bluuebunny/crossref_metadata_2025 huggingface dataset:
Compensatory changes in Ca2+ and myocardial O2 consumption in β-tropomyosin transgenic hearts
Authors: MacGowan Guy A. , Du Congwu , Wieczorek David F. , Koretsky Alan P.
Published: December 2017

Transgenic mice overexpressing β-tropomyosin have increased myofilament Ca2+ sensitivity that we hypothesized would result in altered relationships among pressure and heart rates, intracellular Ca2+, and myocardial O2 consumption. In perfused hearts from transgenic mice there was a marked negative force-frequency response between 6 and 10 Hz with a 30 ± 3% reduction in peak-positive first derivative of pressure development over time (dP/d t) compared with 14 ± 2% in wild-type mice ( P < 0.001). At 8 Hz systolic pressures were normal, though peak systolic intracellular Ca2+ was significantly reduced in transgenic mice versus wild type (726 ± 61 vs. 936 ± 67 nM, P < 0.05) indicating an alteration in the pressure-Ca2+ relationship. Over a wide range of positive and negative inotropic interventions there were normal developed pressures, though marked elevations in myocardial O2 consumption (15–54%). Because pressures are normal and intracellular Ca2+ decreased and myocardial O2 consumption increased, this suggests that these abnormalities are at least in part compensatory mechanisms to the altered myofilament function.
Effect of a maldistribution of microvascular blood flow on capillary O2 extraction in sepsis
Authors: Ellis Christopher G. , Bateman Ryon M. , Sharpe Michael D. , Sibbald William J. , Gill Ravi
Published: December 2017

Inherent in the remote organ injury caused by sepsis is a profound maldistribution of microvascular blood flow. Using a 24-h rat cecal ligation and perforation model of sepsis, we studied O2 transport in individual capillaries of the extensor digitorum longus (EDL) skeletal muscle. We hypothesized that erythrocyte O2 saturation (So 2) levels within normally flowing capillaries would provide evidence of either a mitochondrial failure (increased So 2) or an O2 transport derangement (decreased So 2). Using a spectrophotometric functional imaging system, we found that sepsis caused 1) an increase in stopped flow capillaries (from 10 to 38%, P < 0.05), 2) an increase in the proportion of fast-flow to normal-flow capillaries ( P< 0.05), and 3) a decrease in capillary venular-end So 2 levels from 58.4 ± 20.0 to 38.5 ± 21.2%, whereas capillary arteriolar-end So 2levels remained unchanged compared with the sham group. Capillary O2 extraction increased threefold ( P < 0.05) and was directly related to the degree of stopped flow in the EDL. Thus impaired O2 transport in early stage sepsis is likely the result of a microcirculatory dysfunction.
Nitric oxide induces apoptosis by activating K+channels in pulmonary vascular smooth muscle cells
Authors: Krick Stefanie , Platoshyn Oleksandr , Sweeney Michele , McDaniel Sharon S. , Zhang Shen , Rubin Lewis J. , Yuan Jason X.-J.
Published: December 2017

Nitric oxide (NO) is an endogenous endothelium-derived relaxing factor that regulates vascular smooth muscle cell proliferation and apoptosis. This study investigated underlying mechanisms involved in NO-induced apoptosis in human and rat pulmonary artery smooth muscle cells (PASMC). Exposure of PASMC to NO, which was derived from the NO donor S-nitroso- N-acetyl-penicillamine, increased the percentage of cells undergoing apoptosis. Increasing extracellular K+concentration to 40 mM or blocking K+channels with 1 mM tetraethylammonia (TEA), 100 nM iberiotoxin (IBTX), and 5 mM 4-aminopyridine (4-AP) significantly inhibited the NO-induced apoptosis. In single PASMC, NO reversibly increased K+currents through the large-conductance Ca2+-activated K+(KCa) channels, whereas TEA and IBTX markedly decreased the KCacurrents. In the presence of TEA, NO also increased K+currents through voltage-gated K+(Kv) channels, whereas 4-AP significantly decreased the Kvcurrents. Opening of KCachannels with 0.3 mM dehydroepiandrosterone increased KCacurrents, induced apoptosis, and further enhanced the NO-mediated apoptosis. Furthermore, NO depolarized the mitochondrial membrane potential. These observations indicate that NO induces PASMC apoptosis by activating KCaand Kvchannels in the plasma membrane. The resulting increase in K+efflux leads to cytosolic K+loss and eventual apoptosis volume decrease and apoptosis. NO-induced apoptosis may also be related to mitochondrial membrane depolarization in PASMC.
Comparative analysis of aortic impedance and wave reflection in ferrets and dogs
Authors: Burattini R. , Campbell K. B.
Published: December 2017

