Platelet and White Cell Reactivity to Top-Load Intravenous Perfluorocarbon Infusion in Healthy Sheep.

BACKGROUND: Perfluorocarbon emulsions (PFCs) are intravenous artificial oxygen carriers with enhanced gas solubility. As lipid micelle nanoparticle emulsions, PFCs may have a class effect that causes degrees of thrombocytopenia. Understanding the extent of the platelet effects, including mechanism and potential inflammation after PFC infusion, is important for safe human trials. METHODS: Normal sheep (Dorper) were infused with 5 mL/kg of Oxygent (w/v 60% PFC) or Perftoran (w/v 20% PFC). Controls received 6% Hetastarch or were naive. Blood samples were analyzed from baseline, time 0 (the end of infusion), 3 and 24 hours, and 4 and 7 days. Platelet count, plateletcrit, mean platelet volume, platelet distribution width, and CD-62p (a platelet activation-dependent membrane protein) were measured. Neutrophils, monocytes, and total white blood cell counts were analyzed. RESULTS: In these inflammatory cell lines, there were no consistent changes or cellular activation after PFC infusion. A decrease (<10% from baseline and naive controls) in platelet count was seen on day 4 after Oxygent infusion (3 g/kg), which recovered by day 7. No platelet effect was seen in Perftoran (1 g/kg). Plateletcrit, mean platelet volume, and platelet distribution width did not change significantly at any time point among the groups. CD-62p, ADP, and collagen aggregometry showed no significant change in platelet function. CONCLUSION: There was no evidence of overall reduction in platelet number, or any correlation with the change in platelet activation or inhibition. Therefore, the risk of increased thrombosis/bleeding after PFC intravenous infusion is low in this non-trauma sheep model.

Essential Role of Patient Blood Management in a Pandemic: A Call for Action.

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and "flattening the curve" while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient's own blood. This multinational and diverse group of authors issue this "Call to Action" underscoring "The Essential Role of Patient Blood Management in the Management of Pandemics" and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.

Anti-N and anti-Doa immunoglobulin G alloantibody-mediated delayed hemolytic transfusion reaction with hyperhemolysis in sickle cell disease treated with eculizumab and HBOC-201: case report and review of the literature.

BACKGROUND: Delayed hemolytic transfusion reaction (DHTR) with hyperhemolysis is a potentially fatal complication resulting from alloimmunization that can cause severe hemolysis of both transfused and intrinsic red blood cells (RBCs). Patients with sickle cell disease often receive multiple RBC units during their lifetime and thus are likely to develop alloantibodies that increase the risk for DHTR. Treatment to decrease hemolysis includes intravenous immunoglobulin (IVIG), steroids, eculizumab, rituximab, and plasmapheresis in addition to erythropoietin (EPO), intravenous (IV) iron, vitamin B12, and folate to support erythropoiesis. RBC transfusion is preferably avoided in DHTR due to an increased risk of exacerbating the hemolysis. CASE REPORT: We report a rare case of anti-N and anti-Doa immunoglobulin (Ig)G alloantibody-mediated life-threatening DHTR with hyperhemolysis in a patient with hemoglobin SS after RBC transfusion for acute chest syndrome who was successfully treated with eculizumab and HBOC-201 (Hemopure) in addition to steroids, IVIG, EPO, IV iron, and vitamin B12. HBOC-201 (Hemopure) was successfully used as a RBC alternative in this patient. CONCLUSION: Anti-N and anti-Doa IgG alloantibodies can rarely cause severe life-threatening DHTR with hyperhemolysis. HBOC-201 (Hemopure) can be a lifesaving alternative in this scenario. Our report also supports the use of eculizumab in DHTR; however, prospective studies are needed to determine the appropriate dose and sequence of eculizumab administration.

Vitamin B12 for the treatment of vasoplegia in cardiac surgery and liver transplantation: a narrative review of cases and potential biochemical mechanisms.

