bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Binding, Release, and Metabolism of Norepinephrine in Normal and Transplanted Dog Hearts
Authors: POTTER LINCOLN T. , COOPER THEODORE , WILLMAN VALLEE L. , WOLFE DAVID E.
Published: June 2012

The ability of normal and transplanted dog hearts to make, bind, store, and metabolize norepinephrine was studied. Transplanted hearts were used in order to assess the effects of adrenergic denervation. Normal hearts bound large quantities of administered C

14

-dopamine and synthesized considerable quantities of norepinephrine in both the atria and ventricles. Isolated perfused normal hearts steadily removed about 56% of infused
dl
-H

3

-norepinephrine; a binding mechanism was the major means of inactivation of the amine. Uptake of radioactive norepinephrine was greater in the ventricles than in the atria because they received more of the amine, and the turnover rate of the labeled amine was also highest in the ventricles. Subcellular fractionation of the bound amine demonstrated that it was localized in particles of microsomal size; radioautographic studies demonstrated the presence of H

3

-norepinephrine only in association with nerves. About 57% of the H

3

-norepinephrine released from normal hearts was metabolized, primarily by O-methylation.

After autotransplantation, and degeneration of postganglionic sympathetic nerves, the average catecholamine content of the hearts fell to 1.2% of normal, C

14

-dopamine uptake and formation of norepinephrine were reduced to a few per cent of normal, and the uptake and retention of H

3

-norepinephrine was 6.1% of normal under the conditions used. Binding of norepinephrine to unknown sites in the transplanted tissue served temporarily as an important mechanism of inactivation of the amine, but this norepinephrine was very rapidly released and nearly 85% metabolized, again predominantly by O-methylation. The fine structure of the transplanted tissues was barely distinguishable from that of normal hearts by electron microscopy. In vitro assays of catechol-O-methyltransferase and monoamine oxidase showed little change in activity upon adrenergic denervation. These results demonstrate the importance of the adrenergic innervation of the heart for the normal synthesis, storage and inactivation of norepinephrine.
Biphasic Action of Acetylcholine on Ventricular Myocardium
Authors: HOLLENBERG MILTON , CARRIERE SERGE , BARGER A. CLIFFORD
Published: June 2012

Intracoronary infusions of acetylcholine have demonstrated two actions of this neurohumoral agent on ventricular myocardium: 1) an antagonism to the more forceful contractions evoked by adrenergic stimuli (sympathomimetic drugs or stellate stimulation), and 2) a sympathomimetic or positive inotropic effect (? release of a positive inotropic substance from the myocardium). The increased contractility ("rebound") was observed only after the infusion of acetylcholine was stopped; in the presence of physostigmine the "rebound" was absent. Atropine blocked both the cardio-inhibitory and cardio-excitatory actions of acetylcholine. Failure of hexamethonium and bretylium to block the "rebound" suggests that acetylcholine acts at a peripheral site. The possible catecholamine nature of the agent could not be established by direct analysis of coronary venous blood, by the use of an adrenergic beta receptor blocking agent or by pretreatment of the animals with reserpine; neither drug blocked the "rebound."
Effect of Intravascular Isotope Content on the Isotopic Determination of Coronary Collateral Blood Flow
Authors: BLOOR COLIN M. , ROBERTS LATHROP E.
Published: June 2012

Simultaneous determinations of myocardial blood volume (using I

131

-PVP), myocardial blood flow (using H
3
2
O), and coronary collateral myocardial blood flow (using retrograde flow) were made in dogs after left circumflex artery ligation. Intravascular H
3
2
O content at the end of the H
3
2
O infusion was calculated as the product of myocardial blood volume and the final arterial H
3
2
O concentration.

When correction is made for intravascular H
3
2
O content the resulting flow measured by H
3
2
O is nearly identical to the retrograde flow. These results indicate that radioactive isotopes can be used to measure blood flow if correction is made for the intravascular isotope content. The identity of corrected H
3
2
O flows with retrograde flows also indicates the applicability of isotopic methods for the measurement of coronary collateral blood flow.
Action of Lobeline on Pulmonary Artery Mechanoreceptors of the Cat
Authors: BEVAN JOHN A. , KINNISON GERALD L.
Published: June 2012

1. The effects of lobeline (15 to 45 µg/kg) and of local changes of pulmonary artery pressure on the afferent activity of single neurone preparations of pulmonary artery mechanoreceptors have been studied in the intact cat. Pulmonary artery pressure was monitored via a double lumen balloon catheter passed into the pulmonary artery.

2. Pulmonary artery mechanoreceptors were distinguished from systemic mechanoreceptors by applying two simple tests to all mechanoreceptors found by random selection of single fibers from the right cervical vagus. The afferent activity of pulmonary mechanoreceptors closely followed induced changes of pulmonary artery pressure, whereas other arterial mechanoreceptors did not. Pulmonary artery pressure was increased by the rapid injection of 2 ml dextran into the right atrium and was reduced by inflation of the intravascular balloon.

3. In the absence of a rise in pulmonary artery pressure, lobeline increased the afferent activity in two phases. The early response, which was seen in 17 of the 18 fibers studied, occurred within one to two seconds after injection and was characteristically a variable and moderate response. This effect is caused probably by the diffusion of lobeline to sensory endings within the pulmonary artery wall. The delayed response occurred about eight to ten seconds later. The activity of afferent fibers was intensified conspicuously and frequencies up to 300/sec were recorded. It is probable that this is due to the action of lobeline carried by the vasa vasorum to the intramural receptors.

