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Biomedical subjects

R D Murray

Publications and source records attributed to R D Murray.

At least 145 records · Page 8Linked to original sources

Metabolic quotients and oxygen extraction across the uterus of the post-term pregnant rabbit under chronic steady-state conditions.

The extraction of oxygen by the uterus in the term rabbit has been found to be very high. During post-term pregnancy, the fetuses of the rabbit are approximately 40% larger, despite a reduction in placental weight of approximately 30%. The purpose of our study was to investigate the changes that occur in the maternal rabbit to allow survival of the fetus under these conditions. Post-term pregnancies were induced in 5 white New Zealand rabbits by injections of chorionic gonadotropin and progesterone on the 26th day of gestation. Catheters were placed surgically on day 28, and blood samples were taken daily from the femoral artery and uterine veins starting at day 31. Each sample was analyzed for pH, PCO2, PO2, oxygen capacity and saturation, glucose, beta-hydroxybutyrate, lactate and acetoacetate. Coefficients of extraction were calculated for oxygen and metabolic quotients were calculated for each substrate. These data are compared with those obtained for the term rabbit in previous studies. There was a significant increase in the coefficient of oxygen extraction in the post-term animals; however, the metabolic quotients across the uterus were not significantly different between the term and the post-term rabbit.

Animals↗

Short-chain fatty acid profile in the colon of newborn piglets using fecal water analysis.

Short-chain fatty acid production and assimilation is unlikely to occur at significant levels in the newborn because the colon at birth is sterile, and only gradually acquires an anaerobic flora. This study profiled short-chain fatty acid levels in the colon lumen over the initial 21 days of life. Fecal samples were removed surgically from the cecum, right, and left colon from 36 York piglets, 0-21 days of life. Samples were subjected to in vitro dialysis and centrifugation methods to quantitate fecal water short-chain fatty acids, electrolytes, osmolality, and pH. A three-way analysis of variance examined piglet age, colon site of fecal samples, and method of fecal water analysis, for each variable. No differences were found between techniques of fecal water collection. Newborns showed production of short-chain fatty acids as early as the 1st day of life in limited amounts. Levels were stable between days 5 and 14, and then abruptly accumulated in the lumen. Acetate was predominant early, with propionate and butyrate responsible for late peaks. The production and assimilation of short-chain fatty acids was nearly complete proximal to the left colon. Age and colon site showed significant interactions for each fatty acid (p less than 0.001). The combined osmolar contributions of short-chain fatty acids and electrolytes accounted completely for the luminal osmolality after the 2nd wk of life. Previously there was an "osmolar gap" suggesting that lactose or its breakdown products were present in the lumen and were being removed by pathways other than through short-chain fatty acid production.

Anaerobiosis↗

Uteroplacental unit as a source of elevated circulating prorenin levels in normal pregnancy.

Circulating levels of inactive renin, that is, prorenin, are increased in normal pregnant women. To determine whether the uteroplacental unit secretes prorenin into the maternal circulation, we measured enzymatically active and inactive renin in plasma simultaneously obtained from the radial artery and uterine vein of 12 normotensive, nonlaboring patients undergoing elective cesarean section at term. We also measured these forms of renin in the umbilical arterial and venous blood of these patients. Our data reveal that the levels of inactive renin in both arterial and uterine venous blood of normal pregnant women are significantly higher than in peripheral venous blood of nonpregnant, normotensive control subjects; normotensive term patients have a ratio of plasma inactive to active renin of 9:1 in contrast to the 1:1 ratio in normotensive nonpregnant subjects; there is a significant uterine arteriovenous difference of prorenin (66.2 +/- 24.4 ng/ml/hr, p less than 0.05) but not of active renin (1.8 +/- 1.5 ng/ml/hr, not significant). These results suggest that the uteroplacental unit contributes to the elevated prorenin levels at term pregnancy.

Cesarean Section↗

The contribution of salivary amylase to glucose polymer hydrolysis in premature infants.

