Topical cutaneous application of carbon dioxide via a hydrogel for improved fracture repair: results of phase I clinical safety trial

Abstract Background Clinicians have very limited options to improve fracture repair. Therefore, it is critical to develop a new clinically available therapeutic option to assist fracture repair biologically. We previously reported that the topical cutaneous application of carbon dioxide (CO2) via a CO2 absorption-enhancing hydrogel accelerates fracture repair in rats by increasing blood flow and angiogenesis and promoting endochondral ossification. The aim of this study was to assess the safety and efficacy of CO2 therapy in patients with fractures. Methods Patients with fractures of the femur and tibia were prospectively enrolled into this study with ethical approval and informed consent. The CO2 absorption-enhancing hydrogel was applied to the fractured lower limbs of patients, and then 100% CO2 was administered daily into a sealed space for 20 min over 4 weeks postoperatively. Safety was assessed based on vital signs, blood parameters, adverse events, and arterial and expired gas analyses. As the efficacy outcome, blood flow at the level of the fracture site and at a site 5 cm from the fracture in the affected limb was measured using a laser Doppler blood flow meter. Results Nineteen patients were subjected to complete analysis. No adverse events were observed. Arterial and expired gas analyses revealed no adverse systemic effects including hypercapnia. The mean ratio of blood flow 20 min after CO2 therapy compared with the pre-treatment level increased by approximately 2-fold in a time-dependent manner. Conclusions The findings of the present study revealed that CO2 therapy is safe to apply to human patients and that it can enhance blood flow in the fractured limbs. Trial registration This study has been registered in the UMIN Clinical Trials Registry (Registration number: UMIN000013641, Date of registration: July 1, 2014).

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Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650532 ◽

1996 ◽

Vol 76 (01) ◽

pp. 111-117 ◽

Cited By ~ 10

Author(s):

Yasuto Sasaki ◽

Junji Seki ◽

John C Giddings ◽

Junichiro Yamamoto

Keyword(s):

Blood Flow ◽

Thrombus Formation ◽

Dependent Manner ◽

Red Cell ◽

Cell Velocity ◽

Red Cell Velocity ◽

The Mean ◽

Wall Shear ◽

Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

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Faculty Opinions recommendation of Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1099324.555762 ◽

2008 ◽

Author(s):

Sulpicio Soriano

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Metabolic Rate ◽

Flow Velocity ◽

Blood Flow Velocity ◽

Cerebral Blood Flow Velocity ◽

Cerebral Metabolic Rate ◽

Normal Humans ◽

Carbon Dioxide Response

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Water exchange-assisted vs. carbon dioxide-insufflated single-balloon enteroscopy: randomized controlled trial

Endoscopy ◽

10.1055/a-1459-4571 ◽

2021 ◽

Author(s):

Shaopeng Liu ◽

Tao Dong ◽

Yupeng Shi ◽

Hui Luo ◽

Xianmin Xue ◽

...

Keyword(s):

Carbon Dioxide ◽

Randomized Controlled Trial ◽

Adverse Events ◽

Water Exchange ◽

Controlled Trial ◽

Control Group ◽

Balloon Enteroscopy ◽

Randomized Controlled ◽

Single Balloon ◽

Single Balloon Enteroscopy

Background and study aims Single-balloon enteroscopy (SBE) is a valuable but difficult modality for the diagnosis and treatment of small-bowel diseases. The water exchange (WE) method has the advantage of facilitating intubation during colonoscopy. Here, we evaluated the effects of WE on procedure-related variables related to SBE. Patients and methods This randomized controlled trial was conducted in a tertiary-care referral center in China. Patients with attempt at total enteroscopy (ATE) were randomly allocated to undergo WE-assisted (WE group) or carbon dioxide-insufflated enteroscopy (CO2 group). All patients were planned to undergo both antegrade and retrograde procedures. The primary outcome was the total enteroscopy rate (TER). Secondary outcomes included maximal insertion depth, positive findings, procedural time and adverse events. Results In total, 110 patients were enrolled, with 55 in each group. Baseline characteristics between the two groups were comparable. TER was achieved in 58.2% (32/55) of the WE group and 36.4% (20/55) of the control group (p=0.022). The estimated intubation depth was 521.2±101.4 cm in the WE group and 481.6±95.2 cm in the CO2 group (p=0.037). The insertion time was prolonged in the WE group compared with CO2 group (178.9±45.1 min vs. 154.2±27.6 min, p<0.001). Endoscopic findings and adverse events were comparable between the two groups. Conclusions The WE method improved TER and increased intubation depth during SBE. The use of WE did not increase complications of enteroscopy. Clinical trial registation: https://clinicaltrials.gov/， NCT01942863.

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Impact of transient hypotension on regional cerebral blood flow in humans

Clinical Science ◽

10.1042/cs20140751 ◽

2015 ◽

Vol 129 (2) ◽

pp. 169-178 ◽

Cited By ~ 45

Author(s):

Nia C.S. Lewis ◽

Kurt J. Smith ◽

Anthony R. Bain ◽

Kevin W. Wildfong ◽

Tianne Numan ◽

...

