bluuebunny/crossref_metadata_2025 huggingface dataset:
Static pressure-flow relation in the total systemic vascular bed of the dog and its modification by the baroreceptor reflex.
Authors: Sagawa K , Eisner A
Published: June 2012

To evaluate arterial baroreceptor reflex control of total systemic vascular resistance, we studied the relation between mean arterial blood pressure (P) and mean aortic flow (Q) before and after the reflex was abrogated. In 12 dogs with a perfusion pump interposed at the vena-caval-right atrial junction, Q was kept at 60, 80, 100, 120, and 140 ml/min kg-1 for up to 20 minutes. There was little time-dependent change in P at any of these flows. When the reflex was intact, the mean P-Q curve was only slightly convex to the pressure axis; its linearized slope was 0.55 mm Hg-min-kg/ml and its pressure axis intercept was 44 mm Hg. After section of the sinovagal nerves, administration of hexamethonium (30 mg/kg, iv) and norepinephrine (3-5 mug/kg min-1, iv), or both, the slope became 0.96 mm Hg-min-kg/ml and the pressure axis intercept was about 3 mm Hg. Similar findings were obtained in 3 closed-chest dogs in which P was servocontrolled and Q was measured. Therefore, we think that the conventional practice of calculating total peripheral resistance as P/Q and evaluating reflex control of it in terms of the changes in that value involves only a small error in the moderately sub -and supranormal flow range.
Comparative uptake of rat and human serum low-density and high-density lipoproteins by rat aortic smooth muscle cells in culture.
Authors: Stein O , Stein Y
Published: June 2012

Rat aortic smooth muscle cells in culture were exposed to rat and human serum (LDL) and high-density (HDL) lipoproteins labeled with 125-I. 125-I-lipid was taken up preferentially from all of the lipoproteins used. 125-I-protein uptake of both rat LDL and HDL was significantly higher than that of the corresponding human lipoproteins, and human LDL was preferred to human HDL. The uptake of delipidated high-density apolipoproteins of either rat or human origin was very low. About 3-4% of the interiorized rat LDL and HDL was catabolized during 48 hours of incubation. On electron microscopic autoradiography of cells incubated with rat 125-I-LDL, the concentration of label, representing mainly 125-I-protein, was associated with secondary lysosomes. These results suggest that, if the protein uptake represents particle uptake, the preferential uptake of human LDL compared with human HDL could account in part for the finding that LDL acts as a more potent feedback suppressor of 3-hydroxy-3-methylglutaryl CoA reductase than does HDL.
Disorders of cellular electrophysiology produced by ischemia of the canine His bundle.
Authors: Lazzara R , El-Sherif N , Scherlag B J
Published: June 2012

In the first 4 hours after occlusion of the anterior septal coronary artery, 18 dogs developed bundle branch block, heart block, or both. The hearts were then excised, and preparations were dissected to expose the His bundle and the bundle branches, which were superfused with modified Tyrode's solution at 37 degrees C. In the His bundle and the most proximal bundle branches, resting potentials were reduced and diminutive action potentials had slow upstrokes, often with notches or steps. Action potentials were generated by fibers that had resting potentials between--40 and --50 mv. Conduction was impaired; conduction velocities less than 0.01 m/sec were sometimes observed. In more severely affected cells, refractoriness outlasted repolarization. Encroachment on the prolonged refractory period resulted in further diminution of action potentials and continuous rather than intermittent block. More commonly, the response to rapid rate took the form of intermittent block with progressive conduction delay in the series of conducted beats, culminating in a blocked beat (Wenckebach sequence). There was a fatigue factor that accumulated at short cycle lengths and depressed the action potential. Automaticity was not enhanced, but pacemaker function was abnormal. The threshold potential shifted erratically, and pacemaker potentials sometimes were intermittently diminished, resulting in intermittent failure to propagate. During prolonged superfusion, there was a tendency to recover with a drift of the maximum diastolic potentials toward more negative levels. None of these changes were found in ten hearts excised from dogs in which the coronary artery had not been ligated.
Detection of latent function in acutely ischemic myocardium in the dog: comparison of pharmacologic inotropic stimulation and postextrasystolic potentiation.
Authors: Dyke S H , Urschel C W , Sonnenblick E H , Gorlin R , Cohn P F
Published: June 2012

In poorly perfused myocardium with resultant ischemic dysfunction, augmentation of contractility can, under certain conditions, be used to detect viable but ordinarily noncontracting muscle. Two methods of inotropic augmentation, pharmacologic inotropic stimulation and postextrasystolic potentiation (PESP), were studied in acutely ischemic canine myocardium with controlled coronary blood flow. A caliper length gauge to record segmental shortening and left ventricle pressure was used to construct pressure-length loops. Acute regional ischemia depressed segmental function: early segmental shortening decreased (-20 plus or minus 0.02% [SE]) and frequent dyskinesia occurred. Restoring coronary blood flow corrected segmental shortening to control levels. During acute regional ischemia, PESP consistently augmented segmental function (+49 plus or minus 0.03%) and abolished dyskinesia. Pharmacologic inotropic stimulation with isoproterenol or calcium administered into the coronary arteries did not produce a comparable improvement in segmental function (+9 plus or minus 0.05%). Although early shortening markedly increased with pharmacologic stimulation, there was no consistent change in total shortening, and the area of the pressure-length loop decreased. Due to late dyskinesia, there was a decrease in injection shortening. Systemically administered pharmacologic agents accentuated early dyskinesia but caused no consistent change in total shortening. Unlike PESP, pharmacologic agents either worsened segmental function or caused responses that were minimum and inconsistent; such responses clearly cannot be used to identify viable ischemic myocardium.
A renin inhibitor from rabbit kidney: conversion of a large inactive renin to a smaller active enzyme.
Authors: Leckie B J , McConnell A
Published: June 2012

