bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysophosphatidyl choline potentiates Ca2+ accumulation in rat cardiac myocytes
Authors: Sedlis S. P. , Corr P. B. , Sobel B. E. , Ahumada G. G.
Published: December 2017

Lysophosphoglycerides are amphiphilic phospholipids that accumulate in ischemic myocardium and elicit electrophysiological alterations in normoxic Purkinje fibers and ventricular muscle that are analogous to alterations characteristic of ischemic tissue in vivo and that are compatible with altered sarcolemmal permeability to divalent cations. To assess directly the potential influence of lysophosphoglycerides on calcium transport, we characterized changes in the accumulation of 45Ca2+ by cultured cardiac myocytes exposed to selected concentrations of lysophosphatidyl choline (LPC). Perfusion for 10 min with 80 microM LPC augmented the amount of 45Ca2+ in myocytes compared with that in control cells (5.1 +/- 0.7 vs. 2.8 +/- 0.26 nmols Ca2+/mg protein, respectively; P less than 0.005) but did not alter total cell calcium content measured by atomic absorption spectrometry (11.6 +/- 1.0 nmols/mg protein), suggesting equivalent augmentation of bidirectional Ca2+ flux by LPC. In contrast, perfusion for 15 min with 100 microM LPC not only augmented 45Ca2+ accumulation but also increased total cellular Ca2+ content, as the quantity of 45Ca2+ accumulated reached 16.9 +/- 1.4 nmols/mg protein, a value substantially exceeding the normal total Ca2+ content (P less than 0.0025 compared with control cells). In contrast to results observed after only a 5-min exposure to 100 microM LPC, Ca2+ accumulation induced by 15 min of perfusion was not precluded by verapamil (10(-8)M), could not be reversed by perfusion without LPC, and was associated with complete cessation of beating, markedly altered morphology, and substantial depletion of cellular creatine kinase activity. Thus LPC may not only contribute to malignant ventricular dysrhythmias but also may potentiate ischemic injury by facilitating calcium ingress.
beta-Adrenergic activity and cardiovascular response to severe respiratory acidosis
Authors: Steinhart C. R. , Permutt S. , Gurtner G. H. , Traystman R. J.
Published: December 2017

The mechanism responsible for the depressive myocardial effects of severe respiratory acidosis is unclear; however, sympathetic stimulation and catecholamines are known to be involved. The influence of beta-adrenergic receptor activity on the myocardial response to severe respiratory acidosis was studied in 18 anesthetized, mechanically ventilated dogs. Arterial CO2 tension (PaCO2) was raised by increasing the inspired CO2 fraction in O2. In control animals, as PaCO2 increased, heart rate (HR) decreased (PaCO2 approximately 110 mmHg), then returned to control (PaCO2 approximately 220 mmHg), whereas arterial blood pressure (Pa) and cardiac output (Q) remained unchanged from prehypercapnia levels. At PaCO2 greater than 350 mmHg, Pa, HR, and Q decreased and left ventricular function (LVF) curves were depressed. Death occurred at a PaCO2 of 404 +/- 25 mmHg (pH 6.48 +/- 0.02). In a second group of animals, administration of isoproterenol during the increase in PaCO2 did not result in depression of myocardial function, and death did not occur even at a significantly higher PaCO2 (PaCO2 496 +/- 12 mmHg; pH 6.39 +/- 0.02) than in the control group. Administration of propranolol to a third group of animals as PaCO2 increased did not change Pa, HR, and Q; however, LVF curves indicated a more rapid and severe depression of myocardial performance than in control, and death occurred at a significantly lower PaCO2 (PaCO2 220 +/- 25 mmHg; pH 6.65 +/- 0.02). We conclude that beta-adrenergic receptor stimulation can prevent hypercapnic heart failure and that beta-adrenergic receptor activity is involved in the mechanism responsible for this failure.
Effect of stimulation of ansa subclavia on regional myocardial O2 supply and O2 consumption
Authors: Buchweitz E. , Weiss H. R.
Published: December 2017

Cardiac sympathetic nerve stimulation produces increases in various indices of cardiac work and metabolism. To determine how these increased O2 demands are met, the effects of stimulation of the ansa subclavia on regional arterial and venous O2 saturation, O2 extraction, blood flow, and O2 consumption were determined in the hearts of 16 pentobarbital-anesthetized open-chest dogs. Microspectrophotometric observations of small regional arteries and veins in quick-frozen hearts to determine regional O2 extraction were combined with regional blood flow measurements with radioactive microspheres to determine regional myocardial O2 consumption by the Fick principle. Ansa subclavia stimulation produced significant increases in maximum rate of pressure development, heart rate, and blood pressure. Under control conditions, venous O2 saturation was lower and O2 extraction higher in the subendocardial compared with the subepicardial region of the left ventricle. While sympathetic stimulation did not alter the mean O2 extraction or venous O2 saturation values, there were no longer significant subepicardial vs. subendocardial differences in these parameters. Flow and O2 consumption in these regions increased proportionally during stimulation. The ratio of O2 supply to O2 consumption was not significantly altered by ansa subclavia stimulation, indicating that sympathetic stimulation produced no adverse effect in either region.
Peritoneal lymphatic uptake of fibrinogen and erythrocytes in the rat
Authors: Flessner M. F. , Parker R. J. , Sieber S. M.
Published: December 2017

