Perfluorocarbon emulsion improves oxygenation of the cat primary visual cortex.

Tissue PO2 was measured in the primary visual cortex of anesthetized, artificially ventilated, normovolemic cats to evaluate the effect of small doses [1 g perfluorocarbon (PFC)/kg] of a PFC emulsion (1 g PFC/1.1 ml emulsion; Alliance Pharmaceutical, San Diego, CA) on brain oxygenation. The change in tissue PO2 (DeltaPO2), resulting from briefly changing the respiratory gas from room air to 100% oxygen, was measured before and after intravenous infusion of the emulsion. Before emulsion, DeltaPO2 was 51.1 +/- 45.6 Torr (n = 8 cats). Increases in DeltaPO2 of 34.0 +/- 26.1 (SD) % (n = 8) and 16. 3 +/- 8.4% (n = 6) were observed after the first and second emulsion infusions, respectively. The further increase in DeltaPO2 after the third dose (7.9 +/- 10.5%; n = 7) was not statistically significant. The observed increases in tissue oxygenation as a result of the PFC infusions appear to be the result of enhanced oxygen transport to the tissue.     

Oxygenation of the cat primary visual cortex.

Tissue PO2 was measured in the primary visual cortex of anesthetized, artificially ventilated normovolemic cats to examine tissue oxygenation with respect to depth. The method utilized 1) a chamber designed to maintain cerebrospinal fluid pressure and prevent ambient PO2 from influencing the brain, 2) a microelectrode capable of recording electrical activity as well as local PO2, and 3) recordings primarily during electrode withdrawal from the cortex rather than during penetrations. Local peaks in the PO2 profiles were consistent with the presence of numerous vessels. Excluding the superficial 200 microm of the cortex, in which the ambient PO2 may have influenced tissue PO2, there was a slight decrease (4.9 Torr/mm cortex) in PO2 as a function of depth. After all depths and cats were weighted equally, the average PO2 in six cats was 12.8 Torr, with approximately one-half of the values being 相似文献   

Effect of 100% O2 on hypoxic eucapnic ventilation

We measured ventilation in nine young adults while they breathed pure O2 after breathing room air and after 5 and 25 min of hypoxia. With isocapnic hypoxia (arterial O2 saturation 80 +/- 2%) mean ventilation increased at 5 min and then declined, so that at 25 min values did not differ from those on room air. After 3 min of O2 breathing, ventilation was greater than that on room air or after 25 min of isocapnic hypoxia, whether the hyperoxia had been preceded by hypoxia or normoxia. During transitions to pure O2 breathing, ventilation was analyzed breath by breath with a moving average technique, searching for nadirs before and after increases in PO2. After both 5 and 25 min of hypoxia, O2 breathing was associated with transient depressions of ventilation, which were greater after 25 min than after 5 min. Significant depressions were not observed when hyperoxia followed room air breathing, and O2-induced nadirs after hypoxia were lower than those observed during room air breathing. O2 transiently depressed ventilation after hypoxia but not after room air breathing. These results suggest that the normal ventilatory response to isocapnic hypoxia has two components, an excitatory one from peripheral chemoreceptors, which is turned off by O2 breathing, and a slower inhibitory one, probably of central origin, which is affected less promptly by O2 breathing.     

Pulmonary gas exchange and acid-base state at 5,260 m in high-altitude Bolivians and acclimatized lowlanders.

