Responses of innervated and denervated gut to whole-body hypoxia

1987 ◽  
Vol 62 (2) ◽  
pp. 651-657 ◽  
Author(s):  
S. L. Dodd ◽  
C. E. King ◽  
S. M. Cain
Keyword(s):  
Blood Flow ◽  
Neural Activity ◽  
Whole Body ◽  
O2 Uptake ◽  
Severe Limitation ◽  
Energy Stores ◽  
Anesthetized Dogs ◽  
Extrinsic Innervation ◽  
O2 Supply ◽  
O2 Deficit

As a significant user of O2 at rest (20% of whole body), the gut may be subject to more severe limitation of O2 supply during global hypoxia than more vital areas because of preferential redistribution of blood flow. Accordingly, its accumulation of O2 deficit during hypoxia and its excess O2 use during normoxic recovery might be altered by extrinsic neural activity. We measured blood flow and O2 uptake in whole body (WB) and gut segments while anesthetized dogs were ventilated with 9% O2–91% N2 for 30 min followed by 30-min normoxic recovery. In six dogs extrinsic innervation to the gut segment was left intact and it was severed in another six animals. O2 deficit and excess were the accumulated differences from the normoxic O2 uptake for both gut and WB corrected for O2 stores changes. The intact gut, although only 4% body wt, incurred 22% of WB O2 deficit but contributed only 8% to WB O2 excess. The imbalance (gut excess was only 44% of gut deficit) implied that O2 using functions were curtailed during hypoxia without obligating an energy stores deficit. Denervation did not alter these quantitative relationships. Blood flow responses to transition between normoxia and hypoxia were only transiently altered. Extrinsic innervation apparently plays no major role in gut responses to WB hypoxia.

Analysis of oxygen delivery and uptake relationships in the Krogh tissue model

1989 ◽  
Vol 67 (3) ◽  
pp. 1234-1244 ◽  
Author(s):  
P. T. Schumacker ◽  
R. W. Samsel
Keyword(s):  
Blood Flow ◽  
Critical Point ◽  
Real Data ◽  
Whole Body ◽  
O2 Uptake ◽  
Highly Sensitive ◽  
O2 Extraction ◽  
O2 Supply ◽  
Experimental Findings ◽  
O2 Delivery

Normally, tissue O2 uptake (VO2) is set by metabolic activity rather than O2 delivery (QO2 = blood flow X arterial O2 content). However, when QO2 is reduced below a critical level, VO2 becomes limited by O2 supply. Experiments have shown that a similar critical QO2 exists, regardless of whether O2 supply is reduced by progressive anemia, hypoxemia, or reduction in blood flow. This appears inconsistent with the hypothesis that O2 supply limitation must occur by diffusion limitation, since very different mixed venous PO2 values have been seen at the critical point with hypoxic vs. anemic hypoxia. The present study sought to begin clarifying this paradox by studying the theoretical relationship between tissue O2 supply and uptake in the Krogh tissue cylinder model. Steady-state O2 uptake was computed as O2 delivery to tissue representative of whole body was gradually lowered by anemic, hypoxic, or stagnant hypoxia. As diffusion began to limit uptake, the fall in VO2 was computed numerically, yielding a relationship between QO2 and VO2 in both supply-independent and O2 supply-dependent regions. This analysis predicted a similar biphasic relationship between QO2 and VO2 and a linear fall in VO2 at O2 deliveries below a critical point for all three forms of hypoxia, as long as intercapillary distances were less than or equal to 80 microns. However, the analysis also predicted that O2 extraction at the critical point should exceed 90%, whereas real tissues typically extract only 65–75% at that point. When intercapillary distances were larger than approximately 80 microns, critical O2 extraction ratios in the range of 65–75% could be predicted, but the critical point became highly sensitive to the type of hypoxia imposed, contrary to experimental findings. Predicted gas exchange in accord with real data could only be simulated when a postulated 30% functional peripheral O2 shunt (arterial admixture) was combined with a tissue composed of Krogh cylinders with intercapillary distances of less than or equal to 80 microns. The unrealistic efficacy of tissue O2 extraction predicted by the Krogh model (in the absence of postulated shunt) may be a consequence of the assumed homogeneity of tissues, because real tissues exhibit many forms of heterogeneity among capillary units. Alternatively, the failure of the original Krogh model to fully predict tissue O2 supply dependency may arise from basic limitations in the assumptions of that model.

