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Biomedical subjects

S M Cain

Publications and source records attributed to S M Cain.

At least 73 records · Page 4Linked to original sources
PubMed1988

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

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.

Animals↗
PubMed1988

Regional hemodynamic responses to hypoxia in polycythemic dogs.

Polycythemia increases blood viscosity so that systemic O2 delivery (QO2) decreases and its regional distribution changes. We examined whether hypoxia, by promoting local vasodilation, further modified these effects in resting skeletal muscle and gut in anesthetized dogs after hematocrit had been raised to 65%. One group (CON, n = 7) served as normoxic controls while another (HH, n = 6) was ventilated with 9% O2--91% N2 for 30 min between periods of normoxia. Polycythemia decreased cardiac output so that QO2 to both regions decreased approximately 50% in both groups. In compensation, O2 extraction fraction increased to 65% in muscle and to 50% in gut. When QO2 was reduced further during hypoxia, blood flow increased in muscle but not in gut. Unlike previously published normocythemic studies, there was no initial hypoxic vasoconstriction in muscle. Metabolic vasodilation during hypoxia was enhanced in muscle when blood O2 reserves were first lowered by increased extraction with polycythemia alone. The increase in resting muscle blood flow during hypoxia with no change in cardiac output may have decreased O2 availability to other more vital tissues. In that sense and under these experimental conditions, polycythemia caused a maladaptive response during hypoxic hypoxia.

Animals↗
PubMed1988

Cardiorespiratory consequences of fluorocarbon reactions in dogs.

Cardiorespiratory responses to 2 ml intravenous doses of fluorocarbon emulsions were investigated in dogs anaesthetised with pentobarbitone and artificially ventilated with air. Systemic and pulmonary artery pressures were measured using catheters in the femoral artery and external jugular vein. Oxygen consumption was obtained by analysis and measurement of expired gases and cardiac output was calculated using the Fick principle. Venous return from the hind limb was isolated using tourniquets at thigh and ankle regions and venous effluent was measured. Homogeneity of muscle blood flow was calculated using a saline washout technique. 24 of 28 dogs reacted to Oxypherol (FC-43) and 7 of 11 reacted to Fluosol-DA (FDA) (n.s.); 2 of 3 dogs unresponsive to FDA reacted to FC-43. The reactions consisted of severe, statistically significant, systemic hypotension with decreases in cardiac output and limb blood flow. Pulmonary and systemic vascular resistances were increased and body and limb muscle oxygen delivery and oxygen consumption were decreased. Reactions tended to be more severe following FC-43. Effects were maximal at 3-4 minutes after fluorocarbon administration. Changes had usually recovered at 40-60 minutes though oxygen debts were still being repaid. It is clear that acute myocardial depression was produced. Homogeneity of limb muscle flow was still significantly reduced at "recovery" and this we attribute to complement activation and embolisation of the microvasculature.

Animals↗
PubMed1987

Critical oxygen delivery levels during shock following normoxic and hyperoxic haemodilution with fluorocarbons or dextran.

Fluosol-DA 20% (FDA), an emulsion of fluorocarbons in a glucose electrolyte solution can deliver physiologically significant amounts of oxygen (O2) to the tissues and improve ischaemic hypoxia. To investigate its effect on critical oxygen delivery level (QO2c), four groups of six phenobarbitone anaesthetised air-ventilated splenic clamped mongrel dogs were haemodiluted to a haematocrit (Hct) of 25%; two groups with FDA and two with 6% dextran solution. Oxygen consumption (VO2) was derived from expired gas measurement and analysis, or by using a spirometer and carbon dioxide absorption. Whole body O2 flux (QO2) was calculated from mixed venous and arterial O2 contents and the Fick-derived cardiac output. QO2 was progressively decreased by haemorrhaging in steps of 1.5-2.5 ml per kg. Hct was kept at 25% using packed cells. VO2/QO2 pairs were calculated at each step and QO2c was determined for each animal by least squares fitting of data with 2 straight lines. Analyses of variance were performed. QO2c was significantly less in the FDA and O2 (F+O) group than either the dextran and O2 (D+O) or dextran and air (D+A) groups. Analysis of O2 extraction at QO2c, which effectively normalized results for differences in resting, VO2, had significantly better extraction in the FDA and air (F+A) than the D+A group. When fluorocarbon- and plasma-dissolved oxygen was subtracted, the O2 extraction in the F+A group was significantly better than in the D+A and F+O groups. The results imply that normoxic FDA haemodilution in animals respiring air can improve O2 delivery and that hyperoxia interferes with this process.

Animals↗
PubMed1987

The concept of a critical oxygen delivery.

