Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes

We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments.     

Leukotrienes C4 and D4 do not increase filtration coefficient of excised perfused guinea pig lungs

We tested the direct effects of leukotriene (LT) C4 or D4 on the pulmonary vascular fluid filtration coefficient (Kf) by adding these LT's to the cell-depleted perfusate of excised guinea pig lungs. Pulmonary arterial (Ppa) and airway (Paw) pressures were monitored, and left atrial pressure was kept constant during 10 min of constant-flow perfusion. Kf's were then calculated by two methods [Drake and colleagues (KfD), Am. J. Physiol. 234 (Heart Circ. Physiol. 3): H266-H274, 1978; and Goldberg (KfG), Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H189-H198, 1980] from the change in lung weight resulting from a no-flow zone 3 hydrostatic stress applied for 20 min. With no LT's (Tyrode's buffer alone), the mean +/- SE Paw was 9.0 +/- 0.7 cmH2O and the Ppa was 14.2 +/- 1.1 cmH2O throughout the 10-min perfusion. The KfD and KfG were 1.239 +/- 0.169 and 1.586 +/- 0.223 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. The mean +/- SE lung wet-to-dry ratio (W/D) after the 20-min hydrostatic stress was 16.7 +/- 1.6. Within 30-45 s of adding 4 micrograms of LTC4 or LTD4, Paw and Ppa both increased and remained elevated throughout the perfusion period. The KfD and KfG were 1.586 +/- 0.223 and 2.071 +/- 0.234 ml X min-1 X mmHg-1 X 100 g lung-1, respectively, and the W/D was 18.1 +/- 1.7 after LTC4 (all P greater than 0.4 compared with Tyrode's buffer alone) and 1.417 +/- 0.200 and 1.851 +/- 0.244 ml X min-1 X mmHg-1 X 100 g lung-1, respectively, with a W/D of 20.5 +/- 1.3 after LTD4 (all P greater than 0.4 compared with Tyrode's buffer alone).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of alveolar hypoxia on pulmonary fluid filtration in in situ dog lungs

We have studied the effect of alveolar hypoxia on fluid filtration characteristics of the pulmonary microcirculation in an in situ left upper lobe preparation with near static flow conditions (20 ml/min). In six dogs (group 1), rate of edema formation (delta W/delta t, where W is weight and t is time) was assessed over a wide range of vascular pressures under two inspired O2 fraction (FIO2) conditions (0.95 and 0.0 with 5% CO2-balance N2 in both cases). delta W/delta t was plotted against vascular pressure, and the best-fit linear regression was obtained. There was no significant difference (paired t test) in either threshold pressure for edema formation [18.3 +/- 1.8 and 17.1 +/- 1.2 (SE) mmHg, respectively] or the slopes (0.067 +/- 0.008 and 0.073 +/- 0.017 g.min-1. mmHg-1.100g-1, respectively). In another seven dogs (group 2), delta W/delta t was obtained at a constant vascular pressure of 40 mmHg under four FIO2 conditions (0.95, 0.21, 0.05, and 0.0, with 5% CO2-balance N2). Delta W/delta t for the four conditions averaged 0.60 +/- 0.11, 0.61 +/- 0.11, 0.61 +/- 0.10, and 0.61 +/- 0.10 (SE) g.min-1.mmHg-1.100g-1, respectively. No significant differences (ANOVA for repeated measures) were noted. We conclude that alveolar hypoxia does not alter the threshold for edema formation or delta W/delta t at a given microvascular pressure.     

