bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal oxygen uptake, oxygenation, and acid-base balance as a function of uterine blood flow
Authors: Wilkening R. B. , Meschia G.
Published: December 2017

The rate of O2 delivery to the pregnant uterus (FaO2) was decreased in chronic sheep preparations by mechanical occlusion of uterine blood flow. The relationship of uterine venous O2 saturation (SVO2) to FaO2 was curvilinear with convexity toward the SVO2 axis. As SVO2 decreased, there was a decrease in uterine and umbilical venous O2 tension (PO2), with no appreciable reduction of the PO2 difference between the two veins and a decrease in the umbilical vein O2 delivery rate. Fetal O2 uptake and base excess remained normal as the umbilical vein O2 delivery rate was reduced from 1.1 to 0.6 mmol . min-1 . kg-1 but decreased markedly at an O2 delivery rate less than 0.5. Umbilical venous CO2 tension (PCO2) was higher than, and strongly correlated with, uterine venous PCO2 (R = 0.954). These observations support a venous equilibration model of ovine placental exchange and demonstrate that under normal physiological conditions the O2 supply to the fetal lamb is approximately twice the value necessary to maintain an adequate fetal O2 uptake and a normal fetal base excess.
A nonsurgical canine model of chronic left ventricular myocardial dysfunction
Authors: Carlyle P. F. , Cohn J. N.
Published: December 2017

A simple technique of producing left ventricular myocardial damage accompanied by chronic complete heart block in dogs is described. The method is accomplished by repetitive transmyocardial DC shock with a guide wire introduced percutaneously and positioned in the left ventricle along the intraventricular septum and an external paddle at the left ventricular apex. Twelve weeks after the procedure significant hemodynamic changes included a fall in heart rate from a control of 76 +/- 19 (SD) to 43 +/- 9 beats/min (P less than 0.001), a rise in left ventricular filling pressure from 9 +/- 4 to 28 +/- 10 mmHg (P less than 0.001), and a fall in cardiac output from 3.1 +/- 1 to 2.3 +/- 0.6 l/min (P less than 0.05). Weekly echocardiography revealed a progressive increase in left ventricular end-diastolic diameter from 3.56 +/- 0.72 to 4.84 +/- 0.47 cm (P less than 0.01). Survival rate was 70%. Therefore, this relatively noninvasive technique is an effective means of producing chronic left ventricular myocardial dysfunction in the dog.
Different cardiac and renal inhibitory and excitatory areas in rabbit hypothalamus
Authors: Okada Y. , Ninomiya I.
Published: December 2017

The hypothalamic area was stimulated in anesthetized rabbits at a large number of selected points, and the effects on the simultaneously recorded right cardiac sympathetic nerve activity (CSNA) and renal nerve activity (RNA) were analyzed quantitatively. Four characteristic patterns of CSNA and RNA responses could be observed. The most striking finding was the presence of opposite responses of CSNA and RNA at many hypothalamic stimulus points, in addition to the conventionally observed CSNA and RNA responses in the same direction. By a new method, we drew hypothalamic maps for CSNA and RNA response magnitudes. These maps show that the excitatory areas of CSNA and RNA are surrounded by respective inhibitory areas. Although the excitatory areas of CSNA and RNA correspond with each other on the right side, they are not identical on the left side. These data suggest that the heart and kidney are controlled by sympathetic nerve activities originating from different hypothalamic neural groups in the rabbit.
Norepinephrine content and disposition in large and small pulmonary artery of dog
Authors: Rorie D. K. , Tyce G. M.
Published: December 2017

Comparisons were made between large and small pulmonary arteries in 1) the content of norepinephrine (NE) and 2) the disposition of released NE. Endogenous NE was measured by liquid chromatography with electrochemical detection. The disposition of NE was studied using superfused strips of arteries previously incubated in l-[3H]NE. Superfusate was collected continuously before, during, and after electrical stimulation. 3,4-Dihydroxyphenylglycol (DOPEG) was shown to be of neuronal, and O-methylated metabolites to be of extraneuronal, origin. Thus extraneuronal uptake was estimated directly by measuring the O-methylated metabolites in the superfusate, and neuronal uptake followed by metabolism was estimated by measuring [3H]DOPEG. The magnitude of the neuronal uptake fraction entering vesicles for reuse was estimated from the compensatory increases in [3H]NE and O-methylated metabolites when neuronal uptake was blocked. The predominant route of disposition for NE was neuronal uptake in the small arteries (41% of released NE) but was extraneuronal uptake or NE overflow in the large vessels (35 and 37% of released NE, respectively). Recapture of NE by storage vesicles was greater in small than in large vessels (22 and 7%, respectively, of released NE).
Intercompartmental fluid shifts due to glucose release during hemorrhage in rabbits
Authors: Mohsenin V. , DuBois A. B.
Published: December 2017

Intercompartmental fluid shifts were studied in 18 anesthetized New Zealand White rabbits after hemorrhage. During graded hemorrhage the plasma volume spontaneously replaced was proportional both in time and amount to the hyperosmolar response. This, in turn, was mainly due to hyperglycemia. In 5 fed rabbits and 5 rabbits unfed for 40 h, all subjected to 16 ml/kg of hemorrhage, plasma volume replacement was closely correlated with the hyperglycemic response. Plasma glucose concentration gradually increased in fed animals throughout a 2-h posthemorrhagic period, whereas the hyperglycemic response ceased 15 min after hemorrhage in unfed animals, and further fluid shift also stopped. During the first 30 min after hemorrhage most of the fluid that shifted into the bloodstream came from the interstitial space, as judged by a lack of change in plasma sodium and chloride concentrations. However, during the second hour of the posthemorrhagic period of well-fed rabbits, plasma sodium and chloride concentrations decreased, suggesting that dilute fluid had shifted from the cells to the interstitial space and bloodstream. We concluded that the hyperglycemic response during and after hemorrhage played a significant role in plasma volume replacement, but this was less after a period of food deprivation.
Serotonin accumulation in granules of storage pool-deficient platelets of Chediak-Higashi cattle
Authors: Meyers K. M. , Seachord C. L. , Benson K. , Fukami M. , Holmsen H.
Published: December 2017

