bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the exocrine pancreas secondary to altered small intestinal function in the CF mouse
Authors: De Lisle Robert C. , Isom Kathryn S. , Ziemer Donna , Cotton Calvin U.
Published: December 2017

The exocrine pancreas of the cystic fibrosis (CF) mouse ( cftrm1UNC) is only mildly affected compared with the human disease, providing a useful model to study alterations in exocrine function. The CF mouse pancreas has ∼50% of normal amylase levels and ∼200% normal Muclin levels, the major sulfated glycoprotein of the pancreas. Protein biosynthetic rates and mRNA levels for amylase were not altered in CF compared with normal mice, and increases in Muclin biosynthesis and mRNA paralleled the increased protein content. Stimulated pancreatic amylase secretion in vitro and in vivo tended to be increased in CF mice but was not statistically significant compared with normal mice. We show for the first time that the CF mouse duodenum is abnormally acidic (normal intestinal pH = 6.47 ± 0.05; CF intestinal pH = 6.15 ± 0.07) and hypothesize that this may result in increased signaling to the exocrine pancreas. There were significant increases in CF intestinal mRNA levels for secretin (310% of normal, P < 0.001) and vasoactive intestinal peptide (148% of normal, P < 0.05). Furthermore, CF pancreatic cAMP levels were 147% of normal ( P < 0.01). These data suggest that the CF pancreas may be chronically stimulated by cAMP-mediated signals, which in turn may exacerbate protein plugging in the acinar/ductal lumen, believed to be the primary cause of destruction of the pancreas in CF.
Resection upregulates the IGF-I system of parenterally fed rats with jejunocolic anastomosis
Authors: Gillingham Melanie B. , Kritsch Karen R. , Murali Sangita G. , Lund Pauline Kay , Ney Denise M.
Published: December 2017

Rats maintained with parenteral nutrition following 60% jejunoileal resection plus cecectomy exhibit minimal adaptive growth in the residual jejunum but a dramatic adaptive growth in the residual colon. Coinfusion of insulin-like growth factor I (IGF-I) with parenteral nutrition induces jejunal growth but has minimal effects in the colon. Our objective was to study the role of the endogenous IGF-I system in the differential responses of jejunum and colon to resection and/or IGF-I during parenteral nutrition. We measured concentrations of immunoreactive IGF-I in plasma, jejunum, and colon, IGF-I receptor binding, and levels of IGF receptor, IGF-I, IGF binding protein (IGFBP)-3 and IGFBP-5 mRNA in residual jejunum and colon 7 days after resection and/or IGF-I treatment. IGF-I receptor number was increased (74–99%) in jejunum and colon due to resection; IGF-I mRNA was increased 5-fold in jejunum and 15-fold in colon due to resection. Resection increased circulating IGFBPs but did not alter plasma IGF-I concentration. Resection induced colonic growth in association with significantly greater colonic IGFBP-5 mRNA and significantly lower colonic immunoreactive IGF-I. IGF-I treatment had no significant effect on IGF-I mRNA or IGF-I receptor number. Concentrations of plasma and jejunal immunoreactive IGF-I were significantly increased in rats given IGF-I in association with jejunal growth. IGF-I treatment significantly increased IGFBP-5 mRNA in the jejunum, which also correlated with jejunal growth. Thus resection upregulated IGF-I receptor number and IGF-I mRNA in residual jejunum and colon, but differential adaptation of these segments correlated with differential regulation of IGFBP-5 mRNA.
Synthesis of hepatic secretory proteins in normal adults consuming a diet marginally adequate in protein
Authors: Jackson Alan A. , Phillips Gary , McClelland Irene , Jahoor Farook
Published: December 2017

The plasma concentration and hepatic synthesis rates of albumin, transthyretin, very low-density lipoprotein apolipoprotein B-100 (VLDL-apoB-100), high-density lipoprotein apolipoprotein A-1, fibrinogen, α1-antitrypsin, and haptoglobin were measured in six normal adults before and after consuming a protein intake of 0.6 g · kg body wt−1· day−1for 7 days. The synthesis of hepatic proteins was measured from the incorporation of [2H5]- phenylalanine, following prime/continuous infusion, using plasma VLDL-apoB-100 isotopic enrichment to represent the precursor pool. Synthesis of albumin declined by 50% ( P < 0.001) following the lower-protein diet, VLDL-apoB-100 declined by 20% ( P< 0.001), and apoA-1 declined by 16% ( P < 0.05). By contrast, synthesis increased for fibrinogen (50%, P< 0.05) and haptoglobin (90%, P < 0.001). This pattern of change, with decreased synthesis of nutrient transport proteins and increased formation of acute-phase proteins, suggestive of a low-grade inflammatory response, was accompanied by increased plasma concentration of the inflammatory cytokine interleukin 6 (30%, P < 0.05). The pattern of change in the synthesis of hepatic secretory proteins following 7 days on the low-protein diet may be of functional relevance for lipid transport and the capacity to cope with stress.
Effects of CXC chemokines on neutrophil activation and sequestration in hepatic vasculature
Authors: Bajt Mary Lynn , Farhood Anwar , Jaeschke Hartmut
Published: December 2017

