confirmed that stimuli were below the electroporation threshold. Modeling indicates that heating of the blood vessels during stimulation (< 0.2 °C) is too low to cause vasoconstriction. Conclusions: We demonstrate that low-voltage stimuli induce reversible vasoconstriction through neural pathways, while high-voltage stimuli activate non-neural pathways, likely in addition to neural stimulation. Different stimuli providing precise control over the extent of arterial and venous constriction as well as relaxation rate could be used to control bleeding, perfusion or blood pressure. Keywords: Electrical stimulation, Electroceuticals, Vasoconstriction
Background For decades, electrical stimulation of cardiac striated muscle has been successfully utilized in pacemakers and defibrillators. Recently, electrical control of vascular smooth muscle has been proposed to treat bleeding in non-compressible wounds [1–3]. Understanding the vasoconstriction pathways activated by electrical stimuli will help create safe and effective devices for electrical control of blood vessels. Constriction of blood vessel involves both neural and non-neural pathways. Non-neural vasoconstriction mechanisms include mechanical stretching (myogenic) [4, 5], release of endothelin-1 [6, 7] and uridine *
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