Intact and thoracic duct-cannulated rats were dialyzed at various intraperitoneal pressures with 5% bovine serum albumin solutions containing 125I-fibrinogen or 51Cr-erythrocytes. Lymphatic transport rates were calculated from the mass of tracer passing into the plasma space as function of tracer concentration in the peritoneal fluid during dialysis periods ranging between 143 and 360 min. Peritoneal protein concentrations were constant over the duration of the experiments. The calculated lymph flow rate was independent of intraperitoneal pressure and in intact rats averaged 2.85 +/- 1.22 microliters/min for uptake of 125I-fibrinogen and 2.60 +/- 1.17 for uptake of 51Cr-erythrocytes. However, the observed fluid loss rates from the peritoneal cavity were sensitive to the intraperitoneal pressure and were 5 to 20 times the calculated lymph flow rate. Mass balance experiments in two rats dialyzed with 125I-fibrinogen indicated that a significant proportion (28%) of tracer leaving the peritoneal cavity is absorbed by the anterior muscle wall of the abdomen and is probably trapped there because of its large molecular weight. Results from 125I-fibrinogen and 51Cr-erythrocyte uptake experiments both indicated that only approximately 30% of the total lymphatic drainage of the peritoneal cavity passes through the thoracic duct in rats.
Regression of myocardial hypertrophy and influence of adrenergic system
Authors: Sen S. , Tarazi R. C.
Published: December 2017

Studies of regression of myocardial hypertrophy in spontaneously hypertensive rats (SHR) suggest that the adrenergic system may play an important role in the reversal of hypertrophy. The effect of propranolol on reversal of hypertrophy, however, is still controversial. This study describes the effect of propranolol, given alone or in combination with hydralazine in different ratios for 4 wk, on blood pressure (BP), ventricular weight, and myocardial catecholamine (MC) concentrations. The data show that a certain ratio of propranolol to hydralazine (750:30) leads to moderate BP control (196-156 mmHg) without increased MC (634 vs. 552 ng/g) and moderately reduced hypertrophy. Reduction of BP alone with increased MC (hydralazine alone) or reduction of MC without BP control (propranolol alone) failed to reduce hypertrophy. A significant correlation between both ventricular weight and heart rate with MC (r = 0.6) was obtained by multiple regression analysis. This study suggests that adrenergic factors seem to play an important role in modulating structural cardiac response to variations in arterial pressure.
Local auxotonic systolic force and work in canine right ventricular free wall
Authors: Piene H. , Covell J. W.
Published: December 2017

Regional auxotonic force (F) and segment length (SL) were measured in the right ventricular (RV) free wall of 10 anesthetized dogs. F was obtained with a Feigl force gauge and SL with ultrasonic crystals positioned in the inflow or outflow region and in the longitudinal or transverse direction. Although the time courses of right ventricular pressure and force were almost identical, the timing of right ventricular ejection had little relationship to specific parts of the force-segment-length loop. Thus local F vs. SL loops were of irregular form signifying local lengthening or shortening in isovolumic periods. Local work, i.e., F vs. SL loop area, increased linearly with cardiac output (CO), which was varied by volume expansion or reduction. A predominant contribution to total RV work from any particular region and direction was not observed. A "local contribution factor" [eta, defined as (local work/local area)/(total RV work/free wall area)] fell with increased CO from 2.1 +/- 0.5 at 1.1 l/min to 0.7 +/- 0.2 at 4.8 l/min. This observation suggests that transformation of local into total work became more efficient at higher CO or that structures other than the free wall became increasingly important for RV pump function at higher output levels.
Analysis of cardiac adrenergic mechanisms in hypoxic lambs
Authors: Downing S. E. , Lee J. C.
Published: December 2017

Adrenergically mediated inotropic and chronotropic responses to hypoxemia were studied in 12 neonatal lambs ranging from 1 to 10 days of age. Six lambs were adrenalectomized (Adnx) and six were sham operated. Inotropic changes were assessed from measurements of left ventricular dP/dtmax under controlled hemodynamic conditions. Atropine (1 mg) was given and hypoxia produced by adding N2 to the respirator. In the sham-operated lambs, dP/dtmax increased as a function of the level of hypoxemia. With a mean arterial O2 partial pressure (PaO2) of 21.7 +/- 2.0 Torr, dP/dtmax averaged 17 X 10(2) mmHg/s above control values. Adnx did not reduce resting dP/dtmax, but comparable levels of hypoxemia elicited a much smaller increase (5 X 10(2) mmHg/s) in this group (P less than 0.02). In the sham-operated lambs, ganglionic blockade with tetraethylammonium chloride (TEAC, 100 mg) reduced the hypoxic response to similar values (6.5 X 10(2) mmHg/s). These residual inotropic responses were completely abolished by beta-adrenergic blockade with practolol (4 mg/kg). Chronotropic changes were identical in both groups (18.7 beats/min) and abolished by TEAC alone. It is concluded that the major fraction of adrenergic inotropic stimulation during hypoxemia is derived from the adrenal glands and that autonomic neural function is essential to the release process. Heart rate responses are independent of adrenal integrity. A residual source of inotropic stimulation, blocked by practolol, is derived from unidentified sources.
Sodium dependence of carnitine transport in isolated perfused adult rat hearts
Authors: Vary T. C. , Neely J. R.
Published: December 2017

