bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic and metabolic adjustments during exercise and shock avoidance in dogs
Authors: Langer A. W. , Obrist P. A. , McCubbin J. A.
Published: December 2017

The purpose of this study was to examine whether the hemodynamic and metabolic consequences of a physical (treadmill excercise) and behavioral (signaled shock-avoidance) stressor could be differentiated. To do this, direct continuous recordings of cardiac output, systolic and diastolic blood pressure, and discrete determinations of the arterial-mixed venous oxygen ((a-v)O2) content difference were analyzed in six dogs during exposure to three grades of treadmill exercise and when working on a shock-avoidance task. The results indicated that in five animals the relationship between cardiac output and the (a-v)O2 difference during shock-avoidance conditioning was significantly different from the corresponding pattern observed during exercise. In four animals the data suggested that avoidance conditioning, relative to exercise stress, elicited overperfusion. Behavioral stress also produced reliable elevations in diastolic and systolic blood pressure. These results suggest that, when compared to physical stress, behavioral stress can produce a dissociation of cardiovascular and metabolic processes in the presence of acute pressor responses.
Development and regression of exercise-induced cardiac hypertrophy in rats
Authors: Hickson R. C. , Hammons G. T. , Holoszy J. O.
Published: December 2017

Adult female rats were exercised by daily swimming. All the increase in heart weight induced by the exercise occurred within 14 days and averaged 30%. The half times of the increases in heart weight and total protein content were about 4.5 days, whereas that of cytochrome c, which was used as a mitochondrial marker, was 6.5 days. The total amounts of DNA and of hydroxyproline in the heart, which were used to evaluate the degree of connective tissue hyperplasia, increased only slightly (8% and 10%, respectively). Other animals were subjected to the same swimming program for 21 days. Groups of rats were killed at various time intervals after stopping exercise. Heart weight, total protein content, and total cytochrome c content decreased rapidly initially, with 60% of the total regression of hypertrophy occurring during the first week. Thereafter, heart weight fell more gradually toward the sedentary control value. The hydroxyproline content of the heart, which was increased 10%, did not decrease during the regression of the hypertrophy.
Effect of angiotensin II receptor blockade by [Sar1-Ala8]angiotensin II in hemorrhagic shock
Authors: Trachte G. J. , Lefer A. M.
Published: December 2017

An angiotensin II receptor antagonist, [Sar1-Ala8]angiotensin II (saralasin), was infused at 60 (microgram/kg)/h into cats to examine its effect in hemorrhagic shock. Aprotinin (1,000 (KIU/kg)/h) was also administered to cats to determine how kinin inhibition effects angiotensin receptor blockade in shock. Saralasin was infused into shocked and sham-shocked cats. Aprotinin was administered to additional cats receiving either saralasin or its vehicle. Hemorrhaged cats treated with saralasin revealed a postoligemic preservation of mean arterial bloood pressure and superior mesenteric artery blood flow (SMAF). Final pressures were 48 +/- 12 mmHg and 81 +/- 9 mmHg with vehicle and saralasin treatment, respectively, and final SMAF were 2.5 +/- 0.5 (ml/kg)/min in cats receiving vehicle and 5.5 +/- 0.6 (ml/kg)/min in those receiving saralasin. Total plasma proteolysis was diminished by both saralasin and aprotinin, exhibiting elevations of free amino-nitrogen groups of 2.5-fold and 2-fold over initial as compared to a 3.5-fold elevation in vehicle-treated shocked cats. Myocardial depressant factor (MDF) activities were also suppressed by saralasin compared to shocked cats receiving vehicle (24 +/- 4 units vs. 59 +/- 3 units). These results indicate that blockade of angiotensin II actions in hemorrhagic shock is beneficial.
Influence of albuterol on erythropoietin production and erythroid progenitor cell activation
Authors: Przala F. , Gross D. M. , Beckman B. , Fisher J. W.
Published: December 2017

The effect of albuterol, a potent beta2-adrenergic agonist, on kidney production of erythropoietin (Ep) was studied. Its effects on erythroid colony (CFU-E) formation in vitro in rabbit bone marrow cultures were also assessed. Albuterol produced a significant increase in plasma Ep levels in conscious rabbits following 7 h intravenous infusion (50 (microgram/kg)/min). This effect was blocked by pretreatment of the rabbits with butoxamine (5 mg/kg ip), a potent beta2-adrenergic blocker. Albuterol in doses of 10(-10) to 10(-8) M in combination with Ep was also found to produce a significant increase in the numbers of CFU-E in the plasma clot culture system of rabbit bone marrow. This effect was blocked completely by DL-propranolol (10(-8) M) and by butoxamine (10(-8) M). The data presented suggest that albuterol, a potent activator of beta2-adrenergic receptors, increases kidney production of Ep in vivo and also produces a direct effect in combination with Ep on the proliferation of the erythroid progenitor cell compartment.
Circulating catecholamines and control of plasma renin activity in conscious dogs
Authors: Johnson M. D. , Shier D. N. , Barger A. C.
Published: December 2017

Uninephrectomized dogs were prepared with indwelling catheters in the aorta, inferior vena cava (IVC), and renal artery, and after recovery they were studied in the conscious state. Basal aortic epinephrine and norepinephrine concentrations were 57 +/- 11 and 101 +/- 18 pg/ml, respectively. Elevation of epinephrine concentration to over 2,000 pg/ml by IVC infusion resulted in a sustained 3.5-fold increase in plasma renin activity (PRA), with only a transient decrease in arterial blood pressure. The PRA response to epinephrine was completely blocked by l-propranolol; isoproterenol increased PRA more than did epinephrine. Increasing norepinephrine concentration to 1,600 pg/ml by IVC infusion resulted in only a 1.5-fold increase in PRA. Infusion of epinephrine or norepinephrine directly into the renal artery to achieve similar increments of renal arterial concentration did not increase PRA. Insulin injection or hemorrhage resulted in elevations of arterial epinephrine (but not norepinephrine) concentration greater than the concentrations achieved during IVC infusion in these studies. We conclude that circulating epinephrine in the physiologic range plays a role in the control of PRA by activation of an extrarenal beta-receptor.
A multichannel telemetry system for recording cardiovascular neural signals
Authors: Yonezawa Y. , Ninomiya I. , Nishiura N.
Published: December 2017

