Abstract
BackgroundImage-guided high intensity focused ultrasound has been used as an extracorporeal cardiac pacing tool and to enhance homing of stem cells to targeted tissues. However, molecular changes in the myocardium after sonication have not been widely investigated. Magnetic-resonance (MR)-guided pulsed focused ultrasound (pFUS) was targeted to the rat myocardium over a range of pressures and the microenvironmental and histological effects were evaluated over time.MethodsEight-to-ten-week-old Sprague–Dawley rats received T2-weighted MR images to target pFUS to the left ventricular and septum without cardiac or respiratory gating. Rats were sonicated through the thoracic wall at peak negative pressures (PNP) from 1 to 8 MPa at a center frequency of 1 MHz, 10 ms pulse duration and 1 Hz pulse repetition frequency for 100 pulses per focal target. Following pFUS, myocardium was harvested over 24 h and subjected to imaging, proteomic, and histological measurements.ResultspFUS to the myocardium increased expression of cytokines, chemokines, and trophic factors characterized by an initial increase in tumor necrosis factor (TNF)-α followed by increases in pro- and anti-inflammatory factors that returned to baseline by 24 h. Immediately after pFUS, there was a transient (< 1 h) increase in N-terminal pro b-type natriuretic peptide (NT-proBNP) without elevation of other cardiac injury markers. A relationship between PNP and expression of TNF-α and NT-proBNP was observed with significant changes (p < 0.05 ANOVA) ≥ 4 MPa compared to untreated controls. Contrast-enhanced ex vivo T1-weighted MRI revealed vascular leakage in sonicated myocardium that was accompanied by the presence of albumin upon immunohistochemistry. Histology revealed infiltration of neutrophils and macrophages without morphological myofibril changes in sonicated tissue accompanied by pulmonary hemorrhage at PNP > 4 MPa.ConclusionsMR-guided pFUS to myocardium induced transient proteomic and histological changes. The temporal proteomic changes in the myocardium indicate a short-lived sterile inflammatory response consistent with ischemia or contusion. Further study of myocardial function and strain is needed to determine if pFUS could be developed as an experimental model of cardiac injury and chest trauma.
Highlights
Image-guided high intensity focused ultrasound has been used as an extracorporeal cardiac pacing tool and to enhance homing of stem cells to targeted tissues
PFUS effect on molecular and cardiac injury markers To evaluate the molecular effects of pulsed focused ultrasound (pFUS) on myocardium, rats (n = 5/group) were sonicated at various peak negative pressures (PNP) (i.e., 0 = sham, 1, 3, 4, 6, 8 MPa) and euthanized 4 h posttreatment
When the myocardium was sonicated with PNP > 3 MPa, NT-proBNP was significantly elevated compared to sham control (p < 0.05 analysis of variance (ANOVA)) (Fig. 2b)
Summary
Image-guided high intensity focused ultrasound has been used as an extracorporeal cardiac pacing tool and to enhance homing of stem cells to targeted tissues. Magnetic-resonance (MR)-guided pulsed focused ultrasound (pFUS) was targeted to the rat myocardium over a range of pressures and the microenvironmental and histological effects were evaluated over time. CVD can result in high blood pressure, myocardial infarction, stroke or sudden death if left untreated [2–4]. Numerous treatment options for CVD include lifestyle changes, pharmacological therapy, and surgery that have variable clinical outcomes depending on the severity of. The implantation of cardiac pacemakers, a common clinical option for treating arrhythmias, can result in improved cardiac function and quality of life [7]. This procedure is associated with some morbidity due to infection and the surgical procedure [8]
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