In healthy tissues, decreases in oxygen delivery (QO2 = cardiac output X arterial O2 content) do not lower oxygen consumption (VO2) because tissue O2 extraction increases proportionately. When delivery is reduced below a critical threshold, VO2 falls because tissue extraction exceeds a critical threshold, and cannot compensate for the reduction in delivery. In the adult respiratory distress syndrome and perhaps in septicemia, tissue extraction capacity is impaired, leading to O2 supply dependency despite normal or increased overall delivery. This pathologic supply dependency could be caused by a loss in autoregulatory capacity, by disrupted blood flow distribution secondary to peripheral microembolization, or to other factors interfering with efficient tissue distribution of QO2 with respect to VO2. Alternatively, the increased VO2 may be consumed in biochemical pathways not associated with ATP production, or in the production of oxygen radicals or hydrogen peroxide. To the extent this abnormal dependence of VO2 on QO2 reflects tissue hypoxia, clinical interventions which decrease systemic delivery should be evaluated with regard to possible deleterious effects on organ system function.

Hemodynamics↗
PubMed1987

Peripheral vascular responses to fluorocarbon administration.

To detect the local effect of hyperoxia on skeletal muscle vasculature, 2.5-ml boluses of oxygenated or deoxygenated fluorocarbon emulsion (F-O2 or F-N2) were washed through the hindlimb of anesthetized dogs at prevailing arterial pressure. Instantaneous hematocrit changes at the outflow were registered and stored in digital form with the red cells serving as the nondiffusible tracer in the resulting washout curves. A gamma density function was fitted and the gamma index (1/square root of alpha) was derived as a measure of skewness or perfusion heterogeneity. After recovery from the initial hypotensive reaction to fluorocarbon emulsion, washout curves for F-O2 and F-N2 were registered and blood samples were taken during 40 min of normoxia followed by 40 min of hypoxic hypoxia. The initial reaction to fluorocarbon significantly increased the gamma index so that the experiments began with a high index of perfusion heterogeneity in the limb vasculature. No significant difference was seen between F-O2 and F-N2 in normoxia but F-O2 maintained greater heterogeneity during hypoxia. The increased heterogeneity observed after the fluorocarbon reaction correlated highly with the severity of the hypotensive reaction which was also found to correlate inversely with the ability of the limb musculature to increase the O2 extraction ratio with onset of hypoxia. This blunting of microcirculatory reactivity to hyperoxia and hypoxia was attributed, in part, to the initial transient fluorocarbon reaction, possibly mediated by complement activation.

Animals↗
PubMed1987

Responses of innervated and denervated gut to whole-body hypoxia.

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.

Animals↗
PubMed1987

Muscle O2 deficit during hypoxia and two levels of O2 demand.

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.

Animals↗
PubMed1987

Regional O2 uptake during hypoxia and recovery in hypermetabolic dogs.

The regional distribution of O2 deficit in muscle and nonmuscle tissues was measured in hypermetabolic dogs ventilated with a low inspired O2 fraction and was compared with excess O2 used in these regions during normoxic recovery. O2 uptake was stimulated by 2,4-dinitrophenol (DNP). Arterial, mixed venous, and muscle venous blood samples were drawn before, during, and after severe hypoxia (9% O2-91% N2) for the calculation of hindlimb O2 uptake and cardiac output. The O2 deficit and excess O2 uptake in recovery were calculated as the cumulative differences between normoxic control and respective hypoxic and recovery O2 uptake values. The DNP data were compared with data previously obtained in our laboratory. A greater whole-body O2 deficit was incurred in the DNP group during hypoxia and was associated with a larger O2 use in recovery. The total O2 deficit was equally distributed between muscle and nonmuscle tissues, but more excess O2 use occurred in nonmuscle tissues. The greater excess O2 used by nonmuscle tissues may have been associated with the restoration of intracellular ion concentrations brought about by the increased activity of energy-using membrane pumps.

2,4-Dinitrophenol↗
PubMed1987

Systemic and intestinal limits of O2 extraction in the dog.

When systemic delivery of O2 (QO2 = QT X CaO2, where QT is cardiac output and CaO2 is arterial O2 content) is reduced by bleeding, the systemic O2 extraction ratio [ER = (CaO2 - CVO2)/CaO2, where CVO2 is venous O2 content] increases until a critical limit is reached below which O2 uptake (VO2) becomes limited by O2 delivery. During hypovolemia, reflex increases in mesenteric arterial tone may preferentially reduce gut blood flow so that the onset of O2 supply dependence occurs in the gut before other regions. We compared the critical O2 delivery (QO2c) and critical extraction ratio (ERc) of whole body and an isolated segment (30-50 g) of small bowel in seven anesthetized paralyzed dogs ventilated with room air. Systemic QO2 was reduced in stages by controlled hemorrhage as arterial O2 content was maintained, and systemic and gut VO2 and QO2 were measured at each stage. Body QO2c was 7.9 +/- 1.9 ml X kg-1 X min-1 (ERc = 0.69 +/- 0.12), whereas gut O2 supply dependency occurred when gut QO2 was 34.3 +/- 11.3 ml X min-1 X kg gut wt-1 (ERc = 0.63 +/- 0.09). O2 supply dependency in the gut occurred at a higher systemic QO2 (9.7 +/- 2.7) than whole-body QO2c (P less than 0.05). The extraction ratio at the final stage (maximal ER) was less in the gut (0.80 +/- 0.05) than whole body (0.87 +/- 0.06). Thus during reductions in systemic QO2, gut VO2 was maintained by increases in gut extraction of O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

O2 delivery to contracting muscle during hypoxic or CO hypoxia.

