bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA synthesis in coronary collaterals after coronary artery occlusion in conscious dog
Authors: Pasyk S. , Schaper W. , Schaper J. , Pasyk K. , Miskiewicz G. , Steinseifer B.
Published: December 2017

With [3H]thymidine, DNA synthetic activity in coronary collateral arterioles was assessed in dogs subjected to progressive stenosis of the left circumflex coronary artery for different periods (36 h-5 days). Coronary flow, reactive hyperemia, and pressure gradient (aortic pressure, peripheral coronary pressure) were measured. Normal animals and animals with sham operations served as controls. Labeling of nuclei was seen in seven of the constricted dogs. Proliferative activity was highest at the level of the smallest diameters of the collateral vessels (midzone). There was heavy labeling in intima and media. Adventitial and myocardial mesenchymal cells also incorporated [3H]thymidine. No radioactive DNA was found in control animals. The data suggest that the active growth process in collaterals after constriction of the left circumflex coronary artery appears early, as there is evidence of collateral growth after 36 h of constriction. Peak growth as evidenced by [3H]thymidine incorporation was reached when the occlusion period was 4 days.
Effects of increased venous pressure on albumin- and IgG-excluded volumes in muscle
Authors: Bell D. R. , Mullins R. J.
Published: December 2017

The effect of elevated venous pressure on the extravascular distribution space of albumin and gamma-immunoglobulin G (IgG) in muscle was studied in anesthetized rabbits. In nine rabbits, venous pressure in one leg was increased from 8 to 28 mmHg while the other leg served as a control. Samples of plasma and prenodal muscle lymph were collected for 4 h before taking samples of the gastrocnemius muscle. Lymph was collected from a femoral lymphatic after ligating the popliteal efferent lymphatic. The extracellular and plasma spaces in the tissue samples were measured using 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and 125I-human serum albumin, respectively. The protein spaces were calculated from measurements of endogenous albumin and IgG concentrations using rocket electroimmunoassay. Albumin and IgG were both excluded from 50% of the interstitial space at lymph concentration. After venous congestion, the interstitial volume was twice that of control. Lymph flow increased from 0.82 +/- 0.18 to 4.44 +/- 0.64 microliters/min. The extravascular mass of albumin and IgG increased. There was no change in the excluded volume fraction for albumin but a decrease in that for IgG. Changes in interstitial protein exclusion in skeletal muscle after pressure elevation may not be important in oncotic buffering of the edema.
Measurement of coronary sinus blood flow by fiber-optic laser Doppler anemometry
Authors: Kilpatrick D. , Linderer T. , Sievers R. E. , Tyberg J. V.
Published: December 2017

The Doppler shift of a laser has been used to measure the velocity of blood in the coronary sinus of the dog. The laser was delivered along a fine fiber-optic probe, which was also used to receive the reflected light. The Doppler shift was measured from the output of a digital spectrum analyzer. This measurement, proportional to the velocity of blood, was correlated with the blood flow measured by an electromagnetic flowmeter. Studies were performed on 112 successful maneuvers in eight consecutive anesthetized dogs. In the minimally damped electromagnetic flow traces, the correlation between coronary sinus blood flow velocity and coronary sinus blood flow was high (r greater than 0.95). This measurement will give absolute flow values only if the exact dimensions of the coronary sinus are known. The linear relationship of coronary sinus velocity and flow supports the postulate that coronary sinus dimension remains similar during normal and high flows. This technique, fiber-optic laser Doppler anemometry, is an accurate measure of relative coronary sinus blood flow. It is suitable for use in human coronary sinuses, especially to monitor the effect of interventions.
Detection of takeoff potential from intracellular recordings
Authors: McGillivray R. , Wald R. W.
Published: December 2017

