bluuebunny/crossref_metadata_2025 huggingface dataset:
Equivalent circuit technique for lymph flow studies
Authors: Drake R. E. , Allen S. J. , Katz J. , Gabel J. C. , Laine G. A.
Published: December 2017

Lymph vessels branch and interconnect in a manner similar to a complex electronic circuit. Accordingly, we have applied circuit analysis techniques to the analysis of lymphatic systems. A lymph vessel is cannulated and the "equivalent circuits" are determined for the parts of the vessel upstream and downstream of the site of cannulation. Each equivalent circuit consists of a single resistor in series with a single pressure source. A diode is included to represent the lymphatic valves. The lymph flow rate may be determined by calculating the flow in the circuits when they are connected to each other. This technique can be applied to larger lymph trunks that receive lymph from many tissues.
Activation of a cranial vasodilator pathway during seizures in rats
Authors: Faraci F. M. , Motley M. G. , Heistad D. D.
Published: December 2017

The purpose of this study was to determine whether seizures, which activate sympathetic nerves, also activate a vasodilator pathway to extracranial tissues of the head. Blood flow was measured with microspheres during control conditions and seizures in anesthetized, paralyzed rats. Seizures were produced by bicuculline or pentylenetetrazole. During seizures in rats with intact sympathetic nerves, blood flow to masseter muscle decreased and blood flow to tongue did not change. Following bilateral cervical sympathetic denervation or high spinal cord section, seizure produced marked increases in blood flow to masseter and tongue. These vasodilator responses, which were confined to the cephalic circulation (and were not observed in biceps femoris) were blocked by hexamethonium. The vasodilator response to seizures in masseter and tongue was not significantly attenuated after atropine. Thus seizures activate a dilator pathway to extracranial tissue of the head, sympathetic nerves limit the increase in blood flow produced by activation of the cranial dilator pathway during seizures, and vasodilatation in masseter and tongue during seizures is mediated primarily by a noncholinergic mechanism.
Pulmonary vascular pressure-flow relationship in canine oleic acid pulmonary edema
Authors: Boiteau P. , Ducas J. , Schick U. , Girling L. , Prewitt R. M.
Published: December 2017

We tested the hypothesis that the increased impedance to flow in canine oleic acid (OA) lung injury is predominantly due to an increase in effective downstream pressure (EDP), obtained by extrapolating to zero flow the linear portion of the pulmonary artery pressure (PAP)/flow (Q) relationship. PAP-Q coordinates were obtained in eight anesthetized, O2-ventilated dogs by varying Q through systemic arteriovenous fistulae. PAP-Q lines were obtained before and approximately 5 h after injection of OA. A second group of six dogs served as a time control (TC) group. There was a linear relationship between PAP and Q in both experimental and control groups (mean r value 0.948). The presence of pulmonary edema in the OA group caused the EDP to almost double, from 7 to 12 mmHg (P less than 0.01). In contrast, EDP remained constant in TCs. Incremental vascular conductance (IVC), slope of the PAP/Q line, decreased (P less than 0.05) a similar amount in both groups. The above findings are consistent with the modeling of the pulmonary circulation according to a Starling resistor in that large amounts of edema changed EDP but not incremental conductance.
Evidence against high pressure, arterial baroreceptors in the abdominal viscera of cats
Authors: Martin S. E. , Longhurst J. C.
Published: December 2017

The abdominal viscera of cats have been postulated to contain a site of cardiovascular regulation. In particular, a baroreceptive function has been ascribed to splanchnic afferent nerves. We wished to determine whether afferents with a cardiac-rhythmic discharge functioned as arterial baroreceptors. Nineteen afferents with a cardiac rhythmic discharge were studied. All afferents were A fibers, whose endings were located in either the pancreas, mesentery, or porta hepatis region. We examined their characteristics of discharge with regard to changes in mean pressure, pulse pressure, and dP/dt of the arterial pulse. Hemodynamic alterations were achieved by intravenous administration of isoproterenol, norepinephrine, or phenylephrine and by occlusion of the descending thoracic aorta. After isoproterenol, increases in nerve activity occurred when pulse pressure and dP/dt were increased but while mean pressure was decreasing, indicating that mean pressure was not the stimulus for discharge of these afferents. Additionally, under similar hemodynamic conditions, afferents did not demonstrate reproducible patterns of activity. The afferents generally discharged with one impulse per cardiac cycle, rarely with two to three impulses per cycle. None demonstrated a bursting pattern even when arterial blood pressure was quite elevated. The spontaneous pattern of discharge changed frequently, often after the viscera were repositioned, and sometimes remained even after complete occlusion of the aorta. The data indicate that these visceral afferents do not respond as high pressure, arterial baroreceptors. All afferents adapted extremely rapidly and exhibited a low gain (0.02 +/- 0.00 impulses X s-1 X mmHg-1), indicating that these fibers would be ineffective in signaling physiologically significant changes in hemodynamic variables. The data from this study do not support the existence of baroreceptors in the abdominal viscera of cats.
Role of mineralocorticoids and glucocorticoids in blood pressure regulation in normotensive rats
Authors: Yagil Y. , Koreen R. , Krakoff L. R.
Published: December 2017