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Carotid Artery ◽

Internal Carotid Artery ◽

Vertebral Artery ◽

Regional Cerebral Blood Flow ◽

Internal Carotid ◽

Regional Cerebral Blood

Diameter reductions in the internal carotid artery (ICA) and vertebral artery (VA) contribute to the decline in brain blood with hypotension. The decline in vertebral blood flow with hypotension was greater when carbon dioxide was low; this was not apparent in the ICA.

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The effect of five per cent carbon dioxide on the response of muscle blood flow to isoproterenol in man

Clinical Pharmacology & Therapeutics ◽

10.1002/cpt197314121 ◽

1973 ◽

Vol 14 (1) ◽

pp. 21-25 ◽

Cited By ~ 1

Author(s):

C. Xanalatos ◽

Lindsay MacDonell ◽

E. Larbi ◽

I. M. James

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Muscle Blood Flow ◽

Cent Carbon Dioxide

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Effects of Prostaglandin E1 or Trimethaphan on Local Cerebral Blood Flow and Carbon Dioxide Reactivity During Cerebral Aneurysm Surgery

Journal of Neurosurgical Anesthesiology ◽

10.1097/00008506-199307000-00003 ◽

1993 ◽

Vol 5 (3) ◽

pp. 143-150 ◽

Cited By ~ 3

Author(s):

Kazuo Abe ◽

Ikuto Yoshiya

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Cerebral Aneurysm ◽

Prostaglandin E1 ◽

Aneurysm Surgery ◽

Local Cerebral Blood Flow ◽

Carbon Dioxide Reactivity

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Increased blood flow to lower limbs after plasma exchange in two patients with familial hypercholesterolemia

Atherosclerosis ◽

10.1016/0021-9150(82)90206-4 ◽

1982 ◽

Vol 41 (2-3) ◽

pp. 421-425 ◽

Cited By ~ 8

Author(s):

A. Postiglione ◽

P. Rubba ◽

N. Scarpato ◽

A. Iannuzzi ◽

M. Mancini

Keyword(s):

Blood Flow ◽

Plasma Exchange ◽

Familial Hypercholesterolemia ◽

Lower Limbs ◽

Increased Blood Flow

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Determination of Low Blood Flow Limits for Arteriovenous Carbon Dioxide Removal

ASAIO Journal ◽

10.1097/00002480-199609000-00110 ◽

1996 ◽

Vol 42 (5) ◽

pp. M845-849 ◽

Cited By ~ 18

Author(s):

ROBERT L. BRUNSTON ◽

WEIKE TAO ◽

AKHIL BIDANI ◽

VICTOR J. CARDENAS ◽

DANIEL L. TRABER ◽

...

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Carbon Dioxide Removal

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Effect of CO2 and 100% O2 on cerebral blood flow in preterm infants

Journal of Applied Physiology ◽

10.1152/jappl.1980.48.3.468 ◽

1980 ◽

Vol 48 (3) ◽

pp. 468-472 ◽

Cited By ~ 75

Author(s):

F. A. Leahy ◽

D. Cates ◽

M. MacCallum ◽

H. Rigatto

Keyword(s):

Carbon Dioxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Preterm Infants ◽

Cerebral Circulation ◽

Pressure Change ◽

Venous Occlusion ◽

Co2 Sensitivity ◽

Important Regulator ◽

Carbon Dioxide Pressure

To determine 1) the effect of arterial CO2 change on the neonatal cerebral circulation and 2) whether 100% O2 would produce significant decrease in cerebral blood flow (CBF), we studied 24 preterm infants to explain the late (5 min) hyperventilation observed in them during hyperoxia. Of these, 12 were studied before and during inhalation of 2-3% CO2 and 12 before and during the inhalation of 100% O2. We measured CBF by a modification of the venous occlusion plethysmography technique and found that CBF increased 7.8% per Torr alveolar carbon dioxide pressure change and that it decreased 15% with 100% O2. These findings suggest that 1) CO2 is an important regulator of CBF in the perterm infant, 2) CBF-CO2 sensitivity in these infants may be greater than in adult subjects, 3) 100% O2 reduced CBF significantly, and 4) a decrease in CBF during administration of 100% O2 may be at least partially responsible for the increase in ventilation with hyperoxia.

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Design and Research of Carbon Dioxide Automatic Measuring Instrument

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.706-708.704 ◽

2013 ◽

Vol 706-708 ◽

pp. 704-707

Author(s):

Qiang Liu ◽

Tao Wu

Keyword(s):

Carbon Dioxide ◽

Dependent Manner ◽

Measuring Instrument ◽

Automatic Measuring ◽

Important Material ◽

System Composition ◽

Working Principle ◽

Automatic Measuring Instrument ◽

Dose Dependent ◽

Photosynthesis And Respiration

Carbon dioxide is the very important material of plants when they are making food by means of photosynthesis. The concentration of carbon dioxide restricts photosynthesis and respiration in a dose-dependent manner. Therefore, keeping stability concentration of carbon dioxide is quite important for plant to grow rapidly. This paper mainly introduced the system composition and working principle of carbon dioxide automatic measuring instrument, the system taking Freescale MCU as control core. The instrument can collect signal, display data and reset by connecting with the PC. The experiment result states clearly this carbon dioxide automatic measuring instrument has practical value and application significance.

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