A multichannel telemetry system was developed for use with chronically instrumented unrestrained cats. This system can simultaneously record efferent and afferent cardiovascular neural signals, bioelectrical noise arising near the electrode recording the neural signals, EEG, ECG, and a standard calibration signal. The miniature (18 cm3), lightweight (24 g), telemeter is a five-channel, time-multiplexed, pulse width modulation (PWM)/FM device employing a high frequency subcarrier (60 kHz) and two sampling frequencies (30 kHz and 6 kHz). The device is powered by two small 120 mA . h silver oxide cells; it has an indoor transmission range of 10 m and can operate for 48 h. One channel transmits a standard signal (a square wave of 100 Hz and 200 mVp-p) used to monitor and regulate the system's performance. When the variation in either the amplitude or frequency of the standard signal is greater than 10% of the control value, the transmitted bioelectrical signals are automatically discarded.
Effect of positive end-expiratory pressure on ventricular function in dogs
Authors: Prewitt R. M. , Wood L. D.
Published: December 2017

Artificial ventilation with positive end-expiratory pressure (PEEP) reduces venous return by raising intrathoracic pressure. To determine whether PEEP decreases cardiac output further by depressing myocardial function, we constructed Starling curves, using rapid dextran infusion in 7 anesthetized dogs ventilated with zero (ZEEP) and 20 cm PEEP. The changes in stroke volume and in left ventricular stroke work (LVSW) when PEEP was added or removed were significantly greater than could be attributed to the corresponding change in transmural left ventricular end-diastolic pressure (LVEDPTM) on these Starling curves. To the extent that PEEP did not alter left ventricular diastolic volume-pressure characteristics, these data indicated PEEP depressed ventricular function. Identical changes with PEEP in cardiac output (-30%), esophageal pressure (+10 cmH2O), and left ventricular function were observed after pulmonary edema was induced with oleic acid. These results confirm and extend recent suggestions that high levels of PEEP depress left ventricular function in dogs, accounting for about half of the reduction in cardiac output before and during acute pulmonary edema.
Effect of DOCA-NaCl hypertension on pre- and postcapillary resistance in isolated hindlimbs of dogs
Authors: Brock T. A. , Diana J. N.
Published: December 2017

Measurements of precapillary resistance (Ra), postcapillary resistance (Ra), postcapillary resistance (Rv), capillary filtration coefficient (Kf), and mean capillary hydrostatic pressure (Pci) were made during constant-flow perfusion of isolated hindlimbs from control and deoxycorticosterone acetate (DOCA)-NaCl-treated hypertensive dogs by the isogravimetric method. Both Ra and Rv were found to be significantly increased in the hypertensive group, even after maximal vasodilatation with papaverine. The net decreases in Ra and Rv following papaverine infusion were not significantly different between control and hypertensive animals. These results suggest that the observed increases in Ra and Rv were due to structural adaptation (increased wall-to-lumen ratio). Nonpapaverinized hindlimbs from hypertensive dogs exhibited a significant 40% reduction in Kf, suggesting that capillary surface area for fluid exchange was decreased. The compliance of the hindlimb vascular bed was found to be significantly decreased in the hypertensive group. Pci of both groups of hindlimbs were not different between groups and was not affected by papaverine. This result suggests that net capillary permeability to plasma proteins in this preparation was not changed by hypertension.
Effects of sodium chloride on early and chronic phases of malignant hypertension in rats
Authors: Rojo-Ortega J. M. , Queiroz F. P. , Genest J.
Published: December 2017

Malignant hypertension was induced in Sprague-Dawley rats by a complete aortic ligation above the left renal artery. The effects of saline (0.9% NaCl) administration on the development and course of the malignant hypertensive vascular disease were studied and the treated rats were compared to non-saline-treated animals and to sham-operated controls in the early and chronic phases of the disease. In the early phase, blood pressure, hematocrit, body weight, and hypertensive vascular disease were characteristic of the malignant hypertensive process and were without significant difference in saline- and non-saline-treated animals. In contrast, the sham-operated rats remained normotensive and did not present abnormal histological findings. Plasma renin activity although decreased in the hypertensive saline-treated animals was not suppressed. In the chronic phase, NaCl administration caused an average increase of 40 g body weight during the 1-wk period this solution was given, but did not result in any improvement in blood pressure levels and vascular disease in treated rats compared to non-saline-treated animals.
Scattering of cerebral blood flow estimates using 133Xe intracarotid injection
Authors: Celsis P. , Marc-Vergnes J. P. , Charlet J. P. , Sevin A.
Published: December 2017

Computer-generated and real curves were used to study the random error in the blood flow estimates calculated from xenon-133 cerebral clearance curves. The initial count rate affects the scattering under a threshold of 5,000 counts/s, but above this figure its influence is negligible. Flow values, relative weight of gray matter, and processes of analysis have also an effect. For the stochastic analysis, a theoretical standard deviation calculable from each experimental curve was proved. For other methods, empirical formulas were established. Using these formulas, intervals of uncertainty can be calculated allowing a useful comparison of the results obtained on the same patient, from different areas or from subsequent tests. Such intervals also allow the comparison of mean flow values obtained from a particular curve by the three usual processes of analysis. With high initial count rates, more than 75% of the intervals of uncertainty are disjointed. This suggests that the random error plays little part in the differences observed.
Effect of calcium on strophanthidin-induced electrical and mechanical toxicity in cardiac Purkinje fibers
Authors: Vassalle M. , Lin C. I.
Published: December 2017