Pulmonary gas exchange and acid-base state were compared in nine Danish lowlanders (L) acclimatized to 5,260 m for 9 wk and seven native Bolivian residents (N) of La Paz (altitude 3,600-4,100 m) brought acutely to this altitude. We evaluated normalcy of arterial pH and assessed pulmonary gas exchange and acid-base balance at rest and during peak exercise when breathing room air and 55% O2. Despite 9 wk at 5,260 m and considerable renal bicarbonate excretion (arterial plasma HCO3- concentration = 15.1 meq/l), resting arterial pH in L was 7.48 +/- 0.007 (significantly greater than 7.40). On the other hand, arterial pH in N was only 7.43 +/- 0.004 (despite arterial O2 saturation of 77%) after ascent from 3,600-4,100 to 5,260 m in 2 h. Maximal power output was similar in the two groups breathing air, whereas on 55% O2 only L showed a significant increase. During exercise in air, arterial PCO2 was 8 Torr lower in L than in N (P < 0.001), yet PO2 was the same such that, at maximal O2 uptake, alveolar-arterial PO2 difference was lower in N (5.3 +/- 1.3 Torr) than in L (10.5 +/- 0.8 Torr), P = 0.004. Calculated O2 diffusing capacity was 40% higher in N than in L and, if referenced to maximal hyperoxic work, capacity was 73% greater in N. Buffering of lactic acid was greater in N, with 20% less increase in base deficit per millimole per liter rise in lactate. These data show in L persistent alkalosis even after 9 wk at 5,260 m. In N, the data show 1) insignificant reduction in exercise capacity when breathing air at 5,260 m compared with breathing 55% O2; 2) very little ventilatory response to acute hypoxemia (judged by arterial pH and arterial PCO2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial PO2 despite lower ventilation; and 4) better buffering of lactic acid. These results support and extend similar observations concerning adaptation in lung function in these and other high-altitude native groups previously performed at much lower altitudes.     

Oxygen uptake capacity of the amphibious fish - Amphipnous cuchia (Ham) (Symbranchiformes, Amphipnoidae)

The O2 uptake capacity of Amphipnous cuchia has been determined in relation to standard temperature of 25 degrees C. The measurement of O2 uptake indicates nearly 75% of the oxygen demand to be met through the air breathing organs and 25% by the skin and vestigeal gill through water in a normal habitat. The total VO2 during aerial-aquatic gas exchange is 60.5 ml/kg/hr. The prevention of surfacing resulted in a lower O2 uptake rate (38.29 ml/kg/hr). During submergence, the utilisation of air sacs for extracting O2 by regular pumping of water in and out is peculiar to the fish. Under normal respiratory conditions (air + water), the slope for O2 uptake through air is 0.72, 0.23 for water and 0.57 for both air + water. The average ratio borne by the fish for aquatic/air breathing (ml/kg/min) is higher in fishes below 60 g body weight, and aquatic respiration predominates in fishes weighing less than 6.0 g.     

Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1.

Hypoxia-inducible factor (HIF)-1 is stabilized by hypoxia and iron chelation. We hypothesized that HIF-1 might be involved in pulmonary vascular regulation and that infusion of desferrioxamine over 8 h would consequently mimic hypoxia and elevate pulmonary vascular resistance. In study A, we characterized the pulmonary vascular response to 4 h of isocapnic hypoxia; in study B, we measured the pulmonary vascular response to 8 h of desferrioxamine infusion. For study A, 11 volunteers undertook two protocols: 1) 4 h of isocapnic hypoxia (end-tidal PO(2) = 50 Torr), followed by 2 h of recovery with isocapnic euoxia (end-tidal PO(2) = 100 Torr), and 2) 6 h of air breathing (control). For study B, nine volunteers undertook two protocols while breathing air: 1) continuous infusion of desferrioxamine (4 g/70 kg) over 8 h and 2) continuous infusion of saline over 8 h (control). In both studies, pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by Doppler echocardiography via the maximum pressure gradient during systole across the tricuspid valve. Results show a progressive rise in pressure gradient over the first 3-4 h with both isocapnic hypoxia (P < 0.001) and desferrioxamine infusion (P < 0.005) to increases of ~16 and 4 Torr, respectively. These results support a role for HIF-regulated gene activation in human hypoxic pulmonary vasoconstriction.     

Initiation of oral breathing in lambs in response to airway obstruction: mechanisms.

