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Objective To discuss how hypoxaemia might be harmful and why horses are particularly predisposed to developing it, to review the strategies that are used to manage hypoxaemia in anaesthetized horses, and to describe how successful these strategies are and the adverse effects associated with them. Databases used Google Scholar and PubMed, using the search terms horse, pony, exercise, anaesthesia, hypoxaemia, oxygen, mortality, morbidity and ventilation perfusion mismatch. Conclusions Although there is no evidence that hypoxaemia is associated with increased morbidity and mortality in anaesthetized horses, most anaesthetists would agree that it is important to recognise and prevent or treat it. Favourable anatomical and physiological adaptations of a horse for exercise adversely affect gas exchange once the animal is recumbent. Hypoxaemia is recognised more frequently in horses than in other domestic species during general anaesthesia, although its incidence in healthy horses remains unreported. Management of hypoxaemia in anaesthetized horses is challenging and often unsuccessful. Positive pressure ventilation strategies to address alveolar atelectasis in humans have been modified for implementation in recumbent anaesthetized horses, but are often accompanied by unpredictable and unacceptable cardiopulmonary adverse effects, and some strategies are difficult or impossible to achieve in adult horses. Furthermore, anticipated beneficial effects of these techniques are inconsistent. Increasing the inspired fraction of oxygen during anaesthesia is often unsuccessful since much of the impairment in gas exchange is a direct result of shunt. Alternative approaches to the problem involve manipulation of pulmonary blood away from atelectatic regions of the lung to better ventilated areas. However, further work is essential, with particular focus on survival associated with general anaesthesia in horses, before any technique can be accepted into widespread clinical use. [ABSTRACT FROM AUTHOR]

Introduction Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of β-cells and in experimental animal research. Exendin-4 can be radiolabeled with 68 Ga, 111 In or 99m Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic β-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D). The compound, which is administered subcutaneously (SC) may cause nausea, vomiting and a minor increase in the heart rate (HR). However, possible side-effects on cardiovascular functions after intravenous (IV) administration have not been reported. This study describes the Exendin-4 dose at which cardiovascular side-effects occur in pigs and cynomolgus monkeys. The IV effect of the tracer on insulin secretion is also investigated in pigs. Methods Seven clinically healthy littermate pigs (40 days old) were used; three of them were made diabetic by streptozotocin (STZ). All pigs underwent PET imaging under general anesthesia to examine the glucagon-like peptide-1 receptor (GLP-1R) in β-cells with radiolabeled Exendin-4. A baseline tracer dose IV [ 68 Ga]Exendin-4 (0.025 ± 0.010 μg/kg) followed by a competition dose IV [ 68 Ga]Exendin-4 (3.98 ± 1.33 μg/kg) 60 min later were administered. Blood samples were taken and analyzed for insulin secretion by using ELISA. Cardiovascular and respiratory variables were monitored throughout the experiment. Results Immediately after administration of the high dose [ 68 Ga]Exendin-4 the HR rose from 122 ± 14 to 227 ± 40 bpm (p < 0.01) and from 100 ± 5 to 181 ± 13 bpm (p < 0.01) in healthy non-diabetic and diabetes-induced pigs, respectively. The tachycardia was observed for > 2 h and one healthy non-diabetic pig suffered cardiac arrest 3 h after the IV [ 68 Ga]Exendin-4. Arrhythmia was detected by listening to the heart with a stethoscope up to 4 days after the [ 68 Ga]Exendin-4 injection. In all animals, no effect on the cardiovascular system was registered after the low dose of IV [ 68 Ga]Exendin-4. Insulin secretion increased (p < 0.05) when IV [ 68 Ga]Exendin-4 was given in dosages ≥ 0.14 μg/kg. Conclusions Intravenous administration of ≥ 2.8 μg/kg [ 68 Ga]Exendin-4 resulted in severe tachycardia and arrhythmias in healthy non-diabetic and diabetes-induced pigs, and the insulin secretion was stimulated in healthy non-diabetic animals when ≥ 0.14 μg/kg [ 68 Ga]Exendin-4 was given. [ABSTRACT FROM AUTHOR]