The separate role of mineralocorticoid and glucocorticoid hormone action in maintaining arterial pressure was studied in normotensive rats. Four groups were prepared: adrenalectomized (ADX) rats given 6 micrograms aldosterone/24 h (ALDO; n = 9) or 10 micrograms dexamethasone/24 h (DEX; n = 9) by intraperitoneal Alzet pumps, shamoperated controls (control; n = 10) and ADX rats with no hormone replacement (ADX; n = 9). All groups were given 1% NaCl + 2.5% glucose drinking solution. Measurements of plasma corticosterone and aldosterone and urinary aldosterone excretion confirmed the adequacy of the experimental groups. Forty-eight hours after ADX or sham, base-line intra-arterial mean arterial pressure (MAP) in conscious undisturbed rats was similar in the four groups. Captopril (1 mg/kg iv) produced a similar reduction in MAP in ALDO (-11 +/- 2 mmHg) and DEX (-12 +/- 1 mmHg) groups, despite a lower plasma renin activity (PRA) in ALDO (2.0 +/- 0.7 and 6.0 +/- 1.5 ng X ml-1 X h-1, respectively; P less than 0.05). dP (Me)TyrAVP (50 micrograms/kg iv) caused a greater decrease in MAP in ALDO (-15 +/- 3 mmHg) than in DEX (-8 +/- 1 mmHg; P less than 0.05). Combined blockade with both antagonists resulted in a greater MAP reduction in ALDO (-29 +/- 4 mmHg) than in DEX (-15 +/- 4 mmHg; P less than 0.05). These results indicate that glucocorticoid hormone action maintains arterial pressure in ADX rats by mechanisms similar to normal rats and largely independent of the renin-angiotensin system and vasopressin. In contrast, mineralocorticoid replacement alone in ADX rats requires increased participation of both peptide systems for maintenance of arterial pressure.
Chronic measurement of cardiac output in unanesthetized rats using miniature thermocouples
Authors: Osborn J. W. , Barber B. J. , Quillen E. W. , Abram R. J. , Cowley A. W.
Published: December 2017

A thermodilution technique is described for measuring steady-state cardiac output (CO) in conscious rats for periods of 2–3 wk. The method utilizes small implantable aortic thermocouples inserted via the femoral artery at the time of placement of other chronic indwelling catheters. Data are presented to validate the accuracy and reproducibility of the technique by acute in situ comparison with electromagnetic flowmeter measurements. Responses in chronically instrumented rats were tested with hemorrhage and infusions of vasodilator and vasoconstrictor agents administered repeatedly over a period of 9 days. The results show that the system is capable of measuring CO chronically and provides reproducible responses for periods of at least several weeks. We conclude that these methods provide a single, inexpensive, and accurate way to measure steady-state CO in conscious, unrestrained rats.
Chronic measurement of cardiac output in unanesthetized rats using miniature thermocouples
Authors: Osborn J. W. , Barber B. J. , Quillen E. W. , Abram R. J. , Cowley A. W.
Published: December 2017

Page H1365: J. W. Osborn, Jr., B. J. Barber, E. W. Quillen, Jr., R. J. Abram, and A. W. Cowley, Jr. “Chronic measurement of cardiac output in unanesthetized rats using miniature thermocouples.” Page H1367: Substitute correct Fig. 2.

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Autoregulatory escape from vasoconstriction of intestinal circulation in developing swine
Authors: Buckley N. M. , Jarenwattananon M. , Gootman P. M. , Frasier I. D.
Published: December 2017

The capability of the developing intestinal circulation to maintain a vasoconstrictor response during postganglionic adrenergic nerve stimulation or norepinephrine infusion was examined in 34 swine aged 6 h to 2 mo anesthetized with pentobarbital sodium. Aortic and portal venous pressures, electrocardiogram (ECG), and blood flow (F) through the superior mesenteric artery were recorded, and intestinal vascular resistance (MVR) was calculated as mean pressure difference per mean F. Baroreceptor reflex inhibition by bilateral occlusion of the carotid arteries increased MVR, section of the splanchnic nerve and postganglionic fibers decreased MVR, and short-latency F decreases were obtained during mesenteric nerve stimulation (MNS). Latencies for the decreases in F shortened with age and with increasing MNS frequency (5–17 Hz) at any age. Prolonging MNS for 60 s at 10 or 12 Hz led to sustained high MVR in 6-h to 7-day-old animals; however, MVR decreased toward control before the end of the 60-s MNS period in animals 1 to 2 mo old. Intra-arterial infusion of norepinephrine (0.5 microgram X kg-1 X min-1) decreased F and increased MVR in all animals; but by 5 min of infusion, F was returning toward control level in all but the youngest. This demonstration that the least mature intestinal circulation was least capable of autoregulatory escape from vasoconstriction provides further evidence of its functional immaturity.
Effect of theophylline on adenosine production in the canine myocardium
Authors: McKenzie J. E. , Steffen R. P. , Haddy F. J.
Published: December 2017

Adenosine is thought to participate in local regulation of coronary blood flow. However, competitive antagonists of adenosine fail to block myocardial active hyperemia. We examined the effect of locally administered theophylline on active hyperemia and myocardial adenosine production during intracoronary isoproterenol infusion in the dog heart. Isoproterenol decreased coronary resistance and increased myocardial adenosine production. Infusion of theophylline at a rate that attenuated the vasodilator response to exogenously administered adenosine failed to attenuate the increase in coronary blood flow produced by isoproterenol. However, theophylline plus isoproterenol produced greater increases in myocardial adenosine production than isoproterenol alone. The curves relating resistance and adenosine in the presence of theophylline fell to the right of those in the absence of theophylline. These findings suggest that the failure of theophylline to attenuate isoproterenol hyperemia in the dog heart results at least in part from an increase in adenosine concentration at the arteriole to a level beyond that blocked by this competitive antagonist and that adenosine may in fact play a role in isoproterenol-induced active hyperemia.
Deinhibition of cardiac Na+-K+-ATPase after exposure to exogenous phospholipase A2
Authors: Colvin R. A.
Published: December 2017

