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Biomedical subjects

R C Harris

Publications and source records attributed to R C Harris.

At least 145 records · Page 8Linked to original sources
PubMed1990

Bicarbonate loading in the thoroughbred: dose, method of administration and acid-base changes.

Two studies were undertaken in an attempt to investigate the optimal dose, route and time course required to 'bicarbonate load' the Thoroughbred. During the first study a test solution of sodium bicarbonate (NaHCO3) and a control solution of water were administered via a nasogastric tube to six horses. Blood acid-base status was determined immediately prior to and for 24 h following intubation. During the second study a standardised feed was given to four horses, with and without NaHCO3 supplementation. This was followed by a further trial involving the addition of glucose and NaHCO3 to a standardised feed. During Study 1, plasma pH peaked 8 h after NaHCO3 intubation (7.433 +/- 0.020) and levels were still elevated above control values 12 h post intubation. Although there was a trend for blood PCO2 to be elevated above control values at all times after NaHCO3 administration, values were only significantly different at 4 and 5 h post intubation. The patterns of change in plasma HCO3- and blood base-excess after NaHCO3 administration were similar. Values peaked between 3 and 6 h post intubation and were still above control values 12 h post intubation. In Study 2 attempts to alter acid-base status by presenting NaHCO3 mixed with feed were unsuccessful because horses failed to consume the total mix, despite attempts to mask the unpalatable nature of the feed by adding glucose. The results suggest that future studies investigating the influence of NaHCO3 on exercise performance and metabolism should possibly involve administration of NaHCO3 in a greater quantity than is administered conventionally (0.3 g/kg). More meaningful results may be obtained if NaHCO3 is administered as a solution, via a nasogastric tube, at least 3 h prior to exercise.

Acid-Base Equilibrium↗
PubMed1990

Loop diuretic-sensitive potassium flux pathways of rat glomerular mesangial cells.

Glomerular mesangial cells are smooth muscle-like contractile cells that mediate hormonal regulation of glomerular filtration. To gain better understanding of ionic events that accompany contraction/relaxation of these cells, flux pathways of K+ and their regulation by vasoactive agents were investigated in cultured rat mesangial cells using 86Rb+ as a tracer. Of total 86Rb+ influx (16.6 +/- 0.6 nmol x mg protein -1 x min-1), 46% was inhibited by 2 mM ouabain. Loop diuretics inhibited 43% of ouabain-insensitive 86Rb+ influx (3.9 +/- 0.2 nmol x mg protein-1 x min-1). Half-maximum inhibition was observed at 2 and 0.4 microM for furosemide and bumetanide, respectively. Loop diuretic-sensitive 86Rb+ influx was dependent on extracellular Na+ and Cl-; a hyperbolic dependency on extracellular Na+ was noted with apparent Michaels constant of 39 mM while a sigmoidal dependency on extracellular Cl- was present, which, assuming 1:1:2 stoichiometry for Na(+)-K(+)-Cl-, produced an apparent mean affinity constant of 64 mM. Moreover, a fraction of amiloride-insensitive 22Na+ influx was found to be sensitive to furosemide and dependent on extracellular K+ and Cl-, further indicating the presence of Na(+)-K(+)-Cl- cotransport. Efflux of 86Rb+ followed first-order kinetics, of which 60% was inhibitable by furosemide. Manipulations of extracellular osmolarity revealed that these furosemide-sensitive 86Rb+ flux pathways were coordinately regulated in response to osmotic stress. Concentration-dependent stimulation of Na(+)-K(+)-Cl- cotransport-mediated 86Rb+ influx was induced by two vasoconstrictors, angiotensin II (ANG II) and arginine vasopressin (AVP), and by a vasodilator, atrial natriuretic peptide (ANP).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1990

Association between muscle acetyl-CoA and acetylcarnitine levels in the exercising horse.