The role of calcium in the electrical and mechanical toxicity induced by strophanthidin (10(-6) M) was studied in canine Purkinje fibers perfused in vitro. Strophanthidin caused an increase in contractile force ("therapeutic effect") followed by a subsequent decrease and by the onset of arrhythmias ("toxic effects"). The onset of arrhythmias occurred sooner in low- and later in high-calcium solutions with respect to the normal calcium. The positive inotropic (therapeutic) effect of strophanthidin was reduced or prevented by caffeine (1 mM) or by high calcium. The late (toxic) decline in force during exposure to strophanthidin was temporarily reversed by decreasing [Ca]o to a low value. Similarly, the contractile force decreased when [Ca]o was increased from 8.1 to 16.2 mM and this decline was transiently reversed when [Ca]o was reduced to a low value. It is concluded that in Purkinje fibers 1) electrical toxicity may occur independently of an intracellular calcium accumulation, and 2) the mechanical toxicity may be due to an excessive accumulation of calcium in the fiber.
Avian cerebral blood flow: influence of the Bohr effect on oxygen supply
Authors: Grubb B. , Jones J. H. , Schmidt-Nielsen K.
Published: December 2017

To clarify the problems of altitude tolerance in birds, we studied the combined effect of hypocapnia and hypoxia on cerebral blood flow (CBF) in ducks. CBF was measured by the xenon clearance method. Normocapnic hypoxia causes CBF to increase when the arterial O2 tension (PaO2) falls below 60--70 mmHg. Hypocapnic hypoxia significantly shifts the blood flow curve so that blood flow does not increase until a lower PaO2 (50--60 mmHg) is reached. This gives the appearance that hypocapnia suppresses the hypoxia-induced increase in CBF. However, due to the Bohr effect, the hypocapnic blood contains significantly more O2 than does the normocapnic blood at the same PaO2. Therefore, when CBF is expressed as a function of O2 content, rather than PO2, CBF in the hypocapnic group does not differ significantly from the CBF in the normocapnic group. We interpret this to mean that because of the significantly greater oxygen content of the hypocapnic blood at a given PaO2, the degree of hypoxia experienced by these brains is not as severe as that experienced by the normocapnic brains.
Rabbit cardiovascular responses to aortic nerve stimulation at fixed carotid pressure
Authors: Stinnett H. O. , Peterson D. F. , Bishop V. S.
Published: December 2017

In pentobarbital-anesthetized rabbits with aortic nerves cut, reflex heart rate and mean arterial pressure (MAP) changes were quantified in response to maximal central stimulation of the left aortic nerve (LANS) before and during steady-state changes in isolated carotid intrasinus pressure (ISP). To distinguish possible vagally mediated cardiopulmonary influences, responses were measured before and after vagotomy. Changes in MAP observed by altering ISP within +/- 15 mmHg of the equilibrium pressure (EP) were linear and inversely correlated to changes in ISP, with a slope of approximately 3 both before and after vagotomy (r greater than or equal to 0.929, P less than 0.05). The peak fall in MAP during LANS was dependent upon ISP. The change in the MAP responses to LANS for each mmHg change in ISP ranged from 1.7 with vagi intact to 1.3 after vagotomy. Heart rate was unaltered by isolation of the carotid sinus and was independent of the small changes in ISP between +/- 15 mmHg of EP. These results indicate that blood pressure changes elicited by the aortic baroreflex are extremely sensitive to the degree of carotid sinus compensation. Thus, to assess the sensitivity of any arterial reflex area, the existing level of compensation by other barosensitive areas must be known.
Arterial wall properties and dietary atherosclerosis in the racing greyhound
Authors: Cox R. H. , Detweiler D. K.
Published: December 2017

The effects of experimental (dietary) atherosclerosis on arteries from racing greyhounds were studied. Measurements of pressure and external diameter were made on islated carotid and iliac arteries under active (norepinephrine, 5 microgram/ml) and passive (zero Ca2+ and 2 mM EGTA) smooth muscle conditions. Iliac arteries from diet-fed animals demonstrated substantial intimal lesions, but the carotid arteries were usually grossly involved. Arteries from atherosclerotic animals were stiffer during passive conditions, with the iliac arteries having the greater changes. In iliac arteries from treated animals, collagen and elastin contents were decreased, and the collagen-to-elastin ratio was increased; in carotid arteries from treated animals, elastin content was increased and the collagen-to-elastin ratio was decreased. The maximum range of control of arterial wall mechanics by smooth muscle was diminished in treated iliacs but unchanged in carotids. Both force development and constriction responses associated with smooth muscle activation were diminished in treated iliacs but unchanged in treated carotids. Mechanical properties of series elastic elements in treated iliacs were stiffer, but treated carotids were unchanged.
Plasma epinephrine and control of plasma renin activity: possible extrarenal mechanisms
Authors: Johnson M. D. , Fahri E. R. , Troen B. R. , Barger A. C.
Published: December 2017