Renin in extracts of frozen rabbit kidney exists in two forms: active (molecular weight about 37,000) and inactive (molecular weight about 55,000) renin. The inactive form becomes active after exposure to pH 2.5 at 4 degrees C. If extracts are chromatographed on DEAE cellulose, the inactive renin dissociates into active renin plus a renin inhibitor (molecular weight about 13,000). The inhibitor recombines with active renin if the two are incubated together at 37 degrees C. The inhibitor is destroyed by acid treatment at pH 2.5 at 4 degrees C. We conclude that the activation of inactive renin is due to destruction of the inhibitor by acid. The inactive material may be a renin proenzyme or a storage form of active renin combined with inhibitor.
Baroreceptor reflex effects on transient and steady-state hemodynamics of salt-loading hypertension in dogs.
Authors: Cowley A W , Guyton A C
Published: June 2012

Intact dogs were compared with barorecptor-denervated dogs to determine the extent to which the baroreceptor reflexes delay the onset and offset transients and alter the final steady-state levels of salt-loading hypertension. Two months after their renal mass had been reduced to about one-third of normal, hypertension was produced in both groups of dogs by continuous intravenous infusion of isotonic saline (190 ml/kg day-1). Major hemodynamic variables were recorded continuously 24 hours/day throughout the experimental period. Both groups of dogs had similar control 24-hour arterial blood pressure values: intact dogs averaged 112 plus or minus 4.1 (SE) mm Hg, and denervated dogs averaged 110 plus or minus 4.3 mm Hg. Both groups reached the same average plateau of elevated arterial blood pressure: intact dogs averaged 142 plus or minus 4.8 mm Hg, and denervated dogs averaged 142 plus or minus 8.7 mm Hg. After the start of salt loading, the denervated dogs reached their plateau level of arterial blood pressure in an average of 8 hours compared with nearly 24 hours for the intact dogs. Cardiac output also rose more rapidly in the denervated dogs and reached a maximum elevation of 26% above the control level in an average of 7.4 hours compared with a maximum elevation of 40% above control in the intact dogs in 18 hours. Total peripheral resistance fell below the control level during the entire first day of infusion in the intact dogs but was somewhat elevated in the denervated dogs. When the saline infusion stopped, arterial blood pressure in both groups returned to control levels within 24 hours. The results indicate that the major action of the baroreceptor reflexes on the onset of salt-loading hypertension is to slow the development of hypertension by modifying the total peripheral resistance; the final steady-state level of hypertension is unaffected by the baroreceptor reflexes.
"Prorenin" in human plasma?
Authors: Sealey J E , Laragh J H
Published: June 2012

An increase in plasma renin activity was demonstrated in plasma from normal subjects and most patients with essential hypertension after prolonged storage of the plasma at -20 degrees C. No change in renin substrate concentration was observed after storage for 12 months, and the rate of angiotensin generation during incubation with a fixed amount of added human renin was not increased. It therefore seems unlikely that the observed increase in renin activity was due to changes in plasma activators or inhibitors. The data are consistent with the activation of an inactive form of renin, tentatively called "prorenin" in normal subjects averaged from 1 to 2 ng/ml/hr, and did not change during sodium deprivation. However, three of four patients studied who had low-renin essential hypertension secreted abnormally large amounts of "prorenin" in response to sodium depletion. In these patients, subsequent sodium administration was associated with a return of "prorenin" to baseline levels.
Urinary kallikrein excretion in spontaneously hypertensive rats.
Authors: Geller R G , Margolius H S , Pisano J J , Keiser H R
Published: June 2012

Urinary kallikrein was similar in 16-week-old Wistar/Kyoto (W/Ky) and spontaneously hypertensive (SH) rats, but at 23 weeks the SH rats excreted significantly less kallikrein. When dietary sodium was restricted, kallikrein excretion increased in the W/Ky but not in the SH rats. On high dietary sodium the opposite occurred: kallidrein excretion increased in the SH but not in the W/Ky rats. The pattern of urinary kallikrein excretion has some similarity to that seen in human hypertensive disease, i.e., the SH rat excretes less kallikrein than the normotensive control at 23 weeks of age and does not show an increased excretion when fed a low sodium diet. However, the rise in kallikrein shown by the SH rat on a high sodium diet is unique for this hypertensive model.
Effect of varying perfusion pressures on the output of sodium and renin and the vascular resistance in kidneys of rats with "post-salt" hypertension and Kyoto spontaneous hypertension.
Authors: Tobian L , Johnson M A , Lange J , Magraw S
Published: June 2012