Objective The study aimed to investigate the effect of varying pulse lengths of inhaled nitric oxide (iNO), and 2.5 hours of continuous pulse-delivered iNO on pulmonary gas exchange in anaesthetized horses. Study Design Experimental study. Animals Six Standardbred horses. Methods Horses received acepromazine, detomidine, guaifenesin, thiopentone and isoflurane in oxygen, were positioned in dorsal recumbency and were breathing spontaneously. iNO was on average pulsed during the first 20, 30, 43 or 73% of the inspiration in 15 minute steps. The pulse length that corresponded to the highest (peak) partial pressure of arterial oxygen (PaO2) in the individual horses was determined and delivered for a further 1.5 hours. Data measured or calculated included arterial and mixed venous partial pressures of O2 and CO2, heart rate, respiratory rate, expired minute ventilation, pulmonary and systemic arterial mean pressures, cardiac output and venous admixture. Data (mean ± SD) was analysed using anova with p < 0.05 considered significant. Results Although the pulse length of iNO that corresponded to peak PaO2 varied between horses, administration of all pulse lengths of iNO increased PaO2 compared to baseline. The shortest pulse lengths that resulted in the peak PaO2 were 30 and 43% of the inspiration. Administration of iNO increased PaO2 (12.6 ± 4.1 kPa [95 ± 31 mmHg] at baseline to a range of 23.0 ± 8.4 to 25.3 ± 9.0 kPa [173 to 190 mmHg]) and PaCO2 (8.5 ± 1.2 kPa [64 ± 9 mmHg] to 9.8 ± 1.5 kPa [73 ± 11 mmHg]) and decreased venous admixture from 32 ± 6% to 25 ± 6%. The increase in PaO2 and decrease in venous admixture was sustained for the entire 2.5 hours of iNO delivery. Conclusions The improvement in arterial oxygenation during pulsed delivery of iNO was significant and sustained throughout 2.5 hours of anaesthesia. Clinical relevance Pulsed iNO potentially could be used clinically to counteract hypoxemia in anaesthetized horses. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effects of meloxicam on renal function in dogs anaesthetized and rendered hypotensive with acepromazine-thiopental-isoflurane. Animals Eight healthy beagles, four males and four females, 25.6 ± 19.3 months old and weighing 12.8 ± 2.0 kg. Materials and methods Either meloxicam suspension at a dose of 0.133 mL kg−1 (0.2 mg kg−1) or 0.133 mL kg−1 saline solution (control), were given by mouth (PO) in a randomized, cross-over fashion. The treatment or control was given 3 hours before anaesthesia. Dogs were sedated with intramuscular acepromazine 0.1 mg kg−1. Anaesthesia was induced with intravenous thiopental, followed by tracheal intubation and maintenance with isoflurane in oxygen and air, delivered using a semi-closed breathing system. Renal function was quantified using serum biochemistry, urinalysis and glomerular filtration rate measured by scintigraphy. Analysis of variance or Friedmananova were used for statistical analysis. Results Values (mean ± SD) for mean arterial blood pressure did not differ significantly between treatments but was low (54 ± 7 mmHg) during anaesthesia. Glomerular filtration rate did not differ significantly between treatments or over time, and results of urine and serum analysis were within reference ranges after meloxicam treatment. Conclusions and clinical relevance Meloxicam caused no adverse effects on renal function when given to healthy dogs anaesthetized and rendered hypotensive with acepromazine, thiopental and isoflurane. [ABSTRACT FROM AUTHOR]

Objectives To compare pulmonary function and gas exchange in anaesthetized horses during and after breathing either O2-rich gas mixtures or air. Animals Six healthy standard bred trotters (age range 3–12 years; mass range 423–520 kg), four geldings and two mares. Study design Randomized, cross-over experimental study. Methods Horses were anaesthetized on two occasions with tiletamine-zolazepam after pre-anaesthetic medication with acepromazine, romifidine and butorphanol. After endotracheal intubation and positioning in left lateral recumbency, animals were allowed to breathe spontaneously. One of two, randomly allocated inspired gas treatments was provided: either i) room air (fractional concentration of inspired O2 [F IO2] = 0.21) provided throughout anaesthesia; or ii) an O2-rich gas mixture (F IO2 = >0.95) for 15 minutes, followed by room air. The