Our modified version of the T-tube arterial model (consisting of two parallel, loss-free transmission paths terminating in lumped loads of complex and frequency-dependent nature) was applied to experimental measurements of ascending aortic pressure and of ascending and descending aortic flows taken from dogs and ferrets. Our aim was to provide quantitative evaluation of the aortic pressure and flow pulse wave components as they relate to the distribution of arterial properties and relate to wave travel and reflection in mammalians of consistently different size and shape. Estimated effective lengths (distances to effective reflection sites) of the head-end ( d h) and body-end ( d b) transmission paths were ∼12 and 30 cm, respectively, in the dog and 6.5 and 13 cm, respectively, in the ferret. These lengths and distributions of estimated arterial properties were consistent with the difference in the body size and with the more central location of the heart in the ferret's body than it is in the dog's body. In both animal species the ascending aortic pressure and flow waves could be interpreted in terms of forward and reflected components arising from the two distinct effective reflection sites, although the higher d h/ d b ratio in the ferret determined the presence of one broad, indistinct minimum in the modulus of ascending aortic impedance in the frequency range from 0 to 10 Hz, rather than two distinct minima as observed in the dog.
Effects of single- and biventricular pacing on temporal and spatial dynamics of ventricular contraction
Authors: Wyman Bradley T. , Hunter William C. , Prinzen Frits W. , Faris Owen P. , McVeigh Elliot R.
Published: December 2017

Resynchronization is frequently used for the treatment of heart failure, but the mechanism for improvement is not entirely clear. In the present study, the temporal synchrony and spatiotemporal distribution of left ventricular (LV) contraction was investigated in eight dogs during right atrial (RA), right ventricular apex (RVa), and biventricular (BiV) pacing using tagged magnetic resonance imaging. Mechanical activation (MA; the onset of circumferential shortening) was calculated from the images throughout the left ventricle for each pacing protocol. MA width (time for 20–90% of the left ventricle to contract) was significantly shorter during RA (43.6 ± 17.1 ms) than BiV and RVa pacing (67.4 ± 15.2 and 77.6 ± 16.4 ms, respectively). The activation delay vector (net delay in MA from one side of the left ventricle to the other) was significantly shorter during RA (18.9 ± 8.1 ms) and BiV (34.2 ± 18.3 ms) than during RVa (73.8 ± 16.3 ms) pacing. Rate of LV pressure increase was significantly lower during RVa than RA pacing (1,070 ± 370 vs. 1,560 ± 300 mmHg/s) with intermediate values for BiV pacing (1,310 ± 220 mmHg/s). BiV pacing has a greater impact on correcting the spatial distribution of LV contraction than on improving the temporal synchronization of contraction. Spatiotemporal distribution of contraction may be an important determinant of ventricular function.
Dissociation of contraction and potassium efflux in smooth muscle
Authors: Hurwitz Leon , Tinsley Betty , Battle Frank
Published: December 2017

Normally, a pilocarpine induced contraction of the isolated guinea pig ileum is associated with a change in potassium transport across cell membranes. Bathing the tissue in a Ca-free medium will effect a dissociation between the contractile response and the potassium efflux. The replacement of Tyrode's solution by a Ca-free medium elicits a slight increase in smooth muscle tone followed by a return to a state of relaxation. Within an hour the contractile response to pilocarpine becomes negligible. This lack of response to pilocarpine applies to circular as well as longitudinal smooth muscle. In contrast to the changes which occur in muscle tone the efflux of potassium, following withdrawal of Ca ion, undergoes a sudden rise and remains above normal. The administration of pilocarpine, after the tissue has been bathed in the Ca-free medium for 1 or 2 hours, will still evoke a moderate additional increase in potassium efflux. Replacement of Ca ion with an equimolar quantity of Mg ion causes the contractile response to pilocarpine to disappear sooner than it would have in a simple calcium-free medium. Here, too, the potassium efflux of the tissue rises and after 1 hour responds to pilocarpine with a further increase. Thus, pilocarpine can modify potassium transport in the isolated ileum regardless of its effect on smooth muscle tone.
Purine derivatives in lymph from the thoracic duct of the rat
Authors: Dietrich L. S. , Siegel George J.
Published: December 2017

Adenine, guanine, cytosine, uracil and uric acid were found in measurable amounts in rat lymph. No detectable quantities of nucleosides were observed. The quantity of acid soluble nucleosides found was equivalent to that which would be expected from the lymphocytes present in the lymph samples analyzed. Lymph collected for a 45-hour period following the injection of 7.5 µc of glycine-2-C14 contained no significant amount of labeled purine derivatives. At the end of this period, liver tissue, however, still contained appreciable quantities of labeled acid-soluble nucleotides. Lymph collected for a similar period of time after the injection of 4.6 µc of nicotinamide-7-C14 contained very small amounts of radioactivity.
Comparison of magnesium and potassium efflux from incubated rat diaphragms
Authors: May George , Barnes Benjamin A.
Published: December 2017

Intracellular magnesium has been shown to be less available for prompt isotopic exchange than intracellular potassium in the intact mammal. Therefore, an experiment was completed to establish if magnesium would leave a tissue as readily as potassium under conditions known to cause a loss of the latter ion. Rat diaphragms were incubated at 37° and 3°C. After a 4-hour incubation at 3° it was observed that the potassium loss was greater than 50% of the initial tissue concentration, and the loss of magnesium was less than 20% of the initial concentration. These studies indicate that intracellular magnesium is restricted in a way different from that of potassium. The muscle loss of potassium and retention of magnesium at 3°, when metabolic processes were greatly reduced, are consistent with the concept of greater lability of intracellular potassium as revealed by isotope studies and with the concept of the dependence of intracellular potassium concentrations on metabolic activity in distinct contrast to intracellular magnesium.
Contractility of muscle in solutions of low electrolyte concentration
Authors: Bozler Emil
Published: December 2017

