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PubMed1995

Axial movements of rat mandibular incisors measured under artificial respiration with halothane anaesthesia.

The axial movements of rat incisors were recorded continuously for over 20 h. The rats were anaesthetized with halothane delivered by intratracheal intubation using an artificial respirator. A haemostatic clamp was used to immobilize the jaw and the displacement detector exhibited high resolution, good linearity and low drift. The previously impeded and unimpeded eruption rates (the average extrusive movements) were 406 and 548 microns/24 h, respectively. The previously unimpeded rate was lower than the normal unimpeded rates obtained by other investigators. It appears that the eruptive movement of the previously unimpeded incisor was inhibited by halothane anaesthesia. Circadian rhythm was not observed in the eruption rates of previously impeded or unimpeded incisors. Following the i.p. injection of a lethal dose of pentobarbital sodium, the incisors retracted. The average intrusive movement was significantly greater in the previously impeded group (29 microns) than in the previously unimpeded group (12 microns) at 30 min after the lethal injection. It is assumed that the elimination of the pushing force at death may cause the stretched periodontal fibres to recoil, thereby pulling the tooth in an intrusive direction. It is also likely that the mechanical strength of the ligament is reduced in the previously unimpeded group by repeated shortening of the incisors; therefore the force needed to retract previously unimpeded incisors may be less than that needed to retract previously impeded incisors.

Animals↗

PubMed2005

Aerosolized nanogram quantities of plasmid DNA mediate highly efficient gene delivery to mouse airway epithelium.

The lung is an important target of gene therapeutic interventions. In contrast to intratracheal instillation, inhalation would be the most practical route of administration in clinical applications. Here we show that aerosolized nanogram quantities of pDNA complexed to PEI (350 ng) yielded transfection levels 15-fold higher than a 140-fold higher dose (50 microg) of the same vector applied directly to the lungs of mice via intratracheal intubation. An important efficacy parameter is the osmolarity of the aerosol and not biophysical properties of the nebulized vector. Vectors formulated and nebulized in hypoosmotic distilled water yielded 57- and 185-fold higher expression levels than those in isotonic 5% glucose or Hepes-buffered saline, respectively. Pretreatment of mice with nebulized indomethacin, which prevents water-induced airway alteration, resulted in lower gene expression, whereas pretreatment with EGTA or polidocanol, which modulate tight-junction activity, had no effect. These results, together with histological analysis of regional lung deposition and gene expression, suggest that a temporary water-induced hypoosmotic shock permeabilizes the epithelium sufficiently to allow vector uptake. The so far observed inefficiency of nonviral gene delivery to the airways may be the result of an inappropriate method of vector administration.

Aerosols↗

PubMed1990

Internal jugular phlebectasia in two siblings: manometric and histopathologic studies of the pathogenesis.

Two brothers, 4 years and 6 years of age, presented with a swelling in the right side of the neck. Ultrasonography and venography confirmed a diagnosis of phlebectasia of the right internal jugular vein (IJV). In an attempt to elucidate the etiology of this rare lesion, venous pressures in both the dilated right IJV and in the left IJV were taken under general anesthesia with intratracheal intubation at the time of surgery in each patient. No significant difference in pressure elevation with increase of intrathoracic pressure by overinflating the breathing bag was observed between the right and left IJV, suggesting that there would be no mechanical obstructive process generated on exertion, in each case. Microscopic examinations of a dissected portion of the dilated IJV showed paucity of muscle layer of the vein wall in the younger patient, and absence of that in the elder. Therefore, we assume that congenital muscle defect of the right IJV wall, rather than mechanical obstruction in the lower neck or the mediastinum, might cause phlebectasia. To our knowledge, this is the first report of IJV phlebectasia in siblings.

Child↗

PubMedDate not supplied

Prehospital trauma care in Tehran: potential areas for improvement.

