Biomedical subjects

A R Hohimer

Publications and source records attributed to A R Hohimer.

At least 37 records · Page 2Linked to original sources

PubMed1991

Fetal cerebral blood flow and metabolism during oligemia and early postoligemic reperfusion.

The early time period following ischemia may be of pathogenetic importance in hypoxic-ischemic brain injury. Global cerebral oligemia was induced in ten late gestation fetal sheep by inflation of a balloon occluder around the brachiocephalic artery. Cerebral blood flow, oxygen, glucose, and lactate net flux, and oxygen delivery were measured by the Fick principle following 1 h of oligemia and at 5, 30, and 60 min of postoligemic reperfusion. During oligemia, cerebral blood flow decreased by 74 +/- 10% (mean +/- SD) and oxygen consumption decreased by 34 +/- 24%. The glucose:oxygen quotient was elevated throughout the oligemic period. In the early (5 min) reperfusion period, blood flow and oxygen delivery were not different from control but oxygen consumption was persistently depressed by 27 +/- 32%; fractional extraction of oxygen was 0.38 +/- 0.10 during control and 0.24 +/- 0.09 during early reperfusion. The venous oxygen tension increased modestly from 15.2 +/- 2.4 to 18.0 +/- 1.7 mm Hg; the postoligemic venous pO2 was limited by the lack of reactive hyperemia combined with the low arterial pO2 of the intrauterine environment. Postoligemic carbohydrate fluxes could not be differentiated from control possibly due to blood-brain barrier limitations. These factors may be related to the relative resistance of the fetal brain to hypoxic-ischemic injury.

Animals↗

PubMed1991

Unidirectional transport of glucose and lactate into brain of fetal sheep and guinea-pig.

The first-passage multiple-indicator dilution method was used to measure blood to brain transport of D- and L-glucose, D- and L-lactate and sucrose relative to 22Na, an impermeable reference tracer, in fetal sheep. Fractional extraction for D-glucose was 0.315 +/- 0.051 (S.E.M.) at normal glucose levels and fell to 0.198 +/- 0.041 at 5.2 +/- 0.4 mM-glucose. Fractional extractions for L-glucose, D- and L-lactate and sucrose were not different from zero. No specific blood-brain transport system was detected for L-lactate in fetal sheep in vivo (fractional extraction = -0.024 +/- 0.019). Uptake of L-lactate into isolated microvessels from fetal sheep cerebrum in vitro showed a slightly higher rate (32.2 +/- 8.9 pmol min-1 (mg protein)-1) than that for D-lactate (22.6 +/- 5.6). In fetal guinea-pigs, the carotid arterial injection method with tritiated water as the permeable reference was used to measure the brain uptake index (BUI). BUI was determined for D-glucose (0.304 +/- 0.065) sucrose (0.008 +/- 0.001), L-lactate (0.418 +/- 0.112) and D-lactate (0.071 +/- 0.024). Unidirectional influx calculated from these measurements and estimates of cerebral blood flow showed that transport would be rate-limiting for cerebral glucose utilization at arterial glucose levels below 0.5 mM in fetal sheep and 1.7 mM in fetal guinea-pig. In fetal sheep, but not in fetal guinea-pigs, lactate efflux may be limited by brain-blood transport.

Animals↗

PubMed1991

Hemodynamics and organ blood flow in fetal sheep subjected to chronic anemia.

To investigate cardiovascular adaptation to chronic anemia we studied eight ovine fetuses made anemic by serial isovolemic hemorrhage and seven nonanemic controls. After 1 wk carotid arterial oxygen content was reduced to 1.6 +/- 0.2 ml/dl and hematocrit to 13.3 +/- 1.6% in anemic fetuses compared with 6.9 +/- 1.2 ml/dl and 32.4 +/- 3.9% in controls. Cardiac output was higher in the anemic group (753 +/- 102 vs. 490 +/- 66 ml.min-1.kg fetus-1) as stroke volume and heart rate both increased. Blood flow to the carcass, skin, kidneys, intestines, brain, and heart was increased. Vascular resistance fell in all tissues except the placenta. Central venous pressure, arterial pH, plasma total protein, and blood volume were not different although extravascular fluid accumulated in six of the anemic fetuses. The estimated capillary hydrostatic pressure was greater in anemic (7.6 +/- 1.8 mmHg) than control fetuses (5.0 +/- 1.5 mmHg) and the ratio of precapillary to postcapillary resistance was less. We conclude that reduction in the ratio of precapillary to postcapillary resistance in chronic fetal anemia increases blood flow, oxygen delivery, and capillary hydrostatic pressure.