Flow-volume characteristics in the pulmonary circulation

Isolated ferret and canine lungs were used to validate a method for assessing determinants of vascular volume in the pulmonary circulation. With left atrial pressure (Pla) constant at 5 mmHg, flow (Q) was raised in steps over a physiological range. Changes in vascular volume (delta V) with each increment in Q were determined as the opposite of changes in perfusion system reservoir weight or from the increase in lung weight. At each level of Q, the pulmonary arterial and left atrial cannulas were simultaneously occluded, allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation before occlusion. Hypoxia (inspired PO2 25 Torr) in ferret lungs, which causes intense constriction in arterial extra-alveolar vessels, had no effect on the slope of the Ps-Q relationship, interpreted to represent the resistance downstream from compliance (control 0.025 +/- 0.006 mmHg.ml-1.min, hypoxia 0.030 +/- 0.013). The Ps-axis intercept increased from 8.94 +/- 0.50 to 13.43 +/- 1.52 mmHg, indicating a modest increase in the effective back-pressure to flow downstream from compliant regions. The compliance of the circulation, obtained from the slope of the relationship between delta V and Ps, was unaffected by hypoxia (control 0.52 +/- 0.08 ml/mmHg, hypoxia 0.56 +/- 0.08). In contrast, histamine in canine lungs, which causes constriction in veins, caused the slope of the Ps-Q relationship to increase from 0.013 +/- 0.007 to 0.032 +/- 0.006 mmHg.ml-1.min (P less than 0.05) and the compliance to decrease from 3.51 +/- 0.56 to 1.68 +/- 0.37 ml/mmHg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Locus of hypoxic vasoconstriction in isolated ferret lungs

To determine whether hypoxic pulmonary vasoconstriction (HPV) occurs mainly in alveolar or extra-alveolar vessels in ferrets, we used two groups of isolated lungs perfused with autologous blood and a constant left atrial pressure (-5 Torr). In the first group, flow (Q) was held constant at 50, 100, and 150 ml.kg-1 X min-1, and changes in pulmonary arterial pressure (Ppa) were recorded as alveolar pressure (Palv) was lowered from 25 to 0 Torr during control [inspired partial pressure of O2 (PIO2) = 200 Torr] and hypoxic (PIO2 = 25 Torr) conditions. From these data, pressure-flow relationships were constructed at several levels of Palv. In the control state, lung inflation did not affect the slope of the pressure-flow relationships (delta Ppa/delta Q), but caused the extrapolated pressure-axis intercept (Ppa0), representing the mean backpressure to flow, to increase when Palv was greater than or equal to 5 Torr. Hypoxia increased delta Ppa/delta Q and Ppa0 at all levels of Palv. In contrast to its effects under control condition, lung inflation during hypoxia caused a progressive decrease in delta Ppa/delta Q, and did not alter Ppa0 until Palv was greater than or equal to 10 Torr. In the second group of experiments flow was maintained at 100 ml.kg-1 X min-1, and changes in lung blood volume (LBV) were recorded as Palv was varied between 20 and 0 Torr. In the control state, inflation increased LBV over the entire range of Palv. In the hypoxic state inflation decreased LBV until Palv reached 8 Torr; at Palv 8-20 Torr, inflation increased LBV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of outflow pressure on lung lymph flow in unanesthetized sheep

Studies in anesthetized animals have shown that the flow rate from lung lymphatics (QL) depends on the pressure at the outflow end of the vessels (Po). We tested this in unanesthetized sheep prepared with chronic lung lymph cannula. We measured QL with the lymph cannula held at various heights above the olecranon and calculated Po as the height + QL X cannula resistance. QL decreased with increases in Po (delta QL/delta Po = -8.2 +/- 6.4 microliter X min-1 X cmH2O-1, mean +/- SD). We increased QL by raising left atrial pressure or infusing Ringer solution or Escherichia coli endotoxin and found that QL was even more sensitive to Po (delta QL/delta Po = -32 +/- 22). Cannula resistance caused a 9-70% reduction in QL. Changes in QL caused by increasing Po were not associated with changes in lymph protein concentration for up to 330 min. This indicates that increases in Po shunt lymph away from cannulated vessels but do not substantially effect microvascular filtration rate. The shunted lymph may flow into other vessels or collect in the lung. We conclude that QL does not accurately represent microvascular filtration rate because it depends on the cannula resistance and position at which the investigator chooses to place the cannula.     