Platelets from cattle with the Chediak-Higashi (CH) syndrome are virtually devoid of dense granules, serotonin (5-HT), and stored ATP and ADP. The present study determined how the handling of 5-HT in normal cattle platelets differed from that in CH cattle platelets. Normal and CH platelets accumulated 5-[14C]HT to the same extent. After normal and CH platelets were incubated with 5-HT for 12 h most 5-HT is still intact, indicating that it was protected from metabolism. Part of the newly acquired 5-HT in normal and CH platelets was in a pool that was rapidly released by 5 U/ml of thrombin, suggesting that 5-HT was, in part, within granules. Subcellular fractionation studies showed that, whereas most of the newly acquired 5-HT in normal platelets was located in the dense granule fractions, about one fourth was found in the lighter granule fraction that was enriched in alpha-granules. The dense granule fraction was virtually absent in CH platelets, and most of the granule 5-HT was associated with the lighter granule fraction. The mixed granule fraction from CH platelets accumulated 5-HT but the uptake was about 10% of that from normal platelets. Unlike normal granules the uptake of 5-HT by CH granules was only slightly inhibited by reserpine but was reversed by NH4Cl and nigericin treatment.
Effect of coronary occlusion on arrhythmias and conduction in the ovine heart
Authors: Euler D. E. , Spear J. F. , Moore E. N.
Published: December 2017

The proximal left circumflex coronary artery was occluded for 1 h in 16 open-chest sheep anesthetized with pentobarbital sodium. Epicardial conduction was monitored at three or four sites within the ischemic zone and one site in the normal zone. Eight of the sheep developed ventricular fibrillation within the first 15 min of occlusion; the remaining sheep survived the 1-h observation period. In the sheep that developed spontaneous ventricular fibrillation, the circumflex perfused a significantly greater amount of the left ventricle (44 +/- 3 vs. 39 +/- 3%; P = 0.008). The occurrence of spontaneous ventricular fibrillation was invariably preceded by a period of sustained (0.5-4 min) ventricular tachycardia. Six of the surviving sheep developed episodes of sustained (2-10 min) tachycardia that were self-terminating. The ischemic zone electrograms showed continuous fractionated electrical activity during both self-terminating tachycardias and tachycardias ending in fibrillation. The continuous epicardial electrical activity did not appear to cause the tachycardias but rather occurred as a result of the tachycardias. The genesis of ventricular tachycardia and fibrillation in this model may involve mechanisms different from ischemia-induced ventricular tachycardia and fibrillation in canine and porcine hearts.
Cardiovascular changes from expiration to inspiration during IPPV
Authors: Santamore W. P. , Heckman J. L. , Bove A. A.
Published: December 2017

In vitro studies indicated that one ventricle can influence diastolic distensibility and systolic function of the opposite ventricle. Based on these in vitro observations, ventricular interdependence was examined in 12 anesthetized dogs. Right (RV) and left (LV) ventricular volumes and pressures and esophageal pressure (EP) were simultaneously measured during intermittent positive-pressure ventilation (IPPV) at zero end-expiratory pressure. Volumes were calculated from cineradiographic positions of endocardial, radiopaque markers. A comparison of the data obtained at end expiration with the data obtained at peak inspiration shows that EP decreased (4.6 +/- 0.3 to -2.1 +/- 0.2 mmHg, P less than 0.05) and RV end-diastolic volume increased (31.0 +/- 1.3 to 36.3 +/- 1.6 ml, P less than 0.05), whereas LV end-diastolic pressure increased (6.8 +/- 1.6 to 8.3 +/- 1.5 mmHg, P less than 0.05) and LV end-diastolic volume decreased (33.6 +/- 1.3 to 32.9 +/- 1.3 ml). The data indicate decreased LV distensibility as RV diastolic volume increased. As for systolic function, a comparison of end-expiration and peak inspiration data shows that RV ejection fraction increased (0.48 +/- 0.03 to 0.55 +/- 0.03 P less than 0.05) and RV stroke volume increased 5.6 +/- 1.0 ml, whereas LV ejection fraction decreased (0.54 +/- 0.03 to 0.52 +/- 0.03, P less than 0.05) and LV stroke volume decreased 0.8 +/- 0.6 ml. The decreased LV ejection fraction and stroke volume may suggest systolic interaction between the ventricles. The data indicate that the cardiovascular response to IPPV is complex, with ventricular interdependence being an important element.
Effect of tolbutamide on myocardial energy metabolism
Authors: Kramer J. H. , Lampson W. G. , Schaffer S. W.
Published: December 2017

Exposure of rat hearts perfused with 5 mM glucose and 5 mM acetate to tolbutamide led to a dramatic stimulation in glucose utilization and glycolytic flux. This effect was concentration dependent, with the largest response occurring at a tolbutamide concentration of 0.6 mM. Measurement of tissue glycogen content revealed that the higher concentrations of tolbutamide also enhanced glycogenolysis, indicating that the increase in glycolysis was caused by an increase in both glucose consumption and glycogen mobilization. On the basis of the determination of key metabolic intermediates, it was concluded that the stimulation of anaerobic metabolism was mediated by an activation of both phosphofructokinase and phosphorylase. The observed increase in glycolytic flux was associated with a rise in lactate production; however, the most pronounced effect of the drug was the stimulation of glucose oxidation. Thus the percentage of oxygen used in the oxidation of glucose was dramatically increased. Calculations also revealed that the contribution of glucose to overall ATP production rose from 8% in the absence of tolbutamide to about 30% in the presence of the sulfonylurea.
Substrate dependence of myocardial response to hypoxia in the presence of theophylline
Authors: Snow T. R. , Caspar T.
Published: December 2017