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.

Animals↗
PubMed1986

The physiologic reserve in oxygen carrying capacity: studies in experimental hemodilution.

The mechanisms by which the body attempts to avoid tissue hypoxia when total body oxygen delivery is compromised during acute anemia are reviewed. When the hematocrit is reduced by isovolemic hemodilution the compensatory adjustments include an increase in cardiac output, redistribution of blood flow to some tissues, and an increase in the whole body oxygen extraction ratio. These responses permit whole body oxygen uptake to be maintained until the hematocrit has been lowered to about 10%. Several factors are discussed which contribute to the increase in cardiac output during acute anemia including the reduction in blood viscosity, sympathetic innervation of the heart, and increased venomotor tone. The latter has been shown to be dependent on intact aortic chemoreceptors. With respect to peripheral vascular responses, the rise in coronary and cerebral blood flows which occur following hemodilution is proportionally greater than the increase in cardiac output while the opposite is true for kidney, liver, spleen, and intestine. Skeletal muscle does not contribute to a redistribution of blood flow to more vital areas during acute anemia despite its relatively large anaerobic capacity. Overall, peripheral compensatory adjustments result in an increased oxygen extraction ratio during acute anemia which reflects a better matching of the limited oxygen supply to tissue oxygen demands. However, some areas such as muscle are relatively overperfused which limits an even more efficient utilization of the reduced oxygen supply. Studies of the response of the microcirculation and the extent to which sympathetic vascular controls are involved in peripheral blood flow regulation are necessary to further appreciate the complex pattern of physiological responses which help ensure survival of the organism during acute anemia.

Anemia↗
PubMed1986

The role of alpha-adrenergic receptors in carbon monoxide hypoxia.

The importance of alpha-adrenergic receptors in the cardiac output and peripheral circulatory responses to carbon monoxide (CO) hypoxia was studied in anesthetized dogs. Phenoxybenzamine (3 mg/kg i.v.) was injected to block alpha-receptor activity and the data obtained were then compared with those from a previous study of CO hypoxia in unblocked animals. Values for cardiac output, hindlimb blood flow, vascular resistance, and oxygen uptake were obtained prior to and at 30 and 60 min of CO hypoxia which reduced arterial oxygen content by approximately 50%. alpha-Adrenergic blockade resulted in a lower (p less than 0.05) control value for cardiac output than observed in unblocked animals, but no differences were present between the two groups at 30 or 60 min of CO hypoxia. Similarly, limb blood flow was lower (p less than 0.05) during the control period in the alpha-blocked group but rose to the same level as that in the unblocked animals at 60 min of COH. No change in limb blood flow occurred during CO hypoxia in the unblocked group. These findings demonstrated that during CO hypoxia alpha-receptor mediated venoconstriction does not contribute to the cardiac output response and alpha-receptor mediated vasoconstriction probably does prevent a rise in hindlimb skeletal muscle blood flow.

Animals↗
PubMed1986

Adrenergic and local control of O2 uptake during and after severe hypoxia.

The distribution of whole-body O2 supply during severe hypoxia and recovery and its relation to the regional distribution of O2 deficit and repayment was studied. Mongrel dogs were anesthetized, paralyzed, and ventilated to maintain an end-tidal PCO2 between 35 and 40 Torr. In one group, the alpha- and beta-adrenergic receptors were blocked to eliminate neural and humoral adrenergic influences. In a second group, alpha-adrenergic receptors were stimulated to decrease O2 delivery by excessive vasoconstriction. In a third group, beta-adrenergic receptors were stimulated to increase O2 delivery. Whole-body and hindlimb muscle O2 uptake and vascular responses were measured during normoxic control, 15 or 30 min of severe hypoxia (9% O2 in N2), and 20 or 30 min of normoxic recovery, respectively. The whole-body O2 deficit and excess O2 uptake in recovery were partitioned into muscle and nonmuscle areas. The data showed that neural or humoral influences had little effect on the regional distribution of the total O2 deficit and O2 excess in recovery. The O2 deficit could be decreased somewhat by increasing delivery, but the amount of excess O2 used in recovery was unaffected. This suggested that the excess O2 use in recovery was more a function of an energy deficit during hypoxia and not an O2 deficit.

Animals↗
PubMed1986

Acute lung injury. Assessment of tissue oxygenation.

The physiologic factors governing oxygen delivery to the peripheral tissues are briefly reviewed to show how tissue PO2 is defended when acute lung injury causes arterial hypoxemia. A loss of recruitable capillary reserve in the tissues may be another serious consequence of the same events that cause lung injury in the adult respiratory distress syndrome, and may cause a defect in tissue oxygen extraction.

Animals↗