Distinct microhemodynamic efficacy of arteriogenesis and angiogenesis in critically ischemic skin flaps.

Angiogenesis and arteriogenesis are regenerative vascular mechanisms dedicated to cope with critical ischemia after the interruption of the anatomical axial blood supply. The aim of the present study was to visualize, quantify and monitor the orchestration of these mechanisms and their microhemodynamic efficacy. A murine skin flap model was used that allowed for repetitive investigation of identical vascular structures by intravital microscopy. In the conduit arterioles, diameter and relative length increased to 133 ± 20% and 260 ± 80% over 7 days, respectively (both P<0.01), which reduced vascular resistance in this segment to 82 ± 35%. After 1 week, a peak in accumulation of activated leukocytes could be observed in the postcapillary venules (P<0.01) without relevant hemodynamic changes. Thereafter, the arteriolar remodeling was replaced by angiogenesis. Functional capillary density was increased to 141 ± 10% (P<0.01) and capillary diameter to 123 ± 6% (P<0.01) after 14 days. Both mechanisms of vascular regeneration were associated with increases in the capillary perfusion index, to 194 ± 42% (P<0.05) after 7 days and 366 ± 21% after 14 days (P>0.01). Immunohistochemical analysis revealed a correlation of arteriogenesis with eNOS upregulation and of angiogenesis with VEGF upregulation in the corresponding vessels. In conclusion, arteriogenesis was the initial regenerative mechanism leading to arteriolar remodeling, reduction in vascular resistance, and increase in capillary perfusion over the first 7 days. Thereafter, capillary perfusion was improved by angiogenesis in terms of an increase in functional capillary density.

The choice of anesthesia influences oxidative energy metabolism and tissue survival in critically ischemic murine skin.

In surgical animal studies anesthesia is used regularly. Several reports in the literature demonstrate respiratory and cardiovascular side effects of anesthesiologic agents. The aim of this study was to compare two frequently used anesthesia cocktails (ketamine/xylazine [KX] versus medetomidine/climazolam/fentanyl [MCF]) in skin flap mouse models. Systemic blood values, local metabolic parameters, and surgical outcome should be analyzed in critical ischemic skin flap models. Systemic hypoxia was found in the animals undergoing KX anesthesia compared with normoxia in the MCF group (sO(2): 89.2% +/- 2.4% versus 98.5% +/- 1.2%, P < 0.01). Analysis of tissue metabolism revealed impaired anaerobic oxygen metabolism and increased cellular damage in critical ischemic flap tissue under KX anesthesia (lactate/pyruvate ratio: KX 349.86 +/- 282.38 versus MCF 64.53 +/- 18.63; P < 0.01 and glycerol: KX 333.50 +/- 83.91 micromol/L versus MCF 195.83 +/- 29.49 micromol/L; P < 0.01). After 6 d, different rates of flap tissue necrosis could be detected (MCF 57% +/- 6% versus KX 68% +/- 6%, P < 0.01). In summary we want to point out that the type of anesthesia, the animal model and the goal of the study have to be well correlated. Comparing the effects of KX and MCF anesthesia in mice on surgical outcome was a novel aspect of our study.