After 2 h of exogenous phospholipase A2 (PLA2) exposure, membrane phospholipid decreased from 3.22 +/- 0.31 to 1.06 +/- 0.13 mumol/mg (33% of control). All classes of phospholipid, except sphingomyelin, were hydrolyzed, whereas total cholesterol content was unaffected. Increases in nonesterified fatty acids (NEFA) were reflected primarily in oleic (18:1), linoleic (18:2), and arachidonic (20:4). Na+-K+-adenosinetriphosphatase (ATPase) activity was inhibited to 29% of control by 2 h of PLA2 treatment, and this inhibition was reversed (albeit, not completely after 5 min of PLA2 treatment) by removal of the hydrolysis products with 0.1% bovine serum albumin (BSA). In contrast, the apparent binding capacity for [3H]ouabain was not affected by PLA2 treatment. Unmasking of latent [3H]ouabain binding by alamethicin was utilized to estimate changes in the proportion of sealed vesicles present before and after PLA2 treatment. PLA2 treatment resulted in a time-dependent loss of sealed vesicles that paralleled the time course of phospholipid hydrolysis and was not reversed by washing with BSA. These studies demonstrate that cardiac Na+-K+-ATPase activity is inhibited by accumulation of endogenously produced lysophospholipids and NEFA. In contrast, loss of vesicle integrity may result from both accumulation of endogenously produced hydrolysis products and membrane phospholipid depletion.
Blood and isoproterenol reduce capillary permeability in cat hindlimb
Authors: Watson P. D. , Wolf M. B. , Beck-Montgomery I. S.
Published: December 2017

In an earlier study, plasma was observed to counteract the permeability-increasing effects of blood-free perfusion when papaverine was present in the perfusate. To determine if this plasma effect was still present in the absence of papaverine, cat hindlimbs were perfused with a blood-free albumin-electrolyte solution, and capillary filtration coefficient (CFC) was measured. These data were compared with CFC values obtained when blood, plasma, or isoproterenol were present in the albumin perfusate. In separate groups of animals, CFC was observed to be 0.017 +/- 0.006 (SD, n = 26) ml X min-1 X mmHg-1 X 100 g muscle-1 during blood-free albumin perfusion, 0.012 +/- 0.002 (n = 24) when blood was present, 0.014 +/- 0.003 when isoproterenol was present, and 0.010 +/- 0.002 (n = 33) when both blood and isoproterenol were present. In a separate study, it was observed that 1) isoproterenol could reduce CFC by 11% when added to blood-free perfusate, 2) plasma had a similar but smaller and more variable effect than isoproterenol, 3) plasma had no consistent effect on CFC when added to a blood-free albumin perfusate containing isoproterenol, and 4) blood could reduce CFC significantly (P less than 0.005), from 0.014 +/- 0.003 to 0.0094 +/- 0.002 (n = 7), when added to a blood-free albumin perfusate containing isoproterenol. It was concluded that, in the absence of papaverine, the principal CFC-reducing effect of blood lay in the cell fraction and that isoproterenol had a small CFC-reducing effect under blood-free conditions. This result contrasts with the plasma effect reported earlier.
Albumin and IgG in skin and skeletal muscle after plasmapheresis with saline loading
Authors: Mullins R. J. , Powers M. R. , Bell D. R.
Published: December 2017

The acute effect of removing plasma equivalent to 1.7% body wt and replacing it with saline equivalent to 10% body wt on the extravascular distribution of water, albumin, and immunoglobulin G (IgG) in skin and skeletal muscle was studied in anesthetized rabbits. The plasma protein concentration decreased by 43%. Prenodal lymph was collected from hindpaw skin or skeletal muscle. The extracellular and plasma volumes in excised tissue samples were measured using 51Cr-labeled ethylenediaminetetraacetic acid and 125I-labeled albumin, respectively. The protein spaces were calculated from measurements of endogenous albumin and IgG concentrations using immunochemical techniques. Lymph flow from both tissues increased more than twice control, whereas the lymph total protein concentration decreased to less than one-half control. Three to six hours after the saline infusion, the skin interstitial volume was 30% greater than control, whereas the extravascular masses of albumin and IgG were 20% greater than control. For muscle, the interstitial volume was twice the control value, whereas the extravascular masses of albumin and IgG were not significantly altered. There was a large decrease in the lymph protein concentration after acute plasmapheresis. However, there was not an acute decrease in the extravascular albumin or IgG masses from skin or skeletal muscle. This may be due to the presence of the collagen matrix and edema fluid.
Chronic measurement of cardiac output in unanesthetized rats using miniature thermocouples
Authors: Osborn J. W. , Barber B. J. , Quillen E. W. , Abram R. J. , Cowley A. W.
Published: December 2017

Page H1365: J. W. Osborn, Jr., B. J. Barber, E. W. Quillen, Jr., R. J. Abram, and A. W. Cowley, Jr. “Chronic measurement of cardiac output in unanesthetized rats using miniature thermocouples.” Page H1367: corrected Fig. 2 should be substituted.