Isolated kidneys from both "post-salt" normotensive and hypertensive rats were perfused with blood from donor rats at varying pressures. At 130 mm Hg inflow pressure 15 "post-salt normotensive" kidneys put out 0.75 muEq Na/min/g kidney while 14 "post-salt hypertensive" kidneys put out 0.28 mu-Eq Na/min/g (P less than 0.001), a 63% reduction. They also put out 55% less water (P less than 0.002). Thus, if "hypertensive" kidneys are perfused at normal pressures, they put out subnormal amounts of Na and H-2-O. Such Na and H-2-O retention maintains the hypertensive state. Normal Na output in these kidneys was only reached at hypertensive (160) inflow pressures. This shift in the "pressure natriuresis" curve explains in part how some "hypertensive" kidneys maintain hypertension. These "hypertensive" kidneys have grossly abnormal autoregulation curves, each increment of pressure actually producing progressively greater increments of blood flow. Isolated kidneys from Kyoto hypertensive and normotensive rats showed no difference in Na and H-2-O excretion at 130 mm Hg inflow pressure. Thus, a tendency to Na retention demonstrable in the isolated kidney is apparently not supporting Kyoto hypertension. Moreover, isolated kidneys form Kyoto hypertensive rats released significantly lower amounts of renin at all levels of inflow pressure, averaging a 70% lower rate than Kyoto normotensive kidneys (P less than 0.01). Hence, Kyoto hypertension is not supported by a supernormal renin release inherent in the kidney. One can speculate that Kyoto hypertensive rats normally have an elevated sympathetic tone which stimulates release of renin. The denervation which occurs in isolating kidneys might therefore produce a proportionally greater percentage loss of sympathetic influence in these kidneys, which could possibly account for some of their reduced renin release. These Kyoto hypertensive kidneys are apparently not "reset" to maintain hypertension with either Na or renin.
Role of renin in the pathogenesis of renal hypertension.
Authors: Gulati O P , Carretero O A , Oza N B , Fernandez L A , Schork A
Published: June 2012

To test the hypothesis that renin is circulating in pressor amounts in renal hypertension, two-kidney Goldblatt hypertension was produced in rats. After hypertension had been present for a variable period of time (4 to 21 days), the ischemic kidney was removed, and an infusion of rat renin was started immediately to replace the endogenous renin that the ischemic kidney had been releasing. Since the amount of renin released by the clipped kidney was not known, the amount infused was regulated by a feedback mechanism set to keep the mean blood pressure at the same level as before ipsilateral nephrectomy. Hypertension remission was therefore prevented by this procedure. The PRA at the end of the renin infusion was similar to that prior to the ipsilateral nephrectomy. This finding indicates that the levels of the PRA circulating in renal hypertension are within the pressor range, thus supporting the hypothesis that renin plays a role in the pathogenesis of the acute or semiacute phase of renal hypertension. However, the participation of other factors cannot be ruled out since no correlation was found between PRA and blood pressure.
Evidence for a new mineralocorticoid in patients with low-renin essential hypertension.
Authors: Sennett J A , Brown R D , Island D P , Yarbro L R , Watson J T , Slaton P E , Hollifield J W , Liddle G W
Published: June 2012

Patients with low-renin essential hypertension have certain features consistent with excessive mineralocorticoid activity. Because known mineralocorticoids are normal in the majority of low-renin essential hypertension patients, an unknown mineralocorticoid was sought in the urine of such patients. Urine extracts from patients with low-renin essential hypertension were assayed for mineralocorticoid activity in adrenalectomized rats and found to contain more such activity than could be accounted for by the known mineralocorticoids in the extracts. The factor responsible for the unexplained mineralocorticoid activity was purfied and then identified by mass spectral analysis as 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA). Synthetic 16beta-OH-DHEA was found to have a mineralocorticoid potency one-fortieth that of aldosterone in the rat bioassay. The mineralocorticoid effects of both the urine extracts and the synthetic steroid were blocked in the rat by spironolactone, a mineralocorticoid antagonist. A specific assay for 16beta-OH-DHEA was developed, and its level in the urine was found to be elevated in patients with low-renin essential hypertension.
Effect of salt depletion and propranolol on blood pressure and plasma renin activity in various forms of hypertension.
Authors: Geyskes G G , Boer P , Vos J , Leenen F H , Mees E J
Published: June 2012

The effect of propranolol therapy on the mean arterial pressure (MAP) and plasma renin activity (PRA) was studied in three groups of hypertensive patients who were also treated with saliuretics. Group A: In 14 patients with essential hypertension on chlorthalidone treatment, an additional daily dose of 640 mg propranolol for two months led to a significant reduction of the MAP (from 124 to 105 mm Hg) and PRA (from 5.3 to 2.0 ng AI/ml/hr standing). There was no correlation between MAP reduction and either the original levels or change in PRA. Group B: In 14 patients with essential hypertension and 5 with renal artery stenosis studied on a fixed salt intake, the plasma and extracellular volumes, PRA, and blood pressures were recorded before and after three days of diuretic induced salt depletion and, with maintenance of the depleted state, after three days of propranolol. Salt depletion resulted in a decrease in MAP from 132 to 128 mm Hg (NS), and PRA increased from 3.4 to 22.3 ng AI/ml/hr (P less than 0.01). There was no correlation between change in MAP and PRA control values, PRA change, or any of the volume parameters. Addition of propranolol was followed by a rapid MAP decrease to 111 mm Hg (P less than 0.01), and the PRA dropped to a mean of 8.5 (P less than 0.01). No correlation was found between change in MAP and change in PRA. The patients with renal artery stenosis did not differ in their reactions from those with essential hypertension. Group C: In five patients with moderate renal failure and normal to expanded 82-Br distribution volume, propranolol lowered MAP by 10% and lowered the PRA in all five. Salt depletion by furosemide to 82-Br volumes below normal resulted in a 10% decrease of MAP and a marked rise in PRA. In this state propranolol was followed by a further MAP reduction of 18% and a decrease in PRA. There was no quantitative relationship between MAP and PRA change during either of the treatment regimes. It is concluded that in various forms of hypertension, the blood pressure can be effectively lowered by combining diuretics and propranolol regardless of the pretreatment PRA level.
Effects of extracellular calcium and sodium on depolarization-induced automaticity in guinea pig papillary muscle.
Authors: Katzung B G
Published: June 2012