Previous work from our laboratory has shown that physiological increments of circulating epinephrine concentration increase plasma renin activity (PRA) by an extrarenal beta-receptor mechanism. In the present experiments, epinephrine was infused intravenously at 125 ng.kg-1.min-1 for 45 min in trained, conscious dogs. PRA rose 3 to 5-fold, as previously described, and was accompanied by a transient decline of mean arterial pressure, decreased plasma potassium concentration, and increased hematocrit. Prior splenectomy to maintain hematocrit constant did not attenuate the PRA response to epinephrine. The kidneys of 4 dogs were denervated and constrictor cuff was placed around the renal artery. Renal denervation did not alter the PRA response to intravenous epinephrine infusion. A transient decline in renal perfusion pressure produced by cuff constriction only transiently increase PRA. Neither maintenance of a constant plasma potassium concentration nor oral administration of indomethacin altered the PRA response to epinephrine. We conclude that intravenous epinephrine increases PRA by a mechanism independent of the renal nerves, changes in renal perfusion pressure, hematocrit, plasma potassium concentration, and plasma prostaglandins.
Renin release with carotid occlusion in the conscious dog: role of renal arterial pressure
Authors: Rocchini A. P. , Barger A. C.
Published: December 2017

Page H108: A. P. Rocchini and A. C. Barger. “Renin release with carotid occlusion in the conscious dog: role of renal arterial pressure.” Page H110: the second line of the addendum should read carotid sinus hypotension.
Adenosine content of skeletal muscle during active hyperemia and ischemic contraction
Authors: Phair R. D. , Sparks H. V.
Published: December 2017

If newly formed adenosine is the mediator of active hyperemia in skeletal muscle, tissue adenosine must increase and remain elevated during sustained muscle contraction. We tested this prediction using isolated canine anterior calf muscles. Muscle samples were obtained before and during contraction by punch biopsy and adenosine was measured by spectrophotometric enzyme assay. Tissue adenosine content didnot increase significantly above the precontraction level during either the 2- or 6-Hz contraction. We estimated (by infusing adenosine) that the adenosine concentration required to cause a dilation equal to that observed during 6-Hz contractions was 3.7 X 10(-5) M. We would have detected an increase in tissue adenosine if this concentration were established in as little as 10% of the skeletal muscle interstitium during free flow. These results indicate that adenosine released into the whole interstitial space is not the cause of free-flow exercise hyperemia.
Resistance and volume changes caused by nitroprusside in the dog
Authors: Rubin S. A. , Misbach G. , Lekven J. , Parmley W. W. , Tyberg J. V.
Published: December 2017

Changes in vascular volume caused by a pharmacologic agent are frequently inferred rather than directly measured. We investigated the effects of nitroprusside in 8 dogs divided into 2 groups: control and splenectomized. We anesthetized the dogs using pentobarbital, and surgically prepared a veno-right atrial bypass preparation whose controlled cardiac output and external reservoir allowed measurement of both changes in vascular resistance and changes in vascular volume. In both groups, blood pressure (mean +/- SD) decreased at each successive level of nitroprusside: 114 +/- 24 mmHg (base line), 101 +/- 19 mmHg (45 microgram/min), 90 +/- 16 mmHg (90 microgram/min), 81 +/- 17 mmHg (180 microgram/min), 68 +/- 18 mmHg (360 microgram/min). Nitroprusside caused a large and similar decrease in vascular resistance in both groups. In the control group, vascular volume increased above base line 5.5 +/- 2.7, 8.3 +/- 3.2, 11.6 +/- 2.9, and 14.7 +/- 3.5 ml/kg at each successive level of nitroprusside infusion, whereas in the splenectomized group vascular volume increased above base line 0.9 +/- 0.3, 2.5 +/- 1.0, 3.3 +/- 1.1, and 4.0 +/- 1.3 ml/kg at each successive level of nitroprusside infusion, but increased significantly less than the control group. We concluded that nitroprusside decreases vascular resistance and increases vascular volume and that the spleen is the major site of changes in vascular volume caused by nitroprusside.
Evaluation of a screen oxygenator suitable for small animal organ perfusion
Authors: Hanna B. D. , Lioy F.
Published: December 2017

A small vertical screen oxygenator was built using a stainless steel screen enclosed in a Plexiglas box as the oxygenating surface. The unit was primed with 35 ml dextran-diluted blood (Hct 25.1 +/- 0.6%. mean +/- SE) and tested in cats with a partial cardiopulmonary bypass circuit. An oxygen saturation of more than 95% was always obtained, even when the incoming venous saturation was as low as 15%. The O2 exchange capacity was minimally affected by changes in blood flow (1.5 to 70 ml/min) through the unit. CO2 extraction was not flow limited over the range tested. Output PCO2 was 33.3 +/- 0.6 mmHg and pH was 7.29 +/- 0.02. These results were obtained when 3% CO2 in O2 was passed through the oxygenator chamber at 1.0 to 5.0 l/min. The performance of the unit was stable for periods up to 4 h. The small priming volume and reliable performance make this oxygenator suitable for organ perfusion in small experimental animals.
Myocardial and coronary vascular responses to insulin in the diabetic lamb
Authors: Downing S. E. , Lee J. C.
Published: December 2017

Diabetes mellitus was produced in 9 lambs by giving alloxan monohydrate, 150 mg/kg, 24 h prior to study, and these were compared with 12 control animals. Responses to insulin, 20 U/kg, were studied in each. Measurements of LV dP/dtmax, coronary sinus flow (CF) and myocardial extraction and uptake of O2, glucose and fatty acids (NEFA) were made using a hemodynamically controlled preparation described previously (Am. J. Physiol. 244: 1381, 1973). Initial arterial glucose (G) averaged 328 mg/dl in the diabetics compared with 110 mg/dl in controls. G fell to 160 mg/dl 90 min after insulin in the diabetics, and to 25 mg/dl in the controls. Initial LV dP/dtmax values were identical in both groups and showed similar increases of about 800 mmHg/s 30 min after insulin (P less than 0.001). However, initial CF was lower and resistance higher in diabetics than controls. After insulin, CF increased 50% in controls but only 10% in diabetics. Because inotropic responsiveness and O2 metabolism were the same in both groups, altered coronary vascular smooth muscle reactivity in the diabetics may explain these findings.
Reninlike enzymatic activity in the cerebral microvessels of the rat
Authors: Kowaloff H. , Gavras H. , Brecher P.
Published: December 2017