The experiments reported here were designed to determine whether stimulating glycogenolysis with theophylline affects the ability of isolated rabbit papillary muscles to sustain and recover from a transient hypoxic episode (15 min). Different substrates [glucose (Glc), pyruvate (Pyr), and butyrate (BA)] were used to either support the glycogen levels or permit their depletion. To evaluate the metabolic consequences, the dynamic relation (coupling coefficient) between the oxidation-reduction level of the intramitochondrial pyridine nucleotide NADH and the mechanical power was determined using a microfluorometer. In the absence of theophylline, the presence of Glc was associated with a smaller decrease in developed tension (tau) during the hypoxic period (Glc 53 +/- 5%) when compared with the nonglycolytic substrates (Pyr 33 +/- 5% or BA 31 +/- 6%). The extent of the recovery was not dependent on the available substrate. The addition of theophylline was accompanied by a substrate-dependent increase in tau: Glc 153 +/- 9%, Pyr 134 +/- 9%, and BA 116 +/- 7%. Theophylline increased the impact of the hypoxic episode on mechanical performance: Glc 17 +/- 4%, Pyr 4 +/- 4%, and BA 6 +/- 5%. With Glc, recovery was comparable to control. For the nonglycolytic substrates, recovery of mechanical function was depressed (Pyr 69 +/- 7%, BA 71 +/- 6%), and there was a significant loss of metabolic sensitivity. These data show that the inotropic response to theophylline is in part determined by the available substrate; theophylline exacerbates the impact of a hypoxic episode, and this effect may be due to the metabolic consequences of its presence.
Length-dependent sensitivity at lengths greater than Lmax in vascular smooth muscle
Authors: Price J. M. , Davis D. L. , Knauss E. B.
Published: December 2017

Previous work has shown that vascular smooth muscle sensitivity depends on muscle length (arterial circumference) at lengths equal to and less than that for maximum active force (Lmax). In the present study dose-response curves were obtained from dog anterior tibial artery rings at lengths equal to or longer than Lmax. The curves were compared with dose-response curves obtained at lengths less than Lmax. The agonist concentration for half maximal response (ED50) was determined by graphical estimation and by calculation from a best-fit curve. The results show that with norepinephrine (NE) stimulation 1) ED50 decreased significantly at each step when the rings were stretched from Lmax to 1.15 Lmax and then to 1.30 Lmax; 2) ED50 increased significantly when length was decreased from 1.15 to 1.00 Lmax; 3) ED50 decreased significantly at each step when the rings were stretched from 0.70 Lmax to Lmax and then to 1.30 Lmax; and 4) for NE concentration greater than the ED50 at Lmax, active stress was significantly higher at Lmax than at 0.70 Lmax or 1.30 Lmax. For an NE concentration less than the ED50 at Lmax, the active stress at 1.30 Lmax was higher than the active stress at Lmax and at 0.70 Lmax. The results show that sensitivity of vascular smooth muscle continually increases with stretch and does not have a maximum at the length for maximum active force.
Evaluation of methods for estimating infarct size by myosin LC2: comparison with cardiac enzymes
Authors: Nagai R. , Chiu C. C. , Yamaoki K. , Ohuchi Y. , Ueda S. , Imataka K. , Yazaki Y.
Published: December 2017

The relationship between histologically determined infarct size and release or peak levels of circulating cardiac enzymes and myosin light chain 2 (LC2) was studied. Myocardial infarction was produced by ligating the left anterior descending coronary artery in 18 conscious closed-chest dogs. Creatine phosphokinase (CPK), cytosolic and mitochondrial isozymes of aspartate transaminase (sAST and mAST) in the plasma, and LC2 in the serum were measured serially until 10 days after infarction, when infarct size was determined histologically [range 4.0-38.8% of the left ventricular weight (%LV)]. Infarct size correlated most closely with LC2 release (r = 0.82, P less than 0.001) and less closely with peak sAST (r = 0.59, P less than 0.01), peak mAST (r = 0.49, P less than 0.05), peak CPK (r = 0.22), and CPK release (r = 0.14). The correlation between infarct size and CPK release was improved by limiting the analysis to the dogs with infarct size of less than 20% LV (n = 11, r = 0.53, P less than 0.1). Because, among cardiac enzymes and LC2, CPK activity decayed most rapidly in the lymph fluid when incubated in vitro, degeneration of CPK in the lymph stream may contribute to the nonlinear relationship between infarct size and CPK release.
Abnormal baroreflex control in renal hypertension is due to abnormal baroreceptors
Authors: Guo G. B. , Thames M. D.
Published: December 2017