In heart muscle, the intracellular carnitine concentration is approximately 40 times higher than the plasma carnitine concentration, suggesting the existence of an active transport process. At physiological serum carnitine concentrations (44 microM), 80% of total myocardial carnitine uptake occurs via a carrier-mediated transport system. The mechanism of this carrier-mediated transport was studied in isolated perfused rat hearts. Carnitine transport showed an absolute dependence on the extracellular sodium concentration. The rate of carnitine transport was linearly related to the perfusate sodium concentration at every perfusate carnitine concentration examined (15-100 microM). Total removal of extracellular sodium completely abolished the carrier-mediated transport. Decreasing the perfusate potassium concentration from a control of 5.9 to 0.6 mM stimulated transport by 35%, whereas increasing the extracellular potassium concentration from 5.9 to 25 mM reduced transport by 60%. The carrier-mediated transport was inversely proportional to the extracellular potassium concentration. Acetylcholine (10(-3) M), isoproterenol (10(-7) M), or ouabain (10(-3) did not alter the rate of carnitine transport. Addition of tetrodotoxin (10(-5) stimulated carnitine transport by about 40%, while gramicidin S (5 X 10(-6) M) decreased uptake by about 18% relative to control. The data provide evidence that carnitine transport by cardiac cells occurs by a Na+-dependent cotransport mechanism that is dependent on the Na+ electrochemical gradient.
Pressor responses of rats to vasopressin: effect of sodium, angiotensin, and catecholamines
Authors: Burnier M. , Brunner H. R.
Published: December 2017

The pressor response to lysine vasopressin was tested in groups of male Wistar, Brattleboro, Wistar-Kyoto, and spontaneously hypertensive rats. Moreover, the influence of sodium intake, angiotensin II, saralasin, captopril, norepinephrine, and isoproterenol on vasopressin pressor responses was evaluated. The right iliac artery and one or both femoral veins of the animals were catheterized under light ether anesthesia. The experiments were carried out following a 2-h stabilization period with the rats awake and semirestrained. Pressor responsiveness was evaluated acutely on the basis of dose-response curves (0.5-4 mU). In the Wistar rats, angiotensin II (10 and 30 ng/min) and isoproterenol (10 ng/min) markedly decreased the response to vasopressin, whereas variations in sodium intake and blood pressure per se did not seem to exert any influence. Norepinephrine (250 ng/min) slightly enhanced the pressor responsiveness to the smaller doses of lysine-vasopressin. Brattleboro rats with congenital diabetes insipidus were less sensitive to vasopressin than the other animals, and neither angiotensin II nor isoproterenol induced any change. In conclusion, the pressor responsiveness to vasopressin can vary considerably depending on several factors. These must be taken into account when evaluating the possible pressor role of vasopressin in experimental and clinical settings.
Effects of gamma-aminobutyric acid on neural regulation of the canine sinus node
Authors: Neely B. H. , Hageman G. R. , James T. N.
Published: December 2017

The direct effects of gamma-aminobutyric acid (GABA) on the sinus node and its neural regulation were studied by selective perfusion of the sinus node artery (SNA) in 26 open-chest pentobarbital-anesthetized dogs. GABA (1-1,000 micrograms/ml, 2 ml, SNA) produced no direct effect on intrinsic sinus rate, but in several experiments (at 1 microgram/ml) it produced an inconsistent augmentation of the sinus tachycardia due to right stellate stimulation. At all other concentrations tested (10-1,000 micrograms/ml), GABA did not significantly alter the sinus node response to stellate stimulation. Local alpha-receptor blockade with phentolamine or muscarinic receptor blockade with atropine through the SNA prior to the perfusion of GABA did not change the sinus node responses. GABA (10-1,000 micrograms/ml, 2 ml, SNA) significantly attenuated (by 45-80% of control) the sinus bradycardia due to stimulation of the right vagosympathetic trunk. The sinus node response to selective perfusion of norepinephrine or acetylcholine (0.01 micrograms/ml, 2 ml, SNA) was not affected by GABA. The stellate augmentation (when present) and vagal attenuation were both antagonized by perfusion of picrotoxin (1,000 micrograms/ml, 2 ml, SNA). It is concluded that GABA does not exert any direct effect on the sinus node but may indirectly influence sinus rate by an effect on local nerves or ganglia.
Precautions for measuring blood flow during anemia with the microsphere technique
Authors: Rosenberg A. A. , Jones M. D. , Koehler R. C. , Traystman R. J. , Lister G.
Published: December 2017

Preliminary data from a study of the effects of anemia on organ blood flow showed large discrepancies between cardiac output measured with the microsphere technique and simultaneous values calculated by the Fick principle. The most likely explanation was that the reference sample drawn according to our standard procedure underestimated the microsphere concentration in arterial blood, resulting in erroneously high blood flow values. In the present experiments we compared our usual reference sample, from a small catheter advanced from a peripheral artery into the brachiocephalic artery (withdrawal rate 1.3 ml/min), with a simultaneous sample from a larger catheter withdrawn at the much higher rate (7.89 ml/min). At hematocrits above 32%, microsphere concentrations from the two catheters were similar, but below 32% the concentration of microspheres in blood from the larger catheter was 30-50% more than from the smaller. The discrepancy was not altered by changing the injection site from left ventricle to left atrium and thus was probably not the result of poor mixing within the heart. It may have been the result of nonhomogeneous distribution of microspheres within larger vessels, perhaps as a consequence of laminar flow and axial streaming of both red blood cells and microspheres during anemia. Whatever the cause, it was possible to eliminate the difference by withdrawing from the smaller catheter at a more rapid rate (2.46 ml/min).
Hemodynamic responses to acute carboxyhemoglobinemia in the rat
Authors: Kanten W. E. , Penney D. G. , Francisco K. , Thill J. E.
Published: December 2017