The measurement of takeoff potential from intracellular recordings of the cardiac action potential may be useful in the study of the cardiac action potential may be useful in the study of spontaneous automaticity and of the effects of cardioactive drugs on active propagation. We describe a circuit capable of detecting and storing the membrane potential at a point where the slope of the membrane potential exceeds a preset value. The capability of this circuit to track the takeoff potential was tested using intracellular recordings from cardiac Purkinje fibers during spontaneous automaticity as well as during electrical stimulation.
Beat-by-beat control of cardiac output in awake dogs with atrioventricular block
Authors: Wyss C. R. , Bennett T. D. , Scher A. M.
Published: December 2017

In dogs with atrioventricular block and implanted ascending aortic flow probes, cardiac output can be controlled on each beta. The procedure is implemented through on-line use of a digital computer. The algorithm has three steps: 1) aortic flow is measured and integrated to give stroke volume; 2) at the end of ejection, the program computes how long the current beat must be to keep cardiac output at a target level; and 3) the ventricle is stimulated at the proper time. Cardiac output can be controlled over a range of 60-110% of normal in a resting dog. This range can be expanded by combining hemorrhage or volume infusion with the control procedure.
Mechanism of higher oxygen consumption rate: pressure-loaded vs. volume-loaded heart
Authors: Suga H. , Hisano R. , Hirata S. , Hayashi T. , Ninomiya I.
Published: December 2017

The greater cardiac oxygen consumption (VO2) under pressure than under volume load has been accounted for by the greater ventricular wall force under pressure load. We cannot fully agree with this because the wall force has not always been uniquely correlated with VO2. We attempted to account for the greater VO2 under pressure load by the ventricular systolic pressure-volume area (PVA), which we previously showed uniquely correlated with VO2. In isolated supported canine hearts, we produced servo-controlled ejecting contractions the stroke work (SW) of which was doubled from control by doubling ejection pressure (P) with comparable stroke volume (SV) and by doubling Sv with comparable P. Despite comparable increments in SW from 370 to 680 mmHg.ml under two different loads, VO2 and PVA increased significantly more under pressure load (from 0.033 ml O2/beat and 800 mmHg.ml to 0.0560 and 1,800, respectively) than under volume load (increasing to 0.038 and 1,200, respectively; P less than 0.01). These results suggested to us a new mechanism underlying the greater VO2 under pressure load.
Regional blood flows measured in Mongolian gerbil by a modified microsphere method
Authors: Matsumoto M. , Kimura K. , Fujisawa A. , Matsuyama T. , Asai T. , Uyama O. , Yoneda S. , Abe H.
Published: December 2017

Regional blood flow to major organs and regional cerebral blood flow were determined in seven anesthetized male gerbils by a modified microsphere method. Carbonized microspheres, 15 micrometers in diameter and labeled with 85Sr or 141Ce, were injected into the left ventricle by cardiac puncture through the closed thorax, and reference samples of known volume were withdrawn from tail-artery cannula. No significant hemodynamic alterations were observed during microsphere administration, and extraction of 15-micrometers microspheres by the pulmonary or systemic capillary beds was nearly 100%. The adequacy of mixing of microspheres in the left ventricle was also validated. The absolute regional blood flow to various organs and regional cerebral blood flow were expressed in terms of milliliters per minute per gram tissue weight, and the values mostly agreed with those reported previously in rats. The results indicate that the reference sample method can be applied to the gerbil. This method should allow the gerbil, which is an animal widely used in stroke research, to be conveniently used for hemodynamic studies when organ blood flow and regional cerebral blood flow are necessary.
Utilization of endogenous lipid, glycogen, and protein by rabbit aorta
Authors: Odessey R. , Chace K. V.
Published: December 2017

