Intravital study on the effect of extracorporeal shock waves on microcirculation and neoangiogenesis using an in vivo wound model in dorsal skinfold chamber

Status:

completed 12/2011

Aims:

Impaired blood supply of the wound tissue leads to delayed wound healing and increases the rate of wound infections. Extracorporeal shock waves (ECSW) have an effect on biological tissue. Their effect on the microvasculature in the wound bed is not well understood. The experiment was designed to reveal whether the microcirculation and the new blood vessel formation in a wound can be influenced by ECSW.

Activities/Methods:

The experiments were conducted in an in vivo system. A novel wound model was established using the transparent dorsal skinfold chamber of the mouse. In the process an intramuscular lesion of a defined size was created within the observation window. The application of Extracorporeal shock waves (ECSW) was performed using a specifically developed device, the Diver box. Shock waves with an energy flux density of 0.1 mJ/mm² were used and administered using a defocused applicator head. The intravital microscopic analyzes and the evaluation of microcirculatory parameters were performed over a period of 10 days (d0, d2, d4, d6, d10). The study groups: group 1 (500 pulses at d0), group 2 (500 pulses at d0 and d6), group 3 (1000 impulses at d0), Group 4 (1000 impulses at d0 and d6), Group 5 (control group, no application of ECSW).

Results:

- The model of the intramuscular lesion offered a realistic and reproducible situation for intravital investigation of wound closure and new blood vessel formation - The newly developed application device offered for the first time the possibility to apply ECSW adequately without energy loss in vivo and protect the biological tissue from harmful phase-reversed wave. - The effect of different impulse rates and application frequencies of ECSW could be analyzed directly intravital. - The application of ECSW to the wound led to accelerated wound closure. Significantly accelerated reduction of the wound area was observed in the treatment groups. - The effectiveness of ECSW depends on the impulse rate. It could be observed that a impulse rate of 1000 impulses at the same energy density is significantly more effective as compared to a impulse rate of 500 impulses with respect to the wound area reduction. - The frequency of application has also a significant effect on the rate of wound closure. This phenomenon was detected for high-impulse application. - The application of ECSW leads to an increase of the functional microvessel density in the wound area. - Two different mechanisms, which cause the increase of functional microvessel density, were observed: (1) The recruitment of existing, initially not perfused microvessels, which opened their lumen as a result of the application of ECSW. (2) The actual blood vessel formation, formation of new blood vessels by sprouting from existing microvessels, which was intensified by application ECSW. - ECSW have an effect on the leukocyte-endothelium interactions. - Impaired microcirculation and tissue damage due to the application of ECSW were not detected. Conclusion: Our study results indicate that ECSW promote wound healing and blood vessel formation. Specifically for plastic and reconstructive surgery this results in a number of relevant indications for the clinical application of ECSW. In particular, the improvement of burn wound healing and survival of flaps after reconstructive surgery build the main focus area. The application of extracorporeal shockwaves as a noninvasive therapeutical strategy offers a promising approach for expanding the current treatment regime. Prospective clinical investigations are under preparation.

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