Social support, knowledge of infant development, and maternal confidence among adolescent and adult mothers

The action of phospholipase A2 (PLA2) and related inflammatory mediators on the formation of hypoxic pulmonary arterial hypertension was studied. 30 Sprague-Dawley rats were equally divided into three groups at random: normal control group, hypoxic group and the group pretreated with dexamethasone plus hypoxia. The pulmonary arterial pressure (PAP) was measured by inserting a microcatheter into the pulmonary artery. After 30 min of hypoxia, the activity of PLA2, platelet activating factor (PAF), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) were measured in blood and lung tissue, and it was found that the mean pulmonary arterial pressure (mPAP), the PLA2 activity, PGE2, TXB2 and PAF in blood and lung tissue were significantly increased; but pretreatment with dexamethasone relieved the changes mentioned above. In hypoxia, a positive correlations was found between the PLA2 activity and mPAP, PAF, PGE2, TXB2 respectively; positive correlations were also found between PAF, PGE2, TXB2 and mPAP. In conclusion, PLA2 induced the release of inflammation mediators, which may play roles in the formation of the acute hypoxic pulmonary arterial hypertension.     

Preservation of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane anesthesia compared to the conscious state in chronically instrumented dogs

BACKGROUND: The authors' objective was to assess the extent to which sevoflurane and desflurane anesthesia alter the magnitude of hypoxic pulmonary vasoconstriction compared with the response measured in the same animal in the conscious state. METHODS: Left pulmonary vascular pressure-flow plots were generated in seven chronically instrumented dogs by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. Pressure-flow plots were generated during normoxia and hypoxia on separate days in the conscious state, during sevoflurane (approximately 3.5% end-tidal), and during desflurane (approximately 10.5% end-tidal) anesthesia. Values are mean+/-SEM. RESULTS: In the conscious state, administration of the hypoxic gas mixture by conical face mask decreased (P < 0.01) systemic arterial PO2 from 94+/-2 mmHg to 50+/-1 mmHg and caused a leftward shift (P < 0.01) in the pressure-flow relationship, indicating pulmonary vasoconstriction. The magnitude of hypoxic pulmonary vasoconstriction in the conscious state was flow-dependent (P < 0.01). Neither anesthetic had an effect on the baseline pressure-flow relationship during normoxia. The magnitude of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane was also flow-dependent (P < 0.01). Moreover, at any given value of flow the magnitude of hypoxic pulmonary vasoconstriction was similar during sevoflurane and desflurane compared with the conscious state. CONCLUSION: These results indicate that hypoxic pulmonary vasoconstriction is preserved during sevoflurane and desflurane anesthesia compared with the conscious state. Thus, inhibition of hypoxic pulmonary vasoconstriction is not a general characteristic of inhalational anesthetics. The flow-dependent nature of the response should be considered when assessing the effects of physiologic or pharmacologic interventions on the magnitude of hypoxic pulmonary vasoconstriction.     

Effects of physical training in a hypobaric chamber on the physical performance of competitive triathletes

The effects of training in a hypobaric chamber on aerobic metabolism were studied in five high performance triathletes. During 3 weeks, the subjects modified their usual training schedule (approximately 30 h a week), replacing three sessions of bicycling exercise by three sessions on a cycle ergometer in a hypobaric chamber simulating an altitude of 4,000 m (462 mm Hg). Prior to and after training in the hypobaric chamber the triathletes performed maximal and submaximal exercise in normoxia and hypoxia (462 mm g). Respiratory and cardiac parameters were recorded during exercise. Lactacidaemia was measured during maximal exercise. Blood samples were drawn once a week to monitor blood cell parameters and erythropoetin concentrations. Training in the hypobaric chamber had no effect on erythropoiesis, the concentrations of erythropoetin always remaining unchanged, and no effect on the maximal oxygen uptake (VO2max) and maximal aerobic capacity measured in normoxia or hypoxia. Submaximal performance increased by 34% during a submaximal exhausting exercise performed at a simulated altitude of 2,000 m. During a submaximal nonexhausting test, ventilation values tended to decrease for similar exercise intensities after training in hypoxia. The changes in these parameters and the improved performance found for submaximal exercise may have been the result of changes taking place in muscle tissue or the result of training the respiratory muscles.     