The initiating step of neutrophil-induced cytotoxicity in the liver is the recruitment of these phagocytes into sinusoids. The aim of our study was to compare the efficacy of systemic exposure with individual inflammatory mediators on neutrophil activation and sequestration in the hepatic vasculature of C3Heb/FeJ mice as assessed by flow cytometry and histochemistry, respectively. The CXC chemokine macrophage inflammatory protein-2 (MIP-2; 20 μg/kg) induced a time-dependent upregulation of Mac-1 (318% at 4 h) and shedding of L-selectin (41% at 4 h). MIP-2 treatment caused a temporary increase of sinusoidal neutrophil accumulation at 0.5 h [97 ± 6 polymorphonuclear leukocytes (PMN)/50 high-power fields (HPF)], which declined to baseline (8 ± 2) at 4 h. The CXC chemokine KC was largely ineffective in activating neutrophils or recruiting them into the liver. Cytokines (tumor necrosis factor-α and interleukin-1α) and cobra venom factor substantially increased Mac-1 expression and L-selectin shedding on neutrophils and caused stable sinusoidal neutrophil accumulation (170–220 PMN/50 HPF). Only cytokines induced venular neutrophil margination. Thus CXC chemokines in circulation are less effective than cytokines or complement in activation of neutrophils and their recruitment into the hepatic vasculature in vivo.
Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans
Authors: Law Ngai-Moh , Bharucha Adil E. , Undale Anita S. , Zinsmeister Alan R.
Published: December 2017

The cholinesterase inhibitor neostigmine indirectly stimulates muscarinic M1/M2/M3 receptors, thereby reducing colonic distension in acute colonic pseudo-obstruction. We investigated the dose-response profile for the colonic sensorimotor effects of neostigmine and bethanechol, a direct muscarinic M2/M3 agonist in humans. A barostat-manometric assembly recorded phasic pressures, tone, and pressure-volume relationships (compliance) in the descending colon and rectum of 30 healthy subjects who received intravenous neostigmine (0.25, 0.75, or 1.5 mg; n = 15) or subcutaneous bethanechol (2.5, 5, or 10 mg; n = 15). Sensation to luminal distension was also assessed. Thereafter, the effects of neostigmine and bethanechol on colonic transit (geometric center) were compared with those of saline by scintigraphy in 21 subjects. Both drugs increased colonic phasic pressure activity, reduced rectal compliance, and enhanced urgency during rectal distension. Neostigmine also reduced colonic and rectal balloon volumes, reflecting increased tone by an average of 12% and 25% for the highest dose, respectively. Only neostigmine reduced colonic compliance, accelerated colonic transit [mean geometric center at 90 min 2.5 vs. 1.0 (placebo)], and increased pain perception during colonic distension. We conclude that neostigmine has more prominent colonic motor and sensory effects than bethanechol. Moreover, neostigmine induces coordinated colonic propulsion, perhaps by stimulating muscarinic M1 receptors in the myenteric plexus.
Dominant-negative TAK1 induces c-Myc and G0exit in liver
Authors: Bradham Cynthia A. , Hatano Etsuro , Brenner David A.
Published: December 2017

Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), a serine/threonine kinase, is reported to function in the signaling pathways of TGF-β, interleukin 1, and ceramide. However, the physiological role of TAK1 in vivo is largely unknown. To assess the function of TAK1 in vivo, dominant-negative TAK1 (dnTAK1) was expressed in the rat liver by adenoviral gene transfer. dnTAK1 expression abrogated c-Jun NH2-terminal kinase and c-Jun but not nuclear factor (NF)-κB or SMAD activation after partial hepatectomy (PH). Expression of dnTAK1 or TAM-67, a dominant-negative c-Jun, induced G0exit in quiescent liver and accelerated cell cycle progression after PH. Finally, dnTAK1 and TAM-67 induced c- myc expression in the liver before and after PH, suggesting that G0exit induced by dnTAK1 and TAM-67 is mediated by c- myc induction.
Endogenous neurotensin facilitates enterohepatic bile acid circulation by enhancing intestinal uptake in rats
Authors: Gui Xianyong , Dobner Paul R. , Carraway Robert E.
Published: December 2017

Initial studies on the digestive hormone neurotensin (NT) showing that intestinal NT mRNA expression and blood levels were altered in rats fed chow containing bile acid (BA) and the BA chelator cholestyramine led us to investigate the role of NT in the enterohepatic circulation of BA. In fasted, anesthetized rats with common bile ducts cannulated for bile collection, intravenous NT infusion (10 pmol · kg−1· min−1) enhanced BA output relative to control over 3 h in animals administered donor bile into the duodenum (30 μl/min). This suggested that the effect of NT was on the return of BA from the intestine to the liver, which is rate determining in the normal process. In rats prepared as described above and administered [3H]taurocholate ([3H]TC; 5 mM, 1 ml) duodenally, NT infusion (3–10 pmol · kg−1· min−1) increased the [3H]TC recovery rate in bile approximately twofold, whereas sulfated CCK-8 (12–50 pmol · kg−1· min−1) had no effect. To investigate the roles of endogenous NT and CCK, we administered [3H]TC into the rat duodenum or lower jejunum and tested the effect of the NT antagonist SR-48692 (2 nmol · kg−1· min−1) or CCK-A antagonist lorglumide (100 nmol · kg−1· min−1). SR-48692 reduced the [3H]TC recovery rate by ≅50% and ≅24% in the duodenum and jejunum, respectively, whereas lorglumide had no effect. These results suggest that NT or a similar peptide is an endogenous regulator of enterohepatic BA cycling, which acts by enhancing BA uptake in the intestine.
Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach
Authors: Ozaki Noriyuki , Gebhart G. F.
Published: December 2017