OBJECTIVE: To evaluate the existing prehospital trauma care system in Tehran, Iran. METHODS: This was a cross-sectional study in which all trauma-related dispatches of Tehran's emergency medical services (EMS) system were evaluated-during 18 randomly selected days from September 22,1997, to March 17,1998. Emergency medical technicians completed a checklist for all trauma cases, and the criteria for this performance evaluation were different partial time intervals in each dispatch and different procedures that had been done for the patients. RESULTS: The means of the "dispatch-beginning-to-scene-arrival interval" and "scene-arrival-to-scene-leaving interval" were 10 and 18 minutes, respectively (median: 10 minutes, range 0-55 minutes for the first; and median: 15 minutes, range 1-165 minutes for the second time interval). The mean of the "dispatch-beginning-to-hospital-arrival interval" was 45 minutes (median: 42 minutes, range: 5-170 minutes). Among advanced life support (ALS) procedures that include cardiac monitoring, intratracheal intubation, intravenous fluid therapy, nasogastric tube insertion, defibrillation, and tracheostomy, only intravenous fluid therapy had been administered for the patients. The patients, however, had received different kinds of basic life support (BLS) that include initial evaluation, bleeding control, oxygen administration, splinting, suction use, and cardiopulmonary resuscitation. CONCLUSION: The prolonged response, scene, and dispatch-beginning-to-hospital-arrival intervals compared with those for a developed EMS system indicate one potential area for improvement. Furthermore, significant differences in the field of prehospital care (conducting no ALS procedure) showed that ambulance equipment and training of EMS personnel are two other potential sites for improvement.

Adult↗

PubMed1993

Formation and repair of benzo[a]pyrene-DNA adducts in cultured hamster tracheal epithelium determined by 32P-postlabeling analysis and unscheduled DNA synthesis.

Hamster tracheal organ cultures were used to investigate the relationship between DNA adduct formation measured directly by the 32P-postlabeling assay, and the DNA damage measured indirectly by the unscheduled DNA synthesis (UDS) assay. Hamster tracheas were treated with three concentrations of benzo[a]pyrene (B[a]P) for 2 days. Postlabeling and UDS assays were also carried out a few days after removal of the B[a]P. Furthermore, the types of B[a]P-DNA adducts formed in the in vitro organ culture were qualitatively compared with those formed in vivo after intratracheal intubation of B[a]P attached to Fe2O3 particles. In vivo only one adduct was detected by 32P-postlabeling. This adduct cochromatographed with the trans-addition produce of dG and (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). In vitro, a clear B[a]P-DNA adduct pattern was also found with the 32P-postlabeling assay. Four different adducts were found. The main adduct spot migrated to the same position on the thin-layer chromatogram as the in vivo adduct. B[a]P-DNA adduct formation was both time- and dose-dependent. During the first day after removal of B[a]P the adduct levels still increased, thereafter they decreased at all B[a]P concentrations. A time- and dose-dependent increase in UDS was observed in the tracheal epithelial cells treated with B[a]P in vitro. After removal of the B[a]P, UDS decreased immediately, in contrast to the formation of DNA adducts. The results of the present study show that B[a]P induces time- and dose-dependently both DNA adducts and UDS in hamster tracheal organ culture. Moreover, the main DNA adduct formed in vitro, dG-(+)-anti-BPDE, was the same as that found in vivo.

Animals↗

PubMed1998

Effects of adenosine on cardiopulmonary functions and oxygen-derived variables during endotoxemia.