The utilization of endogenous stores by rabbit aorta in vitro was measured. In substrate-free medium glycogen disappearance may account for less than 20% of the tissue O2 consumption during incubations of less than 2-3 h. At longer times (or in the presence of glucose) glycogen catabolism is negligible. Calculations from the rate of proteolysis suggest that oxidation of endogenously generated amino acids accounts for less than 7-10% of the oxygen consumption. Furthermore, the presence of amino-oxyacetate, a transaminase inhibitor, did not alter the ATP-ADP ratio. By contrast, measurements of the disappearance of tissue triglyceride indicate that endogenous lipid could meet the fuel requirements of the aorta. Direct measurement of intracellular fatty acid oxidation was obtained by measuring acyl carnitine specific activity and 14CO2 production from [1-14C]palmitate. Fatty acid oxidation could account for at least 90% of the total O2 consumption, and 83% of the fatty acids consumed were derived from endogenous tissue stores. Octanoate was found to inhibit both exogenous and endogenous fatty acid oxidation. These findings may indicate that shorter-chain fatty acids may be preferentially utilized by the aorta.
Changes in intracellular Ca2+ activity with stimulation in sheep cardiac Purkinje strands
Authors: Lado M. G. , Sheu S. S. , Fozzard H. A.
Published: December 2017

One hypothesis to explain increased contraction strength with increased stimulation rate in heart muscle requires that stimulation increase intracellular Na+ activity(aiNa). This is proposed to increase intracellular Ca2+ activity (aiCa) via the Na-Ca exchange mechanism. Several indirect studies have supported the idea that aiNa is increased with stimulation, and more recently we have directly demonstrated aiNa elevation with Na+-sensitive microelectrodes. We now report aiCa to be elevated after trains of stimuli at different rates in sheep cardiac Purkinje strands. The resting level of aiCa in six strands was 93 +/- 15 (SE) nM, and it increased to 162 +/- 20 nM after stimulation at 3 Hz. The recovery of aiCa was exponential, and the time constants of 80-120 s were similar to those previously found for aiNa. A positive force-frequency relation was found in sheep Purkinje fibers that correlated with the increased aiCa. The results support the hypothesis that the Na-Ca exchange system plays an important role in the force-frequency phenomenon.
Microvascular response to blockade of prostaglandin synthesis in rat skeletal muscle
Authors: Faber J. E. , Harris P. D. , Joshua I. G.
Published: December 2017

The contribution of endogenous prostaglandins (PGs) to the control of arteriolar diameter in the microcirculation is incompletely defied and has only been studied in drug-anesthetized animals. To test the possibility that endogenous PGs are tonically released to exert a net dilator influence at certain levels in the microcirculation, television microscopy was used to quantitate the arteriolar responses in the rat cremaster muscle to local blockade of PG synthesis with indomethacin. Rats were decerebrated by a midcollicular transection and were allowed to recover from surgical anesthesia. The cremaster muscle with intact circulation and innervation was suspended by sutures in a temperature-controlled Krebs bath. Diameters, vasomotion frequency, and vasomotion amplitude of arterioles at several anatomic levels were measured before and after local inhibition of PG synthesis in the presence and absence of alpha-adrenergic receptor blockade. Inhibition of PG synthesis produced marked constriction (42-66% of control) at all arteriolar levels, with greater responses occurring in the smaller arterioles. PG synthesis blockade increased vasomotion frequency in arterioles that exhibited spontaneous vasomotion during control periods, and blockade induced vasomotion in vessels lacking spontaneous vasomotion. Pretreatment with phentolamine significantly attenuated the constriction and augmentation of vasomotion. These data indicate that dilator PGs participate in the moment-to-moment regulation of arteriolar tone and local blood flow in skeletal muscle. Further, their mechanism of action may involve alterations in neuronal norepinephrine release or alpha-receptor sensitivity.
Membrane currents, contractions, and aftercontractions in cardiac Purkinje fibers
Authors: Lipsius S. L. , Gibbons W. R.
Published: December 2017