Spontaneous activity of the frog's stomach muscle ceased after immersion in isosmotic sucrose solution, but was restored after the addition of a small amount of CaCl2. Similarly, the sartorius which had become nonexcitable in sucrose solution gave nonconducted responses on electric stimulation after the addition of about 1 mM CaCl2. As an explanation of excitatory phenomena in nearly electrolyte free solutions it is suggested that the responses are due to activation of an intracellular conduction mechanism.
Relation of pancreatic exocrine to nutrition of the rat
Authors: Uram J. A. , Friedman Leo , Kline O. L.
Published: December 2017

Pancreatectomy in the rat, sufficient to induce severe diabetes, is without practical effect on the absorption of the nutrients of purified diets. Attempts to reduce the contribution of small residual fragments of pancreas revealed that the rat is capable of normal or near normal digestion with less than 1% of the contribution of its exocrine pancreas. The ability of the duct-ligated rat to re-establish exocrine flow was demonstrated, and a procedure was developed to circumvent this adaptation. This produced rats with highly variable abilities to absorb nutrients. The intestine is implicated as a major factor determining the ability of an animal to absorb nutrients in the absence of pancreatic exocrine secretions.
Effect of cortisone on protein loss and carbohydrate gain in normal and simulated altitude-exposed mice
Authors: Berry L. Joe , Smythe Dorothy S.
Published: December 2017

Protein catabolism and carbohydrate spared or synthesized following injection of 5 mg cortisone in fasted normal mice were equal, but in fasted, altitude-exposed mice (simulated 20,000 ft. continuously for 3–5 wk.) there was less carbohydrate increase than protein decrease. In fed mice of both groups a balance between protein loss and carbohydrate increase was observed after cortisone, but the absolute quantities involved were less in altitude-exposed animals. Fasted altitude-exposed mice excreted more urinary nitrogen than controls. However, administration of bacterial endotoxin to the hypoxic group decreased the urinary nitrogen to normal levels. ACTH failed to increase urinary nitrogen under these conditions in both groups. Altitude-exposed mice were also significantly more susceptible to endotoxin than normal mice. Both glutamic-oxaloacetic and glutamic-pyruvic transaminases were lower in the livers of altitude-exposed mice than in normal animals. These enzymes were also lower 4 weeks after adrenalectomy and 17 hours after the injection of 5 mg cortisone.
Histamine and anaphylaxis on adrenal medullary secretion in dogs
Authors: Robinson Robert L. , Jochim Kenneth E.
Published: December 2017

The adrenal medullary secretion of catecholamines was followed for a variable period of time in dogs after the intravenous injection of histamine or the production of anaphylaxis. The adrenal vein was cannulated and the adrenal blood, which was collected at intervals, was assayed for catecholamines by the method of von Euler and Floding. The course of the adrenal medullary secretion, after the injection of histamine, was also studied in a series of cross circulation experiments. The results indicate that histamine and anaphylaxis increased the output of epinephrine and norepinephrine 4–60 times the control output. The maximum output was always found in the first adrenal blood sample collected after histamine injection or production of anaphylaxis. The period of augmented secretion lasted 15 minutes or longer depending on the dose of histamine or the severity of the anaphylactic response. The return of the catecholamine output to control levels closely paralleled the recovery of the mean arterial blood pressure. The quantity of the catecholamines released could be expected to produce marked physiological effects.
Interaction of adrenals and thyroid in maintenance of body temperature of rats exposed to cold
Authors: Fregly Melvin J.
Published: December 2017

The effects of cortisone acetate and thyroxine, administered separately or in combination, on colonic cooling rate (CCR) have been studied in restrained, adrenalectomized rats subjected to air at 5°C. Thyroxine alone at 5.0 µg/day reduced the rapid CCR of adrenalectomized rats but failed to return it to that of sham-operated rats. Cortisone acetate alone at 1.0 mg/day reduced CCR but also failed to restore it to normal. A higher dose (2.0 mg/day) was even less effective. Administration of 5.0 µg/day thyroxine simultaneously with 2.0–2.5 mg cortisone acetate returned CCR to that of sham-operated rats. Simultaneous administration of cortisone acetate with graded doses of thyroid stimulating hormone (TSH) to adrenalectomized rats resulted in greater reduction of CCR than with either treatment alone. Cortisone acetate did not appear to interfere either with tissue utilization of thyroxine or with thyroid gland response to TSH administration. The cooling test has also proved a useful tool for comparing potencies of a synthetic (dexamethasone) and a naturally occurring steroid (progesterone) with that of cortisone acetate. Dexamethasone is estimated to have a potency 700 times that of cortisone acetate, while progesterone is only one-third as potent.
Survival time of hypothermic white rats (15°C) and ground squirrels (10°C)
Authors: Popovic V.
Published: December 2017

The survival times of intensively cooled white rats decrease with their body temperatures. When cooled by Giaja's technique and maintained afterwards at a body temperature of 15°C rats survived 9 hours, but they could be revived by rewarming only during the first 5.5 hours of survival (biological survival). Similar biological survival times were found when the rats were cooled by other techniques, whether the cooling was much quicker or much slower. The survival time was also independent of the rate of rewarming from hypothermia. Survival was shortened by cooling after administration of sodium pentobarbital. Biological survival of young 40-gm rats at 15°C body temperature was 19 hours, 14 hours longer than that of hypothermic adults. Level of O2 consumption of hypothermic young rats differed from those of hypothermic adult animals.
Plasmin-antiplasmin complex as a reservoir of fibrinolytic enzyme
Authors: Ambrus Clara M. , Markus Gabor
Published: December 2017