We determined if baroreflex control (BC) of lumbar sympathetic nerve activity (LSNA) is preserved despite impaired control of heart rate (HR) in rabbits with 6 wk of renal hypertension (HT). Baroreflex responses were determined during transient or steady-state increases (phenylephrine, PE) or decreases (nitroglycerin or caval occlusion) in arterial pressure. Impaired BC of HR was confirmed in conscious and anesthetized HT rabbits with all baroreflexes intact. In contrast, BC of LSNA was preserved in anesthetized HT rabbits. We further determined whether this selective impairment of BC of HR but not of LSNA could be due to an abnormality in the central nervous system (CNS) or in the afferent limb of the baroreflex. With only the left aortic depressor nerve (ADN) intact (other arterial baroreceptor afferents cut), BC of both HR and LSNA in HT was significantly impaired during infusion of PE. However, responses of HR and LSNA to afferent electrical stimulation of the left ADN (all arterial baroreceptor afferents cut) were similar in HT and normotensive controls. We conclude that 1) BC of LSNA is preserved in renal HT even though control of HR is impaired; 2) selective impairment of BC of HR in HT results from an abnormality in the afferent limb of baroreflex and not in CNS; 3) this abnormality in the afferent limb is not sufficient to impair BC of LSNA when all baroreflexes are intact but is sufficient after partial arterial baroreceptor denervation.
Influence of circulating NE and Epi on adipose tissue vascular resistance and lipolysis in humans
Authors: Hjemdahl P. , Linde B.
Published: December 2017

The effects of circulating norepinephrine (NE) and epinephrine (Epi) on vascular resistance in subcutaneous adipose tissue and the calf as well as on plasma glycerol, an indicator of lipolysis, were studied in healthy volunteers. Adipose tissue blood flow was determined by the local clearance of 99mTcO-4 or 133Xe. The two isotopes gave similar results. Calf blood flow was determined by venous occlusion plethysmography. Intravenous infusion of NE caused increases in systolic and diastolic blood pressures, adipose tissue and calf vascular resistances, and plasma glycerol and a decrease in plasma insulin and heart rate, all of which were significant when arterial plasma NE was elevated from 1.17 +/- 0.14 to 8.38 +/- 0.30 nM (n = 16). Epi reduced diastolic and mean arterial pressures and adipose tissue and calf vascular resistances and increased plasma glycerol without affecting systolic blood pressure or plasma insulin. An increase of arterial plasma Epi from 0.20 +/- 0.03 to 1.15 +/- 0.05 nM (n = 6) was sufficient to induce vasodilatation in adipose tissue and lipolysis. Human adipose tissue differs from canine adipose tissue inasmuch as Epi causes vasodilatation in humans (present results) but vasoconstriction in the dog (previous results), presumably due to a predominance of vascular beta 2-adrenoceptors in human and beta 1-adrenoceptors in canine adipose tissue. Furthermore, Epi is a considerably more potent lipolytic hormone than NE in humans but not in the dog. Our results indicate that both NE and Epi may influence human adipose tissue blood flow and lipolysis as circulating hormones.
Permeability of single capillaries to intermediate-sized colored solutes
Authors: Curry F. E. , Huxley V. H. , Adamson R. H.
Published: December 2017

The fiber matrix theory of capillary permeability was evaluated by measuring permeability coefficients to colored solutes with Stokes radii between 0.5 and 1.76 nm. In vivo calibration of a microscope photometer established the range of linearity for optical density measurements from a rectangular window that included the test capillary and surrounding tissue. In individually perfused capillaries of frog mesentery the following permeability coefficients, expressed as mean +/- SE X 10(5) cm/s were obtained: azure C (mol wt 277), 11.0 +/- 0.2; patent blue violet (566), 3.95 +/- 0.67; Evans blue (960), 1.15 +/- 0.23; microperoxidase (1,900), 1.13 +/- 0.31; and FITC-dextran 3 (3,400), 0.48 +/- 0.18. There is significant restriction to diffusion of all solutes larger than azure C. Fibers 0.5 nm in radius occupying 8.5% of the volume of intercellular junctions (area 2.2 X 10(-3) cm2/cm2, depth 0.6 X 10(-4) cm) account for the 22-fold range of measured permeabilities. The fiber density estimated is larger than that required to describe water flow through the junction. Negative charges on solutes larger than 0.5 nm radius may contribute to exclusion and restriction to diffusion in intercellular junctions.
Postnatal regulation of 2,3-DPG in sheep erythrocytes
Authors: Mueggler P. A. , Carpenter S. , Black J. A.
Published: December 2017

The erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentrations of sheep change markedly during the 1st mo following birth. From measurements of erythrocyte glycolytic enzymes and intermediate concentrations, we have identified the mechanism regulating erythrocyte 2,3-DPG in postnatal sheep. The postnatal changes in erythrocyte 2,3-DPG do not result from qualitative or quantitative changes in the intracellular activities of the Rapoport-Luebering shunt enzymes, 2,3-DPG mutase or 2,3-DPG phosphatase. The postnatal 2,3-DPG changes result from changes in the erythrocyte concentration of 1,3-DPG, which is controlled by other reactions in the glycolytic pathway. Neither changes in the glycolytic control enzymes (hexokinase, phosphofructokinase, and pyruvate kinase) nor changes in the intrinsic glycolytic rate can account for these 1,3-DPG concentration changes. 1,3-DPG concentrations are regulated by the in vivo glycolytic rate, which is controlled by the intracellular concentration of glucose, the glycolytic substrate. Glucose concentrations are 0.3 mmol/l cells in erythrocytes of fetal sheep (135-140 days gestational age), increase following birth to a peak of 3.8 mmol/l cells by the 1st wk of age, and then decline to the normal adult levels of 0.5 mmol/l cells by the end of the 1st mo.
Local cerebral PO2, PCO2, and blood flow measurements by mass spectrometry
Authors: Seylaz J. , Pinard E. , Meric P. , Correze J. L.
Published: December 2017