We examined relationships between isometric tension and membrane currents in sheep Purkinje fibers voltage clamped by the two-microelectrode method. Oscillatory restitution of contractility was accompanied by a small oscillation in membrane current and by an aftercontraction. The membrane current oscillation resembled the transient inward current (TI) others have reported in the presence of strophanthidin. Twitches produced by voltage clamp depolarizations did not correlate with net outward current in normal solution, but when the early outward current was blocked by 0.5 mM 4-aminopyridine, the residual outward current did correlate with twitches elicited by strong depolarizing clamps, particularly in solutions containing higher than normal calcium concentrations. The results illustrate important similarities and differences between membrane current behavior in sheep Purkinje fibers and behavior others have reported in calf fibers. Correlations between restitution, aftercontractions, and TI's, and between twitch tension and a component of outward current, may arise because of calcium regulation of membrane conductance, electrogenic Na-Ca exchange, or a combination of these and other mechanisms.
Internal capacitance and resistance allow prediction of right ventricle outflow
Authors: Campbell K. B. , Ringo J. A. , Wakao Y. , Klavano P. A. , Alexander J. E.
Published: December 2017

The relationship between right ventricle afterloading pressure (P) and outflow (Q) was studied in three isolated canine right ventricle (RV) preparations. Right atrial pressure was held constant while graded elevations in P were induced with stepwise occlusions of the right and left branches of the pulmonary artery. P and Q signals were collected and analyzed using a digital computer system. Data were analyzed by assuming a model structure for the RV and comparing resultant model predictions of Q with actual observations. The model structure was modified in accordance with the discrepancy between prediction and observation to improve the model's predictive capability. The initial model tested was the time-varying linear relationship between ventricular volume and pressure. Utilizing this model, accurate predictions of RV outflow in the face of varying pressure afterloads could not be made. The addition of a series resistance to this elementary model resulted in marked improvement in predictive performance. The addition of greater complexity to the model gave only marginal improvement to the model's predictive capability. It was concluded that a time-varying capacitance and series resistance adequately model internal properties of the RV that relate outflow to afterloading pressure.
Relaxant responses to transmural stimulation and nicotine of dog and monkey cerebral arteries
Authors: Toda N.
Published: December 2017

In helical strips of dog and monkey cerebral arteries contracted with prostaglandin F2 alpha, transmural stimulation and nicotine produced relaxations that were abolished by tetrodotoxin and hexamethonium, respectively. These responses were attenuated by quinidine, whereas relaxations of dog coronary arteries to transmural stimulation and isoproterenol were unaffected. Treatment with vasoactive intestinal polypeptide (VIP) and substance P (SP) abolished the relaxant response of cerebral arteries to repeated applications of VIP and SP, respectively; however, after VIP or SP, a normal relaxant response to transmural stimulation or nicotine was produced. Aminophylline suppressed relaxations induced by ATP but not by nerve stimulation. VIP, SP, and adenosine 5'-triphosphate (ATP) relaxed dog cerebral arteries; the responses were unaffected by quinidine. However, only VIP and ATP relaxed monkey cerebral arteries, and SP contracted the arteries. Acetylcholine contracted monkey arteries, in which transmural stimulation produced a relaxation. It may be concluded that nerves innervating the cerebrospinal wall are stimulated electrically and chemically by nicotine, resulting in the arterial relaxation. However, a vasodilator transmitter was not identified. Quinidine appears to selectively antagonize the action of the transmitters on cerebroarterial smooth muscle.
A mechanism for reduced myocardial carnitine levels in diabetic animals
Authors: Vary T. C. , Neely J. R.
Published: December 2017

The effects of substrates, fasting, and diabetes on carnitine transport into the myocardial cells were characterized in perfused adult rat hearts. Increasing the level of acetyl carnitine and decreasing the level of free carnitine by perfusion with various substrates did not alter the rate of carnitine transport. Carnitine transport was enhanced by the perfusion with palmitate. At low work, addition of 1.2 mM palmitate increased carnitine transport by 33%, whereas high work + 1.2 mM palmitate stimulated transport 60% over that of glucose-perfused hearts. The enhancement of carnitine transport correlated with a rise in tissue levels of long-chain acyl carnitine. When the level of long-chain acyl carnitine was increased prior to measurement of carnitine transport, the enhancement of uptake seen with palmitate as substrate was not observed. Carnitine transport in hearts from 48-h-fasted or diabetic animals was not different from transport in hearts of fed animals. Diabetes resulted in decreased tissue levels of carnitine. The decrease was observed after 48 h of severe diabetes and after several weeks of mild diabetes. In each case, low tissue levels of carnitine were associated with reduced serum carnitine. Serum carnitine decreased to a value near the Km for carnitine transport in diabetic animals. It is concluded that a decreased rate of transport due to lower serum carnitine may be responsible for reduced levels of carnitine seen in diabetic hearts.
Role of renal nerves in onset and maintenance of spontaneous hypertension
Authors: Norman R. A. , Dzielak D. J.
Published: December 2017