Oxygen-tension-dependent pulmonary vascular responses to vasoactive agents

There have been recent indications that oxygen may nonspecifically oppose pulmonary vasoconstriction induced by a few vasoactive agents. Therefore, we examined the effect of four inspired oxygen tensions on the pulmonary vascular responses to exogenous prostaglandin F2alpha (PGF2alpha), serotonin (5-HT), 2-methylhistamine (2-MeH)(an H1-receptor agonist), histamine (after H2-receptor blockade with metiamide), and prostaglandin E1 (PGE1) in anesthetized dogs. An oxygen tension dependency on the pulmonary vascular responses to these vasoactive agents was observed, with each agent exhibiting maximal responses at different ranges of oxygen tension. PGF2alpha and PGE1 were most effective during hypoxia, while 5-HT, histamine, and 2-MeH produced maximal responses during normoxia. A comparison of dose-response curves for PGF2alpha during breathing of two inspired oxygen tensions indicated a decreased sensitivity, but not decreased reactivity, with the higher oxygen tension. The action of variable oxygen tensions on pulmonary vascular responsiveness to vasoactive agents suggests another role for oxygen in the control of the pulmonary circulation. It is not clear if oxygen acts non-specifically on the vascular smooth muscle, or if it alters the metabolic mechanisms of vasoactive agent action.     

Time-course and reversibility of the hypoxia-induced alterations in cerebral vascularity and cerebral capillary glucose transporter density

The adult rat adapts to prolonged moderate hypobaric hypoxia by polycythemia, increased brain vascularity, and increased density of the brain capillary glucose transporter (GLUT-1). We now report on the time-course and reversibility of these adaptive alterations. Adult male Wistar rats were subjected to hypobaric hypoxia at 0.5 atmosphere for periods of 4 days or 1, 2 or 3 weeks, and compared to normoxic littermate controls. Reversibility of the effects of hypoxia was studied in rats subjected to hypobaric hypoxia for 3 weeks and then allowed to recover at normobaric conditions for 3 additional weeks. Cerebral vascularity was studied in cross-sections of the cerebral cortex that were immunocytochemically stained with a GLUT-1 antibody. The density of GLUT-1 was determined in isolated cerebral microvessels by quantitative autoradiography of immunoblots. Blood hematocrit and cerebral microvascularity did not significantly increase after 4 days of hypoxia, but were significantly increased at 1, 2 and 3 weeks of hypoxia. Three weeks of normoxic recovery after 3 weeks of hypoxia reversed the polycythemia and cerebral hypervascularity. However, the density of GLUT-1 in isolated cerebral microvessels, which was significantly increased after 1 and 3 weeks of hypoxia, remained elevated after 3 weeks of normoxia.     

Carbon monoxide inhibits hypoxic pulmonary vasoconstriction in rats by a cGMP-independent mechanism

Hypoxia activates erythropoietin-producing cells, chemoreceptor cells of the carotid body and pulmonary artery smooth muscle cells (PSMC) with a comparable arterial PO2 threshold of some 70 mmHg. The inhibition by CO of the hypoxic responses in the two former cell types has led to the proposal that a haemoprotein is involved in the detection of the PO2 levels. Here, we report the effect of CO on the hypoxic pulmonary vasoconstriction (HPV). Pulmonary arterial pressure (PAP) was measured in an in situ, blood-perfused lung preparation. PAP in normoxia (20% O2, 5% CO2) was 15.2+/-1.8 mmHg, and hypoxia (2% O2, 5% CO2) produced a DeltaPAP of 6.3+/-0.4 mmHg. Addition of 8% or 15% CO to the hypoxic gas mixture reduced the DeltaPAP by 88.3+/-2.7% and 78.2+/-6.1% respectively. The same levels of CO did not affect normoxic PAP nor reduced the DeltaPAP produced by angiotensin II. The effect of CO was studied after inhibition of the NO-cyclic guanosine monophosphate (cGMP) cascade with N-methyl-l-arginine (5.10(-5) M) or methylene blue (1.4.10(-4) M). It was found that both inhibitors more than doubled the hypoxic DeltaPAP without altering the effectiveness of CO to inhibit the HPV. In in vitro experiments we verified the inhibition of guanylate cyclase by measuring the levels of cGMP in segments of the pulmonary artery. Cyclic GMP levels were 1.4+/-0.2 (normoxia), 2.5+/-0.3 (hypoxia) and 3.3+/-0.5 pmole/mg tissue (hypoxia plus 8% CO); sodium nitroprusside increased normoxic cGMP levels about fourfold. Methylene blue reduced cGMP levels to less than 10% in all cases, and abolished the differences among normoxic, hypoxic and hypoxic plus CO groups. It is concluded that CO inhibits HPV by a NO-cGMP independent mechanism and it is proposed that a haemoprotein could be involved in O2-sensing in PSMC.     

Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension

BACKGROUND: Monitoring left ventricular preload is critical to achieve adequate fluid resuscitation in patients with hypotension and sepsis. This prospective study tested the correlation of the pulmonary artery occlusion pressure, the left ventricular end-diastolic area index measured by transesophageal echocardiography, the arterial systolic pressure variation (the difference between maximal and minimal systolic blood pressure values during one mechanical breath), and its delta down (dDown) component (= apneic - minimum systolic blood pressure) with the response of cardiac output to volume expansion during sepsis. METHODS: Preload parameters were measured at baseline and during graded volume expansion (increments of 500 ml) in 15 patients with sepsis-induced hypotension who required mechanical ventilation. Each volume-loading step (VLS) was classified as a responder (increase in stroke volume index > or = 15%) or a nonresponder. Successive VLSs were performed until a nonresponder VLS was obtained. RESULTS: Thirty-five VLSs (21 responders) were performed. Fluid loading caused an overall significant increase in pulmonary artery occlusion pressure and end-diastolic area index, and a significant decrease in systolic pressure variation and delta down (P < 0.01). There was a significant difference between responder and nonresponder VLSs in end-diastolic area index, systolic pressure variation, and dDown, but not in pulmonary artery occlusion pressure. Receiver-operator curve analysis showed that dDown was a more accurate indicator of the response of stroke volume index to volume loading than end-diastolic area index and pulmonary artery occlusion pressure. A dDown component of more than 5 mmHg indicated that the stroke volume index would increase in response to a subsequent fluid challenge (positive and negative predictive values: 95% and 93%, respectively). CONCLUSION: The dDown component of the systolic pressure variation is a sensitive indicator of the response of cardiac output to volume infusion in patient with sepsis-induced hypotension who require mechanical ventilation.     

Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat

Pulmonary vascular remodeling, produced by cell hypertrophy and extracellular matrix protein synthesis in response to hemodynamic stress, regresses after reduction of blood pressure, possibly by proteolysis of structural proteins. To test this postulate, we assessed the breakdown of extracellular matrix proteins and expression of collagenase and elastase in pulmonary arteries of rats exposed to hypoxia (10% O2 for 10 d) followed by normoxia. During hypoxia, contents of collagen and elastin increased in pulmonary arteries and latent rat interstitial collagenase was expressed without increased collagenolytic activity or mRNA levels. At 3 days after normoxia, collagen and elastin contents decreased coincident with the new appearance of activated collagenase and transient increases in collagenolytic and elastolytic activities. The amount of immunoreactive collagenase, localized predominately in connective tissue-type mast cells, was increased in the adventitia and media of hypertensive vessels. We conclude that mast cells containing latent collagenase are recruited into the outer walls of pulmonary arteries during remodeling. It is possible that mast cell-derived collagenase contributes to collagen breakdown in pulmonary arteries during early recovery from hypoxia and plays a role in restoration of vascular architecture.     

Altered rhodopsin regeneration in diabetic mice caused by acid conditions within the rod photoreceptors