The effects of carbon monoxide on the hemodynamics of the adult rat were investigated. A number of parameters were measured using an open-chest, chloralose-urethan anesthetized preparation. Our experiments showed this anesthetic agent to have several advantages over pentobarbital sodium. One group inhaled 150 ppm CO for 0.5-2 h, carboxyhemoglobin (HbCO) reaching 16%. Heart rate, cardiac output, cardiac index, dF/dtmax (aortic), and stroke volume rose significantly; mean arterial pressure, total peripheral resistance, and left ventricular systolic pressure fell, whereas stroke work, left ventricular dP/dtmax, and stroke power changed little. These effects were evident at a HbCO saturation as low as 7.5% (0.5 h). A second group inhaled 500 ppm CO for 5-48 h, HbCO reaching 35-38%. The same parameters changed in the same direction as in the first group, with mean arterial pressure and peripheral resistance remaining depressed, while heart rate, cardiac output, cardiac index, and stroke volume remained elevated. Heart rate and arterial systolic pressure were also monitored in conscious rats; rats in one group inhaled 500 ppm CO for 24 h, and rats in a second group were injected with a bubble of pure CO ip. In both cases heart rate was sharply elevated and blood pressure depressed as HbCO saturation increased. Both parameters recovered on CO washout. There was no significant difference between the response to inhaled vs. injected CO.
Increased sensitivity to angiotensin in uterine arteries from pregnant rabbits
Authors: Moisey D. M. , Tulenko T.
Published: December 2017

This study was designed to compare the vascular reactivity intrinsic to uterine and femoral arterial smooth muscle from pregnant (0.92 term) and nonpregnant rabbits to angiotensin II (ANG II), norepinephrine (NE), and potassium chloride (KCl) using the isolated helical strip technique. Comparing dose-response relations, arteries from both groups were equally sensitive to NE and KCl. Uterine arteries from pregnant rabbits, however, exhibited a greater sensitivity to the vasoconstricting effects of ANG II (P less than 0.01). This selective increase in sensitivity to ANG II was not observed in femoral arteries. The altered ANG II response in uterine arteries from pregnant rabbits was unaffected by pretreatment with cocaine or phenoxybenzamine, thus ruling out an adrenergic mechanism mediating the response. In addition, evaluation of saralasin affinity (KB) for the uterine arterial ANG II receptor suggested that it was not altered in pregnancy. However, preincubation of uterine arteries from pregnant rabbits with meclofenamate or indomethacin consistently attenuated the ANG II response (P less than 0.05). Therefore, this study demonstrated that 1) uterine arteries from term pregnant rabbits show a selective and specific enhancement to ANG II vasoconstriction, and 2) this increased response of ANG II results from the local ANG II stimulation of synthesis of prostaglandins by the uterine arterial wall that have a net vasoconstricting action.
Outward current and repolarization in hypoxic rat myocardium
Authors: Conrad C. H. , Mark R. G. , Bing O. H.
Published: December 2017

We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.
Compensatory response to hemorrhage in conscious dogs on normal and low salt intake
Authors: Kopelman R. I. , Dzau V. J. , Shimabukuro S. , Barger A. C.
Published: December 2017

The compensatory response to moderately severe hemorrhage (30 ml/kg) was studied in chronically catheterized conscious dogs maintained on normal and low salt intake. Although the fall in blood pressure and the increase in heart rate were similar in the two salt states, the salt-restricted animals had significantly greater rises in plasma renin activity and plasma catecholamines following hemorrhage than did the normal salt dogs. To compare further the relative roles of the alpha-adrenergic system and the renin-angiotensin system in the maintenance of blood pressure following hemorrhage, pharmacologic blockade with either phentolamine or converting enzyme inhibitor was performed 20 min after the completion of the hemorrhage. These latter experiments demonstrated that salt restriction resulted in a significantly greater role for the renin-angiotensin system. Moreover, interruption of the renin-angiotensin system blunted the anticipated rise in catecholamines and heart rate during the additional hypotension induced by converting enzyme blockade after hemorrhage.
Effect of antiplatelet antibody on platelet shape change, volume, and morphology
Authors: Colman R. W. , Nachmias V. T. , Cines D. B. , Schreiber A. D.
Published: December 2017

We extended our studies of the effect of antibody on human platelets. Monomeric immunoglobulin G (IgG) (rabbit) antiplatelet antibody was interacted with human platelets in the absence of complement and the early morphological changes monitored. Platelet shape change, assessed by a rheooptical approach, was noted within 20 s and was proportional to antibody concentration. Antiplatelet antibody-induced shape change was also accompanied by a change in apparent platelet volume, as measured in the resistive particle counter. Scanning and transmission electron microscopy confirmed a disk-to-sphere transformation associated with the formation of bulbous, short surface projections or pseudopodia. In contrast, ADP-induced disk-to-sphere transformation was associated with the development of long, thin filopodia emanating from the platelet. These specific effects of antiplatelet antibody may result in altered platelet function.
Changes in dog gracilis muscle adenosine during exercise and acetate infusion
Authors: Steffen R. P. , McKenzie J. E. , Bockman E. L. , Haddy F. J.
Published: December 2017

