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Biomedical subjects

E O Fuller

Publications and source records attributed to E O Fuller.

At least 19 recordsLinked to original sources

Preservation of donor heart function and high-energy stores by continuous perfusion with synthetic plasma at 22 degrees C.

We evaluated high-energy phosphate (HEP) levels and the ability to perform work in rat hearts preserved by standard techniques (0.9% NaCl arrest and storage at 4 degrees C) and by continuous coronary perfusion at 22 degrees C, pH 7.25, and 55 mm Hg for 4 or 8 hr with Krebs-Henseleit buffer (KHB), modified Morgan's solution (MCS), or a medium developed in our lab (physiologically complete medium or PCM). Cardiac work was evaluated in the rewarmed hearts with use of a working heart preparation at left atrial pressures of 10, 15, and 20 cm H2O, and by measurement of aortic flow, coronary flow, heart rate, and peak systolic pressure. HEP levels in the hearts continuously perfused were significantly higher (p less than .05) than those in the hearts stored at 4 degrees C. The functional recovery of hearts preserved by storage in cold saline for 4 or 8 hr was significantly less (p less than .01) than the recovered function of hearts preserved for comparable periods by perfusion at 22 degrees C with either MCS or PCM. The results indicate that continuous perfusion at 22 degrees C with a more physiologic medium is superior to hypothermic arrest and storage at 4 degrees C for the preservation of donor heart function and HEP levels.

Animals↗

Mitochondrial respiration following acute hypoxia in the perfused rat heart.

Mitochondria isolated from tissues of hypoxic animals have increased respiratory capacity (State 3 respiration) when assayed in vitro at ambient oxygen tensions. The present study utilized the isolated perfused rat heart to determine whether or not this change could be produced in the absence of the neural and hormonal changes that accompany hypoxia in vivo. Following 10-min single pass retrograde perfusion with normoxic Krebs-Henseleit buffer (PO2 greater than or equal to 600 mmHg), perfusion was continued for up to 15 min with either normoxic or hypoxic buffer (PO2 less than or equal to 150 mmHg). After 10 min of hypoxic perfusion State 3 respiration of the mitochondria from the hypoxic hearts was 13 to 15% higher (P less than or equal to 0.05) than that of normoxic hearts when assayed with either glutamate/malate or succinate as substrate but was unchanged when TMPD and ascorbate was the substrate. Succinate-supported State 4 respiration of the hypoxic mitochondria also showed a small (10%) but significant (P less than or equal to 0.05) increase. These changes were not abolished by preperfusing the heart with propranolol (10(-7), 10(-6), or 10(-5) M) indicating that the response was not attributable to release of local stores of catecholamines. Respiratory control and ADP/O ratios as well as contents of cytochrome c and aa3 of the mitochondria from the hypoxic hearts were similar to those of normoxic hearts indicating that the mitochondria remained intact and tightly coupled. We concluded that the hypoxia-induced increase in mitochondrial State 3 respiration, while independent of neural and hormonal influences from the body requires an intracellular event, since they cannot be reproduced by subjecting isolated mitochondria to hypoxia in vitro.

Adenosine Diphosphate↗

Pregnancy-induced changes in sheep uterine and carotid arteries.

To characterize the effects of pregnancy on vascular tissue, intact segments of the uterine and carotid arteries were removed from nonpregnant and near-term pregnant sheep. Pressure-diameter relations were measured on isolated segments under activated (122 mM K+, 10(-4) M phenylephrine) and passive (0.1 mM Ca2+, 10(-5) M iodoacetic acid) conditions. DNA and RNA were determined spectrophotometrically. Collagen, elastin, and water contents were also measured. Pregnancy had no effect on either the mechanics or the biochemical properties of the carotid artery. However, there was a marked increase in internal radius in the uterine artery with pregnancy (0.060 +/- 0.016 vs. 0.198 +/- 0.019 cm). Active tangential stress increased, as did passive stiffness of the uterine artery. The collagen fraction decreased during pregnancy (57.2 +/- 2.4 vs. 45.7 +/- 2.2%), while elastin and RNA remained unchanged. A small decrease in DNA produced a significant increase in the RNA-to-DNA ratio. These data suggest that, in pregnancy, the uterine artery selectively undergoes a characteristic hypertrophy of its vascular smooth muscle.

Animals↗

Effects of cardiac work and leucine on protein turnover.

