bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of systole on coronary pressure-flow relations in the right ventricle of the dog
Authors: Bellamy R. F. , Lowensohn H. S.
Published: December 2017

Downey and Kirk's hypothesis that ventricular systole inhibits coronary blood flow by forming vascular waterfalls was examined in conscious chronically instrumented dogs by studying the effect of right ventricular systole on right coronary blood flow. Diastolic and systolic pressure-flow relations were constructed at resting-level flow and peak flow reactive hyperemia from phasic pressure and flow tracings recorded in nine dogs with right ventricular pressures ranging between 14 and 154 mmHg. Linear relations were found between aortic pressure and right coronary flow during diastolic and during systole when peak ventricular pressure was less than systemic. At resting-level flow and when peak ventricular pressure was less than one-half systemic, systole translated the diastolic relation to a higher zero-flow-intercept pressure and did not alter the slope of the relation. We interpret the data as showing that ventricular systole inhibits coronary blood flow by augmenting a vascular waterfall mechanism that exists during diastole.
Chronic arterial and venous access in the unrestrained rat
Authors: Burt M. E. , Arbeit J. , Brennan M. F.
Published: December 2017

A system is described for chronic cannulation of the thoracic aorta and superior vena cava in the rat. This system employs a protective stainless steel coiled spring and water tight swivel and allows chronic infusion of solutions and simultaneous intermittent blood sampling for prolonged periods of time in the undisturbed unanesthetized rat. The rats (200-250 g) lost approximately 25 g in the immediate postoperative period, but then gained weight at a relatively normal rate (cannulated rats, 2.23 g/day; control rats, 2.29 g/day).
Role of neural pathways in renin response to intravascular volume expansion
Authors: Fisher S. J. , Malvin R. L.
Published: December 2017

This study was designed to evaluate the physiological importance of cardiopulmonary receptors with vagal afferents in controlling renin release during perturbations in blood volume. Intravascular volume of chloralose-anesthetized dogs was expanded by 7.5 ml/kg body wt, with an isotonic isoncotic solution containing 3% dextran for colloid. Volume expansion resulted in a 50% decline in renin secretion. However, volume expansion after bilateral cervical vagotomy, the proposed afferent limb of the reflex, also suppressed renin release. In another group of animals, the left kidney was surgically denervated and the right kidney extirpated, and again infusion suppressed resin release. In all groups, the infusion significantly suppressed renin release when compared to each dog's own control period, as well as when compared to the corresponding time controls. Our data indicate that the renin response to intravascular volume expansion was not mediated solely by the vagi or renal nerves. A combination of intrarenal factors may, however, have been responsible for the suppression of renin release observed. Our results do not support the hypothesis that the renin-angiotensin system is an efferent limb of the cardiopulmonary reflex during adjustments to alterations in blood volume.
Indomethacin-induced pulmonary vasoconstriction in the conscious newborn lamb
Authors: Lock J. E. , Olley P. M. , Soldin S. , Coceani F.
Published: December 2017

The pulmonary vascular effects of indomethacin were studied in chronically-instrumented conscious newborn lambs, 2-12 wk old. Flows were measured in right and left pulmonary arteries; indomethacin was injected into only one lung; and constriction or dilation was assessed from the proportion of pulmonary flow directed to the injected vs. the noninjected lung. Indomethacin was a pulmonary vasoconstrictor in all animals, its threshold dose being 0.01 mg/kg. The constriction after a dose of 0.1 mg/kg was associated with plasma indomethacin levels sufficient to inhibit prostaglandin (PG) synthesis. However, chronic indomethacin therapy (3 mg/kg per day orally) for 3 days, though resulting in similar plasma indomethacin levels, altered neither base-line pulmonary tone nor the pulmonary vascular responses to hypoxia, acetylcholine, bradykinin, or histamine. Pretreatment with indomethacin did abolish the pulmonary effects of a further intravenous dose of the drug. Our results indicate that production of a pulmonary PG may help to maintain normal vessel relaxation. However, the neonatal lung adapts to chronic inhibition of PG synthesis, maintaining normal vascular tone and homeostasis. Pulmonary PGs may play a role in, but are not essential for, normal neonatal pulmonary vascular control.
Intravascular mechanoreceptor modulation of renal sympathetic nerve activity in the cat
Authors: Echtenkamp S. F. , Gilmore J. P.
Published: December 2017

Experiments were performed in chloralose-anesthetized cats to characterize intravascular mechanoreceptro input to renal nerve activity in the intact and vagotomized sinoaortic-denervated states. High-pressure intravascular mechanoreceptors were stimulated by rises in arterial pressure caused by norepinephrine. Low-pressure intravascular mechanoreceptors were stimulated by progressive blood volume expansion (14-23%) at a rate of 4.4 or 17.6 ml/min. In addition, veratrine was used to stimulate directly both high- and low-pressure receptors. In the intact animal the administration of norepinephrine or blood volume expansion was associated with substantial decreases in renal nerve activity. Veratrine also caused a large dose-related decrease in renal nerve activity. However, in the vagotomized sinoaortic-denervated animal there was no change in renal nerve activity with norepinephrine, volume expansion, or veratrine administration. These experiments demonstrate that the major afferent pathways for renal sympathetic circulatory reflexes are confined to the carotid sinus and aortic and vagus nerves. No evidence was found for a significant contribution from sympathetic afferent nerves.
Effect of converting enzyme inhibition on glucocorticoid hypertension in the rat
Authors: Elijovich F. , Krakoff L. R.
Published: December 2017