When streptokinase-activated, urokinase-activated, or spontaneously activated human plasmin is mixed with increasing amounts of human antiplasmin, caseinolytic effect decreases much more rapidly than fibrinolytic effect. At concentrations of antiplasmin at which caseinolytic effect completely disappears, considerable fibrinolytic activity persists. Authors suggest that fibrin can compete for plasmin with antiplasmin while other proteins may be less effective in this respect. This may explain the specificity of plasmin for fibrin in vivo, in the presence of the inhibitor. Antiplasmin may play an important physiological role in protecting normal plasma proteins while allowing lysis of fibrin clots by plasmin.
Effect of perfusion of liver on properdin titers in dogs subjected to hemorrhagic shock
Authors: Blattberg Benjamin , Maldonado Carlos , Levy Matthew N.
Published: December 2017

Previously it was demonstrated that plasma properdin levels decline in dogs as a result of hemorrhagic shock. The possibility that the liver may be a source of properdin and also a site for detoxification of the endotoxins formed during oligemia suggested that perfusion of the liver might prevent this fall in properdin titer. Seventeen dogs, in which the liver was autoperfused by way of the splenic vein, were bled to 35 mm Hg arterial pressure and maintained at this level until they took back 40% of their maximum bled volume, or were in oligemia for 4–5 hours. Liver perfusion failed to prevent the decline in properdin titer; in fact, there was a significantly greater ( P = 0.04) fall in the liver-perfused group than in the control animals. Furthermore, there were no significant differences in survival time or duration of oligemia.
Composition of beagle dog milk
Authors: Luick Jack R. , Parker Harold R. , Andersen A. C.
Published: December 2017

A statistical study has been made of the composition of the major C-containing compounds taken from beagle dog milk during the 3rd through 5th week of lactation. The mean values are as follows: 26% total solids, 13% fat, 3.3% lactose and 9.8% protein. Total solid content was found to vary with fat content according to the equation: % total solids = 15.6 + 0.85 % fat.
Relationship between cardiac toxicity of K and acute alterations of blood pH and pCO2
Authors: Young Daniel T. , Monroe Edwin W. , Craige Ernest
Published: December 2017

Dog heart-lung preparations were studied to determine the relationship between the toxicity of elevated potassium and the blood pH and pCO2. During hyperkalemia, a) a change from hypercapneic acidosis to hypocapneic alkalosis produced electrocardiographic deterioration after a delay of 3–5 minutes; cardiac function improved during alkalosis until ECG deterioration occurred; b) increase of pH produced by hypertonic bicarbonate infusion during hypercapnia improved mechanical performance; ECG also improved, even when pCO2 was later decreased; c) infusion of hypertonic NaCl during hypercapnia partially prevented ECG deterioration after reduction of pCO2. These experiments indicate that potassium toxicity is aggravated by acute reduction of pCO2. This may not be due solely to the change in pH, since similar pH increase from bicarbonate infusion did not make the ECG worse. Reduction of [Ca++] by pH increase is not the cause of ECG deterioration; if it were, ECG should be more affected in bicarbonate and NaCl infusion experiments than in the others. The cause of ECG deterioration with reduction of pCO2 remains unknown.
Thyroid influence in reactions to O2 at atmospheric pressure
Authors: Smith Charles W. , Bean John W. , Bauer Robert
Published: December 2017

Experiments were carried out to determined what effect increased thyroid might have on the reactions induced in normal and hypophysectomized rats by continuous exposure to O2 at atmospheric pressure (OAP). Feeding desiccated thyroid or injecting thyroxine increased the noxious effects of OAP. The data support the interpretation a) that the development of hypercapnemia and hypooxemia secondarily to the initial pulmonary damage (probably induced by O2, per se, or in combination with small amounts of CO2) is rapidly increased by thyroid; b) that this further aggravates the initial pulmonary damage by direct action on the pulmonary vasculature and indirectly by central stimulation of the sympatho-adrenomedullary and hypophyseal-adrenocortical axes with a resultant release of adverse neurogenic and hormonal influence on the lungs. Other important thyroid effects which may augment the toxicity of OAP are discussed as is their possible involvement in the experimental production of hyaline membrane disease and retrolental fibroplasia. The data provide supporting evidence that the protection which hypophysectomy affords against O2 toxicity is due in part to the attendant elimination of thyrotropin and the resultant reduction of thyroid secretion.
Pre- and postglomerular resistance changes in the isolated perfused kidney
Authors: Hinshaw Lerner B. , Flaig Robert D. , Carlson Curtis H. , Thuong Nguyen K.
Published: December 2017

The objective of the present study was to evaluate the relative roles of pre- and postglomerular vascular resistance changes in the autoregulation phenomenon. Experiments were performed on isolated dog kidneys perfused during ureteral occlusion. Ureteral pressures were assumed to approximate Bowman capsule extravascular pressure. As renal artery pressure was progressively elevated through the autoregulatory range, ureteral, intrarenal venous, and tissue pressures were measured; glomerular and peritubular capillary pressures were estimated, and pre- and postglomerular resistances were calculated. Results indicate that autoregulation of renal blood flow is brought about by the combined effects of increased tissue pressure and Bowman capsule extravascular pressure. Progressive increases in postglomerular resistance are responsible for the rise in ‘over-all’ renal resistance. Data provide evidence for the absence of the ‘myogenic reflex’ as a causal factor in autoregulation. Results are in agreement with previous reports of Winton and Gómez regarding glomerular pressure estimations and renal segmental resistance calculations.
Active transport of Diodrast and phenolsulfonphthalein from cerebrospinal fluid to blood
Authors: Pappenheimer J. R. , Heisey S. R. , Jordan E. F.
Published: December 2017