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Energy production, O2 consumption, and blood flow reserve in experimental aortic valve disease
Authors: Qian S. F. , Brum J. M. , Bove A. A.
Published: December 2017

Left ventricular energy production and its relation to myocardial O2 consumption and blood flow reserve were studied in 11 dogs with surgically produced valvular aortic stenosis (AS, 6 of 11) or combined stenosis and insufficiency (AS + AI, 5 of 11), and 7 dogs undergoing sham operation (S). Two months after operation the combined AS + AI group had the highest left ventricular mass (S, 4.85 +/- 0.53; AS, 6.38 +/- 0.90; AS + AI, 7.23 +/- 0.39 g/kg), left ventricular end-diastolic pressure (S, 2.1 +/- 1.6; AS, 6.3 +/- 1.7; AS + AI, 8.6 +/- 3.1 mmHg), left ventricular end-diastolic volume (S, 61.1 +/- 8.5; AS, 73.0 +/- 7.8; AS + AI, 95.8 +/- 20.9 ml), and stroke work. At rest, total left ventricular myocardial blood flow was increased in AS and AS + AI compared with sham (S, 89 +/- 8; AS, 135 +/- 19; AS + AI, 164 +/- 9 ml/min, P less than 0.05); and coronary resistance was lower in both AS and AS + AI groups. Peak-to-resting flow ratio determined by adenosine vasodilation was reduced in AS and AS + AI despite normal resting function (peak-to-resting flow ratio: S, 6.78 +/- 2.24; AS, 3.19 +/- 0.58, AS + AI, 3.99 +/- 0.84, P less than 0.02). Peak-to-resting flow ratio was inversely proportional to left ventricular mass. In turn the degree of hypertrophy correlated with the total power requirement of the left ventricle, regardless of the type of overload lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of cardiac sympathetic nerve stimulation on regional coronary blood flow
Authors: Haws C. W. , Green L. S. , Burgess M. J. , Abildskov J. A.
Published: December 2017

The purpose of this study was to examine the effects of cardiac sympathetic nerve stimulation on regional coronary blood flow following beta-blockade. In 17 anesthetized dogs treated with propranolol (2 mg/kg iv) regional myocardial perfusion was measured (microspheres) during control and during stimulation of the ventrolateral, ventromedial, or recurrent cardiac nerve (8–10 V, 4-ms pulses at 10 Hz for 30 s). Ventrolateral nerve stimulation produced 25.5 +/- 3.4 and 23.5 +/- 3.1% (mean +/- SE) decreases in coronary blood flow in the posterior and lateral quadrants of the left ventricle. These changes were significantly greater than the 8.5 +/- 2.9, 11.5 +/- 3.0, and 3.7 +/- 2.8% decreases in the anterior and septal left ventricle and right ventricle, respectively (P less than 0.01). Ventromedial nerve stimulation produced 18.6 +/- 2.8, 15.4 +/- 2.8, and 10.1 +/- 3.2% decreases in flow in the anterior, septal, and lateral left ventricle, respectively. These changes were significantly greater than the 5.3 +/- 3.8 and 9.9 +/- 3.6% decrease in the posterior left ventricle and right ventricle (P less than 0.01). Recurrent cardiac nerve stimulation produced 16.4 +/- 2.1, 15.6 +/- 2.2, and 13.6 +/- 2.5% decreases in flow in the anterior and septal left ventricle and right ventricle, respectively. These changes were significantly greater than the 5.2 +/- 3.2 and 5.4 +/- 3.0% changes in the posterior and lateral quadrants (P less than 0.01). Ventrolateral nerve stimulation resulted in a small but significant increase in the endocardial-to-epicardial blood flow ratio in the posterolateral left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)
Voltage- and time-dependent block of iK1 underlying Ba2+-induced ventricular automaticity
Authors: Imoto Y. , Ehara T. , Matsuura H.
Published: December 2017

The mechanism underlying the Ba2+-induced automaticity was studied in isolated guinea pig ventricular myocytes using the whole-cell clamp method and a patch electrode. In the presence of 0.1–0.3 mM Ba2+, application of a weak depolarizing current induced repetitive firing of spontaneous action potentials. Application of tetrodotoxin or Ca2+ channel blockers and removal of external Na+ and Ca2+ did not abolish the rhythmic activity, thereby suggesting that activation of inward currents played no crucial role in the generation of this rhythmicity. Voltage-clamp studies revealed that Ba2+ blocked the inward rectifier K+ current (iK1) in a voltage- and time-dependent manner with a greater and more rapid block at more negative potentials. This Ba2+ action could quantitatively be fitted with a model of the conventional bimolecular adsorption isotherm with a voltage-dependent dissociation constant. Simulation studies using this model showed that a membrane model, in which only the iK1 system and a small leak conductance were incorporated, could reproduce an automatic activity similar to that seen experimentally. Thus, in isolated ventricular cells, the voltage- and time-dependent block of iK1 by Ba2+ appears to be one important mechanism underlying the automaticity.
Beta-adrenergic function in a congestive cardiomyopathy model
Authors: Staley N. A. , Einzig S. , Noren G. R. , Surdy J. E. , Elsperger J.
Published: December 2017

We investigated the cardiac beta-adrenergic-adenylate cyclase (AC) system in turkeys inbred for congestive cardiomyopathy (CCM) and the relation of this system to echocardiographically determined left ventricular shortening fraction (LVSF) in individual 56-day-old birds. The isoproterenol (Iso)-stimulated, NaF-stimulated, and basal AC activities in CCM birds were decreased to 69, 72, and 86%, respectively, of control values, P less than 0.05. By linear regression analysis there was significant direct correlation of initial LVSF in CCM birds with each of the following: change in heart rate (HR) after Iso function; Iso-stimulated, NaF-stimulated, and basal AC activities, and density of beta-adrenergic receptors. In addition, we investigated the effect of Iso infusion (0.4 microgram X kg-1 X min-1) on systemic hemodynamics. In CCM birds the initial LVSF was 72% of the control value, P less than 0.01; the initial HR was 112% of the control value, P less than 0.01. During Iso infusion both the LVSF and HR in control birds were increased, whereas in CCM turkeys with marked cardiac dilatation neither of these parameters changed. In 10-day-old CCM turkeys, which show no cardiac dilatation, NaF-stimulated AC activity was reduced to 70% of the control values, whereas basal and Iso-stimulated AC activities were unchanged. Thus an abnormality in the beta-adrenergic-adenylate cyclase system is present in CCM birds before development of cardiac dilatation; when cardiac dilatation is severe, a global defect in this system can be directly related to depressed inotropic and chronotropic responsiveness to Iso infusion in individual turkeys.
Endothelial extraction of tracer water varies with extravascular water in dog lungs
Authors: Chinard F. P. , Cua W. O.
Published: December 2017