BACKGROUND: We sought to describe changes in spirometric variables and lung volume subdivisions in healthy subjects and patients with chronic obstructive pulmonary disease (COPD) during moderate acute hypobaric hypoxia as occurs during air travel. We further questioned whether changes in lung function may associate with reduced maximum ventilation or worsened arterial blood gases. METHODS: Ambulatory patients with COPD and healthy adults comprised the study populations (n = 27). We obtained baseline measurements of spirometry, lung volumes and arterial blood gases from each subject at sea level and repeated measurements during altitude exposure to 8000 ft (2438 m) above sea level in a man-rated hypobaric chamber. RESULTS: Six COPD patients and three healthy subjects had declines in FVC during altitude exposure greater than the 95% confidence interval (CI) for expected within day variability (p < 0.05). Average forced vital capacity (FVC) declined by 0.123 +/- 0.254 L (mean +/- SD; 95% CI = -0.255, -0.020; p < 0.05) for all subjects combined. The magnitude of decline in FVC did not differ between groups (p > 0.05) and correlated with increasing residual volume (r = -0.455; <0.05). Change in maximum voluntary ventilation (MVV) in the COPD patients equaled -1.244 +/- 4.797 L x min(-1) (95% CI = -3.71, 1.22; p = 0.301). Decline in maximum voluntary ventilation (MVV) in the COPD patients correlated with decreased FVC (r = 0.630) and increased RV (r = -0.546; p < 0.05). Changes in spirometric variables for patients and controls did not explain significant variability in the arterial blood gas variables PaO2, PaCO2 or pH at altitude. CONCLUSIONS: We observed a decline in forced vital capacity in some COPD patients and normal subjects greater than expected for within day variability. Spirometric changes correlated with changes in reduced maximum voluntary ventilation in the patients but not with changes in resting arterial blood gases.     

Pyridoxalated hemoglobin polyoxyethylene conjugate does not restore hypoxic pulmonary vasoconstriction in ovine sepsis

OBJECTIVES: Hypoxic pulmonary vasoconstriction, a protective mechanism, minimizes perfusion of underventilated lung areas to reduce ventilation-perfusion mismatching. We studied the effects of sepsis on hypoxic pulmonary vasoconstriction and attempted to determine whether hypoxic pulmonary vasoconstriction is influenced by pyridoxalated hemoglobin polyoxyethylene conjugate, a nitric oxide scavenger. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational intensive care unit at a university medical center. SUBJECTS: Nineteen female merino sheep, divided into three groups: group 1, controls (n = 5); group 2, sheep with sepsis (n = 6); and group 3, septic sheep treated with pyridoxalated hemoglobin polyoxyethylene conjugate (n = 8). INTERVENTIONS: All sheep were instrumented for chronic study. An ultrasonic flow probe was placed around the left pulmonary artery. After a 5-day recovery, a tracheostomy was performed and a double-lumen endotracheal tube was placed. Animals in groups 2 and 3 received a 48-hr infusion of live Pseudomonas aeruginosa (6 x 10(4) colony-forming units/kg/hr). After 24 hrs, sheep in group 3 received pyridoxalated hemoglobin polyoxyethylene conjugate (20 mg/kg/hr) for 16 hrs; sheep in groups 1 and 2 received only the vehicle. Hypoxic pulmonary vasoconstriction was repeatedly tested by unilateral hypoxia of the left lung with 100% nitrogen. Hypoxic pulmonary vasoconstriction was assessed as the change in left pulmonary blood flow. MEASUREMENTS AND MAIN RESULTS: In the animals in group 1, left pulmonary blood flow decreased by 62 +/- 8 (SEM)% during left lung hypoxia and remained stable during repeated hypoxic challenges throughout the study period. After 24 hrs of sepsis, left pulmonary blood flow decreased from 56 +/- 10% to 26 +/- 2% (group 2) and from 50 +/- 8% to 23 +/- 6% (group 3). In the sheep in group 2, there was no adaptation over time. Pulmonary shunt fraction increased. Pyridoxalated hemoglobin polyoxyethylene conjugate had no effect on hypoxic pulmonary vasoconstriction or pulmonary shunt. The animals receiving the bacterial infusion developed a hyperdynamic circulatory state with hypotension, decreased systemic vascular resistance, and increased cardiac output. Pyridoxalated hemoglobin polyoxyethylene conjugate increased mean arterial pressure and systemic vascular resistance but did not influence cardiac index. Pulmonary arterial pressure was increased during sepsis and increased even further after pyridoxalated hemoglobin polyoxyethylene conjugate administration. Oxygenation and oxygen delivery and uptake were not affected by pyridoxalated hemoglobin polyoxyethylene conjugate. CONCLUSIONS: Hypoxic pulmonary vasoconstriction is blunted during sepsis and there is no adaptation over time. It is not influenced by pyridoxalated hemoglobin polyoxyethylene conjugate. Pyridoxalated hemoglobin polyoxyethylene conjugate reversed hypotension and, with the exception of an increase in pulmonary arterial pressure, had no adverse effects on hemodynamics or oxygenation.     