Oxygen transport during anemic hypoxia in pigs: effects of digoxin on metabolism

1992 ◽  
Vol 263 (1) ◽  
pp. H208-H217
Author(s):  
A. Saltiel ◽  
D. J. Sanfilippo ◽  
R. Hendler ◽  
G. Lister
Keyword(s):  
Blood Flow ◽  
Supply And Demand ◽  
Linear Increase ◽  
Tissue Hypoxia ◽  
Whole Body ◽  
O2 Consumption ◽  
O2 Transport ◽  
O2 Supply ◽  
Relationship Of ◽  
O2 Deficit

We tested whether digoxin would limit tissue hypoxia during severe anemia by improving peripheral O2 distribution or decreasing O2 demands. Hematocrit (Hct) was reduced in eight control and eight digoxin-treated pigs from 27-28% to 17-18, 11-12, and 7-8%. Whole body and hindlimb blood flow, O2 transport, O2 extraction, and O2 consumption and serum catecholamines (epinephrine and norepinephrine) were determined at each Hct. Arterial and femoral venous lactate and O2 deficit were obtained to reflect tissue hypoxia. Cardiac output was significantly greater (P less than 0.05) with digoxin, as expected, but there were no differences in hindlimb blood flow. Also, whole body and hindlimb O2 extractions were equal in both groups for similar levels of O2 transport, suggesting that digoxin did not alter the relationship of O2 flow to metabolism in regional circulations. As whole body O2 consumption fell, controls accumulated more (P less than 0.05) O2 deficit and arterial lactate than the digoxin group. Furthermore, the slope demonstrating the linear increase of lactate with respect to O2 deficit was much steeper in controls (y = 1.11 + 0.06x) than in digoxin (y = 1.36 + 0.02x), suggesting that there were differences in the degree of tissue hypoxia for comparable O2 deficit. This may be attributed to the marked differences in catecholamine response: epinephrine was higher in controls at Hct of 7-8% and norepinephrine was higher at Hcts of 11-12 and 7-8%. Digoxin may have inhibited the release of catecholamine or reduced the stimulus for catecholamine secretion during anemia. We speculate that digoxin markedly improved the balance between peripheral O2 supply and demand during anemia by inhibiting catecholamine thermogenesis, thereby decreasing O2 demands. This may explain some of the salutary effects of glycosides in high-output cardiac failure with normal ventricular function.

Total and hindlimb oxygen deficit and "repayment" in hypoxic anesthetized dogs

1983 ◽  
Vol 55 (3) ◽  
pp. 913-922 ◽  
Author(s):  
R. P. Adams ◽  
S. M. Cain
Keyword(s):  
Skeletal Muscle ◽  
Time Course ◽  
Oxygen Deficit ◽  
Whole Body ◽  
Beta Blockade ◽  
O2 Uptake ◽  
Deficit Accumulation ◽  
Regional Patterns ◽  
Anesthetized Dogs ◽  
O2 Deficit

Whole-body (WB) and hindlimb [(HL), paw excluded] O2 uptake (VO2) were measured in 26 anesthetized paralyzed dogs while they were ventilated with 9% O2-91% N2 for 15- and 30-min periods and with room air during recovery periods. Ten of the dogs were pretreated with 1 mg/kg propranolol (beta-Blockade). O2 deficit during hypoxia and the excess O2 used during recovery were obtained by assuming that VO2 would have followed the time course described by a line connecting prehypoxic and postrecovery VO2. Amounts of O2 deficit and excess were corrected for changes in O2 stores. O2 excess was seldom as great as O2 deficit in either WB or HL and the two quantities were not obviously related. The rate of HL O2 deficit accumulation decreased with time in hypoxia, whereas WB O2 deficit remained constant. All of HL VO2 was attributed to skeletal muscle so that WB O2 deficit and excess could be partitioned into muscle and nonmuscle portions. The rate of nonmuscle O2 deficit accumulation increased with time, but the nonmuscle portion of O2 excess decreased after the longer hypoxic period. beta-Blockade accentuated but did not change these qualitative relationships. We concluded that neither WB nor HL O2 deficits were fully matched by O2 excess and that regional patterns of O2 deficit accumulation and “repayment” did not necessarily parallel those for WB.

