bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous measurement of renal blood flow changes to renal nerve stimulation and intra-arterial drug administration in the rat
Authors: Fink G. D. , Brody M. J.
Published: December 2017

A method is described for continuous measurement of renal blood flow in the anesthetized rat without dissection of the renal artery. Blood flow and arterial pressure were measured in an extracorporeal flow circuit between the carotid artery and an aortic pouch from which the left renal artery was the only outlet. Injection into the flow circuit allowed delivery of drugs directly into the arterial blood supply of the kidney. Electrical stimulation of undamaged periarterial renal kidney. Electrical stimulation of undamaged periarterial renal nerves was possible since the renal artery remained undisturbed. Extracorporeal autoperfusion of the rat kidney produced renal flow and resistance measurements that did not differ from those obtained with a flow probe placed directly on the renal artery. Renal nerve stimulation was found to cause renal vasoconstriction due to activation of alpha-adrenergic receptors by norepinephrine released from postganglionic sympathetic neurons. Renal vascular responses to a variety of intra-arterial vasoactive agents were also determined. The method described here allows the evaluation of renal vascular control in the variety of disease states for which suitable rat models have been developed.
Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase
Authors: Keely S. L. , Lincoln T. M. , Corbin J. D.
Published: December 2017

In the isolated perfused rat heart, epinephrine produced a rapid, concentration-dependent increase in cyclic adenosine 3',5'-monophosphate (cAMP), activation of cAMP-dependent protein kinase, activation of phosphorylase, and increase in contractile force. At epinephrine concentrations of 1 micron or less, acetylcholine antagonized all these beta-adrenergic effects and also increased cyclic guanosine 3',5'-monophosphate (cGMP) levels. When used alone, acetylcholine produced a rapid elevation of cGMP and markedly diminished contractile force but did not significantly lower basal cAMP levels or cAMP-dependent protein kinase activity. The data suggest that changes in cAMP-dependent protein kinase activity can explain the antagonism of epinephrine-induced activation of phosphorylase by acetylcholine, but cannot completely account for the inhibitory effect of the cholinergic agent on contractile force.
Effects of endurance exercise on coronary collateral blood flow in miniature swine
Authors: Sanders M. , White F. C. , Peterson T. M. , Bloor C. M.
Published: December 2017

Coronary collateral blood flow was measured in 7 miniature pigs, exercise trained (ET) for 10 mo by running about 35 km/wk, and in 10 sedentary control pigs (SC). In acute, open-chest preparations, radiolabeled (85SR, 141CE, or 51Cr) microspheres, 15 +/- 5 micron in diameter, were injected into the left atrium during each of three conditions: control (C), total occlusion of the left circumflex artery (TO), and TO plus mechanically elevated aortic pressure (TOP). Blood flow to the circumflex bed during control condition in ET and SC was 0.36 +/- 0.07 (SE) and 0.43 +/- 0.10 ml.g-1.min-1, respectively. During TO, circumflex flow in ET and SC fell to 0.05 +/- 0.01 and 0.06 +/- 0.01 ml.g-1.min-1, respectively. In the presence of TOP, left circumflex flow in ET and SC rose to 0.11 +/- 0.04 and 0.11 +/- 0.02 ml.g-1.min-1, respectively. Blood flow to the tissue bed of the left anterior descendens was the same in both groups of pigs under all conditions. Thus, 10 mo of endurance exercise training seems to have no effect on the development of coronary collaterals in the left ventricles of pig hearts.
Regulation of cerebral blood flow in the ovine fetus
Authors: Jones M. D. , Sheldon R. E. , Peeters L. L. , Makowski E. L. , Meschia G.
Published: December 2017

The effects on fetal cerebral blood flow (Qc) of changes in the carotid arterial and sagittal sinus venous PO2, PCO2, and oxygen content were studied in the chronically catheterized ovine fetus in utero at 130–140 days of gestation. Forty-seven measurements of Qc were made in 20 fetuses with radioactive microspheres. In 11 of these animals, 84 measurements of cerebral arteriovenous differences of oxygen content were performed, permitting an indirect measurement of cerebral blood flow (Qc*), assuming a constant cerebral metabolic rate. Arterial and, in 11 animals, sagittal sinus blood was withdrawn for analysis of PO2, PCO2, oxygen content, and pH at the time of the flow measurements. Preliminary analysis showed the best predictor of Qc and Qc* to be the reciprocal of the arterial oxygen content (1/CaO2). Multiple linear regression analysis combining the effects of 1/CaO2 with arterial PCO2 (PaCO2) gave the following equations: Qc = 458.8 (1/CaO2) + 2.68 PaCO2 - 107.93 (R2 = 0.68); Qc* = 435.54 (1CaO2) + 2.20 PaCO2 - 75.03 (R2 = 0.86). As a result of the hyperbolic relationship between Qc (and Qc*) and CaO2, changes in CaO2 at the low levels found during intrauterine life exert an important influence on the fetal cerebral circulation.
Sympathetic vasomotor outflows to hindlimb muscles of the cat
Authors: Sonnenschein R. R. , Weissman M. L.
Published: December 2017

