Absolute quantification (ml blood/sec ∗ mm2 tissue) of normal vs. diabetic foot skin microvascular blood perfusion: Feasibility of FM-PPG measurements under clinical conditions.

Fluorescence-mediated photoplethysmography (FM-PPG) is the first routine clinical methodology by which to quantifiably measure tissue blood perfusion in absolute terms (mL blood/sec ∗ mm2 tissue). The FM-PPG methodology has been described in detail previously in this journal (MVR 114, 2017, 92-100), along with initial proof-of-concept measurements of blood perfusion in both ocular and forearm skin tissues. The motivation for the current study was to investigate whether FM-PPG can be used readily and routinely under realistic clinical conditions. The vehicle for doing this was to measure medial foot capillary blood flow, i.e., tissue perfusion, in 7 normal subjects, mean = 6.76 ±â€¯2.29 E-005 mL/(sec ∙ mm2), and lesion-free areas of 8 type-2 diabetic patients with skin ulceration, mean = 4.67 + 3.15 E-005 mL/(sec ∙ mm2). Thus, perfusion in the diabetics was found to be moderately lower than that in the normal control subjects. Earlier skin perfusion measurements in medial forearms of 4 normal subjects, mean = 2.64 + 0.22 E-005 mL/(sec ∙ mm2), were lower than both the normal and diabetic foot perfusion measurements. Variability in the heartbeat-to-heartbeat blood perfusion pulses in the skin capillaries, defined as the ratio of the standard deviation among beat-to-beat pulses divided by the mean perfusion of those pulses, was determined for each subject. Average variability in foot skin was 21% in the diabetic population, versus 16% for normal subjects; and it was 18% in forearm skin. We conclude that absolute quantitative FM-PPG measurement of skin blood perfusion at the level of nutritive capillaries is feasible routinely under clinical conditions, allowing for quantitative measurement of skin tissue blood perfusion in absolute terms.

Platelet function in humans is not altered by hyperbaric oxygen therapy.

A pilot survey of platelet function was performed on 6 patients undergoing hyperbaric oxygen therapy (2.0 ATA O2 for 2 hours, 6 days/week) for prophylaxis against osteoradionecrosis. Blood was drawn immediately prior to and after the first, tenth and twentieth treatment for measurements of platelet aggregation, ATP release and expression of activated alphalIb3 integrin. No significant differences were observed due to hyperbaric oxygen exposures.

Blood flow and ionic responses in the awake brain due to carbon monoxide.

This study examined the effect of 2000 ppm CO on the brain of an awake rat. Measurements of regional perfusion as well as metabolic, ionic and electrical activities were used to examine whether mechanisms responsible for changes in brain perfusion were separable from those attributable to compromises in neuronal metabolism. Exposure to 2000 ppm CO resulted in elevation of cerebral blood flow. The stability of mitochondrial NADH redox level during CO exposure indicated that tissue hypoxia did not develop. The elevation in blood flow was inhibited by L-nitroarginine methyl ester, indicating that nitric oxide was responsible for the CO-induced elevation in blood flow. Exposure to 2000 ppm CO also triggered a significant decrease in pH and rise in extracellular potassium ion, possibly due to ion-pump inhibition. The amplitude of the electrocorticogram wave activity decreased, indicative of a compromise to physiological activity. These changes were not observed in rats anesthetized with pentobarbital during CO exposure, although anesthesia had no effect on the CO-induced elevation in blood flow and there was still no change in mitochondrial NADH redox level. We concluded that CO acts by separate mechanisms to alter cerebral vasoactivity and neuronal metabolic responses and that both processes are independent of hypoxic stress.

Hyperbaric oxygenation affects rat brain function after carbon monoxide exposure.

The application of hyperbaric oxygenation (HBO2) has been recommended for correction of neurological injury in severely CO-poisoned patients. However, the mechanisms of HBO2 action on brain mitochondrial function under the circumstances is not yet understood completely. In the present study, the effect of HBO2 on the rat brain after CO exposure was evaluated by measuring the intramitochondrial NADH and its responses to anoxic test or repetitive induction spreading depression (SD) leading to brain activation. A unique monitoring system for bilateral monitoring of brain NADH redox state was used. Rats were exposed to 3000 ppm CO for 30 (group A) or 60 min (C). In groups B and D, after CO exposure, the rats were exposed to HBO2 (3 atm abs for 30 min). Following CO exposure in groups A and C, a definite decrease in the amplitude of the NADH response and significant increase in the number of waves of NADH was noted during induced cortical SD. Anoxic test in these two groups led to a significant decrease of maximum levels of NADH (reduction) at the end of observation. The amplitude, and the number of SD waves and magnitude of NADH deviation during anoxic test in group B after application of HBO2, was not significantly different from the values measured under the initial conditions. However, in group D, tendency of maintenance of the parameter's initial level was weaker or absent. The results obtained indicated that suppression of brain energy metabolism is a characteristic manifestation of CO poisoning in rats. Restoration of cerebral energy metabolism by adequate dosage of HBO2 may become an important factor for recovery of brain activities after CO poisoning.

[Hyperbaric oxygen inhibits neutrophil infiltration and reduces postischemic brain injury in rats]. / Giperbaricheskii kislorod ingibiruet infil'tratsiiu neitrofilov i oslabliaet postishemicheskoe porazhenie mozga u krys.

