bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular properties of small-conductance Ca2+-activated K+ channels expressed in murine colonic smooth muscle
Authors: Ro Seungil , Hatton William J. , Koh Sang Don , Horowitz Burton
Published: December 2017

Small-conductance Ca2+-activated K+ (SK) channels are important participants in inhibitory neurotransmission in gastrointestinal smooth muscles. Three isoforms of an SK channel family were cloned from murine proximal colon smooth muscle. The transcripts encoding these subunits (SK1, SK2, and SK3) were detected in murine proximal colon and other peripheral tissues. The mRNA of each subunit was expressed at different levels in murine and canine colonic smooth muscles. The mRNA quantitative ratio of SK transcriptional expression in murine proximal colon is SK2 > SK3 > SK1; transcriptional expression of SK isoforms in canine proximal colon is minimal. SK3 immunohistochemical localization in murine small intestine (jejunum) and proximal colon showed immunoreactivity in circular and longitudinal muscularis. In transversely sectioned muscularis, staining was localized at the cell membrane in smooth muscle cells. Immunoreactivity was more intense in myenteric ganglia between longitudinal and circular muscularis and neuronal processes in circular and longitudinal muscularis. Transient expression of mSK1, mSK2, and mSK3 in COS cells resulted in Ca2+-activated voltage-independent channels. mSK1 is less sensitive to apamin compared with SK2 and showed intracellular Ca2+ sensitivity (10−8 to 10−6 M) in asymmetrical K+ (5/140 mM K+) gradients. Our results suggest that SK channel expression varies in colonic myocytes from different species and may contribute differentially to inhibitory junction potentials.
II. Gastric motility: lessons from mutant mice on slow waves and innervation
Authors: Huizinga Jan D.
Published: December 2017

The stomach harbors a network of interstitial cells of Cajal (ICC) associated with Auerbach's plexus as well as intramuscular ICC within the muscle layers that make close apposition contact with nerve varicosities. ICC are critical for slow-wave generation, making ICC the pacemaker cells of the gut, allowing rhythmic peristaltic motor patterns in the mid- and distal stomach. ICC also play a role in neurotransmission, but its importance relative to direct muscle innervation is still under investigation. The role of ICC in many control functions of gastric motility in humans needs further examination. The pathophysiology of ICC in disease can be partially assessed by immunohistochemistry and electron microscopy on tissue samples. Electrogastrogram measurements may also play a role, but this technique needs further refinement. Communication between ICC and muscle may involve electrical coupling, metabolic coupling through gap junctions, or secretion of nitric oxide or carbon monoxide.
COX inhibition excites enteric nerves that affect motility, alkaline secretion, and permeability in rat duodenum
Authors: Nylander Olof , Hällgren Anneli , Sababi Manaf
Published: December 2017

In anesthetized rats, the cyclooxygenase (COX) inhibitor indomethacin induces duodenal motility, increases duodenal mucosal alkaline secretion (DMAS), and evokes a transient increase in duodenal paracellular permeability (DPP). To examine whether enteric nerves influence these responses, the duodenum was perfused with lidocaine. Motility was assessed by measuring intraluminal pressure, and DPP was determined as blood-to-lumen clearance of 51Cr-EDTA. DMAS was assessed by titration. In control animals, few contractions occurred during saline perfusion and lidocaine did not alter this condition. Perfusion with 0.03–0.1% lidocaine did not affect DMAS or DPP whereas 0.3–1% lidocaine reduced DMAS and increased DPP. Indomethacin induced motility and doubled DMAS. Application of 0.03% lidocaine on the duodenal serosa reduced motility and DMAS whereas 0.03% lidocaine applied luminally inhibited DMAS only. Higher concentrations of lidocaine abolished the increase in DMAS and changed the motility pattern to numerous low-amplitude contractions, the latter effect being blocked by iloprost. The lidocaine-induced increases in DPP were markedly higher than in controls. We conclude that indomethacin activates enteric nerves that induce motility, increase DMAS, and decrease DPP.
Hepatic and extrahepatic factors critical for liver injury during lipopolysaccharide exposure
Authors: Moulin Frederic , Copple Bryan L. , Ganey Patricia E. , Roth Robert A.
Published: December 2017

Bacterial endotoxin [lipopolysaccharide (LPS)] causes liver injury in vivo that is dependent on platelets, neutrophils [polymorphonuclear leukocytes (PMNs)], and several inflammatory mediators, including thrombin. We tested the hypothesis that thrombin contributes to LPS-induced hepatocellular injury through direct interactions with platelets and/or PMNs in vitro. Perfusion of isolated livers from LPS-treated rats with buffer containing thrombin resulted in a significant increase in alanine aminotransferase (ALT) activity in the perfusion medium, indicating hepatocellular damage. This effect was completely abolished by prior depletion of PMNs from the LPS-treated donor rats but not by depletion of platelets, suggesting interaction between thrombin and PMNs in the pathogenesis. Thrombin did not, however, enhance degranulation of rat PMNs in vitro, and it was not directly toxic to isolated rat hepatocytes in the presence of PMNs even after LPS exposure, suggesting that hepatocellular killing by the PMN-thrombin combination requires the intervention of an additional factor(s) within the liver. In livers from naive donors perfused with buffer containing PMNs and LPS, no injury occurred in the absence of thrombin. Addition of thrombin (10 nM) to the medium caused pronounced ALT release. These results indicate that thrombin and PMNs are sufficient extrahepatic requirements for LPS-induced hepatocellular damage in intact liver.
Platelets modulate ischemia/reperfusion-induced leukocyte recruitment in the mesenteric circulation
Authors: Salter James W. , Krieglstein Christian F. , Issekutz Andrew C. , Granger D. Neil
Published: December 2017