Blood flow to the hindlimb muscles of chloralose-anesthetized, paralyzed cats was monitored with an electromagnetic flowmeter on the femoral artery. The functional pathways of the sympathetic constrictor and dilator innervations to the vasculature of these muscles were determined by measuring changes in vascular conductance during electrical stimulation of 1) ventral roots T12-L7 (exit of preganglionic fibers from the spinal cord and entrance into the sympathetic chain), 2) the distally intact sympathetic chain at successive levels between the L1 and L7 ganglia (presence of caudally running vasomotor fibers in the chain at each level), and 3) isolated sympathetic ganglia L2-L7 (exit of postganglionic vasomotor fibers from the chain at each level). Our results indicate that vasoconstrictor fibers emerge from ventral roots T12-L4 with maximum functional outflow at L1-L3; the fibers course downward through the sympathetic chain to exit from the chain mainly at L5-L7 or below. In contrast, the preganglionic origin of cholinergic vasodilator fibers, tested after blocking the constrictor fibers with bretylium, is limited to ventral roots L2-L5, with maximum outflow at L4. The vasodilator fibers leave the sympathetic chain to enter the spinal nerves at the same levels as the vasoconstrictor fibers.
Reproducible and uniform cardiac ischemia: effects of antiarrhythmic drugs
Authors: Hondeghem L. M. , Cotner C. L.
Published: December 2017

The in vivo response of cardiac tissue to ischemia is inherently nonuniform, and as a result the drug effects in the latter are subject to great variability. We therefore designed a preparation that could reproducibly respond to uniform ischemia: Langendorff-perfused rabbit hearts in which ischemia was induced by stopping the perfusion. In this preparation therapeutic concentrations of antiarrhythmic drugs have no-to-moderate effects on conduction and excitability of perfused tissue, while markedly depressing these parameters in ischemic tissue. This selectivity for depression of ischemic tissue increases as the ischemia progresses. Antiarrhythmic drugs can in this way markedly attenuate the abnormal electrical activity of the ischemic tissue (responsible for arrhythmias) while minimally affecting this activity in normal tissue.
Measurement of multiple simultaneous small dimensions and study of arterial pressure-dimension relations in conscious animals
Authors: Pagani M. , Baig H. , Sherman A. , Manders W. T. , Quinn P. , Patrick T. , Franklin D. , Vatner S. F.
Published: December 2017

This paper describes the development of several important modifications that were incorporated into the ultrasonic, transit-time dimension system in order to obtain multiple simultaneous, instantaneous, and continuous measurements of the external dimensions of the aorta and its major branches in conscious, unrestrained animals. At operation a pair of small piezoelectric crystals was sutured to arterial adventitia, and a miniature pressure gauge was implanted in the vessel at the same cross-sectional plane. After recovery from surgery, wall motion was not altered appreciably and scarring was minimal. This technique allows long-term monitoring of aortic pressure-dimension relations and is applicable for small (fetal and neonatal) as well as large (adult dogs and sheep) animals. When vessel wall thickness is measured, stress-radius analysis can be performed so as to compute vascular elastic stiffness as a function of stress. Moreover, the suitability for radiotelemetry of the pressure and dimension signals measured with this technique enables the study of these parameters in unrestrained animals, e.g., during spontaneous severe exercise.
Measurement of myocardial PCO2 with a microelectrode: its relation to coronary sinus PCO2
Authors: Case R. B. , Felix A. , Wachter M.
Published: December 2017

A micro-PCO2 electrode, with dimensions of 1 x 10 mm, and a 63% response time of 14 s was inserted into the left ventricular myocardium of the pentobarbital-anesthetized dog. Continuous recordings were made of myocardial PCO2 (PmCO2), arterial PCO2 (PaCO2), and coronary sinus PCO2 (CSPCO2) during variation of respiratory rate. PmCO2 and CSPCO2 were compared at varying coronary flow. PmCO2 was similar to and closely followed changes in CSPCO2. The difference between PmCO2 and CSPCO2 was -0.52 +/- 3.63 (SD) mmHg, and PmCO2 exceeded PaCO2 by 20.69 +/- 5.12 mmHg. After coronary occlusion, PmCO2, rose promptly, but CSPCO2 was only slightly elevated until the occlusion was released, when a CO2 efflux into the coronary sinus occurred. It is concluded that the electrode measures extracellular PCO2 and that extracellular and myocardial PCO2 are essentially equal. PmCO2 rises rapidly following coronary occlusion.
Effect of central venous pressure on arterial baroreflex control of heart rate
Authors: Takeshita A. , Mark A. L. , Eckberg D. L. , Abboud F. M.
Published: December 2017

There is considerable evidence that the level of afferent cardiopulmonary receptor activity modulates sinus node responses to arterial baroreflex stimulation in experimental animals. We tested the hypothesis that this reflex interaction occurs also in man by measuring sinus node responses to arterial baroreceptor stimulation with phenylephrine injection or neck suction, before and during changes of central venous pressure provoked by lower body negative pressure or leg and lower trunk elevation. Variations of central venous pressure between 1.1 and 9.0 mmHg did not influence arterial baroreflex mediated bradycardia. Baroreflex sinus node responses were augmented by intravenous propranolol, but the level of responses after propranolol was comparable during the control state, lower body negative pressure, and leg and trunk elevation. Sinus node responses to very brief baroreceptor stimuli applied during the transitions of central venous pressure also were comparable in the three states. We conclude that physiological variations of central venous pressure do not influence sinus node responses to arterial baroreceptor stimulation in man.
Regional oxygen consumption and supply in the dog heart: effect of atrial pacing
Authors: Weiss H. R.
Published: December 2017