PURPOSE: Hydroxocobalamin, or vitamin B12 (V-B12), is frequently used to treat smoke inhalation and cyanide poisoning. Recent reports have also described its use to treat vasoplegia in cardiac surgery and liver transplantation. This narrative review discusses this "off-label" indication for V-B12, focusing on the potential biochemical mechanisms of its actions. SOURCE: PubMed, Cochrane, and Web of Science databases were searched for clinical reports on the use of V-B12 for vasoplegia in cardiac surgery and liver transplantation, with the biochemical mechanisms discussed being based on a survey of the related biochemistry literature. PRINCIPAL FINDINGS: Forty-four patients have been treated with V-B12 for vasoplegia in various isolated case reports and one series. Although 75% of patients have increased blood pressure in response to V-B12, there were some "non-responders". The true efficacy remains unknown because clinical trials have not been performed, and significant reporting bias likely exists. Plausible biochemical explanations exist for the potential beneficial effects of V-B12 in treating vasoplegia, including binding nitric oxide and other gasotransmitters. Additional research is required to clarify if and how these mechanisms are causally involved in effective clinical responders and non-responders. CONCLUSIONS: Although anecdotal reports utilizing V-B12 for vasoplegia are available, no higher-level evidence exists. Future work is necessary to further understand the dosing, timing, adverse events, and biochemical mechanisms of V-B12 compared with other therapies such as methylene blue.

Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: a case series.

PURPOSE: Vasoplegia is a clinical syndrome marked by severe arteriolar vasodilatation, hypotension, and low systemic vascular resistance refractory to multiple vasopressor treatment. We report our experience with hydroxocobalamin (B12) infusion as a potential rescue adjunct for refractory vasoplegia during cardiopulmonary bypass (CPB). METHODS: We performed a retrospective chart review of 33 patients undergoing cardiac surgery between 1 January 2013 and 31 December 2015, who were given intravenous B12 for refractory hypotension during, or immediately following, CPB. We assessed mean arterial pressure (MAP) responses using semi-parametric group-based models (trajectory analysis). Vasopressor use was evaluated by norepinephrine-equivalent rates calculated five minutes prior, and up to 60 min following, B12 administration. RESULTS: Patients were mostly male (82%), had a mean (SD) age of 53 (13) yr, and median (IQR) EuroSCORE mortality index of 9 [4-40]. Four patterns of MAP responses to B12 were identified. In Group 1 ("poor responders") nine of 33 patients (27%) had the highest median [IQR] mortality risk (EuroSCORE 40 [4-52]), lowest mean pre-B12 MAP (50 mmHg), and minimal hemodynamic response in spite of continued vasopressor support. In contrast, Group 2 "responders" (8/33, 24%) showed a brisk MAP response (> 15 mmHg) to B12, sustained for > 60 min post-infusion, with 50% vasopressor reduction. Groups 3 and 4 had the lowest median mortality risk (EuroSCORE 8) and highest pre-B12 MAP (72 mmHg). Although Group 3 patients ("sustainers"; 9/33, 27%) showed a sustained MAP improvement, those in Group 4 ("rebounders"; 7/33, 21%) were characterized by hypertensive overshoot followed by a decrease in MAP. CONCLUSION: These data indicate considerable heterogeneity in patient response to B12, potentially dependent on both patient preoperative condition and non-standardized time of administration. B12 may provide a useful alternative therapy for refractory hypotension and vasoplegia, but controlled clinical trials to assess efficacy are needed.

Heparin: Effects upon the Glycocalyx and Endothelial Cells.

Unfractionated heparin (UFH) is the most widely used injectable medication in the United States. UFH is a poly-dispersed, relatively impure combination of many polysaccharides known as a glycosaminoglycan. It is used as the primary anticoagulant for heart surgery as well as for active treatment of deep venous thrombosis, vascular thrombosis, stroke, and many other potentially catastrophic clotting syndromes. Many perfusionists and cardiac team members know little of the biology of UFH other than its use for cardiopulmonary bypass. UFH is very similar to heparin sulfate, found on the surface of endothelial cells. Heparan sulfate protects endothelial surfaces from inflammatory attack and serves as a mechano-transducer for vascular shear. UFH and all glycosaminoglycans have far reaching pleotropic actions. This review elaborates on some of fascinating unique biology of these polysaccharides. Perhaps a number of the complex complications attributed to CPB are either caused by, or set up to occur by the complicated biology of UFH?

A Comparison of a New Ultrasound-Based Whole Blood Viscoelastic Test (SEER Sonorheometry) Versus Thromboelastography in Cardiac Surgery.