Anemia↗

PubMed1991

Vascular lactic acid infusions do not alter the incidence of fetal breathing movements or their inhibition by acute hypoxemia.

Hypoxemia transiently inhibits the incidence of fetal breathing movements (FBM), but their incidence returns to normal after several hours despite maintained hypoxemia. We hypothesized that the lactic acidosis associated with prolonged systemic hypoxemia might mediate the adaptation of the hypoxemic inhibition of FBM. In sheep fetuses, the incidence of FBM was measured in a control hour and during 6 h of i.v. infusion of L-lactic acid, which raised the blood lactate concentrations to levels seen with moderate hypoxemia. FBM were observed at the same incidence as during control during each of the first 4 h (all approximately 40%). In the 5th h of lactic acid infusion, fetal hypoxemia was induced by lowering maternal inspired oxygen fraction and FBM occurred only 8 +/- 1% (SEM) of that hour. In a subsequent normoxemic recovery hour, the incidence of FBM remained below control levels. In the same animals on a different day, a similar hypoxemia induced without the acid infusion caused a comparable inhibition of FBM, but the incidence of FBM returned to the control level in a subsequent recovery hour. A moderate peripheral lactic acidosis does not blunt the inhibition of FBM evoked by acute hypoxemia and is not a likely explanation for the return of FBM during prolonged hypoxemia but actually might mediate some of the inhibition.

Acidosis, Lactic↗

PubMed1990

Theophylline stimulates fetal breathing movements during hypoxia.

The respiratory responses to theophylline during normoxia and hypoxia were determined in 13 unanesthetized fetal sheep. Theophylline (plasma levels approximately 111 mumol/L) increased the incidence of fetal breathing movements measured over 120 min from 37.7 +/- 4.8% to 61.1 +/- 5.7% (SEM) in normoxic fetuses. In isocapnic hypoxia (arterial O2 tension approximately 1.86 kPa), theophylline increased the incidence from 20.0 +/- 6.3 to 52.0 +/- 6.1%. Theophylline also resulted in an increase in the slope of inspiration during both normoxia and hypoxia. We conclude that adenosine modulates fetal respiratory drive during normoxia and hypoxia.

Adenosine↗

PubMed1989

The effect of electrocortical state on cerebral carbohydrate metabolism in fetal sheep.

We measured hemispherical cerebral blood flow and arteriovenous differences across the cerebral cortex for glucose, oxygen, and lactate during the two primary electroencephalographic patterns (high and low voltage) in unanesthetized, near-term fetal sheep. Oxygen consumption was 127 mumol/min/100 g brain in high voltage and was 14% higher in low voltage. Glucose uptake was 19 mumol/min/100 g and was 37% higher in low voltage. Cerebral blood flow was 112 ml/min/100 g and was 29% higher in low voltage. The glucose:oxygen quotient increased from 0.91 in high voltage to 1.08 in low voltage. There was a net lactate efflux of 3.2 mumol/min/100 g during low voltage compared to a net influx of 3.3 mumol/min/100 g in high voltage. During high voltage the fetal brain uses a small amount of lactate for oxidative metabolism. During low voltage, glucose uptake exceeds the oxygen uptake needed for completely aerobic consumption, and a portion of the energy utilized by the brain is produced anaerobically.

Animals↗

PubMed1989

The effect of elevated blood glucose on the electroencephalogram and cerebral metabolism during short-term brain ischemia in fetal sheep.

The effect of cerebral ischemia on cerebral metabolism and the electroencephalogram was studied with and without prior glucose infusion in near-term normoxic fetal sheep. At normal blood glucose levels, the electroencephalogram decreased in amplitude during ischemia. At elevated blood glucose levels the electroencephalographic amplitude was much less attenuated by ischemia although Fast Fourier Transforms revealed a shift toward slower frequencies. Under either normal or elevated blood glucose conditions, ischemia caused cerebral oxygen consumption to decrease, glucose uptake to increase, and a net efflux of lactate to occur. Elevated blood glucose appears to help maintain electroencephalographic activity during ischemia, perhaps by fueling additional anaerobic energy production. The relationship between the electroencephalogram, brain metabolism, and brain damage remains to be defined.

Animals↗

PubMed1989

Effects of cephalic hypotension, hypertension, and barbiturates on fetal cerebral flood flow and metabolism.