alternative treatment was delivered at the second anaesthetic. Respiratory and haemodynamic variables and the distribution of ventilation-perfusion (VA/Q) ratios (using the multiple inert gas elimination technique) were determined in the standing conscious horse (baseline) after sedation and during anaesthesia. Results Breathing O2-rich gas was associated with a decreased respiratory rate ( p = 0.015) increased PaCO2 ( p < 0.001) and increased PaO2 ( p = 0.004) compared with breathing air. All horses developed intrapulmonary shunt during anaesthesia, but shunt was significantly greater (13 ± 5%) when O2-rich gas was delivered compared with air breathing (5 ± 2%; p = 0.013). Ten minutes after O2-rich gas was replaced by air, shunt remained larger in horses that had initially received oxygen compared with those breathing air ( p = 0.042). Mixed venous oxygen tensions were significantly lower during sedation than at baseline ( p < 0.001) and during anaesthesia ( p < 0.001). Conclusions During dissociative anaesthesia, arterial oxygenation was greater when horses breathed gas containing more than 95% oxygen, compared with when they breathed air. However, breathing O2-rich gas increased intrapulmonary shunt and caused hypoventilation. The intrapulmonary shunt created during anaesthesia by high inspired O2 concentrations remained larger when F IO2 was reduced to 0.21, indicating that absorption atelectasis produced during O2-rich gas breathing persisted throughout anaesthesia. Clinical relevance In healthy horses undergoing short-term dissociative anaesthesia, air breathing ensures a level of oxygen delivery that meets tissue demand. There is no benefit to horses in breathing O2-rich gas after the gas supply is discontinued. On the contrary, the degree of shunt induced by breathing O2-rich gas persists. The clinical relevance of this during recovery requires investigation. [ABSTRACT FROM AUTHOR]

To compare the effects of spontaneous breathing and mechanical ventilation on haemodynamic variables, including muscle and skin perfusion measured with laser Doppler flowmetery, in horses anaesthetized with isoflurane.Prospective controlled study.Ten warm-blood trotter horses (five males, five females). Mean mass was 492 kg (range 420–584 kg) and mean age was 5 years (range 4–8 years).After pre-anaesthetic medication with detomidine (10 μg kg−1) anaesthesia was induced with intravenous (IV) guaifenesin and thiopental (4–5 mg kg−1 IV) and maintained using isoflurane in oxygen. The horses were positioned in dorsal recumbency. In five animals breathing was initially spontaneous (SB) while the lungs of the other five were ventilated mechanically using intermittent positive pressure ventilation (IPPV). Total anaesthesia time was 4 hours with the ventilatory mode changed after 2 hours. During anaesthesia, heart rate (HR) cardiac output (&Qdot;t) stroke volume (SV) systemic arterial blood pressures (sAP), and pulmonary arterial pressure (pAP) were recorded. Peripheral perfusion was measured in the semimembranosus and gluteal muscles and on the tail skin using laser Doppler flowmetry. Arterial (a) and mixed venous (&vmacr;) blood gases, pH, haemoglobin concentration [Hb], haematocrit (Hct), plasma lactate concentration and muscle temperature were measured. Oxygen content, venous admixture (&Qdot;s/&Qdot;t) oxygen delivery (DO2) and oxygen consumption (&Vdot;O2) were calculated.During mechanical ventilation, HR, sAP, pAP,&Qdot;t, SV,&Qdot;s/&Qdot;tand PaCO2 were lower and PaO2 was higher compared with spontaneous breathing. There were no differences between the modes of ventilation in the level of perfusion, DO2,&Vdot;O2, [Hb], (Hct), or plasma lactate concentration. After the change from IPPV to SB, left semimembranosus muscle and skin perfusion improved, while muscle perfusion tended to decrease when SB was changed to IPPV. Low-frequency flow motion was seen twice as frequently during IPPV compared with SB.Mechanical ventilation impaired cardiovascular function compared with SB in horses during isoflurane anaesthesia. Muscle and skin perfusion changes occurred with ventilation, although further studies are needed to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