Increased oxygen consumption associated with breathing activity in fetal lambs

To examine the relationship between fetal O2 consumption and fetal breathing movements, we measured O2 consumption, umbilical blood flow, and cardiovascular and blood gas data before, during, and after fetal breathing movements in conscious chronically catheterized fetal lambs. During fetal breathing movements, O2 consumption increased by 30% from a control value of 7.7 +/- 0.7 (SE) ml X min-1 X kg-1. Umbilical blood flow was 210 +/- 21 ml X min-1 X kg-1 before fetal breathing movements; in 9 of 16 samples it increased by 52 +/- 12 ml X min-1 X kg-1, while in the other 7 it decreased by 23 +/- 9 ml X min-1 X kg-1. Umbilical arterial and venous O2 partial pressures and pH fell during fetal breathing movements, and the fall was greater when umbilical blood flow was decreased. Partial CO2 pressure rose in both vessels, and again the increase was greatest when umbilical blood flow fell during fetal breathing movements. Also associated with a fall in umbilical blood flow was the transition from low-amplitude irregular to large-amplitude regular fetal breathing movements. It is concluded that fetal breathing movements increase fetal O2 demands and are associated with a transient deterioration in fetal blood gas status, which is most severe during large-amplitude breathing movements.     

Effect of hematocrit reduction on hormonal and metabolic responses to exercise

We wished to determine the effect of a 25% hematocrit reduction on glucoregulatory hormone release and glucose fluxes during exercise. In five anemic dogs, plasma glucose fell by 21 mg/dl and in five controls by 7 mg/dl by the end of the 90-min exercise period. After 50 min of exercise, hepatic glucose production (Ra) and glucose metabolic clearance rate (MCR) began to rise disproportionately in anemics compared with controls. By the end of exercise, the increase in Ra was almost threefold higher (delta 15.1 +/- 3.4 vs. delta 5.2 +/- 1.3 mg X kg-1 X min-1) and MCR nearly fourfold (delta 24.6 +/- 8.8 vs. delta 6.5 +/- 1.3 ml X kg-1 X min-1). Exercise with anemia, in relation to controls resulted in elevated levels of glucagon [immunoreactive glucagon (IRG) delta 1,283 +/- 507 vs delta 514 +/- 99 pg/ml], norepinephrine (delta 1,592 +/- 280 vs. delta 590 +/- 155 pg/ml), epinephrine (delta 2,293 +/- 994 vs. delta 385 +/- 186 pg/ml), cortisol (delta 6.7 +/- 2.2 vs. delta 2.1 +/- 1.0 micrograms/dl) and lactate (delta 12.1 +/- 2.2 vs. delta 4.2 +/- 1.8 mg/dl) after 90 min. Immunoreactive insulin and free fatty acids were similar in both groups. In conclusion, exercise with a 25% hematocrit reduction results in 1) elevated lactate, norepinephrine, epinephrine, cortisol, and IRG levels, 2) an increased Ra which is likely related to the increased counterregulatory response, and 3) we speculate that a near fourfold increase in MCR is related to metabolic changes due to hypoxia in working muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Right ventricular function in the hypoxaemic fetal sheep