The effect of altered perfusion pressure (cephalic arterial pressure minus sagittal venous pressure) on cerebral blood flow was examined in chronically catheterized fetal sheep under ganglionic blockade. Perfusion pressure was decreased by partial inflation of a brachiocephalic artery occluder and increased by an intravenous angiotensin II infusion. Cerebral flood flow was measured with radiolabeled microspheres. On average, 45% +/- 3% (SEM) reductions in perfusion pressure were accompanied by 49% +/- 4% decreases in cerebral blood flow. Increases in perfusion pressure of 42% +/- 3% were associated with 45% +/- 7% increments in cerebral flood flow. The cerebral oxygen consumption was not significantly altered in either case. We also investigated the effect of pentobarbital on fetal cerebral oxygen consumption and cerebral blood flow at normal and at altered perfusion pressure. At normal perfusion pressure pentobarbital caused a 27% +/- 5% decrease in cerebral oxygen consumption that was associated with a 44% +/- 4% decrement in cerebral blood flow and a slight widening of the arteriovenous oxygen content gradient. In this hypometabolic cerebral state, alterations in perfusion pressure were again accompanied by proportional changes in cerebral blood flow. Both perfusion pressure and the cerebral oxygen consumption appear to be important determinants of fetal cerebral blood flow.

Animals↗

PubMed1989

Cerebral carbohydrate metabolism during severe ischemia in fetal sheep.

The effect of cephalic hypotension on brain metabolism was studied in 10 unanesthetized, normoxic (PaO2 greater than 17 mm Hg), late-gestation fetal lambs. Perfusion pressure (cephalic arterial minus sagittal venous pressure) was 40 +/- 1 mm Hg (SEM) during control and was reduced to 10 +/- 1 by occlusion of the Grachio-cephalic artery. Cerebral blood flow was measured with microspheres, and arterial and sagittal vein blood samples were analyzed for oxygen content, glucose, and lactate. During the occlusion, oxygen consumption decreased from 125 +/- 8 to 95 +/- 4 (p less than 0.05) (all values mumol 100 g-1 min-1), and glucose uptake increased from 20 +/- 3 to 25 +/- 1 (p less than 0.05). During the control period, there was no net lactate flux; during the occlusion, lactate excretion was 5.7 +/- 1.4 (p less than 0.005). The control glucose and oxygen uptakes demonstrated a normal 6:1 molar ratio; however, during the occlusion, 9.4 mumol 100 g-1 glucose min-1 were taken up in excess of expected aerobic glucose metabolism. If all of this glucose were anaerobically metabolized to lactate, three times the measured efflux would be produced. The transport properties of the fetal blood-brain barrier may be important factors in perinatal brain injury.

Animals↗

PubMed1989

Vascular pressure-volume relationships in pregnant and estrogen-treated guinea pigs.

We investigated the relationship between mean circulatory filling pressure (MCFP) and blood volume in nonpregnant (NP), estrogen-treated (E), and pregnant (P) guinea pigs. Reversible circulatory arrest was produced by rapid ventricular pacing or acetylcholine in unanesthetized animals remote from surgery. MCFP (mmHg) was higher for E (7.1 +/- 0.3) than for NP (5.8 +/- 0.5) or P (5.3 +/- 0.4). The gradient for venous return, the difference between MCFP and right atrial pressure (mmHg), did not differ in NP- (6.0 +/- 0.5), P- (5.8 +/- 0.5), or E- (5.8 +/- 0.4) treated animals. Capacitance, the blood volume (ml/kg) at an MCFP of 6 mmHg, was increased in P (84 +/- 6) and E (89 +/- 7), compared with NP (64 +/- 5) animals. Compliance, the ratio of the change in volume to change in pressure in the range of 6-12 mmHg (ml.kg-1.mmHg-1), was greater in P (4.4 +/- 0.3) than NP (3.5 +/- 0.3) animals. Hexamethonium blockade did not affect MCFP, capacitance, or compliance. We conclude that the effect of blood volume expansion on the circulation in pregnancy cannot be predicted from knowledge of MCFP-blood volume relationships in the nonpregnant animal, because capacitance and compliance are altered. Estrogen administration to nonpregnant animals reproduces some of these effects.

Animals↗

PubMed1989

Effect of asphyxia on respiratory activity in fetal sheep.