To determine whether salivary amylase of premature infants can function as a surrogate for pancreatic amylase, we evaluated its production in the infant, acid resistance, and hydrolytic potency in a simulated oropharyngeal, gastric, and intestinal environment. The activity of salivary amylase in 11 prematures varied between 1 and 33 U/ml; the isozymic profile and acid resistance of the premature salivary amylase were identical to those of the enzyme of adults. A "modular" formula containing 7 g/dl of a 14C labeled long chain glucose polymer with degrees of polymerization ranging between 18 and 29 glucose units was prepared. Salivary amylase, 1.1 U/ml, was added to this formula. The progressive breakdown of the 14C polymers as the milk was subjected to oropharyngeal, gastric, and intestinal phase environments was evaluated by quantifying the liberation of short-chain oligomers from the 14C labeled substrates. The gastric pH was varied between 2 and 5 and the gastric incubation time was either 5 or 180 min. Substantial gastric phase breakdown only occurred after 3 h of exposure at the higher pHs of 4 (12%) and 5 (32%). During the intestinal phase, salivary amylase activity resumed. Prior gastric phase pH affected ultimate intestinal phase breakdown, p less than 0.001; after 5-min gastric phases at pHs ranging from 2 to 5, the intestinal phase breakdown ranged from 17 to 55%. We conclude that the limited salivary amylase in the saliva of premature infants can produce significant glucose polymer digestion in both the stomach and small intestine but the digestion falls substantially short of that accomplished by usual concentrations of pancreatic amylase.

Adult↗

Effect of DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid on the blood pressure response to vasoactive substances.

The importance of kininase I (carboxypeptidase N) in the catabolism of circulating kinins is not known. DL-2-Mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA) has been reported to be an inhibitor of kininase I both in vitro and in vivo. In order to evaluate the possible role of kininase I in the in vivo inactivation of bradykinin, the authors studied the blood pressure responses of pentobarbital-anesthetized rats to bradykinin before and after the i.v. administration of MGTA (a 10-mg/kg bolus followed by 1 mg/kg/min continuous infusion). MGTA potentiated bradykinin-induced hypotension. The specificity of MGTA for kininase I was tested using other peptide and nonpeptide vasoactive substances. MGTA potentiated the hypertension due to angiotensin I, angiotensin II and vasopressin, but it did not affect the response to phenylephrine. On the other hand, MGTA did not potentiate the hypotensive action of acetylcholine, but it did potentiate that of sodium nitroprusside. The potentiation of bradykinin-induced hypotension is compatible with inhibition of kininase I by MGTA. The data suggest, however, that MGTA is not selective for any enzyme that inactivates kinins, inasmuch as other peptides and nonpeptide vasoactive substances are also potentiated.

3-Mercaptopropionic Acid↗

Uterine and whole body oxygen extractions in the pregnant rabbit under chronic steady-state conditions.

Seventeen pregnant rabbits were studied under conscious, unstressed conditions after catheterization of the right ventricle (RV), a femoral artery (A), and a uterine vein (UV). Respiratory gas tensions, pH, and oxygen saturations and contents were determined serially throughout the latter half of gestation. The uterine coefficient of oxygen extraction increased with gestational age (R = 0.86) and became 60.6% +/- 0.3% during the last 4 days of pregnancy. To compare uterine perfusion with whole body perfusion in relationship to oxygen demands, the (Ao2 - UVo2/Ao2 - RVo2) ratio was computed. The ratio was greater than or equal to 1 after 20 days of gestation, which demonstrated that in regard to oxygen demands the rabbit uterus is relatively underperfused compared to the rest of the maternal organism in the last part of pregnancy. A comparison with analogous data in other species demonstrates that the pregnant rabbit, like the guinea pig, has a much lower rate of uterine blood flow than does the pregnant sheep. These interspecies differences in the perfusion rate and oxygen extraction of the pregnant uterus are related to differences in placental structure.

Animals↗

Renin release from isolated afferent arterioles.