The purpose of these experiments was to assess effects of cardiac work and leucine in hearts supplied only glucose or substrate and hormone mixtures that simulated plasma. Rates of protein degradation greatly exceeded protein synthesis in Langendorff preparations supplied glucose. This severely negative nitrogen balance was brought closer to zero by provision of more complete substrate mixtures. Cardiac work further improved the nitrogen balance by stimulating protein synthesis in hearts supplied glucose (mixture 1), glucose-insulin-glucagon-lactate-beta-hydroxybutyrate (mixture 2), or palmitate-beta-hydroxybutyrate-glucose (mixture 3) and inhibiting protein degradation in hearts supplied glucose. Cardiac work did not affect the rates of either protein synthesis or degradation in hearts provided insulin-lactate-glucose (mixture 4). The increase in protein synthesis was associated with increased rates of peptide chain initiation. Addition of 1 mM leucine had an additional effect to restore nitrogen balance to zero or to achieve positive balance in working hearts supplied substrate and hormone mixture 2.

Adenosine Triphosphate↗

Glycogenolytic rates and cAMP in livers of rats running at different treadmill speeds.

The purposes of this study were to determine the effect of different work rates on the rate of liver glycogenolysis and to determine the relationship between liver adenosine 3',5'-cyclic monophosphate (cAMP) levels and the glycogenolytic rate. Rats were run at treadmill speeds ranging from 10 to 34 m/min up a 15% grade for either 30 or 60 min. Both the magnitude of the decrease in liver glycogen and the increase in hepatic cAMP were dependent on the running speed and the duration of running. At the highest work rate a disproportionate acceleration in the liver glycogenolytic rate was observed compared with that at lower work loads, thus resulting in a curvilinear relationship between work rate and liver glycogenolytic rate. A high degree of correlation was found between the liver glycogenolytic rate and hepatic cAMP concentration (r = 0.98). This observation is consistent with the idea that hepatic glycogenolytic rates are determined by cAMP-mediated mechanisms.

Animals↗

Adrenal hormones and liver cAMP in exercising rats--different modes of anesthesia.

We have compared five different modes of anesthesia (iv and ip pentobarbital sodium, ether, CO2, and cervical dislocation) with respect to their effects on liver glycogen, liver adenosine 3',5'-cyclic monophosphate (cAMP), blood glucose and lactate, plasma corticosterone, norepinephrine, and epinephrine in resting rats and in rats run on a treadmill at 26 m/min for 30 min. Ether, CO2, and cervical dislocation were found to be unsuitable due to the marked elevation in plasma catecholamines seen in both resting and exercising rats. Injection of pentobarbital sodium ip required an average of 8 min before onset of surgical anesthesia as opposed to less than 5 s for iv pentobarbital. Exercising rats anesthetized with ip pentobarbital showed markedly lower plasma catecholamines compared with rats given iv pentobarbital. Hepatic cAMP increased in response to exercise in all groups except the ip pentobarbital group. This is most likely due to the long delay between the end of the exercise and freezing of the liver in the ip pentobarbital-anesthetized animals. We conclude that iv injection of pentobarbital is the most suitable method of anesthesia for obtaining accurate measurements of plasma stress hormones, substrates, and metabolites and of hepatic cAMP and glycogen in resting and exercising rats.

Adrenal Cortex Hormones↗

Endurance training in the rat. I. Myocardial mechanics and biochemistry.

The effects of physical training and detraining on cardiac structure and myocardial mechanics were studied in young and adult male rats trained by graded treadmill running for 12 wk and compared with sedentary controls. Detraining was produced by training for 12 wk followed by 6 sedentary wk. A training effect was demonstrated by increased succinate dehydrogenase activity in skeletal muscle (trained 10.0 +/- 1.2 mumol . g-1 . min-1; sedentary 6.4 +/- 0.8 mumol . g-1 . min-1; P less than 0.05). Although heart weight-to-body weight ratios were increased in trained rats of both ages, left ventricular fiber diameters and myocardial RNA, DNA, and collagen content were unchanged by training. Active and passive mechanics (myocardial contractility and stiffness) were studied in left ventricular papillary muscles and did not differ significantly between groups, with the exception of depressed contractility observed in young trained rats [(e.g., papillary peak developed isometric tension at Lmax (length at peak tension)] was 2.64 +/- 0.24 g/mm2 in trained vs. 3.59 +/- 0.22 g/mm2 in sedentary (P less than 0.01). This difference was abolished by detraining. Papillary muscle contractile responses to calcium, norepinephrine, and hypoxia were not altered by training or detraining. In conclusion, moderate endurance training did not result in significant cardiac hypertrophy, altered myocardial stiffness, or consistent changes in myocardial contractility.