Cannulas were implanted in the lateral ventricles, cisterna magna and subarachnoid spaces of goats. Perfusion with synthetic cerebrospinal fluid (CSF) permitted study of exchange rates of test materials between CSF perfusion fluid and blood. Diodrast or phenolsulfonphthalein in low concentrations is removed from ventriculocisternal perfusate by a process of active transport resembling secretion by the proximal tubules of the kidney. The transfer maximum is 2–3 µg/min. and is reached at an inflow concentration of about 20 µg/ml. Active transport occurs from a volume of about 2 ml (total CSF volume is c 20 ml) located in the region of the 4th ventricle and cisterna magna. The choroid plexus of the 4th ventricle could be the site of active transport. After inhibition of active Diodrast transport, a passive component of transfer is revealed. Comparative studies with creatinine, fructose and inulin show that passive transfer takes place by diffusion as well as by absorption in bulk. Rates of passive transfer of these substances (per unit concentration difference) are comparable in magnitude with diffusion rates from the capillaries in 1 gm of skeletal muscle.
Transmembrane fluxes in ventricular fibrillation
Authors: Briggs Arthur H. , Holland William C.
Published: December 2017

Transmembrane fluxes of K and the rate of net entry of Na were determined in isolated perfused rabbit hearts before and during ventricular fibrillation. These results were compared to previous flux measurements in atrial fibrillation. Control ventricles in low (K)0 media lost K at a rate of 8 pmoles cm–2sec–1. This was 2 1/2 times greater than the rate of K loss in control atria. The initiation of both atrial and ventricular fibrillation was associated with an increased K efflux, decreased K influx and marked increase of Na influx. The data were interpreted to suggest that both atrial and ventricular fibrillation are initiated by the same basic mechanism; that is an increase in Na entry above a critical value (K leaving the tissue in exchange). This critical value can be easily attained in perfused ventricles by lowering the (K)0.
Mechanism of action of angiotensin and bradykinin on smooth muscle in situ
Authors: Khairallah Philip A. , Page Irvine H.
Published: December 2017

Atropine inhibited the contractile response of isolated guinea pig ileum to angiotensin by 60–70%. This inhibition could be reversed with neostigmine. Morphine, which is known to prevent the release of acetylcholine from the nerve endings, also inhibited the response to angiotensin. The response to bradykinin under the same circumstances was not altered, nor was the response of the uterus to angiotensin and bradykinin. Except for tetraethylammonium chloride (TEAC), the quaternary nitrogen blocking agents had no effect on the ileal response to angiotensin. TEAC potentiated the response of the ileum to both angiotensin and bradykinin, even after the administration of atropine. Depolarizing doses of nicotine and tetramethylammonium chloride inhibited the response of the ileum to angiotensin without altering the response to bradykinin. Results thus suggest that angiotensin acted both by stimulating ganglion cells and smooth muscle. In the intestines, the ganglion stimulating effect was preponderant. Bradykinin, on the other hand, acted on smooth muscle cells only. TEAC potentiation of the response to the polypeptides was by direct action on the smooth muscle independent of its ganglion blocking effect.
Reserpine action on the central nervous system of the cat
Authors: Hamel E. G. , Kaelber W. W.
Published: December 2017

Recordings of spontaneous activity and induced arousal in cats with permanently implanted electrodes have failed to demonstrate any effect by reserpine on arousal pathways. Recordings of spontaneous and induced activity of the rhinencephalon have indicated that this region is not involved in any specific fashion by reserpine. Evidence is presented that the miotic effect of reserpine requires the integrity of most of diencephalon but that the effect may be produced with the central sympathetic connections interrupted.
Ventricular activation process and genesis of QRS complex in the goat
Authors: Hamlin Robert L. , Scher Allen M.
Published: December 2017

The pathways of ventricular excitation in the interventricular septum and the free walls of the ventricles were determined in the goat. During the first 5 msec. of the QRS complex, activity occurs in a cup-shaped zone formed around the apex of the left ventricular cavity, consisting of the left endocardial portions of the septum and the endocardium of the free wall. Within the next 10 msec. of the QRS, the apical third of the septum is excited, simultaneously, from both the left and the right ventricular endocardial surfaces. Also, all of the ventricles, except the bases and a small epicardial apical area of the left ventricle, are excited with almost a single burst of depolarization. During the next 3–5 msec. the ventricular bases and the small apical epicardial area are excited along with the middle third of the interventricular septum. The final 15 msec. of the QRS and approximately 3 msec. of the following isoelectric period are inscribed during activation of the basilar third of the septum.
Relations between coronary flow and work of the heart
Authors: Rosenblueth A. , Alanís J. , Rubio R. , Pilar G.
Published: December 2017