A new in vitro system was developed in which renin release was studied in the absence of tubules, glomeruli, and macula densa. Rabbit afferent arterioles were isolated by microdissection and incubated in medium 199 for consecutive 15-min periods. Renin concentration of incubation media and arteriolar tissue was measured using partially purified rabbit angiotensinogen. Basal renin release rate was 0.68 +/- 0.06 ng of angiotensin I (AI) X hr-1 X arteriole-1/hr incubation of arterioles (x +/- SEM, N = 29), and remained stable for 60 min. The renin release rate was 2.76 +/- 0.22% of arteriolar renin content each hour, and there was a significant correlation between the two (r = 0.73, P less than 0.01). Renin release increased from 0.56 +/- 0.07 to 1.71 +/- 0.17 ngAI X hr-1 X arteriole-1/hr (P less than 0.01, N = 6) during exposure to isoproterenol (8.1 X 10(-5) M) and returned to basal values during the recovery period. Dietary sodium depletion resulted in a significantly greater arteriolar renin content (86.1 +/- 17.5 ngAI X hr-1/arteriole) compared with that from rabbits on a normal sodium diet (26.8 +/- 2.51 ngAI X hr-1/arteriole). However, sodium depletion did not alter the basal renin release rate suggesting that sodium depletion increased renin content in a storage pool rather than a pool contributing to basal release. It is concluded that the isolated afferent arteriole is a good model for the study of renin release in the absence of tubules, glomeruli, and macula densa.

Animals↗

Efficient storage system for breath hydrogen.

Recommended materials for breath hydrogen collection (plastic syringes with twist lock closure) are only adequate for relatively brief periods because of gradual hydrogen loss and considerable variability between duplicate samples. To document the most favorable storage conditions for breath hydrogen, we compared hydrogen retention in plastic syringes using a conventional twist-in-lock closure versus a simple, inexpensive syringe closure, a Critocap. Hydrogen retention was studied at 25, 5, and -20 degrees C in two different syringe brands over 72 h of storage. An analysis of variance confirms the superiority of Critocaps over twist-in-lock closures (p less than 0.001). Reliability was maximal when samples were placed in environments less than 5 degrees C. When storage time was extended to 7 days, mean hydrogen retention was 86 +/- 6% (means +/- SD).

Breath Tests↗

Effects of synthetic atrial natriuretic factor in the isolated perfused rat kidney.

It is known that atrial extracts (AE) and synthetic atrial natriuretic factor (ANF) can increase glomerular filtration rate (GFR) and electrolyte and water excretion both in vivo and in vitro. It is not clear, however, if ANF-induced increases in filtered load (increased GFR) are required to produce natriuresis and diuresis. We perfused isolated rat kidneys with AE or synthetic ANF at constant pressure in a single-pass system. Extracts of atrial tissue (1 mg/ml) and high concentrations of ANF (31 and 61 ng/ml) significantly increased both GFR and electrolyte and water excretion. During continued infusion of ANF, GFR stabilized at increased levels, but sodium and water excretion continued to increase. After the termination of infusions, GFR and potassium excretion returned to control levels, but sodium and water excretion remained significantly elevated. Infusion of a low concentration of ANF (3 ng/ml) significantly increased sodium and water excretion without changing either GFR or potassium excretion. We conclude that increases in GFR are not a prerequisite for natriuresis and diuresis in response to ANF, but that increases in GFR can potentiate the response. Furthermore, our data suggest that ANF increases potassium excretion only if it increases GFR.

Animals↗

Effect of urinary alkalinization on the intrarenal formation of kinins.

Alterations in the urinary excretion rate of kallikrein (UKKV) have frequently been assumed to reflect alterations in the intrarenal generation of kinins. Since other factors such as urinary pH and the activity of renal kininases may affect the intrarenal concentration of kinins, we investigated the effect of urinary alkalinization on kinin excretion in the presence and absence of kininase II inhibition. Urine was collected from the ureters of rats during control (ctl) (0.15 M NaCl infusion) and experimental (exp) periods. During exp periods, group I (time control) was infused with 0.15 M NaCl, group II with 0.3 M NaCl, and groups III and IV with 0.3 M NaHCO3, all at 0.12 ml/min. Prior to the ctl period, group IV was pretreated with the kininase II inhibitor captopril (40 mg/kg). During the exp period, urinary kinin excretion (UKiV) increased significantly in all groups ([exp - ctl] UKiV = 21 +/- 7, 27 +/- 9, 52 +/- 14, and 70 +/- 9 pg X min-1 X kg-1 in groups I, II, III, and IV, respectively). Urinary pH increased significantly in groups II, III, and IV. The increases in UKiV and pH were significantly greater in the bicarbonate-infused rats than in control. Partial correlation coefficients show that UKiV correlates with a high degree of significance only with urinary pH (r = 0.6). During the ctl period, UKiV in the captopril-pretreated rats was not different from that in other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Possible role of adenosine in the macula densa mechanism of renin release in rabbits.