In multiple indicator-dilution experiments, transvascular passage of a permeating indicator is conventionally derived from the up-slope separation of the curve of the permeating indicator from that of a vascular reference and is expressed as the extraction (Ec). Extraction may be limited by the barrier (barrier-limited distribution). It may be limited by the volume of distribution accessible to it; in the time domain of an indicator-dilution experiment, the passage to and distribution in the extravascular volume are rapid relative to the velocity of blood in the exchange vessels. We examine here the relations of the extraction of tracer water as tritium oxide (THO) [Ec(THO)] and of the extraction of tracer sodium as 22Na [Ec(22Na)] to extravascular lung water, delta V wev, by adding isotonic fluid to the gas phase of the lungs. The net convective transvascular passage of water is negligible relative to the transendothelial molecular exchange. In 10 experiments in vivo and in 10 experiments in isolated perfused lungs, Ec(THO) increases as delta V wev increases. Ec(22Na) and the permeability-surface area product (PS) for 22Na do not change as delta V wev increases. We conclude that the extraction of THO is determined mainly by the volume accessible to it (flow- or volume-limited distribution) and that the extraction of 22Na is determined mainly by the resistance of the endothelium (barrier-limited distribution). A diffusion limitation in the added alveolar fluid rather than a barrier limitation at the endothelium may moderate Ec(THO).
Purine efflux after cardiac ischemia: relevance to allopurinol cardioprotection
Authors: Grum C. M. , Ketai L. H. , Myers C. L. , Shlafer M.
Published: December 2017

Allopurinol is thought to protect hearts against damage due to hypoxia or ischemia by inhibiting xanthine oxidase and oxygen radical generation. We subjected isolated rabbit hearts, equilibrated by perfusion at 37 degrees C, to 1 h of global ischemia at 27 or 37 degrees C with or without brief pretreatment with 100 microM allopurinol. The total absence of xanthine or uric acid in the coronary effluent following ischemia, the presence of hypoxanthine (25 +/- 4 microM peak concentration), and the failure of allopurinol to alter purine washout profiles or postischemic cardiac function suggest that rabbit myocardium lacks xanthine oxidase or dehydrogenase. Data obtained with a similar rat heart preparation showed appreciable formation of xanthine (12 +/- 2 microM peak) and uric acid (10 +/- 3 microM). Allopurinol pretreatment inhibited xanthine and uric acid formation and significantly improved key indicators of postischemic left ventricular function. We conclude that there is species dependency in the myocardial activity of xanthine oxidase or dehydrogenase, that when present it can be inhibited by acute allopurinol pretreatment, and that xanthine oxidase activity and its ability to generate oxygen radicals are not universal contributors to cardiac ischemic damage.
Control of cardiac function and venous return in thyrotoxic calves
Authors: Gay R. , Lee R. W. , Appleton C. , Olajos M. , Martin G. V. , Morkin E. , Goldman S.
Published: December 2017

The mechanisms responsible for maintenance of the high-output state associated with thyrotoxicosis have been investigated by measurement of cardiac-function curves and venous compliance during ganglionic blockade with trimethaphan. Thirteen calves were injected daily with L-thyroxine (200 micrograms/kg) for 12–14 days. Thyroxine treatment increased heart rate (70%), left ventricular systolic pressure (22%), cardiac output (120%), left ventricular maximum rate of pressure development (dP/dt) (56%), and total blood volume (18%) and decreased systemic vascular resistance (39%). These hemodynamic changes persisted during ganglionic blockade or autonomic blockade with atropine and propranolol. Cardiac-function curves in conscious thyrotoxic calves were displaced upward and to the left. Mean circulatory filling pressure (MCFP), measured during anesthesia, was increased from 8 +/- 1 to 12 +/- 1 mmHg. During autonomic and ganglionic blockade MCFP remained elevated after treatment with thyroxine. Venous compliance decreased from 2.1 +/- 0.2 to 1.3 +/- 0.1 ml X mmHg-1 X kg-1 after thyroxine. Unstressed vascular volume was increased from 52.3 +/- 1.1 to 67.1 +/- 0.9 ml/kg. Thus the elevated cardiac output and new cardiac-function curve in thyrotoxicosis are associated with a combination of increased inotropic state, increased blood volume, and decreased venous compliance. These effects are not the result of autonomic influences and may represent direct actions of thyroid hormone on the heart and peripheral venous circulation.
Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats
Authors: Bonham A. C. , Gutterman D. D. , Arthur J. M. , Marcus M. L. , Gebhart G. F. , Brody M. J.
Published: December 2017