OBJECTIVES: To determine the effects of a prophylactic intravenous infusion of adenosine on cardiopulmonary functions and oxygen-derived variables in a porcine model of endotoxemia. DESIGN: Prospective, randomized, placebo-controlled, unblinded study. SETTING: University research laboratory. SUBJECTS: Thirty country bred pigs, aged 6 to 7 wks, weighing 24.9 +/- 0.65 (SEM) kg body weight. INTERVENTIONS: Pigs were anesthetized by i.v. pentobarbital and fentanyl, intratracheally intubated, and mechanically normoventilated with a gas mixture of nitrous oxide/oxygen = 1:1. Intravascular catheters were inserted to allow for determination of arterial, central venous blood pressure, pulmonary artery occlusion pressure, cardiac output, and sampling of blood for gas analyses. Group 1 (n = 10) received a 330-min intravenous infusion of Salmonella abortus equi endotoxin (5 microg/kg body weight x hr). Group 2 (n = 10) received an additional intravenous infusion of adenosine (150 microg/kg body weight x min), started 30 mins before the infusion of endotoxin. Control groups 3 and 4 (n = 5 for both groups) received adenosine or physiologic saline, respectively. MEASUREMENTS AND MAIN RESULTS: Parameters of cardiopulmonary function and oxygen-derived variables were calculated from pulmonary artery catheter measurements and blood gas analyses using standard formula. Plasma concentrations of purine compounds (adenosine, inosine, hypoxanthine) were determined by high-performance liquid chromatography. Since tumor necrosis factor-alpha plays a central role in the development of endotoxic shock, concentrations of this cytokine were determined in serum by enzyme-linked immunosorbent assay. Infusion of adenosine before the beginning of the infusion of endotoxin increased plasma concentrations of the nucleoside from 193 +/- 72 to 553 +/- 65 nmol/L and decreased the systemic vascular resistance by 50%. Although acting as a potent vasodilator under control conditions, adenosine did not aggravate the arterial hypotension elicited by endotoxemia but significantly increased cardiac output by a comparably small decrease in systemic vascular resistance, prevention of pulmonary vasoconstriction, and improvement of left ventricular performance. Despite significant pulmonary vasodilation, gas exchange was not worsened but slightly improved by adenosine. With the increase in cardiac output and arterial oxygenation, systemic oxygen delivery almost doubled. This adenosine-induced oxygen flux was not a surplus but was most likely utilized by tissues, as suggested by the much earlier beginning of the increase in the systemic oxygen consumption and the attenuation of the decrease in the gastric mucosal pHi. No effects of adenosine were observed on the endotoxin-induced increase in serum concentrations of tumor necrosis factor-alpha. CONCLUSIONS: Infusion of adenosine might be useful to improve flow-dependent oxygen delivery and tissue oxygenation during endotoxic shock without the induction of adverse cardiopulmonary side effects. The beneficial hemodynamic effects of adenosine appear not to be mediated by the inhibition of the release of tumor necrosis factor-alpha.

Adenosine↗

PubMedDate not supplied

CT demonstration of massive cerebral air embolism from pulmonary barotrauma due to cardiopulmonary resuscitation.

A 77-year-old man with loss of consciousness, circulatory collapse, and apnea caused by myocardial infarction underwent cardiopulmonary resuscitation with intratracheal intubation and manual bag ventilation. Computed tomography of the head demonstrated massive air embolism in the entire cerebral circulation. The patient was diagnosed as brain dead the next day. Demonstration of massive cerebral air embolism on head CT is presented.

Aged↗

PubMed2005

Epilepsy in Wolf-Hirschhorn syndrome (4p-).

PURPOSE: We investigated the evolution of epilepsy, seizure types, and effective drugs in Wolf-Hirschhorn syndrome, which is a malformation syndrome often with refractory seizures and status epilepticus. METHODS: We reviewed 11 cases of Wolf-Hirschhorn syndrome (age range, 2-25 years; SD, 7.2 years) and who were treated in Osaka University or Osaka Medical Center of Research Institute for Maternal and Child Health. RESULTS: In all patients, febrile or afebrile convulsions had developed. Epileptic seizures included alternative hemiconvulsions, generalized tonic-clonic seizures, focal clonic seizures, tonic seizures, and epileptic spasms. Seizures were often induced by a high fever or a hot bath. Status epilepticus occurred in all patients, including one patient who died at the first status epilepticus. In some cases, intratracheal intubation was needed because of respiratory insufficiency. The effective antiepileptic drugs for long-term use were sodium bromide (four of four), followed by clorazepate (CLP; one of two), and nitrazepam (NZP; two of four). Sodium bromide was particularly effective for preventing status epilepticus. The mean age of last status epilepticus in patients receiving sodium bromide (1 year 8 months) was significantly younger than that in those not treated with sodium bromide (3 year 4 months). CONCLUSIONS: We identified that, in most patients of Wolf-Hirschhorn syndrome, the frequency of both seizures and status epilepticus decreased gradually after age 5 years. However, during infancy, status epilepticus sometimes resulted in permanent disability or even death. We propose that sodium bromide should be used as the initial treatment for the prevention of the development of status epilepticus associated with Wolf-Hirschhorn syndrome.