The renin-angiotensin system was evaluated by inhibition of converting enzyme (CEI) and by testing sensitivity to angiotensin II (AII) in sodium-depleted rats made hypertensive by methylprednisolone (MP), 20 mg/kg im. During a 2-wk period blood pressure rose 38 +/- 4 mmHg (P less than 0.001) in MP and 3 +/- 4 mmHg in controls. After pentobarbital anesthesia, intra-arterial pressure and dose-response curves to AII were determined, before and after SQ14225 (d-3-mercapto-2-methylpropranoyl-l-proline) (1 mg/kg iv). CEI reduced pressure significantly in both MP and controls, although the decrease was smaller in the former (P less than 0.05). Pressor responses to AII were nearly identical in MP and controls and were enhanced to a similar extent by CEI. Ganglionic blockade with pentolinium tartrate, given after CEI, did reduce the pressure in both groups to equal levels. Responses to AII after pentolinium were similar to those obtained after CEI alone. These results indicate that the renin component of glucocorticoid hypertension during sodium deficiency is smaller than that of the normotensive controls. No evidence of glucocorticoid-induced vascular hypersensitivity to AII was detected in this model of experimental hypertension.
Physical characteristics of pulmonary artery stenosis murmurs in calves
Authors: Gross D. R. , Lu P. C. , Dodd K. T. , Hwang N. H.
Published: December 2017

To better understnad the characteristics of cardiovascular murmurs and turbulent energy transmission, we made simultaneous measurements of pressure (sound) and velocity fluctuations in the vicinity of surgically produced stenoses in the pulmonary artery of calves. We did a spectral analysis of these data and found an identifiable break frequency at which the slopes of the pressure fluctuations changed. By use of these break frequencies and the corresponding blood jet velocity and vessel diameter measurements, Strouhal numbers were calculated. The jet velocity, Reynolds number, Strouhal number, and unsteadiness parameter values changed when the vessel was stenosed. When the power spectrum curves for the velocity fluctuations and the sound were compared, they tended to show a correlation between break frequencies. We speculate that this apparent correlation indicated a transfer from turbulent to acoustic energy.
Adaptive regulation of wall shear stress to flow change in the canine carotid artery
Authors: Kamiya A. , Togawa T.
Published: December 2017

To study the adaptive response of the vascular wall to blood flow changes, an arteriovenous shunt was constructed between the common carotid artery and the external jugular vein in 12 dogs. Six to eight months postoperatively, the arterial internal radius (r) was determined by angiography and/or the use of pressure-volume relationship. The results showed that r increased with increased flow load (f) and vice versa. Wall shear rate (gamma) was calculated from gamma = 4f/(tau r3), assuming laminar flow. The value of gamma, initially proportional to f, had recovered almost to the control level (within 15%) due to the vessel dilatation or atrophy during the chronic experiment, when f was less than 4 times the control. Transendothelial protein permeability, evaluated at the T-1824-stained surface by a reflectometric method, also showed a close correlation with wall shear (r = 0.934). A local autoregulatory mechanism of wall shear stress involving protein turnover in the vascular wall is suggested.
Effect of adenosine on transmural myocardial blood flow distribution in the awake dog
Authors: Rembert J. C. , Boyd L. M. , Watkinson W. P. , Greenfield J. C.
Published: December 2017

Studies were conducted to determine the effects of adenosine on transmural myocardial blood flow distribution. Both maximal and submaximal vasodilatory doses of adenosine were infused into awake resting dogs chronically instrumented with coronary flow probes and aortic and left atrial pressure catheters. Radioactive microspheres (8-10 micron) were used to determine regional coronary blood flow. Four experimental protocols were evaluated: 1) the effects of maximal (1.00 mg . kg-1 . min-1) as well as submaximal (0.45 mg . kg-1 . min-1) vasodilatory levels of adenosine, 2) the dose-response characteristics of adenosine, 3) the dose-response characteristics of dipyridamole, and 4) the effects of adenosine in the presence of an increased arterial PO2. The data indicate that maximal vasodilatory doses of adenosine have little effect on the endocardial-to-epicardial blood flow ratio, whereas submaximal doses result in a marked preferential endocardial perfusion. This relative increase in endocardial perfusion was not altered by hyperoxia. Dipyridamole, in submaximal doses, produced a similar preferential flow to the endocardial layer. These data demonstrate that the vasodilator reactivity to adenosine infusion is greater in the endocardial layer,
Ventricular recovery properties and QRST deflection area in cardiac electrograms
Authors: Abildskov J. A. , Evans A. K. , Lux R. L. , Burgess M. J.
Published: December 2017

We measured QRST deflection areas in cardiac surface electrograms of dogs and determined their relation to changes of refractory period induced by localized myocardial warming. Refractory period changes and QRST deflection areas were highly correlated with an average correlation of 0.95 over multiple activation sequences. For a single activation sequence, refractory period change was also highly correlated with ST-T deflection area, but over multiple activation sequences this correlation was reduced and the pooled variance of ST-T deflection areas was over 18 times greater than that of QRST area. No relation between QRST deflection area and the absolute value of refractory period over various cardiac sites was evident. Findings suggest that a particular set of ventricular recovery properties cannot be defined on the basis of QRST deflection areas, but that changes of recovery properties can be recognized on that basis.
Disposition of norepinephrine during nerve stimulation in dog saphenous vein
Authors: Rorie D. K. , Muldoon S. M. , Tyce G. M.
Published: December 2017

