Therapeutic Ultrasound Promotes Reperfusion and Angiogenesis in a Rat Model of Peripheral Arterial Disease

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jpNishida et al demonstrated the potential of SWT as a treatment for IHD; in a porcine model of chronic IHD, SWT improved ejection fraction, wall thickening, myocardial blood flow and capillary density compared with sham therapy. 5 Similar results were demonstrated in porcine models of acute myocardial infarction 6 and ischemia-reperfusion injury. 7 Human studies soon followed, with Fukumoto et al first describing decreased angina and nitroglycerine use, and improved nuclear myocardial perfusion among patients with IHD who underwent SWT 3 times a week for 3 weeks. 8 Following small randomized, double-blinded trials, 9-11 clinical use of SWT for IHD has spread through Japan, Israel, and parts of Europe, where it received CE Mark approval in 2010. 12 However, clinical use has yet to spread globally, potentially due to the small subject size and efficacy of clinical trials.Unlike SWT, therapeutic ultrasound (TUS) is an acoustic technique in which multiple cycles of a single-frequency (usually 1-10 MHz) sinusoidal ultrasound wave are transmitted from an extracorporeal-focused source into the tissue of interest ( Figure 1B). The frequency, amplitude and duration of the lobal burdens of ischemic heart disease (IHD) and peripheral arterial disease (PAD) have been increasing. 1 IHD leads to approximately 7.2 million deaths per year, 2 and PAD affects over 200 million patients globally. 3 While modern revascularization methods such as bypass graft surgery and percutaneous interventions have decreased morbidity and mortality associated with these diseases, these treatments remain limited by small vessel disease and the risks of reoperation. 4 Thus, there is a strong need for novel, noninvasive and effective therapies for the promotion of angiogenesis for the treatment of these diseases. Editorial p 1906Extracorporeal shock wave therapy (SWT) is an acoustic treatment modality that sends individual acoustic shock waves in a beam focused onto the area of interest. Each shock wave consists of an approximately 1 μs-long, positive (compressional) pulse followed by a longer (~5 μs), lower amplitude negative (rarefactional) pressure pulse ( Figure 1A). In a landmark study, Therapeutic Ultrasound Promotes Reperfusion and Angiogenesis in a Rat Model of Peripheral Arterial DiseaseBabak Nazer, MD; Farzin Ghahghaie, MD; Risa Kashima, PhD; Tatiana Khokhlova, PhD; Camilo Perez, BSc; Lawrence Crum, PhD; Tom Matula, PhD; Akiko Hata, PhDBackground: Shock wave therapy (SWT) is an acoustic technology clinically used for the non-invasive treatment of ischemic heart disease (IHD). Therapeutic ultrasound (TUS) has more recently been developed for the same indication, although its effects on reperfusion and angiogenesis have yet to be directly compared to those of SWT.

Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

“…Several reports showed that LIPUS repairs damaged peripheral nerve [31], accelerates healing of fractures [32, 33] and enhances angiogenesis [34, 35]. A recent report showed that LIPUS significantly enhances endothelial proliferation and induces angiogenesis [34].…”

The effects of ultrasound and shockwave treatment on muscle regional oxygen saturation using near-infrared spectroscopy

“…Therapeutic pressure waves are often used to treat various musculoskeletal disorders as they are assumed to have thermal and mechanical effects on the target tissue resulting in an increased local metabolism and microcirculation, decreased pain and muscle tension, inhibition of muscle spasms, and accelerated healing [1,9,10,11,16,19,27]. At present, with the development and availability of precise research techniques in medicine, the assessment of possible therapeutic effect of physical therapy treatments including their dosage should be based on the objective findings of examination, supplemented by the evaluation of patient's medical condition and his/her subjective feelings.…”

“…According to our hypothesis, the heat generated during the treatment induces a reaction in the form of vasodilation and improvement of microcirculation, which increases the supply of oxygen to tissues, which -with simultaneous temperature rise and metabolism improvement -promotes its utilisation. According to the literature evidence, thermal and mechanical effects on the target tissue result in an increased local metabolism and microcirculation, promote re-perfusion and angiogenesis, reduce pain and muscle tension, inhibit muscle spasms, and accelerate healing [16,27,43]. Some researchers believe that these changes could account for the improved tissue repair which allegedly follows ultrasound therapy [44].…”

“…Some research indicates that ESWT also improved microcirculation and increased metabolism [6]. In large animal and human studies, ESWT has demonstrated the capacity to promote angiogenesis, tissue perfusion, and improvement in angina endpoints [27]. For example, Notarnicola et al [37] assessed the effects of extracorporeal shockwave therapy on tissue perfusion in the treatment of tendinopathies.…”

“…Ultrasound therapy is a more flexible technology, as it allows adjustment of all acoustic treatment parameters to optimise non-thermal bio-effects. Shockwave therapy only allows control of pulse repetition frequency and amplitude [27]. The presented differences can be important in terms of the potentially obtained trophic effect [27].…”