Based on evidence implicating the central nervous system in the regulation of coronary vascular resistance and the knowledge that the hypothalamus is a central site for integration of cardiovascular control, studies were undertaken to determine if electrical stimulation in the hypothalamus produced coronary vasoconstriction. In anesthetized cats, following beta-adrenergic receptor blockade, stimulation in perifornical lateral hypothalamus produced a transient decrease in coronary blood flow velocity (30 +/- 5%), a small pressor effect (7 +/- 2 mmHg), and an initial decrease in hindquarter blood flow velocity (51 +/- 5%). The decrease in coronary flow velocity, which had an onset latency of 1-3 s and a duration of 5-15 s, was abolished by ipsilateral stellate ganglionectomy and by intravenous and intracoronary prazosin. The coronary vasoconstriction produced by hypothalamic stimulation was not different from that produced by cardioaccelerator nerve stimulation. These results suggest that electrical stimulation of a hypothalamic site produces an alpha-adrenergic receptor-mediated decrease in coronary blood flow that is unmasked by beta-adrenergic receptor blockade, requires the integrity of ipsilateral cardiac sympathetic innervation, and mimics the coronary response to cardioaccelerator nerve stimulation.
Temperature distribution cannot predict local cardiac metabolism
Authors: Duijst P. , Elzinga G. , Westerhof N.
Published: December 2017

The objective of this study was to investigate if local myocardial metabolism can be determined from the transmural temperature distribution. Heat produced metabolically in the myocardium is carried away by the coronary blood and by diffusion. Transport by coronary flow (convectional heat loss) was determined from the coronary blood flow and the transcoronary temperature difference. This measured value was compared with one predicted from measured oxygen consumption, assuming a slab of tissue for the left ventricular free wall with homogeneous flow distribution and homogeneous metabolism. Measured and predicted convectional heat loss could not be shown to differ. Endocardial and epicardial heat production were estimated in two ways: 1) from the transmural temperature distribution (AT) and 2) from local flow (radioactive microspheres) and oxygen consumption (AO2). Ideally the ratio AT/AO2 should be unity. For flows in the resting physiological state (up to 100 ml X min-1 X 100 g-1) this ratio was not statistically different from one for both endocardium and epicardium: 0.86 +/- 0.11 and 1.09 +/- 0.07 (SE), respectively. For larger flows the ratio reduced to 0.66 +/- 0.08 endocardially. It is concluded that overall left ventricular metabolism can be predicted from conventional heat loss and that for physiological, but not for increased flow, the transmural temperature distribution predicts local metabolism.
Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus
Authors: Heyliger C. E. , Prakash A. , McNeill J. H.
Published: December 2017

Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca2+ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca2+ transport, little appears to be known about its Ca2+ transporting capability in the diabetic myocardium. In this regard, we have examined the status of the cardiac sarcolemmal Ca2+ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection (55 mg/kg iv). Ca2+ pump activity assessed by measuring its Ca2+-stimulated adenosine triphosphatase and Ca2+-uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca2+ pump is defective in the diabetic myocardium and may be involved in the altered Ca2+ transport of the heart during diabetes mellitus.
Quantification of O2 consumption and arterial pressure as independent determinants of coronary flow
Authors: Vergroesen I. , Noble M. I. , Wieringa P. A. , Spaan J. A.
Published: December 2017

The steady-state relationship between coronary arterial blood flow (CBF) and both myocardial O2 consumption (MVO2) and coronary arterial pressure (P) was explored in anesthetized dogs and goats. Both species were subjected to constant pressure perfusion of the left main coronary artery by an external pressure-controlling circuit. In addition a group of goats was studied with normal aortic perfusion using an occluder around the left main coronary artery to vary coronary arterial pressure. The statistical analysis revealed that despite the direct effect of P on MVO2 (the Gregg effect) the effects of both variables on CBF were independent and linear over a wide range of P and MVO2 so that multiple regression analysis with a linear equation (CBF = a X P + b X MVO2 + c) gave an excellent fit which was not improved by the introduction of an addition interactive term b3MVO2 X P. The mean correlation coefficient for all animals was greater than 0.9. From these data we conclude that any factor regulating coronary arterial flow would be influenced by both MVO2 and perfusion pressure in an independent way. This study characterizes the stationary behavior of local coronary flow control. Hence, it specifies quantitatively the relations to be predicted by hypotheses aiming to explain this control mechanism.
Effect of dietary fish oil on myocardial phospholipids and myocardial ischemic damage
Authors: Hock C. E. , Holahan M. A. , Reibel D. K.
Published: December 2017

The effect of dietary fish oil on myocardial phospholipids and ischemic damage to the heart was studied in the rat. Four weeks of feeding 5% (i.e., 12 energy percent) menhaden oil (MO) produced both profound changes in the fatty acyl composition of phospholipids in myocardial membranes and a significant reduction in the loss of creatine kinase following coronary artery ligation compared with feeding 5% (i.e., 12 energy percent) corn oil (CO). The MO diet did not change the content of either phospholipids or cholesterol in the heart. However, dietary MO resulted in significant elevations in the percent of fatty acids in the total phospholipids that were saturated, the n-3/n-6 ratio and the double-bond index. The changes in total phospholipids were not uniform for all phospholipid classes. Although the n-3/n-6 ratio was increased in each of the individual phospholipids examined, the predominant n-3 fatty acid incorporated (i.e., 20:5, 22:5, 22:6) differed among the major phospholipid classes. Also, the percent saturation was elevated in phosphatidylcholine with no change in double-bond index, whereas both the percent saturation and double-bond index were elevated in phosphatidylethanolamine. Thus dietary MO resulted in selective alterations in individual myocardial phospholipids. These membrane changes may be involved in the observed reduction of ischemic damage in the heart.
Cholinergic vasodilator mechanism in human fingers
Authors: Coffman J. D. , Cohen R. A.
Published: December 2017