This study was designed to examine: (a) the effects of adenosine and its analogues on renin release in the absence of tubules, glomeruli, and macula densa, and (b) whether adenosine may be involved in a macula densa-mediated renin release mechanism. Rabbit afferent arterioles (Af) alone and afferent arterioles with macula densa attached (Af + MD) were microdissected and incubated for two consecutive 30-min periods. Hourly renin release rate from a single arteriole (or an arteriole with macula densa) was calculated and expressed as ng AI X h-1 X Af-1 (or Af + MD-1)/h (where AI is angiotensin I). Basal renin release rate from Af was 0.69 +/- 0.09 ng AI X h-1 X Af-1/h (means +/- SEM, n = 16) and remained stable for 60 min. Basal renin release rate from Af + MD was 0.20 +/- 0.04 ng AI X h-1 X Af + MD-1/h (n = 6), which was significantly lower (P less than 0.0025) than that from Af. When adenosine (0.1 microM) was added to Af, renin release decreased from 0.72 +/- 0.16 to 0.24 +/- 0.04 ng AI X h-1 X Af-1/h (P less than 0.025; n = 9). However, when adenosine was added to Af + MD, no significant change in renin release was observed. N6-cyclohexyl adenosine (an A1 adenosine receptor agonist) at 0.1 microM decreased renin release from Af from 0.69 +/- 0.14 to 0.39 +/- 0.12 ng AI X h-1 X Af-1/h (n = 5, P less than 0.05). However, 5'-N-ethylcarboxamide adenosine (an A2 adenosine receptor agonist) either at 0.1 microM or at 10 microM had no effect. Theophylline, at a concentration (10 microM) that does not block phosphodiesterase but does block adenosine receptors, increased renin release from Af + MD from 0.21 +/- 0.03 to 0.46 +/- 0.08 ng AI X h-1 X Af + MD-1/h (P less than 0.05; n = 8). The results are consistent with the hypotheses that adenosine decreases renin release via the activation of A1 adenosine receptors, and that adenosine may be an inhibitory signal from the macula densa to juxtaglomerular cells.

Adenosine↗

Concentration dependency of the renal vascular and renin secretory responses to adenosine receptor agonists.

Exogenous adenosine inhibits renin secretion and can either vasoconstrict or vasodilate the renal vasculature in vivo. In previous experiments, we found that micromolar concentrations of N6-cyclohexyl adenosine and 5'-N-ethylcarboxamide adenosine, analogs which are relatively selective for A1 and A2 adenosine receptors, respectively, tended to have opposite effects on both afferent arteriolar resistance and renin secretory rate in isolated rat kidneys perfused at constant pressure. Because the affinities of A1 and A2 receptors differ considerably, the purpose of the present experiments was to determine the concentration dependencies of the renal hemodynamic (perfusion pressure or perfusate flow, glomerular filtration rate, filtration fraction) and the renin secretory effects of adenosine, N6-cyclohexyl adenosine and 5'-N-ethylcarboxamide adenosine. Both the renovascular and the renin secretory effects of CHA were biphasic; at submicromolar concentrations, total and afferent arteriolar resistances were increased and renin secretion was inhibited. At higher concentrations, these effects were reversed or abolished. 5'-N-Ethylcarboxamide adenosine and adenosine decreased total and segmental (afferent and efferent) resistances and stimulated renin secretion. Taken together, the results are consistent with the suggestions that A1 and A2 receptors mediate inhibition and stimulation of renin secretion, that afferent arteriolar A1 and A2 receptors mediate constriction and dilation and that efferent arteriolar A2 receptors mediate dilation.