The effects of atrial pacing on the relationship of O2 supply to demand were studied on a regional basis in the dog heart. Experiments were conducted on fourteen hearts, seven in control pentobarbital-anesthetized, open-chest dogs and seven in dogs paced at 225 beats/min. Regional O2 extraction was determined by a microspectrophotometric method, and coronary blood flow was measured with radioactive microspheres. There was an 89% increase in coronary blood flow, a small but significant decrease in O2 extraction, and an increase in O2 consumption with atrial pacing. With pacing the increase in blood flow and the decrease in O2 extraction were uniform throughout the heart. In control hearts, right ventricular blood flow and O2 consumption were lower than the mean in the septal or left ventricular free wall. In the left ventricular free wall in control, the subepicardial region had a lower O2 consumption and O2 extraction than the subendocardial region. These differences were also preserved during pacing. Due to the large increase in coronary blood flow, the relationship of oxygen supply to demand was improved by atrial pacing.
Myocardial energetics during isometric twitch contractions of cat papillary muscle
Authors: Cooper G.
Published: December 2017

During myocardial tetanus, when activation is maximum and constant, there is a linear relationship throughout contraction between oxygen consumption (MVo2) and the cumulative product of active tension and time (integral of AT). The goal of this study was to determine the relation of MVo2 to integral of AT during isometric myocardial twitch contractions. Ten right ventricular cat papillary muscles were studied in a flow respirometer. MVo2 was determined during contractions unloaded from Lmax to a slack length at successive 100-ms intervals after stimulation. In contrast to the linear relationship observed during tetanus, MVo2/integral of AT varied during twitch contractions: when the muscles were made slack 100 ms after stimulation MVo2/integral of AT was 389 +/- 51 (SE) (nl of O2/mg of dry muscle)/(N of active tension/mm2.s of active tension). This value was 94 +/- 7 at peak active tension and was constant thereafter. There was a continuous increase in cumulative MVo2 as integral of AT increased; before integral of AT began, MVo2 was 0.41 +/- 0.04 (nl of O2/mg)/contraction at Lmax and 0.22 +/- 0.04 at a slack length; at peak isometric tension MVo2 was 1.84 +/- 0.19; for a complete contraction MVo2 was 2.89 +/- 0.25. These data support two concepts 1) activation energy is small and dependent on initial length and tension; and 2) integral of AT is variably energy dependent throughout the entire isometric twitch contraction.
Determination of frequency response from step response: application to fluid-filled catheters
Authors: Glantz S. A. , Tyberg J. V.
Published: December 2017

The performance of a fluid-filled catheter can be described by reporting its undamped natural frequency and damping ratio. These parameters can be measured by subjecting the catheter to sinusoidally varying pressures at a wide variety of frequencies to obtain the frequency response. They can also be computed from the response to a step change in pressure, which is often easier to produce. This paper derives the required equations and includes a graph which permits one to look up the undamped natural frequency after measuring the period and decay rate of the oscillation following a step change in pressure.
Carotid sinus reflex function in the alloxan diabetic rabbit
Authors: Matisoff D. N. , Lee J. C. , Downing S. E.
Published: December 2017

Baroreflex function was studied in three groups of adult rabbits. Seven animals were given alloxan (100-200 mg/kg) and became diabetic (group D) with mean blood sugar values of 348 +/- 30 mg/dl. Eight animals were given alloxan, but did not develop significant hyperglycemia (135 mg/dl) (group A). Nine controls (group C) were also studied (glucose, 101 mg/dl). All animals were anesthetized with pentobarbital (30 mg/kg). Blood pressure (BP) and heart rate (HR) responses to bilateral carotid occlusion (BCO) were measured before and after depressor nerve sectioning (DNx) and sinus nerve sectioning (SNx). Before sectioning, BCO caused a rise in BP of 30 +/- 4 mmHg in group C. 35 +/- 3 in group A, and 36 +/- 4 in group D. HR increased about 13 beats/min in each group. After DNx, resting BP increased in group C from 97 to 104 mmHg (P less than 0.005), but no change occurred in the other groups. Responses to BCO were significantly but similarly enhanced in all groups after DNx. HR did not increase in group D. Resting BP increased after SNx only in the controls (group C). Differences in BP elevation with BCO before and after SNx ("pure" reflex response) were identical, averaging about 35 mmHg. Thus, no alteration of BP or HR responses to BCO was identified in early alloxan diabetes. However, resting tone in the buffer nerves may have been less.
Effects of sympathetic nerves on cerebral blood flow in awake dogs
Authors: Marcus M. L. , Heistad D. D.
Published: December 2017

Although cerebral blood vessels are densely innervated by sympathetic nerve fibers, the functional significance of the nerves is controversial. Because previous studies have been primarily performed in anesthetized animals, it is possible that failure to observe prominent neural control of the cerebral circulation was secondary to anesthetic-induced depression of the sympathetic nervous system. Therefore, we studied sympathetic control of the cerebral circulation in 11 awake chronically instrumented dogs. Total and regional cerebral blood flow was measured with 15-micrometer microspheres at control blood pressure and during three levels of progressive hemorrhagic hypotension. Sympathetic nerves had only a small effect (11% decrease; P less than 0.05) on flow to the cerebrum during moderate hypotension (mean arterial pressure 49 +/- 2 mmHg). Also, during severe hypotension, there was a bilateral redistribution of brain blood flow that tended to preserve flow to the medulla. Although these studies suggest that sympathetic nerves have a definite constrictor effect on cerebral vessels, the data support the concept that the functional importance of sympathetic nerves to cerebral vessels is limited.
Cardiovascular actions of beta-phenylethylamine
Authors: Liang C. S. , Sprecher D.
Published: December 2017