Partial pressures of intracerebral tissue gases (PO2, PCO2) and local cerebral blood flow (local CBF) were determined simultaneously by means of a single cannula implanted stereotaxically in a given structure. Minute quantities of the gases (O2, CO2, and tracer gas) were withdrawn continuously. After a short period of tracer (He) inhalation, CBF was measured by determination of the clearance rate (T1/2). The measurements of PO2 and PCO2 were continuous and quantitative, whereas the measurements of local CBF were sequential and quantitative. The results obtained for local CBF were compared with those found with two other methods (H2 clearance by polarography, thermoclearance) in the same structure of the same animal.
Chronic renal venous catheterization in fetal sheep
Authors: Iwamoto H. S. , Rudolph A. M.
Published: December 2017

To measure certain aspects of renal function it is necessary to monitor both renal arterial and venous blood. We describe a technique for chronically implanting a catheter in the renal vein of fetal lambs. Catheters have been inserted into the left renal vein in 11 fetuses at 120-125 days gestation and maintained for periods of 6-11 days (mean 8.7 +/- 2.2). We have determined that the catheter does not influence renal blood flow or alter renal morphology. We have also ascertained that the blood sampled from the renal venous catheter is not contaminated with blood from the inferior vena cava. This technique can be used to examine many aspects of renal physiology in the chronically instrumented fetal animal.
Intrinsic heart rate in the dog determined by pharmacologic denervation
Authors: Brunsting J. R. , Schuil H. A. , Zijlstra W. G.
Published: December 2017

Intrinsic heart rate was measured in 19 dogs in 76 experiments after autonomic blockade, using various forms of anesthesia. Measurements were made in conscious dogs (n = 16) and in dogs in neuroleptanesthesia (n = 54) or under pentobarbital sodium (n = 6). Temperature, arterial pH, and blood gases were kept within narrow limits. Adrenergic blockade was achieved by phenoxybenzamine (2 mg X kg-1) and propranolol (2 mg X kg-1, followed by 2 mg X kg-1 X h-1). The parasympathetic system was blocked either by atropine (0.5 mg X kg-1, followed by 0.5 mg X kg-1 X h-1) and hexamethonium (20 mg X kg-1, followed by 10 mg X kg-1 X h-1) or by atropine and bilateral cervical vagotomy. Administration of hexamethonium or vagotomy was needed to block the vagal cardioacceleration unmasked by the administration of muscarinic blocking agents in conscious dogs and in dogs in neuroleptanesthesia. The mean denervated heart rate was 142.8 beats/min. This value is higher than that reported for surgically denervated hearts, the difference very likely reflecting the activity of the intact parasympathetic intrinsic cardiac innervation in surgical preparations. The estimated intraindividual and interindividual SD were 9.7 and 19.4 beats/min, respectively. The highly significant interindividual variation (P less than 0.01) contradicts the concept of an intrinsic heart rate as a practically constant species-dependent quantity.
Differences in K+-induced relaxation of canine femoral and renal arteries
Authors: Bukoski R. D. , Seidel C. L. , Allen J. C.
Published: December 2017

The extent and initial rate of potassium-induced relaxation of canine femoral and renal arteries were measured as a function of potassium concentration [K+]. Both parameters were greater in the renal artery at low [K+]; the dissociation constant for potassium of the femoral artery was greater than that of the renal artery. If potassium-induced relaxation reflects sodium pump activity, then these data indicate that the sodium pumps of the two arteries are different. When we repeated the above experiments in a lowered sodium medium, the rate and extent of potassium-induced relaxation and the apparent affinity for potassium increased in the femoral artery as predicted by kinetic models based on both isolated Na+-K+-ATPase and intact tissue. The same parameters in the renal artery, however, were unaffected by lowered sodium. These results and those presented in the companion paper [Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H604-H609, 1983] can be interpreted to mean that potassium-induced relaxation does not accurately reflect sodium pump function in canine renal arteries.
Effects of calcium channel blockers on isolated carotid baroreceptors and baroreflex
Authors: Heesch C. M. , Miller B. M. , Thames M. D. , Abboud F. M.
Published: December 2017

Our study determined the effects of the calcium antagonists, nifedipine and verapamil, on the carotid sinus baroreceptors and baroreflex. The left carotid sinus region in dogs was vascularly isolated and filled with oxygenated physiological salt solution. Steady-state multiunit activity was recorded from the carotid sinus nerve for sinus pressures of 50-200 mmHg after bathing the carotid sinus region in a solution containing no drug, 10 micrograms/ml nifedipine (n = 6), or 5 micrograms/ml verapamil (n = 5). The slopes of the curves relating carotid sinus nerve activity (% of maximum control) to carotid sinus pressure were control, 0.81 +/- 0.06; nifedipine, 1.29 +/- 0.14; and verapamil, 0.48 +/- 0.06%/mmHg, indicating that nifedipine increased and verapamil decreased the sensitivity of the carotid sinus baroreceptors. Additional studies with bilateral carotid sinus isolation (carotid sinus nerves intact) indicated that nifedipine enhanced and verapamil attenuated carotid baroreflex control of renal sympathetic nerve activity. Pressure-volume curves generated in the isolated carotid sinus showed that effects on smooth muscle do not account for the opposing effects of the two Ca2+ antagonists. Omitting Ca2+ from the physiological solution resulted in increased carotid sinus nerve activity, an effect blocked by verapamil but not nifedipine. Verapamil, but not nifedipine, inhibited veratrine-induced (Na+-dependent) excitation of carotid baroreceptors. Thus the excitatory effects of nifedipine on the carotid sinus baroreceptors are dependent on Ca2+ mechanisms, whereas the inhibitory effects of verapamil may be due mainly to interference with the inward Na+ current.
Sodium depletion induces adrenergic potentiation at prejunctional site
Authors: Wong P. C. , Zimmerman B. G.
Published: December 2017