Treadmill exercise of 2-min duration and increasing intensity resulted in increased formation of acetyl-CoA and acetylcarnitine in working muscle of Thoroughbred horses. At high work intensities a plateau was reached for both acetyl-CoA (approximately 50 mumols/kg dry muscle) and acetylcarnitine (approximately 20 mmol/kg dry muscle). Postexercise concentrations were significantly (P less than 0.001) correlated; [acetylcarnitine] = 349.[acetyl-CoA] + 2.4. The results indicate that approximately 350 mumols acetylcarnitine were accumulated for every 1 mumol acetyl-CoA. Under the conditions of exercise used it is probable that most of the acetyl-CoA formed is generated through the intramitochondrial decarboxylation of pyruvate. The acetyl groups of acetyl-CoA are apparently redistributed throughout the whole cell through formation of acetylcarnitine, which readily transverses the mitochondrial membrane. Despite the redistribution, however, the close correlation between acetylcarnitine and acetyl-CoA would indicate that equilibrium was maintained and that neither acetylcarnitine transferase nor carnitine/acetylcarnitine translocase were rate limiting. There is some question as to whether the changes observed relate directly to exercise itself or to the state in muscle 10 s or more after exercise.

Acetyl Coenzyme A↗
PubMed1990

A regulatory role for large vessels in organ circulation. Endothelial cells of the main renal artery modulate intrarenal hemodynamics in the rat.

After arterial denudation by external rubbing of the left main renal artery, we assessed renal plasma flow rate (RPF) and glomerular filtration rate (GFR) in left and right kidneys of Munich-Wistar rats before and after intravenous infusion of acetylcholine (ACH), atrial natriuretic peptide (ANP), or nitroprusside (NP). In the right kidney RPF and/or GFR increased in response to both endothelium-derived relaxing factor (EDRF)-dependent (i.e., ACH) and -independent vasodilators (i.e., ANP and NP); on average, RPF rose by 22 +/- 4% (P less than 0.005), 19 +/- 10% (P less than 0.005), and 37 +/- 12% (P greater than 0.05), respectively. By contrast, in the left kidney RPF failed to increase after ACH (falling by 23 +/- 10%, P less than 0.001) and rose only in response to ANP and NP. To further evaluate the main renal artery's contribution to renal vasodilation, ACH and another EDRF-dependent agent, histamine, were infused through a micropipette into either the proximal or distal portions of the endothelium-intact renal artery. Proximal infusion of ACH led to increases in RPF and GFR, on average by 8 +/- 2% (P less than 0.025) and 10 +/- 3% (P less than 0.01), while bypassing the arterial endothelium by distal infusion failed to increase RPF and GFR, which fell by 24 +/- 6% (P less than 0.025) and 22 +/- 6% (P less than 0.005), respectively. Similarly, proximal infusion of histamine increased RPF by 12 +/- 3% (P less than 0.05), while distal infusion was virtually without effects on plasma flow. Micropuncture study during intravenous ACH infusion revealed significantly higher afferent and efferent arteriolar resistances and lower ultrafiltration coefficients in denuded versus nondenuded kidneys. These data indicate that the main renal artery is a major regulator of renal blood flow and vascular resistances. Similar to other endothelium-derived substances, EDRF may be elaborated mainly by large vessels and may act on the downstream microcirculatory systems, which determine organ blood flow and transcapillary fluid transfer.

Acetylcholine↗
PubMed1989

Effect of oral L-carnitine on its concentration in the plasma of yearling Thoroughbred horses.

After an oral dose of 10 g of L-carnitine the plasma concentrations of free and total carnitine increased in five yearling thoroughbred horses, reaching a peak two to four hours after administration, but in two horses there was no increase. In the five which responded, the mean (+/- sd) peak increase in total carnitine concentration was 15.1 +/- 6.9 mumol/litre from a predose mean of 18.8 +/- 3.4 mumol/litre, and the mean peak increase in free carnitine concentration was 13.5 +/- 3.1 mumol/litre from a pre-dose mean concentration of 12.5 +/- 2.2 mumol/litre. These changes were similar to those observed previously in a group of adult thoroughbred horses given 10 g of L-carnitine. There was no consistent pattern of change in the concentration of acetylcarnitine in the seven yearling horses.

Acetylcarnitine↗
PubMed1989

Epidermal growth factor binding, stimulation of phosphorylation, and inhibition of gluconeogenesis in rat proximal tubule.