P-selectin-dependent leukocyte-endothelial cell adhesion has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds, including the gut. Because platelet-endothelial (P/E) cell adhesion also occurs in postischemic venules, the possibility exists that the expression of P-selectin on the surface of platelets that are adherent to venular endothelial cells may mediate the leukocyte recruitment elicited by I/R. P-selectin expression [dual radiolabeled monoclonal antibody (MAb) technique] and neutrophil accumulation [myeloperoxidase (MPO) activity] were measured in the postischemic small intestine of untreated rats and rats treated with either antiplatelet serum (APS) or MAbs directed against either P-selectin, GPIIb/IIIa, or fibrinogen. The increases in P-selectin expression and tissue MPO normally elicited by I/R were significantly attenuated in the different treatment groups, suggesting that I/R-induced neutrophil recruitment is a platelet-dependent, P-selectin-mediated process. Intravital microscopy was then employed to examine this process relative to leukocyte-endothelial cell adhesion in postischemic rat mesenteric venules. The recruitment of adherent and emigrated leukocytes after I/R was attenuated by pretreatment with a MAb against, either P-selectin, GPIIb/IIIa, or fibrinogen, as well as an Arg-Gly-Asp peptide. Whereas thrombocytopenia greatly blunted leukocyte emigration, it did not alter the leukocyte adherence response to I/R. These findings suggest that platelet-associated P-selectin contributes to the accumulation of leukocytes in postischemic tissue via a mechanism that alters transendothelial leukocyte migration.
Regulation of gastric epithelial cell development revealed in H+/K+-ATPase β-subunit- and gastrin-deficient mice
Authors: Franic Teo V. , Judd Louise M. , Robinson David , Barrett Simon P. , Scarff Katrina L. , Gleeson Paul A. , Samuelson Linda C. , Van Driel Ian R.
Published: December 2017

The gastric H+/K+-ATPase is essential for normal development of parietal cells. Here we have directly assessed the role of the H+/K+-ATPase β-subunit (H/K-β) on epithelial cell development by detailed quantitation of the epithelial cell types of the gastric mucosa of H/K-β-deficient mice. H/K-β-deficient mice had a 3.1-fold increase in the number of immature cells per gastric unit; however, the numbers of surface mucous and parietal cells were similar to those in the gastric units of wild-type mice. The effect of elevated gastrin levels in the H/K-β-deficient mice was determined by producing mice that are also deficient in gastrin. We demonstrated that the increased production of immature cells and resulting hypertrophy is caused by the overproduction of gastrin. However, the depletion of zymogenic cells, which is another feature of H/K-β-deficient mice, is independent of hypergastrinemia. Significantly, parietal cells of H/K-β- and gastrin-deficient mice had abnormal secretory membranes and were devoid of resting tubulovesicular membranes. Together these data suggest a homeostatic mechanism limiting the number of immature cells that can develop into end-stage epithelial cells and indicate a direct role for H/K-β in the development of mature parietal cells.
Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells
Authors: Akiho Hirotada , Blennerhassett Patricia , Deng Yikang , Collins Stephen M.
Published: December 2017

T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which activate signal transducer and activator of transcription 6 (STAT6) are expressed in the muscularis externa during nematode infection and are candidate mediators of the associated hypercontractility. To determine the locus of action of these cytokines, we examined the IL-4- and IL-13-induced hypercontractility of the isolated muscle cells from STAT6 +/+ and STAT6 −/− mice. We compared the results with cells isolated from Trichinella spiralis-infected STAT6 +/+ and STAT6 −/− mice. Carbamylcholine chloride (Carbachol) induced the contraction of jejunal muscle cells in a concentration-dependent manner maximal contraction (Rmax26.7 ± 1.9%). Cells from T. spiralis-infected STAT6 −/− mice showed the hypertrophy (cell lengths 41.4 ± 0.8 to 89.0 ± 8.7 μm) and hypercontractility (Rmax37.5 ± 1.3%) induced by infection. IL-4Rα mRNA was detected in dispersed smooth muscle cells. Incubation of longitudinal muscle-myenteric plexus (LMMP) with IL-4 and IL-13 enhanced Carbachol-induced muscle contraction (Rmax35.5 ± 1.9 and 32.4 ± 2.9%, respectively). Incubation of LMMP from STAT6 −/− mice with IL-4 did not enhance the contraction. The hypercontractility in T. spiralis-infected mice was attenuated in STAT6 −/− mice ( P < 0.02). These results indicate both IL-4 and IL-13 induce hypercontractility of muscle cells via the STAT6 pathway, and this is the basis for hypercontractility observed in T. spiralis-infected mice.
Effects of intravenous anesthetic agents on left ventricular function in dogs
Authors: Horwitz L. D.
Published: December 2017