We have previously reported that tissue acetate content increases in the canine gracilis muscle during exercise at natural flow. We here report the effects of exercise and infusion of acetate on adenosine content. Muscles were vascularly isolated, perfused naturally, and stimulated to contract isometrically at 0.5, 1.0, or 2.0 Hz for 10 min (n = 6 each). Exercising and contralateral control gracilis muscles were freeze clamped in situ in Wollenberger tongs at the temperature of liquid N2. Force development was maintained during contraction. Resistance decreased as a function of contraction frequency, and adenosine content increased. Tissue adenosine content correlated inversely with resistance (r = -0.57, P less than 0.001), suggesting a role for adenosine in exercise hyperemia. During intra-arterial infusion of sodium acetate into resting muscle, tissue acetate and adenosine contents increased (417-2,193 and 0.88-3.07 nmol/g, respectively), and vascular resistance decreased (17.5-6.01 mmHg X ml-1/min/100 g). Acetate and adenosine contents correlated negatively with resistance (r = -0.83, P less than 0.001, and r = -0.60, P less than 0.05, respectively) and positively with one another (r = 0.58, P less than 0.05). Relative to an infusion of sodium chloride, oxygen consumption, venous PO2, and venous ionized calcium were unaffected. The vasodilatory effect of acetate may be due, in part, to its ability to increase tissue adenosine.
Myocardial relaxation. VI. Effects of beta-adrenergic tone and asynchrony on LV relaxation rate
Authors: Blaustein A. S. , Gaasch W. H.
Published: December 2017

We studied the effect of left ventricular (LV) asynchrony and alterations in beta-adrenergic tone on the systolic load (pressure) dependency of LV isovolumic relaxation rate in anesthetized dogs. The time constant (T) of isovolumic exponential pressure decline was used as an index of relaxation rate. Variably afterloaded LV contractions resulted in a progressive increase in LV end-systolic pressure from 124 +/- 6 in the control beat to 176 +/- 11 mmHg in the third beat and a progressive lengthening of T from 19 +/- 2 to 30 +/- 4 ms. The direct relation between LV end-systolic pressure and T was nearly linear (r = 0.98), and the slope (k) of this relation was taken to reflect the systolic load dependency of T. Administration of isoproterenol (n = 6) produced a decrease in k from 0.11 +/- 0.02 to 0.08 +/- 0.02 (P less than 0.05); with propranolol (n = 6), k increased from 0.08 +/- 0.02 to 0.27 +/- 0.04 (P less than 0.01). Right ventricular epicardial pacing (n = 6) produced an asynchronous LV contraction and an increase in k from 0.09 +/- 0.02 (atrial pacing) to 0.25 +/- 0.04 (P less than 0.01). These studies confirm the dependency of LV relaxation rate on systolic loads and indicate that this form of load-dependent relaxation can be modified by alterations in beta-adrenergic tone and LV asynchrony. The observed alterations suggest the importance of temporal dispersion of the contraction-relaxation sequence as a mechanism responsible for disturbed relaxation.
Ventricular filling pressure as a determinant of coronary blood flow during ischemia
Authors: Dunn R. B. , Griggs D. M.
Published: December 2017

The role of ventricular filling pressure (VFP) as a determinant of coronary blood flow (CBF) in the acutely ischemic ventricle was examined in the open-chest dog under conditions of a reduced, constant coronary artery pressure and an unstable VFP. Blood delivery to different layers of the ventricle and ischemic metabolic changes occurring in these layers were also determined and compared with appropriate control data. A close, inverse, linear relationship between VFP and CBF was found in animals exhibiting a progressive rise in VFP from 6 +/- 0 to 25 +/- 1 mmHg (r = 0.99). A lower endocardial-to-epicardial ratio of delivered blood and a steeper transmural gradient in ischemic metabolic changes were noted in these animals compared with similarly prepared animals exhibiting a stable VFP. The findings demonstrate the importance of VFP as a determinant of CBF during ischemia, and they lend support to the concept that blood flow in the ischemic ventricle is regulated by a preload-dependent transmural gradient in coronary driving pressure.
Reflex modulation of carotid sinus baroreceptor activity in the dog
Authors: Felder R. B. , Heesch C. M. , Thames M. D.
Published: December 2017

Carotid sinus baroreceptor (CBR) sensitivity may be increased by electrical stimulation of sympathetic nerves passing to the carotid sinus region. It remains unknown if reflexly induced changes in efferent sympathetic discharge affect CBR function. In 17 anesthetized dogs, we reflexly induced alterations in sympathetic discharge and recorded CBR activity originating from a vascularly isolated carotid sinus. The stimulus to the baroreceptors was pulsatile with constant mean and pulse pressure. Occlusion of the contralateral common carotid artery (n = 6) resulted in a reflex increase in arterial pressure (116 +/- 10 to 153 +/- 14 mmHg) and an increase (121 +/- 2% of control) in baroreceptor activity (P less than 0.05). Inferior vena caval occlusion (n = 6), which induced a reduction in arterial pressure (145 +/- 19 to 75 +/- 21 mmHg), also provoked an increase (141 +/- 10% of control) in baroreceptor discharge (P less than 0.05). Raising pressure (to 200 mmHg) in the contralateral carotid sinus (n = 7) resulted in a reflex decrease in arterial pressure (169 +/- 16 to 129 +/- 13 mmHg) and a reduction (82 +/- 3% of control) in baroreceptor activity (P less than 0.05). The changes in baroreceptor discharge were abolished by ipsilateral cervical sympathectomy or ganglionic blockade (n = 4). Our findings demonstrate that reflexly induced alterations in the activity of sympathetic fibers innervating the carotid sinuses can modulate baroreceptor discharge.
Effect of caloric restriction on cardiac reactivity and beta-adrenoceptor concentration
Authors: Crandall D. L. , Lai F. M. , Huggins F. J. , Tanikella T. K. , Cervoni P.
Published: December 2017