The relative importance of neuronal and extraneuronal uptake in the disposition of norepinephrine (NE) released by electrical stimulation (ES) from adrenergic nerves in isolated dog saphenous vein was determined. Helical strips of vein were incubated in L-[7-(3)H]NE (1 x 10(-6)M) and mounted for superfusion. Superfusate was collected continuously before, during, and after ES (10 V; 2 ms; 1, 2, and 5 Hz). Measurements were made of [3H]NE and its metabolites in vein and in superfusate. Previous studies have established that 3,4-dihydroxyphenylglycol (DOPEG) is of neuronal origin and O-methylated metabolites (OMM) are of extraneuronal origin. Thus, extraneuronal uptake was estimated directly by measuring the amounts of OMM in superfusate, and neuronal uptake followed by metabolism was estimated by measuring [3H]DOPEG. The magnitude of the neuronal uptake fraction that enters vesicles for reuse was estimated from the compensatory increases in [3H]NE and in OMM when neuronal uptake was blocked. Similar amounts of released NE were taken up by neuronal uptake, by extraneuronal uptake, and diffused out of the synaptic cleft. Between 5-20% of the released NE was sequestered in vesicles for reuse.
Quantitative microautoradiography of arteries: comparison of radioactivity to silver
Authors: Fry D. L. , Mahley R. W. , Oh S. Y. , Lewis S. J. , Plowman F. , Swyt C. R.
Published: December 2017

The local concentration of silver in developed aortic transmural microautoradiographs was compared to the corresponding 125I-labeled albumin radioactivity concentration [ci(x)] in the subjacent tissue. Silver [s(x)] was measured by electron probe X-ray microanalysis (EPA) and the corresponding ci(x) by direct gamma-ray counting. The results show 1) that the relationship between volume-averaged values of radioactivity (ci) and EPA signal (s) is adequately described by ci = Ks, where K is a proportionality constant, and 2) that ci(x) measured by EPA [i.e., Ks(x)] agrees closely with ci(s) measured direcly from en face microtomy slices of corresponding unfixed tissue specimens.
Role of ventrolateral medulla in vasomotor response to cerebral ischemia
Authors: Dampney R. A. , Moon E. A.
Published: December 2017

The ventrolateral medulla has been postulated to contain chemosensitive neurons. This study investigated the role of this region in the generation of the pressor response to cerebral ischemia (CIR) in anesthetized paralyzed artificially ventilated rabbits. A circumscribed and highly sensitive pressor area in the ventrolateral medullary reticular formation 2-4 mm rostral to the obex, separate from the well-known dorsal pressor area, was mapped by use of a stimulating electrode. Electrolytic destruction of this area resulted in a profound reduction in resting mean arterial pressure (MAP). After restoration of baseline MAP with norepinephrine infusion, the CIR was greatly reduced (by mean 70.2% of control), but pressor responses from the dorsal medulla were unaffected. In contrast, lesions of greater size placed in the ventrolateral medulla more caudally did not significantly alter resting MAP and only slightly reduced the CIR (by mean 17.0% of control). Vasomotor responses to stimulation of the ventrolateral pressor area were unaffected by caudal ventrolateral lesions, but greatly reduced by dorsomedial lesions in the same plane. It is concluded that the ventrolateral area is either the site of origin or an essential part of the central vasomotor pathway mediating the CIR and that this pathway projects dorsomedially before descending to the spinal cord.
Regulation of cerebral blood flow in atherosclerotic monkeys
Authors: Heistad Donald D. , Marcus Melvin L. , Piegors Donald J. , Armstrong Mark L.
Published: December 2017

This study was performed to determine the effects of atherosclerosis on cerebral vascular responses to hypercapnia and hypotension. We studied nine normal and eight atherosclerotic anesthetized cynomolgus monkeys. After 20 mo of an atherogenic diet, the common carotid and internal carotid arteries had fibrofatty lesions with some necrosis and calcification, and intracranial arteries had only fatty streak changes. Base-line cerebral blood flow (measured with microspheres) and vascular resistance were similar in the normal and atherosclerotic monkeys. Thus, despite significant obstruction of large extracranial arteries by atherosclerotic lesions, distal vessels dilated to maintain flow normal. Reduction of mean arterial pressure to 51 ± 7 mmHg in atherosclerotic monkeys and 42 ± 4 mmHg in normal monkeys did not decrease cerebral flow because cerebral vessels dilated to maintain flow constant. Cerebral vasodilator responses to hypercapnia, however, were impaired by atherosclerosis. Cerebral blood flow increased from 40 ± 6 (mean ± SE) to 190 ± 17 ml ⋅ min-1 ⋅ 100 g-1 during hypercapnia (PaCO2, = 64 mmHg) in normal monkeys and from 34 ± 2 to 99 ± 20 ml/min (PaCO2, = 65 mmHg) in atherosclerotic monkeys. Measurement of regional blood flow indicated that dilator responses in atherosclerotic monkeys were impaired in cerebral gray and white matter, cerebellum, and brain stem. We conclude that, in a primate model of atherosclerosis, maximal cerebral vasodilator responses to hypercapnia are impaired, but during a less pronounced vasodilator stimulus autoregulatory responses to hypotension are preserved.
Parasympathetic cardiovascular control in human disease: a critical review of methods and results
Authors: Eckberg D. L.
Published: December 2017