Splanchnic nerve fibers innervating the stomach were studied in anesthetized rats; 997 fibers in the T9 or T10 dorsal roots were identified by electrical stimulation of the splanchnic nerve. Thirty-one fibers responded to gastric distension. Extrapolated response thresholds ranged between 0 and 53 mmHg; seven fibers had thresholds for response ≥30 mmHg. Thermo- and/or chemosensitivity was tested in 18 of the 31 fibers. Four of twelve fibers responded to intragastric perfusion of heated saline; none of eight fibers tested responded to perfusion of cold saline. Infusion of glucose, l-arginine, or potassium oleate produced no change in resting activity. Intragastric instillation of 12% glycerol or an inflammatory soup (bradykinin 10−5 M, PGE2 10−5 M, serotonin 10−5 M, histamine 10−5 M, and KCl 10−3 M) and prior heat stimulation sensitized responses to distension. The results reveal the presence of low- and high-threshold mechanosensitive fibers in the splanchnic innervation of the stomach. These fibers have the ability to sensitize, and they likely contribute to pain and altered sensations that can arise from the stomach.
Intracellular trafficking/membrane targeting of human reduced folate carrier expressed inXenopusoocytes
Authors: Subramanian Veedamali S. , Marchant Jonathan S. , Parker Ian , Said Hamid M.
Published: December 2017

The major cellular pathway for uptake of the vitamin folic acid, including its absorption in the intestine, is via a plasma membrane carrier system, the reduced folate carrier (RFC). Very little is known about the mechanisms that control intracellular trafficking and plasma membrane targeting of RFC. To begin addressing these issues, we used Xenopus oocyte as a model system and examined whether the signal that targets the protein to the plasma membrane is located in the COOH-terminal cytoplasmic tail or in the backbone of the polypeptide. We also examined the role of microtubules and microfilaments in intracellular trafficking of the protein. Confocal imaging of human RFC (hRFC) fused to the enhanced green fluorescent protein (hRFC-EGFP) showed that the protein was expressed at the plasma membrane, with expression confined almost entirely to the animal pole of the oocyte. Localization of hRFC at the plasma membrane was not affected by partial or total truncation of the COOH-terminal tail of the polypeptide, whereas a construct of the cytoplasmic tail fused to EGFP was not found at the plasma membrane. Disruption of microtubules, but not microfilaments, prevented hRFC expression at the plasma membrane. These results demonstrate that the molecular determinant(s) that directs plasma membrane targeting of hRFC is located within the backbone of the polypeptide and that intact microtubules, but not microfilaments, are essential for intracellular trafficking of the protein.
Gender differences in cortical representation of rectal distension in healthy humans
Authors: Kern Mark K. , Jaradeh Safwan , Arndorfer Ronald C. , Jesmanowicz Andrzej , Hyde James , Shaker Reza
Published: December 2017

Cerebral cortical processing of information relayed via visceral afferents is poorly understood. We determined and compared cortical activity caused by various levels of rectal distension in healthy male and female subjects. Twenty-eight healthy, young (20–44 yr) volunteer subjects (13 male, 15 female) were studied with a paradigm-driven functional magnetic resonance imaging (fMRI) technique during barostat-controlled rectal distension at perception threshold and 10 mmHg below and above perception threshold. Male subjects showed localized clusters of fMRI activity primarily in the sensory and parietooccipital regions, whereas female subjects also showed activity in the anterior cingulate and insular regions. A progressive increase in maximum percent fMRI signal change and total volume of cortical activity was associated with the intensity of rectal distension pressure in both genders. Regions of cortical activity for below-threshold stimuli showed less substantial signal intensity and volume than responses for threshold and above-threshold stimuli. Volume of cortical activity during rectal distension in women was significantly higher than that for men for all distensions. We conclude that 1) there are substantial differences in female cortical activation topography during rectal distension compared with males; 2) intensity and volume of registered cortical activity due to rectal stimulation are directly related to stimulus strength; and 3) rectal stimulation below perception level is registered in the cerebral cortex.
Blood reservoir function of dog spleen, liver, and intestine
Authors: Carneiro J. J. , Donald D. E.
Published: December 2017

The reflex decrease in blood volume of the spleen, the liver, and the intestine of vagotomized dogs was measured by plethysmographic techniques during bilateral carotid occlusion and moderate and severe hemorrhage. The volume of blood mobilized from each organ during carotid occlusion and moderate hemorrhage was from 6 to 30% of their respective blood volumes and from 55 to 81% during severe hemorrhage. In each experimental situation the spleen exhibited the greatest ability to release blood and the intestine, the least. During moderate hemorrhage (9 ml/kg) the spleen yielded a volume equal to 35% of the blood lost, the liver 14% and the intestine 7%. Comparable figures for severe hemorrhage were 26, 13, and 5%, respectively. This order of ranking the component regions of the splanchnic circulation with regard to function as a blood reservoir may be specific for the dog
Construction of hydraulic cuff occluders for blood vessels
Authors: Shoukas A. A.
Published: December 2017

This report describes the construction technique for a simple and inexpensive cuff occluder for various size blood vessels. The occluder is made from polyvinyl chloride tubing and consist of two main parts, the balloon and catheter section, and the reinforcing back section. The occluders have functioned reliably in chronic dog preparations for up to 3 mo.
Angiotensin II antagonists in dehydrated rabbits without baroreceptor reflexes
Authors: Trippodo N. C. , Coleman T. G. , Cowley A. W. , Guyton A. C.
Published: December 2017