The cardiovascular effects of ketamine hydrochloride and thiopental sodium were studied in 11 dogs. During anesthesia, mean heart rate rose to 185 beats/min with ketamine and 147 beats/min with thiopental. Cardiac output was increased with ketamine but unchanged by thiopental. The maximum first derivative of the left ventricular pressure (dP/dt max) fell by 14% with thiopental but did not change significantly with ketamine. Propranolol resulted in attenuation of the tachycardia and a fall of 10% in dP/dt max with ketamine but had little effect on the response to thiopental. Phentolamine had no consistent effects on either drug. With pentolinium both drugs decreased dP/dt max. Intracoronary injection of ketamine decreased dP/dt max. Adrenalectomy had little effect on the responses to either anesthetic. The results lead to the conclusion that both ketamine and thiopental have myocardial depressant effects, but, whereas thiopental does not alter sympathetic tone, the depressive effects of ketamine are obscured by stimulation of cardiac sympathetic nerves.
Physiologic effects of normal-or low-oxygen-affinity red cells in hypoxic baboons
Authors: Spector J. I. , Zaroulis C. G. , Pivacek L. E. , Emerson C. P. , Valeri C. R.
Published: December 2017

Baboons were bled one-third their red cell mass and were given homologous transfusions of red blood cells to restore the red cell volume. One group of baboons received red blood cells with a normal 2,3-diphosphoglycerate 2,3-DPG) level and normal affinity for oxygen, and in this group the 2,3-DPG level after transfusion was normal. The other group received red blood cells with a 160% of normal 2,3-DPG level and decreased affinity for oxygen, and in this group the 2,3-DPG level after transfusion was 125% of normal. In both groups of baboons, the inspired oxygen concentration was lowered and arterial PO2 tension was maintained at 55-60 mmHg for 2 h after transfusion. During the hypoxic state, systemic oxygen extraction was similar in the two groups, whereas oxygen saturation was lower in the high 2,3-DPG group than in the control animals. Cardiac output was significantly reduced 30 min after the arterial PO2 was restored to normal. These data indicate that red blood cells with decreased affinity for oxygen maintained satisfactory oxygen delivery to tissue during hypoxia.
An implantable semiconductor beta-radiation detector
Authors: Khouri E. M. , Olsson R. A. , Bedynek J. L. , Bass B. G.
Published: December 2017

An implantable beta-radiation detector suitable for the measurement of reginal blood flow in the experimental animal by the indicator clearance principle is described. A lithium-drifted silicon diode encapsulated in a stainless steel case is sutured over the site of interest. A suitable beta-emitting isotope, such as 85Kr in saline solution, is injected into the arterial supply and its calibrated against a mechanical system and showed excellent agreement up to 600 ml/100 g per min. At very high rates beyond the physiological range, flow was underestimated by a maximum of 10%. In vivo comparisons of myocardial blood flow assessed by the beta detector did not agree well with estimates of flow from a precordial counter or by the microsphere technique. Possible reasons are spatial heterogeneity of regional myocardial blood flow, the greatly different masses of tissue involved, or our inability to achieve sufficient numbers of spheres for accuracy in a 50-mg mass of tissue. The unit was still functional after 50 days in a chronic animal.
Cyclic nucleotide metabolism and vasodilation in canine mesenteric artery
Authors: Mailman D. , Pawilk W. , Shepherd A. P. , Tague L. L. , Jacobson E. D.
Published: December 2017

The uptake and extracellular and intracellular metabolism of radioisotopically labeled cyclic 3',5'-adenosine monophosphate (cAMP) and dibutyryl cAMP (DBcAMP) was determined in canine mesenteric arteries incubated in vitro. Intracellular tissue uptake was measured by radioisotope counting and labeled metabolites separated by thin-layer chromatography. Extracellularly, cAMP was extensively metabolized to AMP, adenosine, and Pi. DBcAMP was metabolized to monobutyryl cAMP (MBcAMP) intracellularly. Vasodilation of the mesenteric circulation in vivo was produced by cAMP, its metabolites and DBcAMP. DBcAMP caused greater vasodilation than cAMP but had a response time to its peak effect of 12 min versus 90 s for cAMP. The vasodilator properties of cAMP and DBcAMP were related to their metabolism. It was concluded that the vasodilation caused by cAMP was due to cAMP metabolites produced by extracellular metabolism.
Humoral factor depletion and reticuloendothelial depression during hemorrhagic shock
Authors: Loegering D. J.
Published: December 2017

Circulating opsonic activity and reticuloendothelial system (RES) phagocytic function were determined in anesthetized rats subjected to hemorrhagic shock. Animals were hemorrhaged to and maintained at 40 mmHg arterial blood pressure until they spontaneously took back 5% or 40% of the maximum bled volume. The phagocytic index, as determined by colloid clearance kinetics, was decreased in both groups following reinfusion of the shed blood. The reduction in phagocytic index was associated with decreased liver, unchanged spleen, and increased lung test colloid localization. Plasma opsonic activity, as determined by liver slice bioassay, was decreased 50-60% at 5% and 40% uptake of the maximum shed volume, decreased further 15 min after reinfusion in both groups, and tended to recover 1 h after reinfusion in the 5% uptake group. In vitro hepatic phagocytic activity of liver slices from shocked animals in the presence of normal rat plasma was decreased only in the 40% uptake animals after reinfusion when the arterial blood pressure had decreased to 50 mmHg. These data indicate that the depression of RES phagocytic function during hemorrhagic shock is associated with and may be mediated, in part, by decreased circulating opsonic activity.
Autonomic afferents at T1 in elicitation of volume-induced tachycardia in the dog
Authors: Gupta P. D. , Singh M.
Published: December 2017