Hypoxia in fetal sheep depresses respiratory activity. To determine if this effect is counterbalanced by hypercarbia we studied the effects of two levels of asphyxia produced by occlusions of the maternal uterine artery. Moderate asphyxia (PaO2 16.8 +/- 1.6 (SEM) PaCO2 48.9 +/- 1.0 torr) produced no changes in the percent time fetal breathing movements occupied each hour which ranged from 25.6 +/- 7.0 to 32.4 +/- 6.2%. However, a more marked asphyxia (PaO2 12.0 +/- 0.3, PaO2 57.0 +/- 1.6) resulted in a decrease in fetal respiratory activity to 8.7 +/- 3.7% during the first hour. This depression was sustained over the next 2 h but by the 5th hour breathing had returned to 26.2 +/- 7.3%. We concluded that hypercarbia can offset the respiratory inhibition of acute moderate hypoxia, but not that of a more marked lowering of PaO2 in fetal sheep. Severe asphyxia causes an initial inhibition of respiration which is followed by a return to normal respiratory activity.

Analysis of Variance↗

PubMed1987

Acute anemic hypoxemia produces a transient depression in fetal respiratory activity.

Isovolemic anemia was produced in 11 unanesthetized fetal sheep by withdrawal of blood and replacement with saline-dextran. Fetal hematocrit fell from 36 +/- 1 to 19 +/- 1% (SE). Fetal breathing movements, which were present during 34.4 +/- 5.5% of 3 h before the anemia, occurred 10.1 +/- 5.3, 14.8 +/- 4.4, and 27.1 +/- 6.7% in the 3 h following. The anemia caused a fall in arterial O2 concentration from 8.4 +/- 0.3 to 3.6 +/- 0.1 vol% and sagittal vein PO2 fell from 15.4 +/- 0.5 to 12.4 +/- 0.3 Torr. Cerebral metabolic rate during the period of anemia was 2.9 +/- 0.1 ml.100 g-1.min-1, which was unchanged from the control value of 3.0 +/- 0.2 ml.100 g-1.min-1. Sagittal vein PCO2 (54.2 +/- 1.4 Torr) remained constant after the fetus was made anemic. We conclude that respiratory activity in the sheep fetus is depressed by anemic hypoxemia but that the effect is transient.

Animals↗

PubMed1986

The effect of a calcium channel blocker (nifedipine) on uterine blood flow in the pregnant goat.

The purpose of this study was to analyze the changes in maternal uterine blood flow, maternal arterial blood pressure, and maternal heart rate with the intravenous administration of nifedipine in pregnant, unanesthetized pygmy goats. Bolus injections of 2.5 to 45 micrograms/kg of maternal weight were used. Uterine blood flow did not fall significantly. A transient fall in maternal arterial blood pressure occurred in the first minute after the injection, but the pressure returned to normal after 5 minutes. Maternal heart rate increased immediately after the bolus of nifedipine and returned toward the control value by 30 minutes.

Animals↗

PubMed1985

The effect of exercise on uterine activity in the last eight weeks of pregnancy.

In order to determine if moderate maternal exercise increased uterine activity, a prospective study was done during the last 8 weeks of pregnancy in 17 women. Two forms of exercise were chosen, weight-bearing (running) and non-weight-bearing (stationary bicycle), to study this hypothesis. The results show that with these types of exercise no increase in uterine activity was noted. This is useful information to convey to pregnant patients ready to engage in a physical fitness program.

Adult↗

PubMed1985

The effect of carbonic anhydrase inhibition on breathing movements and electrocortical activity in fetal sheep.

Fetal breathing movements (FBM) indicated by repetitive negative intrathoracic pressures and biparietal electrocorticograms (ECoG) were recorded from 8 fetal sheep for 3 h before (control) and 3 h after the administration of a carbonic anhydrase inhibitor, acetazolamide. FBM and the low voltage (LV) ECoG state occurred 36 +/- 5% (SEM) and 60 +/- 3% of the control period, respectively. Virtually no FBM occurred during high voltage (HV) ECoG while in 57 +/- 6% of the LV state the fetuses were making FBM. The peak magnitude of the negative intrathoracic (tracheal) pressure deflections was 4 +/- 1 Torr. Following acetazolamide the incidence of FBM rose to 53 +/- 4% (P less than 0.01) but there was no significant change in the incidence of the LV state (58 +/- 3%). Most of the increase in the incidence of FBM remained confined to periods of LV ECoG activity so that an increased proportion of this state (88 +/- 2%, P less than 0.001) was occupied with respiratory efforts. The amplitude of the FBM also increased to 8 +/- 1 Torr (P less than 0.05). The increased incidence and depth of FBM is most likely due to an elevated hydrogen ion concentration and differs from a fetal respiratory acidosis induced by increasing the inspired CO2 fraction to the ewe in that the respiratory stimulation induced by acetazolamide is not associated with an increased incidence of the permissive LV ECoG state.