The objective of this study was to examine the effect of sodium depletion on basal sympathetic adrenergic vascular tone and vasoconstrictor responses to adrenergic nerve stimulation and norepinephrine in pentobarbital-anesthetized dogs. Mean arterial pressure, tibial blood flow, and tibial vascular resistance were not significantly different between sodium-replete and sodium-deplete dogs. However, plasma renin activity (PRA) was 11-fold higher in sodium-deplete dogs (P less than 0.01). Sympathetic denervation in sodium-replete and -deplete dogs resulted in a similar decrease in tibial vascular resistance. Nerve stimulation at 0.25 and 0.5 Hz caused 40 +/- 5 and 48 +/- 5% decreases, respectively, in tibial blood flow in sodium-replete dogs and 71 +/- 3 and 77 +/- 3% decreases, respectively, in sodium-deplete dogs (P less than 0.01). Responses to norepinephrine administered intra-arterially were similar in both groups. Neither captopril nor saralasin reduced the potentiated responses to nerve stimulation in sodium-deplete dogs. Bilateral nephrectomy 24 h prior to the experiment reduced PRA to an undetectable level in both sodium-replete and -deplete dogs and equalized the responses to nerve stimulation and norepinephrine in both groups. Because bilateral nephrectomy, but neither captopril nor saralasin, abolished the potentiated responses in sodium depletion, a renal hormone other than renin or vascular angiotensin II may be responsible for this prejunctional adrenergic potentiation.
Developmental changes in oxygenation and circulatory responses to hypoxemia in lambs
Authors: Sidi D. , Kuipers J. R. , Teitel D. , Heymann M. A. , Rudolph A. M.
Published: December 2017

We studied moderate [fractional inspired O2 (FIO2) 0.09] and severe (FIO2 0.06) hypoxemia in 21 lambs (group 1, 1 wk old; group 2, 3-4 wk old; group 3, 5-7 wk). With moderate hypoxemia, all groups increased heart rate, cardiac output, and pulmonary arterial pressure and decreased systemic and pulmonary vascular resistance; cardiac output and pulmonary arterial pressure increases were less in group 1, because of higher resting values. With severe hypoxemia, heart rate increased similarly, cardiac output was unchanged, and aortic pressure fell associated with severe metabolic acidosis or arrhythmias. Regional blood flow changed similarly in all groups; heart and brain flow increased, carcass flow was unchanged, and skin, GI tract, and kidney flow fell. O2 consumption (VO2) and mixed venous PO2 decreased, though O2 saturation was higher in group 1 due to the lower O2 half-saturation pressure of hemoglobin. With a given decreased VO2 there was more metabolic acidosis in older lambs and an increased VO2 after termination of hypoxemia, suggesting greater O2 debt. As in the fetus, young lambs are better able to tolerate a decreased VO2 than older lambs.
Both protein and blood cells reduce coronary microvascular permeability to macromolecules
Authors: McDonagh P. F.
Published: December 2017

A number of studies report that isolated Krebs-perfused hearts deteriorate with time, develop edema, and demonstrate a progressive increase in coronary vascular resistance. However, hearts perfused with filtered blood are more stable with regard to cardiac function and coronary resistance. The changes observed in the Krebs hearts may be due to a "permeability"-type edema. The purpose of this study was to systematically determine whether adding protein and blood cells to a Krebs perfusate affected coronary microvascular permeability to macromolecules. The rat heart preparation employed allowed direct visualization and quantification of transcoronary macromolecular leakage. We observed severe transcoronary leakage of fluorescent albumin (FITC-BSA) when FITC-BSA was later added after 20 min of perfusion with Krebs. Leakage was decreased by including 2 g/100 ml albumin (BSA) in the initial perfusate but was not further reduced by increasing the BSA concentration to 5 g/100 ml. However, adding washed blood cells to the initial perfusate did further reduce FITC-BSA leakage. The index of FITC-BSA exchange, the O/I ratio, was 0.70 +/- 0.02 (+/- SE) for Krebs perfusate, 0.55 +/- 0.03 for Krebs-BSA, and 0.45 +/- 0.02 for Krebs-BSA-blood cells, indicating significant effects for both protein and blood cells (P less than 0.05). The results suggest that both protein and blood cells are necessary to maintain the semipermeable characteristics of the coronary exchange vessels.
Plasma-soluble marker for intraorgan regional flows
Authors: Little S. E. , Bassingthwaighte J. B.
Published: December 2017

Measurement of regional plasma flow is needed to quantitate the delivery of substrates and drugs to cells. For estimating regional plasma flows an ideal deposition marker should be 100% extracted during transorgan passage and retained until local tissue concentrations can be measured. To escape quickly, the tracer must penetrate capillary endothelial cells rapidly. To be retained, it must bind or be transformed or accumulated by cells. Desmethylimipramine (DMI, mol wt 266.3), a norepinephrine reuptake inhibitor, is suitable. On injection of [3H]DMI and 131I-albumin simultaneously into the coronary artery inflow of isolated Ringer-perfused rabbit hearts at 37 degrees C, extractions were greater than 99% at plasma flows (Fs) up to 2.3 ml X g-1 X min-1 and greater than 94% with Fs up to 5.1. Retention at Fs less than 2.3 averaged 99.0 +/- 0.55% (SD, n = 6) at 0.5 min, 98.4 +/- 0.5% at 1 min, and 96.6 +/- 1.1% or greater than 95% at 3 min. Retentions were similar in two dog hearts in situ. With Fs greater than 3 ml X g-1 X min-1, there was greater escape, 4.2 +/- 2.7% at 1 min and 6.8 +/- 4.2% at 3 min. The fractional escape rates of loss at 2 min or more were about 1%/min at all flows, suggesting that the spatial profiles of deposition did not change thereafter. Thus DMI is nearly ideal as a "molecular microsphere."
Effect of vasopressin antagonist and saralasin on regional blood flow following hemorrhage
Authors: Pang C. C.
Published: December 2017