A variety of experimental approaches have been used to alter reflex parasympathetic cardiovascular control in normal human subjects and in patients with cardiovascular diseases. This review critically appraises several of these methods (the Valsalva maneuver, upright tilt, lower body negative pressure, pressor drug infusion, neck suction, and coronary arteriography) and summarizes the normal response patterns of healthy subjects and the abnormal response patterns of some patients with cardiovascular disease. Tests of parasympathetic function tend to be heterogeneous; they are not standardized, and, therefore, valid comparisons between results from different studies may be difficult to make. Moreover, although most of these tests are simple to perform, they may provoke surprisingly complex alterations of afferent and efferent autonomic activity. Notwithstanding these methodological difficulties, the research area of human parasympathetic cardiovascular control may have great importance, because parasympathetic reflex mechanisms are involved in diseases of major public health significance for which animal models may be imperfect or nonexistent.
Improved performance of ischemic canine myocardium in response to nifedipine and diltiazem
Authors: Perez J. E. , Sobel B. E. , Henry P. D.
Published: December 2017

To characterize the effects of Ca2+ antagonists on the performance of the ischemic myocardium, we administered nifedipine and diltiazem to chloralose-anesthetized dogs with coronary artery occlusion and monitored segmental myocardial shortening in ischemic and nonischemic zones with implanted ultrasonic length gauges. Other dogs were treated with nitroglycerin or nitroprusside for comparison. Dosage of all drugs was adjusted to reduce mean aortic pressure by no more than 5 mmHg. Segmental shortening was expressed as percent of control value before occlusion. In control dogs (n = 8), shortening in ischemic zones 20 and 80 min after occlusion averaged -16 +/- 2% and -17 +/- 2%, indicating paradoxical elongation. With nifedipine (1 +/- 0.4 microgram . kg-1 . h-1; n = 8), shortening of ischemic segments before treatment did not differ from controls, but after 60 min of treatment was markedly improved, averaging 31 +/- 4% (P < 0.05). Diltiazem (10 +/- 2 microgram . kg-1 . h-1; n = 8) produced a similar improvement in shortening in ischemic zones. However, nitroglycerin (177 +/- 20 microgram . kg-1 . h-1; n = 8) and nitroprusside (43 +/- 10 microgram . kg-1 . h-1; n = 8) failed to improve shortening in ischemic regions. Thus, Ca2+ antagonists improved performance in ischemic zones, but nitroglycerin and nitroprusside did not.
Hyperosmotic NaCl and severe hemorrhagic shock
Authors: Velasco I. T. , Pontieri V. , Rocha e Silva M. , Lopes O. U.
Published: December 2017

Intravenous infusions of highly concentrated NaCl (2,400 mosmol/l; infused volume 4 ml/kg; equivalent to 10% of shed blood), given to lightly anesthetized dogs in severe hemorrhagic shock, rapidly restore blood pressure and acid base equilibrium toward normality. No appreciable plasma volume expansion occurs for at least 12 h, indicating that fluid shift into the vascular bed plays no essential role in this response. Initial effects wee sustained indefinitely; long term survival was 100%, compared to 0% for a similar group of controls treated with saline. Hemodynamic analysis of the effects of hyperosmotic NaCl showed that these infusions substantially increase mean and pulse arterial pressure, cardiac output and mesenteric flow, whereas heart rate was slightly diminished. These effects immediately follow infusions with no tendency to dissipate with time (6-h observation). We conclude that hyperosmotic NaCl infusions increase the dynamic efficiency of the circulatory system, enabling it to adequately handle oxygen supply and metabolite clearance, despite a critical reduction of blood volume.
Ventricular systolic pressure-volume area as predictor of cardiac oxygen consumption
Authors: Suga H. , Hayashi T. , Shirahata M.
Published: December 2017

We scrutinized the recently reported correlation between the canine left ventricular systolic pressure-volume area (PVA) and cardiac oxygen consumption rate per beat (Vo2) by use of an improved method of Vo2 assessment. PVA is the specific area in the pressure-volume (PV) plane bounded by the end-systolic and end-diastolic PV lines and the systolic segment of the PV loop. Different from the previous study in which Vo2-PVA data from isovolumic and ejecting contractions were pooled for analyses, we analyzed Vo2-PVA data from the two different modes separately to examine whether there was any difference of Vo2-PVA relationship between them. The results indicated that the linear regressions of Vo2 on PVA were virtually the same for isovolumic and ejecting contractions. The regression line was Vo2 (ml O2/beat) = a[PVA (mmHg x ml x beat-1)] + b, where a = 1.64 (+/- 0.12 SE) X 10(-5) (ml O2/beat)/(mmHg x ml x beat-1) and b = 0.015 +/- 0.002 ml O2/beat in 10 hearts. We conclude that PVA serves as a reliable predictor of Vo2 regardless of the mode of contraction in a given left ventricle with a stable inotropic background.
Platelet adhesion and release: interfacial concentration of released materials
Authors: Adams G. A. , Feuerstein I. A.
Published: December 2017

Platelet deposition on collagen-coated glass and release from adherent platelets were studied in tube flow. Shear rates between 80 and 320 s-1 were evaluated by use of washed porcine platelets radiolabeled with 51Cr and [3H]serotonin in Tyrode solution containing albumin, apyrase, and red blood cells. Cell accumulation was highest at the tube's inlet and was directly proportional to exposure time for all positions up to 20 cm from the entrance and for times up to 800 s. Release was lowest at the inlet, 60%, and increased to 90% downstream. The accumulation and release information served as input to a calculation that yielded ADP surface concentration values at the tube's surface. These ranged from 0.6 microM at 80 s-1 to 1.8 microM at 320 s-1. In a turbidimetric device, ADP concentrations of 0.5, 1.0, and 5.0 microM were required to induce shape change, 10 and 80% aggregation, respectively. Aggregation was also obtained with subthreshold ADP and collagen in combination. We surmise that platelet shape change could have occurred adjacent to the surface in preparation for adhesion, aggregation, and release at the surface, and that ADP and collagen acted synergistically.
Effects of small changes of blood volume on oxygen delivery and tissue oxygenation
Authors: Sarelius I. H. , Sinclair J. D.
Published: December 2017