Blood pressure effects of angiotensin II antagonists were studied in sham-operated and baroreceptor-denervated rabbits in the normal water-replete state or after 6 days of water deprivation (dehydrated). Experiments were performed in awake rabbits. Dehydrated rabbits had significantly higher plasma sodium concentrations, hematocrits, and plasma renin activities, but lower plasma potassium concentrations and body weights than water-replete rabbits. Administration of angiotensin II antagonists caused a significant decrease in mean arterial pressure in dehydrated rabbits (-16 mmHg in sham-dehydrated and -19 mmHg in denervated-dehydrated) but not in water-replete ones, whether the baroreceptor reflexes were intact or not (-1 mmHg in sham replete and -4 mmHg in denervated replete). The open-loop feedback gain of the renin-angiotensin system in blood pressure control was calculated as -1.6. The results demonstrate an important role of angiotensin II in blood pressure regulation during the high-renin, dehydrated state, but not during the normal renin, water-replete state. Abolishment of baroreceptor reflexes did not unmask an important role of normal levels of angiotensin II in blood pressure regulation.
Instantaneous force-velocity-length relations in isolated dog heart
Authors: Weber K. T. , Janicki J. S.
Published: December 2017

The mechanics of left ventricular contraction were investigated in terms of instantaneous mural force, mid-wall circumferential fiber shortening velocity (dL/dt), and fiber length (L) in seven servo-regulated hearts. The steady-state response of series of variably preloaded or afterloaded allasotonic contractions were utilized. Norepinephrine (0.55-1.38 mug/min) or propranolol (0.07-0.14 mg/min) were given to alter inotropic background. For any given contractile state and initial L, maximum dL/dt was not attained instantly but after a finite time of ejection (39 ms +/- 0.2 SE; range, 24-60) and from a lesser length (92% +/- 0.5 SE; range, 83-99) than present at end diastole. Beyond this initial period instantaneous dL/dt was dependent on both instantaneous force and length while independent of time after contraction and initial L. Instantaneous dL/dt also varied with contractile state, e.g., dL/dt was less after propranolol and greater after norepinephrine. Peak dL/dt for all conditions was a function of the extent of shortening (r = 0.90). Thus, the trajectory describing instantaneous force, velocity, and length provides a useful description of both the mechanical behavior and contractile state of the ventricular myocardium.
Mucopolysaccharide osmotic pressure in the measurement of interstitial pressure
Authors: Snashall P. D.
Published: December 2017

Subatmospheric pressures were recorded from cotton wicks inserted into Wharton's jelly of human umbilical cords (mean=-7.6+/-5.0 (SD) cmH2O; n=10). Hyaluronate concentrations (mean=0.69+/-0.30 g/100 g) and wick pressures correlated negatively (r=-0.825; P less than 0.01) but calculated hyaluronate osmotic pressures (mean=4.0+/-2.7 cmH2O) were insufficient to explain the full wick pressure. In model systems composed of asbestos fibers (mean radius=0.5 micron) and 0.9% saline, subatmospheric pressures were recorded which varied with the volume of saline added. When hyaluronate (1 g/100 g) was substituted for saline, lower wick pressures were recorded at each volume. The pressure lowering effect of hyaluronate was not seen in a matrix of glass fibers (mean radius=1.0 micron). It is suggested that the effect of hyaluronate in asbestos fibers is due to its immobilization by the matrix and the consequent development of osmotic pressure recorded via the wick. In the coarser glass-fiber matrix, hyaluronate was not immobilized and therefore had no osmotic effect. These experiments support the hypothesis that subatmospheric interstitial pressures result from osmotic pressure of immobilized mucopolysaccharide macromolecules.
Noninvasive measurements of digital arterial pressure and compliance in man
Authors: Nakayama R. , Azuma T.
Published: December 2017

A noninvasive method was developed for measuring the digital arterial pressure and the compliance by using a fingertip pneumoplethysmograph and a pneumatic cuff. The compliance (C) of the digital artery was obtained from the peak amplitude of the volume pulse wave (deltaVp-a) under the effect of the cuff pressure (Po-a) by the equation: C = deltavp-a/(Ps - P-o-a) during the dicrotic phase defined in this study. The normal mean value was 11.37 +/- 0.59 X 10(-5) cm3/mmHg. On lowering of the cuff pressure, the moment when the deltaVp value becomes positive is regarded as the systolic pressure (Ps). At the end of the dicrotic phase, the mean amplitude (deltaVss') of the pulse wave during one pulse cycle (SS') and the ratios (deltaVss'/deltaVsd), where deltaVsd is the mean amplitude of the wave during the systolic period (SD), of successive waves after a particular wave fail to increase at the same rate when the cuff pressure decreased below the diastolic pressure. The cuff pressure corresponding to this particular wave is regarded as the diastolic pressure (Pd). The mean value of the mean digital pressure of normotensive subjects was 80.6 +/- 1.2 mmHg.
Pressure and flow changes during Valsalva-like maneuvers in dogs following volume infusion
Authors: Wilkinson P. L. , Stowe D. F. , Tyberg J. V. , Parmley W. W.
Published: December 2017

In eight dogs anesthetized with chloralose and urethan, Valsalva-like maneuvers (VLMs) were performed and central blood volume (CBV) measured following incremental volume loading with blood-dextran. Changes in blood pressure during VLM were characterized by 1) maximum change in systolic pressure (deltaPmax) during VLM; 2) change in systolic pressure during the first five beats of VLM (deltaP1-5); and 3) the change in pulse pressure during the first 10 beats of VLM. In three dogs, we also measured changes in right and left atrial pressure (PRA, PLA), esophageal pressure (PE), and pulmonary and aortic blood flow. We found that volume loading produced a continuous spectrum of hemodynamic changes culminating in the "square-wave" response. deltaPmax and deltaP1-5 correlated with changes in CBV. Changes in hemodynamic responses were produced by increases in CBV, and by incomplete prevention of systemic venous return during VLM. The mechanism of the square-wave response may be a combination of both these effects, with the latter the more significant of the two.
Cardiac cellular responses to altered nutrition in the neonatal rat
Authors: Hollenberg M. , Honbo N. , Samorodin A. J.
Published: December 2017