Intravenous infusion of blood elicited tachycardia in anesthetized dogs with beta-receptor blockade (dogs with vagal efferents intact but cardiac sympathetic efferents blocked) and bradycardia in dogs with combined beta-receptor blockade and rhizotomy at T1 (dogs with vagal efferents intact but cardiac sympathetic efferents plus autonomic afferents at T1 blocked). This suggests that tachycardia elicited by volume in infusion may be partly due to a reflex with its afferent pathway at the T1 segment of the spinal cord and its efferent pathway in the vagi. Moreover, infusion evoked bradycardia in dogs with right-sided rhizotomy at T1, which was not significantly different from the response elicited in dogs with bilateral rhizotomy at T1. Additionally, the tachycardia response induced in dogs with ventral or dorsal rhizotomy at T1 was significantly different from the bradycardia response elicited in dogs with both dorsal and ventral rhizotomy at T1. These results suggest that the afferent pathway predominates on the right side, and its entry at T1 may be via both dorsal and ventral roots.
Carotid body chemoreceptor reflexes and their interactions in the seal
Authors: Elsner R. , Angell-James J. E. , de Burgh Daly M.
Published: December 2017

In the anesthetized spontaneously breathing harbor seal Phoca vitulina stimulation of the carotid body chemoreceptors by intracarotid injections of sodium cyanide or by hypoxic hypercapnic blood causes an increase in tidal volume, respiratory frequency, and respiratory minute volume. The heart rate invariably decreased. Experimental dives caused apnea and bradycardia. When the carotid bodies are stimulated within 10 s of the commencement of a dive, the chemoreceptor-respiratory response is abolished, but the chemoreceptor-cardioinhibitory response is considerably enhanced. Electrical stimulation of the central cut end of a superior laryngeal nerve also causes apnea and bradycardia; stimulation of the carotid body now fails to produce a respiratory response but the cardioinhibitory effect is enhanced. These results indicate that the carotid bodies cause reflexly hyperventilation and bradycardia, and that these responses are considerably modified by other inputs to the central nervous system.
An extracorporeal shunt for the measurement of coronary flow in the closed-chest dog
Authors: Yeager J. C. , Scott J. B. , Haddy F. J.
Published: December 2017

An extracorporeal shunt circuit interposed between the left carotid artery and the left coronary ostium employs an electromagnetic flowmeter to measure coronary blood flow in the closed-chest anesthetized dog. Flow may be measured with the animal's arterial pressure as the driving force; introduction of a roller pump, or a roller pump and a negative feedback pressure controller allows for constant flow or constant pressure modes. During occlusion of the circuit or cessation of pump flow, retrograde coronary blood flow can be collected for measurement. The construction of the circuit is relatively simple and inexpensive, using common laboratory materials and a commercially available electromagnetic flowmeter and probe.
Metabolism of adenine nucleotides in the cultured fetal mouse heart
Authors: Kaufman I. A. , Hall N. F. , DeLuca M. A. , Ingwall J. S. , Mayer S. E.
Published: December 2017

Intact beating fetal mouse hearts in organ culture were deprived of oxygen and glucose for up to 4 h, resulting in loss of beating, an 80% fall in ATP, reduction of energy charge from 0.85 to 0.48, and doubling of total nucleoside concentration. Radiolabeled adenine nucleotides were degraded to hypoxanthine and inosine, which were lost from the hearts into the medium during the deprivation period. Adenosine and adenine also appeared in the medium when adenosine deaminase was inhibited. After 24 h of O2 and glucose resupply, ATP returned to 60% of control, and energy charge rose to 0.76. Labeled nucleosides and bases remaining in the heart or exogenous labeled adenine were utilized to resynthesize ATP. [14C]glycine was rapidly taken up by recovering hearts but was not used for de novo adenine nucleotide synthesis. Ability to recover ATP and spontaneous contraction appear related to residual nucleotide and nucleoside content rather than to energy charge.
Positive inotropic response to inosine in the in situ canine heart
Authors: Jones C. E. , Thomas J. X. , Devous M. D. , Norris C. P. , Smith E. E.
Published: December 2017

Effects of inosine on left ventricular contractile force, circumflex blood flow, heart rate, and arterial pressure were investigated in mongrel dogs. Infusion of 50 ml of 10, 25, or 50 mM inosine into the right atrium over 5 min produced arterial blood inosine concentrations of 20-120 microM. Infusion of inosine concentrations of 10 mM or greater produced statistically significant increases in contractile force and circumflex blood flow (P less than 0.05). The increases in contractile force and circumflex blood flow caused by 50 inosine were approximately 40% and 110%, respectively. No statistically significant increases in heart rate or arterial pressure were observed during infusion of inosine at any concentration. Administration of propranolol (2 mg/kg) in no way altered the effects of inosine on contractile force or circumflex blood flow. Thus, the present study suggests that inosine in concentrations which may be produced in the myocardium during stressful conditions causes a substantial effect on the inotropic state of the heart and that the effects of inosine are not mediated through adrenergic mechanisms.
Osmotic flow through the placental barrier of chronically prepared sheep
Authors: Armentrout T. , Katz S. , Thornburg K. L. , Faber J. J.
Published: December 2017