4. By combining the results following balloon inflation and dextran injection, the relationship between impulses per heart beat and mean pulmonary artery pressure was established for a number of pulmonary artery mechanoreceptors in the intact animal.

5. Pulmonary artery mechanoreceptors were insensitive to doses of veratridine and relatively insensitive to doses of phenyldiguanide which, in the intact cat, produce equivalent reflexogenic responses as lobeline (45 µg/kg).

6. Other intrathoracic sensory endings studied, including atrial and ventricular stretch receptors, Hering-Breuer receptors, and systemic mechanoreceptors, were completely insensitive to the doses of lobeline used in these experiments.

7. These results support earlier experiments which suggested that when lobeline is injected, its reflex effect from the pulmonary vascular bed, namely depression of ventilation, is due to its action on a pressure- or stretch-sensitive area in the region of the bifurcation of the pulmonary artery.
Renal Vein Renin and Juxtaglomerular Activity in Sodium-Depleted Subjects
Authors: AJZEN HORACIO , SIMMONS JOHN L. , WOODS JAMES W.
Published: June 2012

Ten patients requiring surgery for renal cysts or calculi and having no evidence of secondary hyperaldosteronism were divided, as volunteers for special study, into experimental and control groups. After base line studies, the experimental group was given a diet containing 87 mEq of sodium and 1.0 g of chlorothiazide daily for ten days. Control subjects ate a normal diet. At operation, samples of peripheral and renal venous blood were obtained for measurement of renin activity and renal biopsy was taken for determination of the juxtaglomerular index.

Increased renin in renal venous plasma and hypergranularity of the juxtaglomerular apparatus were found in sodium-depleted subjects but not in control subjects. These findings confirm results previously found in animals.
Contribution of Intravascular Receptors to the Renal Responses Following Intravascular Volume Expansion
Authors: GILMORE JOSEPH P. , WEISFELDT MYRON L.
Published: June 2012

The renal responses to acute isotonic, isooncotic intravascular volume expansion have been studied in the normal dog, the vagotomized dog, and the dog with carotid sinus denervation. It was observed that either vagotomy or carotid sinus denervation attenuates significantly the diuretic response to intravascular volume expansion without influencing significantly the natriuretic response. The results indicated that carotid sinus receptors and receptors which have afferent fibers in the vagus nerves contribute substantially to the control of plasma volume by a mechanism which influences free water excretion. The receptors of the low pressure system probably play a primary role under conditions of hypervolemia while receptors of the high pressure system appear to play a primary role under conditions of hypovolemia.
Increased Pulmonary Vascular Resistance in the Dependent Zone of the Isolated Dog Lung Caused by Perivascular Edema
Authors: WEST JOHN B. , DOLLERY COLIN T. , HEARD BRIAN E.
Published: June 2012

Measurements of the distribution of blood flow in an isolated dog lung made with radioactive xenon showed a great increase in vascular resistance in the dependent zone of the lung in the presence of a raised pulmonary venous pressure in some preparations. Evidence that this increased vascular resistance was caused by perivascular edema consisted of the general correlation with interstitial edema, the regional distribution of the effect, the sensitivity to the arteriovenous pressure difference, the effect of certain infusions particularly hypertonic urea, and the demonstration of edema around the small arteries and veins in rapidly frozen sections. The mechanism of the increased resistance is postulated as an interference with the tethering effect of the lung parenchyma which normally holds the vessels open. The possible role of this mechanism in the increased pulmonary vascular resistance of patients with pulmonary venous hypertension is discussed.
Durations of Transmembrane Action Potentials and Functional Refractory Periods of Canine False Tendon and Ventricular Myocardium:
Authors: MOORE E. NEIL , PRESTON JAMES B. , MOE GORDON K.
Published: June 2012

In vitro studies have shown that alterations in the ionic composition of the perfusion fluid, substitution of blood or plasma for Tyrode's solution, time lapse following removal of the cardiac preparation from the animal, and addition of varying amounts of acetylcholine and/or epinephrine, do not change differentially the functional refractory period and action potential duration of false tendon and papillary muscle fibers; false tendon values exceeded those of papillary muscle in all of the above conditions. Cycle length was the only variable found to influence differentially false tendon and papillary muscle functional refractory periods and action potential durations. At very short cycle lengths, produced by premature responses, the functional refractory period and action potential duration of false tendon and papillary muscle cells approached each other. In some experiments the functional refractory periods of premature false tendon responses were less than corresponding values for papillary muscle. The relationship between the action potential durations and functional refractory periods of canine epicardial and endocardial cells was investigated also. It was found that the epicardial cells had a shorter functional refractory period and action potential duration than endocardial units when studied at physiological rates.
Relationship Between Instantaneous Aortic Flow and the Pressure Gradient
Authors: GREENFIELD JOSEPH C. , FRY DONALD L.
Published: June 2012