Regenerative discharge of action potentials is induced in mammalian papillary muscles by passage of small depolarizing currents. In this paper, the effects of various extracellular calcium and sodium concentrations and of tetrodotoxin on this phenomenon were studied in guinea pig papillary muscles in a sucrose gap chamber. Phase 4 diastolic depolarization was found to be associated with an increase in membrane resistance. The slope of phase 4 depolarization was decreased by reductions in extracellular calcium or sodium concentration. The range of maximum diastolic potentials and the thresholds from which regenerative potentials arose were reduced, especially at the positive limit of potentials, by a reduction in either ion. It was concluded that both calcium and sodium influence diastolic depolarization and participate in the regenerative action potentials of depolarization-induced ventricular automaticity.
Effect of sympathetic denervation on smooth muscle cell proliferation in the growing rabbit ear artery.
Authors: Bevan R D
Published: June 2012

The effect of sympathetic denervation on the uptake of 3H-thymidine (3H-Tdr) into the ear artery of a growing rabbit was studied in vitro and in vivo. Uptake into the right artery was compared with that into the left 2 and 3 weeks after left superior cervical ganglionectomy in 4-week-old rabbits. Denervation was confirmed by the absence of catecholamine fluorescence. The total uptake of 3H--Tdr was determined by scintillation spectrometry, and its distribution in the artery wall was studied by light microscope autoradiography. The denervated ear artery took up significantly less DNA precursor and exhibited fewer labeled vascular smooth muscle cell nuclie in the tunica media than did the control artery. These findings suggest that sympathetic innervation influences the proliferation of vascular smooth muscle in growing rabbits.
Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium.
Authors: Chen C M , Gettes L S , Katzung B G
Published: June 2012

We studied the effects of quinidine and lidocaine on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)max, and on the recovery kinetics of (dV/dt)max in guinea pig papillary muscles. The steady-state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)max in progressively earlier premature action potentials. Lidocaine caused a dose-dependent decrease in (dV/dt)max, shifted the curve defining the steady-state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)max. Quinidine caused a dose-dependent decrease in (dV/dt)max but did not alter the shape of the curves defining either the steady-state relationship or the recovery kinetics of (dV/dt)max. Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)max are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs.
Effect of norepinephrine and fluid administration on pulmonary extravascular water volume in dogs.
Authors: Ellis J H , Murray J F
Published: June 2012

The effects of norepinephrine-induced vasoconstriction on pulmonary extravascular water volume (PEWV) and central volume were studied before and after intravenous volume expansion with 5% dextrose and water (20 ml/kg body weight). PEWV was measured by double isotope dilution and gravimetric analysis and assessed by electron photomicrography. Comparisons were made with saline-treated control dogs. Thirty-six dogs were studied after they had been anesthetized with sodium pentobarbital. PEWV determined by indicator dilution increased during norepinephrine infusion, especially after volume expansion; in contrast, PEWV in control dogs was constant despite similar increases in pulmonary arterial and left atrial pressures. However, measurements of PEWV by gravimetric analysis and inspection of electron photomicrographs failed to reveal extravascular accumulation of water in vasoconstricted dogs. Thus, it was concluded that the increased PEWV measured by indicator dilution in norepinephrine-treated dogs compared with that in saline-treated dogs reflects more complete perfusion of pulmonary capillaries and access of the diffusible indicator to additional lung tissues and spaces. Improved capillary filling presumably is attributable to peripheral vasoconstriction and redistribution of blood into the thorax. PEWV determined by gravimetric analysis in dogs that had had open-chest procedures for lung biopsy and electron photomicrography was significantly less than that in dogs with their chests closed throughout the experiments. Although the mechanism for the water loss in unknown, the difference must be recognized when the results from various types of experiments are compared.
Control of myocardial oxygen tension by sympathetic coronary vasoconstriction in the dog.
Authors: Feigl E O
Published: June 2012