Rats reared in litters of 18, 12, and 6 to determine whether preweanling nutritional state would alter rates of cardiac cell division, weighed 31.7, 39.1, 48.2 g, respectively, at 21 days of age. Weights of left ventricles also increased (93.2, 123.5, and 167.2 mg) as did those of right ventricles (29.9, 43.2, and 54.3 mg). Total DNA content rose in both ventricles in the pups reared 6 per litter vs. those reared 18 per litter (6/litter vs. 18/litter), but more so in the left ventricle (79%) than in the right (24%). Autoradiography confirmed that this increase in ventricular DNA resulted from increased proliferation of cardiac muscle cells, fibroblasts, and vascular endothelial cells. When 3H-labeled thymidine was injected on day 1, autoradiographs prepared on day 21 reflected an increased dilution of label in the 6/litter rats, consistent with enhanced proliferation. The labeling index and grains per nucleus of left ventricular muscle cells of the 6/litter rats were 29% (P less than 0.005) and 20% (P less than 0.001) less than those of the 18/litter rats. Less vigorous but definite hyperplasia occurred in the right ventricle, which appeared to respond with an increase more in cell size than in cell number.
Effects of prostaglandins and endoperoxide analogs on canine saphenous vein
Authors: Goldberg M. R. , Hebert V. S. , Kadowitz P. J.
Published: December 2017

Contractile effects of prostaglandins (PGs) have not been widely studied in the canine saphenous vein, as in vitro model for venous function. We studied responses to two PG endoperoxide analogs (PGEA) and to monoenoic and bisenoic PGs of the A, B, E, and F series in helical strips of canine saphenous veins. Isometric changes in force were measured. All agents elicited marked contractions. PGEA were several orders of magnitude more potent than either primary PGs or other venoconstrictors, including norepinephrine. E- and A-types PG had unusual concentration and contraction at high concentration. B-types PG evoked a biphasic contractile response. Bisenoic PGs tended to be more potent than monoenoic PGs of the same type. These results show that canine saphenous veins are highly responsive to PGs and PGEA. These data suggest that these substances could influence venous tone in vivo. However, PG-induced changes in venous tone would depend on which PG or intermediate was present, on PG concentration, and on the prior state of venous tone.
Estrogen attenuation of the development of hypertension in spontaneously hypertensive rats
Authors: Hoeg J. M. , Willis L. R. , Weinberger M. H.
Published: December 2017

To examine the effects of estrogen on the development of high blood pressure in rats with a genetic predisposition toward hypertension, we administered to rats of the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) strains 0.05 mg mestranol daily from ages 4 to 13 wks. Control animals of each strain received corn oil placebos. Systolic blood pressure was measured by a microphonic tail-cuff technique twice a week after the rats were 6 wks of age. Estrogen treatment in SHR was associated with a significant reduction in the level of hypertension attained, but estrogen treatment had no effect on blood pressure in WKY. Estrogen prevented normal growth in SHR and WKY, but this effect (reproduced in another group of SHR and WKY by restriction of food intake) was not related to the lower blood pressures seen in estrogen-treated SHR. Thus, it appeared that estrogen administration attenuated the rise in blood pressure normally seen in SHR and that this attenuation was independent of the estrogenic effect on body weight.
Non-uniform strain distribution in papillary muscles
Authors: Pinto J. G. , Win R.
Published: December 2017

Measurements of surface strains were made on small segments of intact papillary muscles of cats and rabbits. The measured strain is found to be non-uniform, both along the length and across the diameter of the papillary. This observation introduces difficulty in interpreting the data from experiments on the mechanics of the papillary muscle.
A closed-chest canine model for cross-sectional echocardiographic study
Authors: Franklin T. D. , Weyman A. E. , Egenes K. M.
Published: December 2017

Cross-sectional echocardiography has been limited in the intact dog due to the intervening lobes of the left lung. Previous echo studies of the canine heart have utilized implanted transducers, catheter-tip transducers, or opened-chest preparations. The pericardial cradle technique described in this paper provides an acoustical window for echo studies of the entire heart in the closed-chest dog that has several advantages over these prior preparations. The left lung was retained by attaching the pericardium to the thoracic wall in a simple prestudy operation. Cross-sectional real-time echocardiographic studies have been performed on 52 anesthetized animals that were prepared in this manner. The studies were video taped for frame-by-frame analysis.
Chronology and mode of reinnervation of the surgically denervated canine heart: functional and chemical correlates
Authors: Kaye M. P. , Randall W. C. , Hageman G. R. , Geis W. P. , Priola D. V.
Published: December 2017

This study was undertaken to evaluate functionally the time and pattern of inotropic and chronotropic efferent cardiac reinnervation of the deneravated canine heart and to correlate functional data with regional myocardial catecholamine content and supersensitivity to norepinephrine. Our data indicate that efferent autonomic reinnervation takes place first in the atria, followed by a base-to-apex sequence in the ventricles, and that such reinnervation is functionally effective 9-12 mo after denervation. The return of neural function parallels the return of measurable quantities of myocardial norepinephrine and is accompanied by a decrease in supersensitivity to exogenous norepinephrine. The return to apparently complete functional reinnervation, however, cannot be quantitatively related to myocardial levels of catecholamine. Segmental myocardial supersensitivity to norepinephrine is sequentially reversed during progressive adrenergic reinnervation.
Step function input to the rat kidney by shifting between auto- and alloperfusion
Authors: Rasmussen S. N.
Published: December 2017