An electromagnetic flow sensor was placed on the distal aorta of sheep fetuses in utero, and catheters were placed in a femoral artery and the common umbilical vein. Catheters were also placed in a carotid artery and a uterine vein of the pregnant ewe. Three days postoperatively maternal plasma was hyperosmotic with respect to fetal plasma by all methods: +5.8 +/- 1.4 SE by vapor-pressure osmometry, +2.2 +/- 0.7 SE by freezing-point depression osmometry corrected for bicarbonate loss; and +3.26 mosmol/liter by chemical measurement of plasma constituents. Maternal or fetal plasma was made hypertonic in vivo by infusion of concentrated solutions of mannitol, sucrose, or NaCl. Transplacental water flux was calculated from placental blood flows and arteriovenous differences in water content of the blood. The apparent osmotic conductivity of the placenta was 61 ml2-mosmol-1-kg-1, but this value should be divided by an unknown reflection coefficient to yield the true osmotic conductivity. Separate measurements were made of the placental diffusional permeability of Na+ and Cl- in five chronically prepared sheep fetuses: PSNa+ =0.20 +/- 0.04, PSCl- = 0.27 +/- 0.04 ml/(min-kg fetus). There was a highly significant positive regression between (total) placental permeability and fetal weight.
Water and electrolyte acquisition across the placenta of the sheep
Authors: Conrad E. E. , Faber J. J.
Published: December 2017

Fetal plasma is known to be hyperosmotic with respect to maternal plasma. Although some solutes are actively transported across the placenta and occur in higher concentrations in fetal than in maternal plasma, the total concentration difference is reversed by an opposite difference in the concentrations of electrolytes. Calculations on the basis of the Kedem and Katchalsky equations for a homogeneous membrane demonstrate that active solute transfer and a physiologically plausible hydrostatic pressure difference account for the known rates at which water and electrolytes are accumulated in the fetus. Best estimates of the membrane parameters (per kilogram fetal weight) are PSNa, Cl = 0.23 ml-min-1-kg-1, LpS = 5-10(-6) cm5-min-1-kg-1-dyne-1, and sigma NaCl approximately equal to 0.5. (where PS is the permeability-surface area product, LpS is the filtration coefficient, or sigma is the Staverman reflection coefficient). The driving forces for water and electrolyte transfer (active transfer and hydrostatic pressure) are not used as regulators. Rather, electrolyte permeability, which is the major constraint on fetal growth, and which continuously increases during gestation, makes possible the exponential increase in fetal weight during gestation.
Effect of sex difference and pregnancy on the normal reactive hyperemia curve
Authors: Vyden J. K. , Takano T. , Nagasawa K. , Ogawa T. , Groseth-Robertson M. , Swan H. J.
Published: December 2017

The 10-min reactive hyperemia reaction was studied in a group of normal males, 10 normal females, 10 females in each trimester of pregnancy, and 10 females 6 wk postpartum. Sex difference had a marked effect on the hyperemic reaction, in that 5 and 15 s after release of circulatory arrest, the mean forearm blood flow in normal males was significantly reduced below that of normal females. During pregnancy there was a shift in the reaction of the pregnant female toward that in the normal male. In the 1st trimester of pregnancy, 5 s after circulatory arrest the mean forearm blood flow was diminished below that of the normal female; in the 2nd and 3rd trimesters at 5 s, the reaction was significantly diminished below that of the normal female. At 6wk postpartum, the reaction was essentially the same as in the nonpregnant female. Although these changes may be explained by a hormonal difference, they portray that there may be a marked difference in vascular reactivity due to sex difference only.
Nonuniform contraction in the isolated cat papillary muscle
Authors: Huntsman L. L. , Day S. R. , Stewart D. K.
Published: December 2017

Microspheres infused into the coronary microcirculation were used as markers to define segments within isolated cat papillary muscles. Video recording and analysis provided measurements of the variations of segment lengths as the muscles contracted at lengths of 76–100% Lmax. In all muscles, segments in the center region were found to shorten during muscle isometric contraction while those in the end regions lengthened. Central shortening was typically 10–15%. In the passive state, segment lengths varied directly with muscle length over a broad range characterized by low force. Segments in the center region, however, displayed an abrupt transition to high stiffness at a certain length while end regions continued to stretch. Force-length relationships obtained for the presumably healthy center segment are significantly different from those obtained for the whole muscle. These results suggest that there may be major difficulties with the interpretation of mechanical measurements on papillary muscles unless contractile inhomogeneity is eliminated or taken into account.
Responses of canine endocardium to stimulation of the upper thoracic roots
Authors: Norris J. E. , Lippincott D. , Wurster R. D.
Published: December 2017

In each of 10 mongrel dogs anesthetized with alpha chloralose, strain-gauge arches were sutured to five epicardial and three endocardial locations. Comparisons of contractile force responses during stimulation of the left and right roots of the same segmental level revealed several differences dependent upon the particular myocardial area observed. Of the three left ventricular endocardial areas studied, the interventricular septum was the most responsive, particularly during stimulation of the right roots. The basal free wall and posterior papillary muscle were more responsive to left-root than to right-root stimulations. Epicardial responses were consistent with those previously reported. Generally, all areas responded to the greatest degree during stimulation of the second roots with the third and first next in order of effectiveness. Although stimulation of each level of preganglionic outflow activated all epicardial and endocardial segments of the myocardium, the magnitude of the changes in contractile force were highly variable dependent upon the specific level of preganglionic outflow and the location of the strain-gauge arch.
Myocardial enzyme activities in guinea pigs during development
Authors: Barrie S. E. , Harris P.
Published: December 2017