The effect of sympathetic alpha-receptor coronary vasoconstriction on myocardial oxygen tension was studied in open- and closed-chest, chloralose-anesthetized dogs. Blood oxygen tension in the coronary sinus and blood flow in the circumflex coronary artery were continuously measured in a three-part experiment. With stimulation of the left stellate ganglion (15 Hz, 3 msec, 4-7 v, 90-second train) under vagotomy control conditions (part 1), heart rate, blood pressure, and coronary blood flow increased, but coronary sinus oxygen tension decreased from 19 mm Hg to 15 mm Hg. In part 2, beta-receptor blockade with propranolol (2.0 mg/kg. iv) in the same dogs blunted the positive inotropic and chronotropic effects of sympathetic stimulation; coronary alpha-receptor vasoconstriction was unmasked, and coronary sinus blood oxygen tension fell from 17 mm Hg to 11 mm Hg. Since increases in oxygen metabolism were blunted, it appeared that the decrease in coronary sinus oxygen tension was caused by alpha-receptor coronary artery vasoconstriction. This hypothesis was tested in part 3 by the addition of alpha-receptor blockade with Dibozane (3.0 mg/kg, iv). Sympathetic stimulation no longer resulted in a change in either coronary vascular resistance or coronary sinus oxygen tension. These results indicate that the fall in oxygen tension during beta-receptor blockade in part 2 was due to alpha-receptor coronary vasoconstriction. Thus, myocardial oxygen tension may be regulated by coronary sympathetic vasomotion as well as by myocardial oxygen metabolism and local vascular control mechanisms.
Role of cardiac, pulmonary, and carotid mechanoreceptors in the control of hind-limb and renal circulation in dogs.
Authors: Mancia G , Shepherd J T , Donald D E
Published: June 2012

Reflex control of hind-limb and renal resistance vessels by cardiac and pulmonary receptors was studied by interrupting afferent vagal nerve traffic when only the heart or only the lungs were in situ in anesthetized dogs with sinoaortic denervation. During normocapnia, interruption of cardiac and of pulmonary vagal traffic decreased hind-limb blood flow (constant-pressure perfusion) by 23% and 21%, respectively. Corresponding decreases in renal blood flow were 23% and 33%. Hypercapnia augmented the decreases in renal blood flow due to the vagal block. Thus, the inhibitions exerted by the heart and lung receptores on these two beds were similar during normocapnia but were greater on the renal vessels during hypercapnia. In closed-chest dogs with their aortic nerves sectioned and their carotid sinus pressure controlled, combined withdrawal of carotid and cardiopulmonary inhibition decreased hind-limb and renal blood flow by about 80% and 40%, respectively, during both normovolemia and hypervolemia. Interruption of cardiopulmonary inhibition was responsible for 17% and 31% of the decrease in hind-limb blood flow at normal and increased blood volumes, respectively; values for the decreases in renal blood flow were 50% and 65%. Thus, cardiopulmonary receptors oppose the vasoconstriction due to carotid hypotension more effectively in the kidney than they do in the hind limb.
Reduced baroreflex sensitivity with volume loading in conscious dogs.
Authors: Vatner S F , Boettcher D H , Heyndrickx G R , McRitchie R J
Published: June 2012

The Bainbridge reflex, i.e., the effect of rapid saline infusion (1.1 +/- 0.1 liters) on heart rate and arterial and atrial blood pressures, was examined in 12 intact conscious dogs; mean arterial blood pressure rose by 33 +/- 3 (SE) mm Hg, mean atrial pressure by 14 +/- 1 mm Hg, and heart rate by 75 +/- 9 beats/min. After beta-receptor blockade, heart rate rose slightly less (+49 +/- 5 beats/min, P = 0.05). Cholinergic blockade, combined cholinergic and beta-receptor, or beta-receptor blockade after vagotomy blocked the heart rate response to the infusion. The rise in heart rate in the face of an increase in arterial blood pressure with volume loading suggested that the arterial baroreceptor reflex was not responding appropriately to the increase in arterial blood pressure. In conscious dogs after denervation of the arterial baroreceptors, the increase in heart rate with volume loading was no greater than that in those dogs with their arterial baroreceptors intact, suggesting that the baroreceptor reflex was not restraining heart rate in the normal response to volume loading. The relationship between the pulse interval (PI) and the systolic arterial blood pressure (SAP) following an intravenous injection of methoxamine was used to evaluate the sensitivity of the baroreceptor reflex in intact conscious dogs. After a mild amount of volume loading, when atrial pressure was 8 +/- 2 mm Hg, the PI/SAP slope was significantly depressed from normal. When atrial pressure was elevated further to 28 +/- 1 mm Hg by volume loading, the slope was further depressed. Thus, arterial baroreflex sensitivity is reduced progressively as atrial pressure is raised by volume loading, an observation that explains how heart rate can rise strikingly in the face of an elevated arterial blood pressure.
Bronchopulmonary arterial shunting without anatomic anastomosis in the dog.
Authors: Hyman A L , Knight D S , Joiner P D , Kadowitz P J
Published: June 2012