Acetazolamide↗

PubMed1985

The effect of castration and sex steroids on ventilatory control in male guinea pigs.

Male guinea pigs (N = 7) given progesterone hyperventilate with PaCO2 falling from control levels of 39.0 +/- 0.6 (SEM) Torr to 32.0 +/- 0.7 Torr after 7 days of treatment. This response was associated with a rise in plasma progesterone concentration to approximately 15 ng ml-1 and a transient rise in plasma 17 beta-estradiol concentrations. To determine the role of the testes in generating the transient estrogen increase as well as the significance of estrogens to the progesterone response, male guinea pigs were castrated and treated either with estradiol or a placebo. Estrogen-treated castrates (N = 15) had a mean PaCO2 of 36.1 +/- 0.8 Torr and the castrates given the placebo (N = 7) had an average PaCO2 of 43.8 +/- 1.2 Torr (P less than 0.001). Both of these castrate groups were also different from intact, untreated males (P less than 0.01). Progesterone concentrations were very low and not different. When progesterone was additionally administered, the PaCO2's fell to 33.0 +/- 0.8 and 38.2 +/- 0.6 Torr for the estrogen- and placebo-treated castrate groups, respectively. The male guinea pig hyperventilates when given progesterone with the magnitude and time course of his response comparable to the human's. The response to progesterone is not critically dependent on the testes or on plasma estrogen concentrations; however, both castration and exogenous estrogen appear to influence PaCO2 without altering plasma progesterone concentrations.

Animals↗

PubMed1985

Insulin hypoglycemia, cerebral metabolism, and neural function in fetal lambs.

The effect of insulin-induced hypoglycemia on cerebral oxidative metabolism (CMRO2) was studied in nine late gestational fetal lambs using the radiolabeled microsphere technique for cerebral blood flow and brachiocephalic to sagittal sinus blood O2 content differences. After 4 h insulin infusion to the fetus, arterial glucose fell from control levels of 0.96 +/- 0.11 (SE) to 0.69 +/- 0.09 mmol X l-1. CMRO2 was reduced from 199 +/- 23 to 155 +/- 22 mumol X 100 g-1 X min-1 (P less than 0.05), and cerebral glucose uptake fell from 31 +/- 4 to 25 +/- 4 mumol X 100 g-1 X min-1 (P less than 0.02). During both euglycemia and hypoglycemia, 6 mumol glucose were taken up for each micromole of O2, indicating that glucose was the sole metabolic substrate for oxidative metabolism. Although there was no change in fetal electrocortical activity during the hypoglycemia, fetal breathing movements were present only 19.4 +/- 3.4% of the hypoglycemic hours compared with 36.8 +/- 2.6% of the control period (P less than or equal to 0.01). These results suggest that during rapidly induced fetal hypoglycemia, blood-brain barrier transport of glucose can limit cerebral glucose and O2 uptake, and this decrease in cerebral metabolism is associated with a lowered incidence of fetal breathing movements.

Animals↗

PubMed1985

Hemodynamics during pregnancy and sex steroid administration in guinea pigs.

We investigated the time course and possible mechanisms by which the maternal cardiovascular system adapts to the demands of pregnancy. Control, 20-, 40-, and 60-day gestation guinea pigs (total 68 days) and nonpregnant virgin female guinea pigs chronically dosed with cholesterol (control), estrogen (17beta-estradiol), progesterone, and estrogen plus progesterone were studied. In vivo heart rates, pressures, cardiac outputs, blood volumes, and in vitro left ventricular pressure-volume relations were measured. There was no difference in heart rate, mean arterial, right atrial, or left ventricular end-diastolic pressures, or left ventricular weights between the various pregnant animals or hormone-dosed animals and their respective controls. By 20 days gestation blood volume (24%, P less than 0.005), cardiac output (22%, P less than 0.005), and stroke volume (22%, P less than 0.05) were increased, whereas uterine blood flow was unchanged. Chronic estrogen administration resulted in similar increases in cardiac output (24%, P less than 0.05), stroke volume (31%, P less than 0.05), and blood volume (13%, P less than 0.05). In vitro left ventricular pressure-volume relations were shifted to the right in all pregnant and hormone-dosed groups. Increases in left ventricular size and output occur before changes in uterine blood flow in guinea pig pregnancy, and these adaptations can be elicited by chronic sex steroid administration.

Animals↗