Epidermal growth factor and insulin share many biological activities, including stimulation of cell proliferation, ion flux, glycolysis, fatty acid and glycogen synthesis, and activation of receptor-linked tyrosine kinase activity. In the kidney, insulin has been shown to regulate transport processes and inhibit gluconeogenesis in the proximal tubule. Since the kidney represents a major source of EGF, the present studies investigated whether proximal tubule contained EGF receptors, whether EGF receptors were localized to apical or basolateral membranes, and whether EGF receptor activation participated in the regulation of an important proximal tubule function, gluconeogenesis. Specific EGF receptors were demonstrated in the basolateral membrane of proximal tubule. Following incubation with 125I EGF, basolateral membranes demonstrated equilibrium binding at 4 degrees C and 23 degrees C. There was 78 +/- 2% specific binding (n = 13). The dissociation constant (Kd) was 1.5 x 10(-9) M and maximal binding was 44 fmol/mg protein. There was ninefold more specific binding to proximal tubule basolateral membrane than to brush border membrane. In basolateral, but not brush border membranes, EGF induced phosphorylation of the tyrosine residues of intrinsic membrane proteins, including a 170 kDa protein, corresponding to the EGF receptor. In the presence of the gluconeogenic substrates, alanine, lactate, and succinate, proximal tubule suspensions synthesized glucose. EGF inhibited glucose production in a concentration-dependent manner over a concentration range of 3 x 10(-11) to 3 x 10(-9) M. In addition, EGF inhibited angiotensin II-stimulated glucose production in the proximal tubule suspensions. EGF did not significantly increase net glucose metabolism nor decrease cellular ATP concentrations. Therefore, these studies demonstrated that rat proximal tubule contained specific receptors for EGF that were localized to the basolateral membrane and linked to tyrosine kinase activity. EGF significantly inhibited proximal tubule glucose production without significantly increasing net glucose consumption.

Animals↗
PubMed1989

Carnosine content of the middle gluteal muscle in thoroughbred horses with relation to age, sex and training.

1. Muscle biopsies were collected from 85 thoroughbred horses and analysed for carnosine content by an automated HPLC method. 2. No significant sex difference was found between colts, geldings and fillies. 3. There was a trend towards lower muscle carnosine contents with age, which was only significant between 1-year-old untrained horses and 4+ year-old horses (P less than 0.002).

Aging↗
PubMed1989

Effect of freeze-drying on measurements of pH in biopsy samples of the middle gluteal muscle of the horse: comparison of muscle pH to the pyruvate and lactate content.

Muscle biopsies taken after exercise, in comparison to those at rest, contain increased amounts of blood and this is a particular problem in studies of the horse. The inclusion of blood in muscle will introduce an upward bias in values of pH measured in muscle homogenates. In an attempt to control this, muscle biopsy samples of the middle gluteal from Thoroughbred horses were freeze-dried and dissected free of blood before determination of pH. Following exercise, muscle pH measured after freeze-drying was similar to that measured in homogenates prepared from frozen samples. In contrast, freeze-drying appeared to increase muscle pH in samples taken at rest. This was probably the result of loss of CO2 during freeze-drying. Muscle pH determined in freeze-dried samples taken at rest and after exercise was linearly related to pyruvate and lactate content (P less than 0.001). It is concluded that muscle samples taken after exercise can be freeze-dried and dissected free from blood before determination of pH, whereas this procedure will cause an alkaline shift in samples taken at rest.

Animals↗
PubMed1989

Glomerular responses to platelet-activating factor in the rat: role of thromboxane A2.

In view of its role as a pro-inflammatory mediator in glomerular injury, we investigated the renal cortical microcirculatory responses to the intrarenal arterial administration of platelet-activating factor (PAF) in the anesthetized euvolemic Munich-Wistar rat. Close arterial administration of PAF led to dose-dependent reductions in renal plasma flow rate (RPF), glomerular filtration rate (GFR), and filtration fraction (FF), in the absence of hypotension or hemoconcentration. Single-nephron (SN) plasma flow rate (QA), SNGFR and SNFF also fell [126 +/- 7 to 101 +/- 6 nl/min (P less than 0.005), 40.6 +/- 2.1 to 21.5 +/- 2.5 nl/min (P less than 0.005), and 0.33 +/- 0.03 to 0.21 +/- 0.03 (P less than 0.025)]. PAF increased pre- and postglomerular arteriolar resistances [2.32 +/- 0.14 to 2.73 +/- 0.19 (P less than 0.005) and 1.32 +/- 0.13 to 1.45 +/- 0.10(10)dyn.s.cm-5 (P less than 0.05)]. PAF infusion also led to a dramatic reduction in the mean value for the glomerular capillary ultrafiltration coefficient, Kf [0.058 +/- 0.012 to 0.020 +/- 0.003 nl.s-1.mmHg (P less than 0.025)]. PAF-induced changes in renal hemodynamics were abolished in the presence of the cyclooxygenase inhibitors, indomethacin and ibuprofen. When administered concomitantly with a thromboxane A2 (TxA2) receptor antagonist, PAF led to significant increases in RPF and GFR. In isolated glomeruli, PAF stimulated the biosynthesis of TxB2 in a dose-dependent manner. Thus PAF depresses rat glomerular function by inducing contraction of arteriolar and mesangial smooth muscle. These effects are likely mediated via the secondary release of TxA2.