The effects of bronchial arterial administration of vasoactive substances on the pulmonary circulation were studied by a new technique for selective catheterization of a bronchial artery in intact dogs. In most experiments, this technique permitted pressor agents to be distributed mainly to one lung with smaller amounts to the other lung. The intercostal arteries were avoided, and in all but 2 of 23 experiments only microscopic quantities of injected India ink could be identified in the distribution of the esophageal and mediastinal branches. These studies indicate that serotonin, angiotensin, histamine, and norepinephrine injected selectively into a bronchial artery increase lobar arterial pressure. Since blood flow was constant and left atrial pressure did not change, the increase in pressure suggests active pulmonary vasoconstriction. Additionally, the responses to bronchial and lobar arterial injections of pressor agents were similar. The contribution of bronchopulmonary shunt flow to pulmonary flow was small, since, under conditions of controlled lobar blood flow, changes in bronchial flow elicited by 65-75-mm Hg changes in bronchial arterial pressure produced little if any change in pressure in the perfused lobar artery or small vein. Bronchoconstriction contributed little to the response to bronchial administration of pressor agents, since responses were similar in the ventilated and the collapsed lobe. Injection of vasoflavine dyes into the bronchial artery showed the close proximity of bronchial and pulmonary arteries and confirmed the bronchial arterial origin of the vasa vasorum of pulmonary arteries. No vasa venorum were identified. Although no direct anatomic bronchial artery-pulmonary artery shunt was identified, ascorbic acid and 5-hydroxydopamine diffused rapidly into intrapulmonary arteries from the bronchial artery. These data suggest that the pulmonary pressor response results from passage of the vasoactive agents from the bronchial artery to the lobar artery through the vasa vasorum and by diffusion. Since no vasa venorum were found, pulmonary venoconstriction probably resulted from pressor agents reaching the veins by way of bronchopulmonary shunt flow. These results suggest a mechanism by which pressor substances present or liberated in the bronchial vascular bed can affect tone in the pulmonary vascular bed.
Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.
Authors: Watanabe A M , Besch H R
Published: June 2012

The purpose of this study was to examine the mechanisms underlying adrenergic-cholinergic antagonism in ventricular myocardium. Myocardial contractility, cyclic adenosine monophosphate (AMP) levels, and cyclic guanosine monophosphate (GMP) levels were measure in isolated guinea pig ventricles after treatment with various inotropic agents given alone and simultaneously with acetylcholine. Acetylcholine alone markedly elevated cyclic GMP levels but did not substantially change myocardial contractility. However, the same concentration of acetylcholine significantly attenuated the inotropic effect of isoproterenol and histamine, two drugs that may act by increasing myocardial levels of cyclic AMP. The decrease in the inotropic response to isoproterenol did not appear to be due to a decrease in the generation of cyclic AMP, because cyclic AMP levels were similar in hearts receiving isoproterenol alone and those receiving isoproterenol with acetylcholine. Dibutyryl cyclic GMP also antagonized the intropic action of isoproterenol. Acetylcholine did not alter the inotropic effects of ouabain, an agent that increases myocardial contractility without changing cyclic AMP levels. These results suggest that cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP.
Inhibition of bradykinin vasodilation and potentiation of norepinephrine and angiotensin vasoconstriction by inhibitors of prostaglandin synthesis in skeletal muscle of the rat.
Authors: Messina E J , Weiner R , Kaley G
Published: June 2012

Recent reports have indicated that vascular responsiveness can be altered by exogenously administered or endogenously released prostaglandins. Furthermore, in certain tissues inhibitors of prostaglandin synthesis have been shown to limit the increase in blood flow in response to bradykinin and to enhance the reduction in blood flow in response to angiotensin and norepinephrine. These findings suggest an important local circulatory role for prostaglandins. We attempted to implicate further prostaglandins in local blood flow regulation by examining the effects of indomethacin (IND) and 5,8,11,14-eicosatetraynoic acid (ETA), inhibitors of prostaglandin synthesis, on microvascular arteriolar responses to bradykinin, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), histamine, norepinephrine, and angiotensin. Male Wistar rats were anesthetized with sodium pentobarbital, and their cremaster muscle was exteriorized and prepared for in vivo microscopic observation of microvessels. Changes in arteriolar luminal diameters in response to topical administration of vasoactive agents were quantified with an image-shearing measuring eyepiece in conjunction with a television microscope and recorder. Local administration of IND or ETA significantly reduced the arteriolar dilation elicited by bradykinin, whereas the responses to PGE1 and PGE2 remained unaltered. Responses to histamine, although somewhat reduced, were not significantly different from control. Vasoconstrictor responses of arterioles elicited by norepinephrine and angiotensin were potentiated by IND or ETA administration. These results indicate that prostaglandins synthetized in skeletal muscle microcirculation in situ (1) mediate, in part, vasodilator responses to bradykinin and (2) modulate vasoconstrictor responses to angiotensin and norepinephrine. Thus, these findings support the hypothesis that prostaglandins are local regulators of microvascular responsiveness.
Precordial and epicardial surface potentials during Myocardial ischemia in the pig. A theoretical and experimental analysis of the TQ and ST segments.
Authors: Holland R P , Brooks H
Published: June 2012

The solid angle theorem was used to analyze the relationships between TQ and ST segment deflections recorded from precordial and epicardial locations and the time course, size, shape, and transmural location of the ischemic process in the ventricular myocardium. Mathematical predictions were compared with experimental data from the intact heart. Precordial electrograms obtained in anesthetized close-chest pigs were compared with epicardial electrograms recorded directly from the heart's surface. Various areas of ischemia were produced by occluding large and small coronary artery branches, and the resultant changes in ischemic shape were delineated with Thioflavin S injections and postmortem ultraviolet photography. Formally derived equations and cumulative experimental data were in close agreement, suggesting that in the ischemic ventricle (1) TQ depression always accompanies ST elevation, (2) TQ and ST segment changes in magnitude and polarity are complex functions of ischemic size, shape, and transmural location; (3) precordial electrocardiogram (ECG) ST segment elevation is directly related to ischemic size; and (4) epicardial ECG ST segment elevation is inversely related to ischemic size. It is thus concluded that precordial and epicardial ECG TQ and ST segment deflections are complex functions of ischemic geometry and that their accurate interpretation with respect to ischemic size and shape and in the presence of pharmacological interventions is often difficult and may be misleading.
Potassium influx in the frog atrium during the cardiac cycle.
Authors: Juncker D F , Lee P Y , Greene E A , Stish R , Lorber V
Published: June 2012