A technique is described that permits instantaneous shifts from autoperfusion of the left kidney of an "experimental" rat to alloperfusion of the same kidney from a "pump" rat (or vice versa). Renal arterial and venous pressures are maintained at normal levels during alloperfusion. The kidney has proved to work satisfactorily during both auto- and alloperfusion as judged from measurements of renal blood flow, urine volume flow, urine osmolality, and fractional extraction of inulin and PAH. The vascular dead space of the system is extremely small. If the blood of the pump rat-experimental rat has been equilibrated with indicator, shifting from auto- to alloperfusion constitutes a practically pure step washin to/washout from the kidney. Reverse effects are obtained by shifting from allo- to autoperfusion. Compared with the bolus injection technique, recirculation problems are minimized because the perfused vascular volume of a single kidney is small compared with the whole-blood volume of the rat.
Cardiopulmonary sympathetic afferent influences on renal nerve activity
Authors: Weaver L. C.
Published: December 2017

Cardiopulmonary sympathetic afferent nerves may affect renal control of intravascular volume by influencing renal sympathetic nerve activity. This influence was evaluated in alpha-chloralose anesthetized, vagotomized, sino-aortic denervated cats. When the afferent nerves were activated with a single electrical stimulus, the renal nerve responded with an excitatory burst of activity followed by a long period of inhibition. This response had characteristics of a supraspinal reflex. Repetitive stimulation of the sympathetic afferent nerve either inhibited or excited renal nerves and increased or decreased systemic blood pressure. The direction of these changes depended on stimulus parameters. No obligatory correlation in the direction of change of nerve activity and blood pressure was observed. Activation of cardiopulmonary sympathetic afferent nerves by intravascular volume expansion inhibited renal nerve discharge. Inhibition was elminated by sectioning the sympathetic afferent nerves. Volume expansion had no effect on lumbar sympathetic discharge monitored simultaneously with renal nerve activity. This observation suggests specificity of reflex influences of these afferent nerves on the kidney. In conclusion, cardiopulmonary sympathetic afferent nerves can reflexly alter renal nerve activity, and therefore may affect renal control of intravascular volume.
Autoregulation of cerebral blood flow during early experimental renal hypertension in the conscious dog
Authors: Allotey J. B. , Klassen G. A.
Published: December 2017

Using the radioactive microsphere technique, cerebral blood flow (CBF) was measured in six conscious dogs before intervention and again on the 3rd-5th days after inducing hypertension by the one-kidney Goldblatt (1-KGH) procedure. Sham-operated controls were also studied. The normal temporal variability of CBF, as well as the precision of the microsphere technique in measuring CBF were also determined in other normal dogs. A left atrial catheter was used for the microsphere injections (15 micrometer diam spheres) and an aortic catheter was used for cardiac output and blood pressure measurements. On the 3rd-5th days after 1-KGH, mean aortic pressure increased from a control value of 94 +/- 7 mmHg to 135 +/- 20 mmHg (P less than 0.005). CBF did not change significantly from the control flow of 57.1 +/- 7.9 ml/100 g per min. Calculated cerebral vascular resistance increased by 47 percent (P less than 0.025) above the control value. Hence, the early phase of experimental renal hypertension is associated with adequate autoregulation of cerebral blood flow.
Role of extravascular protein in capillary-tissue fluid exchange
Authors: Salathe E. P. , Venkataraman R.
Published: December 2017

A mathematical model of capillary-tissue fluid exchange is presented. The effect of variation in plasma and interstitial osmotic pressure that occurs as a result of convection and diffusion of protein is examined. Analytic solutions to the resulting equations are obtained by using the methods of perturbation theory. It is found that fluid exchange can significantly alter the pericapillary interstitial osmotic pressure, reducing both filtration and reabsorption. Variation in plasma osmotic pressure is important only for certain pathological conditions in which excessive filtration occurs. Specific numerical examples are presented which show quantitatively the extent of these effects for various normal and pathological conditions of physiological interest.
Restoration of hemorrhaged plasma volume by gastrointestinal fluid in the dog
Authors: Miller W. L. , Dale H. E.
Published: December 2017

Conscious, intact and splenectomized, male dogs were hemorrhaged 35 percent of their blood volumes (23 +/- 3 and 25 +/- 4 ml/kg, respectively) from carotid loop cannulas. Isotonic saline or glucose solutions were administered by gastric tube in volumes equal to the blood volume hemorrhaged. Plasma volume, mean arterial blood pressure, venous hematocrit, plasma protein concentration, and interstitial fluid pressure were monitored after hemorrhage and after fluid treatment. The magnitudes of plasma volume restoration 8 h after hemorrhage in the nontreated dogs averaged 56 +/- 9 percent of the hemorrhaged volume and did not differ significantly between intact and splenectomized dogs. Plasma volumes, however, were increased significantly by enterally administered fluids. The maximum rates of plasma volume restoration occurred within the 1st h after fluid treatment. Approximately 46 percent and 28 percent of the hemorrhaged plasma volume was replaced by saline and glucose solutions, respectively, during this period. Results support the hypothesis that fluid is absorbed from the gastrointestinal tract following hemorrhage, and that enterally administered fluids restore plasma volume at a rate and to an extent exceeding that provided by net interstitial fluid exchange alone.
Action of prostaglandins, endoperoxides, and thromboxanes on the lamb ductus arteriosus
Authors: Coceani F. , Bishai I. , White E. , Bodach E. , Olley P. M.
Published: December 2017