The effect of a 21-day program of caloric restriction on cardiac reactivity and beta-adrenoceptor number was investigated in male Sprague-Dawley rats. Rats on the restricted diet (Restricted) exhibited significant decreases in body weight, epididymal fat pad, and retroperitoneal fat pad weight as well as the percent of body fat represented by these adipose tissue depots when compared with rats fed ad libitum (Fed). Fed rats exhibited significantly increased total heart weight and total heart protein, but the percent cardiac protein and ratio of heart weight to body weight were similar in Fed and Restricted rats. Isolated atria from Fed and Restricted rats developed similar chronotropic and inotropic responses over a range of isoproterenol concentrations. Although total beta-adrenoceptor number (fmol/heart) was greater in Fed rats, the concentration of beta-adrenoceptors (fmol/mg protein) was remarkably similar regardless of the dietary regimen. Therefore, despite significant decreases in body weight, body fat, and heart weight, the myocardium of Restricted rats maintained the capability of responding to isoproterenol as that of Fed rats, the mechanism of which is at least partially mediated through maintenance of beta-adrenoceptor concentration.
A new thermal sensor for surface-based measurement of local myocardial perfusion
Authors: Castellana F. S. , Case R. B. , Skalak R. , Cho J. M.
Published: December 2017

The transient response of a new thermal sensor for continuous surface-based measurement of local tissue blood flow was evaluated in the beating dog heart. The sensor is 2.5 mm square, tests on the heart, and responds to flow changes only within a region of tissue 3-4 mm below its location on the epicardial surface. Initial studies demonstrate excellent sensitivity, good frequency response with a time constant of the order of 10-11 s, and an ability to continuously monitor changes in local myocardial blood flow during a variety of well-understood interventions, including coronary artery occlusion, reactive hyperemia, and intravenous administration of nitroglycerin and dipyridamole.
Blood flow and norepinephrine effects on liver vascular and extravascular volumes
Authors: Cousineau D. , Goresky C. A. , Rose C. P.
Published: December 2017

The relative effects of changes in hepatic blood flow and in levels of sympathetic activity on liver volumes were ascertained by use of multiple-indicator dilution studies. Portal vein-hepatic vein dilution patterns were obtained following injection of a mixture containing 51Cr-labeled red blood cells (a vascular reference) and 14C-labeled sucrose (a reference extracellular substance). Hepatic blood volume was calculated as the product of liver blood flow and red cell transit times, and interstitial space as the product of plasma flow and the difference between labeled sucrose and red cell transit times. Concentrations of norepinephrine and epinephrine were measured in aorta, portal vein, and hepatic vein. Hepatic blood volume and interstitial space increased with increased blood flow; and elevated plasma norepinephrine levels, especially in portal vein (following either exogenous infusion or activation of peripheral sympathetic fibers) selectively reduced the distending effect of hepatic inflow on the vascular volume. The data provide a description of the in vivo variation in canine liver vascular and interstitial volumes with blood flow and sympathetic activation.
Effects of indomethacin on cerebral blood flow during hypercapnia in cats
Authors: Busija D. W. , Heistad D. D.
Published: December 2017

To study the contribution of prostaglandins to cerebral vasodilatation during hypercapnia, we inhibited prostaglandin synthesis with indomethacin. We measured cerebral blood flow (CBF) in anesthetized cats with 15-micrometers microspheres during normocapnia (PCO2 approximately 33 Torr), moderate hypercapnia (PCO2 approximately 49 Torr), and severe hypercapnia (PCO2 approximately 65 Torr) before and after intravenous administration of vehicle or indomethacin (3 and 10 mg/kg). Hypercapnia produced graded increments in blood flow to all areas of the brain. Administration of indomethacin did not change control CBF or significantly attenuate increases in CBF during hypercapnia. We examined efficacy and specificity of inhibition of prostaglandin synthesis by indomethacin using the cranial window method. Arachidonic acid (100 and 200 micrograms/ml) and acetylcholine (10(-7) and 10(-6)M or 10(-6) and 10(-5) M), dissolved in artificial cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of indomethacin blocked vasodilatation produced by arachidonic acid but did not affect the response to acetylcholine. Thus indomethacin, at a dose that effectively blocks prostaglandin synthesis, did not alter resting CBF or attenuate the increase in CBF during hypercapnia. This study suggests that steady-state cerebral vasodilatation during hypercapnia is largely preserved after inhibition of prostaglandin synthesis.
New technique for detection of changes in QRS morphology of ECG signals
Authors: Blumlein S. L. , Harvey G. , Murthy V. K. , Haywood L. J.
Published: December 2017