The activities of hexokinase, glucose-6-phosphate dehydrogenase, and glycolytic enzymes were higher in the fetal myocardium of the guinea pig than at birth and fell progressively during the 1st mo of life. The alphaHBDH/LDH ratio of H to M subunits of lactate dehydrogenase, was low in the fetus and continued to rise during the 1st mo after birth. The distinction between the left and right ventricular activities of lactate dehydrogenase, which is clear in adult guinea pigs, was absent in the fetus and appeared during postnatal development. Glycogen phosphorylase activity was low in the fetus and at birth. The activities of beta-hydroxyacylcoenzyme A dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and aspartate aminotransferase were low in the fetus, but had reached, or even temporarily exceeded, normal adult levels at birth. Palmitylcarnitine transferase activity was also low in the fetal heart compared with the newborn but continued to increase substantially during the first 2 wk after birth
Creating permanent complete heart block by indirect cauterization without atriotomy
Authors: Shiang H. H. , Kupersmith J. , Wiemann G. F. , Rhee C. Y. , Litwak R. S.
Published: December 2017

We created permanent complete heart block (CHB) in 11 dogs without atriotomy by means of indirect cauterization of the atrioventricular (A-V) bundle with a partially insulated wire placed through a small puncture in the atrial wall and guided by palpation. In six acute studies and five chronic studies, all dogs exhibited permanent CHB. To test the block, isoproterenol increased both atrial and ventricular rates 200%–400% without affecting the block. Atropine had no effect on ventricular rate or block.
Capillary reserve in isometrically contracting dog hearts
Authors: Duran W. N. , Marsicano T. H. , Anderson R. W.
Published: December 2017

Page H276: W. N. Duran, T. H. Marsicano, and R. W. Anderson. “Capillary reserve in isometrically contracting dog hearts.” In the citation of the Journal in the third line of the abstract, the volume number should read 233.
Effect of dihomo-gamma-linolenic acid on the canine pulmonary vascular bed
Authors: Hyman A. L. , Spannhake E. W. , Chapnick B. M. , McNamara D. B. , Mathe A. A. , Kadowitz P. J.
Published: December 2017

The effect of dihomo-gamma-linolenic acid (DGLA), the precursor of the monoenoic prostaglandins (PG), F1alpha and E1, on the pulmonary vascular bed of the intact dog was studied under conditions of controlled pulmonary blood flow. DGLA increased pulmonary vascular resistance in a dose-related manner by constricting intrapulmonary veins and upstream segments, presumably pulmonary arteries. Intrapulmonary injection of DGLA also increased transpulmonary injection of DGLA also increased transpulmonary airway pressure, presumably by increasing airway resistance and decreasing lung compliance or both. The vasoconstrictor response, however, was independent of changes in transpulmonary pressure since similar pressor responses were obtained in ventilated and nonventilated lungs. Further, the response was not dependent on factors or elements in whole blood, since the increase in pulmonary vascular resistance occurred during perfusion with saline or dextran and was enhanced in these media. Conversion of DGLA to PGs by a lung cyclo-oxygenase appears to mediate the response, since it was blocked by indomethacin and dose not occur with injection of nonprecursor long-chain fatty acids. These data suggest that the response to DGLA is due to formation of vasoactive products in the monoenoic PG pathway.
Adrenal contribution to coronary regulation in the newborn
Authors: Downing S. E. , Hellenbrand W. E. , Lee J. C. , Nudel D. B.
Published: December 2017

Evidence for adrenergic regulation of the coronary vessels was sought in 27 newborn lambs. Sympathetic activity was altered by temporarily lowering cephalic perfusion pressure (CPP) from 90 to 20 mmHg while aortic pressure was held constant. Heart rate (HR) and left ventricular dP/dt max increased markedly, while end-diastolic pressure and stroke volume fell. These changes were accompanied by an increase in coronary blood flow (CBF), myocardial O2 consumption (MVO2), and reduced coronary resistance (CF) (P less than 0.005). After beta blockade, which prevented an augmentation of metabolic demand, the same maneuver resulted in coronary vasoconstriction, reflected by reduced CBF and increased CR (P less than 0.02). This response was eliminated by alpha blockade with phentolamine (2 mg/kg). In 13 lambs subjected to bilateral adrenalectomy or sham operation, lowering CPP elicited similar positive chronotropic and inotropic changes, increases of MVO2 and CBF, and reduced CR. Following beta blockade, lowering CPP in the sham group caused coronary constriction. However, no changes in CBF or CR were elicited in the adrenalectomized lambs. These observations indicate that integrity of the adrenal glands is required for adrenergic control of the coronary vessels in the newborn. Chronotropic and inotropic regulation is mediated by direct neural action and is not dependent on adrenal function.
Maternal placental vascular compliance in rabbits
Authors: Brownfield G. L. , Gilbert R. D. , Power G. G.
Published: December 2017

We studied compliance on the maternal side of the placenta of 20 New Zealand white rabbits, using 51Cr and 125I labels to determine erythrocyte, plasma, and whole-blood volumes per gram of placental tissue under varying maternal pressure conditions. At normal maternal arterial (Pa) and venous (Pv) pressures of 71.8 and 5.5 mmHg, placental blood volume (mean +/- SE) was 0.447 +/- 0.051 ml/g placental tissue. When venous pressure was raised (Pa = 45.5, Pv = 12.2) by occluding the inferior vena cava, blood volume increased to 0.729 +/- 0.068 ml/g, a significant 63% rise. However, when arterial pressure was lowered by occluding the aorta in two steps, dropping to Pa = 33.8, Pv = 7.0, and Pa = 13.5, Pv = 5.4, volume did not decrease significantly. We estimated intervillous space pressure (Pivs) from arterial and venous pressures assuming a ratio of venous to total resistance of 0.02. Compliance calculated from the slope of Pivs vs. volume was 0.0471 ml/mmHg per g. Maternal placental hematocrit averaged 27%, appreciably less than the circulating hematocrit of 38%. Overall, the results suggest that placental volume would be maintained during hypotension and would increase when venous pressure is elevated.
Diastolic stress-strain relation of nonexcised blood-perfused canine papillary muscle
Authors: Kitabatake A. , Suga H.
Published: December 2017