Right ventricular function was investigated in seven fetal sheep (125-130 days gestation) hypoxaemic at a mean of 5 days postoperation, and were compared to nine normoxaemic fetal sheep of the same gestation. Arterial O2 and CO2 tensions, pH, and haematocrit values for the hypoxaemic and normoxaemic fetuses were 15.6 +/- 1.0 vs. 20.6 +/- 1.8 torr, 49.4 +/- 4.1 vs. 46.1 +/- 1.6 torr, 7.38 +/- 0.02 vs. 7.39 +/- 0.02, and 29 +/- 7.5 vs. 31 +/- 5.3%, respectively. Right ventricular output and stroke volume were similar in the two groups, 241 +/- 57 vs. 247 +/- 75 ml X min-1 X kg-1 and 1.5 +/- 0.4 vs. 1.5 +/- 0.4 ml X kg-1, respectively. Filling and afterload pressures were also similar in the hypoxaemic and normoxaemic fetuses with right atrial pressure of 3.0 +/- 1.0 vs. 3.7 +/- 1.2 mmHg, and arterial pressure of 42 +/- 5 vs. 43 +/- 4 mmHg, respectively. Ventricular function curves were produced by rapid withdrawal and re-infusion of fetal blood producing curves with a steep ascending limb and a plateau phase. The breakpoint joining the limbs of the control function curve for the hypoxaemic and normoxaemic fetuses were right atrial pressure 2.9 +/- 1.0 vs. 3.4 +/- 1.2 mmHg and a stroke volume of 1.5 +/- 0.5 vs. 1.5 +/- 0.4 ml X kg-1, respectively. Linear regression of stroke volume against arterial pressure from 30-90 mmHg during infusions of nitroprusside and phenylephrine at right atrial filling pressures greater than breakpoint was stroke volume = 0.018 ml X kg-1 X mmHg-1 arterial pressure +/- 2.25 ml X kg-1. This equation is not different from that calculated in normoxaemic fetuses, and demonstrates that the fetal right ventricle is quite sensitive to changes in arterial pressure. These data indicate that reduction in fetal oxygen content by an estimated 40% does not affect fetal right ventricular function.     

Morpho-functional analysis of lung tissue in mild interstitial edema

Mild pulmonary interstitial edema was shown to cause fragmentation of interstitial matrix proteoglycans. We therefore studied compartmental fluid accumulation by light and electron microscopy on lungs of anesthetized rabbits fixed in situ by vascular perfusion after 0.5 ml.kg(-1).min(-1) iv saline infusion for 180 min causing approximately 6% increase in lung weight. Morphometry showed that a relevant portion (44%) of extravascular fluid is detected early in the alveolar septa, 85% of this fluid accumulating in the thick portion of the air-blood barrier. The arithmetic mean thickness of the barrier increased in interstitial edema from 1.06 +/- 0.05 (SE) to 1.33 +/- 0.06 microm. The harmonic mean thickness increased from 0.6 +/- 0.03 to 0.86 +/- 0.07 microm, mostly due to thickening of the thin portion causing an increase in gas diffusion resistance. Despite some structural damage, the air-blood barrier displays a relatively high structural resistance providing a safety factor against the development of severe edema. It is suggested that the increase in extra-alveolar perivascular space occurs as a consequence of fluid accumulation in the air-blood barrier.     

Extra-alveolar veins are contiguous with, and leak fluid into, periarterial cuffs in rabbit lungs.

We previously observed physiological evidence that arterial and venous extra-alveolar vessels shared a common interstitial space. The purpose of the present investigation was to determine the site of this continuity to improve our understanding of interstitial fluid movement in the lung. Orange G and Evans blue dyes were added to the arterial and venous reservoirs, respectively, of excised rabbit lungs as they were placed 20 cmH2O into zone 1 (pulmonary arterial and venous pressures = 5 cmH2O, alveolar pressure = 25 cmH2O). After 10 s or 4 h the lungs were fixed by immersion in liquid N2, freeze-dried, cut into 5-mm serial slices, and examined by light macroscopy. Serial sections of 0.25-0.5 mm were subsequently examined by scanning electron microscopy. In the animals subjected to the zone 1 stress for 4 h, arterial and venous extra-alveolar vessels were surrounded by cuffs of edema. The edema ratio (cuff area divided by vessel lumen area) was greater around arteries than veins and decreased with increasing vessel size. Periarterial cuffs usually contained orange dye and frequently contained both orange and blue dye. Lymphatics containing orange or blue dye were frequently seen in periarterial cuffs. Scanning electron microscopy demonstrated that extra-alveolar veins of approximately 100 microns diameter were anatomically contiguous with arterial extra-alveolar vessel cuffs. In rabbit lungs, both arterial and venous extra-alveolar vessels (and/or alveolar corner vessels) leak fluid into perivascular cuffs surrounding arterial extra-alveolar vessels, and lymphatics located in the periarterial cuff contain fluid that originates from both the arterial and venous extra-alveolar vessels.     