BACKGROUND: Viscoelastic thromboelastography tests such as TEG™ are now routine for assessing the coagulation status of cardiac surgery patients. We compared TEG™ with a new technology, sonic estimation of elasticity via resonance (SEER) sonorheometry, to compare measures of coagulation dynamics of whole blood and assess its potential for rapid, near-point-of-care monitoring of hemostasis during cardiac surgery. METHODS: Whole blood coagulation assessment of a prospective cohort of 50 cardiac surgery patients was performed using SEER sonorheometry and blood samples collected at 4 time points during cardiac surgery: baseline before anesthetic induction, during cardiopulmonary bypass on rewarming, 10 minutes after heparin reversal by protamine, and on patient transfer to the intensive care unit. Clot strength trajectories (G, measured by TEG™; and clot stiffness measured by SEER sonorheometry) and clot times were assessed by repeated-measures mixed models. Strength of association between the 2 methods (clot stiffness and clot times) was assessed using a modified Bland-Altman method for repeated measures; Deming (orthogonal) regression was used to quantify method concordance (constant and proportional bias). RESULTS: Clot strength/stiffness and clot time measures for both techniques showed similar tracking of trajectories. Strength of association between methods was acceptable (correlations, 0.8-0.9); however, Deming regression detected substantial deviation (bias) between techniques. SEER clot stiffness values averaged approximately 10 hPa higher than corresponding G at all time points. Reaction time (TEG™) was 1 to 2.5 minutes longer than corresponding clot times (SEER). Laboratory times (from sample drop-off to results) were substantially less for SEER sonorheometry (median time, 11-17 minutes) compared with nonautomated kaolin TEG™ (median time, 42 minutes). CONCLUSIONS: Currently, no viscoelastic hemostatic analyzer system can be considered the "gold standard"; therefore, differences observed between TEG™ and SEER are of importance only because they show that the methods are not perfectly substitutable. Measurements of clot stiffness determined by the 2 methods were correlated but not interchangeable. Reasons for discrepancies include the substantial difference in the physical methods of inducing coagulation activation in samples and the mathematical assumptions underlying calculations of G. Future studies will be required to evaluate SEER sonorheometry's abilities to identify bleeding diatheses (sensitivity/specificity) or to develop treatment algorithms based on the new tests.

Hextend-perfluorocarbon cocktail inhibits mean arterial pressure response in a rabbit shock model.

BACKGROUND: Hextend (HEX) is standard of care resuscitation fluid for combat-related traumatic hemorrhage. Because HEX has limited oxygen-carrying capacity, combination therapy with oxygen therapeutics could improve oxygen delivery after hemodynamic shock. We hypothesized that addition of perfluorocarbon (PFC) to HEX would improve hemodynamics and oxygen delivery marker response in a rabbit model of hemorrhagic shock. METHODS: Anesthetized New Zealand rabbits (n = 23) were randomly allocated to resuscitation with fresh whole blood (FWB), HEX, or HEX plus PFC (HEX + PFC) after 60 min of hemorrhagic hypotension. Mean arterial pressure (MAP) was sampled every 2-3 min for 120 min postinfusion; MAP profiles were modeled by a one-compartment pharmacokinetic model to determine peak MAP (Pmax), time to peak MAP (tmax), and postinfusion MAP persistence. Arterial blood was sampled every 15 min to examine pH, blood gases PO2 and pCO2, metabolites lactate and glucose, methemoglobin (metHb), and electrolytes. RESULTS: Compared with FWB and HEX, HEX + PFC administration resulted in delayed peak MAP and less persistent (P < 0.0001) MAP elevation; metHb was significantly elevated (P < 0.0001) compared with FWB and HEX. There were no significant differences in PO2, pCO2, or pH. Glucose, hematocrit, and hemoglobin of both HEX and HEX + PFC were significantly lower relative to FWB. Lactate clearance was modest and transient for all treatments; base deficit was significantly more negative for HEX + PFC. CONCLUSIONS: Addition of PFC to HEX did not improve hemodynamics or acidosis. Further dose- and volume-range studies are required to test efficacy of PFC in combination with HEX for hemorrhagic shock.

Report from AmSECT's International Consortium for Evidence- Based Perfusion Consensus Statement: Minimal Criteria for Reporting Cardiopulmonary Bypass-Related Contributions to Red Blood Cell Transfusions Associated With Adult Cardiac Surgery.