To study pulmonary gas exchange and cardiovascular responses to sedation achieved with romifidine and butorphanol (RB) alone, or combined with acepromazine, and during subsequent tiletamine–zolazepam anaesthesia in horses.Six (four males and two females) healthy Standardbred trotters aged 3–12 years; mass 423–520 kg.Randomized, cross-over, experimental study.Horses were anaesthetized on two occasions (with a minimum interval of 1 week) with intravenous (IV) tiletamine–zolazepam (Z; 1.4 mg kg−1) after pre-anaesthetic medication with IV romifidine (R; 0.1 mg kg−1) and butorphanol (B; 25 µg kg−1 IV). At the first trial, horses were randomly allocated to receive (protocol ARBZ) or not to receive (protocol RBZ) acepromazine (A; 35 µg kg−1) intramuscularly (IM) 35 minutes before induction of anaesthesia. Each horse was placed in left lateral recumbency and, after tracheal intubation, allowed to breathe room air spontaneously. Respiratory and haemodynamic variables and ventilation–perfusion (; multiple inert gas elimination technique) ratios were determined in the conscious horse, after sedation and during anaesthesia. One- and two-way repeated-measuresanovawere used to identify within- and between-technique differences, respectively.During sedation with RB, arterial oxygen tension (PaO2) decreased compared to baseline and increasedmismatch was evident; there was no O2 diffusion limitation or increase in intrapulmonary shunt fraction identified. With ARB, PaO2 andremained unaffected. During anaesthesia, intrapulmonary shunt occurred to the same extent in both protocols, andmismatching increased. This was less in the ARBZ group. Arterial O2 tension decreased in both protocols, but was lower at 25 and 35 minutes of anaesthesia in RBZ than in ARBZ. During sedation, heart rate (HR) and cardiac output (&Qdot;t) were lower while arterial-mixed venous oxygen content differences and haemoglobin concentrations were higher in RBZ compared with ARBZ. Total systemic vascular resistance, mean systemic, and mean pulmonary arterial pressures were higher during anaesthesia with RBZ compared to ARBZ.Acepromazine added to RB generally improved haemodynamic variables and arterial oxygenation during sedation and anaesthesia. Arterial oxygenation was impaired as a result of increased shunt andmismatch during anaesthesia, although acepromazine treatment reduceddisturbances and falls in PaO2 to some extent. Haemodynamic variables were closer to baseline during sedation and anaesthesia when horses received acepromazine. Acepromazine may confer advantages in healthy normovolaemic horses. [ABSTRACT FROM AUTHOR]

Abstract Objectives To study in horses (1) the relationship between cardiovascular variables and muscle perfusion during propofol–ketamine anaesthesia, (2) the physiological effects of a single intravenous (IV) detomidine injection, (3) the metabolic response of muscle to anaesthesia, and (4) the effects of propofol–ketamine infusion on respiratory function. Study design Prospective experimental study. Animals Seven standardbred trotters, 5–12 years old, 416–581 kg. Methods Anaesthesia was induced with intravenous (IV) guaifenesin and propofol (2 mg kg-1 ) and maintained with a continuous IV infusion of propofol (0.15 mg kg-1 minute-1 ) and ketamine (0.05 mg kg-1 minute-1 ) with horses positioned in left lateral recumbency. After 1 hour, detomidine (0.01 mg kg-1 ) was administered IV and 40–50 minutes later anaesthesia was discontinued. Cardiovascular and respiratory variables (heart rate, cardiac output, systemic and pulmonary artery blood pressures, respiratory rate, tidal volume, and inspiratory and expiratory O2 and CO2 ) and muscle temperature were measured at pre-determined times. Peripheral perfusion was measured continuously in the gluteal muscles and skin using laser Doppler flowmetry (LDF). Muscle biopsy samples from the left and right gluteal muscles were analysed for glycogen, creatine phosphate, creatine, adenine nucleotides, inosine monophosphate and lactate. Arterial blood was analysed for PO2 , PCO2 , pH, oxygen saturation and HCO3 . Mixed venous blood was analysed for PO2 , PCO2 , pH, oxygen saturation, HCO3 , cortisol, lactate, uric acid, hypoxanthine, xanthine, creatine kinase, creatinine, aspartate aminotransferase, electrolytes, total protein, haemoglobin, haematocrit and white blood cell count. Results Circulatory function was preserved during... [ABSTRACT FROM AUTHOR]