Effect of lung inflation on lung blood volume and pulmonary venous flow

Phasic changes in lung blood volume (LBV) during the respiratory cycle may play an important role in the genesis of the respiratory wave in arterial pressure, or pulsus paradoxus. To better understand the effects of lung inflation on LBV, we studied the effect of changes in transpulmonary pressure (delta Ptp) on pulmonary venous flow (Qv) in eight isolated canine lungs with constant inflow. Inflation when the zone 2 condition was predominant resulted in transient decreases in Qv associated with increases in LBV. In contrast, inflation when the zone 3 condition was predominant resulted in transient increases in Qv associated with decreases in LBV. These findings are consistent with a model of the pulmonary vasculature that consists of alveolar and extra-alveolar vessels. Blood may be expelled from alveolar vessels but is retained in extra-alveolar vessels with each inflation. The net effect on LBV and thus on Qv is dependent on the zone conditions that predominate during inflation, with alveolar or extra-alveolar effects being greater when the zone 3 or zone 2 conditions predominate, respectively. Lung inflation may therefore result in either transiently augmented or diminished Qv. Phasic changes in left ventricular preload may therefore depend on the zone conditions of the lungs during the respiratory cycle. This may be an important modulator of respiratory variations in cardiac output and blood pressure.     

The influence of cardiorespiratory fitness on the decrement in maximal aerobic power at high altitude

There are conflicting reports in the literature which imply that the decrement in maximal aerobic power experienced by a sea-level (SL) resident sojourning at high altitude (HA) is either smaller or larger for the more aerobically "fit" person. In the present study, data collected during several investigations conducted at an altitude of 4300 m were analyzed to determine if the level of aerobic fitness influenced the decrement in maximal oxygen uptake (VO2max) at HA. The VO2max of 51 male SL residents was measured at an altitude of 50 m and again at 4300 m. The subjects' ages, heights, and weights (mean +/- SE) were 22 +/- 1 yr, 177 +/- 7 cm and 78 +/- 2 kg, respectively. The subjects' VO2max ranged from 36 to 60 ml X kg -1 X min -1 (mean +/- SE = 48 +/- 1) and the individual values were normally distributed within this range. Likewise, the decrement in VO2max at HA was normally distributed from 3 ml X kg-1 X min-1 (9% VO2max at SL) to 29 ml X kg-1 X min-1 (54% VO2max at SL), and averaged 13 +/- 1 ml X kg-1 X min-1 (27 +/- 1% VO2max at SL). The linear correlation coefficient between aerobic fitness and the magnitude of the decrement in VO2max at HA expressed in absolute terms was r = 0.56, or expressed as % VO2max at SL was r = 0.30; both were statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of aging on ventilatory response to exercise and CO2

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.     

Respiratory effects of a patent ductus arteriosus in premature newborn lambs

We examined the respiratory effects of a patent ductus arteriosus in 29 premature lambs (131-135 days gestational age) after infiltrating the ductal wall with formaldehyde solution (Formalin) and placing a snare around the ductus to regulate its patency. The lambs were given sheep surfactant, paralyzed, and mechanically ventilated at birth. We first compared 8 lambs with open ductus and 13 lambs with closed ductus during the 12 h after birth. Although lambs with open ductus had greater pulmonary blood flow (301 +/- 36 vs. 188 +/- 11 ml.min-1.kg-1, mean +/- SE, at 12 h of age) and mean pulmonary arterial (44 +/- 3 vs. 33 +/- 2 mmHg) and left ventricular end-diastolic (6 +/- 0.6 vs 4 +/- 0.7 mmHg) pressures, we found no differences in dynamic respiratory compliance (Cdyn = 0.55 +/- 0.07 vs. 0.55 +/- 0.03 ml.cmH2O-1.kg-1), midtidal volume resistance (62 +/- 5 X 10(-3) vs. 62 +/- 7 X 10(-3) cmH2O.ml-1.s), or functional residual capacity (FRC = 27 +/- 3 vs. 26 +/- 2 ml.kg-1). Alveolar-arterial PO2 difference was lower in the lambs with open ductus (238 +/- 65 vs. 362 +/- 37 Torr). Next, we challenged eight lambs with two separate saline infusions (50 ml.kg-1 over 3 min), each given with the ductus alternately closed or open. When the ductus was closed, FRC was unchanged, but Cdyn increased by 18% immediately after the infusion. When the ductus was open, FRC decreased by 16% and Cdyn decreased by 12%. We conclude that the premature lamb is surprisingly resistant to changes in respiratory function from ductal patency during the immediate neonatal period.     