Renal denervation has been reported to delay development of hypertension in Okamoto spontaneously hypertensive rats (SHR) but to have no effect on the final hypertensive state. However, functional reinnervation begins to occur about 1 mo after renal denervation. The arterial pressure of SHR undergoing repeated bilateral renal denervations at the age of 4, 7, 10, 13, and 16 wk was compared with that in sham-operated SHR. In addition, the effect of successive renal denervations at 4, 7, and 10 wk of age in Wistar-Kyoto (WKY) control rats was determined. Both indirect measurement of pressure by the tail-cuff technique and mean arterial pressure (MAP) measurement indicated that renal denervation prevents full expression of hypertension in SHR. MAP in 19-wk-old renal-denervation SHR averaged 159 +/- 5.1 mmHg (SE) vs. 178 +/-0 4.2 mmHg in sham-operated SHR. Renal denervation had no effect on arterial pressure of WKY rats. Renal norepinephrine content in the renal-denervated WKY rats and SHR was less than 20% of that in the sham-operated groups. Successive bilateral renal denervations every 3 wk blocks 30-40% of the expected progressive elevation of arterial pressure in aging SHR.
On-line calorimetry in the arterially perfused rabbit interventricular septum
Authors: Ponce-Hornos J. E. , Ricchiuti N. V. , Langer G. A.
Published: December 2017

A method has been developed to measure myocardial heat production simultaneously with mechanical (developed tension, rate of contraction and relaxation) and metabolic parameters in the arterially perfused interventricular septum of the rabbit. The system allows control of rest tension, frequency of contraction, temperature, and composition of the perfusate. The technique is based on the differential measurement of the heat flux from the muscle to the calorimetric bath. This technique is able to resolve changes in heat production as small as 0.06 mW. The resting heat production measured with the present calorimeter (1.62 +/- 0.1 mW/g wet tissue) agrees with that obtained with thermopiles and with that calculated from measurements of oxygen consumption. The heat per contraction (6.5 +/- 1.4 mJ/g wet tissue) also agreed with that measured with thermopiles in rabbit papillary muscles. The heat production measured at 22 degrees C under severe hypoxia can be fully explained by the addition of the expected change of enthalpy due to the reaction 0.5 glucose-lactate, calculated on the basis of the lactate measured in the perfusate, and the expected change of enthalpy of oxygen consumption [assuming that all remaining O2 in perfusate (0.09 vol%) is used for combustion of glucose]. These results clearly demonstrated the feasibility of this method for the correlation of changes in energy turnover, through the measurement of the heat production, with mechanical and metabolic processes on-line in arterially perfused septum.
Relative error and variability in blood flow measurements with radiolabeled microspheres
Authors: Dole W. P. , Jackson D. L. , Rosenblatt J. I. , Thompson W. L.
Published: December 2017

