## 1 Introduction  
Until an ideal wound dressing device with synergetic effects is designed, skin flaps cannot be totally replaced, especially when a defect with vital structures exposed, such as arteries, nerves, bones, or joints, needs covering. Needless to say, idyllic wound treatment equals a better quality of life, a heavily investigated area for any pathology, considering the growth of life expectancy even in cancer patients [1].  
On the threshold of treating acute or chronic wounds with stem cell techniques and 3D bioprinting devices, wound care companies already provide doctors with a huge variety of dressing choices. However, there is still solid interest for research regarding dermal microcirculation and endothelial response mechanisms [2; 3; 4]. Many of the research products with an already proven benefic angiogenic effect have in common the treatment with drugs or solutions containing nitric oxide [5].  
There have been comprehensive studies of a lot of substances that can reshape the vasculature, or they can increase survival of the modified McFarlane skin flap in rats [6; 7; 8; 9; 10; 11; 12; 13]. This type of flap provides a very well described arterial anatomy, being a so called rando\(-\)axial flap, with a consistent vascular pedicle when caudally based and a predictable area of skin necrosis cranially [8; 14; 15; 16].  
The substances that have been injected or topically applied on the flap can influence the caudal pedicles or the random vascular part of the flap. Platelet rich plasma (PRP) has been investigated through subcutaneous injection in the flaps at a certain distance from the pedicles. It has been proven that it increases the viability of the flap, decreasing the area of necrosis, having pro-angiogenic properties due to the release of factors such as vascular endothelial growth factor (VEGF) or platelet-derived angiogenesis factor (PDAF) [17; 18; 19]. Nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) has also been studied to discover its effects in our model. Depending on the dose administrated, the duration of the treatment, or the route of administration, it might improve or decrease the viability of the flap [20; 21; 22].  
Furthermore, plasma is the fourth aggregate state of matter, following solid, liquid, and gaseous. The production of plasma requires external energy input (e.g., thermal, electrical, and laser radiation) to create a gaseous mixture of charged particles (electrons and ions), excited atoms, molecules, or free radicals. In our study, there was no electrical field applied to the solution. The mixture was activated and administered shortly after the exposure on the plasma's action, as described below. In human patients, the use of plasma is related to its thermal effects on the surface under treatment for some application such as electroauterization, or to its pulsed chemistry, able to generate and deliver a mixture of reactive species to tissues and liquids. Its benefits consist of supporting wound healing, having anti-bacterial and anti-inflammatory effects, and deactivating multi-resistant pathogens, which explains its usage in wound therapy nowadays. There are studies that suggest that treatment with cold atmospheric plasma (CAP) activated therapy should be well balanced to avoid a delayed healing process and tissue damage. This balance refers to the time of exposure to CAP treatment, with several medical devices already on the market for clinical use [23; 24; 25].  
To our knowledge, there are no studies yet regarding the investigation of the cold plasma activated solution through injectable administration in the McFarlane skin flap on rats. The aim of our study was to test the effects of a CAP activated solution on this type of flap and to compare the results with the PRP and L-NAME effects, which are already described in the literature.