The effect of a cholinergic agonist and antagonist on finger blood flow (FBF) was studied in 10 normal subjects. Total finger blood flow was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radioisotope from a fingertip injection. Methacholine in doses of 10-80 micrograms/min was given by constant infusion via a brachial artery catheter. Average FBF (7.4 +/- 2.5 to 10.9 +/- 4.3 ml X min-1 X 100 ml tissue-1) and vascular resistance (22.4 +/- 4.7 to 21.3 +/- 7.0 mmHg X ml-1 X min X 100 ml tissue) were not significantly affected. However, the half time (t1/2) of the disappearance rate decreased from 50.8 +/- 13.4 to 11.1 +/- 1.5 min (P less than 0.01); a decrease occurred in all subjects. In seven subjects, atropine (0.2 mg) had no affect alone but inhibited the effect of methacholine on FCF (t1/2 47.6 +/- 6.2 to 50.2 +/- 6.7 min) and prevented the redness and sweating of the forearm and hand that occurs with this agent. This study demonstrates a muscarinic cholinergic vasodilator mechanism in the fingertip that uniquely increases capillary blood flow.
Hemodynamic effects of vasopressin compared with angiotensin II in conscious rats
Authors: Osborn J. W. , Skelton M. M. , Cowley A. W.
Published: December 2017

The mechanisms whereby arginine vasopressin influences hemodynamic and autonomic function were investigated in conscious rats. In normal rats, 60-min intravenous infusions produced dose-related increases of arterial pressure and total peripheral resistance with marked decreases of both heart rate and cardiac output. Cholinergic blockade with methscopolamine attenuated the bradycardia at higher doses of vasopressin, whereby the fall of cardiac output was not affected. beta-Adrenergic blockade with atenolol attenuated the fall of heart rate seen with lower doses of vasopressin but did not prevent the fall of cardiac output. Ganglionic blockade with methscopolamine and hexamethonium resulted in nearly a 60-fold enhancement of vasopressin pressor sensitivity. This was related to a greater rise of peripheral resistance, since the fall of cardiac output was not altered compared with normal rats. Hemodynamic responses to angiotensin II were determined in other groups of conscious, normal rats and rats with ganglionic blockade. Peripheral resistance increased in the normal rats, whereas the related decreases in cardiac output and heart rate were only 30% of the responses seen with equipressor doses of vasopressin. Ganglionic blockade increased pressor activity only two- to eightfold compared with the 60-fold increase observed with vasopressin. We conclude that vasopressin is a more potent vasoconstrictor than angiotensin II, decreases cardiac output independent of neural mechanisms, and results in withdrawal of sympathetic vascular tone to buffer rises of arterial pressure.
Excitability and oscillatory afterpotentials in isolated sheep cardiac Purkinje fibers
Authors: Terek R. M. , January C. T.
Published: December 2017

Oscillatory afterpotentials, or late afterdepolarizations, are one mechanism postulated to cause cardiac arrhythmias and possibly conduction disturbances. We studied excitability by determining strength-interval curves in Purkinje fibers under normal conditions and during the presence of oscillatory afterpotentials induced by cardiac glycoside toxicity. During exposure to acetylstrophanthidin (0.10–0.15 mg/l), the mean resting potential depolarized 5.6 mV and oscillatory afterpotentials of 3–17 mV appeared. Current threshold for evoking action potentials was reduced below control level (e.g., increased excitability) throughout electrical diastole. Associated with oscillatory afterpotentials was a marked biphasic variation in current threshold giving strength-interval curves a characteristic biphasic shape. During the rising phase of the oscillatory afterpotentials, excitability reached a maximum, whereas the minimum increase in excitability occurred during the falling phase of oscillatory afterpotentials. This biphasic change in excitability remained correlated with the oscillatory afterpotentials at different cycle lengths. Results show that during acetylstrophanthidin toxicity excitability is increased throughout electrical diastole, and characteristic time-dependent changes in excitability occur during oscillatory afterpotentials. Time-dependent changes in excitability were detected with both intra- and extracellular stimulation techniques.
Effect of AVP on pressor responses to peripheral sympathetic stimulation in the rat
Authors: Osborn J. W. , Liard J. F. , Cowley A. W.
Published: December 2017

Studies were carried out to determine whether arginine vasopressin (AVP) could modulate pressor responses to peripheral sympathetic stimulation or potentiate systemic norepinephrine (NE) vasoconstrictor effects. The effects of graded 30-min infusions of AVP (0.02, 0.2, and 2.0 ng X kg-1 X min-1) on the pressor responses to either electrical stimulation of spinal sympathetic outflow or NE injection (0.1, 0.5, and 1.0 micrograms/kg) were determined in central nervous system-ablated rats. Spinal stimulation with increasing frequency (0.25, 0.5, and 1.0 Hz, n = 8) at a constant voltage (20 V) or increasing voltage (8, 10, 15, and 20 V, n = 6) at a constant frequency (1 Hz) elicited significant stimulus-response relationships in mean arterial pressure (MAP). Similarly, NE increased MAP in a dose-related manner. AVP had no significant effect (P less than 0.05) on pressor responses to increasing frequency or voltage stimulation or to NE injection. We conclude that pressor responses to sympathetic stimulation in the rat are not modulated by actions of AVP to inhibit peripheral sympathetic ganglionic transmission or potentiate NE vasoconstrictor effects.
Rat venule mechanical characteristics during venous pressure elevation
Authors: Lang D. J. , Johns B. L.
Published: December 2017