A method for measuring inwardly directed transmembrane tracer flow during the cardiac cycle was developed and applied to a study of 42K influx in frog atrial trabeculae. A fine frog atrial fiber was suspended in a stream of nonisotopic perfusate into which a smaller tracer-containing bolus could be injected, subjecting the fiber to a brief, controlled exposure to the tracer at any desired point in the cardiac cycle. In an experiment, the tissue was exposed to a fixed number of radioactive pulses at a selected point in the cardiac cycle; a brief flush with nonradioactive perfusate removed ambient and extracellular label and an extended wash and removed the remaining intracellular tracer for radioassay. The same procedure was repeated at different points in the cycle, and the resulting tracer uptake at each point measured the relative influx of the particular ion. In this way, a characteristic and reproducible 42K influx profile was demonstrated which exhibited a marked drop below diastolic values during the first 500 msec or so of the action potential followed by a rise and an overshoot above resting values. The time of return to the resting level was somewhat uncertain but was tentatively placed in the vicinity of rapid repolarization. We suggest that the rise and the overshoot reflect the activity of the membrane Na+, K+-adenosinetriphosphatase.
Influence of potassium ions and osmolality on the resting membrane potential of rabbit ventricular papillary muscle with estimation of the activity and the activity coefficient of internal potassium.
Authors: Akiyama T , Fozzard H A
Published: June 2012

Resting membrane potentials of rabbit right ventricular papillary muscles were measured in modified Tyrode's solutions that were isotonic (1.0 X T), hypertonic (1.58 X T), or hypotonic (0.76 X T) at eight different concentrations of external potassium, [K]o, ranging from 0.78 to 100 mM. The amount of hyperpolarization produced by exposure to the hypertonic solutions was relatively constant with an average of 4.6 mv at all levels of [K]o except 0.78 and 1.56 mM. This potential change is much less than the 10.6 mv which would be predicted if the papillary muscles behaved as nearly perfect osmometers and the activity coefficient of intracellular potassium (K) remained constant. The amount of depolarization produced by exposure to the 0.76 X T hypotonic solutions averaged 6.8 mv at all levels of [K]o except 0.78 mM; this value is close to the predicted value of 6.9 mv. Variations in the activity and the activity coefficient of intracellular K were introduced to explain these discrepancies. We estimated that the activity of intracellular K in 1.58 X T hypertonic solution was increased 15-23% compared with that in isotonic solution. This change is much less than the 58% that would be predicted if the papillary muscle behaved as a nearly perfect osmometer. We also estimated that the activity of intracellular K in 0.76 X T hypotonic solution fell 22-26%, which is very close to the predicted value of 24%. The activity coefficient of intracellular K appeared to fall in 1.58 X T hypertonic solution to about 0.76 of its value in isotonic solution. This decline in the estimated activity coefficient of intracellular K could not be attributed to an increase in Coulombic attractive and repulsive forces as predicted by the Debye-Hückel equation for a univalent electrolyte.
Effect of lidocaine on the early inward transient current in sheep cardiac Purkinje fibers.
Authors: Weld F M , Bigger J T
Published: June 2012

We used two experimental techniques to study the effect of lidocaine hydrochloride on the early inward transient (sodium) current as it is reflected by the maximum rate of change of action potential phase 0 (Vmax). We assessed the effect of lidocaine on Vmax as Purkinje fibers were slowly depolarized by increasing the extracellular potassium concentration from 4.0 to 16.0 mM; these voltage-dependent effects were compared with lidocaine's effect on membrane responsiveness (which measures both the time and the voltage dependence of Vmax). We also used a voltage clamp technique to establish the effect of lidocaine on the voltage dependence of Vmax by measuring Vmax 800-1000 msec after transmembrane voltage (Vm) had been changed in small steps. We studied the effect of lidocaine on the time course of early inward transient current reactivation by depolarizing the membrane to -25 +/- 5 mv for 100 msec to inactivate this current, clamping Vm to a repolarized test voltage for various periods, and then measuring phase 0 Vmax of action potentials elicited immediately after termination of the voltage clamp. We showed that lidocaine at 5 mg/liter, but not a 1 mg/liter, shifted the steady-state Vmax- Vm relationship to a more negative position on its voltage axis by about 5 mv and markedly slowed the reactivation of the measure early inward transient current.
Analysis of coronary flow fields in thoracotomized dogs.
Authors: Atabek H B , Ling S C , Patel D J
Published: June 2012

A nonlinear theory of pulsatile flow was used to investigate the detailed flow field in the left circumflex coronary artery of anesthetized open-chest dogs. Studies were carried out under a wide range of blood pressures and flow rates induced by intravenous infusions of dipyridamole. The results indicated that (1) the flow profiles, although less blunt than those in the descending aorta, are still nonparabolic, (2) the wall shear in the coronary arteries maintains a high value through diastole, and (3) during intravenous infusions of dipyridamole both coronary flow and wall shear increase. The peak value of the shear stress during these infusions, which reached 360 dynes/cm2, can approach the yield stress value of 400 dynes/cm2 reported by Fry for endothelial cells.
Hormone interactions in the isolated rabbit heart. Synthesis and coronary vasomotor effects of prostaglandins, angiotensin, and bradykinin.
Authors: Needleman P , Marshall G R , Sobel B E
Published: June 2012