Pain treatment of lactating bitches is a clinically relevant, but complicated issue. Published scientific studies regarding the excretion of drugs in canine milk are scarce. When considering the risk of side effects in their offspring, lactating bitches have traditionally received very restricted analgesic and anti-inflammatory therapy. Our aim was to quantify the concentrations of carprofen in milk from lactating bitches and relate those to potential risks for the puppies. A second aim was to evaluate the impact mastitis may have on the concentration of carprofen in milk. A population of 100 bitches was enrolled in the study, among which 88 were bitches treated with carprofen after cesarean section (Group CS), eight were bitches with painful inflammatory conditions (Group I) and four were bitches with mastitis (Group M). The patients enrolled in the study received carprofen 4 mg/kg sc at day 1 followed by 2 mg/kg po every 12 h for the following 2–5 days. Owners were instructed to collect milk once a day for five days. The concentration of carprofen in the milk was quantified with ultra-performance liquid chromatography-tandem mass spectrometry. The data obtained were statistically analyzed as repeated-measures data with a mixed-model approach. Data were used to calculate the theoretical maximum total daily intake of carprofen by the puppies in order to perform a computerized simulation of the plasma concentration of carprofen in the puppies. Follow-up telephone interviews to check the status of the enrolled bitches and their litters occurred at one week and three-six months after treatment with carprofen. The major finding of the study was that the concentration of carprofen in the milk was <700 ng/mL from bitches undergoing CS or suffering painful conditions other than mastitis. In comparison, administration of 2 mg/kg of carprofen sc or po to adult dogs, results in mean maximal plasma concentrations of 19480 ± 5420 ng/mL (mean ± SD). Moreover, data suggests that inflammation of the mammary gland results in a higher concentration of carprofen in milk (up to 1300 ng/mL). In the computerized simulation, the plasma concentrations of carprofen in puppies in group CS and in group I are one tenth of the concentration in adult dogs receiving carprofen at standard doses. Considering the low excretion into milk, carprofen provides an analgesic alternative to lactating bitches without mastitis. • Little is known about the excretion of drugs in canine milk, leading to restrictive analgesic policy in lactating bitches. • Carprofen is regularly prescribed for the treatment of postoperative pain in dogs. • Concentration of carprofen in the milk of lactating bitches was <700 ng/ml after administration of standard clinical doses. • In the milk of bitches with mastitis the concentration was higher, reaching a maximum of 1300 ng/ml. • Treating lactating bitches free from mastitis with carprofen for a short period is most likely safe for nursing offspring. [ABSTRACT FROM AUTHOR]

Objectives Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion ( [ABSTRACT FROM AUTHOR]

Objective To assess oxygenation, ventilation-perfusion (V/Q) matching and plasma endothelin (ET-1) concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse-delivered inhaled nitric oxide (iNO). Study Design Prospective experimental trial. Animals Healthy adult Standardbred horses. Methods Horses were anaesthetized with isoflurane in oxygen and placed in lateral recumbency. Six control (C group) horses were anaesthetized without iNO delivery and six horses received pulse-delivered iNO (NO group). After 2.5 hours of anaesthesia isoflurane and iNO were abruptly discontinued, inhaled oxygen was reduced from 100% to approximately 30%, and the horses were moved to the recovery stall. At intervals during a 30-minute period following the discontinuation of anaesthesia, arterial and mixed venous blood gas values, shunt fraction ( Q̇s/Q̇t), plasma ET-1 concentration, pulse rate and respiratory rate were measured or calculated. Repeated measures anova and a Bonferroni post hoc test was used to analyze data with significance set at p < 0.05. Results At all time points in the recovery period, NO horses maintained better arterial oxygenation (oxygen partial pressure: NO 13.2 ± 2.7-11.1 ± 2.7 versus C 6.7 ± 1.1-7.1 ± 1.1 kPa) and better V/Q matching ( Q̇s/Q̇t NO 0.23 ± 0.05-0.14 ± 0.06 versus C 0.48 ± 0.03-0.32 ± 0.08%) than C horses. Mixed venous oxygenation was higher in NO for 25 minutes following the