We studied diastolic stiffness of 10 coronary-perfused twitching papillary muscles of the canine right ventricle. The muscle beat at a regular sinus rhythm of 122 +/- 20 (SD) beats/min at 37 degrees C. They were stretched slowly at a constant rate. Diastolic force increased exponentially with the stretch. Calculating Lagrangian stress (sigma) and strain (epsilon) from diastolic force and length, we found a linear relationship between ln sigma and epsilon within the physiological range of strain (0.025 less than epsilon less than 0.4). This indicates that the diastolic stress-strain relationship of the canine papillary muscle can be approximated by a single exponential curve: sigma = a.exp(b.epsilon). The mean +/- SD of the stiffness constant b was 18.0 +/- 3.2 (dimensionless). Our b values are comparable to those of dogs and human subjects, either indirectly assessed from the ventricular pressure-volume relationship or directly obtained in excised quiescent muscle specimens. Different coronary perfusion pressures (75-125 mmHg) in 10 muscles showed a statistically significant positive correlation to b values.
Protein kinase regulation of cardiac phosphorylase activity and contractility
Authors: Dobson J. G.
Published: December 2017

The relationship between cAMP-dependent protein kinase activity and epinephrine-produced activation of phosphorylase and increase in contractility was investigated in the intact working rat heart. Epinephrine was administered as a bolus into the superior vena cava of open-chest preparations and the hearts were rapidly frozen. cAMP increased within 5 s and returned to control within 20-30 s. Protein kinase and phosphorylase kinase activity ratios increased transiently with the same time course as that for cAMP. The phosphorylase activity ratio and the rate of left ventricular pressure development increased maximally within 15 s and returned to control in 30-60 s. Continuous infusion of epinephrine caused a sustained elevation of the protein kinase. Free catalytic protein kinase activity increased proportionately with the dose of epinephrine. The beta-adrenergic blocking agent, practolol, had no effect on the basal levels of the five parameters studied, but did prevent the epinephrine-produced increases. The results suggest that the time course of cAMP-dependent protein kinase activation is appropriate if this enzyme is to play a role in the catecholamine-induced increase in both glycogenolysis and contractility in the in vivo heart.
An intracaval cannulation for obtaining pure, mixed hepatic venous blood samples
Authors: Lautt W. W. , Wong C. , Durham J. S. , Taillon P.
Published: December 2017

A method for obtaining pure, mixed hepatic venous blood is described and evaluated in anesthetized cats. Hepatic vascular congestion does not occur with this “intracaval cannulation”, however small elevations in central venous blood pressure were noted. Although these changes persisted they did not result in systemic vascular congestion, judging from the normal arterial and portal pressures and from the lack of progressive decrease in arterial blood pressure. Blood samples obtained using the intracaval cannulation were shown to contain identical levels of oxygen as those obtained using a more complex surgical preparation. Reflux of blood from the vena cava does not occur during sampling. The responsiveness of this sampling method to rapid changes in venous content was evaluated by following the changes in glucose balance caused by direct stimulation of the hepatic nerves. The responses measured were similar to those measured in a separate set of experiments obtained using blood samples from a surgically isolated hepatic venous supply.
Genetic influence on cadmium-induced hypertension
Authors: Ohanian E. V. , Iwai J. , Leitl G. , Tuthill R.
Published: December 2017

Dahl hypertension-resistant (R) and hypertension-sensitive (S) rats were used to determine whether cadmium-induced hypertension is dependent on genetic predisposition. In experiment I, 16 wk-old R and S rats of both sexes were injected with two doses of cadmium (1 and 2 mg/kg body wt, ip), whereas the controls received the same volumes of saline. Hypertension and renal vascular changes were observed in cadmium-injected S rats but not in R rats. The S females appeared more sensitive than S males to the hypertensinogenic effect of cadmium. In experiment II, groups of weanling female R and S rats were given 0, 1, 2.5, 5, or 10 mg cadmium/liter drinking water and fed either a low-salt (0.4% NaCl) or a high-salt (4% NaCl) diet for 28 wk. Cadmium produced cardiac hypertrophy (1 mg cadmium/liter) and hypertension associated with renal vascular changes (1--5 mg cadmium/ liter), and it enhanced proteinuria (1–10 mg cadmium/liter) in S rats on a low-salt diet. Also, the development of salt-induced hypertension was accelerated in cadmium-fed (1 and 2.5 mg/liter) S rats. These adverse effects of cadmium were not detected in R rats on either salt diet. In experiments I and II, cadmium concentrations in the kidneys and liver of S rats were higher (P less than 0.001) than in those of R rats. These data indicate that genetic differences influence the pathogenesis of cadmium-induced hypertension.
Myocardial infarction in the baboon: regional function and the collateral circulation
Authors: Crozatier B. , Ross J. , Franklin D. , Bloor C. M. , White F. C. , Tomoike H. , McKown D. P.
Published: December 2017