Extrarenal renin has been a subject of considerable interest. Chiefly, studies have focused on brain and vascular renin activity in large arteries. A method now exists for the isolation from the cerebrum of microvascular tissues consisting of arterioles, capillaries and venules. The present study has demonstrated reninlike enzymatic activity within the cerebral microvasculature of the rat that is distinct from plasma renin activity. Maximal activity was observed at pH 4.5 with no measurable activity at pH 7.4. Activity with homologous renin substrate was only 13% of that measured with hog substrate whereas a 400-fold increase in reninlike specific activity was observed when microvessel homogenates were incubated with synthetic tetradecapeptide renin substrate. Bilateral nephrectomy did not affect microvascular reninlike activity. Pepstatin 15 nM, abolished reninlike activity in microvessel homogenates. Mean specific microvessel reninlike activity was 1.15 +/- 0.20 pg angiotensin I . microgram protein-1 . h-1 in control animals. Neither sodium depletion nor DOC-saline administrations caused a significant change in microvascular reninlike activity. It is suggested that the reninlike activity observed in microvessels is an acid protease, perhaps cathepsin D derived from lysosomes.
Coronary occlusion and reperfusion: effects on subendocardial cardiac fibers
Authors: Karaguezian H. S. , Fenoglio J. J. , Weiss M. B. , Wit A. L.
Published: December 2017

Coronary flow and transmembrane potentials of Purkinje and muscle fibers in reperfused infarcts and infarcts caused by permanent coronary occlusion were compared. Purkinje fibers in permanently occluded infarcts at 24 h had markedly reduced resting potentials. Action potential amplitudes, and Vmax were reduced and duration markedly prolonged. In reperfused infarcts, changes in Purkinje fiber transmembrane potentials were not as marked. Action potential duration in 3-day-old permanently occluded infarcts were longer than at 24 h, but in reperfused infarcts durations had returned to normal. Premature impulses conducted more rapidly in the reperfused infarct Purkinje system than in the permanently occluded. Other transmembrane potential parameters of Purkinje fibers in 3-day-old and 9- to 10-day-old reperfused and permanently occluded infarcts were not significantly different from each other. The ventricular muscle cells that survived in reperfused infarcts at all times also had reduced resting potentials and action potentials with decreased amplitudes, reduced Vmax, and prolonged durations. Almost no muscle cells survived in permanently occluded infarcts. Therefore, reperfusion salvages subendocardial fibers and prevents some but not all of the electrophysiological abnormalities.
Dynamics of fluid distribution between the blood and interstitium during overhydration
Authors: Manning R. D. , Guyton A. C.
Published: December 2017

The dynamics fluid volume distribution between the blood and interstitium was studied in 24 anephric conscious dogs by making serial measurements of blood volume, sodium space, and plasma proteins during several different states of hydration. After recovery from splenectomy and unilateral nephrectomy, the remaining kidney was removed, and intravenous infusion of lactated Ringer solution equivalent to 5%, 10%, or 20% of the body weight followed the next day. Blood volume and sodium space were elevated in each infusion group for the entire 25-h postinfusion period of measurements, while total amount of circulating proteins increased in the 10% group and decreased in the 20% group, which blunted the increase in blood volume in this group. During the first 5 h after infusion, the increase in blood volume was proportional to the increase in sodium space up to a sodium space of 50% above control. By 24 h postinfusion the relationship between blood volume (BV%) and sodium space (SS%) as percent control was linear over the entire range of sodium spaces (BV% = 68.0 + 0.32 SS%, r = 0.99).
Intracellular calcium and electrogram in ischemic isolated rat heart
Authors: Carbonin P. , Di Gennaro M. , Valle R. , Beranbei R. , Habed A.
Published: December 2017

The electrogram (EG) of the isolated rat heart during ischemic or anoxic perfusion has been studied. Reduction of the coronary flow rate (CFR) induced an increase of voltage (V) both in unipolar epicardial EG and in transmural bipolar EG. The V increase did not occur during anoxic perfusin. The ischemic increase cannot be due to a disturbance in the His-Purkinje or intraventricular conduction because it was observed also in the circumscribed myocardial area, which was explored by means of the transmural bipolar EG. Likewise it cannot be due to an intramural block because it occurs before one observes an augmentation of epicardial activation time or a decrease of dV/dtmax. Therefore, the ischemic V increase should be due to a modification of transmembrane potential. The variation rate of V, of dP/dt, and of myocardial ATP behaved in a similar way during underperfusion. Varying intracellular Ca2+ by means of a Ca2+-free medium or verapamil reduces the ischemic V increase. The dynamics of the ischemic V increase may be represented in order of succession by: inhibition of oxidative metabolism, augmentation of intracellular Ca2+, increase of K+ conductance, and hyperpolarization of cardiac cells.
Resting blood flow and oxygen consumption in soleus and gracilis muscles of cats
Authors: Bockman Emma L. , McKenzie Jack E. , Ferguson J. L.
Published: December 2017