In the present study, the synthesis and degradation of several potent vasoactive substances influencing coronary resistance were characterized in the isolated perfused rabbit heart. Prostaglandin synthetase activity, angiotensin converting enzyme activity, and bradykininase activity (without angiotensinase) were observed. A prostaglandin E2-like substance appeared to be the ednogenous mediator of the coronary vasodilation produced by bradykinin and angiotensin II (AII). (1) The concentration of this prostaglandinlike substance in the coronary venous effluent was directly proportional to the concentration of the coronary vasocilator stimulus (bradykinin or AII). (2) The prostaglandinlike substance released and the coronary dilation produced by the agonists correlated temporally and quantitatively. (3). Abolition of cardiac biosynthesis of the prostaglandinlike substance by indomethacin also abolished the decrease in coronary resistance produced by the agonists. AII, the most potent naturally occurring vasoconstrictor substance, produced a paradoxical coronary vasodilation because it stimulated cardiac prostaglandin biosynthesis, but the direct coronary vasoconstrictor action of AII could be readily unmasked by indomethacin, which blocks prostaglandin synthesis. The nonapeptide SQ-20881 blocked cardiac biosynthesis of AII (from angiotensin I) and enhanced the coronary vascular effects of bradykinin by interfering with bradykininase activity. Similarly, the AII-receptor antagonist, 1-Sar-8-Ile-AII, blocked the coronary vascular effect of AII.
Glomerular filtration response to elevated ureteral pressure in both the hydropenic and the plasma-expanded rat.
Authors: Blantz R C , Konnen K S , Tucker B J
Published: June 2012

The factors affecting glomerular ultrafiltration with elevated ureteral pressure were examined in both plasma-expanded (2.5% body weight) and hydropenic Munich-Wistar rats. Elevated ureteral pressure (20 mm Hg) alternated as the initial condition in both groups. Glomerular capillary hydrostatic pressure (PG) and Bowman's space pressure (Pt) were measured directly in surface glomeruli with a servonulling device (deltaP = PG - PT), systemic (piA) and efferent (piE) peritubular capillary oncotic pressures were estimated by microprotein methods, and single-nephron glomerular filtration rates (sngfr) were determined by micropuncture techniques under control ureteral pressure and after increased ureteral pressure in both experimental groups. All data were then applied to equations describing the process of glomerular ultrafiltration to define the profile of effective filtration pressure (EFP = deltaP - pi) and the glomerular permeability coefficient (LpA), where sngfr = LpA-EFP. In plasma-expanded rats, sngfr fell from 44.8 +/- 2.2 to 38.5 +/- 1.5 nilters/min g-1 kidney weight (P less than 0.025) with elevated ureteral pressure entirely as a result of a decrease in the hydrostatic pressure gradient (deltaP), since PG did not rise and nephron plasma flow remained constant. In hydropenic rats, sngfr fell from 34.7 +/- 1.6 to 27.3 +/- 1.6 nliters/min g-1 kidney weight with increased ureteral pressure. PG rose 8.7 mm Hg (P less than 0.001) due to an increase in vascular resistance between the peritubular capillaries and the renal vein which prevented the reduction in deltaP. The reduction in sngfr appeared to result from a reduction in LpA resulting in disequilibration of EFP. Nephron plasma flow was not changed. The filtration response to elevated ureteral pressure was modified by the prior state of volume expansion and was not associated with changes in either nephron blood flow or afferent arteriolar resistance.
Electrophysiological actions of disopyramide phosphate on canine ventricular muscle and purkinje fibers.
Authors: Kus T , Sasyniuk B I
Published: June 2012

Disopyramide phosphate is a new antiarrhythmic drug that has been shown to possess significant antiarrhythmic effects in animals and man. In the present investigation, the effects of 2, 5, and 10 mug/ml of disopyramide phosphate were studied on the electrophysiological properties of canine Purkinje fibers and ventricular muscle superfused in vitro. Transmembrane action potentials were recorded from Purkinje fibers in the region of maximum action potential duration (gate), from Purkinje fibers proximal and distal to the gate, and from ventricular muscle. Disopyramide phosphate produced a concentration-dependent decrease in the slope of phase 4 diastolic depolarization of spontaneously beating Purkinje fibers. In all electrically stimulated fibers, the drug decreased the amplitude and the maximum upstroke velocity of the action potential. This depression of phase 0 characteristics was accompanied by a decrease in conduction velocity. In Purkinje fibers located at the gate, a concentration-dependent parallel shift to the right and a depression of the maximum of the membrane responsiveness curve occurred. Effects on action potential duration were variable. Repolarization was altered so that action potentials with dissimilar durations recorded from sites proximal to, at, and distal to the gate became equal. The total action potential duration and the effective refractory period of gate Purkinje fibers were prolonged, but the change in action potential duration was always greater than the change in effective refractory period so that the ratio of the change in duration to the change in refractory period was always greater than one.