The relationship between the pressure gradient and the instantaneous blood flow in the descending thoracic aorta was studied in six dogs. Instantaneous flow was calculated from the pressure gradient using the simple analog approach of Fry and the more elaborate calculations of Womersley. The flows computed by either of these techniques were essentially indistinguishable from one another and compared favorably with the "true" flow. The "true" flow at the point of pressure gradient measurement was determined indirectly from the flow signals of two electromagnetic flowmetering systems, one placed upstream and the other downstream from the point of pressure gradient measurement. The probes were placed sufficient distances from the site at which pressure gradients were measured so that the pulsations of the vessel at that site were unaffected by application and removal of the probes. Thus, the vessel was presumed to be in its normal pulsating state. It is concluded, first, that the simpler approach of Fry is the method of choice in large vessels such as the aorta because the results do not differ appreciably from those using the Womersley approach. Second, the favorable comparison of either of the pressure gradient techniques with the "true" flow is strong evidence for the validity of this method and places the theoretical considerations of Womersley and others on a firmer experimental footing than previously.
Reflex Effects of Cephalic Hypoxia, Hypercapnia, and Ischemia Upon Ventricular Contractility
Authors: DEGEEST HILAIRE , LEVY MATTHEW N. , ZIESKE HARRISON , Nelson Geraldine , Rogoff Thomas
Published: June 2012

The effects of brief periods of cephalic hypoxia, hypercapnia, and ischemia upon the contractility of the normally oxygenated ventricular myocardium were studied in an innervated, isovolumetric, canine left ventricle preparation. The majority of responses to cephalic hypoxia were of two types in preparations with vagi and carotid sinus nerves still intact. (a) More frequently, peak left ventricular pressure changed in biphasic fashion, consisting of an initial depression of contractility followed by subsequent augmentation. (b) Less frequently, a monophasic enhancement of contractility appeared. After transection of either the vagi or the carotid sinus nerves, a monophasic facilitation of contractility was usually evoked by cephalic hypoxia. From these data, it was concluded that two opposing influences act simultaneously upon the ventricular myocardium during cephalic hypoxia in preparations with intact vagi and carotid sinus nerves. Central nervous system hypoxia enhances myocardial contractility; its effect is mediated principally via sympathetic pathways. Hypoxia at the level of the carotid chemoreceptors depresses contractility reflexly; the efferent limb of this reflex is mediated chiefly via the vagi. At any moment in time, the effect upon ventricular contractility is the result of these opposing influences.

Cephalic hypercapnia produced effects similar to those of hypoxia. Cephalic ischemia always evoked a marked, positive inotropic effect upon the ventricles.
Optimal Parameters of Electrical Impulses for Defibrillation by Condenser Discharges
Authors: Peleška Bohumil , Blažek Z. , Rábl M. , Sládkovaá E. , Roth Z.
Published: June 2012

The defibrillation threshold for various wave forms of condenser discharge, using capacitors from 4 to 200 µF, has been measured. Condenser discharge alone was used, or condenser discharge 0.25 henry (20 ohms) with an iron core series inductance, or condenser discharge, 0.29 henry (27 ohms) inductance, but without the iron core. Statistical analysis of the results showed that the last of these three circuits gave the lowest threshold voltage values. Optimal parameters of inductance-altered discharges are obtained with values of 24, 32, and 50 µF.

Detailed analysis of the separate physical parameters of the discharge show that optimal pulse duration is 8.5 to 16.6 msec. Further increase of duration does not decrease the voltage or current for threshold shocks, but merely increases the energy delivered. Pulse duration appears to be one of the more important parameters for successful defibrillation, and for this reason, a series inductance is also important.
Vagus Nerves and Baroreceptor Control of Ventricular Performance
Authors: Levy Matthew N. , Ng Manuel , Lipman Ralph I. , Zieske Harrison , Nelson G.
Published: June 2012

In innervated, isovolumetric left ventricle preparations, sudden elevations of pressure in the isolated carotid sinus elicited a 9.5% depression of left ventricular systolic pressure (LVSP). After blockade of sympathetic neuroeffector junctions by bretylium tosylate, equivalent intrasinusal pressure changes evoked a 6.8% reduction of LVSP. This response could be completely abolished by atropine sulfate or by cooling the cervical vagi. Therefore, under the conditions of the present experiments, the vagus nerves mediated a significant fraction of the reflex depression of ventricular performance induced by carotid sinus baroreceptor stimulation. An appreciable elevation of LVSP was produced by atropine and by vagal cooling after blockade of sympathetic junctions. This enhancement of ventricular performance is an indication of a tonic negative inotropic influence of the vagus nerves upon the ventricular myocardium.
Fibrillation Threshold of Premature Ventricular Responses
Authors: Han Jaok , de Jalon Garcia , Moe Gordon K.
Published: June 2012

The degree of temporal dispersion of recovery of excitability of premature ventricular responses, estimated as the range of local refractory periods at various points on the surface of the right ventricle, is greater within a radius of 10 to 15 mm from the stimulated site than at greater distances. The fibrillation threshold of early premature beats is significantly lower than that of responses initiated in fully excitable tissue. The effect of prematurity on the fibrillation threshold is greater at points near the site of origin of the premature response. The observed spatial and temporal relationships suggest that the fibrillation threshold is related inversely to the degree of asymmetry in the excitable field.
Oxygen Consumption of Arterial Smooth Muscle as a Function of Active Tone and Passive Stretch
Authors: Kosan R. L. , Burton Alan C.
Published: June 2012