With the use of the electrocardiogram (ECG) as a prototype signal, a new technique was devised for detecting signals embedded in noise. Averaged "normal" digitized ECG signals formed a template to which subsequent ECG QRS complexes were compared. The difference between the averaged template signals and subsequent normal beats was white noise, whereas the difference between the template and ectopic beats consisted of nonrandom signal variation. The template to new signal comparison for the zero-, first-, second-, and third-order differences utilized an approximate F test. Accurate detection of abnormal signals associated with high- and low-frequency noise is accomplished with this method, and the practical clinical utility of the method is under study.
Decreased myocardial function and myosin ATPase in hearts from diabetic rats
Authors: Garber D. W. , Neely J. R.
Published: December 2017

The effect of diabetes on cardiac function was determined in isolated rat hearts. Diabetes was induced by injection of alloxan (doses ranged from 37.5 to 60 mg/kg body wt), and the heart were removed and perfused in the working heart preparation. Doses of alloxan ranging from 37.5 to 42 mg/kg did not consistently alter cardiac function even though serum glucose was elevated and serum thyroid hormones were reduced. Injection of 45 mg/kg of alloxan caused a large increase in serum glucose and a larger decrease in thyroid hormones. In this case, ventricular function was more consistently depressed after 1-2 wk. Function was not altered 48 h after injection of 60 mg kg of alloxan. However, when animals were given 60 mg/kg of alloxan and then maintained on insulin for 7 days, depressed cardiac function developed within 4 days after the insulin treatment was stopped. The decline in function involved a decrease in heart rate peak systolic pressure, and left ventricular +dP/dt. It was associated with greatly reduced serum thyroid hormones (both T3 and T4) and lower ventricular Ca2+-activated myosin ATPase activity. Fasting of rats for 4 days also resulted in decreased serum T3 and T4, depressed cardiac function (although heart rate was unchanged), and lower Ca2+-activated myosin ATPase activity.
Detection and quantification of small left-to-right shunts by the phase-plane method
Authors: Fonseca-Costa A. , Magrassi P. , Zin W. A. , Romeo L. J.
Published: December 2017

Sixty-five pairs of indicator-dilution curves were obtained in five anesthetized dogs. After the injection of indocyanine dye into the left atrium, blood was simultaneously sampled through dichromatic cuvette densitometers from the femoral artery and the distal pulmonary artery. Dye-dilution curves were recorded from dogs with normal cardiovascular systems and after the surgical production of left-to-right shunts of different magnitudes. The percent of blood shunting was calculated according to the double sampling method and compared with a new method based on the deviation observed in the terminal portion of the indicator-dilution phase-plane loop. A high level of correlation was observed between both methods (r = 0.961). The phase plane shows its utility in the quantification of small left-to-right shunts. The use of only one sampling site at a peripheral systemic artery is an important advantage because there is complete mixture between shunted and unshunted blood.
Hypoxic responses of sympathetic preganglionic neurons in sinoaortic-denervated cats
Authors: Rohlicek C. V. , Polosa C.
Published: December 2017

The relation between arterial O2 tension (PaO2) and the firing rate of sympathetic preganglionic neurons (SPN) was studied in 16 strands of the cervical sympathetic trunk (CST) during graded isocapnic hypoxia in 11 sinoaortic-denervated central nervous system (CNS)-intact, anesthetized cats. SPN firing rate was independent of PaO2 from normoxia down to a PaO2 of 40 Torr. Below this PaO2 level three response patterns were observed, i.e., an excitatory response (n = 8), a depressant response (n = 3), and a mixed response consisting of a depression of firing at less severe hypoxic levels and an increase in firing rate at more extreme hypoxic levels (n = 5). Similar response patterns were also observed in four strands of the CST in three unanesthetized, sinoaortic-denervated, midcollicular decerebrate preparations. Systemic arterial pressure decreased in all cats as PaO2 decreased. Phrenic nerve activity also decreased in all cats with a course resembling that of the depression of sympathetic firing and disappeared at a PaO2 of 20 Torr. The data suggest that systemic hypoxia in the sinoaortic-denervated, CNS-intact or decerebrate animal activates both excitatory and depressant mechanisms acting on SPNs.
Fastigial stimulation releases vasopressin in amounts that elevate arterial pressure
Authors: Del Bo A. , Sved A. F. , Reis D. J.
Published: December 2017

Electrical stimulation of the cerebellar fastigial nucleus (FN) in anesthetized, paralyzed, and artificially ventilated rat with a 10-s stimulus train (50 Hz) resulted in a stimulus-locked elevation in arterial pressure (AP) and heart rate, the fastigial pressor response (FPR). Blockade of autonomic effectors by chemosympathectomy (produced by treatment with 6-hydroxydopamine) combined with adrenalectomy, or by spinal cord transection at C1, abolished the FPR but unmasked an elevation of AP with longer latency (10-12 s) and duration (2-4 min), termed the residual FPR. The residual FPR was 1) abolished by midbrain transection, 2) blocked by administration of a specific antagonist of the vasopressor response to arginine vasopressin (AVP) [1,d(CH2)5Tyr(Me)AVP], and 3) was absent in homozygous and attenuated in heterozygous rats of the Brattleboro strain. FN stimulation elevated AVP threefold (from 13 +/- 1 to 38 +/- 8 pg/ml, P less than 0.02; n = 6) in intact rats and sevenfold in rats with combined chemosympathectomy and adrenalectomy (from 14 +/- 1 to 96 +/- 11 pg/ml, P less than 0.001; n = 9). Stimulation of the cerebellar FN can release AVP. In the absence of sympathoadrenal effectors, the amount so released is enhanced and capable of elevating AP.
Actions of adenosine on normal and abnormal impulse initiation in canine ventricle
Authors: Rosen M. R. , Danilo P. , Weiss R. M.
Published: December 2017