Prostaglandin (PG) E2, the PG endoperoxides PGG2 and PGH2, and enzymatically generated PGI2 and thromboxane A2 (TXA2) were tested in vitro on circular strips of ductus arteriosus from mature fetal lambs. Both PGE2 and the PG endoperoxides produced a dose-dependent relaxation of the ductus at low PO2 (7-11 torr), and their action was reduced or abolished at high PO2 (410-660 torr). PGE2, however, was more potent than the endoperoxides. The reaction mixture containing PGI2 relaxed the hypoxic ductus, but this response was not due to PGI2 but to two, more stable and as yet unidentified, compounds, one of which is most certainly PGE2. TXA2 was inactive on the vessel at low and high PO2. These results confirm that PGE2 is the most effective PG acting on the ductus and provide further support to the hypothesis that this PG is responsible for patency of the vessel during fetal life. PGE2 action, however, may be complemented by that of another endoperoxide derivative formed in the PGI2 synthetic reaction which remains to be identified.
Comparison of carotid artery mechanics in the rat, rabbit, and dog
Authors: Cox R. H. , Bockus Institute, Philadelphia, Pennsylvania.
Published: December 2017

Cylindrical segments of carotid arteries from rat, rabbit, and dog were studied in vitro in order to compare active and passive mechanical properties, with gross morphology and composition. Pressure-diameter relations were determined under active (norepinephrine) and passive (2 mM EGTA) conditions, and were used to compute values of tangential wall stress, incremental elastic moduli, characteristic impedance, and active smooth muscle responses. The water and connective tissue contents of these segments were also determined. Significant differences were found in the passive mechanical properties of these arteries, with those of the rat being most compliant and those of the dog being the stiffest. These differences were consistent with the connective tissue content of these arteries. The ratio of collagen to elastin was smallest in the rat and largest in the canine carotids. Differences were also demonstrated in the responses to smooth muscle activation. The maximum value of active stress response was essentially the same in the canine and rabbit arteries, both of which were larger than that of the rat carotids. On the other hand, the rabbit vessels produced a larger maximum diameter response than either of the other arteries. Values of incremental elastic modulus were largest at specific values of transmural pressure for the rabbit vessels. This latter fact may make the contractile system more effective in reducing wall diameter in the rabbit arteries in spite of the fact that they did not have the capacity to generate a larger active stress response.
Cardiac performance: independence of adrenergic inotropic and chronotropic effects
Authors: Ilebekk A. , Lekven J. , Kiil F.
Published: December 2017

During right atrial pacing in open-chest anesthetized dogs, the relationships between reduction in stroke volume and rise in heart rate were identical in control experiments, during intravenous infusion of isoproterenol, and after blockade of adrenergic beta-receptors by propranolol. To examine the mechanism of this constant relationship, left ventricular volume was estimated by continuous recordings of myocardial chord length (MCL) between ultrasonic elements inserted into the anterior ventricular wall. Diastolic filling curves were curtailed by raising heart rate and end-diastolic MCL was reduced. At constant heart rate, end-diastolic MCL was not altered by isoproterenol infusion, except for a slight rise at heart rates exceeding 220 beats/min. End-systolic MCL, however, was reduced, accounting for larger stroke volume during isoproterenol than during propranolol infusion. The reduction in end-systolic MCL was constant at all heart rates examined. Hence, chronotropic changes influence end-diastolic volume and inotropic changes influence end-systolic volume; their effects on stroke volume regulation are, therefore, virtually independent.
Myoglobin function in the isolated fluorocarbon-perfused dog heart
Authors: Cole R. P. , Wittenberg B. A. , Caldwell P. R.
Published: December 2017

An isolated dog heart preparation perfused with hemoglobin-free fluorocarbon suspension has been developed to study the role of myoglobin in myocardial function. The coronary vasculature was perfused at constant flow, with oxygen consumption determined from arteriovenous PO2 differences. Muscle function was assessed by measurement of pressures generated in a latex balloon placed in the left ventricle. The perfusate consisted of 20% perfluorotributylamine and 80% Ringer's lactate with 16 mM glucose. Steady-state oxygen consumption decreased from 0.30 to 0.11 ml/min per gram dry weight left ventricle, as perfusate PO2 decreased from 690 to 150 mmHg. Left ventricular pressure generation and oxygen consumption were determined before and after addition of 8 mM sodium nitrite, which changed functional ferrous myoglobin to high-spin ferric myoglobin. Over the range of perfusate PO2 studied, nitrite addition did not alter mechanical performance or myocardial oxygen consumption. These data suggest that those conditions necessary for substantial myoglobin-facilitated diffusion of oxygen in the myocardium are not present in the isolated fluorocarbon-perfused dog heart.
Lungs from chronically hypoxic rats have decreased pressor response to acute hypoxia
Authors: McMurtry I. F. , Petrun M. D. , Reeves J. T.
Published: December 2017