Gaps remain in our understanding of the contribution of bypass-related practices associated with red blood cell (RBC) transfusions after cardiac surgery. Variability exists in the reporting of bypass-related practices in the peer-reviewed literature. In an effort to create uniformity in reporting, a draft statement outlining proposed minimal criteria for reporting cardiopulmonary bypass (CPB)- related contributions (i.e., RBC data collection/documentation, clinical considerations for transfusions, equipment details, and clinical endpoints) was presented in conjunction with the American Society of ExtraCorporeal Technology's (AmSECT's) 2014 Quality and Outcomes Meeting (Baltimore, MD). Based on presentations and feedback from the conference, coauthors (n = 14) developed and subsequently voted on each proposed data element. Data elements receiving a total of 4 votes were dropped from further consideration, 5-9 votes were considered as "Recommended," and elements receiving ≥10 votes were considered as "Mandatory." A total of 52 elements were classified as mandatory, 16 recommended, and 14 dropped. There are 8 mandatory data elements for RBC data collection/documentation, 24 for clinical considerations for transfusions, 13 for equipment details, and 7 for clinical endpoints. We present 52 mandatory data elements reflecting CPB-related contributions to RBC transfusions. Consistency of such reporting would offer our community an increased opportunity to shed light on the relationship between intra-operative practices and RBC transfusions.

Effects of perfluorocarbon emulsions on microvascular blood flow and oxygen transport in a model of severe arterial gas embolism.

BACKGROUND: Arterial gas embolism (AGE) is a clinical problem that occurs directly in cardiopulmonary bypass machines in open-heart surgeries, or indirectly (through cardiac or pulmonary right to left shunts) in dive accidents, resulting in serious morbidity and even death. Perfluorocarbon (PFC) emulsions have been used for the treatment of AGE in an animal model. We hypothesized that PFC emulsions enhance microvascular blood flow, speed bubble resolution, and oxygenation in AGE compared with saline in a model of cremaster muscle from anesthetized rats. MATERIALS AND METHODS: AGE was induced by direct air injection into the femoral artery ipsilateral to the studied cremaster muscle. Microhemodynamics, microvascular, and tissue oxygenation were determined before and after treatment with two different commercial PFC emulsions (C10F20, Oxycyte; Oxygen Biotherapeutics, Inc and C10F18, PHER-O2; Sanguine Corporation, Inc) compared with saline in real time using brightfield and phosphorescence microscopy. RESULTS: Blood pressure and heart rate remained unchanged. Systemic PO2, oxygen (O2) content, and glucose were higher in PFC groups, whereas hematocrit dropped in all groups. Arteriolar blood flow went up 85% and 80% of baseline after C10F20 and C10F18 treatments, respectively, versus 11% after saline treatment. Arteriolar and tissue PO2, and O2 delivery were higher in PFC groups compared with the control group. There was an increase in arteriolar blood flow, reduction in diffusional resistance of O2 in the plasma, and improved tissue oxygenation. CONCLUSIONS: Administration of PFC emulsions in AGE is superior to saline primarily because of surfactant properties along with air bubble reabsorption.

Comment on Saner et al. The Yin and the Yang of Hemostasis in End-Stage Liver Disease. J. Clin. Med. 2023, 12, 5759.

We congratulate you on a quality review of the article on hemostasis in end-stage liver disease by Saner FH et al [...].

Silk Fibroin Particles as Carriers in the Development of All-Natural Hemoglobin-Based Oxygen Carriers (HBOCs).

Oxygen therapeutics have a range of applications in transfusion medicine and disease treatment. Synthetic molecules and all-natural or semi-synthetic hemoglobin-based oxygen carriers (HBOCs) have seen success as potential circulating oxygen carriers. However, many early HBOC products were removed from the market due to side effects from excess hemoglobin in the blood stream and hemoglobin entering the tissue. To overcome these issues, research has focused on increasing the molecular diameter of hemoglobin by polymerizing hemoglobin molecules or encapsulating hemoglobin in liposomal carriers, where immune responses and circulation times remain a challenge. This work looks to leverage the properties of silk fibroin, a cytocompatible and non-thrombogenic biopolymer, known to entrap protein-based cargo, to engineer a silk fibroin-hemoglobin-based oxygen carrier (sfHBOC). Herein, an all-aqueous solvent evaporation technique was used to form silk fibroin particles with and without hemoglobin to tailor the formulation for specific particle sizes. The encapsulation efficiency and ferrous state of hemoglobin were analyzed, resulting in 60% encapsulation efficiency and a maximum of 20% ferric hemoglobin, yielding 100 µg/mL active hemoglobin in certain sfHBOC formulations. The system did not elicit a strong inflammation response in vitro, demonstrating the potential for this particle system to serve as an injectable HBOC.