Occlusion of the anterior descending coronary artery was produced in sedated baboons 7–15 days after implantation of a micromanometer and ultrasonic crystals for measurement of regional left ventricular dimensions in ischemic, marginal, and control segments. One minute after coronary occlusion (CO), ischemic segments exhibited a marked systolic bulge with wall thinning, and percent systolic shortening of marginal segments decreased. Over the ensuing weeks, there was a progressive increase of end-diastolic lengths in marginal and ischemic segments, whereas systolic shortening in these segments did not improve significantly. Control segments did not change. In control baboons, the coronary collateral index was 55 +/-25 (SE) compared to 560 +/- 74 in normal dogs. One month after CO, the collateral index was 543 +/- 144 in baboons compared to 6,685 +/- 716 in dogs, regions of normal tissue were seen in the infarct (14.2 +/- 2% of left ventricular mass). Minimal coronary collateral development in the baboon provides a likely explanation for differences from the dog in regional functional responses and in the character of the infarct.
Effects of hypertonic mannitol on cardiac lymph in nonischemic myocardium
Authors: Ali M. , Ellis A. , Pick R. , Glick G.
Published: December 2017

This investigation was designed to elucidate the effects of hypertonic mannitol on the nonischemic myocardium. In anesthetized open-chest dogs, we collected cardiac lymph for 2 h before and for 4 h during the infusion of hypertonic mannitol or normal saline. We studied the changes in the volume of lymph flow and the release of lysosomal enzyme acid phosphatase and protein into the cardiac lymph. In group 1 (n = 7) and group 3 (n = 8), the effects of 1-h and 4-h infusions of mannitol were studied, respectively. In these dogs, mannitol caused significant rises in lymph flow and release of total acid phosphatase into the cardiac lymph. In group 3, protein efflux increased significantly. In group 2 (n = 5) and group 4 (n = 4), infusion of normal saline for 1 and 4 h did not significantly change the release of total acid phosphatase and proteins into the cardiac lymph. Thus, infusion of hypertonic mannitol for 1--4 h in the nonischemic myocardium may have some deleterious effects because of its apparent ability to impair lysosomal membranes and to increase capillary permeability.
Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force. II
Authors: Keely S. L. , Eiring A.
Published: December 2017

The effects of histamine on heart cAMP-dependent protein kinase activity, cAMP levels, phosphorylase activity, and contractile force was investigated in the perfused guinea pig heart. To accurately determine the protein kinase activity ratio in guinea pig heart, it was necessary to measure kinase activity in whole homogenates immediately after homogenization of the tissue. Histamine produced a rapid dose-dependent increase in cAMP and the protein kinase activity ratio followed by increased in contractile force and phosphorylase activity. There was a good correlation between the degree of protein kinase activation and the increase in phosphorylase and force. The beta-adrenergic blocking agent propranolol did not reduce the effects of histamine, but metiamide, a potent H2-receptor antagonist, greatly attenuated all the effects of histamine. The data support the hypothesis that increases in heart cAMP-dependent protein kinase activity produce corresponding increases in contractile force and phosphorylase activity.
Plasma and lymph dopamine-beta-hydroxylase and norepinephrine during carotid occlusion
Authors: Velasquez M. T. , Alexander N.
Published: December 2017

Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) levels in superior mesenteric venous (SMV) and arterial blood and in intestinal lymph were determined sequentially before and during carotid artery occlusion (CAO) in anesthetized rabbits. During the first 15 min of CAO, SMV plasma NE increased 77% but SMV plasma DBH increased only 11%. During the second 15 min of CAO, SMV NE declined to 36% above control but SMV DBH rose further and peaked to 29% above control after CAO was released; arterial DBH and NE showed small insignificant changes. Lymph DBH and NE increased simultaneously throughout the period of CAO. Increases in mean arterial pressure during CAO correlated with superior mesenteric venous NE (r = 0.58, P less than 0.01). In additional experiments, hepatic vein plasma NE was 74% lower than portal vein NE. Thus, during acute sympathetic activation, DBH and NE increase in mesenteric venous plasma and intestinal lymph but the peak response of plasma DBH lags behind that of NE. The degree of NE change in the general circulation is minimized due to hepatic clearance of NE.
Whole body response of the peripheral circulation following hemorrhage in the rat
Authors: Samar R. E. , Coleman T. G.
Published: December 2017

Changes in mean circulatory filling pressure (MCFP) after hemorrhage reflect the whole-body response of the peripheral circulation to restore the driving force for venous return. In this study, changes in MCFP were measured for 15 min following a rapid 8 ml/kg hemorrhage. Three groups of rats were studied: 1) conscious, untreated; 2) conscious, ganglion blocked; and 3) pentobarbital anesthetized. In all three groups, hemorrhage decreased MCFP approximately 2.6 mmHg immediately after hemorrhage. In the conscious untreated rat, MCFP recovered 1.3 mmHg in 15 min; 83% of this recovery was complete within 2 min, and over 50% was complete by 30 s posthemorrhage. With ganglionic blockade, recovery was slowed to about 70% of that in the conscious, untreated animal during the first 5 min after hemorrhage. MCFP recovery was substantially depressed by pentobarbital, averaging only 42% of that in the untreated animal 5 min after hemorrhage. The results demonstrate that peripheral changes can quickly restore nearly 50% of the MCFP decrease occurring immediately after mild hemorrhage and that about one-third of this response is mediated by the sympathetic nervous system. Pentobarbital anesthesia greatly inhibits recovery, although its repressive mechanism is not known.