Our aim was to assess the mechanisms determining the reflex formation of an oral airway in response to nasal obstruction (NO) and tracheal obstruction (TO). In nine conscious lambs (14-37 days old) NO was effected by blockade of nasal tubes; TO was later effected by blockade of an endotracheal tube. We measured arterial O2 saturation, PO2, PCO2, and pH and the depth and duration of inspiratory efforts when mouth opening (MO) occurred. Responses were compared when NO and TO followed breathing of room air, rebreathed air, and 100% O2. After both NO and TO, MO was initiated most rapidly after lambs rebreathed air and least rapidly after they breathed 100% O2. Similar changes in blood gases and pH were measured when MO occurred after air breathing and rebreathing; however, the extent of these changes was greater during TO than during NO. After 100% O2 was breathed, MO occurred when lambs were still hyperoxic, but they were more hypercapnic and acidemic than after breathing air or rebreathed air. There were no differences, related to prebreathed gases or site of airway occlusion, in the depth of inspiratory efforts at the time of MO. We conclude that the formation of an oral airway requires a critical level of inspiratory drive in the presence of airway obstruction. After the prebreathing of different gases, differences in response latency and blood gases at the time of MO can be attributed to the attainment of this threshold level of inspiratory drive. The formation of an oral airway is facilitated by, but not dependent on, receptors in the upper airway.     

Development of O2 tolerance in rabbits with no increase in antioxidant enzymes

Instillation of exogenous surfactant into rabbits exposed to 100% O2 increases survival time and decreases alveolar epithelial injury. In this study we investigated whether rabbits with increased levels of endogenous pulmonary surfactant are more resistant to hyperoxia. Rabbits were exposed to 100% O2 for 64 h and then returned to room air for 8 days (preexposed). At this time, they had normal gas exchange and alveolar permeability to solute and increased levels of lavageable alveolar phospholipids compared with control rabbits breathing air (26 +/- 2 vs. 12 +/- 2 mumol/kg). Preexposed rabbits survived significantly longer than control rabbits when reexposed to 100% O2 (166 +/- 24 vs. 80 +/- 6 h; n = 7; P less than 0.05) and had significantly higher values of total lavageable phospholipids after 72 h in 100% O2 (15 +/- 2 vs. 5 +/- 2 mumol/kg). Controls developed arterial hypoxemia after 72 h in 100% O2. On the other hand, preexposed rabbits maintained arterial PO2 values greater than 100 Torr throughout the hyperoxic exposure and developed progressive respiratory acidosis. Specific activities of CuZn and Mn superoxide dismutase, catalase, and glutathione peroxidase in lung homogenates and isolated alveolar type II pneumocytes of preexposed rabbits were unchanged from those of controls before O2 reexposure and after 72 h in 100% O2. We concluded that 1) increases in pulmonary antioxidant enzyme specific activities are not necessary for the development of O2 tolerance in rabbits and 2) pulmonary surfactant may play a role in O2 adaptation.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.     

Role of hemoglobin P50 in O2 transport during normoxic and hypoxic exercise in the dog

High hemoglobin affinity for O2 [low PO2 at 50% saturation of hemoglobin (P50)] could degrade exercise performance in normoxia by lowering mean tissue PO2 but could enhance O2 transport in hypoxic exercise by increasing arterial O2 saturation. We measured O2 transport at rest and at graded levels of steady-state exercise in tracheostomized dogs with normal P50 (28.8 +/- 1.8 Torr) and again after P50 was lowered (19.5 +/- 0.7 Torr) by sodium cyanate infusions. Measurements were made during ventilation with room air (RA), 12% O2 in N2, or 10% O2 in N2. Cardiac output (QT) as a function of O2 consumption (VO2) was not altered by low P50 at any inspired O2 fraction (P greater than 0.05). With RA exercise, arterial content (CaO2) and O2 delivery (QT X CaO2) were unchanged at low P50, whereas mixed venous PO2 was reduced at each level of VO2. With exercise in hypoxia, CaO2 and O2 delivery were significantly improved at low P50 (P less than 0.05). Mixed venous PO2 was lower than control during 12% O2 (P less than 0.05) but not different from control during 10% O2 exercise at low P50. Despite a presumed decrease in tissue PO2 during RA and 12% O2 exercise, exercise performance and base excess decline were not significantly worse than control levels. We conclude that, in canine steady-state exercise, hemoglobin P50 is not an important determinant of tissue O2-extraction capacity during normoxia or moderate hypoxia. In extreme hypoxia, low P50 may help to maintain tissue PO2 by enhancing systemic O2 delivery at each level of QT.     

Oxygen transport to exercising leg in chronic hypoxia

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.     

Effects of training on muscle O2 transport at VO2max.