In contrast to previous reports, the results of the present study indicate that vascular responses of isolated soleus muscles of cats are functionally similar to those of gracilis muscles. Vascularly isolated muscles were perfused under free-flow conditions. Venous outflow was measured by a drop counter. Resting blood flows were similar in soleus (n = 16) and gracilis (n = 12) muscles, 6.6 ± 1.2 and 3.8 ± 0.6 ml ⋅ min-1 ⋅ 100 g-1, respectivley (P > 0.05). Resting oxygen consumption averaged 0.26 ± 0.06 and 0.33 ± 0.10 ml O2 ⋅ min-1 ⋅ 100 g-1 for soleus (n = 10) and gracilis muscles (n = 5), respectively (P > 0.05). In four animals, blood flow to soleus muscles measured by the microsphere technique was 2.0 ± 0.3 ml ⋅ min-1 ⋅ 100 g-1 before and 4.6 ± 2.1 ml ⋅ min-1 ⋅ 100 g-1 after isolation of its circulation. Before isolation, blood flow to gracilis muscle was 2.0 ± 0.1 ml ⋅ min-1 ⋅ 100 g-1 after isolation of its circulation. Both soleus and gracilis muscles exhibited active hyperemia. Autoregulation of blood flow in both muscles was weak. However, oxygen supply exceeded demand because oxygen consumption was maintained as blood flow decreased in response to reductions in perfusion pressure. There was no evidence of blood flow-limited oxygen consumption. Thus, the soleus muscles of the present study not only have low-resting blood flows and oxygen consumptions, but their responses to physiological stimuli are similar to those of gracilis muscles.
Endogenous anticoagulation during extracorporeal perfusion: generation of a heparinlike inhibitor
Authors: Murphy T. L. , Walker F. J. , Taylor F. B. , Beller-Todd B. , Archer L. T. , Sofer S. S. , Hinshaw L. B.
Published: December 2017

Studies were done to define the coagulation defect that develops in hemodynamically stable anesthetized dogs perfused on our arteriovenous extracorporeal system without added heparin. After 45 min, the dogs developed whole blood clotting times (WBCT) greater than 24 h. There was an associated decrease in ADP-induced platelet aggregation and a drop in factor V, VIII, and X levels of 75.8, 33.5, and 46.8%, respectively. Despite an increase in fibrinogen degradation products, there was no significant change in fibrinogen level or platelet count. An inhibitor of thrombin and factor Xa clotting of plasma appeared that was "heparinlike", because it stimulated the inactivation of factor Xa by antithrombin III (ATIII) but not by O-methyl isoureamodified ATIII. Thrombin inhibition by ATIII was also stimulated. The inhibitor was heat stable, adsorbed by BaSO4, and neutralized by protamine. Infusion of protamine sulfate into two perfused dogs neutralized the inhibitor and brought the WBCT from greater than 24 h to less than control. Six dogs developed inhibitor levels equivalent to 0.98 to 6.15 U/ml heparin. Five eviscerated dogs in which the hepatic artery was ligated developed peak plasma inhibitor levels of 3.2 +/- 1.0 U/ml. Thus, the endogenous heparinlike inhibitor is a major contributor to the anticoagulated state induced with our perfusion system and may have an extrahepatic origin.
Effect of arterial stretch on transmural albumin and Evan's blue dye transport
Authors: Fry D. L. , Mahley R. W. , Oh S. Y.
Published: December 2017

The influence of arterial wall circumferential stretch (lambda) on the 32-min diffusive mural uptake of 125I-albumin and of Evan's blue dye (EBD) across the injured endothelial surface was studied in the intimal-medial preparation of the canine descending thoracic aorta (DTA). Albumin uptake (MA nmol/cm2) was measured by standard gamma counting techniques and the corresponding EBD uptake (ME) by the reflectance method. MA and ME were measured at a physiological stretch (lambda = 1.4) and at a hypertensive stretch (lambda = 1.8) at four equispaced locations (z) along the DTA. When lambda was changed from 1.4 to 1.8, the average percentage change of MA was -2% and of ME was -4%. These decreases were not significant (P greater than 0.10), and we conclude that arterial wall stretch exerts only minor influence on the parameters governing albumin and EBD-albumin accumulation in the intimal surface of the deendothelialized arterial intimal-medial tissue system.
Enhanced beta-adrenergic-receptor responsiveness in hypoxic neonatal pulmonary circulation
Authors: Lock J. E. , Olley P. M. , Coceani F.
Published: December 2017

The influence of alveolar hypoxia on pulmonary vascular adrenergic receptors was studied in conscious newborn lambs. In control animals, pulmonary vessels were directly constricted by epinephrine and norepinephrine, but were unaffected by isoproterenol. Pulmonary resistance (PVR) was also unaffected by propranolol, thus implying minimal beta-receptor activity under normoxic conditions. Hypoxia raised PVR but also modified the pulmonary vascular responses to catecholamines: isoproterenol became a dilator, whereas the constrictor effects of epinephrine and norepinephrine were abolished. Although beta-blockade did not alter base-line PVR, propranolol increased the constrictor response to hypoxia, implying that hypoxia increases beta-adrenergic activity or reactivity in the pulmonary circulation. Consistent with this hypothesis are the following: 1) in alpha-blocked lambs, epinephrine was without local effects during normoxia, but caused vasodilation during hypoxia; 2) the absent constrictor response to epinephrine during hypoxia is fully restored by propranolol; and 3) although alpha-blockade blunts the hypoxic constrictor response, the full response is restored when beta-blockade is added. These results indicate that the hypoxic constrictor response is partially opposed by increased beta-mediated vasodilation. These enhanced beta-receptor effects are due, at least in part, to increased beta-receptor reactivity of unknown mechanism.
Role of vasa vasorum in nourishment of the aortic wall
Authors: Heistad D. D. , Marcus M. L. , Larsen G. E. , Armstrong M. L.
Published: December 2017