The mean total coronary flow of dog hearts, perfused via the aorta by a donor dog, was recorded. The amount of work performed by the recipient heart was varied within wide ranges. Its aortic pressure was also varied, thus determining changes in the coronary flow. When the frequency of stimulation of the heart and the aortic pressure are maintained constant, changes of the work performed do not result in changes of the coronary flow. When the working conditions of the heart are maintained constant, changes of the coronary flow do not cause any variations of the amount of work performed. The work performed does not affect the pressure-flow relationships. It is concluded that with adequate circulation there is a wide margin of safety in the oxygen supply to the ventricle. The heart can increase its work importantly without producing or requiring an increase of its coronary flow.
Effect of substituted phenols on movement of water and protein across the intestine
Authors: Tidball C. S.
Published: December 2017

The action of three substituted phenols on intestinal net water movement in jejunal loops in situ has been studied in the anesthetized dog. The ability of these compounds to influence intestinal net water movement paralleled their previously reported ability to stimulate oxygen uptake and to produce cessation of cleavage in fertilized sea urchin eggs which are thought to be manifestation of their property to uncouple oxidative phosphorylation. Thus two effective uncouplers produced decreases in net absorption at a concentration of 1 x 10–3 m/l. and net secretion at a concentration of 1 x 10–2 m/l. A less effective uncoupler produced no change in water movement at a concentration of 1 x 10–3 m/l. and only a decrease in net absorption at a concentration of 1 x 10–2 m/l. The substituted phenols produced increases in the amount of protein which could be recovered from the lumen, but the changes in water movement produced by substituted phenols were independent of the mechanism responsible for the protein release.
Physiological factors influencing radiorubidium flux across isolated rabbit mesentery
Authors: Berndt W. O. , Gosselin R. E.
Published: December 2017

A technique is described for measuring in vitro the permeability of rabbit mesentery to Rb86 ion. Equations for passive diffusion are adequate to describe the rubidium flux through this membrane, but unlike passage through collodion, transport through mesentery exhibits a high temperature coefficient. Mesentery reacts in ways that are analogous in some respects to the behavior of intact capillaries. For example, the permeability is increased by lowering the extracellular calcium ion concentration or the pH. Hydroxytryptamine (5-HT) also elevates the Rb86 flux, an effect that can be reversed by salicylate but not by lysergic acid diethylamide (LSD). The nature of the transport process is discussed, and it is suggested that isolated mesentery may serve as a useful model for predicting chemical effects on capillary permeability.
Comparative behavior of strontium-calcium and cesium-potassium in the fowl
Authors: Monroe R. A. , Wasserman R. H. , Comar C. L.
Published: December 2017

Under normal dietary conditions, but with varying levels of calcium, radiocalcium was preferentially used over radiostrontium as shown by double tracer studies with growing cockerels (ORbone-diet = 0.6). With laying hens the bone, egg shell and egg yolk showed the expected OR value of 0.5–0.6; the plasma and egg white, however, showed OR values greater than 1, about 1.5. Studies with Cs137 and K42 indicated a nonuniformity of accumulation among tissues. The high Cs*/K* ratios in kidney appeared to result from a comparatively lowered capacity for potassium accumulation.
Hypertensive vascular disease in DCA-treated rats given Na or Li supplement
Authors: Hall C. E. , Ware R. W. , Cross E. , Hall O.
Published: December 2017

The effect of desoxycorticosterone treatment was assessed in uninephrectomized animals drinking NaCl, LiCl or distilled water. Those drinking NaCl solution developed polydipsia, polyuria and hypertensive cardiovascular disease. Animals on LiCl which grew well developed equally severe hypertensive vascular disease but neither polydipsia nor polyuria, whereas those in which growth was inhibited remained normotensive. The same dosage of DCA produced severe hypertensive vascular disease even in rats drinking only distilled water. It appears that at high dosage of steroid the dietary sodium is sufficient to sensitize the vascular system to hormonal effects. The addition of further Na to the diet does not appreciably worsen the hypertension, but does cause a high mortality. The addition of lithium to drinking fluid markedly reduces fluid consumption and leads to impaired growth in some animals, but exerts no antihypertensive effects in animals which grow well. Various aspects of the response are discussed.
Contractile activities of mammalian smooth muscles in chloride-deficient media
Authors: Kao C. Y. , Gluck S.
Published: December 2017

When the chloride ion of the medium around uterine or intestinal smooth muscles was replaced by nitrate, bromide, iodide or thiocyanate, the phasic contractions were potentiated, and marked tonic contractions were induced. The changes in the phasic contractions resembled those in skeletal muscle in having stronger and longer-lasting ‘twitch’ contractions, in exhibiting some dependence of these changes on the concentration of the substituting anions, and in having some changes in electrical excitability. The tonic contractions were accompanied by markedly increased spike discharges, which occurred with a slight increase rather than a decrease of the resting potential. Tonic contraction could be elicited in sodium-free medium by using sucrose or by using sequentially choline chloride and choline nitrate as substitutes. Distinct roles of sodium and chloride in the contractile activities were recognizable upon resupplying these two ions separately to preparations deprived of both. It was concluded that presence of external sodium was necessary for phasic contractions, and presence of external chloride necessary for relaxation from tonic contractions.
Erythrocyte life span in normal mice and in radiation bone marrow chimeras
Authors: Goodman Joan Wright , Smith L. H.
Published: December 2017