The mean oxygen consumption of relaxed isolated vascular smooth muscle segments was found to equal 0.61±0.94 SEM µliter/mg wet wt/hr in a medium of buffered Ringer-glucose, and 0.65±0.05 SEM uliter/mg wet wt/hr in a solution of dog plasma. The resting muscle RQ was found to equal 0.99±0.01 SEM in buffered Ringer-glucose solution. When stimulated by addition of epinephrine the muscle segment contracted on the average by 9% of its initial diameter with a corresponding increase of its oxygen consumption by an average of 30% over its relaxed value. It was noticed that with increased initial circumferential stretch of the muscle segment, the amplitude of contraction was much greater when a given amount of catecholamine was added. This increase of sensitivity to catecholamine produced by initial stretch, was accompanied by a parallel increase of oxygen consumption by the contracted muscle. A qualitative correlation between an estimated degree of contraction of arterial muscle and its oxygen consumption was demonstrated. More quantitative correlation will have to depend upon better methods of measuring both the tension developed and the degree of initial stretch.
Cardiovascular and Somatic Reflexes in Experimental Allergic Encephalomyelitis
Authors: Baum Thomas , Rosenthale Marvin E. , Shropshire Allen T. , Datko Louis
Published: June 2012

Experimental allergic encephalomyelitis (EAE) in rats is characterized by flaccid hindlimb paralysis, urinary incontinence and fecal impaction. Somatic and cardiovascular reflexes were studied in these animals. At varying degrees of stretch of the gastrocnemius-soleus-plantaris group of muscles or of the anterior tibial muscle, stimulation of the sciatic nerve increased the isometric tension of these muscles similarly in normal and paralyzed rats. Reflex contraction of the anterior tibial muscle was produced in normal rats by posterior tibial nerve stimulation. This response was completely blocked in paralyzed rats. Stimulation of the central end of the ligated sciatic nerve at various parameters reduced blood pressure. The magnitude of this effect was less in the paralyzed group. Although vasoconstriction in the perfused hindquarters resulting from bilateral stimulation of the cervical vagus was also reduced in paralyzed rats, the response to lumbar sympathetic chain stimulation was the same in both groups. Thus, in EAE the peripheral nerve-muscle elements in blood vessels and the skeletal muscle responded normally but effects requiring the participation of the central nervous system were depressed.
Vascular Impedance of the Femoral Bed
Authors: O'Rourke Michael F. , Taylor Michael G.
Published: June 2012

Pressure/flow relationships in the femoral artery have been expressed as the vascular impedance of the femoral bed. The results obtained were consistent and reproducible under control conditions with irregular as well as with regular heart rates; vasoconstriction and vasodilation caused the changes in vascular impedance predicted from theoretical principles. In a mathematical model similar results were obtained when realistic values of the dimensions and physical properties of the femoral vascular bed were used. Arterial pressure/flow relationships expressed as vascular impedance provide valuable information on the properties of the vascular bed beyond.
Reactivity of the Vessels of Collapsed and Ventilated Lungs to Drugs and Hypoxia
Authors: Barer Gwenda R.
Published: June 2012

1. In anaesthetised cats the left lung was collapsed by obstructing a ventilating tube which had been wedged into the left bronchus. If the cat had been ventilated with oxygen beforehand, the lung became gas-free in one to five minutes.

2. Blood flow to the left lung diminished rapidly as the lung collapsed and in about ten minutes was reduced by about 65%. Pulmonary vascular resistance increased greatly and these changes persisted after denervation of the lungs.

3. Vascular resistance of collapsed lungs could be reduced substantially by several drugs (acetylcholine, small doses of histamine, theophylline ethylenediamine, isopropylnoradrenaline, adrenaline) so that it must depend to some extent on increased vascular tone.

4. Vessels of collapsed lungs constricted when the oxygen saturation of the blood reaching them was reduced. This was demonstrated in vivo both before and after denervation of the lungs and after adrenalectomy and also in isolated perfused lungs. This effect is large enough to account for the changes in the pulmonary circulation which follow collapse of a lung. The time course and magnitude of the pulmonary vasoconstriction which took place during hypoxia were similar in collapsed and ventilated lungs.

5. The effects of a number of naturally occurring vasoconstrictor substances on the pulmonary circulation were compared with the effect of hypoxia. Noradrenaline caused weak but definite vasoconstriction of the pulmonary vessels, in a majority of cats; dopamine and tyramine had a more powerful constrictor effect and 5-hydroxytryptamine a much more powerful effect. Doses of histamine also usually caused pulmonary vasoconstriction.

6. Dibenamine and phenoxybenzamine reduced greatly or abolished the pulmonary vasoconstriction which accompanies hypoxia in collapsed or ventilated lungs. Guanethidine sometimes reduced or abolished it. Dibenamine and phenoxybenzamine reduced pulmonary vascular resistance. Pulmonary vasoconstriction during hypoxia was less frequently observed in cats treated with reserpine than in normal cats.

7. Lysergic acid diethylamide did not alter the pulmonary vasoconstrictor effect of hypoxia in doses which reversed the pulmonary vasoconstrictor action of 5-hydroxytryptamine. Mepyramine did not abolish (but may have sometimes diminished) the effect of hypoxia on the pulmonary vessels, in doses which reversed or abolished the pulmonary vasoconstrictor effect of histamine.
Pulsatile Flow Patterns in Distensible Tubes
Authors: Attinger E. O. , Sugawara H. , Navarro A. , Anné A.
Published: June 2012

Pulsatile flow patterns in polyvinyl tubes were visualized by means of streaming birefringence and compared with those obtained using an electromagnetic flowmeter.