Vasa vasorum are present in the middle and outer layers of media in the thoracic aorta of dogs and humans. To examine the role of vasa vasorum in nourishment of the aorta, we ligated four contiguous pairs of intercostal arteries in anesthetized dogs. These arteries are the source of vasa to the descending aorta but not the aortic arch. Blood flow through vasa vasorum was measured with microspheres. Acute intercostal ligation did not reduce conductance in the aortic arch but reduced conductance in the middle third of the descending aorta from 7 +/- 1 to 3 +/- 0.7 (SE) ml.min-1.100 g-1.mmHg-1 (P less than 0.05). After intercostal ligation, infusion of adenosine (5 mumol.kg-1.min-1 iv) increased conductance in the aortic arch 3- to 4-fold but did not increase conductance in the descending aorta. Six to ten days after intercostal ligation, conductance in the middle third of the descending aorta remained low. Vasodilator capacity was partially restored in outer layers of the descending aorta, probably by collateral vessels or formation of new vessels. Morphological changes ranged from broad bands of necrosis to patchy areas of cell loss, primarily in middle layers of descending aorta. We conclude that vasa vasorum are critical in nourishment of aortic media.
Responses of the atrial myocardium to cardiac sympathetic nerve stimulation
Authors: Masuda Y. , Levy M. N.
Published: December 2017

The cardiac responses to sympathetic nerve stimulation were measured in open-chest, anesthetized dogs before and after infusions of cocaine, which were given to inhibit the neuronal uptake of norepinephrine. Cocaine did not augment the inotropic or chronotropic responses, but it did retard their decay after cessation of sympathetic stimulation. Before cocaine, the half-times for decay of the chronotropic, atrial inotropic, and ventricular inotropic responses were 28.4 +/- 2.2, 29.8 +/- 2.7, and 22.1 +/- 1.9 (+/- SE) s, respectively. After cocaine, however, the half-times were significantly greater (147 +/- 12.0, 51.4 +/- 3.9, and 32.9 +/- 2.5 s, respectively). The cocaine-induced prolongation of the decay time in a given cardiac tissue is a measure of the relative efficacy of neuronal uptake as a mechanism for dissipating the neurally released norepinephrine. Our data indicate, therefore, that among the various cardiac tissues that we studied, the neuronal uptake mechanism is least effective in the ventricular myocardium, somewhat more effective in the atrial myocardium, and most effective in the sinoatrial nodal region.
Biaxial mechanical properties of the pericardium in normal and volume overload dogs
Authors: Lee M. C. , LeWinter M. M. , Freeman G. , Shabetai R. , Fung Y. C.
Published: December 2017

The two-dimensional mechanical properties of the pericardium from dogs with a normal or chronically enlarged heart were studied in vitro. A 3.0-cm-square piece of the pericardium overlying the right and/or left ventricle was excised. An approximately 1.0-cm-square target was marked at the center, and its dimension was measured electrooptically. When immersed in physiological saline at 37 degrees C, the specimen was stretched and unloaded sinusoidally in one direction while force in the transverse direction was held constant. The tension-stretch relationship was highly reproducible and was insensitive to strain rate in the range of 0.002-0.1 Hz. Hysteresis was present. The pericardium was mostly anisotropic; however, the direction of maximal compliance varied among dogs. The elastic properties of the pericardium overlying the left and right ventricles were the same in most cases. Substantial stress relaxation was observed; in contrast, insignificant creep developed over 30 min. In five dogs with chronic cardiac dilatation due to an infrarenal aortocaval shunt, the tension-stretch curves were shifted significantly to the right (i.e., greater deformation at the same tension level). However, the pericardial viscoelastic properties and thickness were unchanged. In other words, chronic cardiac dilatation resulted in a more compliant pericardium.
Intracoronary naloxone in hemorrhagic shock: dose-dependent stereospecific effects
Authors: Lechner R. B. , Gurll N. J. , Reynolds D. G.
Published: December 2017

Treatment with naloxone improves cardiovascular function and survival in a variety of shock models, and numerous sites and mechanisms for its action have been proposed. Data presented in this article support the hypothesis that in hemorrhagic shock naloxone exerts its beneficial hemodynamic effects by acting primarily at cardiac opiate receptors. Naloxone or its stereoisomer (d-naloxone) were administered intravenously (iv) and directly into the coronary circulation (ic) in dogs anesthetized with pentobarbital sodium and subjected to hemorrhagic shock. Treatment with naloxone (2.0 mg/kg iv or 0.2 mg/kg ic) resulted in significant improvements in arterial pressure, myocardial contractility, and cardiac output. Treatment with saline or naloxone (0.2 mg/kg iv) were without beneficial effect. The hemodynamic responses to naloxone administered into the coronary circulation were dose dependent and stereospecific. These data support the hypothesis that naloxone exerts its salubrious effects in canine hemorrhagic shock by acting at cardiac opiate receptors.
alpha 1-Receptor localization in rat heart and kidney using autoradiography
Authors: Muntz K. H. , Garcia C. , Hagler H. K.
Published: December 2017