Adenosine↗

Plasma hormone changes in cows during induced or spontaneous calvings and the early post partum period.

Plasma progesterone, oestradiol, 13,14-dihydro, 15-keto, prostaglandin F2 alpha (PGFM) and luteinising hormone were measured in daily samples from eight dairy cows for 15 days before and after spontaneous calving, and compared to patterns obtained from 15 cows during and after induction of parturition with dexamethasone +/- prostaglandin. The average (+/- sd) length of pregnancy in the control cows was 285 +/- 3.04 days compared to 264 +/- 7.4 days in the induced group. Only nine cows required prostaglandin on day 11 after dexamethasone, which resulted in all nine calving 1.7 +/- 0.3 days later. Eight of the 15 treated cows retained the fetal membranes; however, the calving to first heat interval for all treated cows was 46.7 +/- 10 days (range 30 to 66 days) and calving to conception 52.4 +/- 17 days (range 30 to 85 days) compared to 42.1 +/- 15 days (range 28 to 64 days) and 76.5 +/- 24 days (range 54 to 115 days) respectively for the eight cows which calved without induction. The pre-partum hormone profiles were similar in all cows. Hormone profiles in the post partum period were also similar in all cows, irrespective of previous history. Baseline values for progesterone and oestradiol were not reached until 4.6 +/- 1.7 days and 2.75 +/- 0.7 days post partum respectively, whereas PGFM values increased for two or three days, reaching baseline levels 8.87 +/- 2.10 days later. Five cows had secondary peaks of PGFM on days 5,6 and 7. Luteinising hormone values increased steadily after calving in all cows.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Induction of parturition in cattle using dexamethasone and cloprostenol: economic performance and disease incidence after treatment.

Details are given of clinical management and disease problems associated with the routine induction of parturition on a herd basis, as well as the veterinary costs involved. A review of the economic performance of cows calved by this method is made and some guidelines laid down as to the conditions under which such a technique could be used as a management tool.

Animals↗

Effects of adenosine receptor agonists in the isolated, perfused rat kidney.

Two subclasses of adenosine receptors, A1 and A2, have been described. The purpose of these experiments was to determine and compare the renal effects of several adenosine receptor agonists: adenosine (Ado), 2-chloroadenosine (2CA, nonselective), N6-cyclohexyladenosine (CHA, A1 selective), and N6-ethylcarboxamide adenosine (NECA, A2 selective). Rat kidneys were perfused at constant pressure (105 +/- 5 mmHg) using a Krebs-Henseleit buffer containing 3.5 g/100 ml Ficoll and 1.0 g/100 ml bovine serum albumin. Three clearance periods were obtained in each kidney, i.e., control, experimental [drug at 1 microM or vehicle (NaCl)], and recovery. Perfusate flow was increased by Ado, 2CA, and NECA but not affected by CHA. Glomerular filtration was increased by NECA, decreased by CHA, and not affected by Ado and 2CA. Afferent arteriolar resistance was decreased by NECA, increased by CHA, and unaffected by Ado and 2CA. Efferent arteriolar resistance was decreased by all agonists. CHA tended to decrease renin secretion whereas NECA significantly increased it. The results suggest that the renal vasculature possesses both A1 and A2 adenosine receptors and that activation of A2 receptors mediates arteriolar dilation and stimulation of renin secretion whereas activation of A1 receptors mediates arteriolar constriction and possibly inhibition of renin secretion.

2-Chloroadenosine↗

Induction of parturition in a commercial dairy herd: clinical management and treatment.

Twenty-six dairy cattle were treated with dexamethasone during medium to late pregnancy to induce premature calving. Thirteen produced calves within an average of 5-6 days of treatment. The remainder were given a subsequent injection of cloprostenol 10 days after the steroid treatment and, with one exception, all calved within the following two days. A high incidence of retained placenta was experienced, in common with other methods of inducing parturition, but this was not generally found to be associated with detrimental effects on health or fertility.

Animals↗