Silk Fibroin Particles as Carriers in the Development of Hemoglobin-Based Oxygen Carriers.

Oxygen therapeutics have a range of applications in transfusion medicine and disease treatment. Synthetic molecules and all-natural or semi-synthetic hemoglobin-based oxygen carriers (HBOCs) have seen success as potential circulating oxygen carriers. However, many early HBOC products stalled in development due to side effects from excess hemoglobin in the blood stream and hemoglobin entering the tissue. To overcome these issues, research has focused on increasing the molecular diameter of hemoglobin by polymerizing hemoglobin molecules or encapsulating hemoglobin in liposomal carriers. This work leverages the properties of silk fibroin, a cytocompatible and non-thrombogenic biopolymer, known to entrap protein-based cargo, to engineer a fully protein-based oxygen carrier. Herein, an all-aqueous solvent evaporation technique was used to form silk particles via phase separation from a bulk polyvinyl alcohol phase (PVA). Particles size was tuned, and particles were formed with and without hemoglobin. The encapsulation efficiency and ferrous state of hemoglobin were analyzed, resulting in 60% encapsulation efficiency and a maximum of 20% ferric hemoglobin, yielding 100 µg/mL active hemoglobin in certain sfHBOC formulations. The system did not elicit a strong inflammation response in vitro, demonstrating the potential for this particle system to serve as an injectable HBOC.

In vivo microvascular mosaics show air embolism reduction after perfluorocarbon emulsion treatment.

Massive arteriolar gas embolism (AGE) has never been evaluated in vivo using intravital microscopy and previous perfluorocarbon (PFC) emulsions were only effective in AGE when administered before AGE. We implemented a new system for quantitative studies of massive AGE using brightfield microscopy and tested a treatment with a third-generation PFC emulsion after massive AGE. We studied bubble dynamics in cremaster muscles from anesthetized rats after AGE was induced by direct air injection into the femoral artery ipsilateral to the studied muscle. Using a motorized microscope stage and a color camera, in vivo microvascular mosaics were produced on-line from over 2000 digital images to evaluate multiple networks in order to investigate the distribution, lodging, breaking, reduction and moving of 105 air bubbles in microvessels. Thirty minutes after PFC treatment, there was a reduction of 80% in bubble volume while untreated and saline-treated rats showed significantly smaller decreases of 33% and 40%, respectively (p<0.05). Air bubbles also dissolved into a larger number of smaller bubbles after PFC treatment. The proposed methodology may prove useful for rapid in vivo data acquisition from large networks. Since large air bubbles broke-up, decreased in length and volume, and moved toward smaller microvessels, the study provides quantitative data to support a mechanism by which PFC may improve tissue blood flow following massive AGE. The findings suggest that this new generation of PFC emulsions administered after severe AGE may reach compromised microvascular networks and provide help to alleviate microvascular obstruction by increasing air bubble reabsorption.

Critical oxygen delivery: the crux of bypass with a special look at the microcirculation.

The microcirculation can be defined as those vascular structures where respiratory gas flux occurs. These are generally the arterioles, venules, and capillaries. Larger vascular conduits tend to have thicker walls, are at considerable distance from cellular sites of oxygen utilization, and therefore contribute little to oxygen flux. The microcirculation is complex, not a simple straight line of parallel groups of pipes with unidirectional flow. Rather, the complex network has most vascular structures not open (held in reserve) and often has bidirectional flow. Understanding the movement of O2, CO2, and other gases within this network has only recently been the center of focused research. The cardiopulmonary bypass machine is meant to keep the microcirculation normal, but research is demonstrating major changes within. This review looks at what is known today in spontaneously perfusing animals as well as early findings noting differences in cardiopulmonary bypass. We, as yet, do not understand all the mechanisms involved in the changes of the microcirculation so thoughts regarding future areas for research are discussed.