beta-Phenylethylamine increased mean aortic blood pressure, total peripheral vascular resistance, left ventricular dP/dt, and (dP/dt)/P in chloralose-anesthetized dogs. Pretreatment with phentolamine reduced the increases in aortic blood pressure and total peripheral vascular resistance produced by beta-phenylethylamine, whereas, the effects of beta-phenylethylamine on left ventricular dP/dt and (dP/dt)/P were abolished by propranolol. beta-Phenylethylamine pretreatment, but increased both after phentolamine pretreatment. Furthermore, both the cardiac and vascular effects of beta-phenylethylamine were abolished by desipramine. These results indicate that beta-phenylethylamine exerts both positive inotropic and vasoconstrictory effects, probably by releasing endogenous norepinephrine from the adrenergic nerve endings.
Morphological and physiological correlation of bradykinin-induced macromolecular efflux
Authors: Svensjo E. , Arfors K. E. , Raymond R. M. , Grega G. J.
Published: December 2017

Bradykinin applied topically for 4 min produced marked dose-related increases in the number of fluorescent dextran (mol wt 145,000) vascular leakage sites exclusively from small postcapillary venules--evidence for an increase in macromolecular permeability. The increase in macromolecular permeability was short-lived, making repeated applications possible. The number of bradykinin-induced venular fluorescent dextran leakage sites could be greatly reduced by the simultaneous topical application of isoproterenol, and this antagonism of the increase in macromolecular permeability could be prevented by pretreatment with propranolol. The topical application of papaverine failed to antagonize the increase in the number of venular leakage sites of fluorescent dextran by bradykinin. A continuous 90-min superfusion of bradykinin elicited an initial marked increase in the number of fluorescent dextran venular leakage sites, which then waned after 20-30 min, returning to near control despite the continued superfusion with bradykinin. In canine forelimbs the bradykinin-induced increase in protein efflux, total protein transport, and lymph flow also peaked in approximately 30 min and then waned markedly despite continued local intra-arterial infusions of this agent for prolonged periods. The morphological data from the cheek pouch agrees well with the physiological data from the forelimb, suggesting that an increase in protein efflux in the canine forelimb could be readily explained by an increase in the number of large pores.
Digoxin-norepinephrine response and calcium blocker effects in vascular smooth muscle
Authors: Flaim S. F. , DiPette D. J.
Published: December 2017

The mechanism of potentiation by digoxin of the response of vascular smooth muscle to norepinephrine was investigated in 5-cm intact segments of rabbit carotid artery. Segments were mounted in a chamber and perfused at constant pressure while flow and upstream and downstream pressures were recorded and resistance was calculated. Each vessel was perfused with a submaximal vasoconstricting concentration of norepinephrine (6 x 10(-6)M) alone, in the presence of digoxin (6 x 10(-5)M), and during exposure to both digoxin and one of the following calcium antagonists: lanthanum chloride (5 x 10(-4)M procaine hydrochloride (5 x 10(-3)M), or verapamil (5 x 10(-5)M). Digoxin potentiated the response to norepinephrine alone by 20% (P less than 0.01), to norepinephrine plus lanthanum chloride by 10% (P less than 0.001), and to norepinephrine plus procaine hydrochloride by 17% (P less than 0.001). Digoxin did not potentiate the norepinephrine response in the presence of verapamil. These data suggest that the mechanism of digoxin potentiation of the norepinephrine response in vascular smooth muscle may involve an alteration in a cellular calcium sequestration or release process. The potential cellular sites that may contribute to this phenomenon are discussed.
Extracorporeal circulation system for coronary artery perfusion in the closed-chest dog
Authors: Kroll K. , Hendriks F. F. , Schipperheyn J. J.
Published: December 2017

An adjustable constant-flow coronary artery perfusion system has been developed for use in the anesthetized closed-chest dog. Coronary flow and perfusion pressure measurements are obtained over the entire autoregulatory range. Coronary flow was briefly diverted to a bypass cannula and then returned to its original level. Coronary vasodilatation resulted in a fall of perfusion pressure below its preocclusion value, but recovery of vascular tone was complete in about twice the time required during unrestricted reactive hyperemia. It is concluded that no flow debt repayment is required for the restoration of vascular tone after brief occlusions. In the measurements made with this system, intramyocardial pressure distribution is not influenced by thoracotomy, pericardotomy, or positive-pressure respiration, and surgical trauma is minimal.
Pulmonary and systemic vascular responses of perinatal goats to prostaglandins E1 and E2
Authors: Cassin S. , Tyler T. , Leffler C. , Wallis R.
Published: December 2017