Abnormalities, Multiple↗

PubMed1992

Disodium cromoglycate in the treatment of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) has become the most common form of chronic lung disease in the neonate. Recently, we have experienced a severe case of BPD and examined the effect of disodium cromoglycate (DSCG) on BPD. The gestational age and birthweight of the patient were 27 weeks and 1,000 g, respectively. Although RDS subsided after surfactant replacement therapy, the arterial-alveolar oxygen tension ratio (a/APO2) gradually decreased and FiO2 increased with age, respectively, and pure oxygen supplementation was eventually required after 67 days of life. The DSCG treatment was commenced at 80 days of life. After 6 days of the inhalation therapy, a/APO2 gradually increased. After 10 days of the treatment, the baby was extubated. While the baby was intubated, intratracheal lavage fluid samples were obtained. Eosinophilic cationic protein (ECP) and polymorphonuclear (PMN) elastase concentrations were determined. ECP and PMN elastase concentrations of intratracheal lavage fluids gradually decreased with the DSCG treatment. These results may indicate that DSCG has led to an improvement of pulmonary function and facilitated weaning from mechanical ventilation in an infant with BPD.

Bronchoalveolar Lavage Fluid↗

PubMedDate not supplied

Characterization of Pneumocystis carinii preparations developed for lipid analysis.

Pneumocystis carinii organisms were isolated from viral antibody-negative rats that had been infected by intratracheal intubation of organism preparations tested negative for common bacteria and fungi. Infection scores of lungs from infected animals at the time of parasite isolation was > 5 (100-1,000 organisms/oil immersion field). Electron microscopy of heavily infected lungs revealed that the pathogens adhered to Type I pneumocytes and to each other, resulting in obstructions up to several cell layers thick, which extended into the alveolar lumen. Protocols for purifying the organisms were developed to optimize separation from each other and from host cells, and to optimize preparation purity, recovery efficiency, and organism viability. The study tested mucolytic agents, sieving, various centrifugation speeds, lysis of host cells by osmotic shock and filtration through membranes of different pore diameter. Final preparations contained no intact host cells as determined by light microscopy. Only minor amounts (< 5%) of host debris were detected by electron microscopy. Most organisms and their pellicles were ultrastructurally intact but no longer adhered to one another. The final preparation was characterized biochemically by quantitation of the specific lung surfactant marker surfactant protein A, which indicated > 99.5% purity. The total non-P. carinii protein in the final preparation (< 6%, depending on the level of infection) was estimated by the protein content of pelletable material resulting from processing uninfected lungs in an identical manner. Elimination of free cholesterol and phospholipids from host lung tissue was monitored during the purification process. Exogenous stigmasterol, added as an extracellular marker, decreased during the purification process and was undetectable in the final organism preparation. Yields of 10(8)-10(9) organisms/rat were routinely obtained. Viability, assessed by the calcein acetoxymethyl ester-propidium iodide assay, was 80-95%.

Animals↗

PubMed1989

Intratracheal exposure of rats to Aspergillus fumigatus spores isolated from sawmills in Sweden.