The purpose of this study was to compare the in vivo mechanical characteristics during venous pressure elevation of two sizes of venules in the intestinal muscularis of anesthetized Wistar rats. The two venules studied were the first-order venule (1V), ID = 71.2 +/- 3.3 microns [12] (means +/- SE [n]) and the small collecting vein (SCV), ID = 134.4 +/- 9.1 microns [12]. Vessel diameters and servonull pressures were measured as venous pressure was elevated with a snare about the vein of the isolated segment. The distension characteristics of the two vessels were significantly different, with the 1V evidencing greater strains (percent change from control diameter) and in vivo distensibilities [D = (delta lumen area/lumen area)/delta pressure] than the SCV at all pressure elevations above control. The 1V and SCV mean wall elastic moduli (calculated using Rhodin's measurements of venule control wall thickness) reflected these differences: the initial 1V wall Young's modulus was low and changed little during the vessel distension, whereas the SCV modulus was greater at control and increased sharply with strain in a nonlinear fashion. Although a portion of these differences can be attributed to different initial hoop wall stress levels, the SCV elastic modulus was significantly greater than the 1V modulus at comparable levels of wall stress. Both active and passive factors may contribute to these in vivo differences in elastic modulus, but this experiment does not distinguish between them.
Effects of coronary occlusion on arterial baroreflex control of heart rate and vascular resistance
Authors: Trimarco B. , Ricciardelli B. , Cuocolo A. , Volpe M. , De Luca N. , Mele A. F. , Condorelli M.
Published: December 2017

This study was planned to assess whether circumflex coronary occlusion (CO) impairs the arterial baroreflex control of heart rate (HR) and hindlimb vascular resistance (HVR), and to determine the mechanisms involved in the mediation of these phenomena. Increasing doses of phenylephrine and nitroglycerin were given intravenously to anesthetized dogs with a constant flow-perfused hindlimb before and during 30-s CO. The reflex responses were assessed by the changes in HR and hindlimb perfusion pressure evoked by changes in arterial pressure following phenylephrine and nitroglycerin administration. During CO, there was an attenuation of the reflex control of HR and HVR as compared with control conditions. The application of lidocaine on the left ventricular epicardial surface was able to prevent the effect of CO on both the baroreflex responses. The intravenous administration of atropine prevented only the impairment in arterial baroreflex control of HR induced by CO. After the injection of phentolamine into the perfused hindlimb, the baroreflex had no effect on HVR either before or during CO. Finally, intravenous administration of propranolol failed to modify the effect of CO on both the baroreflex responses. These data indicate that CO attenuates the arterial baroreflex control of both HR and HVR through the stimulation of left ventricular receptors. The effect on HR is mediated by the parasympathetic system, whereas the effect on HVR is due to sympathetic efferents.
Positive inotropic effects of acetylcholine and BAY K 8644 in embryonic chick ventricle
Authors: Tsuji Y. , Tajima T. , Yuen J. , Pappano A. J.
Published: December 2017

BAY K 8644 augmented Ca2+-dependent action potentials and evoked a positive inotropic effect in embryonic chick ventricle. These effects are consistent with the properties of this Ca channel "agonist" whose actions are independent of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphorylation. At low to intermediate concentrations (10(-8) to 10(-6) M), the cholinergic agonists acetylcholine, carbachol, and oxotremorine inhibit Ca2+-dependent action potentials and contractions in embryonic ventricle only in the presence of drugs that cause cAMP accumulation. The prediction that low to intermediate concentrations of these cholinergic agonists should not inhibit the effects of BAY K 8644 on Ca2+-dependent action potentials and contractions was borne out experimentally. This result is consistent with the cAMP hypothesis for muscarinic inhibition. It is noteworthy that all cholinergic agonists tested evoked a positive inotropic effect at high concentrations (greater than 10(-6) M) in the presence or absence of BAY K 8644. The positive inotropic effect was initiated by muscarinic receptors for it was blocked by atropine and was independent of endogenous catecholamines, since it occurred in the presence of propranolol. It is speculated that the positive inotropic effect of muscarinic agonists in embryonic heart muscle is related to stimulation of phosphoinositide metabolism.
Effect of aortic constriction on the functional border zone
Authors: Gallagher K. P. , Ning X. H. , Gerren R. A. , Drake D. H. , Dunham W. R.
Published: December 2017

To evaluate how aortic constriction affects nonischemic myocardium adjacent to the perfusion boundary (the "functional border zone"), we measured systolic wall thickening (dWT) with sonomicrometers in eight anesthetized, open-chest dogs. The locations of the wall thickening measurements relative to the perfusion boundary (PB) were determined with myocardial blood flow (microspheres) maps constructed from multiple, small tissue samples. In nonischemic myocardium more than 10 mm from the PB produced by circumflex coronary occlusion, dWT increased significantly from 2.57 +/- 0.62 (mean +/- SD) to 3.24 +/- 0.73 mm (P less than 0.01). Within 10 mm of the PB, however, dWT did not change significantly (2.48 +/- 0.79 to 2.38 +/- 0.66 mm, NS). When the aorta was mechanically constricted, peak systolic pressure increased approximately 50%. Wall thickening decreased to the same relative degree in nonischemic muscle less than 10 mm and more than 10 mm from the perfusion boundary. By fitting sigmoid curves to the data, we estimated the extent of nonischemic dysfunction. It averaged 26 +/- 6 degrees (6-8 mm of endocardial circumference) during coronary occlusion alone and it was not significantly different (29 +/- 11 degrees) after aortic constriction. Thus elevated afterload affects nonischemic myocardium uniformly and does not increase the size or relative severity of the functional border zone.