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Biomedical subjects

S M Cain

Publications and source records attributed to S M Cain.

At least 91 records · Page 5Linked to original sources
PubMed1985

The role aortic chemoreceptors during severe CO hypoxia.

The importance of aortic chemoreceptors in the circulatory responses to severe carbon monoxide (CO) hypoxia was studied in anesthetized dogs. The aortic chemoreceptors were surgically denervated in eight dogs prior to the induction of CO hypoxia, with nine other dogs serving as intact controls. Values for both whole body and hindlimb blood flow, vascular resistance, and O2 uptake were determined prior to and at 30 min of CO hypoxia in the two groups. Arterial O2 content was reduced 65% using an in situ dialysis method to produce CO hypoxia. At 30 min of hypoxia, cardiac output increased but limb blood flow remained at prehypoxic levels in both groups. This indicated that aortic chemoreceptor input was not necessary for the increase in cardiac output during severe CO hypoxia, nor for the diversion of this increased flow to nonmuscle tissues. Limb O2 uptake decreased during CO hypoxia in the aortic-denervated group but remained at prehypoxic levels in the intact group. The lower resting values for limb blood flow in the aortic-denervated animals required a greater level of O2 extraction to maintain resting O2 uptake. When CO hypoxia was superimposed upon this compensation, an O2 supply limitation occurred because the limb failed to vasodilate even as maximal levels for O2 extraction were approached.

Animals↗
PubMed1985

Hindlimb vascular responses to sympathetic augmentation during acute anemia.

The effect of increased sympathetic activity on skeletal muscle blood flow during acute anemic hypoxia was studied in 16 anesthetized dogs. Sympathetic activity was altered by clamping the carotid arteries bilaterally below the carotid sinus. One group (n = 8) was beta blocked by administration of propranolol (1 mg/kg); a second group (n = 8) was untreated. Venous outflow from the left hindlimb was isolated for measurement of blood flow and O2 uptake (VO2). After a 20-min control period, both carotid arteries were clamped (CC) for 20 min followed by a 20-min recovery period. The sequence was repeated after hematocrit was lowered to about 15% by dextran exchange for blood. Prior to anemia, CC did not alter cardiac output or limb blood flow in either group. After induction of anemia, hindlimb resistance was higher with CC in the beta block than in the no block group. Both limb blood flow and VO2 fell in the beta-block group with CC during anemia. Beta block also prevented the additive increases in whole body VO2 seen with CC and induction of anemia. The data showed that the increased vasoconstrictor tone that was obtained with beta block during anemia was successful in redistributing the lower viscosity blood away from resting skeletal muscle, even to the point that muscle VO2 was decreased.

Adrenergic beta-Antagonists↗
PubMed1985

Peripheral vascular responses to hypoxic hypoxia after aortic denervation.

We wished to see whether aortic chemoreceptors and other vagal afferent traffic played an essential role in the circulatory adjustments to hypoxic hypoxia. Aortic chemoreceptors were denervated (AD) in one group (n = 6) of anesthetized dogs, bilateral cervical vagotomy (V) was done on a second group (n = 6), and a third group (n = 6) was sham-operated to serve as a control. Venous outflow from the left hindlimb was isolated. After a 20-min control period of ventilation with room air, the animals were ventilated for 60 min with 9% of O2 in N2. Arterial, mixed venous, and hindlimb venous blood samples were taken every 20 min. The cardiac output response to hypoxic hypoxia was attenuated at 40 and 60 min in both the AD and V groups (p less than 0.05). Hindlimb blood flow increased equally in all three groups during hypoxia. The pressor response at the onset of hypoxia (20 min) was abolished in the AD and V groups, but mean arterial pressure fell to similar levels in all three groups by 60 min of hypoxia. We concluded that reflex aortic chemoreceptor stimulation during hypoxia augmented cardiac output mostly by effects on the venous side of the circulation but played no role in skeletal muscle vascular responses to hypoxic hypoxia.

Afferent Pathways↗
PubMed1985

Circulatory responses to 2,4-dinitrophenol in dog limb during normoxia and hypoxia.