Decline in peripheral chemoreceptor excitatory stimulation during acute hypoxia in the lamb

Chemoreceptor function was studied in eight 2- to 3-day-old unanesthetized lambs to sequentially assess hypoxic chemoreflex strength during an 18-min exposure to hypoxia [inspired O2 fraction (FIO2) = 0.08]. The immediate ventilatory (VE) drop in response to five breaths of pure O2 was measured at 3, 7, and 15 min during hypoxia. Each lamb was studied again at 10-11 days of age. At 2-3 days of age VE increased, with the onset of hypoxia, from 658 +/- 133 (SD) ml.min-1 X kg-1 to a peak of 1,124 +/- 177 ml.min-1 X kg-1. A dampening of the VE response then occurred, with a mean decline in VE of 319 ml.min-1 X kg-1 over the 18-min hypoxia period. Each pure O2 test (Dejours test) resulted in an abrupt fall in VE (delta VEDejours). This VE drop was 937 +/- 163, 868 +/- 244, and 707 +/- 120 ml.min-1 X kg-1 at 3, 7, and 15 min of hypoxia, respectively. Comparing the three O2 tests, delta VEDejours was significantly decreased by 15 min, indicating a loss of about one-fourth of the O2 chemoreflex drive during hypoxia. Testing at 10-11 days of age revealed a smaller VE decline during hypoxia. O2 tests at the beginning and end of the hypoxic period were not significantly different, indicating a smaller loss of hypoxic chemoreflex drive in the more mature animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of fetal heat production using differential calorimetry

These experiments were undertaken to measure heat production of fetal lambs in utero by using differential calorimetry. We used the principle that fetal heat production, H(fetus), can be calculated from measurements of base-line temperature difference between mother and fetus, delta T(fetus), heat introduced from an external source, H(heater), and the increase in body temperature, delta T(heater), that results, i.e., H(fetus) = H(heater) X delta T(fetus)/delta T(heater). We placed microheaters (1.8 mm diam) in the inferior vena cavae of eight near-term lambs and placed thermistors and catheters into maternal and fetal vessels and amniotic fluid. Five days later, fetal arterial temperature averaged 0.54 +/- 0.02 degrees C (SE) higher than maternal arterial temperature. When the heater was turned on to dissipate 29-103 cal/min, fetal temperature increased to approach 0.1-0.5 degrees C higher than control; the final temperature was estimated using the rate of increase during the first 20 min. Fetal heat production averaged 47.1 +/- 4.1 cal X min-1 X kg-1 during the warming phase in these lambs, which weighed 3.26 +/- 0.36 kg. This value would be 3-4% less if corrected for the increase in metabolic rate caused by heating, assuming a Q10 of 2.5. Fetal heating did not alter fetal heart rate, blood pressure, or blood gas values significantly, nor was hemolysis visible in plasma samples. When heat production was calculated from the decrease in fetal temperature after the heater was turned off, an average value of 41.2 +/- 2.5 cal X min-1 X kg-1 was found. Because this value is comparable to the heating phase, fetal metabolic rate and the insulating properties of the fetal shell are not likely to have been changed by the heating.     