Collateral ventilation and pulmonary arterial smooth muscle in the coati

Collateral ventilation can participate in ventilation-perfusion regulation by shifting normoxic gas into hypoxic lung regions. In species lacking collateral pathways, such as cattle and swine, ventilation-perfusion balance must rely heavily on hypoxic vasoconstriction, which may explain why their muscular pulmonary arteries are much thicker than those of other animal species. The presence of these unusually muscular vessels in turn may account for the vigorous pressor response to acute hypoxia in these species. The only other species known to lack collateral ventilation is the coati. To determine whether coatis fit the pulmonary circulatory pattern of cattle and swine, we measured pulmonary arterial wall dimensions and pulmonary vascular responsiveness to acute airway hypoxia in 11 adult coatis. Hypoxia caused impressive pulmonary arterial hypertension [normoxia = 17 +/- 1 (SE) Torr, hypoxia = 40 +/- 2 Torr, cardiac output unchanged]. The medial thickness of muscular pulmonary arteries (50-300 microns) was 17.1 +/- 1.8% (SD) of external diameter, a thickness unprecedented in normotensive adult mammals. We conclude that coatis fit the pattern of other species lacking collateral ventilation, since they have thick-walled pulmonary arteries and a vigorous pressor response to hypoxia.     

Leiomyosarcoma of the gingiva. Apropos of a case. Review of the literature]

Effects on erythropoiesis and blood pressure as well as physical performance and mental effects were studied in 15 healthy subjects during intermittent exposure to normobaric hypoxia corresponding to either 2000 m (6 persons) or 2700 m (9 persons) above sea level; another group (5 persons) also served as controls at normoxia. The concept "live high-train low" was used for 10 d consecutively and the exposure to hypoxia was 12 h/d. Blood pO2 and oxygen saturation were significantly decreased during the 10 d at hypoxia. [Hb] and Hct decreased significantly after 2 d in hypoxia and then returned to pre-study levels. Erythropoietin was significantly elevated in both hypoxia groups during the initial 3-5 d. Reticulocytes were significantly increased during 7 d of hypoxia. Submaximal and maximal oxygen uptake, blood pressure at rest and during exercise and the profile of mood states (POMS test) did not change during the study. In conclusion, intermittent normobaric hypoxia for 10 d resulted in a significant stimulation of erythropoiesis. Staying at normobaric hypoxia may serve as a complement to an ordinary altitude level sojourn.     

Evaluation of a pulsatile pediatric ventricular assist device in an acute right heart failure model

BACKGROUND: The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume = 9 mL) in a neonatal lamb model of acute right ventricular failure. METHODS: Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n = 5) had no mechanical support whereas experimental group 2 (n = 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery. RESULTS: All results are expressed as mean +/- standard deviation and analyzed by Student's t test. A p value less than 0.05 was considered statistically significant. Base-line measurements were not significantly different between groups and included systemic arterial pressure, 80.6 +/- 12.7 mm Hg; right atrial pressure, 4.6 +/- 1.6 mm Hg; mean pulmonary arterial pressure, 15.6 +/- 4.2 mm Hg; left atrial pressure, 4.8 +/- 0.8 mm Hg; and cardiac output, 1.4 +/- 0.2 L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, 38.8 +/- 10.4 mm Hg; right atrial pressure, 16.8 +/- 2.3 mm Hg; left atrial pressure, 1.4 +/- 0.5 mm Hg; and cardiac output, 0.6 +/- 0.1 L/min. All group 1 animals died at a mean of 71.4 +/- 9.4 minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, 68.0 +/- 13.0 mm Hg; right atrial pressure, 8.2 +/- 2.3 mm Hg; left atrial pressure, 6.4 +/- 2.1 mm Hg; and cardiac output, 1.0 +/- 0.2 L/min. CONCLUSIONS: The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates.     