At low flow rates the frequency spectrum of the birefringence pattern is similar to that of volume flow. As the flow rates are progressively increased, irregular eddies appear, particularly during deceleration of flow, first in the central core and later spreading into the peripheral sleeve. They are characterized by a wide frequency spectrum.

The concepts of laminar and turbulent flow are reviewed and evidence is presented which indicates that the power losses associated with the observed eddies are negligible with respect to the losses due to the average flow and its pulsatile components of low frequency.

Flow disturbances observed in the arterial tree appear to be similar in character to those found in the present study. It is unlikely that they can account for significant discrepancies between experimental and theoretically predicted pressure-flow relations.
Failure of D- and L-Thyroxine to Protect Cholesterol and Oil Fed Cockerels Against Coronary Atherogenesis
Authors: Jain Savitri , Pick Ruth , Johnson Philip J. , Katz Louis N.
Published: June 2012

In cockerels, L-thyroxine was significantly more active biologically than an equivalent dose of D-thyroxine, or even four times the dose, as demonstrated by the effects on body weights, organ weights and comb index.

In cockerels fed an atherogenic diet, the plasma cholesterol concentrations in all the thyroxine-treated groups were significantly lower than in the control groups.

No consistent effect of D-thyroxine on thoracic aorta atherosclerosis was observed. However, L-thyroxine had some protective action in the one experiment done.

Despite suppression of hypercholester-olemia, no protection against coronary atherosclerosis was seen with the administration of either L- or D-thyroxine. In fact, with an increase in dose of D-thyroxine to 4 mg, there developed actually an increase in the percentage of coronary vessels showing atherosclerosis.

These observations confirm once again the importance of avoiding reliance exclusively on blood cholesterol levels when judging the effects of hormones on atherogenesis.
Errors in the Processing of Dye Dilution Curves
Authors: Kelman G. Richard
Published: June 2012

Errors of two kinds occur in the processing of dye dilution curves:

1) Individual estimates of the decay constant of a dye curve are subject to random errors causing a variability of up to 10% in the calculated cardiac output, and of up to 4% in the estimated vascular volume.

2) The use of an inappropriate numerical integration formula can cause an additional error of up to 5% in the calculated cardiac output. This may be avoided by using either the trapezoid rule or Simpson's rule. The planimeter measures areas with sufficient accuracy for routine determination of cardiac output.
Effect of Regional Hypoxia on the Distribution of Pulmonary Blood Flow in Man
Authors: Lopez-Majano Vincent , Wagner Henry N. , Twining Ralph H. , Tow Donald E. , Chernick Victor
Published: June 2012

In ten patients with chronic lung disease unilateral airway hypoxia was produced by having them breathe 100% nitrogen administered for seven minutes via a Carlens catheter while the other lung received 100% oxygen.

The partition of pulmonary arterial blood flow between the two lungs was determined by radioisotope scanning following intravenous injection of I
131
macroaggregated human serum albumin (MAA) both during bilateral air breathing and unilateral hypoxia.

Unilateral hypoxia produced a 42% decrease in pulmonary blood flow to the hypoxic lung due to ipsilateral vasoconstriction. The response to N
2
was greater when given to the diseased lung, suggesting that the pulmonary vascular bed of the involved lung was incapable of accepting a large increase in the proportion of the cardiac output because the vascular bed was already compromised by disease.

Ventilation on the hypoxic side increased by 1.4 liters/min while there was no change on the side receiving 100% oxygen. Since unilateral hypoxia produced both a decreased blood flow and an increased ventilation, it is suggested that the lung is capable of altering regional perfusion and ventilation in a manner ideally suited to minimize the change in alveolar and pulmonary capillary oxygen tension.
Cardiovascular Responses to Epinephrine During Acute Hypercapnia in Dogs: Effects of Autonomic Blocking Drugs
Authors: Manley Emmett Steadman , Woodbury Robert Arthur , Nash Clinton B.
Published: June 2012

The reduction of cardiovascular responsiveness to epinephrine which develops during hypercapnia has been investigated in the pen-tobarbital-anesthetized dog. Parameters evaluated include arterial blood pH and pressor, chronotropic, and inotropic responses to epinephrine. Hypercapnia was induced by ventilation with either 15 or 30% carbon dioxide for a constant interval (either 2 or 10 minutes) before administration of epinephrine.

In this species and under the conditions employed, it was shown that the chronotropic, pressor, and inotropic responses to epinephrine were reduced in that order by hypercapnia. These responses were found to be reduced both in amplitude and duration. Phentolamine enhances the cardiac blocking activity of carbon dioxide. The depressor response to epinephrine, following phentolamine, was found to be exquisitely sensitive to elimination by hypercapnia. Cardiac stimulatory responses elicited by acetylcholine in atropinized dogs were not reduced by the intensity of hypercapnia employed in this study. The degree of refractoriness to epinephrine produced by high concentrations of CO
2
was less in those animals that had been exposed previously to high concentrations of carbon dioxide. Arterial blood pH determinations were found to be misleading when employed as an index of epinephrine responsiveness.