Effects of prostaglandins of the E series and their metabolites on pulmonary and systemic circulations of newborn and exteriorized fetal goats (anesthetized with chloralose) were evaluated in situ using an isolated perfused left lung lobe preparation. Prostaglandin E1 (PGE1) and, to a lesser extent, prostaglandin E2 (PGE2) infusions resulted in decreases of pulmonary vascular resistance (PVR) of fetal and neonatal goats. Infusions of PGE1 or PGE2 (less than 2 microgram.kg-1.min-1 for 1 min) directly into left pulmonary arterial blood did not affect systemic arterial pressure (SAP). Infusions of PGEs (greater than 2 microgram.kg-1.min-1 for 1 min) resulted in decreases in SAP and heart rate. The dose-response characteristics of the pulmonary circulation in response to PGE1 and PGE2 were not different in fetal and newborn goats. Fetal asphyxia did not alter the dose-response characteristics of pulmonary circulation in response to PGE1. Metabolites (15-keto) of PGE1 and PGE2 had no effect upon PVR or SAP of perinatal goats. These results demonstrate in perinatal mammals 1) vasodilator action of PGE1 and PGE2 on the pulmonary and systemic circulations, and 2) catabolism by the lungs of these prostaglandins.
Depressed responsiveness of the carotid sinus reflex in conscious newborn animals
Authors: Vatner S. F. , Manders W. T.
Published: December 2017

The responsiveness of the carotid sinus reflex was evaluated by comparing the effects of bilateral carotid occlusion (BCO) in conscious adult dogs and puppies on measurements of arterial pressure, cardiac output, heart rate, and calculations of total peripheral resistance (TPR). In eight adult dogs, BCO increased mean arterial pressure by 57 +/- 6%, TPR by 48 +/- 5%, and heart rate by 45 +/- 15%. In puppies, BCO induced smaller increases (P less than 0.05) in mean arterial pressure (30 +/- 5%) and TPR (29 +/- 4%), while heart rate did not change. After elimination of opposing vagal and aortic baroreceptor reflexes, the differences in responses to BCO of mean arterial pressure and TPR between adults and newborns were even greater. Thus, the carotid baroreceptor reflex appears to be depressed in the newborn when compared with the fully developed reflex in the normal, conscious adult.
External assessment of myocardial metabolism with [11C]palmitate in rabbit hearts
Authors: Klein M. S. , Goldstein R. A. , Welch M. J. , Sobel B. E.
Published: December 2017

To determine whether the rate of fatty acid utilization, reflecting myocardial oxygen consumption under steady-state conditions, can be assessed noninvasively, we assayed positron emission from [11C]palmitate (100 muCi) in isolated rabbit hearts and after intra-atrial injection in vivo. In 11 isolated hearts, clearance of 11C-radioactivity during a monoexponential portion of residue detection curves correlated with tension-time index (TTI)(r = 0.86) and peak dP/dt (r = 0.89). Among 9 hearts prelabeled with [14C]palmitate, 14CO2 production from neutral lipid stores correlated with TTI (r = 0.83). In vivo the decline of 11C-radioactivity was 1st order and constant when physiological conditions were maintained constant (slope of the semilog plot = 0.099 +/- 0.002 (SE) in counts/min) (n = 2 animals, 7 injections). Decline of activity changed predictably when oxygen requirements were increased by administration of methoxamine. Thus, residue detection of [11C]palmitate 1) permits external assessment of global myocardial metabolism in vitro, and 2) reflects effects of interventions that alter the rate of substrate utilization in vivo, and should, therefore, permit comparison of rates of regional myocardial metabolism in patients with detection of radioactivity by positron-emission transaxial tomography.
Influence of volume dilution, lactate, phosphate, and calcium on mitochondrial functions
Authors: Mukherjee A. , Wong T. M. , Templeton G. , Buja L. M. , Willerson J. T.
Published: December 2017

Oxidative phosphorylation of isolated canine myocardial mitochondria has been evaluated after exposure to different concentrations of phosphate (5--50 mM), lactate ion in excess (5--40 mM, pH 7.4), calcium (50--270 nmol/mg protein), to lactic acidosis (pH 6.3), and to mitochondrial protein dilution (in vitro volume expansion) for 10 min to 8 h. The influence of phosphate and lactate ion addition, lactic acidosis, and in vitro volume expansion on mitochondrial function were studied in the isolation medium (0.18 M KCl, 0.5% BSA (bovine serum albumin), with or without Tris-EDTA, pH 7.4) prior to evaluation of mitochondrial function in the assay medium (0.25 M sucrose, 10 mM Tris-HCl, and 10 mM inorganic phosphate, pH 7.4). The effect of calcium addition was assessed in the assay medium. The results of these studies demonstrate that each of these interventions detrimentally alters mitochondrial oxidative phosphorylative ability. The most severe mitochondrial functional impairment resulted from phosphate or calcium addition. The detrimental effect of phosphate and in vitro volume expansion was partially corrected by the addition of cytochrome c.
Electrocardiographic changes after bilateral carotid sinus denervation in the rat
Authors: Baur H. R. , Pierach C. A.
Published: December 2017

The effect of bilateral carotid sinus denervation (CSD) on the ECG and on the monophasic ventricular action potential (MAP) was studied in 28 and 4 rats, respectively. After CSD, T wave changes, similar to those seen in man after carotid endarterectomy, were observed and mean Q-T prolongations of 19 ms were recorded (P less than 0.001). Mean MAP increased by 10 ms (P less than 0.02). P-QRS and heart rate remained stable. Propranolol, 10 mg/kg iv, before CSD and 10 mg.kg-1.day-1 iv for 2 days prevented all ECG abnormalities. Atropine, 1 mg/kg iv, before CSD and 2.5 mg.kg-1.day-1 iv for 2 days had no effect. Isoproterenol, 0.02-0.06 microgram iv, after CSD produced further lengthening of the MAP and Q-T interval. Blood gases and electrolytes remained unchanged, and cardiac histology was unremarkable. These results suggest that CSD produces alterations in cardiac sympathetic activity in the rat leading to MAP and Q-T prolongations and to changes in the T wave form. Similar mechanisms may be operative after carotid endarterectomy in man.
Preferential streaming of ductus venosus blood to the brain and heart in fetal lambs
Authors: Edelstone D. I. , Rudolph A. M.
Published: December 2017