Five strains of Aspergillus fumigatus (A, B, D, H, and K) isolated from sawmills were used to expose groups of three rats by intratracheal intubation. The dose was 10(9) spores per rat. At 48 h after administration, two rats from the D group and all rats from the K group died with symptoms of strong dyspnea and tachypnea. At 72 h postadministration and after, some animals showed mild to moderate dyspnea and tachypnea. Autopsies of all animals were performed, including a histopathological examination of the lungs. At 72 h after administration, two distinct morphological groups were identified histopathologically. Severe necrotizing pneumonia characterized by the presence of abundant fungal hyphae was seen in animals that died spontaneously within 48 h postadministration and rats with bronchopneumonia and was characterized by the presence of numerous fungal spores. There was an obvious difference in pathogenicity among the strains of A. fumigatus. Strains D and K were more pathogenic, and only the rats exposed to these strains showed the presence of fungal hyphae in the lungs. The mycotoxin gliotoxin that is produced by A. fumigatus and has antiphagocytic activity was not detected in the spores from any of the A. fumigatus strains.

Animals↗

PubMed1992

Percutaneous trigeminal rhizotomy and percutaneous cordotomy under general anesthesia.

Most percutaneous procedures for the treatment of pain are done under local anesthesia and considerable pain can be involved. If the patient is elderly or confused because of severe pain, it is difficult or impossible to perform these procedures successfully. We treated 3 elderly patients with trigeminal neuralgia and 1 patient with severe bone pain due to metastatic osteosarcoma in the lumbosacral region by percutaneous trigeminal rhizotomy and percutaneous cordotomy under general anesthesia with intratracheal intubation. We conclude that percutaneous trigeminal rhizotomy and percutaneous cordotomy can be safely done under general anesthesia.

Aged↗

PubMed1997

Recent progress in treating patients with cleft palate.

Over the last 4 decades remarkable progress has been made in the treatment of cleft palate: the rate of attaining normal or nearly normal speech after surgery has risen from about 65% 40 years ago to nearly 90% or more nowadays. One of the main factors is intratracheal intubation anesthesia that has made the surgery much safer and easier. Improved surgical technique and speech therapy also played a great role. This paper deals with two problems: (1) Slight velopharyngeal incompetence: The combined use of fiberscopy and fluorovideoscopy can provide useful information as to: (a) the exact place of the faulty articulation, (b) the detailed pattern of inconsistent velopharyngeal function, (c) changes in articulation induced by speech therapy, and (d) the relation between velopharyngeal function and faulty articulation. All the above information greatly facilitates speech therapy for cleft palate speech. It should be done with utmost care though due to possible adverse effects of radiation. (2) Analysis of faulty articulation. It was revealed that faulty articulations such as laryngeal fricative and affricates, pharyngeal stop, and glottal stop in cleft palate speech, secondary to velopharyngeal incompetence, were produced by articulation in the larynx at various sites such as the epiglottis, arytenoids, aryepiglottic folds and vocal folds. These faulty articulation points were located lower than supposed on the basis of auditory perception.

Adolescent↗

PubMed2001

Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.

UNLABELLED: Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention. KEYWORDS: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects

Administration, Topical↗

PubMed1998

[A method of measuring eruptive movement of the rat incisor using a non-contacting displacement detector].

The axial movements of rat incisors were recorded continuously for over 20 hr. The rats were anesthetized with halothane delivered by intratracheal intubation using an artificial respirator. A hemostatic clamp was used to immobilize the jaw. The displacement detector that detects changes in the electric eddy current exhibited high resolution, good linearity and low drift. The average eruption rates of the rat incisor were estimated to be 406 and 516 microns/ 24 hr at 34 and 37 degrees C of the rectal temperature, respectively. The values were within the normal range. We also measured the force needed to restrain eruptive movement of the rat incisor using the same apparatus combined with a load cell. The maximum pushing force was estimated to be 9 mN or 29 mmHg (converted value) on average. Then the effects of adrenaline on axial movement of the incisor and arterial blood pressure were examined. Adrenaline caused a rapid extrusive tooth movement with a nearly simultaneous increase in the blood pressure, followed by a marked intrusive tooth movement and a decrease in blood pressure. These results support the view that the systemic arterial blood pressure and vasculature in the tooth socket play important roles to determine the position of teeth. We assume that our method would be useful to clarify the precise relationship between tooth displacement and vascular change in the tooth socket.