The effects of hemorrhagic hypotension on mean arterial pressure (MAP), cardiac output (CO), and its distribution were investigated in halothane-anesthetized rats using the radioactive microsphere technique. Hemorrhage (12 ml/kg) decreased MAP and CO, increased total peripheral resistance (TPR), and decreased blood flow (BF) to the heart, stomach, intestine, kidneys, skin, cecum, and colon. The effects of antagonists of vasopressin and the renin-angiotensin system on peripheral circulation following hypotensive hemorrhage were also examined using d(CH2)5Tyr(Me)AVP and saralasin, respectively. Injection of the vasopressin antagonist caused a reduction of MAP by reducing TPR and caused an increase of percent distribution of CO to the stomach, skin, cecum, and colon. Intravenous infusion of saralasin caused significant reductions of MAP by reducing TPR. Saralasin caused an increase of percent distribution of CO to the kidneys. The results show that both vasopressin and the renin-angiotensin systems participate in the control of MAP and peripheral vascular resistance following hypotensive hemorrhage in anesthetized rats.
Effect of Na+- or Ca2+-filled liposomes on electrical activity of cultured heart cells
Authors: Bkaily G. , Sperelakis N. , Elishalom Y. , Barenholz Y.
Published: December 2017

Phosphatidylcholine (PC) liposomes were used to deliver their entrapped ions into spontaneously contracting cultured heart cells (reaggregates) prepared from 15-day embryonic chick ventricles (superfused at 8 ml/min). With slowly rising action potentials (AP) (+Vmax less than 30 V/s), when Na+ liposomes were added (13.2% vol/vol), there was a progressive decrease in slope of the pacemaker potential and in firing frequency. Recovery on washout was rapid. When vesicles containing Ca2+ (6.6% vol/vol) were added, there was an immediate decrease in AP duration. Within 10 min, +Vmax, overshoot, maximum diastolic potential, and frequency decreased, and all spontaneous activity stopped within 30 min. Electrical stimulation could not elicit AP responses. Partial recovery of APs occurred after 60 min of washout, but the recovering APs initially were abnormal. Lower liposome concentration (3.3%) had a similar but slower effect. The rapidity of the effects depended on the Ca2+ concentration inside the vesicles (0.15 and 1 M). K+-containing liposomes had no effect. This difference between liposomes containing Na+, Ca2+, and K+ suggests that the effects observed were due to the ions and not to the phosphatidylcholine. Injection of Ca2+ could cause depolarization by the Ca2+-activation of a nonspecific Na+-K+ channel (i.e., gNa, K, (Ca]; inhibition of automaticity by injection of Na+ or Ca2+ could be due to diminution of the electrochemical gradient for inward background depolarizing current. Thus PC liposomes provide a good means for delivering substances inside the cells without altering the electrical properties of the membrane by the lipid vehicle.
Increased adrenal catecholamines in salt-sensitive genetically hypertensive Dahl rats
Authors: Saavedra J. M. , Del Carmine R. , McCarty R. , Guicheney P. , Weise V. , Iwai J.
Published: December 2017

Catecholamine levels and activity of catecholamine-forming enzymes have been quantitated in adrenal glands of Dahl sodium-resistant (R) and sodium-sensitive (S), genetically hypertensive rats maintained on low- or high-salt diets. A high-salt diet results in markedly different changes in the catecholamine metabolism in R and S rats. In R rats, a high-salt diet reduces the activities of tyrosine 3-hydroxylase (TH;-5%) and dopamine beta-hydroxylase (DBH; -18%) as well as the levels of all catecholamines (dopamine -28%, norepinephrine -11%, and epinephrine -28%). In contrast, S rats fed a high-salt diet showed increased TH (+7%) and phenylethanolamine N-methyltransferase (+16%) activities as well as an increased content of adrenal norepinephrine (+13%) and epinephrine (+21%). These findings demonstrate a genetic difference in the effects of a high-salt diet on the synthesis of catecholamines in the adrenal gland of Dahl R and S rats. Hypertension only occurs in S rats on a high-salt diet, concomitant with large increases in the formation of adrenal catecholamines.
Quantitative histochemistry of canine cardiac Purkinje fibers
Authors: Henry C. G. , Lowry O. H.
Published: December 2017

Single canine Purkinje cells were isolated by microdissection and analyzed quantitatively for six enzymes of energy metabolism. Subendocardial Purkinje cells were clearly distinguishable morphologically and biochemically from adjacent myocardium and had enzyme levels comparable with extramural Purkinje cells. Oxidative enzymes, citrate synthase, malate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase were 40-60% lower in Purkinje cells than in myocardium. Lactate dehydrogenase was also 40% lower, but the other glycolytic enzymes, hexokinase and phosphofructokinase, were similar in level in myocardium and Purkinje cells. The results of this study show that it is completely practicable to apply quantitative histochemical analysis to biochemical study of the cardiac conducting system.
Isolation and morphology of calcium-tolerant feline ventricular myocytes
Authors: Silver L. H. , Hemwall E. L. , Marino T. A. , Houser S. R.
Published: December 2017