Effects of hypoxia on urinary organic acid and hypoxanthine excretion in fetal sheep

Severe birth asphyxia leads to a transient organic aciduria and increased hypoxanthine excretion. To investigate its origin and timing, we analyzed urine from 12 late gestation fetal sheep in utero subjected to moderately severe isocapnic hypoxia for 1 h. In six fetuses the carotid sinus nerves were cut to determine whether reflex peripheral vasoconstriction contributed to the changes in excretion. After a control period of 1 h, maternal inspired oxygen was reduced for 1 h so that fetal arterial oxygen tension fell significantly from 2.86 +/- 0.12 kPa (mean +/- SEM) to 1.55 +/- 0.04 kPa. The ewes were returned to normoxia, and monitoring was continued for 1 h. Fetal heart rate, arterial blood pressure, and femoral arterial blood flow (intact fetuses only) were recorded, and arterial pH, blood gases, and lactate were measured. Urine collected via a bladder catheter was analyzed for organic acids and hypoxanthine with gas chromatography-mass spectrometry. In intact fetuses, hypoxia increased excretion of hypoxanthine and several organic acids, notably lactic acid and intermediates of valine catabolism. Changes were apparent by 15 min, significant by 45 min, and maximal after reoxygenation. In denervated fetuses, there were small, significant, increases in organic acids and hypoxanthine by 45 min of hypoxia, but there was no surge in excretion posthypoxia. Hypoxia caused a large, significant, fall in femoral arterial blood flow in intact fetuses. We conclude that the extent of the reflex peripheral vasoconstriction, particularly in skeletal muscle, determines the amount of organic acid and hypoxanthine excretion and may explain similar biochemical disturbances after birth asphyxia. Urinary lactic acid measurement has a potential value for grading birth asphyxia.     

Scorpion venom leads to gastrointestinal ischemia despite increased oxygen delivery in pigs

OBJECTIVES: Scorpion envenomation may be accompanied by metabolic acidosis even in the absence of hypoxia and cardiovascular derangement. We tested the hypothesis that venom causes ischemia of the gastrointestinal tract rather than failure of delivery of oxygen to the periphery. DESIGN: Repeated measures, prospective study in experimental animals. SETTING: University-affiliated hospital research laboratory. INTERVENTIONS: In ten spontaneously breathing, intubated, sedated pigs, purified dried venom (Leiurus quinquestriatus), 0.05 mg/kg, was administered intravenously. Measurements were obtained before (baseline), and 5, 15, 30, 60, 120, 180, and 240 mins after injection. MEASUREMENTS AND MAIN RESULTS: Variables measured included: mean arterial pressure (MAP), heart rate (HR), mean pulmonary arterial pressure, pulmonary artery occlusion pressure, cardiac output, stroke volume, right ventricular ejection fraction (rapid thermistor), left ventricular dimensions (echocardiography), arterial gas tensions, lactate and catecholamine concentrations, gastric interstitial mucosal pH (tonometry), as well as systemic and pulmonary vascular resistances. Within 5 mins after venom injection, there was a hyperdynamic state accompanied by significantly increased MAP (97 +/- 18 to 136 +/- 47 mm Hg, p < .0003), HR (70 +/- 12 to 121 +/- 24 beats/min, p < .00006), and cardiac output (1.88 +/- 0.35 to 2.95 +/- 0.53 L/min, p < .0003), with no change in stroke volume, or pulmonary artery occlusion pressure. Right ventricular ejection fraction increased from 38.1 +/- 4.3 to 48.6 +/- 9.0% (p < .0009) by 15 mins. No change in left ventricular function was observed. There were significant decreases in systemic vascular resistance and pulmonary vascular resistance following envenomation. Arterial and gastric mucosal pH significantly decreased from 7.40 +/- 0.04 to 7.25 +/- 0.07 (p < .0001) for arterial pH, and 7.33 +/- 0.08 to 7.17 +/- 0.13 (p < .00001) for gastric mucosal pH by 30 mins after envenomation. The decrease in arterial pH was not sufficient to account for the change in gastric mucosal pH, indicating gastric mucosal ischemia. Arterial lactate increased from 2.6 +/- 1.4 to 7.4 +/- 1.9 (p < .05 x 10(-8)). There were significant increases in serum epinephrine and norepinephrine values by 5 mins. All hemodynamic variables and catecholamine concentrations returned to baseline by 4 hrs. However, there was persistent arterial and gastric mucosal acidosis and increased lactate concentrations even at 4 hrs. Oxygen delivery remained normal or supernormal for 4 hrs following envenomation. However, despite this finding, systemic and gastric mucosal pH changes indicate impaired gastrointestinal oxygen delivery. CONCLUSIONS: Despite increased peripheral oxygen delivery, scorpion envenomation was associated with evidence of ischemia of the gastrointestinal tract. This association could be due to shunting of blood from metabolically active areas, possibly associated with massive catecholamine release, or a direct toxic effect of the venom on regional oxygen transport at the cellular level.     