In 16 chronically prepared fetal lambs we compared the systemic distribution of ductus venosus blood flow with that of abdominal inferior vena caval blood by simultaneously injecting microspheres labeled with different radionuclides into an umbilical vein and into the abdominal inferior vena cava. A significantly greater proportion of ductus venosus blood flow than of abdominal inferior vena caval blood flow supplied the brain, heart, and upper body; this resulted from streaming of ductus venosus blood flow within the thoracic inferior vena cava with preferential direction of that blood flow through the foramen ovale. Blood flows to upper and lower body structures and placenta calculated from umbilical venous microsphere injections and reference arterial blood samples did not differ from those computed fromabdominal inferior vena caval injections and reference samples. Thus, despite streamline blood flow within the fetal thoracic inferior vena cava, organ blood flows can be accurately measured with either an umbilical venous or an abdominal inferior vena caval injection of microspheres when either is combined with the appropriate reference arterial blood samples.
Transmural distribution of myocardial adenosine content during coronary constriction
Authors: Foley Duane H. , Miller Wayne L. , Rubio Rafael , Berne Robert M.
Published: December 2017

Page H833: Duane H. Foley, Wayne L. Miller, Rafael Rubio, and Robert M. Berne. “Transmural distribution of myocardial adenosine content during coronary constriction.”; Page H833: in line 16 of the abstract the value for adenosine content of the inner segment should be 0.041 ± 0.007. Page H836: the last sentence of the first paragraph should be: There was also a higher level of creatine phosphate in the outer segment than in the middle segment during coronary artery constriction, but this difference was not statistically significant.
Active vascular smooth muscle tone and venous membrane potentials during hemorrhage
Authors: Stekiel W. J. , Willems W. J. , Harder D. R. , Lombard J. H.
Published: December 2017

To clarify mechanisms leading to failure of compensatory vascular tone in splanchnic blood vessels during prolonged hypotensive stress, anesthetized rats were maintained at a constant mean arterial pressure of 35 mmHg by hemorrhage into an external reservoir until 40% autoinfusion of maximum bled volume. In vivo intracellular membrane potentials (Em) of small intestinal mesenteric veins (300--500 micrometers) were measured before and during the compensatory (bleedout) and decompensatory (autinfusion) phases of the hypotensive period to assess the state of vascular smooth muscle (VSM) excitation. During the compensatory phase, Em decreased from -41 +/- 1 mV (prehemorrhage) to -31 +/- 2 mV, and small venous pressures decreased significantly. The onset of cardiovascular decompensation was associated with hyperpolarization (-53 +/- 3 mV), vasodilation, and return of venous pressure to control levels. Although direct electrical stimulation of the VSM and norepinephrine suffusion still produced constriction late in the hypotensive period, venoconstrictor responses to perivascular nerve stimulation failed progressively. This study indicates that failure of adrenergic neuromuscular transmission contributes significantly to the loss of compensatory VSM tone during hemorrhage.
Systolic quick releases of nonexcised blood-perfused canine papillary muscle
Authors: Suga H.
Published: December 2017

Systolic stiffness was studied in five coronary perfused twitching papillary muscles of canine right ventricles. The muscles beat at regular sinus rhythms at 37 degrees C. They were shortened quickly at about 10 muscle lengths/s in the middle of isometric contractions. Systolic force decreased exponentially with the shortening in the force-length diagram. Relating Lagrangian stress (sigma) and strain change (delta epsilon) relative to isometric length calculated from the force-length relationship curve during quick release, I found a linear relationship between ln sigma and delta epsilon. This indicates that the systolic stres-strain relationship of the canine papillary muscle can be approximated by an exponential curve, sigma = sigma m exp(k . delta epsilon), where sigma m = isometric stress at the onset of quick release. The mean +/- SE of the stiffness constant k was calculated to be 55 +/- 8 (dimensionless). These k values are greater than those of excised cat papillary muscles at 37 degrees C reported in literature. This difference in k values may be ascribed to the difference in the mechanical property of the uncut pinned end of the present preparation as opposed to the cut clamped end of the conventional preparation, although the canine and feline papillary muscles may simply have the different k values.
Redox transitions in mitochondria of cat cerebral cortex with seizures and hemorrhagic hypotension
Authors: Hempel F. G. , Kariman K. , Saltzman H. A.
Published: December 2017

Fluorometry and dual-wave-length spectrophotometry were used to detect transitory shifts in the redox state of mitochondrial NADH and cytochrome aa3 in the exposed cerebral cortex of anesthetized paralyzed cats as seizures were induced with pentylenetetrazol. In normotensive animals, NADH and cytochrome aa3 oxidation accompany the seizures, but when the mean arterial pressure (MAP) is reduced to 40.2 +/- 1.1% of the base line by hemorrhaging, the NADH fluorescence response converts to a biphasic oxidation-reduction sequence. In extreme hypotension (MAP lowered to an average of 28%), only NAD reduction transients are observed with seizures, and cytochrome aa3 is oxidized irrespective of the low MAP. Our data show that a reversible perfusion impairment, perhaps inhomogeneous in its distribution, appears in the cortex at the 40% MAP level and modifies electron flux in the respiratory chain between NADH and cytochrome aa3, and uniform oxygen insufficiency is an unlikely cause for the reversal of NADH oxidation toward reduction during seizures under hypovolemic conditions.
Ventilation-induced release of prostaglandinlike material from fetal lungs
Authors: Leffler C. W. , Hessler J. R. , Terragno N. A.
Published: December 2017