To quantify the relative contributions of convective and peripheral diffusive components of O2 transport to the increase in leg O2 uptake (VO2leg) at maximum O2 uptake (VO2max) after 9 wk of endurance training, 12 sedentary subjects (age 21.8 +/- 3.4 yr, VO2max 36.9 +/- 5.9 ml.min-1.kg-1) were studied. VO2max, leg blood flow (Qleg), and arterial and femoral venous PO2, and thus VO2leg, were measured while the subjects breathed room air, 15% O2, and 12% O2. The sequence of the three inspirates was balanced. After training, VO2max and VO2leg increased at each inspired O2 concentration [FIO2; mean over the 3 FIO2 values 25.2 +/- 17.8 and 36.5 +/- 33% (SD), respectively]. Before training, VO2leg and mean capillary PO2 were linearly related through the origin during hypoxia but not during room air breathing, suggesting that, at 21% O2, VO2max was not limited by O2 supply. After training, VO2leg and mean capillary PO2 at each FIO2 fell along a straight line with zero intercept, just as in athletes (Roca et al. J. Appl. Physiol. 67: 291-299, 1989). Calculated muscle O2 diffusing capacity (DO2) rose 34% while Qleg increased 19%. The relatively greater rise in DO2 increased the DO2/Qleg, which led to 9.9% greater O2 extraction. By numerical analysis, the increase in Qleg alone (constant DO2) would have raised VO2leg by 35 ml/min (mean), but that of DO2 (constant Qleg) would have increased VO2leg by 85 ml/min, more than twice as much. The sum of these individual effects (120 ml/min) was less (P = 0.013) than the observed rise of 164 ml/min (mean). This synergism (explained by the increase in DO2/Qleg) seems to be an important contribution to increases in VO2max with training.     

Hydrogel-perfluorocarbon composite scaffold promotes oxygen transport to immobilized cells

Cell encapsulation provides cells a three-dimensional structure to mimic physiological conditions and improve cell signaling, proliferation, and tissue organization as compared to monolayer culture. Encapsulation devices often encounter poor mass transport, especially for oxygen, where critical dissolved levels must be met to ensure both cell survival and functionality. To enhance oxygen transport, we utilized perfluorocarbon (PFC) oxygen vectors, specifically perfluorooctyl bromide (PFOB) immobilized in an alginate matrix. Metabolic activity of HepG2 liver cells encapsulated in 1% alginate/10% PFOB composite system was 47-104% higher than alginate systems lacking PFOB. A cubic model was developed to understand the oxygen transport mechanism in the alginate/PFOB composite system. The theoretical flux enhancement in alginate systems containing 10% PFOB was 18% higher than in alginate-only systems. Oxygen uptake rates (OURs) of HepG2 cells were enhanced with 10% PFOB addition under both 20% and 5% O2 boundary conditions, by 8% and 15%, respectively. Model predictions were qualitatively and quantitatively verified with direct experimental OUR measurements using both a perfusion reactor and oxygen sensing plate, demonstrating a greater OUR enhancement under physiological O2 boundary conditions (i.e., 5% O2). Inclusion of PFCs in an encapsulation matrix is a useful strategy for overcoming oxygen limitations and ensuring cell viability and functionality both for large devices (>1 mm) and over extended time periods. Although our results specifically indicate positive enhancements in metabolic activity using the model HepG2 liver system encapsulated in alginate, PFCs could be useful for improving/stabilizing oxygen supply in a wide range of cell types and hydrogels.     

Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after onset of intense aerobic exercise