To study the distribution of alpha 1-adrenergic receptors in rat heart, kidney, and skeletal muscle, we used light-microscopic autoradiography of [3H]prazosin. Scintillation spectrometry of frozen sections demonstrated rapid binding, saturability, stereospecificity, and agonist and antagonist binding characteristic of an alpha-receptor. For autoradiography, sections were incubated, processed, and grain density quantified using a computer-based image analyzer. Specific alpha 1-receptor binding was found over cardiac myocytes in the left and right ventricles but not over skeletal muscle. Scatchard analyses of specific grain densities over cardiac myocytes gave a dissociation constant (Kd) of 0.55 +/- 0.18 nM (SD, n = 4 rats) and a maximum number of binding sites (Bmax) of 448 +/- 90 grains/10(-2) mm2. Renal arterioles had a higher specific grain density than myocardial arterioles at all concentrations of [3H]prazosin (P less than 0.001). Scatchard analyses showed that renal arterioles had a Kd of 0.27 nM and a Bmax of 1,259 grains/10(-2) mm2, whereas myocardial arterioles had a Kd of 1.64 nM and a Bmax of 183 grains/10(-2) mm2. Arterioles in the flexor carpi radialis muscle were not labeled. Renal cortex tubules had the highest grain density of any structure studied, i.e., higher than grain density over glomeruli or tubules in the renal medulla. These observations indicate that significant differences exist in the distribution and affinity of alpha 1-adrenergic receptors in various vascular beds and parenchymal tissues.
LV filling pressure during PEEP measured by nadir wedge pressure after airway disconnection
Authors: Carter R. S. , Snyder J. V. , Pinsky M. R.
Published: December 2017

Pulmonary arterial occlusion pressure (Ppao) may not accurately reflect left ventricular filling pressure (LVFP) during ventilation with positive end-expiratory pressure (PEEP) because increases in pleural pressure (Ppl) increase measured intrathoracic vascular and cardiac chamber pressures relative to atmospheric while decreasing LVFP by decreasing venous return. Steady-state values of Ppao off PEEP are not useful in understanding the hemodynamics on PEEP because of changes in blood volume distribution and ventricular afterload associated with the removal of PEEP. We hypothesized that changes in Ppao immediately after abrupt airway disconnection from PEEP selectively reflect removal of PEEP-associated Ppl changes prior to other physiological changes. In pentobarbital-anesthetized closed-chest dogs, we compared absolute left atrial pressure and left atrial pressure relative to Ppl (Platm) prior to abrupt disconnection from 15 cmH2O PEEP (on-PEEP), with Ppao at its nadir (nadir Ppao) following airway disconnection in three sequential conditions: control (normal), after propranolol-induced acute ventricular failure, and after oleic acid-induced lung injury. For all conditions at low LVFP (less than 9 Torr), nadir Ppao reflects Platm better than on-PEEP Ppao, while at higher LVFP (greater than 9 Torr), on-PEEP Ppao better reflects Platm than nadir Ppao (P less than 0.05). Accurate predictions of on-PEEP Platm can be made using both on-PEEP and nadir Ppao values in a multiple regression equation.
Angiotensin II, vasopressin, and sympathetic activity in conscious rats with endotoxemia
Authors: Schaller M. D. , Waeber B. , Nussberger J. , Brunner H. R.
Published: December 2017

The role of the sympathetic nervous system, angiotensin II (ANG II), and arginine vasopressin (AVP) in maintaining blood pressure (BP) during endotoxic shock was investigated in 117 conscious male Wistar rats. After intravenous injection of 2 mg Escherichia coli endotoxin, mean BP fell within 5 min by approximately 50 mmHg and rose again to approach base-line levels within 90 min. At that time, plasma renin activity, plasma norepinephrine (NE), and vasopressin levels of the endotoxin-treated animals were, respectively, 12-, 10-, and 54-fold (P less than 0.001) higher than those of the controls. The BP effect of either prazosin (0.125 mg iv), captopril (2.5 mg iv), or d(CH2)5Tyr(Me)AVP (5 micrograms iv), a specific antagonist of the vascular effect of AVP, was evaluated over a 30-min observation period starting 90 min after administration of endotoxin or its vehicle. Captopril reduced mean BP from 116 +/- 1.8 to a low of 109 +/- 2.1 (SE) mmHg (P less than 0.05, n = 8) only in rats pretreated with endotoxin, whereas the vasopressin antagonist had no depressor effect even during endotoxemia. The BP drop induced by prazosin in rats exposed to endotoxin (-21 +/- 3.3 mmHg, n = 6) did not significantly differ from that observed in control rats (-14 +/- 3.4 mmHg, n = 6). A dose-response curve to NE, ANG II, and lysine vasopressin was also performed. In endotoxin-treated rats the mean BP response to all agonists was markedly suppressed (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Carotid chemoreceptor reflex parasympathetic coronary vasodilation in the dog
Authors: Ito B. R. , Feigl E. O.
Published: December 2017

The hypothesis that carotid body chemoreceptor activation with hypoxic-hypercapnic blood elicits reflex coronary vasodilation was investigated. Circumflex or anterior descending coronary artery blood flow was measured in alpha-chloralose-anesthetized, closed-chest dogs. To minimize changes in cardiac metabolism, the heart was paced at a constant rate after atrioventricular heart block, propranolol (1 mg/kg) was given to prevent beta-receptor-mediated alterations in cardiac contractility, and aortic blood pressure was stabilized by means of a blood reservoir. The carotid body regions were vascularly isolated and perfused at constant pressure with arterial blood or hypoxic-hypercapnic blood. Under these conditions, carotid body chemoreceptor stimulation with hypoxic or hypoxic-hypercapnic blood for 90 s produced atrial bradycardia and a transient increase in coronary blood flow of 36–53% above prestimulation values. The augmented coronary flow was accompanied by a transient increase in coronary sinus O2 tension of 4.6–5.7 mmHg. Aortic blood pressure varied less than 10 mmHg. Intracarotid injections of nicotine (0.1 microgram/kg) or cyanide (150 micrograms) produced similar results. The coronary response to chemoreceptor stimulation with hypoxic blood or drugs was abolished when the reflex arc was interrupted with atropine (0.5 mg/kg). It is concluded that transient reflex parasympathetic coronary vasodilation is elicited by hypoxic or hypoxic-hypercapnic stimulation of carotid body chemoreceptors.