Reduction of available catecholamine stores by reserpine, adrenalectomy, or P-286 reduced the pressor refractoriness. Ganglionic blockade was largely ineffective in this respect as was parasympathetic blockade with atropine.
Cardiovascular Effects of Sustained Norepinephrine Infusions. I. Hemodynamics
Authors: Moss Arthur J. , Vittands Ingvar , Schenk Eric A.
Published: June 2012

Norepinephrine (NE) in graded doses of 1, 2, and 4 µg/kg/min was infused for four hours into 14 dogs; 5 dogs served as controls. The systemic pressure and flow, blood volume, hematocrit, arterial blood pH, and oxygen saturation were measured at selected intervals throughout the infusion period. Cardiovascular performance was augmented during the first 15 minutes of the NE infusions, but this effect was not sustained. Thereafter, there was a dose-related decline in cardiac output, systemic pressure and left ventricular work, and an increase in the calculated peripheral vascular resistance. At the highest NE dose rate employed, significant left ventricular failure developed by the second hour of NE administration. The hematocrit increased during the first 15 minutes of NE infusion and remained elevated throughout the infusion period. Sustained hypovolemia was not found during the prolonged NE administration, and severe acidosis (pH < 7.20) was inconstant. The processes which lead to cardiovascular dysfunction during prolonged NE infusion are discussed.
Microelectrode Studies on Concealment of Multiple Premature Atrial Responses
Authors: Moore E. Neil
Published: June 2012

Experiments employing microelectrodes to record from single cells within the AV node and ventricular specialized conduction system during conduction of serially evoked premature atrial responses have demonstrated AV conduction delays and block within both the AV node and ventricular specialized conduction system. The rapid decrease in functional refractory period of fibers within the ventricular specialized conduction system, following a decrease in preceding cycle length, resulted in block within the AV node of most serially concealed premature atrial responses. A one-millisecond change in the time of excitation of a premature atrial response could determine whether block or conduction occurred in the AV node.
Effects of Pulmonary Artery Ligation on Pulmonary Surfactant and Pressure-Volume Characteristics of Dog Lung
Authors: Giammona Samuel T. , Mandelbaum Isidore , Foy James , Bondurant Stuart
Published: June 2012

The effects of pulmonary artery ligation upon pulmonary surfactant and upon the pressure-volume characteristics of the canine lung were studied. Four hours after ligation of one pulmonary artery the two lungs had similar deflation pressure-volume curves and extracts from these lungs had similar surface tension. Two weeks after ligation, the lungs with a ligated PA differed from the contralateral lungs in having a smaller fraction of total volume retained at each pressure during deflation, and extracts with a higher minimal surface tension, and a lower surfactant activity index. Low but significant correlations were observed between the fractional volume at 15 cm H
2
O transpulmonary pressure and the minimal surface tension of the lung extracts (Wilhelmy balance), between the fractional volume of 15 cm H
2
O transpulmonary pressure and the surfactant activity index, and between the surfactant activity index and the lung stability index. These data suggest a close relationship between altered surface forces and the pressure-volume characteristics of the lung after pulmonary artery ligation.
Hemodynamic Effects of Dopamine in the Dog Before and After Alpha Adrenergic Blockade
Authors: MCNOY JOHN L. , GOLDBERG LEON I.
Published: June 2012

Dopamine reacts with blood vessel receptors, causing both dilatation and constriction. In the dog the vasodilator receptors are presentin the renal and mesenteric vascular beds but absent from the vascular beds of the limb. The vasoconstrictor receptors, alpha adrenergic in type, are present in both somatic and visceral regions. The net effect of intravenously administered dopamine on regional flows will depend on the relative intensity of these opposing effects and on changes in blood pressure. The present study was an attempt to evaluate the significance of the vasoconstrictor action of dopamine infused at nonpressor doses, i.e., 3 to 6 µg/kg/min. Renal and femoral blood flows were measured simultaneously, and systemic hemodynamics were evaluated before and after administration of the alpha adrenergic antagonists, phentolamine and phenoxybenzamine.

The results indicate that the vasoconstrictor property of dopamine is masking a mild depressor effect, ranging in magnitude from 10 to 25 mm Hg. Dopamine increases cardiac output independently of its alpha adrenergic properties. Dopamine causes an increase in renal blood flow of equal magnitude before and after alpha adrenergic block but reduces renal vascular resistance to a lower level after alpha block, reflecting the depression in blood pressure. Dopamine does not alter femoral vascular resistance either before or after alpha adrenergic block. However, femoral blood flow is decreased by dopamine after alpha block, secondary to the depression of blood pressure. It is concluded that under the conditions of these studies, alpha adrenergic block enhances the vasodepressor property of dopamine and does not appreciably modify its ability to increase cardiac output and redistribute peripheral blood flow.
Metabolism and Distribution of Intravenously Administered d-Aldosterone-l,2-H
3
in the Arteries, Kidneys, and Heart of Dog
Authors: HOLLANDER WILLIAM , KRAMSCH DIETER M. , CHOBANIAN ARAM V. , MELBY JAMES C.
Published: June 2012

The initial disappearance of intravenously administered H
3
-d-aldosterone from the plasma was associated with a rapid uptake of the labeled aldosterone in the tissues. The subsequent, slower fall off of plasma aldosterone radioactivity appeared to parallel the biological decay of H
3
-aldosterone in the tissues. H
3
-d-aldosterone attained a maximal level in the kidney, liver, heart, and aorta of dog in five to 15 minutes after the aldosterone injection. During and after the time of peak tissue radioactivity, H
3
-aldosterone radioactivity was higher in the kidney, liver, heart, and thoracic aorta than in the plasma. No consistent relationship was observed between the H
3
-aldosterone uptake and the salt, water, and acid mucopolysaccharide content of different portions of the aorta.