The validity of blood flow measurements made using radiolabeled microspheres (reference sample technique) has been well established in a variety of experimental models. Previous studies of the variability of the method emphasize tissue sphere number as the principle source of random variation. However, blood flow measurements depend on sphere distribution to both tissue and reference samples as well as on quantitation of different isotopes in a single tissue sample. In this study we examined the major determinants of relative error and variability in flow rate measurements inherent in the reference sample technique. Error magnitude was predicted from a statistical model, simulated with numerical analogs, and measured in anesthetized dogs with 15-micrometers microspheres. Theoretically, with 2,000 spheres in the reference sample and greater than or equal to 475 spheres in a tissue sample, blood flow can be measured with 10% accuracy at the 95% confidence level and with duplicate variability of 14%. Random errors in isotope quantitation were influenced by the specific activity of the isotope and the fractional distribution of a given isotope over the various energy windows. Suspension of tissue and reference sample spheres at different heights (0.2 cm) resulted in systematic flow errors of up to 13%. When errors due to separation of isotopes and differences in sample height were minimized, the major determinant of variability in flow measurements during simultaneous injection of differently labeled microspheres was the number of spheres in both tissue and reference samples.
Vasodepressor action of angiotensin in conscious chickens
Authors: Nakamura Y. , Nishimura H. , Khosla M. C.
Published: December 2017

In chronically cannulated conscious chickens, Gallus gallus, native chicken angiotensin II ([Asp1,Val5]ANG II) caused biphasic blood pressure responses, a depressor followed by a pressor response. The pressor response appears to be mediated primarily by catecholamines. The depressor responses increased with increasing doses and were accompanied by tachycardia. The onset of the depressor action of [Asp1,Val5]ANG II (2.49 +/- 0.22 s) was nearly as quick as that of acetylcholine or histamine. Replacement of aspartic acid in position 1 with sarcosine or asparagine reduced both depressor and pressor potencies, whereas there was no difference either in depressor or pressor potencies between [Asp1,Val5] and [Asp1,Ile5]ANG II. The depressor response to [Asp1,Val5]ANG II was not inhibited by atropine, a vasopressin antagonist, prostaglandin synthetase inhibitors, methysergide, or propranolol but was blocked markedly by [Sar1, Ile8]ANG II and partially by [Sar1,Thr8]ANG II. The results suggest that the vasodepressor action of ANG II is mediated by angiotensin receptors and may possibly be a direct action on the vascular smooth muscle.
Thromboxane mediates acute pulmonary hypertension in sheep extracorporeal perfusion
Authors: Peterson M. B. , Huttemeier P. C. , Zapol W. M. , Martin E. G. , Watkins W. D.
Published: December 2017

We measured serial plasma concentrations of thromboxane B2 (TXB2), the stable metabolite of the putative pulmonary vasoconstrictor thromboxane A2 (TXA2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of the pulmonary vasodilator prostacyclin (PGI2) by double-antibody radioimmunoassay during partial venovenous bypass in 25 awake sheep. The onset of bypass caused mean pulmonary artery pressure (PAP) to increase from 16 +/- 1 to 28 +/- 2 mmHg at 12 +/- 2 min, due to an increase of pulmonary vascular resistance, followed by a return to control within 45 min. There was no systemic hypoxia. TXB2 increased simultaneously with the onset of pulmonary hypertension (PH) (236 +/- 36 to 700 +/- 120 pg/ml at 0 and 5 min) and peaked at 1,724 +/- 172 pg/ml 10 min after maximum PAP was achieved. Positive pulmonary artery-to-aortic differences of TXB2 were measured. 6-Keto-PGF1 alpha increased from 51 +/- 3 to 842 +/- 367 pg/ml at 35 min. PGF2 alpha was unchanged (130 +/- 45 pg/ml). PH, TXB2, and 6-keto-PGF1 alpha increases were blocked by pretreatment with indomethacin or ibuprofen. PH and TXB2 increases were prevented with an imidazole derivative. PH caused by a continuous infusion of an endoperoxide analog did not induce lung release of TXB2 or PGF2 alpha. We conclude that 1) transient pulmonary vasoconstriction is caused by thromboxane; 2) the lung is the primary site of thromboxane synthesis; and 3) bypass causes selective alterations in arachidonic acid metabolism rather than general activation of the cascade.
Age-related effects of digoxin on myocardial contractility and Na-K pump in sheep
Authors: Hougen T. J. , Friedman W. F.
Published: December 2017