Reversible occlusion of the middle cerebral artery (MCA) was used to test hypothesis that hyperbaric oxygen inhibits the neutrophile infiltration into the ischemic brain thus reducing the brain injury. Treatment with hyperbaric oxygen prior to ischemia or during MCA occlusion significantly reduced neutrophile infiltration, motor disorders, and cerebral infarction volume.

Roles for platelet-activating factor and *NO-derived oxidants causing neutrophil adherence after CO poisoning.

Studies were conducted with rats to investigate whether platelet activating factor (PAF) and nitric oxide (*NO)-derived oxidants played roles in the initial adherence of neutrophils to vasculature in the brain after carbon monoxide (CO) poisoning. Before CO poisoning, rats were treated with the competitive PAF receptor antagonist WEB-2170 or with the peroxynitrite scavenger selenomethionine. Both agents caused significantly lower concentrations of myeloperoxidase in the brain after poisoning, indicating fewer sequestered neutrophils. Similarly, both agents reduced the concentration of nitrotyrosine, indicating less oxidative stress due to *NO-derived oxidants. There were no alterations in whole brain homogenate PAF concentration measured by immunoassay and bioassay, nor were there changes in phosphatidylcholine concentration. Immunohistochemical imaging showed PAF to be more heavily localized within perivascular zones after CO poisoning. Neutrophils colocalized with both PAF and nitrotyrosine in brains of rats killed immediately after CO poisoning. We conclude that qualitative changes in brain PAF are responsible for neutrophil adherence immediately after CO poisoning and that activated neutrophils trigger the initial rise in brain nitrotyrosine. Persistent PAF-mediated neutrophil adherence required production of *NO-derived oxidants because when oxidants were scavenged, neutrophil adherence was not maintained.

Smoke inhalation-induced alveolar lung injury is inhibited by hyperbaric oxygen.

Smoke-induced lung injury in rats was assessed in terms of histopathology, gross mortality, neutrophil accumulation and as capillary leak. Administration of hyperbaric oxygen (HBO2), 2.8 atm abs for 45 min, inhibited adhesion of circulating neutrophils subsequent to smoke inhalation. HBO2 reduced pulmonary neutrophil accumulation whether used in a prophylactic manner, 24 h before smoke inhalation, or as treatment immediately after the smoke insult Emphasis was placed on prophylactic administration of HBO2 to avoid the possibility that beneficial effects may be related to hastened removal of carbon monoxide. Based on all parameters tested, smoke inhalation injury was reduced by prophylactic aadministration of HBO2. The beneficial effect appears related to inhibition of neutroophil adhesion to the vasculature.

Carbon monoxide poisoning: interpretation of randomized clinical trials and unresolved treatment issues.

Since hyperbaric oxygen therapy (HBO2) appeared as a treatment for CO poisoning in 1960, whether and when to use it for CO poisoning have often been debated. HBO2 has been advocated to treat severe CO poisoning to limit delayed and permanent neurologic sequelae. Initially, inferences about efficacy were based on clinical experience and uncontrolled studies, but since1989, six prospective clinical trials have been reported comparing HBO2 and normobaric O2 administration to treat patients with acute CO poisoning. Of the six trials, four found better clinical outcomes among patients receiving HBO2 while two have shown no treatment effect. The most recent and best-designed randomized controlled clinical trial, performed in Salt Lake City, supports the efficacy of HBO2 in severe acute CO poisoning in accordance with scientific rationale and clinical experience. However, a number of important issues remain for future investigation, which could be addressed in a large multi-center trial. Such a trial should attempt to determine the optimal number of HBO2 treatments and the maximum treatment delay from CO poisoning for HBO2 to provide efficacy in patients with specific risk factors for a poor outcome.

Carbon monoxide poisoning--a public health perspective.

Carbon monoxide (CO) may be the cause of more than one-half of the fatal poisonings reported in many countries; fatal cases also are grossly under-reported or misdiagnosed by medical professionals. Therefore, the precise number of individuals who have suffered from CO intoxication is not known. The health effects associated with exposure to CO range from the more subtle cardiovascular and neurobehavioral effects at low concentrations to unconsciousness and death after acute or chronic exposure to higher concentrations of CO. The morbidity and mortality resulting from the latter exposures are described briefly to complete the picture of CO exposure in present-day society. The symptoms, signs, and prognosis of acute CO poisoning correlate poorly with the level of carboxyhemoglobin (COHb) measured at the time of hospital admission; however, because CO poisoning is a diagnosis frequently overlooked, the importance of measuring COHb in suspicious settings cannot be overstated. The early symptoms (headache, dizziness, weakness, nausea, confusion, disorientation, and visual disturbances) also have to be emphasized, especially if they recur with a regular periodicity or in the same environment. Complications occur frequently in CO poisoning. Immediate death is most likely cardiac in origin because myocardial tissues are most sensitive to the hypoxic effects of CO. Severe poisoning results in marked hypotension, lethal arrhythmias, and electrocardiographic changes. Pulmonary edema may occur. Neurological manifestation of acute CO poisoning includes disorientation, confusion, and coma. Perhaps the most insidious effect of CO poisoning is the development of delayed neuropsychiatric impairment within 2-28 days after poisoning and the slow resolution of neurobehavioral consequences. Carbon monoxide poisoning during pregnancy results in high risk for the mother by increasing the short-term complication rate and for the fetus by causing fetal death, developmental disorders, and chronic cerebral lesions. In conclusion, CO poisoning occurs frequently; has severe consequences, including immediate death; involves complications and late sequelae; and often is overlooked. Efforts in prevention and in public and medical education should be encouraged.