We tested whether blood flow to skeletal muscle would increase in proportion to an increase in O2 uptake caused by 2,4-dinitrophenol (DNP). We further tested the metabolic control in the face of a central challenge, hypoxic hypoxia. Three injections of DNP were made at 30-min intervals into the arterial supply of the left hindlimb in anesthetized dogs. Similar experiments were done on a second group of dogs ventilated with 12% O2-88% N2 (DNP and hypoxia). A third group served as time controls. Limb O2 uptake increased in a linear fashion in the DNP group with each injection. The increase in limb O2 uptake fell off with the second and third injections in the DNP and hypoxia group and appeared to be limited by the hypoxia. Limb blood flow increased only with the last injection in that group and not at all in the DNP group. Limb vascular resistance decreased in both the experimental groups relative to the time-related changes in the control group. This became more marked as the O2 extraction ratio exceeded 0.5. Even in the absence of nerve stimulation and active muscle contractions, both distribution and resistance control vessels responded in a coordinated fashion to an increase in O2 uptake. Mild hypoxia enhanced these responses but also appeared to limit a fraction of O2 uptake that may not have been concerned with maintaining tissue energy levels.

Animals↗
PubMed1985

Regulation of the peripheral vasculature and tissue oxygenation in health and disease.

The evidence has become convincing that in certain critical illnesses such as ARDS, there is pathologic disturbance in O2 delivery to the tissues. This disturbance is marked by an abnormal dependency of O2 uptake upon total O2 delivery. Although this has been attributed to mitochondrial dysfunction in the past, current belief is that such apparent dysfunction is secondary to derangement of the microcirculation that causes an impairment in tissue oxygenation. Microembolization and other disturbances in the local regulation of perfusion have been postulated to be responsible for this derangement. The net effect is to increase the diffusion pathway for oxygen from the tissue capillary. Our ability to deal conceptually with this kind of alteration in tissue oxygenation is dependent upon the mathematical model that is applied. We have discussed two generic models for tissue oxygenation to show the constraints imposed upon quantifying the effects of alteration in any single factor upon tissue PO2. The salient factor that has emerged is that creation of greater than normal heterogeneity in flow or its distribution in the peripheral microcirculation has the inevitable consequence of making tissue hypoxic.

Animals↗
PubMed1984

Supply dependency of oxygen uptake in ARDS: myth or reality?

Several reports state that oxygen uptake changed in direct correlation with changes in total oxygen delivery to the tissues in the adult respiratory distress syndrome (ARDS). Oxygen uptake appeared to be limited by oxygen delivery even at normally adequate levels so that uptake was abnormally dependent on supply. These reports are discussed with respect to whether or not such a result could have been due to errors in measurement or to mathematical coupling by relating two quantities that shared a common variable. Having rejected that proposition, animal experiments are cited in which abnormal oxygen supply dependency was produced by microembolization. The accompanying loss of reactive hyperemia and inability to extract oxygen were consistent with a progressive loss of recruitable capillaries. Evidence is presented that the potential for embolization in ARDS is greatly enhanced by activation of the complement and arachidonic acid cascades as well as by the xanthine oxidase system. The resultant use of molecular oxygen by non-ATP producing oxidase systems might also account for the increase of supply dependent oxygen demand in ARDS.

Animals↗
PubMed1984

The role of aortic chemoreceptors during acute anemia.

The importance of aortic chemoreceptors in the circulatory and metabolic responses during acute anemia was studied in anesthetized dogs. Data were obtained from nine dogs in which the aortic chemoreceptors were surgically denervated prior to induction of anemia, and from seven sham-operated dogs. Cardiac output (QT), limb blood flow (QL), limb and whole body oxygen uptake (VO2) were determined at normal hematocrit (Hct) and at 30 min of anemia (Hct = 13%) produced by isovolemic dextran-for-blood exchange. At 30 min of anemia, QT was increased from 91 to 186 mL . kg-1 . min-1 (p less than 0.01) and from 99 to 153 mL . kg-1 . min-1 (p less than 0.01) in the sham and denervated groups, respectively. The increase in QT during anemia was less (p less than 0.05) in the aortic-denervated series. Limb flow was also increased during anemia in both groups (p less than 0.01); the mean value of 89 mL . kg-1 . min-1 in the denervated group was less than that of 130 mL . kg-1 . min-1 observed in the sham animals (p less than 0.05). Whole body VO2 decreased (p less than 0.05) in the denervated group at 30 min of anemia; limb VO2 was maintained at the preanemic control value in both groups. The data indicate that during acute anemia the aortic chemoreceptors contribute to the increase in QT.

Acute Disease↗
PubMed1984

Whole body and hindlimb cardiovascular responses of the anesthetized dog during CO hypoxia.