O2 uptake in bled dogs after resuscitation with hypertonic saline or hydroxyethylstarch

1989 ◽  
Vol 257 (1) ◽  
pp. H238-H243
Author(s):  
K. Reinhart ◽  
T. Rudolph ◽  
D. L. Bredle ◽  
S. M. Cain
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Hypertonic Saline ◽  
Whole Body ◽  
Base Line ◽  
O2 Uptake ◽  
Shed Blood ◽  
Anesthetized Dogs ◽  
O2 Delivery ◽  
O2 Deficit

Hemodynamic and metabolic variables were measured for the whole body and isolated hindlimb of anesthetized dogs during resuscitation from hemorrhagic shock, using a small volume of hypertonic saline or a larger volume of hydroxyethylstarch. Twelve dogs were bled and maintained at a mean arterial pressure (MAP) of 40 mmHg for 30 min. Six dogs were then infused with 7.5% NaCl in 5 ml/kg hydroxyethylstarch (HTS group), and six received 6% hydroxyethylstarch alone (HES group) in an amount to approximate the maximum MAP achieved with hypertonic saline. Hypertonic saline replacement was approximately 16% of shed blood volume compared with 66% for hydroxyethylstarch. With hypertonic saline, cardiac output returned to base line, but O2 delivery did not. Hydroxyethylstarch increased cardiac output above base line, and O2 delivery was near base line. O2 uptake with hydroxyethylstarch peaked at 40% above control at 10 min of resuscitation. Excess O2 uptake in recovery was higher than O2 deficit in hemorrhage with the HES group but not with the HTS group. In the isolated hindlimb, vascular resistance decreased rapidly on hypertonic saline infusion but reached similar levels at 10 min of resuscitation with both fluids. With progressive lowering of blood flow to the pump-perfused hindlimb, ability of limb muscle to extract O2 was the same for the HTS and HES groups. With hemodilution by volume replacement with acellular fluid after hemorrhage, a seemingly adequate cardiac output and arterial pressure may be underresuscitation if O2 delivery does not meet the increased O2 demand.

Regional hemodynamic responses to hypoxia and hypermetabolism in polycythemic dogs

1989 ◽  
Vol 67 (1) ◽  
pp. 96-102 ◽  
Author(s):  
R. L. Stork ◽  
S. L. Dodd ◽  
C. K. Chapler ◽  
S. M. Cain
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Adverse Effects ◽  
Whole Body ◽  
Metabolic Demand ◽  
O2 Uptake ◽  
O2 Extraction ◽  
Anesthetized Dogs ◽  
Resting Muscle ◽  
Increased Blood Flow

Normovolemic polycythemia did not improve the ability of either resting muscle or gut to maintain O2 uptake (VO2) during severe hypoxia because of the adverse effects of increased viscosity on blood flow to those regions. The present study tested whether increased metabolic demand would promote vasodilation sufficiently to overcome those effects. We measured whole body, muscle, and gut blood flow, O2 extraction, and VO2 in anesthetized dogs after increasing hematocrit to 65% and raising O2 demand with 2,4-dinitrophenol (n = 8). We also tested whether regional denervation (n = 8) and hypervolemia (n = 6) affected these responses. After raising hematocrit and metabolism, the dogs were ventilated with air, with 9% O2–91% N2, and again with air for 30-min periods. Reduced blood flow and increased O2 demand, caused by increased blood viscosity and 2,4-dinitrophenol, respectively, increased O2 extraction so that muscle VO2 was nearly supply limited in normoxia. Denervation showed that vasoconstriction had increased in gut and muscle with hypoxia onset but this was overcome after 15 min. By then, muscle was receiving a major portion of cardiac output, whereas gut showed little change. With hypervolemia cardiac output increased in hypoxia but neither gut nor muscle increased blood flow in those experiments. Because regional and whole body VO2 fell in all groups during hypoxia to the same extent found earlier in normocythemic dogs, any real benefit of polycythemia under the conditions of these experiments was dubious at best.