Effects of indomethacin upon ventilation-induced pulmonary vasodilation of fetal goats suggest prostaglandins may be important in perinatal transition of the pulmonary circulation. To further test this hypothesis, left pulmonary arterial and pulmonary venous samples were taken before and after ventilation from anesthetized exteriorized fetal (near-term) goats and sheep utilizing, in different animals, either constant or variable left pulmonary blood flow. Characterization and quantification of prostaglandinlike compounds were accomplished utilizing extraction of acidic lipids, thin-layer chromatography, and tissue cascade bracket bioassay. The primary vascular prostaglandinlike material in both fetal and neonatal animals was PGI2-like (PGI). On passage through the fetal lung, concentrations of prostaglandin I- and E-like compounds decreased considerably. After ventilation and ligation of the umbilical cord, concentrations of both PGE2-like (PGE) and PGI in inferior vena caval blood fell, and there was net production of PGI by the newly ventilated lung. Production of PGI2 by newly ventilated lung could provide an important vasodilator influence that would establish and maintain the low pulmonary vascular resistance that is necessary for successful adaptation to extrauterine life.
Effects of coronary artery occlusion on thoracic spinal neurons receiving viscerosomatic inputs
Authors: Foreman R. D. , Ohata C. A.
Published: December 2017

Action potentials of single cells in the gray matter of the T2 to T4 spinal segments of chloralose-anesthetized cats were recorded during occlusion of the anterior descending branch of the left coronary artery. Only cells responding both to visceral and somatic afferent inputs were examined. In 53% of the cells the discharge frequency was unaffected by coronary artery occlusion (CAO). The remaining 47% could be classified by four response patterns: 1) in 18% frequency increased immediately following the onset of CAO; 2) in 22%, frequency increased 13.6 +/- 3.3 (SE) s after CAO and the increased frequency usually was associated with changes in the configuration of the electrocardiogram; 3) in 3%, frequency increased at the onset of CAO and then increased more approximately 11 s later; 4) in 4%, inhibition of spontaneous activity occurred during CAO. A noxious pinch applied to the somatic receptive field maximally excited 94% and inhibited 6% of the cells. Since viscerosomatic convergence provides a basis for referred pain, these cells could potentially be involved with transmission of nociceptive information to regions of the brain that integrate pain sensations.
Oxygen and vascular smooth muscle contraction revisited
Authors: Chang A. E. , Detar R.
Published: December 2017

The relationship between oxygen pressure measured in a tissue bath (PBO2) and the contractile tension produced by an agonist (contractile responsiveness) was studied in a series of experiments using helical strips cut from thoracic aortas, femoral and deep femoral arteries, and small arteries taken from red and white skeletal muscle of the rabbit. The wall thicknesses of these samples ranged from 200 micron for aortas down to approximately 20 micron for the smallest skeletal muscle arteries. Contractile responsiveness of all samples became progressively depressed when PBO2 was reduced stepwise. The depression produced in the large thick-walled samples occurred at higher PBO2 levels than that produced in the small thin-walled samples. Responsiveness of all of the artery samples was depressed by hypoxia more at low than at high levels of stimulation. In a second series of experiments PO2 at the surface of artery samples (PSO2) was measured using an oxygen-sensitive microelectrode. These measurements in conjunction with calculations of the PO2 within the arterial wall (PWO2) indicated that contractile responsiveness of both large and small artery samples became depressed when PWO2 fell below a lowest-value estimate of 50 Torr. From these findings it is concluded that 1) the sensitivity of vascular smooth muscle cells to hypoxia is similar for large and small arteries; 2) this sensitivity occurs in a range of PO2 that is physiologic for resistance vessels in situ; and 3) this sensitivity to hypoxia cannot be explained by an anoxic core hypothesis and may or may not involve restricted energy metabolism.
Impaired neurogenic control of renal vasculature in renal hypertensive rats
Authors: Fink G. D. , Brody M. J.
Published: December 2017

Renal hypertension is accompanied by alterations in the renal sympathetic innervation involving reduced catecholamine content and histofluorescence. Because the renal nerves are a potentially important factor in the pathogenesis of renal hypertension, the functional significance of renal catecholamine depletion was evaluated. In rats with either one-kidney or two-kidney Grollman hypertension, renal vascular responses to renal nerve stimulation and intraarterial administration of vasoactive hormones were assessed in vivo at various times following renal compression. In the wrapped kidney of one-kidney hypertensive rats, vasoconstrictor responses to renal nerve stimulation were consistently reduced, compared to responses in uninephrectomized control rats, whereas responses to intra-arterial norepinephrine were slightly greater in kidneys from hypertensive animals. In the untouched kidney of rats with two-kidney renal hypertension, vasoconstrictor responses to nerve stimulation were also substantially reduced, although those to norepinephrine were only slightly altered. It was concluded that catecholamine depletion in the kidneys of renal hypertensive animals reflects a diminished capacity of renal sympathetic nerve impulses to produce vasoconstriction. Reduced neurogenic renal vascular resistance may serve to attenuate the rise in blood pressure in renal hypertension.
Changes in pulmonary structure and function induced by monocrotaline intoxication
Authors: Ghodsi F. , Will J. A.
Published: December 2017

Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to be toxic to a variety of domestic and laboratory animals and to humans. Major pathological effects induced by monocrotaline poisoning include hepatic cirrhosis and megalocytosis, venocclusive disease, pulmonary hypertension, and right ventricular hypertrophy. The present investigation explored the structural and functional relationships that exist between pulmonary artery pressure, small pulmonary artery medial thickness, and right ventricular hypertrophy. The results of this physiological and histological study on monocrotaline-intoxicated rats has demonstrated that there is a positive correlation between progressive pulmonary hypertension, thickening of the medical wall of small pulmonary vessels, and right ventricular hypertrophy as a function of time.
Effect of pacing on oxygen supply-to-consumption ratio in ischemic myocardium
Authors: Grover G. J. , Weiss H. R.
Published: December 2017

This study was performed to determine if the partially occluded myocardium could maintain its O2 supply-to-consumption ratio during atrial pacing. In 14 open-chest anesthetized dogs, the left anterior descending coronary artery was occluded to 50% of base-line flow, and in half of the dogs the hearts were paced to 50% above base-line heart rate. Blood flows were determined by use of microspheres before and after occlusion, and O2 supply-consumption variables were determined by use of microspectrophotometry. After occlusion in control and paced groups, blood flow was depressed in the ischemic region compared with the nonischemic region. In paced animals, blood flows in all regions were significantly higher compared with their respective values in nonpaced animals. After pacing, mean O2 consumption was 34% higher (53% in the occluded region) compared with control animals. The O2 supply-to-consumption ratio was similar in the occluded region of paced animals compared with the same region in controls. This ratio was lower in ischemic regions of both groups compared with their respective nonischemic regions. This indicates that, despite a reduced O2 supply-to-consumption ratio in the ischemic area, an unutilized reserve of flow exists.
Measurement of calcium influx in tethered rings of rabbit aorta under tension
Authors: Gleason M. M. , Ratz P. H. , Flaim S. F.
Published: December 2017

Calcium (Ca) influx in vascular smooth muscle is routinely measured in untethered preparations not under passive stretch, and Ca influx data are correlated with data for steady-state isometric tension obtained under parallel conditions from tethered preparations under passive stretch. The validity of this method was tested by simultaneous measurement of Ca influx and tension in tethered rings of rabbit thoracic aorta. Ca influx (45Ca 3-min pulse) and tension were measured at 3 and 30 min after norepinephrine (NE) or KCl and under control (no agonist) conditions. Active tension was significantly altered by variations in passive tension. Ca influx was unaffected by passive tension under control, NE, or KCl conditions, and results were similar at 3 and 30 min. The results confirm the validity of correlating Ca influx data from untethered rings with steady-state contractile response data obtained from tethered rings under similar experimental conditions.
Microvascular pressure, surface area, and permeability in isolated hindquarters of SHR
Authors: Korthuis R. J. , Kerr C. R. , Townsley M. I. , Taylor A. E.
Published: December 2017

The transvascular escape rate (TER) of labeled albumin is reported to increase in essential hypertension. However, the mechanism for this augmented rate of protein efflux is uncertain and may be related to increased microvascular permeability, surface area, and/or pressure. To determine the possible contributions of these mechanisms to increased TER of protein, the osmotic reflection coefficient for total plasma protein, capillary filtration coefficient, and effective capillary pressure were estimated in isolated hindquarters of age-matched (12-13 wk) spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WR) rats. Estimates of the reflection and filtration coefficients were not significantly different in SHR, WKY, and WR. However, capillary pressure was significantly greater in SHR than in normotensive controls. These results indicate that 1) skeletal muscle microvascular permeability and surface area are similar in SHR, WKY, and WR; 2) effective capillary pressure is greater in SHR than WKY or WR; and 3) if TER for protein is elevated in hypertensive skeletal muscle, the primary mechanism for this process may be increased convective transport of protein secondary to elevated microvascular hydrostatic pressure.
Age-related changes of action potential plateau shape in isolated human atrial fibers
Authors: Escande D. , Loisance D. , Planche C. , Coraboeuf E.
Published: December 2017

Because the frequency of atrial arrhythmia increases dramatically with age in humans, we investigated age-related changes of cellular electrical activity in human atrial fibers, utilizing standard microelectrode techniques. Twenty-four atrial samples, uniformly exhibiting fast responses, were selected. Patients were in two different age groups: 10.0 +/- 7.0 mo and 54.4 +/- 9.7 yr. Although mean maximum diastolic electrical potential did not significantly differ, the two groups showed marked dissimilarities in action potential (AP) shape. Adult-type APs always exhibited an initial notch followed by a low-level prolonged plateau, whereas APs of the young were more triangular and had a short plateau approaching zero potential. 4-Aminopyridine (0.5 mM) markedly increased the level of the adult AP plateau without suppressing the initial notch, which disappeared after further addition of caffeine (10 mM). The simultaneous action of the two drugs changed an adult-type AP into a young type. The drug effects were much less marked in young atria. Our results suggest that an age-related increase in transient outward currents can account for the differences in plateau shape described. Moreover, age-related differences in plateau configuration in response to a period of rest suggest a faster repriming kinetic of these currents in adults.