Animals↗

Endurance training in the rat. II. Performance of isolated and intact heart.

The effects of isotonic physical training and detraining on cardiac function were studied in young and adult male rats trained by graded treadmill running and compared with sedentary controls. Absolute left ventricular mass was not increased, and ventricular compliance was not altered by training. Ventricular function curves that plotted peak systolic pressure, maximum rate of rise of left ventricular pressure, cardiac output, coronary flow, or stroke work as a function of atrial filling height in the isolated perfused heart did not demonstrate a training effect in either age group. The cardiac response to hypoxia was also comparable in the trained and sedentary rats. The base-line heart rate of anesthetized rats, in which in situ cardiac function was studied, was lower in the trained rats (321 +/- 14 vs. 377 +/- 8, P less than 0.005). Resting hemodynamics and left ventricular function curves generated from pressure-flow data during volume infusion did not differentiate between the hearts of trained and sedentary rats. In conclusion, a moderate level of endurance training did not enhance cardiac contractility when this was assessed under nonexercise conditions in both the isolated perfused heart and intact in situ heart preparations.

Animals↗

Regulation of protein synthesis and degradation during in vitro cardiac work.

Cardiac work increased protein synthesis in hearts supplied glucose (mixture 1), glucose-insulin-glucagon-lactate-beta-hydroxybutyrate (mixture 2) or palmitate-beta-hydroxybutyrate-glucose (mixture 3). In hearts provided mixture 1, acceleration of synthesis involved increased rates of peptide chain initiation. In these hearts intracellular concentrations of 5 amino acids decreased and 13 others were unchanged, indicating that faster protein synthesis did not depend on increased amino acid availability. In hearts supplied mixtures 2, 3, or 4 (lactate-glucose-insulin), intracellular concentrations of branched-chain amino acids were decreased by work, whereas intracellular levels of some acidic and neutral amino acids increased. Protein degradation was decreased by work in hearts supplied mixtures 1 and 2, but not mixtures 3 and 4. In hearts provided mixture 1, nitrogen balance was negative, but less so in working preparations. Nitrogen balance was zero or positive in working hearts provided mixtures 2 and 4. These studies indicated that in hearts supplied some, but not all, of the substrate mixtures, cardiac work maintained efficiently of protein synthesis and inhibited protein degradation. An improved method for perfusion of working hearts with albumin-containing buffer is described.

Amino Acids↗

Responses of the uterine circulation to sympathetic nerve stimulation.

Pregnant and non-pregnant sheep uteri were perfused in situ with arterial blood at a constant flow rate. Unilateral stimulation (1-2 ma, u ms pulse) of the distal end of the severed sympathetic chain (L3-L4) at frequencies between 5 and 25 Hz produced a graded increase in uterine artery pressure in both horns. At 25 Hz, pressure in the horn ipsilateral to the stimulated sympathetic chain increased by 28 +/ 2% in four pregnant animals and 32 +/ 5% in six non-pregnant ewes. The response of the contralateral horn was significantly smaller than that of the ipsilateral horn (P less than or equal to 0.05). The response was alpha-mediated since it was abolished by local injection of dibenzyline into the middle uterine artery. The responses of the pregnant and non-pregnant animals were similar, indicating that pregnancy did not alter the alpha-adrenergic responses of the uterine vasculature.

Animals↗

Major and collateral components of blood flow to pregnant sheep uterus.

In vivo measurements of vessel diameter, latex injections, and acrylic-cast studies indentified the middle uterine arteries as the main source of blood supply to the pregnant sheep uterus. Collateral circulation stemmed from the dorsal uterine arteries, and the ovarian arteries, and small cervical branches derived from the external iliac arteries (in decreasing order of importance). These morphological observations were related to estimates of collateral flow obtained during isolated, in situ perfusion of the pregnant sheep uterus carried out through the cannulated middle uterine arteries. Collateral blood flow was estimated from the shift of the flow-pressure curve produced by inflation of a balloon catheter advanced into the aorta below the renal arteries. Middle uterine artery flow to one horn increased from 162 +/- 23 ml/min in midgestation to 323 +/- 44 ml/min near term. Collateral uterine blood flow did not change significantly: 82 +/- 15 ml/min in midterm, 74 +/- 9 ml/min near term. Collateral flow consituted a larger fraction of inflow to the horn containing the fetus in 9 of 10 single pregnancies.

Animals↗