Cold atmospheric plasma improves cutaneous microcirculation in standardized acute wounds: Results of a controlled, prospective cohort study.

BACKGROUND: Given the high prevalence of wounds and their challenging treatment, the research of therapies to improve wound healing is of great clinical interest. In addition, the general consequences of developing chronic wounds constitute a large health economic aspect, which underscores the interest in the development of efficient treatment strategies. Direct cold atmospheric plasma (di_CAP) has been shown to have beneficial effects on microcirculation of human tissue (Kisch et al., 2016a). It also affects microbial settlements, which may have supportive effects on wound healing processes (Balzer et al., 2015). To treat these adequately, in our view, the positive effects on wound healing should be objectified by application on standardized wounds. However, wound healing is a complex process, depending on nutrient and oxygen supply by cutaneous blood circulation. In spite of microcirculation has been shown to improve in healthy skin by CAP, a quantification of the effect in a standardized wound model has never been evaluated (Kisch et al., 2016a). Based on this, we hypothesize that CAP also influences the microcirculation in standardized acute wounds in a prospective cohort study. METHODS: Microcirculatory data of 20 healthy subjects (14 males, 6 females; mean age 40.85 ± 15.84 years; BMI 26.83 ± 7.27 kg/m2) were recorded continuously at a standardized acute wound after skin transplantation (donor site) at the thigh. Under standardized conditions, microcirculatory measurements were performed using a combined laser Doppler and photospectrometry system. After baseline measurement, CAP was applied by a dielectric barrier discharge (DBD) plasma device for 90 s to the acute wound area. Immediately after the application, cutaneous microcirculation was assessed for 30 min (min) at the same site. RESULTS: After CAP application, tissue oxygen saturation immediately increased by 5% (92,66 ± 4,76% vs. Baseline 88,21 ± 6,52%, p < 0,01) in the first 60 s and remained significantly elevated for 4 min. Capillary blood flow increased by 19.3% within the first minute of CAP therapy (220.14 ± 65.91 AU vs. Baseline 184.52 ± 56.77 AU, p < 0.001). The statistically highly significant increase in blood flow continued over the entire measurement time. A maximum value was shown in the blood flow in the 15th minute (232.15 ± 58.90 AU, p < 0.001) according to CAP application. With regard to the output measurement, it represents a percentage increase of 25.8%. The measurement of post-capillary venous filling pressure at a tissue depth of 6-8 mm was 59.39 ± AU 12.94 at baseline measurement. After application, there were no significant changes. CONCLUSION: CAP increases cutaneous tissue oxygen saturation and capillary blood flow at the standardized acute wound healing model. These results support recently published data on wound healing after CAP treatment. However, further studies are needed to determine if this treatment can improve the reduced microcirculation in chronic wounds. Moreover, repetitive application protocols have to be compared with a single session treatment approach.

The repetitive application of cold atmospheric plasma (CAP) improves microcirculation parameters in chronic wounds.

BACKGROUND: Chronic wounds, such as venous leg ulcers, diabetic foot ulcers, and pressure ulcers, impose a significant burden on patients and health care systems worldwide. Cold atmospheric plasma (CAP) accelerates wound healing and decreases bacterial load in chronic wounds in both in vitro and in vivo experiments. For the first time, we examined the effects of a repetitive application of CAP on the microcirculation in chronic wounds. HYPOTHESIS: The repetitive application of cold atmospheric plasma application further improves microcirculation in chronic wounds. METHODS: Twenty patients with chronic wounds were treated repetitively with CAP. The repetitive application consisted of three CAP sessions, each lasting 90 s and separated by a 10-minute microcirculation measuring period. Microcirculation parameters were assessed with combined Laser-Doppler-Flowmetry and spectrophotometry in a tissue depth of 2 mm. RESULTS: Tissue oxygen saturation was significantly increased after the first CAP application. The effect amplitude and duration were further increased after the second and third CAP application with a maximum increase by 16,7% (percent change; p = 0,004 vs. baseline) after the third application. There was no significant increase in capillary blood flow until the third CAP application. After the third CAP application, an increase by 22,6% (p = 0,014) was observed. Postcapillary filling pressure was not significantly increased over the measuring period. The repetitive application of CAP further enhances the microcirculation in chronic wounds compared to a single application. CONCLUSION: The repetitive application of CAP boosts and prolongs tissue oxygen saturation and capillary blood flow in chronic wounds compared to a single application. This insight could provide an impetus for new treatment protocols.