We studied the role of adenosine in modulating pacemaker activity in normal and infarcted ventricular tissues. We used standard microelectrode techniques to study the effects of adenosine on impulse initiation in Tyrode's superfused normal canine Purkinje fibers (PF), PF obtained from experimentally infarcted hearts, and BaCl2-superfused PF. Adenosine reduced automaticity of normal PF, whereas beta, gamma-methylene ATP did not. In infarcted and in Ba2+-depolarized PF, adenosine had no effect on automaticity or the action potential. We then used intracellular current injection to vary the membrane potentials of normal PF and found adenosine to depress automaticity more at high than at low membrane potentials. The ability of adenosine to counteract the effects of epinephrine on automaticity also was related to membrane potential. We conclude that adenosine depresses normal automaticity but has little effect on abnormal impulse initiation at low membrane potentials. It therefore appears that in the setting of myocardial infarction or ischemia the extent to which adenosine release will modify the function of normal and ectopic pacemakers will be influenced by the membrane potentials of those pacemakers.
A microcomputer oximeter for whole blood
Authors: Kiel J. W. , Shepherd A. P.
Published: December 2017

A system is described for measuring the percent of oxyhemoglobin in flowing whole blood. The system consists of an Apple II+ computer, a commercially available analog-to-digital converter, a simple electronic circuit to illuminate blood with light at two appropriate wavelengths, and a short program in BASIC. This oximeter is shown to yield a linear measurement of oxyhemoglobin saturation when compared with standard oxygen analyses. Data can be sampled at a sufficiently rapid rate to yield an essentially continuous measurement in typical cardiovascular studies. The system can be implemented by the average investigator from standard electronic components. The oximeter program can be combined into a general-purpose data acquisition program, and 15 analog-to-digital channels remain available for gathering other data.
An intravascular protein osmometer
Authors: Henson J. W. , Brace R. A.
Published: December 2017

Our purpose was to develop an intravascular osmometer for measuring the colloid (i.e., protein) osmotic pressure (COP) of circulating blood. A semipermeable hollow fiber from a Cordis Dow artificial kidney (C-DAK 4000) was attached to polyethylene tubing on one end, filled with saline, and sealed at the other end. This was small enough to be inserted into the vasculature of research animals. Protein osmotic pressure plus hydrostatic pressure was measured by a Statham pressure transducer attached to the hollow fiber. Simultaneously, a second catheter and transducer was used to measure hydrostatic pressure, which was subtracted from the pressure measured from the fiber with an on-line computer. The system was documented by a variety of tests. The colloid osmotic pressure vs. albumin concentration curve determined with the fiber is identical to the curve determined by standard membrane osmometry. The time constant for 2- and 8-cm fibers was 2.6 +/- 0.6 and 1.5 +/- 0.5 (+/- SD) min, respectively. The reflection coefficient (+/- SD) of the fiber for NaCl is 0.042 +/- 0.019 (n = 38); COP measured at varying temperatures (absolute scale) changed linearly as expected from COP = nCRT (i.e., van't Hoff's law). Finally, hollow-fiber osmometers were inserted into femoral veins of dogs and sheep, and blood COP was continuously recorded during osmotic manipulations. In conclusion, we attempted to develop and document a simple method for continuous measurement of intravascular colloid osmotic pressure.
Cardiac sarcolemmal Na+-K+-ATPase: combined effects of propranolol and arachidonyl CoA
Authors: Kramer J. H. , Owens K. , Weglicki W. B.
Published: December 2017

Sarcolemma from adult canine cardiac myocytes (Na+-K+-ATPase activity 71.8 +/- 3.4 mumol . mg protein-1 . h-1) was preincubated (10 min at 37 degrees C, pH 7.2) with 1) 5-250 microM arachidonyl CoA, 2) 2.5 nM- 2.5 mM propranolol, 3) 5-250 microM arachidonyl CoA plus 2.5 mM propranolol or 4) 2.5 nM-2.5 mM propranolol plus 50 microM arachidonyl CoA; after preincubation the Na+-stimulatable activity was assayed. Arachidonyl CoA alone (50 microM, expt 1) elicited maximum stimulation (89% above control), whereas concentrations greater than 125 microM were inhibitory. Preincubation with propranolol alone (expt 2) had no significant effect on activity. However, when membranes were pretreated with both arachidonyl CoA and 2.5 mM propranolol (expt 3) activity was significantly inhibited. Preincubation with concentrations of propranolol greater than 25 microM were required to reverse the stimulatory effect of 50 microM arachidonyl CoA (expt 4). Propranolol and arachidonyl CoA do not have to be present simultaneously to produce an inhibitory effect. Activity was greatly inhibited (87%) when membranes were preincubated with 100 microM arachidonyl CoA followed by addition of 2.5 mM propranolol; no inhibition was observed if preincubation conditions were reversed. These data suggest that propranolol-induced inhibition of the Na+-K+-ATPase is reversible but becomes irreversible when sarcolemma is pretreated with the fatty acyl CoA, either prior to or during propranolol preincubation.