Human error in medicine: change in cardiac operating rooms through the FOCUS initiative.

Human error in medicine is a significant cause of patient mortality. While there has been increased attention to safety in medicine since the Institute of Medicine publication To Err is Human, the profession at large has not progressed to the same degree as other highly complex industries such as aviation and nuclear power. The Flawless Operative Cardiovascular Unified Systems initiative (FOCUS) is a multi-year study/intervention to learn about and to improve human error in cardiac surgery. FOCUS has developed into an ongoing re-focusing through prospective interventional research schemes designed to effect positive change for improved patient care in cardiac surgery. The program was developed in conjunction with the Johns Hopkins University Quality and Safety Research Group using an approach termed locating errors through network surveillance (LENS). The LENS process was undertaken at Johns Hopkins University and another five centers where three major areas were examined observationally: interactions (communication) between operating room cardiac team members, clinical performance of known quality and safety dependent processes, and ergonomics/safety or human-machine interfaces. While collected data is currently being analyzed, preliminary results reveal over 800 human errors noted in the 40 cases observed. The errors observed are being categorized and taxonomy of errors is being created. Categories used in the FOCUS analysis include: teamwork and communication, compliance with existing protocols, knowledge or supervision, vigilance or situational awareness, equipment failure/design, poor operating room design/ergonomics, handoffs and transport problems, lack of professionalism, and ambiguity of responsibility. FOCUS is an initiative to change practice driven by science. Interventions based upon the observations already underway include efforts to decrease infection, adoption of the aviation concept of the "sterile cockpit", briefing and debriefing, reduction of drug error, and peer-to-peer assessment. The first FOCUS data is sobering and shows tremendous possibility for improvement.

Blood management-issues: the panic of coagulopathic bleeding--is there a rational approach?

Blood management is an evolving field of reducing transfusions of allogeneic blood by maximizing multi-modality therapy to optimize red cell mass, reduce red cell loss, and harvest red cells that would have otherwise been discarded. These techniques are highly dependent upon teams working together. The programs are not just focused upon red cells but also on coagulation therapy. Coagulopathy is at times a difficult complex pathologic conundrum. In cardiac surgery the complexity is added to because of the inflammatory effects of anticoagulation, air/blood interfaces, and inflammation. Patients respond variably due to their own genetic and environmental factors. There can be a rational approach, thereby avoiding panic (a normal fear response) if the clinician utilizes not only the available laboratory technologies existing today but also follows published algorithms for treatment. These technologies with their coexisting algorithms have been widely shown to decrease blood usage, yet not to decrease bleeding. That finding suggests that therapy without such guidance wastes expensive pro-coagulant blood products and produces no advantage (a decrease in bleeding). When a therapy produces no advantage all that it leaves the patient with is the side effects or adverse outcomes. Adverse outcomes from coagulation products are real and sobering.

Tissue oxygenation and microvascular hemodynamics in experimental arterial gas embolism.

Microvascular hemodynamic responses to arterial gas embolism (AGE) and local oxygen tensions (PO2) have never been evaluated in vivo using intravital microscopy. A system was implemented to study AGE in real time using brightfield and phosphorescence microscopy as well as laser-induced microvessel occlusion. Bubble dynamics, microhemodynamics and oxygenation were studied following AGE in 61 microvessels and 41 interstitial spaces from 19 anesthetized rats. AGE was induced by direct air injection into the femoral artery ipsilateral to the studied cremaster muscle. Bubble-induced vaso-occlusion was investigated, and microvascular blood flow redistribution were associated with changes in intravascular and interstitial PO2. Microvascular blood flow as well as intravascular and tissue PO2 decreased after microvascular occlusion following microembolism. However, certain areas did not become fully hypoxic since redistribution of blood allowed oxygen to be supplied by nearby microvessels with blood (or plasma) flow or tissue gas diffusion. A linear correlation between interstitial and intravascular PO2 was found during baseline and after AGE. Because some microvessels remain flowing even after AGE, our observations suggest that intravascular therapeutic agents administered during severe AGE may reach microvascular networks and provide additional oxygenation to tissue areas where blood flow is compromised due to occlusion of some microvessels.