Combined Intrahospital Remote Ischemic Perconditioning and Postconditioning Improves Clinical Outcome in ST-Elevation Myocardial Infarction.

RATIONALE: Remote ischemic conditioning (RIC) or ischemic postconditioning (PostC) may protect the myocardium from ischemia-reperfusion injury in patients with ST-segment-elevation myocardial infarction. OBJECTIVE: To determine whether combined intrahospital RIC and PostC or PostC alone in addition to primary percutaneous coronary intervention (PCI) reduce long-term clinical events after ST-segment-elevation myocardial infarction. METHODS AND RESULTS: The present study is a post hoc analysis of a prospective trial which randomized 696 ST-segment-elevation myocardial infarction patients with symptoms <12 hours 1:1:1 to either combined RIC and PostC in addition to primary PCI, PostC alone in addition to primary PCI, or conventional PCI (control). Three cycles of RIC were performed by inflation of an upper arm blood pressure cuff for 5 minutes followed by deflation for 5 minutes. PostC was performed after primary PCI via 4 cycles of 30 seconds balloon occlusions followed by 30 seconds of reperfusion. Major adverse cardiac events consisting of cardiac death, reinfarction, and new congestive heart failure were assessed during long-term follow-up. Follow-up data were obtained in 97% of patients in median 3.6 years after the index event (interquartile range, 2.9-4.2 years). Major adverse cardiac events occurred in 10.2% of patients in the combined RIC and PostC group and in 16.9% in the control group (odds ratio, 0.56; 95% CI, 0.32-0.97; P=0.04). The difference was driven by a significantly reduced rate of new congestive heart failure in the RIC and PostC group (2.7% versus 7.8%; odds ratio, 0.32; 95% CI, 0.13-0.84; P=0.02). In contrast, PostC alone did not reduce major adverse cardiac events compared with controls (14.1% versus 16.9%; odds ratio, 0.81; 95% CI, 0.48-1.35; P=0.41), and the reduction of new congestive heart failure was not statistically significant (3.5% versus 7.8%; odds ratio, 0.43; 95% CI, 0.18-1.03; P=0.05). CONCLUSIONS: Cardioprotection by combined intrahospital RIC and PostC in addition to primary PCI significantly reduced the rate of major adverse cardiac events and new congestive heart failure after ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02158468.

Acute Microcirculatory Effects of Remote Ischemic Conditioning in Superficial Partial Thickness Burn Wounds.

Microcirculation is a critical factor in burn wound healing. Remote ischemic conditioning (RIC) has been shown to improve microcirculation in healthy skin and demonstrated ischemic protective effects on heart, kidney, and liver cells. Therefore, we examined microcirculatory effects of RIC in partial thickness burn wounds. The hypothesis of this study is that RIC improves cutaneous microcirculation in partial thickness burn wounds. Twenty patients with partial thickness burn wounds within 48 hours after trauma were included in this study. RIC was performed with an upper arm blood pressure cuff on a healthy upper arm using three ischemia cycles (5 min inflation to 200 mm Hg) followed by 10-minute reperfusion phases. The third and final reperfusion phase lasted 20 minutes. Microcirculation of the remote (lower/upper extremities or torso) burn wound was continuously quantified, using a combined Laser Doppler and white light spectrometry. The capillary blood flow in the burn wounds increased by a maximum of 9.6% after RIC (percentage change from baseline; P < .01). Relative hemoglobin was increased by a maximum of 2.8% (vs. baseline; P < .01), while cutaneous tissue oxygen saturation remained constant (P > .05). RIC improves microcirculation in partial thickness burn wounds by improving blood flow and elevating relative hemoglobin.