To compare with earlier studies of anemic hypoxia obtained by hemodilution, O2 carring capacity was decreased by carbon monoxide (CO) hypoxia. Arterial O2 content was reduced either 50% (moderate CO) or 65% (severe CO). In two groups of anesthetized dogs (moderate and severe CO) hindlimb innervation remained intact while in a third group (moderate CO) the hindlimb was denervated. Measurements were obtained prior to and at 30 and 60 min of CO hypoxia. Cardiac output was elevated at 30 min of CO hypoxia in all groups (p less than 0.01) and in the severe CO group at 60 min (p less than 0.01). Hindlimb blood flow remained unchanged during CO hypoxia in the intact groups. In the denervated group, hindlimb blood flow was greater (p less than 0.05) than that in the intact groups throughout the experiment. A decrease in mean arterial pressure (p less than 0.01) in all groups was associated with a fall in total resistance (p less than 0.01). Hindlimb resistance remained unchanged during moderate CO hypoxia in the intact group but increased (p less than 0.05) in the denervated group. In the severe CO group hindlimb resistance was decreased (p less than 0.05) at 60 min. The results indicate that the increase in cardiac output during CO hypoxia was directed to nonmuscle areas of the body and that intact sympathetic innervation was required to achieve this redistribution.

Anesthesia↗
PubMed1984

The effects of hyperoxia on oxygen uptake during acute anemia.

The effects of normobaric hyperoxia on the oxygen uptake (VO2) and cardiovascular responses of the whole body and hindlimb during anemia were investigated. Anesthetized, paralyzed dogs were ventilated for 20-min periods with room air (normoxia), 100% O2 (hyperoxia), and returned to room air. Anemia (hematocrit = 15%) was then induced by isovolemic dextran-for-blood exchange and the normoxia, hyperoxia, normoxia sequence was repeated. Whole body VO2 and cardiac output rose following anemia, and then fell (p less than 0.05) with hyperoxia during anemia. These responses were not abolished by beta-blockade with propranolol (1 mg/kg, iv) or bilateral vagotomy. The hindlimb data for blood flow and VO2 were similar in direction to those of the whole body but were more variable. Section of the sciatic and femoral nerves did not appear to have significant effect on the limb responses to hyperoxia. The decrease in whole body and hindlimb VO2 with hyperoxia during anemia may have resulted from a redistribution of capillary blood flow away from exchange vessels in response to the elevated PO2.

Acute Disease↗
PubMed1983

Oxygen uptake and blood flow in canine skeletal muscle during moderate and severe anemia.

The metabolic and cardiovascular adjustments of the whole body and skeletal muscle were studied during moderate and severe acute anemia. In 15 anesthetized dogs, venous outflow from the gastrocnemius-plantaris muscle group was isolated. Cardiac output (QT) muscle blood flow (QM), total body and muscle oxygen uptake (VO2) were determined during a control period, and at 30 and 60 min of either (i) moderate anemia (n = 8) in which the mean hematocrit (Hct) was 25% or (ii) progressive anemia (n = 7) in which the mean Hct values were 25% at 30 min and 16% at 60 min of anemia. Muscle VO2, QT, and QM were increased in both groups at 30 min of anemia. By 60 min, QT and QM declined to preanemic control values in the moderate anemia group; whole body VO2 was maintained at the control level. Arterial oxygen transport was the same in the two groups at both 30 and 60 min of anemia despite the difference in Hct at 60 min. Muscle VO2 showed a further and similar rise in both groups between 30 and 60 min of anemia. These data show that the rise in muscle VO2 during acute anemia was not directly proportional to the degree of the hematocrit reduction. Further, the findings suggest that the muscle VO2 response was related to the decrease in arterial oxygen transport.

Anemia↗
PubMed1983

O2 transport during two forms of stagnant hypoxia following acid and base infusions.

Cardiac output and mean arterial pressure were decreased in two groups of 16 anesthetized paralyzed dogs ventilated by pump. Pericardial tamponade was used in one group, and hemorrhagic hypotension was used in the other. After a 30-min control period and 30 min of circulatory shock by either method, 0.3N HCl was infused into half the dogs in each group and 1.0N NaHCO3 into the other half so that pH was separated by 0.3-0.4 units. The slope of the line relating O2 uptake to total O2 transport (blood flow X arterial O2 concentration) was used to evaluate how well the tissues extracted O2 relative to O2 supply. During the initial shock period before infusion, the slope of the line relating O2 uptake of left hindlimb skeletal muscle to total O2 transport in the limb was almost twice as great as that for the whole body. Acid infusion increased the slope of the whole-body line but did not alter that for the hindlimb. Base infusion, on the other hand, decreased the slope of the line for the limb during hemorrhagic shock but had no other effect. We concluded that acid either improved the distribution of a limiting blood supply to nonmuscle organ systems, or increased tissue capillary PO2 and O2 diffusion by decreasing hemoglobin O2 affinity (HOA), or both. The effect of an increased HOA with base infusion was noticeable in hindlimb skeletal muscle only when volume depletion by hemorrhage presumably greatly increased the normally short intercapillary diffusion distance in muscle.