A technique has been developed for isolating a high yield of Ca2+-tolerant rod-shaped myocytes from the right and left ventricles of cat myocardial tissue. Myocytes were prepared by retrograde perfusion of the coronary arteries via the aorta with a nominally Ca2+-free (20-30 microM) modified Krebs-Henseleit buffer containing 0.12% collagenase. After exposure to physiological levels of Ca2+ (1-2.5 mM), the cells retained rod-shaped morphology, exhibited clear cross striations, and excluded the dye trypan blue (0.4%). Initial percents of viable Ca2+-tolerant rod-shaped cells were 58.6 +/- 3.4 (SE) and 51.8 +/- 3.5 for right and left ventricular cells, respectively. Viability studies demonstrated that these values decreased approximately 10% at the conclusion of a 2-h incubation in 1 mM Ca2+. The total numbers of rod-shaped myocytes obtained were 4.48 X 10(7) and 3.89 X 10(7) in nominal (8-10 microM) and 1 mM Ca2+-containing buffer, respectively. A total of 3.44 +/- 0.40 X 10(6) rod-shaped Ca2+-tolerant myocytes was initially isolated per gram of tissue wet weight. Measurements of cell length, width, and sarcomere length demonstrated no significant differences between right and left ventricular cells suspended in nominal (8-10 microM) and 1 mM Ca2+-containing buffer. No significant difference was found in the percent of binucleate cells when right and left ventricular myocytes were compared. These results demonstrate that a stable population of Ca2+-tolerant myocytes with similar morphological characteristics can be isolated from the right and left ventricles of cat myocardium.
Role of O2-hemoglobin affinity on cerebrovascular response to carbon monoxide hypoxia
Authors: Koehler R. C. , Traystman R. J. , Rosenberg A. A. , Hudak M. L. , Jones M. D.
Published: December 2017

Our previous studies showed that, in contrast to hypoxic and anemic hypoxia, CO hypoxia increased cerebral O2 delivery and decreased cerebral fractional O2 extraction. These changes were correlated with the accompanying decrease in P50 (PO2 at 50% saturation of non-CO bound sites on hemoglobin). To assess directly the role of P50 in the cerebrovascular response to CO, we first performed isovolemic exchange transfusions on unanesthetized newborn lambs, replacing their high-O2-affinity hemoglobin with low-affinity adult sheep donor blood. Exchange transfusion resulted in an average increase in P50 of 10 Torr and in a uniform decrease of regional cerebral blood flow and cerebral O2 delivery of 14%. Thus shifts in P50 can produce cerebrovascular changes during normoxia, implying that the mechanism regulating cerebral blood flow does not have a discrete threshold to an hypoxic stimulus. Induction of CO hypoxia (20-40% carboxyhemoglobin) after the exchange transfusion returned P50 to the control level, and with it restored both cerebral O2 delivery and fractional O2 extraction to the pretransfusion values. We conclude that the fall in P50, rather than a direct tissue effect of CO, is responsible for the relative cerebral overperfusion during CO hypoxia. The importance of the position of oxyhemoglobin dissociation curve as a determinant of cerebral blood flow supports the presence of a highly sensitive, tissue O2-dependent mechanism regulating the cerebral circulation.
A model of dynamic vagus-sinoatrial node interactions
Authors: Michaels D. C. , Slenter V. A. , Salata J. J. , Jalife J.
Published: December 2017

Computer simulations of dynamic vagus-sinoatrial (SA) node interactions were performed using an empirical model. The phasic effects of single vagal trains on pacemaker cycle length obtained experimentally in isolated preparations were summarized in phase response curves (PRCs). These PRCs were used to stimulate the interactions of the sinoatrial pacemaker with single or with repetitive vagal input. For single stimuli, the triphasic inhibitory curve describing the time course of a brief vagal burst (G. Brown and J. Eccles. J. Physiol. London 82: 211–241, 1934; and J. Jalife and G. K. Moe. Circ. Res. 45: 595–607, 1979) was used to predict the PRC at any given spontaneous pacemaker cycle length. In simulations of repetitive vagal input the model predicted the entrainment of the pacemaker. The patterns of interaction were dependent on the shape and amplitude of the PRC as well as on the relationship between the spontaneous pacemaker period and the vagal cycle length. At certain vagal frequencies, stable entrainment of the pacemaker occurred, and the entrained pacemaker period held harmonic relations to the vagal input (i.e., 1:1, 2:1, and so on). At other frequencies, zones of instability were found in which arrhythmic patterns developed. These predictions of the model matched the experimental results very closely. Under some conditions, during simulations with fixed sinovagus coupling intervals, the model generated patterns of sinus activity similar to those occurring experimentally or in patients with apparent sinoatrial block. The model was also capable of generating patterns similar to those obtained in cases of isorhythmic atrioventricular dissociation. The study of these interactions may have important bearing on the understanding of the dynamic control of heart rate by the parasympathetic nervous system and may be used to explain certain cardiac dysrhythmias.
Dietary sodium restriction and development of hypertension in spontaneously hypertensive rats
Authors: Toal C. B. , Leenen F. H.
Published: December 2017

Blood pressure and body weight of conscious spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were measured up to 16 wk of age in animals started at birth on five different sodium-containing diets. SHR on 9 mumol sodium/g food did not show a rise in basal blood pressure; however, when stressed the SHR still exhibited slightly higher blood pressures than WKY. In SHR on 17 mumol sodium/g food the development of hypertension was blunted compared with that of control (101 mumol/g) diet animals. SHR on 26 or 44 mumol sodium/g diet exhibited a development of hypertension similar to that of SHR on control diet. The 26 mumol/g, 44 mumol/g, and control sodium diet groups, regardless of strain, had similar growth rates. By contrast, on 17 mumol sodium/g food both SHR and WKY showed a substantially reduced growth rate, and all animals on 9 mumol sodium/g diet were severely retarded in growth. The results indicate that dietary sodium restriction can ameliorate the development of hypertension in SHR, but only when the sodium levels are so low as to affect overall growth.