Animals↗
PubMed1989

Response of rat inner medullary collecting duct to epidermal growth factor.

Urine is an abundant source of epidermal growth factor (EGF) and prepro-EGF has been localized to the thick ascending limb and distal convoluted tubule of the kidney. However, the functional role of EGF in the kidney is poorly understood. Determination of EGF receptors and functional responses to EGF in intrarenal structures distal to the site of renal EGF production may prove critical to our understanding of the role of this peptide. These studies were designed to investigate the response to EGF of rat inner medullary collecting duct cells in culture and in freshly isolated suspensions. Primary cultures of inner medullary collecting duct cells demonstrated equilibrium binding of 125I-labeled EGF at 4 and 23 degrees C. At 23 degrees C, there was 89 +/- 1% specific binding (n = 30). Scatchard analysis of 125I-EGF binding suggested the presence of both high-affinity binding with a dissociation constant (Kd) of 5 X 10(-10) M and maximal binding sites (Ro) of 2.7 X 10(3) binding sites/cell and low-affinity binding, with Kd of 8.3 X 10(-9) M and Ro of 1.8 X 10(4) binding sites/cell. Bound EGF, 68 +/- 3%, was internalized by 45 min. EGF binding was not inhibited by antidiuretic hormone, atrial natriuretic peptide or bradykinin at 23 degrees C, but there was concentration-dependent inhibition of binding by transforming growth factor-alpha. Incubation with phorbol myristate acetate decreased 125I-EGF binding in a concentration-dependent manner. 125I-EGF binding was also demonstrated in freshly isolated suspensions of rat inner medullary collecting duct cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Leukotriene D4 binding and signal transduction in rat glomerular mesangial cells.

We examined the characteristics of [3H]leukotriene D4 (LTD4) binding to mesangial cells in culture. Binding is stereoselective, specific, saturable, and rapidly reversible. Two binding sites are recognized with dissociation constants and binding site densities at equilibrium of 2.2 and 16.8 nM and 1.1 x 10(4) and 3 x 10(4) binding sites per cell. LTD4, LTE4, (5R,6S)LTD4, LTB4, and the LTD4-receptor antagonist, SKF 104353, competitively inhibit radioligand binding in the following rank order of potency: LTD4 greater than LTE4 = SKF 104353 greater than (5R,6S)LTD4 greater than LTB4. LTD4 also induces time- and concentration-dependent phosphoinositide hydrolysis in mesangial cells. Formation of inositol 1,4,5-trisphosphate (IP3) is maximal at 5 s, followed by a time-dependent increase in inositol monophosphate generation, and inhibited by 100-fold excess concentration of SKF 104353. Addition of LTD4 to mesangial cells is associated with an increase in intracellular pH and dose-dependent stimulation of [3H]thymidine incorporation and mitogenesis. Thus rat mesangial cells possess specific binding sites for LTD4, the activation of which stimulates IP3 formation and induces cellular alkalinization and mitogenic responses. These studies provide insight into the cellular basis for LTD4-mesangial cell interactions, which are of potential pathophysiological relevance during acute glomerular inflammatory injury.

Animals↗
PubMed1989

Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. Elucidation of signal transduction pathways.