discontinuation of anaesthesia (NO 6.3 ± 0.2-4.5 ± 0.07 versus C 4.7 ± 0.6-3.7 ± 0.3 kPa). In both groups of horses arterial oxygenation remained fairly stable; venous oxygenation declined over this time period in the NO group but still remained higher than venous oxygen in the C group. ET-1 concentrations were higher at most time points in C than NO. Changes in other parameters were either minor or absent. Conclusions and Clinical Relevance Delivery of iNO to healthy horses during anaesthesia results in better arterial and venous oxygenation and V/Q matching (as determined by lower Q̇s/ Q̇t) and lower ET-1 concentrations throughout a 30-minute anaesthetic recovery period. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effects of preoperative extradural morphine on the end-tidal isoflurane (Fe′ISO) concentration and on physiological variables in pigs undergoing abdominal surgery. Study design Prospective, randomized, blinded study. Animals Fourteen healthy pigs (20 ± 4 kg) undergoing intestinal cannulation. Materials and methods Anaesthesia was induced with a combination of medetomidine (50 μg kg−1) and tiletamine-zolazepam (2.5 mg kg−1) injected intramuscularly, and was maintained with isoflurane in air and oxygen (FiO2 = 50% O2). In the first group, morphine (0.1 mg kg−1) was administered extradurally before surgery. The second group received an equivalent volume of extradural saline as control. During the experiment, heart and respiratory rates, mean arterial blood pressure, tidal volume and minute ventilation were recorded every 10 minutes. The concentration of Fe′ISO was adjusted, according to the depth of anaesthesia, by an experienced animal nurse. Within treatment groups, time-related changes in Fe′ISO and physiological variables were analysed using a repeated measurementanova. Differences in data between treatment groups were analysed at specific time points using a Mann–Whitney U-test. Results are presented as mean ± SD; p < 0.05 was considered as significant. Results After the onset of action of the morphine, the Fe′ISO required to maintain anaesthesia was significantly lower in the extradural morphine group compared with control. During the expected maximal effect of the drug, Fe′ISO was significantly lower in the morphine group (0.6 ± 0.2%) than in the control group (0.9 ± 0.2%). The decrease in Fe′ISO indicated that the onset of action of morphine was approximately 30 minutes after injection. No significant differences in other clinical variables were found between the groups. Conclusion Pigs that received extradural morphine before abdominal surgery achieved surgical anaesthetic depth at a lower Fe′ISO concentration. Clinical relevance Extradural morphine allows abdominal surgery to be performed at a lower Fe′ISO concentrations. [ABSTRACT FROM AUTHOR]

Abstract Objective To study the effect of the pulsed delivery of nitric oxide (NO) on pulmonary gas exchange in the anaesthetized horses. Design Prospective, controlled randomized. Animals Five healthy Standardbred trotters, three geldings and two mares. Methods The horses were anaesthetized with thiopentone and isoflurane and positioned in dorsal recumbency. Nitric oxide was added as a pulse to the inspired gas during the first half of each inspiration. In three horses the effect of NO on the ventilation–perfusion distribution was also investigated using the multiple inert gas elimination technique. Data were analysed with repeated measures ANOVA. Results During spontaneous breathing, arterial oxygen tension (PaO2) increased with NO inhalation, from 14 ± 2 to 29 ± 3 kPa (105 ± 15 to 218 ± 23 mm Hg) (p < 0.001). Arterial oxygen tension also increased, from 17 ± 3 to 31 ± 5 kPa (128 ± 23 to 233 ± 38 mm Hg) (p < 0.05) during intermittent positive pressure ventilation. The increase in PaO2 was mainly due to a reduced right to left vascular shunt, but ventilation and perfusion matching also improved. The beneficial effect of NO inhalation was lost within 5 minutes of its discontinuation. Conclusion Delivery of NO as a pulse during inspiration is an effective method for counteracting impaired gas exchange caused by anaesthesia in horses. Pulsation has to be continuous because of the transience of NO's therapeutic effect. Clinical relevance Horses with impaired pulmonary gas exchange during anaesthesia can be treated with pulsed NO inhalation. [ABSTRACT FROM AUTHOR]