Circulatory effects of small (approximately 10%) changes in blood volume were examined in resting and exercising dogs: controls; group A (-200 ml blood); group B (+200 ml blood); group C (+200 ml 6% dextran). In exercise, cardiac output (Q) increased more in Group A than controls (510.4 ml . kg-1 . min-1 compared to 429.6 ml . kg-1 . min-1; P less than 0.05); oxygen delivery (cardiac output x arterial O2 content) and mixed venous oxygen tension (PVO2) were unchanged from exercising controls. Hypervolemia (group B) did not change Q or O2 delivery compared to controls, but caused a greater reduction in exercise PVO2 (29.3 mmHg compared to 33.1 mmHg in controls; P less than 0.01). Resting PVO2 as raised in group C (50.0 mmHg compared to 46.3 mmHg; P less than 0.05) and exercise PVO2 was reduced less (35.5 mmHg compared to 33.1 mmHg in controls; P less than 0.05). O2 delivery in exercise was higher than in controls (123.4 ml . kg-1 . min-1 compared to 94.3 ml . kg-1 . min-1; P less than 0.001). During exercise, O2 consumption was raised from base line to 34.9 ml . kg-1 . min-1 in controls and raised further to 41.4 ml . kg-1 . min-1 in group A, 44.4 ml . kg-1 . min-1 in group B, and 41.2 ml . kg-1 . min-1 in group C (P less than 0.01). Changes of blood volume that lie within physiological limits thus significantly modify the circulatory response to changed O2 requirements, and also change the metabolic cost of exercise.
Lung inflation: effects on heart rate, respiration, and vagal afferent activity in seals
Authors: Angell-James J. E. , Elsner R. , De Burgh Daly M.
Published: December 2017

In the anesthetized harbor seal, Phoca vitulina, the Hering-Breuer inflation reflex was weak and comparable to that in humans. Single inflations of the lungs from a syringe during the expiratory phase of normal breathing caused temporary inhibition of breathing and an immediate tachycardia dependent on the integrity of the cervical vagosympathetic nerves. A similar cardiac response occurred when the lungs were artificially inflated during an experimental dive and under conditions in which apnea and bradycardia were reflexly induced by a combination of stimulation of the carotid body chemoreceptors and of the trigeminal or laryngeal input. Recordings from single vagal afferent nerve fibers innervating presumptive pulmonary stretch receptors showed a close relationship between the increase in impulse frequency and increase in lung volume or transpulmonary pressure. It appears that in diving the decrease in pulmonary stretch receptor activity during apnea, combined with cessation of central inspiratory neuronal drive, is an important integrative mechanism that helps development of the reflex bradycardia of trigeminal, carotid, chemoreceptor, and baroreceptor origin.
Calculated dispersion of capillary transit times: significance for oxygen exchange
Authors: Honig C. R. , Odoroff C. L.
Published: December 2017

Probability densities for red cell velocity (V) and capillary length (L) in dog gracilis muscles were computed from mean length and mean velocity assuming two-parameter gamma distributions [Honig, Feldstein, and Frierson, Am. J. Physiol. 233 (Heart Circ. Physiol. 2): H122-H129, 1977]. The distribution of capillary transit times (L/V) was obtained from the ratio of the two gamma distributions. The lower tails of transit time distributions were compared with times thought required for O2 release from capillaries. Results indicate the following. 1) Transit time exceeds O2 release time at rest in all capillaries, regardless of assumptions in the calculation. 2) Transit time appears long enough even in moderate exercise provided mean L is about 1,000 microns and release time is about 100 ms. 3) Capillary recruitment prevents a functional O2 shunt during work at one- to two-thirds maximum O2 uptake (VO2max). 4) Recruitment is insufficient to prevent O2 shunting during exercise to VO2max. 5) Quantitative analysis of O2 transport is severely limited by lack of information about a) microvascular geometry, b) the probability distributions of parameters, and c) the kinetics of O2 release from capillaries.
Adrenergic mechanisms in canine intralobar pulmonary arteries and veins
Authors: Greenberg S. , Kadowitz P. J. , Hyman A. , Curron F. A.
Published: December 2017