Animals↗
PubMed1983

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

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.

Adrenergic beta-Antagonists↗
PubMed1983

Critical O2 transport values at lowered body temperatures in rats.

Whole-body O2 uptake (VO2) in rats was reported not to increase when total O2 transport (TOT = cardiac output X arterial O2 concentration) was increased above normal ranges when body temperature was kept at 38 degrees C (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 53: 660-664, 1982). Similar experiments were performed to see if hypothermic rats at 34 degrees C would increase VO2 with an increased TOT in an effort to generate heat. Anesthetized rats were ventilated with 9 or 12% O2 (hypoxia), room air (normoxia), and O2 (hyperoxia) to vary TOT from 52.6 to 6.6 ml X kg-1 X min-1. VO2 was measured in a closed-circuit, double servospirometer system. Although VO2 was significantly lower at 34 degrees C than the values previously found at 38 degrees C with normoxia and hyperoxia, there was no increase with increasing values of TOT. In spite of a lower plateau value of VO2 at 34 degrees C, the critical value of TOT below which VO2 could not be maintained was nearly the same as at 38 degrees C (22 ml X kg-1 X min-1). The reason for this was that O2 was less completely extracted as TOT was lowered below the critical value in the hypothermic animal. Some of the difficulty in extracting O2 at the tissues was probably due to the decrease in P50 (PO2 at 50% saturation) that occurs with decreased body temperature.

Animals↗
PubMed1983

Peripheral oxygen uptake and delivery in health and disease.

Peripheral O2 uptake is mandated to subserve the energy requirements of tissue and organ systems in an obligatory aerobe such as the human. In addition to this basic need, local O2 demand may also be increased by more general bodily conditions such as fever, increased catecholamine levels, or alkalosis. Blood flow, which brings O2 to the periphery, is closely regulated at the local level to meet O2 demand except where other functional requirements, such as filtering by the kidney, may intervene. In addition to regulation of total flow at the tissue level, the distribution of flow at the microcirculatory level is another important regulatory feature because it determines the capillary surface area available to extract O2. Dominant vasoconstrictor tone is modulated at the local level by a metabolically linked substance such as adenosine or possibly by a direct effect of PO2 on the microvasculature. The precapillary vessels that control distribution are more sensitive to local hypoxia than are the resistance vessels so that blood flow redistribution is a first-line defense. The total blood flow response is made more sensitive by activity of beta-adrenergic vasodilator receptors which are active in this counterpoised system of local blood flow control. Disruption of the microvasculature, such as by microembolization, makes O2 uptake more dependent upon O2 supply than is normally the case. This event is accompanied by a loss of autoregulatory ability. In view of the myriad potential effectors on microvascular smooth muscle, the true wonder is that blood flow and O2 delivery generally are so strongly meshed with O2 uptake at every level of functional organization in the body. It would hardly be surprising, then, if disruption in one part of the system, such as the pulmonary circulation, had a counterpart in the peripheral circulation. This was alluded to in the possible association of O2 supply dependency in the periphery and severe ventilation-perfusion abnormality in the lung during ARDS. It reminds us that deranged processes that are revealed by relatively routine measurements may not be restricted to a single target organ.

Animals↗
PubMed1982

Total and hindlimb O2 uptake and blood flow in hypoxic dogs given dopamine.

Cardiovascular interactions between dopamine and hypoxia were examined in 8 anesthetized, paralyzed dogs ventilated at constant rates. Total and hindlimb (less paw) O2 uptake, blood flow, and vascular resistance were measured with and without dopamine infusion of 10 micrograms/kg . min during both normoxic and hypoxic ventilation. Another 8 dogs were similarly treated after beta-blockade with propranolol infusion (1 mg/kg). During the baseline period, normoxic dopamine significantly increased total O2 uptake, cardiac output, and stroke volume, and significantly decreased total vascular resistance in the control group. Hypoxia decreased total O2 uptake, cardiac output, and heart rate but increased total vascular resistance. Dopamine reversed each of these hypoxic changes and restored total O2 uptake to normoxic levels. Hindlimb measurements were not significantly changed by dopamine or hypoxia in the control group. During hypoxia, beta-blockade abolished dopamine's effects except for the decrease in total vascular resistance. The improvement in cardiac output and O2 transport by dopamine infusion resulted from increased stroke volume during normoxia and from increased heart rate during hypoxia.

Adrenergic beta-Antagonists↗