Average potential erythrocyte life spans measured by disappearance rates of transfused, isologous Cr51-labeled cells in mice of several inbred strains and F1 hybrids varied from 50 to 55 days and the Cr51 half time from 15 to 20 days. Sprague-Dawley rats had a potential red cell life span of 60 days and an apparent half time of 19 days. Normal life spans for isologous and homologous erythrocytes were measured both early and late after irradiation in isologous bone marrow chimeras. Homologous chimeras, early after irradiation and bone marrow transplantation, exhibited severe anemia and rapid rate of depletion of host-type erythrocytes. In contrast, after 2 or more months of chimerism, life spans of both host- and donor-type erythrocytes were normal. Mice with rat marrow transplants functional for at least 2 months never cleared rat red cells rapidly. Sudden and very rapid disappearance of mouse erythrocytes was seen from many, but not all, such chimeras. Erythrocytes from normal rats were depleted more rapidly in chimeras than in normal rats, the potential life span being shortened by about 10 days. Mouse-grown (chimeric) rat erythrocytes were depleted in heterologous chimeras at a rate identical to that of chimeric cells in normal rats and of normal rat cells in chimeras.
Effects of certain steroids on bioelectric current of isolated frog skin
Authors: McAfee Robert D. , Locke William
Published: December 2017

2-methyl-9 α-fluorohydrocortisone and hydrocortisone sodium succinate increase both the rate and duration and, therefore, total quantity of ion transported in the isolated short-circuited frog skin measured over a 24-hour period. The ion transport is directly related to the bioelectric current generated, and based on Ussing's work, is assumed identical to the net flux of sodium ion. These steroids may make available transport energy that is not available to the untreated half of the skin by rerouting enzymatic pathways or by lowering the resistance of the membrane to ion transport and thereby more efficiently utilizing the energy available for transport.
Differences in thyroidal iodine concentration and T/S ratio among strains of mice and rats
Authors: Silverstein E. , Bates R. W.
Published: December 2017

The weight, stable iodine concentration and thyroid-to-serum (T/S) ratio of the thyroid gland was measured in 12 strains of mice and 4 strains of rats. Strain differences of as much as twofold in thyroidal iodine concentration usually increased with age. Mean thyroidal iodine concentration tended to vary inversely with T/S ratio in mice and directly in rats, but no intrastrain correlation was apparent, nor was there a consistent sex difference. The thyroidal iodine concentration was not consistently related to T/S among the strains of mice or rats on stock diet. Therefore, iodine concentration in the thyroid and genetic constitution are only two of many factors responsible for the level of the T/S ratio.
Renal failure in the alligator
Authors: Coulson Roland A. , Hernandez Thomas
Published: December 2017

Intraperitoneal injection of d-serine into alligators produced renal failure characterized by decreased NH4HCO3 excretion, increased NaCl and NaHCO3 excretion, decreased uric acid clearance, and acidemia. Oliguria or anuria was common in the early stages. Blood uric acid levels as high as 70 mg% were observed. In some respects the loss in renal tubular function resembled that found in alligators kept in the cold. Alligators severely dehydrated or injected with theophylline or insulin also excreted a urine deficient in NH4HCO3 and rich in NaCl. The injection of glycine, a good ammonia precursor, reversed the picture in these alligators but not in those damaged by d-serine. It was concluded that in severe renal damage NH4HCO3 cannot be synthesized, regardless of the amino acid level of the blood, and that salt and base are lost as a consequence. The loss of extracellular salts due to failure of the ammonia mechanism is the most prominent feature in renal failure in the alligator.
Calcium and metabolism of I131 in rats and homogenates of rat thyroid
Authors: Gandra Yaro Ribeiro , Coniglio John G.
Published: December 2017

The goitrogenic effect of calcium was studied by the use of I131 in intact rats and in rat thyroid slices. Rats receiving excess dietary calcium had larger thyroids than controls. Enlargement of the thyroid was accompanied by increased content of inorganic iodine and decreased content of organic iodine. In vitro studies showed that thyroid enlargement was associated with greater total iodine uptake. Addition of calcium to the incubation medium decreased the total iodine uptake of thyroid slices. The reduction occurred as a consequence of interference with the conversion of inorganic iodine to organic iodine. No decrease in inorganic iodine content was observed. The ratios of bound iodine to free iodine were constantly smaller in the thyroid groups receiving calcium supplement. The results of the in vitro studies suggest that calcium interference is due, at least in part, to a direct effect on thyroid tissue.
Morphine inhibition of plasma corticosteroid levels in chronic venous-catheterized rats
Authors: Slusher Margaret A. , Browning Barbara
Published: December 2017

Unanesthetized rats with chronic venous catheters show a diurnal increase in plasma corticosteroid levels at 5 pm over those noted at 9 and 10 am and 3 pm. At 10 am, 1 hour after the injection of morphine via the catheter, a 390% increase in plasma corticosteroid levels was noted. Eight hours after injection of morphine these levels were depressed 51% when compared with saline-injected controls. Results indicate morphine initially elicits a hypersecretion of ACTH by direct activation of the pituitary-adrenal axis and not via sensory stimulation accompanying the stress of intravenous injection of the drug. A secondary effect of morphine, inhibitory in action, appears exerted on neurogenic factors regulating diurnal variation in plasma corticosteroid levels.
Recovery after anaphylaxis of isolated guinea pig ileum segments
Authors: Greisman Sheldon E.
Published: December 2017