The age-dependent effects of an acute nontoxic, positively inotropic dose of digoxin on myocardial monovalent cation active transport were determined in fetal, newborn, and adult sheep. Thirty-five lightly sedated, closed-chest animals were instrumented to record electrocardiogram, left ventricular (LV) pressure, and rate of change of LV pressure (LV dP/dt). Ouabain-inhibitable uptake of Rb+ (86Rb+) was measured in both right ventricular (RV) and LV slices from control animals and in animals infused with [3H]digoxin (0.04 mg/kg) sufficient to cause an increase in LV dP/dt without toxicity. Sixty minutes after digoxin, LV dP/dt increased 123% over base-line values in fetuses, 131% in newborns, and 165% in adult animals. RV and LV myocardial digoxin concentrations were similar in all groups. Rb+ active transport was significantly reduced in both RV and LV tissue from all animals 60 min after digoxin. Control animals showed no significant changes in contractility or Rb+ active transport among the control group of fetal, newborn, or adult sheep. Acute infusions of digoxin increased LV contractility in each age group and was accompanied by digoxin-induced inhibition of myocardial Rb+ active transport. No age-related differences in the extent of Rb+ active transport among control or among digoxin-treated animals were observed under these experimental conditions. These studies suggest that the differential response to the therapeutic and toxic effects of digoxin in sheep of various ages does not reside in an age-dependent response of the myocardial sodium pump to digoxin.
Comparison of carotid sinus baroreceptor sensitivity in newborn and adult rabbits
Authors: Tomomatsu E. , Nishi K.
Published: December 2017

The impulse activity in single baroreceptor fibers of the carotid sinus nerve to the carotid sinus was studied in newborn rabbits (9--11 days old) during nonpulsatile perfusion of in vitro carotid sinus preparations. Results were compared with those obtained from adult rabbits. Seventy-eight baroreceptor fibers from 10 newborn rabbits showed lower threshold pressure (54.6 +/- 2.5 mmHg) than that of 59 fibers from adult rabbits (74.2 +/- 4.1). The gain of 14 baroreceptors from newborn rabbits (0.62 +/- 0.07 impulses . s-1 . mmHg-1) was higher than that of 21 baroreceptors from adult rabbits (0.38 +/- 0.03). Results provided direct evidence that carotid sinus baroreceptors in the newborn animals were more sensitive to pressure changes than those in the adult. It is suggested that depressed baroreceptor reflex activity previously observed in most newborn animals is not due to underdeveloped afferent activity of the baroreceptors but to other mechanisms including the efferent control systems.
Na+-K+ exchanges in canine arterial and venous smooth muscle
Authors: De Mey J. G. , Vanhoutte P. M.
Published: December 2017

The effect of altering active sodium transport was compared in the denervated canine femoral artery and saphenous vein, which respond differently to a variety of humoral and physical stimuli. Potassium removal and ouabain caused contractions that were larger in the vein than in the artery. Activation of sodium transport, by exposing sodium-loaded preparations to potassium, caused transient ouabain-sensitive relaxations in both blood vessels; depending on the contractile agonist used, this relaxant effect was comparable (BaCl2) in both preparations or was larger (norepinephrine) in the artery than in the vein. In both the artery and the vein, potassium-induced relaxations were larger during contractions evoked by BaCl2 than those caused by norepinephrine. In the vein, contractions caused by acetylcholine were inhibited by potassium to the same extent as those caused by BaCl2. These results 1) are compatible with a contribution of sodium transport mechanism to the control of cell membrane permeability for extracellular calcium in vascular smooth muscle; 2) suggest that active sodium-calcium exchanges are functionally more important in venous than in arterial smooth muscle; and 3) illustrate that the heterogeneous behavior of vascular smooth muscle of different anatomic origins reflects differences in excitation-contraction coupling.
Effects of prostacyclin on hepatic vasculature and metabolism of renin in conscious dogs
Authors: Echtenkamp S. F. , Davis J. O. , Freeman R. H. , Dietz J. R. , Villarreal D.
Published: December 2017