We measured pressor responses in blood-perfused lungs from rats kept at low altitude (LA, 1,520 m) and from rats exposed to simulated high altitude (HA, 4-6 wk at 4,270 m) to see if lungs from chronically hypoxic rats were hyper- or hyporeactive to acute airway hypoxia. HA lungs had bigger pressor responses to intra-arterial angiotensin II, prostaglandin F2alpha, and norepinephrine, but smaller responses to airway hypoxia than did LA lungs. The dose-response curve to hypoxia in HA lungs was shifted to the right of that in LA lungs. Thus, HA lungs were hyperreactive to intra-arterial agonists, but were hyporeactive to acute airway hypoxia. In contrast, additional experiments with rats that had been exposed to HA for 5 wk and then returned to LA for 3 days showed that the lungs from such post-HA rats were hyperreactive to acute airway hypoxia. The decreased pressor responsiveness to acute hypoxia in lungs from chronically hypoxic rats could have been due to an increased activity of some endogenous vasodilator or to some abnormality in the mechanism that couples hypoxia to contraction of the vascular smooth muscle.
Human platelet chemotaxis: requirement for plasma factor(s) and the role of collagen
Authors: Lowenhaupt R. W.
Published: December 2017

Platelets are actively mobile in plasma in vitro and, in addition, they migrate specifically and directionally toward added intact collagen (chemotaxis). Native human, bovine, and equine collagen, suspended in plasma, induce a chemotactic response in human platelets. However, heat-denatured and dinitrofluorobenzene-treated collagen fail to attract platelets. Platelets migrate directionally and specifically to intact native collagen incubated in plasma over a large distance (6 mm) in a very short time (total 15 min), as observed in a newly designed micromaze apparatus. Platelets obtained from donors deficient in plasma factors XII, IX, and VIII showed normal migration and chemotaxis in normal plasma and in their respective factor-deficient plasmas. Although nondirectional movement (mobility) was normal, platelets from a donor deficient in factor XI did not exhibit chemotaxis toward collagen in either factor XI-deficient plasma or in normal plasma. The results indicate that 1) collagen is a physiological substrate for the chemotactic phenomenon, 2) intact chemical and/or structural integrity of collagen is required for the induction of platelet chemotaxis, 3) at least one plasma constituent, factor XI, plays an essential role in the chemotactic phenomenon, and 4) contact between collagen and a plasma factor is essential for normal chemotaxis.
Endotoxin and myocardial failure: role of the myofibril and venous return
Authors: Bruni F. D. , Komwatana P. , Soulsby M. E. , Hess M. L.
Published: December 2017

The effects of gramnegative endotoxin-induced myocardial failure in the pentobarbital-anesthetized dog were examined by monitoring its influence on cardiac myofibrillar ATPase activity. Myofibrils were isolated from endo- and epicardial portions of the left ventricular wall. ATPase activities were determined in animals treated with 4 mg/kg endotoxin and monitored 5 h, in animals monitored for 5 h without endotoxin (controls), and in animals implanted with a unilateral femoral shunt and given endotoxin. No differences were seen in the activities between the endo- and epicardial portions of any preparation. Activity was significantly depressed in endotoxemic animals. Increasing venous return by 313 +/- 71 ml/min significantly increased coronary flow by reducing coronary vascular resistance and prevented any observed depression of myofibrillar ATPase activity. In in vitro studies, adding endotoxin directly to a myofibril preparation did not modify normal activity. It appears that the mechanical and myofibrillar dysfunctions are due to the action of endotoxin at sites not associated with the actomyosin ATPase, but may be due to the production of an intermediary agent in concert with a decreased venous return.
Preferential distribution of inhbititory cardiac receptors in left ventricle of the dog
Authors: Walker J. L. , Thames M. D. , Abboud F. M. , Mark A. L. , Klopfenstein H. S.
Published: December 2017

The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by sensory endings in the left ventricle activated by intracoronary injection of nicotine or veratridine into left anterior descending (LAD) or circumflex (Cx) coronary arteries in the dog. Injection of nicotine or veratridine into the Cx consistently resulted in larger decreases in heart rate, arterial pressure, and in gracilis perfusion pressure than were observed following injection of the same dose into the LAD. Vagotomy abolished the cardioinhibitory and vasodepressor responses to intracoronary nicotine or veratridine. The weight of left ventricle perfused by LAD or Cx was not different (43.5 +/- 1.65 and 44.5 +/- 2.2 g, respectively. These data indicate that chemical activation of sensory endings with vagal afferents in the inferoposterior left ventricle of the dog results in larger cardionhibitor and vasodepressor responses than result from activation of respects in the anterior left ventricle. Further, these data provide strong evidence that these sensory endings which are chemically activated are preferentially distributed to the inferoposterior left ventricle.
Effect of hypoxia on mechanical function in the neonatal mammalian heart
Authors: Jarmakani J. M. , Nakazawa M. , Nagatomo T. , Langer G. A.
Published: December 2017

The effect of 30 min of hypoxia followed by reoxygenation on mechanical function was studied in isolated, arterially perfused, neonatal rabbit and dog hearts. All studies were performed at a perfusion rate of 2.5 ml/g-min, at a pacing rate of 60 beats/min and at 27 degrees C. The muscles were perfused with Krebs-Henseleit solutions equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia). In the newborn rabbit and dog, both the developed tension (DT) and the maximal rate of tension development (dT/dtmax+) decreased during the first 3 min of hypoxia and then recovered to values not different from control. The effect of hypoxia on DT and dT/dtmax+ was inversely related to age in both the rabbit and dog. The equations describing the decline in DT and dT/dTmax+ during hypoxia and the recovery during reoxygenation were best expressed by two or three exponentials. Time to peak tension and half time to relaxation decreased during hypoxia and the decrease was also inversely related to age. The fact that the newborn was able to maintain normal mechanical function during hypoxia suggests that the newborn is capable of maintaining normal myocardial ATP levels due to enhanced flux through the glycolytic pathway.