Muscle O2 deficit during hypoxia and two levels of O2 demand

1987 ◽  
Vol 62 (4) ◽  
pp. 1384-1391 ◽  
Author(s):  
C. E. King ◽  
S. L. Dodd ◽  
S. M. Cain
Keyword(s):  
Blood Flow ◽  
Supply And Demand ◽  
Hypoxic Hypoxia ◽  
Similar Amount ◽  
O2 Uptake ◽  
Tension Development ◽  
O2 Extraction ◽  
O2 Supply ◽  
End Tidal ◽  
O2 Deficit

We have examined the relative deficits in tension development and O2 uptake in contracting skeletal muscle during severe hypoxic hypoxia. Anesthetized mongrel dogs were ventilated to maintain an end-tidal PCO2 between 35 and 40 Torr. Venous outflow from the gastrocnemius muscle was measured using an electromagnetic flow probe. The tendon was cut and attached to a strain gauge. The muscle was stimulated to contract isometrically at 2 or 4 Hz for 20 min. Hypoxia (9% O2 in N2) was then imposed for 30 min, followed by 30 min of normoxia. Blood flow first increased in proportion to the contraction frequency and then increased further a similar amount in both groups during hypoxia. O2 extraction and blood flow reached maximal levels during hypoxia in the 2-Hz group. The further O2 deficit that was accumulated during 4 Hz and hypoxia was, therefore, a result of the greater discrepancy between O2 supply and demand. O2 uptake decreased more in hypoxia than did developed tension. These results are best explained by ATP supplementation from nonaerobic energy sources that was promoted by the free-flow condition of hypoxic hypoxia.

Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis

1994 ◽  
Vol 76 (3) ◽  
pp. 1166-1171 ◽  
Author(s):  
C. E. King ◽  
M. J. Melinyshyn ◽  
J. D. Mewburn ◽  
S. E. Curtis ◽  
M. J. Winn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Methyl Ester ◽  
Whole Body ◽  
O2 Uptake ◽  
Arterial Inflow ◽  
Anesthetized Dogs ◽  
Nos Inhibitor ◽  
The Right ◽  
Oxide Synthase

The nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used to determine whether the decrease in canine hindlimb blood flow (QL) with NOS inhibition would limit skeletal muscle O2 uptake (VO2). Arterial inflow and venous outflow from the hindlimb were isolated, and the paw was excluded from the circulation. Pump perfusion from the right femoral artery kept the hindlimb perfusion pressure near the auto-perfused level. Six anesthetized dogs received L-NAME (20 mg/kg i.v.), whereas another group of five dogs received the stereospecific enantiomer N omega-nitro-D-arginine methyl ester (D-NAME 20 mg/kg i.v.). Efficacy of NOS inhibition was tested with intra-arterial boluses of acetylcholine. QL was measured continuously, and whole body and hindlimb VO2 were measured 60 and 120 min after L-NAME or D-NAME. Whole body VO2 remained at control levels, but cardiac output decreased from 117 +/- 17 to 57 +/- 7 ml.kg-1.min-1 60 min after L-NAME (P < 0.05) and remained at that level for the duration of the experiment. Cardiac output was significantly higher in the D-NAME group than in the L-NAME group at 60 min. After L-NAME, QL fell 24% but VO2 increased from 5.2 +/- 0.4 to 7.4 +/- 0.6 ml.kg-1.min-1 (P < 0.05). No change in QL or VO2 occurred after D-NAME. NOS inhibition did not limit hindlimb VO2, despite decreases in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic and circulatory responses of normoxic skeletal muscle to whole-body hypoxia

1988 ◽  
Vol 65 (5) ◽  
pp. 2063-2068 ◽  
Author(s):  
D. L. Bredle ◽  
C. K. Chapler ◽  
S. M. Cain
Keyword(s):  
Perfusion Pressure ◽  
Muscle Blood Flow ◽  
Autologous Blood ◽  
Whole Body ◽  
Membrane Oxygenator ◽  
O2 Uptake ◽  
Ici 118,551 ◽  
Autoregulatory Escape ◽  
Beta 2 ◽  
O2 Supply

Whole-body hypoxia may increase peripheral O2 demand because it increases catecholamine calorigenesis, an effect attributable to beta 2-adrenoceptors. We tested these possibilities by pump-perfusing innervated hindlimbs in eight dogs with autologous blood kept normoxic by a membrane oxygenator while ventilating the animals for 40 min with 9% O2 in N2 (NOB group). Similar periods of normoxic ventilation preceded and followed the hypoxic period. A second group (n = 8, beta B) was pretreated with the specific beta 2 blocker ICI 118,551. Hindlimb O2 uptake was elevated by 25 min of hypoxia in NOB, whereas whole-body O2 uptake was reduced. Limb O2 uptake remained elevated in recovery, but all effects on limb O2 uptake were absent in beta B. Hindlimb resistance and perfusion pressure increased in hypoxia in both groups, and there was little evidence of local escape from reflex vasoconstriction. These results clearly indicated that global hypoxia increased O2 demand in muscle when the local O2 supply was not limited and that beta 2-receptors were necessary for this response. Autoregulatory escape of limb muscle blood flow from centrally mediated vasoconstriction during whole-body hypoxia was also shown to be practically nil, if normoxia was maintained in the limb.

