Thermally-Mediated Ultrasound-Induced Contraction of Equine Muscular Arteries In Vitro and an Investigation of the Associated Cellular Mechanisms

Abstract

We have previously shown that MHz frequency ultrasound causes contraction of the carotid artery in vitro. We now extend this investigation to equine mesenteric arteries and investigate the cellular mechanisms. In vitro exposure of the large lateral cecal mesenteric artery to 4-min periods of 3.2 MHz continuous wave ultrasound at acoustic powers up to 145 mW induced reversible repeatable contraction. The magnitude of the response was linearly dependent on acoustic power and, at 145 mW, the mean increase in wall stress was 0.020 ± 0.017 mN/mm(2) (n = 34). These results are consistent with our previous study and the effect was hypothesised to be thermally mediated. A 2°C temperature rise produced an increase in intracellular calcium, measured by Fluo-4 fluorescence. Inhibition of the inward-rectifier potassium ion channel with BaCl(2) (4 μM) increased the response to ultrasound by 55% ± 49%, indicating a similar electrophysiologic basis to the response to mild hyperthermia. In small mesenteric arteries (0.5-1.0 mm diameter) mounted in a perfusion myograph, neither ultrasound exposure nor heating produced measureable vasoconstriction or a rise in intracellular calcium and we conclude that temperature-sensitive channels are absent or inactive in these small vessels. It, therefore, appears that response of blood vessels to ultrasound depends not only on the thermal properties of the vessels and surrounding tissues but also on the electrophysiology of the smooth muscle cells.

An experimental system for the study of ultrasound exposure of isolated blood vessels

“…A mesenteric artery, with intraluminal flow, was located at the bottom of a 37 • C Krebs-Ringer filled tank and imaged with an inverted microscope during exposure from above for 4 min at 3 MHz 0.18 MPa PNP. Similarly to the results from equine arteries, ultrasound induced constriction was seen in large mesenteric arteries but not in small ones, leading the authors to attribute this result to a lack of temperature sensitive channels in these vessels (Martin et al 2012). Isolated mouse aortas, containing circulating drug-bearing liposomes in intraluminal buffer, have been used in a study of drug delivery (Hitchcock et al 2010).…”

“…Invagination was associated with EC separation (Chen et al 2010a(Chen et al , 2010b. Martin et al (2012) investigated changes in wall tension and mesenteric vessel diameter in isolated equine arteries (external diameter: 0.5-8 mm). The temperature at the focus of the acoustic field where the vessel was situated was measured using a soft-tissue thermal test object, but no attempt was made to monitor acoustic cavitation.…”

In Vivo Vasospasm Induction by Ultrasound Application in the Chicken Chorioallantoic Membrane Model

“…A complex interplay between the endothelial cells lining the vessel wall and the smooth muscle cells of the underlying tissue determines the vascular tone. This cellular interaction depends on a wide range of signals, including free radicals such as nitric oxide (NO) that are exchanged between the two cell populations and on mechanical forces that are transduced mainly by the endothelial cells [ 17 ]. Frequency-dependent, ultrasound-induced changes in vascular tone have been described in the literature.…”

“…Ultrasound is widely used in medicine for diagnostic and therapeutic reasons. Several tissue effects of ultrasound including vessel contraction have been described in previous experimental studies [ 16 , 17 ]. A contraction of the carotid artery could be demonstrated after continuous wave sonication for four minutes using a 3-MHz ultrasound probe [ 16 ].…”

Interaction of ultrasound with microporous polyethylene scaffolds

“…More than just images, the use of elastography techniques and Doppler effect enables ultrasound to measure mechanical properties of biological tissues [9] and the rate and direction of blood flow [10] for diagnostic purposes as well. As a therapeutic tool, it can be used to deliver genes and drugs into cells for the treatment of cancers [11][12][13][14], induce arterial contraction [15,16] or function as a surgical tool for noninvasive removal of tumors through thermal ablation or cavitation [17,18]. In addition, ultrasonic waves have also been shown to promote healing in nerves [19,20], bones [21,22], skin [23] and cartilage [24] through direct stimulation of biological cells and chemicals (e.g.…”