The responses of canine intralobar pulmonary arteries (IPA) and veins (IPV) to transmural nerve stimulation (TNS), and exogenously administered norepinephrine (NE) were studied to evaluate the alpha-adrenergic neuroeffector system in the canine pulmonary vasculature. IPA and IPV elicited contractions in response to both NE (10(-10) to 10(-5) M) and TNS (0.5-32 Hz, 2 ms duration and delay). The equilibrium (steady state) contractile responses of IPA and IPV to TNS were abolished with the adrenergic neuronal blocking agents guanethidine and bretylium and the depolarization blocking agent tetrodotoxin in concentrations which did not affect the responses to NE or KCl. The contractile responses of IPA and IPV to TNS and NE were reduced in a concentration-dependent way, by the alpha-adrenergic receptor-blocking agents phentolamine, tolazoline and clonidine. The contractile responses of IPA and IPV to TNS and NE were enhanced after inhibition of neuronal reuptake of NE (uptake1) with cocaine, as well as after blockade of extraneuronal reuptake of NE (uptake2) with hydrocortisone. Analysis of the equilibrium responses of the IPA and IPV to TNS and NE with an Arunlakshana-Schild plot to define the concentration of alpha 1-receptor antagonists necessary to double the ED50 for TNS and NE (defined as the pA2), demonstrated that the postsynaptic alpha-receptors of IPV differed from that of IPA. These data support the conclusions that IPA and IPV 1) contain a functional adrenergic innervation and neuroeffector system, 2) contract in response to both TNS and NE, 3) demonstrate the presence of mechanisms for both uptake1 and uptake2 of NE, and 4) IPV contain postsynaptic alpha-receptors that may differ from each other.
Regional blood flows in salt loading hypertension in the dog
Authors: Liard J. F.
Published: December 2017

An intravenous infusion of isotonic sodium chloride, 196 ml/kg per day, was administered for several days to eight dogs with their renal mass reduced. Mean arterial pressure, cardiac output (electromagnetic flowmeter), and regional blood flows (radioactive microspheres) were measured sequentially and the results compared with those obtained in six control dogs. The salt-loaded animals exhibited on the 1st day of the infusion a 25% increase of arterial pressure and cardiac output. Blood flows to the kidney, the splanchnic area, the skin, and the bone were not significantly changed, whereas skeletal muscle blood flow almost doubled. After several days, cardiac output returned toward control values but pressure remained elevated. Skeletal muscle blood flow, as most other regional flows, did not differ significantly from control values at that time. In four dogs studied 6 h after starting a faster saline infusion, most of the increase in cardiac output was also distributed to the skeletal muscle. Total peripheral resistance changes did not reflect the resistance of individual beds, because vasoconstriction appeared early in some areas but was masked by prominent, although transient, vasodilation in skeletal muscle.
An observed pressor effect of the cerebellum during endotoxin shock in the dog
Authors: Janssen H. F. , Lutherer L. O. , Barnes C. D.
Published: December 2017

The current study investigates the possibility that the cerebellum may be involved in the regulation of mean arterial pressure (MAP) during endotoxin shock in the anesthetized dog. The effect of intravenously injected Escherichia coli endotoxin on MAP in the cerebellectomized dog was compared to that observed in the intact animal. Even though removal of the cerebellum did not significantly affect MAP in a control group, the cerebellectomized animal (unlike the intact animal) was unable to recover from the initial hypotension typically seen immediately following an intravenous endotoxin injection. Previous investigators have demonstrated that stimulation of fastigial nuclei in the cerebellum increases MAP via beta-adrenergic activation of the renin-angiotensin system. Captopril (SQ 14,225, an angiotensin I-converting enzyme inhibitor) was used to determine whether this system could be responsible for the maintenance of MAP during endotoxin shock. When continuously infused into the intact dog given endotoxin, captopril suppressed MAP to a level similar to that of the cerebellectomized group. A similar response pattern to endotoxin was also observed in animals with a spinal transection at C2.
Diabetes alters the myocardial cAMP-protein kinase cascade system
Authors: Ingebretsen W. R. , Peralta C. , Monsher M. , Wagner L. K. , Ingebretsen C. G.
Published: December 2017

An isolated perfused working rat heart preparation was used to assess the effect of alloxan-induced diabetes on the cAMP cascade system. Diabetes did not alter basal cAMP, cGMP content, or protein kinase or phosphorylase activities, but depressed (50%) isoproterenol-induced changes in cAMP content and protein kinase activity ratios. In contrast, phosphorylase activation and increased left ventricular pressure (LVP) were unaltered by diabetes. The relationship between cAMP and protein kinase activation is linear in hearts from both normal and diabetic rats. Diabetes did not alter this relationship. The relationship between protein kinase and phosphorylase activation or increases in LVP is also linear. An increase in the slopes obtained with diabetic hearts (P less than 0.05) was observed, suggesting an increased gain in the amplification cascade to protein kinase. The in vivo administration of insulin diminished this response. Thus, diabetes alters the ability of heart to accumulate cAMP and alters the gain of the amplification cascade system subsequent to protein kinase activation. This second effect may indicate an unmasking of a parallel regulatory pathway and in the beta-adrenergic regulation of phosphorylase activity and LVP.
Arterial baroreceptor reflexes in young and old racing greyhounds
Authors: Cox R. H. , Bagshaw R. J. , Detweiler D. K.
Published: December 2017

The characteristics of the carotid sinus baroreceptor (CSB) reflex control of arterial pressure-flow relations were studied in young (18 mo) and old (10.5 yr) racing greyhounds anesthetized with chloralose. Pressure and flow were simultaneously measured in the ascending aorta, the celiac, superior mesenteric, renal, and iliac arteries under steady-state conditions of pulsatile perfusion of the isolated carotid sinuses before and after bilateral cervical vagotomy. Operating-point (OP) values of mean pressure were not significantly different between the young or old greyhounds, but OP values of cardiac output were lower and of peripheral resistance were higher in the older animals. OP values of regional resistances were higher in the older animals, but only those of the celiac and mesenteric beds were significantly different. Values of OP sensitivity of central hemodynamic variables were not decreased in the older animals. OP values of renal and iliac resistance sensitivity tended to be lower in the older animals. The overall range of control of the various hemodynamic variables by the CSB was lower in the older group only in the case of iliac resistance. The characteristics of the CSB were not uniformly depressed in the older animals but were relatively well maintained compared with those of the younger group.
Transcapillary osmotic flows in the in vitro perfused heart
Authors: Vargas F. F. , Blackshear G. L.
Published: December 2017