O2 delivery to contracting muscle during hypoxic or CO hypoxia

1987 ◽  
Vol 63 (2) ◽  
pp. 726-732 ◽  
Author(s):  
C. E. King ◽  
S. L. Dodd ◽  
S. M. Cain
Keyword(s):  
Blood Flow ◽  
Gastrocnemius Muscle ◽  
Dissociation Curve ◽  
Muscle Preparation ◽  
O2 Uptake ◽  
Oxyhemoglobin Dissociation Curve ◽  
O2 Extraction ◽  
O2 Supply ◽  
O2 Delivery ◽  
Oxyhemoglobin Dissociation

The consequences of a decreased O2 supply to a contracting canine gastrocnemius muscle preparation were investigated during two forms of hypoxia: hypoxic hypoxia (HH) (n = 6) and CO hypoxia (COH) (n = 6). Muscle O2 uptake, blood flow, O2 extraction, and developed tension were measured at rest and at 1 twitch/s isometric contractions in normoxia and in hypoxia. No differences were observed between the two groups at rest. During contractions and hypoxia, however, O2 uptake decreased from the normoxic level in the COH group but not in the HH group. Blood flow increased in both groups during hypoxia, but more so in the COH group. O2 extraction increased further with hypoxia (P less than 0.05) during concentrations in the HH group but actually fell (P less than 0.05) in the COH group. The O2 uptake limitation during COH and contractions was associated with a lesser O2 extraction. The leftward shift in the oxyhemoglobin dissociation curve during COH may have impeded tissue O2 extraction. Other factors, however, such as decreased myoglobin function or perfusion heterogeneity must have contributed to the inability to utilize the O2 reserve more fully.

Adrenergic vasoconstriction augments tissue O2 extraction during reductions in O2 delivery

1994 ◽  
Vol 76 (4) ◽  
pp. 1454-1461 ◽  
Author(s):  
L. A. Maginniss ◽  
H. Connolly ◽  
R. W. Samsel ◽  
P. T. Schumacker
Keyword(s):  
Blood Volume ◽  
Supply And Demand ◽  
Sympathetic Tone ◽  
Whole Body ◽  
Metabolic Demand ◽  
O2 Extraction ◽  
Limit Blood Flow ◽  
Anesthetized Dogs ◽  
O2 Supply ◽  
O2 Delivery

When systemic O2 delivery is reduced, increases in systemic O2 extraction are facilitated by sympathetically mediated increases in vascular resistance that limit blood flow to regions with low metabolic demand. Local metabolic vasodilation competes with this vasoconstriction, thereby effecting a balance between tissue O2 supply and demand. This study examined the role of sympathetically mediated vasoconstriction on the critical level of O2 extraction in hindlimb and whole body during progressive reductions in O2 delivery. In anesthetized dogs, the left hindlimb was vascularly isolated and its O2 delivery was decreased in stages by reducing the speed of an occlusive pump. In a normovolemic group (n = 6), blood volume was maintained to minimize sympathetic tone while flow to the hindlimb was reduced. In a hypovolemic group (n = 6), blood volume was removed in stages to augment sympathetic tone progressively while flow to the limb was reduced simultaneously. A phenoxybenzamine group (n = 6) was identical to the hypovolemic group, except that alpha-adrenergic effects were inhibited with phenoxybenzamine (3 mg/kg). The systemic critical O2 extraction ratio in the phenoxybenzamine group (0.60 +/- 0.06) was less than for the hypovolemic group (0.71 +/- 0.04; P = 0.004). In the hindlimb, critical O2 extractions were significantly less in the normovolemic (0.46 +/- 0.17) and phenoxybenzamine (0.49 +/- 0.10) groups compared with the hypovolemic group (0.72 +/- 0.10; P < or = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

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