Subcellular fractionation of the tissues indicated that most of the H
3
-aldosterone taken up by the tissues was present in the supernatant fraction and not bound to subcellular particles. Radioautography revealed a high concentration of H
3
-aldosterone along the cell walls of the convoluted tubular cells and along the walls of the glomerular capillaries, arterioles, and Bowman's capsule. In the heart H
3
-aldosterone localized along the cell walls of the heart muscle cells, whereas in the aorta the hormone appeared to accumulate over the cytoplasm of the smooth muscle cells. The uptake and distribution of H
3
-aldosterone in the tissues were not altered by pretreatment with the aldosterone antagonist, spironolactone.
A Cardiac Factor in Hypertensive Responses
Authors: COOPER THEODORE , PEISS CLARENCE N. , WILLMAN VALLEE L. , RANDALL WALTER C.
Published: June 2012

Patterns of blood pressure response to direct and reflex activation of the central nervous system were compared in normal dogs and in dogs after cardiac autotransplantation. Interventions which regularly result in elevated systemic blood pressure in the normal, anesthetized dog may produce attenuated pressor reactions, or even depressor reactions, in the dog with a cardiac autotransplant. The differences in response patterns indicate a significant contribution by the heart to the pressor response of the intact dog.
Reflex Vasoconstrictor and Vasodilator Responses in Man
Authors: ABBOUD FRANCOIS M. , ECKSTEIN JOHN W.
Published: June 2012

The application of ice to the forehead and the Valsalva maneuver are known to cause reflex vasoconstriction by stimulation of adrenergic pathways of the sympathetic nervous system. In the experiments reported here, the effects of these stimuli on blood flow to the forearm of man were studied after intra-arterial injection of adrenergic blocking drugs. Changes in flow were measured with water plethysmographs applied to both forearms. One forearm served as "control," and the other forearm, into which the drugs were injected, was the "experimental" one.

The stimuli caused a consistent reduction of flow to the control forearm, but after the intra-arterial infusion of small doses of guanethidine there was increased flow to the experimental arm simultaneous with decreased flow to the control arm. The increased flow in response to the stimuli was accentuated after phentolamine and reduced after atropine.

The results indicate that the application of ice to the forehead and the Valsalva maneuver stimulate adrenergic vasoconstrictor pathways and cholinergic vasodilator pathways simultaneously. The vasoconstrictor response predominates, and the vasodilator effect is unmasked only after adrenergic blockade. It appears, therefore, that mental stresses are not the only stimuli which can cause reflex cholinergic vasodilatation in the forearm of man. Work by others would suggest that leg exercise may also cause cholinergic dilatation after adrenolytic agents. It is possible that cholinergic vasodilatation may play a role in the severe orthostatic fall in blood pressure, as well as in the exercise hypotension, observed in patients treated with guanethidine.
Intrarenal Distribution of Blood Flow in Dogs during Hemorrhagic Hypotension
Authors: CARRIERE SERGE , THORBURN GEOFFREY D. , O'MORCHOE CHARLES C. C. , BARGER A. CLIFFORD
Published: June 2012

Renal medullary blood flow was well maintained for several hours after blood loss which produced hypotension. Renal cortical blood flow was altered by trauma and mild hemorrhage even though blood pressure remained normal; rate of blood flow through the subcapsular, peritubular capillaries decreased to the level of that in the outer medulla. With further hemorrhage and the development of hypotension, rate of blood flow in large cortical areas was reduced to that of the outer medulla. With prolonged hypotension, the rate of blood flow in most of the cortex approached outer medullary rate and a single exponential could describe the flow in this combined area. Small regions of even slower flow rate began to appear in the outer cortex; patches of tissue appeared to be completely ischemic. The progression of cortical ischemia noted in these experiments may provide additional evidence for the pathogenesis of the patchy tubular necrosis noted in hemorrhagic shock.
Atrial Contribution to Stroke Volume in Dogs with Chronic Heart Block
Authors: SNYDER JOSEPH H. , BENDER FRANZ , KITCHIN ARTHUR H. , ZITNIK RALPH S. , DONALD DAVID E. , WOOD EARL H.
Published: June 2012

In dogs studied without thoracotomy, under morphine-pentobarbital anesthesia and with an average heart rate of 71 beats/minute, atrial systole contributes to ventricular function to a small but significant degree. Stroke volume increased by 7 to 8% when atrial systole was timed to occur 0.1 second prior to closure of the atrioventricular valves, and decreased a similar magnitude when the contribution of atrial systole to ventricular filling was rendered ineffective by the use of an A-V delay of zero so that atrial emptying into the ventricles was prevented by the closed A-V valves. Increases or decreases in right atrial pressure of several centimeters of water induced by infusion of 6% dextran and by hemorrhage, respectively, were not associated with demonstrably significant alterations in these effects.
Sympathetic and Parasympathetic Interactions upon the Left Ventricle of the Dog
Authors: LEVY MATTHEW N. , NG MANUEL , MARTIN PAUL , ZIESKE HARRISON , Rogoff Thomas
Published: June 2012