We investigated the actions of endothelin in anesthetized rats and cultured mesangial cells. Intravenous infusion of endothelin (10 pmol/min) decreased renal blood flow by 44% at 20 min without changing arterial pressure, which subsequently rose significantly from 124 +/- 3 to 133 +/- 4 mmHg over 60 min. Micropuncture during the nonhypertensive period revealed increases in afferent (65%) and efferent (82%) arteriolar resistances, thereby reducing nephron plasma flow rate. The glomerular ultrafiltration coefficient (Kf) fell from 0.097 +/- 0.035 to 0.031 +/- 0.011 nl/(s.mmHg) as did single nephron filtration rate (41 +/- 3 to 19 +/- 3 nl/min). Addition of 5 nM endothelin to mesangial cells plated on a silicone rubber substrate increased the intensity and number of tension-generated wrinkles, and caused their reappearance in forskolin prerelaxed cells. 20-30 s following exposure of fura-2 loaded mesangial cells to 10 nM endothelin, single cell intracellular calcium concentration ([Ca]i) increased from a mean baseline value of 66 +/- 11 (SE) to a peak of 684 +/- 250 nM (P less than 0.05) followed by a sustained elevation at 145 +/- 42 nM. Anion exchange HPLC revealed rapid (15 s) and dose-dependent stimulation of inositol 1,4,5-trisphosphate (IP3) generation following exposure of [3H]myoinositol preloaded mesangial cells to 10-100 nM endothelin. Endothelin also led to intracellular alkalinization of 2'7'-bis(2-carboxy-ethyl)-5(and-6)carboxyfluorescein (BCECF)-loaded mesangial cells and its addition was associated with dramatic augmentation of mitogenic activity. Thus, endothelin exerts potent constrictor effects on renal arterioles which precede its systemic hypertensive action. It lowers Kf and contracts mesangial cells, likely through stimulation of IP3 generation and elevation of [Ca]i. It is a potent mesangial cell mitogen. These studies define functional responses and signal transduction pathways for endothelin in the rat kidney and propose a potential role for this peptide in the control of mesangial cell function, glomerular filtration rate, and renal vascular tone.

Animals↗
PubMed1988

Changes in haematology and plasma biochemistry during maximal exercise in greyhounds.

The haematological and biochemical changes associated with racing over 235 and 420 metres were studied in 23 greyhounds. Blood samples were collected while the dogs were resting and immediately after and 30 minutes after racing. Significant increases in red blood cell count, haemoglobin concentration and haematocrit occurred. The increase in haematocrit was accompanied by increases in total plasma protein and creatinine concentrations. Blood lactate increased to 11.4 and 13.2 mmol/litre over 235 and 420 metres, respectively, and plasma glucose increased to 7.9 and 8.2 mmol/litre. After the 420 metres, the mean plasma ammonia concentration was 256 mumol/litre. Plasma free fatty acid concentrations also increased after dogs had run both distances. The highest concentrations of glycerol and uric acid were found 30 minutes after exercise.

Animals↗
PubMed1988

The effect of oral L-carnitine supplementation on the muscle and plasma concentrations in the Thoroughbred horse.

1. L-carnitine was administered orally to thoroughbred horses for 58 days. 2. Acceptability and effects on plasma, muscle and urine concentration were studied. 3. Ten-60 g/day (as 2-3 doses) was acceptable with no deleterious effects. 4. One x 10 g L-carnitine significantly raised the plasma-free carnitine concentration (7 hr post) from 21.2 to 31.8 mumol/l; 2 x 30 g increased the mean to 36.5 mumol/l. 5. Plasma acetylcarnitine increased from approximately 1 to 5.5 mumol/l (7 hr post) on 2 x 30 g/day. 6. Muscle total carnitine was unchanged over 58 days. 7. Urinary output accounted for 3.5-7.5% of added carnitine, indicating low intestinal absorption.

Administration, Oral↗
PubMed1988

A new device for emergency percutaneous transtracheal ventilation in partial and complete airway obstruction.

Several methods of percutaneous transtracheal ventilation have been described for the immediate relief of upper airway obstruction when conventional methods fail. This study was conducted to determine whether a single percutaneously placed catheter introducer (Arrow Emergency Infusion Device [EID]) could provide access adequate for percutaneous transtracheal ventilation with standard ventilatory modalities in an obstructed airway. Ten mongrel dogs were anesthetized, intubated, and monitored (for pulse, blood pressure, ECG, and arterial blood gases). The endotracheal tube was occluded. When the dogs became hypoxic and hypercarbic, the Arrow EIDs were inserted transtracheally and the dogs were ventilated with either a Bear 1 Adult Ventilator or a Mapleson D system. Percutaneous transtracheal ventilation by the Arrow EID adequately ventilated dogs with controlled partial (95%) or complete airway obstruction from hypoxic and hypercarbic states. The ease of insertion, decreased associated complications, ability to ventilate with easily available devices, and use with complete airway obstruction make the EID an effective device for transtracheal ventilation.

Airway Obstruction↗