Hearts were removed from rabbits anesthetized with pentobarbitol sodium, heparinized, and then perfused through the aorta with Ringer solution. Addition of sucrose to the perfusate caused an osmotic transcapillary flow (Jv). Measurements of Jv with two independent methods, one using the rate of organ weight change and the other the variation of effluent concentration of an impermeant dye (Blue dextran), agreed very closely, giving an initial Jv per unit concentration and wet heart weight of 0.306 (microliters/s) (mmol/l).g (corrected for viscosity, 25 degrees C). Because dye dilution was free of vascular volume interference, its agreement with weight measurements suggests that vascular volume changes were relatively small. Measurements using 51Cr-labeled erythrocytes supported the above conclusion. The effect of temperature and concentration on Jv was ascribed to viscosity changes. Organ condition remained stable for several hours, based on maximum ventricular pressure (107 +/- 6.4 cmH2O) and dP/dt (1,145 +/- 98 cmH2O/s) values close to those in blood-perfused rabbit hearts. Repeat weight response to osmotic testing showed approximately 5% variation during an experiment.
Decreased total venous capacity in Goldblatt hypertensive rats
Authors: Yamamoto J. , Trippodo N. C. , MacPhee A. A. , Frohlich E. D.
Published: December 2017

Mean circulatory filling pressure (MCFP) and total blood volume (BV) were determined in conscious rats during the early, intermediate, and chronic phases of one-kidney, one-clip Goldblatt hypertension. MCFP was determined from arterial and venous plateau pressures during brief circulatory arrest, which was accomplished by inflating an indwelling right atrial balloon. BV as determined from plasma volume (125I-albumin), arterial hematocrit, and the F-cells factor. As compared with one-kidney sham groups, MCFP was significantly increased in one-kidney, one-clip Goldblatt hypertensive groups at 3, 14, and 28 days postclipping, whereas no significant differences in BV between hypertensive and normotensive groups were observed at any of these time periods. Total vascular compliance, estimated by measuring MCFP before and immediately after rapid BV changes, was significantly decreased in all one-kidney, one-clip Goldblatt hypertensive groups. These results indicate that venous constriction was increased and whole-body venous capacity was decreased in all three phases of one-kidney, one-clip Goldblatt hypertension studied. The mechanism leading to increased venous constriction in one-kidney, one-clip Goldblatt hypertension remains to be elucidated.
Mechanism of cerebral arteriolar abnormalities after acute hypertension
Authors: Kontos H. A. , Wei E. P. , Dietrich W. D. , Navari R. M. , Povlishock J. T. , Ghatak N. R. , Ellis E. F. , Patterson J. L.
Published: December 2017

Acute severe hypertension induced by intravenous norepinephrine or angiotensin in anesthetized cats equipped with a cranial window caused prolonged arteriolar vasodilation associated with reduced responsiveness to arterial hypercapnia or hypocapnia and passive response to changes in arterial blood pressure. Scanning and transmission electron microscopy of such pial arterioles showed discrete destructive endothelial lesions the density of which correlated with the degree of vasodilation. Abnormalities of the vascular smooth muscle were seen in all dilated arterioles but affected only a small number of smooth muscle cells. The oxygen consumption of pial arterioles from cats subjected to hypertension was significantly reduced in comparison to that of vessels from normal animals. The arteriolar abnormalities induced by hypertension were inhibited by pretreatment with inhibitors of cyclooxygenase (indomethacin or AHR-5850) or by topical application on the brain surface of scavengers of free oxygen radicals (mannitol or superoxide dismutase). The results suggest that the mechanism of the arteriolar abnormalities from acute hypertension involves a sudden increase in prostaglandin synthesis that leads to generation of free oxygen radicals.
Cardiac contractility and sarcolemmal calcium binding in several cardiac muscle preparations
Authors: Bers D. M. , Philipson K. D. , Langer G. A.
Published: December 2017

Striking correlations are found between cardiac contractility and Ca2+ binding to isolated cardiac sarcolemma in rabbit, neonatal rat, and frog ventricular tissue. Deviations from this correlation are seen in the adult rat ventricle and rabbit atrium. The observation of this correlation in the three former tissues and under various ionic conditions suggests that this correlation is not coincidental and that Ca2+ bound to the cardiac sarcolemma is of major importance in the control of myocardial contractility. The data are consistent with a functional Ca2+-induced Ca2+ release system in the sarcoplasmic reticulum (SR) of all the tissues (which is controlled by Ca2+ entry from sarcolemmal sites), with the adult rat ventricular and rabbit atrial SR Ca2+ release being much more sensitive to CA2+. It is suggested that the frog, neonatal rat, and rabbit ventricles depend more directly on the entry of Ca2+ from sarcolemmal sites for the control of tension development, whereas the adult rat ventricle and rabbit atrium depend to a greater extent on CA2+ released from the SR.
Increased activity of carotid sinus baroreceptors by sympathetic stimulation and norepinephrine
Authors: Tomomatsu E. , Nishi K.
Published: December 2017