This study investigated whether hyperoxic breathing (100% O(2)) or increasing oxidative substrate supply [dichloroacetate (DCA) infusion] would increase oxidative phosphorylation and reduce the reliance on substrate phosphorylation at the onset of high-intensity aerobic exercise. Eight male subjects cycled at 90% maximal O(2) uptake (VO(2 max)) for 90 s in three randomized conditions: 1) normoxic breathing and saline infusion over 1 h immediately before exercise (CON), 2) normoxic breathing and saline infusion with DCA (100 mg/kg body wt), and 3) hyperoxic breathing for 20 min at rest and during exercise and saline infusion (HYP). Muscle biopsies from the vastus lateralis were sampled at rest and after 30 and 90 s of exercise. DCA infusion increased pyruvate dehydrogenase (PDH) activation above CON and HYP (3.10 +/- 0.23, 0.56 +/- 0.08, 0.69 +/- 0.05 mmol x kg wet muscle(-1) x min(-1), respectively) and significantly increased both acetyl-CoA and acetylcarnitine (11.0 +/- 0.7, 2.0 +/- 0.5, 2.2 +/- 0.5 mmol/kg dry muscle, respectively) at rest. However, DCA and HYP did not alter phosphocreatine degradation and lactate accumulation and, therefore, the reliance on substrate phosphorylation during 30 s (CON, 51.2 +/- 5.4; DCA, 56.5 +/- 7.1; HYP, 69.5 +/- 6.3 mmol ATP/kg dry muscle) and 90 s of exercise (CON, 90.6 +/- 9.5; DCA, 107.2 +/- 13.0; HYP, 101.2 +/- 15.2 mmol ATP/kg dry muscle). These data suggest that the rate of oxidative phosphorylation at the onset of exercise at 90% VO(2 max) is not limited by oxygen availability to the active muscle or by substrate availability (metabolic inertia) at the level of PDH in aerobically trained subjects.     

Effects of ethomersol on cerebrovascular blood circulation and oxygen metabolism of the brain in acute transient ischemia and recirculation

Intravenous infusion of ethomersol (50 mg/kg during 60 min) decreased cerebral tissue hypoxia at the end of acute cerebral ischemia in cats (30-min occlusion of both carotid and both vertebral arteries). In recirculatory period ethomersol prevented the postischemic hypoperfusion and especially hypo-oxygenation. Ethomersol-induced reduction of Hb-affinity to O2 was demonstrated.     

Fetal breathing, sleep state, and cardiovascular responses to graded anemia in sheep

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2-3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.     

Effect of alpha adrenergic blockade on brain blood flow and ventilation during hypoxia in newborn piglets.

The influence of cardiovascular changes on ventilation has been demonstrated in adult animals and humans (Jones, French, Weissman & Wasserman, 1981; Wasserman, Whipp & Castagna 1974). It has been suggested that neonatal hypoxic ventilatory depression may be related to some of the hemodynamic changes that occur during hypoxia (Brown & Lawson, 1988; Darnall, 1985; Suguihara, Bancalari, Bancalari, Hehre & Gerhardt, 1986). To test the possible relationship between the cardiovascular and ventilatory response to hypoxia in the newborn, eleven sedated spontaneously breathing piglets (age: 5.9 +/- 1.6 days; weight: 1795 +/- 317 g; SD) were studied before and after alpha adrenergic blockade with phenoxybenzamine. Minute ventilation (VE) was measured with a pneumotachograph, cardiac output (CO) by thermodilution and total and regional brain blood flow (BBF) with radiolabeled microspheres. Measurements were performed while the animals were breathing room air and after 10 min of hypoxia induced by breathing 10% O2. Hypoxia was again induced one hour after infusion of phenoxybenzamine (6 mg/kg over 30 min). After 10 min of hypoxia, in the absence of phenoxybenzamine, the animals responded with marked increases in VE (P less than 0.001), CO (P less than 0.001), BBF, and brain stem blood flow (BSBF) (P less than 0.02). However, the normal hemodynamic response to hypoxia was eliminated after alpha adrenergic blockade. There were significant decreases in systemic arterial blood pressure, CO, and BBF during hypoxia after phenoxybenzamine infusion; nevertheless, VE increased significantly (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of 10% O2 on the continuous breathing induced by O2 or O2 plus cord occlusion in the fetal sheep.