Following anaphylactic contraction of actively sensitized, isolated guinea pig ileum segments in a continuously aerated system, spontaneous relaxation ensues. Interruption of aeration during anaphylactic contraction consistently inhibited the relaxation phase. If aeration was resumed, relaxation promptly ensued. Such relaxation was not an all-or-none reaction, but could be made to occur in stepwise fashion by intermittent interruption of aeration. These effects of interruption of aeration on muscle tone during anaphylaxis appeared specific, since opposite tone changes were observed during contractions induced with exogenous histamine. Studies with Tyrode's solution, pretreated with 100% O2 or with 98.5% O2–1.5% CO2, suggested that the mechanism of action of aeration was, in part at least, mediated by an oxygen-dependent process and implicated the active participation of intracellular histamine-inactivating systems. Although postanaphylactic ileum relaxation was also accelerated in Tyrode's solution pretreated with 100% N2, this effect differed in important details from accelerated relaxation in oxygenated systems and appeared to depend upon impaired ability of the contractile system to respond to released histamine.
Biliary excretion of injected conjugated and unconjugated bilirubin by normal and Gunn rats
Authors: Arias Irwin M. , Johnson Lois , Wolfson Sonia
Published: December 2017

Conjugated and unconjugated bilirubin were injected intravenously at different times into normal rats and homozygous, jaundiced Gunn rats. As was expected, Gunn rats did not excrete injected unconjugated bilirubin in the bile. After the intravenous injection of conjugated bilirubin into normal rats, approximately twice as much bilirubin appeared in the bile per 100 g of body wt within 10 min than after the injection of comparable amounts of unconjugated bilirubin. This difference probably reflects the time required for cellular uptake and conjugation of bilirubin prior to excretion. The maximal biliary bilirubin excretory rate in Gunn rats following the administration of conjugated bilirubin was 56±8.4 (S.D.) µg of bilirubin excreted/100 g body wt/min. This does not differ significantly from the maximal biliary bilirubin excretory rate observed in normal rats after infusions of either conjugated or unconjugated bilirubin. This demonstrates that conjugation alone does not limit metabolism of bilirubin by normal rat liver. These studies, when considered in the light of other investigations, suggest that the ability to excrete conjugated bilirubin is the limiting factor in metabolism of bilirubin by normal rat liver.
Effects of intracranial stimulation on denervated nictitating membrane of the cat
Authors: Rothballer Alan B. , Sharpless Seth K.
Published: December 2017

The effect of intracranial stimulation on the chronically denervated nictitating membrane of the encéphale isolé cat has been studied. After eliminating sympathoadrenal discharge, we found that the nictitating membrane responds to direct stimulation of the brain stem and certain cranial nerves through: 1) an intrinsic sensitivity to direct mechanical stimulation which develops in the smooth-muscle fibers of the nictitating membrane after chronic denervation; 2) an effect by way of the greater superficial petrosal nerve, producing retraction of the nictitating membrane from diffusion of acetylcholine onto the sensitized smooth muscle from secretomotor fibers innervating nearby orbital glands; and 3) finally, after exclusion of cranial nerve effects, one can still, under optimal conditions, obtain retraction of the nictitating membrane after stimulation of the reticular formation, an effect that is tentatively ascribed to the release of a humoral factor from some intracranial source. The bearing of these findings on previous work in which the nictitating membrane has been used as an indicator of circulating neurohumors is discussed.
Anodal block of conduction in the optic tract
Authors: Vastola E. F.
Published: December 2017

Anodal polarization of optic tract fibers just behind the chiasm has been found to produce reversible block of conduction in first and second tract fibers within a sufficiently restricted distance from the tip of the polarizing electrode to suggest that this procedure may be applicable to studies of the function of pathways in the central nervous system. Rushton's expression for the steady current flow across the sheath of an insulated conductor indicates that threshold should vary inversely as the square root of fiber diameter. This expression gives a ratio of 1.4:1 for the threshold current for block in second tract fibers relative to the threshold current for first tract fibers, and our observed ratio of 1:1 was not believed to be significantly different from the theoretical value. The predicted increase in threshold of fibers less than 2.5 µ in diameter was confirmed by our finding that the first and second tract spikes could be depressed by anodal current that did not alter the later third and fourth tract spikes.
Effect of hyperoxia, hypercapnia, and hypoxia on blood-cerebrospinal fluid barrier
Authors: Lending Miriam , Slobody Lawrence B. , Mestern Joan
Published: December 2017

The effect was evaluated in puppies and adult dogs by measuring the rate of passage of radioactive iodinated human serum albumin from plasma into the cerebrospinal fluid and by determining the plasma and cerebrospinal fluid glutamic oxalacetic transaminase and lactic dehydrogenase activities. Arterial O2 concentration and saturation, CO2, and pH determinations were obtained. In puppies, hypercapnia was associated with marked respiratory acidosis and produced a great increase in the rate of transfer of albumin I131 from plasma to cerebrospinal fluid. Prolonged hypoxia also produced a definite increase in permeability of the blood-cerebrospinal fluid barrier. Increased concentration ratios of cerebrospinal fluid enzyme activity/plasma enzyme activity were observed in both groups. Hypoxia alone did not cause significant changes. In adult dogs, hypercapnia or hypoxia did not result in comparable findings.