Alveolar Process↗

PubMed2000

Video-assisted contralateral treatment for bronchial stump diastasis after left pneumonectomy.

Postoperative bronchial stump failure is a life-threatening complication, and several surgical approaches and procedures have been developed to close the stump. In this report, we describe a case of left mainstem bronchial stump diastasis after pneumonectomy for lung cancer, in which the bronchial stump was re-closed using a contralateral approach with video-assisted thoracic surgery, with good success. The left main bronchus was closed with an automatic stapler device, but the stump reopened and left pyothorax developed postoperatively. Emergent intratracheal intubation and ventilation was required due to rapid progression of right pyothorax. Under strict nutritional management by IV hyperalimentation, administration of antibiotics to which the organisms were sensitive, and drainage, the patient recovered from pneumonia. However, thoracic air leak increased daily, and reoperation for bronchial diastasis was performed. Using this approach, the left main bronchus near the carina was easily exposed extrapleurally, with only the azygos vein being incised. Video-assisted contralateral treatment was effective in avoiding sternal osteomyelitis due to a transpericardial approach via median sternotomy in the case of mainstem bronchial stump failure, only after left pneumonectomy.

Bronchi↗

PubMed2000

[A patient with life-threatening giant hematoma caused by acquired inhibitor to factor VIII].

A 66-year-old non-hemophiliac man developed widely spreaded hematoma in soft tissues around neck. On the day of admission, he was nearly choked by the giant hematoma which markedly compressed trachea. Initially, to keep air way, an intratracheal intubation using a fiber scope was carried out. Coagulation studies revealed a marked prolongation of activated partial thromboplastin time (129 seconds, control: 24.9-33.2), a diminished activity of factor VIII (less than 1%) and a significant increase of factor VIII inhibitor titer (60 Bethesda unit/ml). We thereby diagnosed coagulopathy related to acquired inhibitor against factor VIII. The general combination therapy of intravenous infusion of both prothrombin complex concentrates and activated prothrombin complex concentrates, prednisolone and plasma exchange successfully stopped expansion of the giant hematoma. However, because the titer of factor VIII inhibitor remained increased and the activity of factor VIII was continued to reduced, cyclosporin was additionally administrated. As a result, the titer of factor VIII inhibitor was markedly improved, but the reduced activity of factor VIII was continued and re-bleeding around neck was observed. We thereby administered steroid pulse therapy, which resulted in complete remission of the disease activity and recovery of factor VIII activity.

Aged↗

PubMed1997

Effect of liposome encapsulated hemoglobin "neo red cells" on severe hemorrhagic shock.

We induced shock by exsanguination and administered Neo Red Cells (NRC) after 30 minutes to experimentally examine the efficacy of NRC on severe shock with respect to hemodynamics and oxygen transport capacity. Seven beagles were used for this experiment. After intravenous anesthesia, intratracheal intubation was performed, and inhalation of 50% oxygen was administered. Animals were exsanguinated through a vein at a rate of 30 mL/min. Animals showing systolic blood pressure of 60 to 69 mmHg were regarded as being in shock. After animals were left untreated for 30 minutes, NRC was administered. This was then repeated. Administration of NRC at a 1.5-fold dose compared to the exsanguinated blood volume was required for animals to recover from shock. Animals tolerated shock 3 times, but did not recover from the 4th shock. Although NRC with approximately one third the viscosity of whole blood was administered, vascular resistance was increased and cardiac output was decreased, resulting in progression of heart failure. In addition, oxygen consumption increased with shock. NRC satisfied oxygen requirements by compensating for the decrease in cardiac output with an increase in AV difference, but erythrocytes were insufficient to increase difference in arterial and venous oxygen content (AV difference), and did not supply sufficient volume of oxygen.

Alkaline Phosphatase↗