Effects of electrical stimulation of sympathetic nerves to the carotid sinus on the discharge of single active baroreceptor fibers of the rabbit were examined in situ and in functionally isolated carotid sinus preparations with an intact sympathetic innervation under controlled conditions of pressure and temperature. Among 30 single units, 18 units responded to sympathetic stimulation of increasing discharge frequency. The excitatory effect of sympathetic stimulation on baroreceptor activity was not abolished by phentolamine (1 mg/kg iv or 10(-6) g/ml in perfusate). In isolated carotid sinus preparations perfused with Krebs-Henseleit solution, various pressure steps were applied to the sinus, and effects of norepinephrine (NE; 10(-9) and 10(-6) g/ml) on activity of nine single baroreceptor units were examined. In the presence of 10(-9) g/ml NE, discharge frequency of all units significantly increased at a given pressure step when compared with the control, whereas NE at a high concentration (10(-6) g/ml) did not produce significant changes in the discharge frequency. It is concluded that NE released by sympathetic nerve endings most likely acts directly on the baroreceptor nerve endings and sensitizes them.
Cardiovascular and body fluid changes after aortic baroreceptor deafferentation
Authors: Werber A. H. , Fink G. D.
Published: December 2017

These experiments were performed to determine the role of fluid volume contraction in the compensatory cardiovascular response to an abrupt neurogenically mediated increase in systemic arterial blood pressure. Acute neurogenic hypertension was produced by selective aortic baroreceptor deafferentation (ABD) in the rat. Salt and water balance, fluid compartment volumes, and arterial pressure were measured before and for 5 days after the induction of hypertension by ABD. In rats with ABD, arterial pressure was increased approximately 30 mmHg 1 day after deafferentation and declined 15-20 mmHg over the next 4 days. Plasma volume and extracellular fluid volume were decreased 5 days after ABD. Urine output did not increase after ABD, and the fluid volume contraction was instead the result of a significant decrease in water intake. Sham-operated rats did not exhibit significant changes in any of these parameters. Sodium balance decreased slightly in both sham-operated and ABD rats postsurgery. These results confirm that fluid volume contraction is a prominent compensatory response to an abrupt rise in arterial pressure, but suggest that this compensation is not necessarily mediated through alterations in renal salt and water excretion.
Effects of prostaglandin D2 on perinatal circulation
Authors: Cassin S. , Tod M. , Philips J. , Frisinger J. , Jordan J. , Gibbs C.
Published: December 2017

Prostaglandin D2 (PGD2) is a powerful antiaggregatory agent and contracts various types of smooth muscle preparations, including isolated canine and bovine pulmonary vessels. Pulmonary vascular responses of anesthetized fetal and adult goats and newborn lambs to PGD2 were evaluated in situ by means of an isolated perfused lower left lobe preparation. These experiments indicate that PGD2 is a pulmonary vasodilator in fetal goats, both a pulmonary vasodilator and vasoconstrictor in newborn lambs depending on the dose used, and a pulmonary vasoconstrictor in adult goats. Evidence is presented of an age-related change in pulmonary vascular response to prostaglandins. The responses of the pulmonary vasculature are dose dependent; however, there is not a significant dose-dependent relationship for systemic arterial pressure or heart rate with intrapulmonary infusions of PGD2. The inhibition of prostaglandin synthesis potentiates the pulmonary response to PGD2 in fetal goats. In contrast with other prostaglandins, PGI2, PGE2, and PGE1, which dilate both the fetal pulmonary and systemic circulations, PGD2 has minimal action on the systemic circulation over a wide range of doses.
Abnormalities in baroreflex control of heart rate in canine heart failure
Authors: White C. W.
Published: December 2017

The mechanism of the attenuated arterial baroreceptor control of heart rate in heart failure was studied in 18 unanesthetized dogs after the development of chronic right-heart failure and compared to 12 control animals. The change in heart rate and arterial pressure in response to increases in right carotid sinus pressure during isolated carotid sinus perfusion was markedly reduced in heart failure (P less than 0.05). After vagotomy the difference in heart rate responses persisted, but was less pronounced (P = 0.065). The chronotropic response to perfusion of the sinus node artery with acetylcholine in heart-failure dogs showed a selectively depressed response, when compared to norepinephrine and hypertonic saline. The ratio of the change in heart rate in heart-failure vs. control dogs was 57% for acetylcholine but was not diminished for hypertonic saline (114%). The effect of direct vagal nerve stimulation on changes in heart rate was also markedly reduced in heart-failure dogs. These studies demonstrate that the alterations in baroreceptor control of heart rate in heart failure involve both the parasympathetic and sympathetic baroreflex efferent limbs. There is, in addition, a depressed responsiveness of the sinus node to cholinergic stimuli.
Continuous positive-pressure ventilation does not alter ventricular pressure-volume relationship
Authors: Fewell J. E. , Abendschein D. R. , Carlson C. J. , Rapaport E. , Murray J. F.
Published: December 2017

To determine whether alterations in the mechanical properties (i.e., stiffening) of the right and left ventricles contribute to the decrease in right and left ventricular end-diastolic volumes during continuous positive-pressure ventilation (CPPV), we studied six dogs anesthetized with chloralose urethane and ventilated with a volume ventilator. We varied ventricular volumes by withdrawing or infusing blood. Pressure-volume curves, constructed by plotting transmural ventricular end-diastolic pressures against ventricular end-diastolic volumes, did not change during CPPV (12 cmH2O positive end-expiratory pressure) compared to intermittent positive-pressure ventilation (IPPV, 0 cmH2O end-expiratory pressure). We conclude that decreased ventricular end-diastolic volumes during CPPV result primarily from a decrease in venous return. Alterations in the mechanical properties of the ventricles do not play a significant role in this response.