Modification of the cutaneous vascular response to exercise by local skin temperature

This study examined how local forearm temperature (Tloc) affects the responsiveness of the cutaneous vasculature to a reflex drive for vasoconstriction. We observed responses in forearm blood flow (FBF) and arterial blood pressure to a 5-min bout of supine leg exercise of moderate intensity (125-175 W) after the forearm had been locally warmed to 36, 38, 40, or 42 degrees C for 48 min. With exercise, FBF fell by 1.82 +/- 0.23, 4.06 +/- 0.58, and 3.64 +/- 1.48 ml X 100 ml-1 X min-1 at 36, 38, and 40 degrees C, respectively, and rose by 2.16 +/- 0.57 ml X 100 ml X min-1 at a Tloc of 42 degrees C (mean +/- SE). Forearm vascular conductance (FVC) fell with the onset of exercise by averages of 2.77 +/- 0.57, 7.02 +/- 0.51, 5.36 +/- 0.85, and 4.17 +/- 0.79 ml X 100 ml-1 X min-1 X 100 mmHg-1 at 36, 38, 40, and 42 degrees C, respectively. Second-order polynomial regression analysis indicated that the reductions in FVC were greatest near a Tloc of 39 degrees C and that at a Tloc of 40 or 42 degrees C the cutaneous vasoconstrictor response to the onset of exercise is attenuated. Although elevated Tloc can be used to increase base-line FBF levels to make cutaneous vasoconstrictor responses more obvious, the direct effects of Tloc on this response must also be considered. We conclude that the optimum Tloc for observing reflex cutaneous vasoconstriction is near 39 degrees C.     

Estimation of blood pressure-related parameters by electrical impedance measurement.

In 13 healthy volunteers a computerized experimental set-up was used to measure the electrical impedance of the upper arm at changing cuff pressure, together with the finger arterial blood pressure in the contralateral arm. On the basis of a model for the admittance response, the arterial blood volume per centimeter length (1.4 +/- 0.3 ml/cm), the venous blood volume as a percentage of the total blood compartment (49.2 +/- 12.6%), and the total arterial compliance as a function of mean arterial transmural pressure were estimated. The effective physiological arterial compliance amounted to 2.0 +/- 1.3 microliters.mmHg-1.cm-1 and the maximum compliance to 33.4 +/- 12.0 microliters.mmHg-1.cm-1. Additionally, the extravascular fluid volume expelled by the occluding cuff (0.3 +/- 0.3 ml/cm) was estimated. These quantities are closely related to patient-dependent sources of an unreliable blood pressure measurement and vary with changes in cardiovascular function, such as those found in hypertension. Traditionally, a combination of several methods is needed to estimate them. Such methods, however, usually neglect the contribution of extravascular factors.     

Pulmonary fibrin microembolism with Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor

We produced pulmonary fibrin microembolism using an infusion of a prothrombin activator (Echis carinatus venom, 30 min, 0.5 NIH thrombin equivalent units/kg) in open-chest mongrel dogs. To determine the nonclotting effects of this venom on edemagenesis we infused an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK, 57 nmol X kg-1 X min-1 for 120 min), alone (n = 5) or with venom (Echis + PPACK, n = 5). The control group (n = 5) was given 1 ml of 0.9% NaCl. A decline in left atrial pressure (means +/- SE, 5.3 +/- 0.4 to 4.0 +/- 0.5 mmHg, P less than 0.05) and cardiac index (149 +/- 10 to 82 +/- 13 ml X min-1 X kg-1, P less than 0.01) in association with a marked increase in pulmonary arterial pressure (14.5 +/- 0.6 to 26.6 +/- 2.5 mmHg, P less than 0.001) and pulmonary vascular resistance (64 +/- 5 to 304 +/- 42 mmHg X ml-1 X min-1 X kg-1, P less than 0.001) was observed after 20 min of venom infusion. During this interval, pulmonary artery wedge pressure increased (4 +/- 1 to 12 +/- 4 mmHg, P less than 0.01) in four of eight animals. Fibrinogen declined below measurable levels and fibrin microemboli were seen in many pulmonary arterioles. These changes were not observed in the Echis + PPACK, PPACK, or control groups. Leukopenia and thrombocytopenia were observed in the Echis and Echis + PPACK groups.(ABSTRACT TRUNCATED AT 250 WORDS)