Measurement of uric acid as a marker of oxygen tension in the lung

Changes in O2 tension such as those associated with hypoxic ischemia or hyperoxia may potentially modulate purine nucleotide turnover and production of associated catabolites. We used an isolated perfused rat lung preparation to evaluate the effect of O2 tension on pulmonary uric acid production. Three O2 concentrations (21%, normoxia; 95%, hyperoxia; 0%, hypoxia) were utilized for both pulmonary ventilation and equilibration of recirculating perfusate. All gas mixtures contained 5% CO2 and were balanced with N2. We used Certified Virus Free Sprague-Dawley male rats weighting 250-300 g, four to five rats in each exposure regimen. After a 10-min equilibration period, we measured uric acid levels at 0 and 60 min in lung perfusate and at 60 min in lung tissue. After 60 min of ventilation/perfusion, we observed significant uric acid accumulation in both lung tissue (25-60%) and perfusate (8- to 10-fold) for all three O2 regimens. However, hypoxia produced substantially greater net uric acid concentrations (net = the difference between zero and 60 min) than either normoxia or hyperoxia (1.5-fold in lung tissue, and 2-fold in perfusate, respectively). The data suggest that pulmonary hypoxia results in greater purine catabolism leading to increased uric acid production. Vascular space uric acid, as measured in the recirculating perfusate, was proportional to lung weight changes (r = 0.99) with hypoxia exhibiting the greatest values, possibly reflecting a linkage between tissue perturbation and uric acid release. Thus, measurement of uric acid may serve as a useful marker of adenine nucleotide turnover and lung injury.     

The effect of low-rose prostaglandin E1 on circulation, respiration and body temperature during surgical anesthesia

We investigated the effects of low-dose prostaglandin E1 (PGE1) on circulation, respiration, and body temperature during surgical anesthesia. We studied 109 adult patients undergoing upper abdominal operations under thoracic epidural combined with inhalational anesthesia. Patients were divided into 2 groups; Control group (n = 42) and PGE1 group (n = 67). In PGE1 group, PGE1 infusion was started at the rate of 0.02 microgram.kg-1.min-1 before the induction of anesthesia and was terminated at the end of surgery. There were no differences between the groups in demographic, anesthetic and surgical characteristics. After treatment with PGE1, arterial pressure decreased slightly but significantly, resulting in lower arterial pressure in PGE1 group than in control group before the induction of anesthesia. After the induction of anesthesia, however, arterial pressure decreased significantly in both groups, and the differences in arterial pressure between the groups were not observed any more during surgery. Heart rate was not different between the groups throughout the study period. Intraoperative urine output was greater in PGE1 group than in control group. PaO2/FIO2 ratio was not different between the groups both before and during anesthesia. Rectal temperature remained slightly but significantly lower in PGE1 group throughout surgery. Rectal-to-palm temperature gradient tended to be smaller in PGE1 group 1 hour after the induction of anesthesia. Low-dose PGE1 reduced arterial pressure. However, the difference in arterial pressure between the groups was so small that the difference disappeared during surgery. Meanwhile, low-dose PGE1 increased urine output, suggesting that renal blood flow was better-maintained with PGE1. In spite of several investigations reporting an unfavorable effect of PGE1 on PaO2, low dose PGE1 did not affect PaO2 in this study. Finally low-dose PGE1 reduced core temperature, though slightly, probably through redistribution of the body heat.     