In canine, isovolumetric, left ventricle preparations, stimulation of the cardiac end of a cut cervical vagus nerve evokes a biphasic change of left ventricular systolic pressure (LVSP). Characteristically, there is a definite reduction of LVSP during the stimulus, followed by a slight increase of LVSP after cessation of stimulation. The magnitude of the reduction of LVSP during vagal stimulation is considerably augmented when sympathetic activity is increased either directly (by electrical stimulation of the left stellate ganglion) or reflexly (by lowering carotid sinus pressure). These results indicate that the effect of vagal stimulation is mediated, at least in part, by antagonizing the positive inotropic influence of the prevailing sympathetic nervous activity. The mechanism of the poststimulation rebound is unknown. It may be due to cardiac sympathetic fibers in the canine vagosympathetic nerve trunks and to the release of catecholamine-like substances in the myocardium.
Increased Susceptibility of the Heart to Ventricular Fibrillation During Metabolic Acidosis
Authors: GERST PAUL H. , FLEMING WILLIAM H. , MALM JAMES R.
Published: June 2012

Alterations of acid-base balance, clearly defined as metabolic or respiratory in origin, were produced in anesthetized dogs; ventricular fibrillation thresholds were determined during these conditions. During metabolic acidosis, we found that the heart became more susceptible to ventricular fibrillation, as indicated by a decrease in the ventricular fibrillation threshold value. During metabolic alkalosis, the threshold to ventricular fibrillation increased. In contrast, similar variations in pH owing to respiratory acidosis and alkalosis did not affect the ventricular fibrillation threshold. Hyperventilation in dogs with metabolic acidosis, even though resulting in alkaline arterial blood pH, did not protect the hearts from the increased susceptibility to ventricular fibrillation which existed as long as a base deficit was present.

These results indicate that the heart is more susceptible to ventricular fibrillation during acidosis caused by metabolic factors and that primary variations in carbon dioxide tension have no such effect. Our study on dogs, under controlled conditions, provides experimental evidence in support of clinical experience which suggests that metabolic acidosis predisposes the heart to ventricular fibrillation.
A Sensitive Method for Assay of Plasma Renin Activity
Authors: LEE MICHAEL R. , COOK WILLIAM F. , MCKENZIE JOHN K.
Published: June 2012

Renin activity is separated from rabbit plasma by globulin precipitation, dialysis, and DEAE cellulose column chromatography with a Tris chloride buffer system and acid elution, followed by ultrafiltration. The plasma renin extract contains no renin substrate and no angiotensinase activity can be detected after incubation with angiotensin for 200 hr. Incubation with a known concentration of rabbit renin substrate, similarly free of renin activity and angiotensinase, at pH 6.0 in 0.1 M phosphate buffer forms angiotensin-like activity at a constant rate for up to 200 hr. Recovery and reproducibility are satisfactory. Evidence is presented that the material in the plasma extract behaves similarly to renin and that the incubation product is indistinguishable from angiotensin.
Effect of Hemorrhage on Arterial Plasma Renin Activity in the Rabbit
Authors: MCKENZIE JOHN K. , LEE MICHAEL R. , COOK WILLIAM F.
Published: June 2012

Arterial plasma renin activity in the rabbit was measured at the beginning and end of a brisk hemorrhage and 40 min later. Activity rose to a mean of two and one-half times the control value during the hemorrhage, and was five times greater than the control 40 min later. The rise in plasma renin activity was not due to anesthesia, as light pentobarbitone produced no change. Conscious rabbits, severely bled from a carotid cannula, 2 to 5 hr after an ether anesthetic, also showed an increase in plasma renin activity at the end of hemorrhage. Forty-eight hours after both kidneys had been removed, renin activity was virtually absent and did not rise after hemorrhage.
Cholinergic Mechanisms in the Sinus Node
Authors: JAMES THOMAS N.
Published: June 2012

Acetylcholine is directly perfused into the canine sinus node in vivo through its cannulated nutrient artery. After atropinization, the chronotropic action from intranodal administration of acetylcholine was identical to that of control injections of Ringer's solution alone. Eserine produced only a negative chronotropic action before, and no significant action after, atropinization. Direct perfusion of the sinus node with hemicholinium (1 mg/ml) completely blocked the response to vagal stimulation but had no effect on the response to stimulation of the stellate ganglion. The evidence is interpreted as indicating that acetylcholine has only a negative chronotropic action in the canine sinus node and that it neither releases significant amounts of local nodal norepinephrine nor is necessary to the normal response of the sinus node to stellate ganglion stimulation.
On the Mechanism of Cardiac Glycoside Action
Authors: STOWRING LINDA , BOWEN WILLIAM J. , MATTINGLY PATRICK , MORALES MANUEL
Published: June 2012

A study has been made of the effect of ouabain and other cardiac glycosides on a faithful model of contraction, viz. the "superprecipitation" which occurs when ATP is added to a suspension of purified myosin B. Structural changes during superprecipitation were followed by a turbidity method, and rates of ATP utilization with a pH stat. At "optimal" concentrations (ca. 10
-9
M and 10
-3
M) these substances approximately double the structural and the ATP utilization rates of the myosin B system, but at no concentration do they affect the ATPase of myosin A. In the one case studied, cardioactivity of the substance appeared to parallel its effect in our test system.