Although the administration of 100% O2 alone or combined with umbilical cord occlusion induces continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990a), the individual contribution of O2 and cord occlusion to the response have not been determined. We hypothesized that if O2 is an important factor in the induction of continuous breathing, administration of O2 low enough (10%) to bring fetal arterial PO2 to about 20 torr while the fetus is breathing continuously should reverse these changes. Thus we subjected 12 chronically instrumented fetal sheep to 10% O2 for 10 minutes after the establishment of continuous breathing by O2 (4 fetuses; 137 +/- 1 days) or by O2 plus umbilical cord occlusion (8 fetuses; 134 +/- 1 days). Arterial PO2 decreased from about 250 torr to 20 torr during 10% O2. This induced a significant decrease in breathing output (EMGdi x f) related primarily to a decrease in frequency (f). In 3/5 experiments in 4 fetuses, with O2 alone, apnoea developed within 4 +/- 0.6 min; in 12/13 experiments in 8 fetuses, with added cord occlusion it developed at 5 +/- 0.6 min. With the decrease in PaO2, electrocortical activity (ECoG) switched from low to high-voltage within 6 minutes in 5/5 experiments (O2 alone) and in 11/13 (O2 plus cord occlusion). The findings suggest that umbilical cord occlusion alone is not sufficient to maintain breathing continuously and an increased PaO2 is needed. We speculate that in the fetus there is a vital link between PaO2, breathing and ECoG with low PaO2 inhibiting and high PaO2 favouring breathing and arousal.     

Pulmonary interstitial pressure and tissue matrix structure in acute hypoxia

Pulmonary interstitial pressure was measured via micropuncture in anesthetized rabbits in normoxia and after breathing 12% O(2). In normoxia [arterial PO(2) = 88 +/- 2 (SD) mmHg], pulmonary arterial pressure and pulmonary interstitial pressure were 16 +/- 8 and -9.6 +/- 2 cmH(2)O, respectively. After 6 h of hypoxia (arterial PO(2) = 39 +/- 16 mm Hg), the corresponding values were 30+/-8 and 3.5+/-2.5 cm H(2)O (P<0.05). Pulmonary interstitial proteoglycan extractability, evaluated by hexuronate assay after 0.4 M guanidinium hydrochloride extraction, was 12.3, 32.4, and 60.6 microg/g wet tissue in normoxia and after 3 and 6 h of hypoxia, respectively, indicating a weakening of the noncovalent bonds linking proteoglycans to other extracellular matrix components. Gel filtration chromatography showed an increased fragmentation of chondroitin sulfate- and heparan sulfate-proteoglycans during hypoxic exposure, accounting for a loss of extracellular matrix native architecture and basement membrane structure. Gelatin zymography demonstrated increased amounts of the proteolytically activated form of gelatinase B (matrix metalloproteinase-9) after hypoxic exposure, providing evidence that the activation of proteinases may play a role in hypoxia-induced lung injury.     

Electrocardiographic evidence for cocaine cardiotoxicity in cat

Recent case studies suggest that cocaine overdose may produce life-threatening cardiac arrhythmias. We therefore investigated its effects on the electrocardiogram (leads II and V1) and arterial blood pressure in cats anesthetized with pentobarbital. Cocaine was administered by intravenous infusion over a 2-min interval at 1 mg/kg in 10 cats. In 5 out of 10 cats an additional infusion of 3 mg/kg cocaine was also administered after hemodynamic and electrocardiographic parameters had returned to control values (i.e., within 10 min). During and following infusion of 1 mg/kg cocaine, no significant change in heart rate or systolic or diastolic blood pressure were found, however the QRS duration increased by 38% (from 46 +/- 5 to 64 +/- 12 ms) (p less than 0.01). Evidence for bundle branch block and (or) premature ventricular beats was observed in 9 out of 10 cats after 1 mg/kg cocaine. Infusion of a further 3 mg/kg cocaine in five cats significantly lowered diastolic blood pressure (from 98 +/- 18 to 64 +/- 28 mmHg; 1 mmHg = 133.3 Pa) (p less than 0.01), and further prolonged QRS to 79 +/- 14 ms, a 75% increase from the mean control value (p less than 0.01). In addition, 1st and 2nd degree atrioventricular block, ventricular extrasystoles, and ectopic rhythms (AV junctional or idioventricular) were observed in four out of five cats given 3 mg/kg cocaine. Mean plasma concentrations of cocaine were 1.37 +/- 0.39 micrograms/mL (4.28 +/- 1.22 microM) (n = 5) at the end of a 1 mg/kg infusion and 2.93 +/- 0.43 micrograms/mL (9.16 +/- 1.34 microM) after a 3 mg/kg infusion (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)