Effects of toborinone on systemic circulation in patients under general anesthesia

Patients with suppressed systemic circulation under general anesthesia received a 20-minute continuous infusion of toborinone at a rate of 5, 10, or 15 micrograms.kg-1.min-1, and the efficacy and safety of the drug were evaluated. Toborinone increased cardiac index (CI) and stroke volume index (SVI) dose-dependently, with significant increases at 10 and 15 micrograms.kg-1.min-1. An increase in CI was observed from 10 minutes after the start of infusion, with a return to the baseline value at 20-30 minutes after the completion of infusion. Toborinone did not affect heart rate at any dose tested, but the drug tended to decrease mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial blood pressure tended to decrease after the start of infusion at all doses tested, and was significantly decreased at 20 minutes after the start of infusion at 10 and 15 micrograms.kg-1.min-1. Systemic vascular resistance and pulmonary vascular resistance decreased at all doses tested. T-wave amplitude on electrocardiaogram (ECG) and oxygen partial pressure in arterial blood decreased at 10 and 15 micrograms.kg-1.min-1. Toborinone increases cardiac output and decreases pre-load and after-load with no effects on heart rate, and, therefore, is thought to be a positive inotropic agent useful in the treatment of circulatory insufficiency. Due care should be exercised to monitor blood pressure, ECG, and arterial blood gas parameters of the patients. The effects of toborinone need to be further investigated in patients with complicated cardiac diseases under general anesthesia and in patients with circulatory insufficiency after surgery, including patients following extracorporeal circulation.     

Prevention of rapid reperfusion-induced lung injury with prostaglandin E1 during the initial period of reperfusion

We have found that the instantaneous restoration of blood flow causes acute dysfunction and massive edema in rat lungs after 4 hours of room temperature ischemia. This is associated with an early increase in pulmonary artery pressure (Ppa) and can be prevented by a stepwise increase in flow rate during the first 10 minutes of reperfusion. The objectives of this study were to determine whether rapid reperfusion causes lung injury after hypothermic preservation, and whether this injury can be attenuated by a short-course of prostaglandin E1 (PGE1). Rat lungs were flushed preserved with low-potassium dextran solution for 12 hours at 4 degrees C and randomly divided into three groups: (1) control (no PGE1); (2) PGE1 only in the flush solution; and (3) PGE1 in both flush solution and blood perfusate during the first 10 minutes of reperfusion. Postpreservation pulmonary function was assessed in an isolated rat lung reperfusion model developed previously. We found that rapid initiation of reperfusion led to significant pulmonary dysfunction, which was attenuated by a short-course of PGE1 in the blood perfusate. The addition of PGE1 to the flush solution alone did not have such an effect. Administration of PGE1 to the blood perfusate during the first 10 minutes resulted in significant lower Ppa and airway pressure and better gas exchange. There was a positive correlation between the peak Ppa during the first 10 minutes of reperfusion and the final shunt fraction. The physical forces generated by the rapid initiation of blood reperfusion appear to induce severe injury. The first 10 minutes of reperfusion seem to be a transition phase in which mechanical factors play an important role relating to ultimate post reperfusion lung function. A short course of PGE1 may be a useful maneuver to prevent rapid reperfusion-induced lung injury.     

Effects of human atrial natriuretic peptide on hemodynamics and pulmonary gas exchanges in cardiac surgery patients

We investigated the effects of human atrial natriuretic peptide (hANP) on hemodynamics and pulmonary gas exchanges in 22 cardiac surgery patients without pulmonary hypertension. In 10 patients, hANP was infused at a rate of 0.2 microgram.kg-1.min-1 throughout the surgery (hANP group), while in other 12 patients hANP was not infused at all (control group). Before cardiopulmonary bypass (CPB), mean arterial pressure and systemic vascular resistance decreased and cardiac output increased significantly in hANP group as compared with those in control group. After weaning from CPB and at the completion of surgery there was no significant difference in these hemodynamic variables between the two groups. Mean pulmonary arterial pressure, pulmonary vascular resistance, arterial pH, arterial oxygen tension, arterial carbon dioxide tension and shunt ratio did not show any significant difference between the two groups throughout surgery. These findings indicate that hANP infusion causes greater systemic vasodilation with less pulmonary vasodilation, and suggest that this systemic vasodilating effect contributes to the improvement of left ventricular function in patients undergoing open heart surgery.