Prostaglandins have been implicated as important regulators of vascular resistance during high-renin states, and they act as potent stimuli for renin release. This study examines the effects of prostacyclin (PGI2) in conscious sodium-replete and -deplete dogs on the hepatic vasculature and on hepatic function and their role in determining the level of arterial plasma renin activity (PRA). Concurrent measurements of kidney function were made for comparison. Conscious trained dogs with chronic indwelling catheters were given intravenous infusions of PGI2. With a low dose of PGI2 (2 x 10(-8) g . kg-1 . min-1) hepatic blood flow increased while splanchnic vascular resistance fell. With a higher dose (8 x 10(-8) g . kg-1 . min-1) mean arterial pressure fell, and both hepatic and renal blood flow increased while splanchnic and renal resistances fell. The PGI2 infusion was accompanied by an increase in PRA. In both sodium-replete and -deplete animals the increases in PRA were accompanied by proportional increases in the hepatic extraction of renin and increases in the hepatic clearance of renin. Small but significant differences were found in the responses of sodium-replete and -deplete animals to PGI2 infusion. These results demonstrate that PGI2 has a potent influence on both the splanchnic and renal vasculatures and the hepatic clearance of renin and thus the role of the liver in determining hyperreninemia.
NAD/NADH: redox state changes on cat brain cortex during stimulation and hypercapnia
Authors: Gyulai L. , Dora E. , Kovach A. G.
Published: December 2017

The redox state of the anterior suprasylvian gyrus of cats was measured during electrical stimulation and under hypercapnia on cast immobilized and artificially respirated. The state of the nicotinamide adenine dinucleotide-reduced nicotinamide adenine dinucleotide (NAD/NADH) redox system was monitored by in vivo fluorometry. Hypercapnia was produced by inhalation of 10, 15, and 30% CO2, respectively. Hypercapnic acidosis led to NADH oxidation. The NADH oxidation under 30% CO2 inhalation was significantly larger (-14.9 +/- 2.9%) than that observed under 10% (-6.5 +/- 1.9%) and 15% CO2 (-7.0 +/- 1.6%) inhalation. Under normocapnic conditions, stimulation induced NAD reduction to NADH (5.5 +/- 0.8%). The magnitude of the NAD reductive response to stimulation was unaffected by 10% CO2 inhalation, but it was decreased by 15 and 30% CO2 inhalation. The increased concentration of NADH upon stimulation is interpreted as resulting from an increased rate of substrate mobilization. The cause of the oxidation of the NADH pool of the cell during hypercapnia is partly due to the direct inhibitory effect of CO2 on the carbohydrate metabolism, but the role of other mechanisms cannot be neglected either.
Relationship of coronary flow and perfusion territory in dogs
Authors: Scheel K. W. , Ingram L. A. , Gordey R. L.
Published: December 2017

In this study the relationship between myocardial flow and perfusion territory at maximal vasodilation was examined for the left anterior descending (A), circumflex (C), right (R), and septal (S) coronary arteries. Average flows to A, C, R, and S were 31.2 +/- 1.5 (SE), 41.2 +/- 13.5 +/- 0.6, and 14.1 +/- 0.6% of total coronary flow. Strong correlations were found between weight and volume, weight and coronary flow, and weight and resistance of the perfusion territories of A, C, R, and S. However, coronary flow (milliliter per minute per gram) to the right ventricle was significantly lower than to the left ventricle. Examination of the distribution of perfusion territories from base to apex of the heart showed that the anterior descending territory increases from base to apex, whereas the right decreases from base to apex. Circumflex flow distribution is relatively uniform between these limits, and the septal artery is most pronounced at midlevel and tapers toward the apex and base.
Right and left ventricular oxygen metabolism in open-chest dogs
Authors: Kusachi S. , Nishiyama O. , Yasuhara K. , Saito D. , Haraoka S. , Nagashima H.
Published: December 2017

A comparison of blood flow and myocardial O2 consumption (MVO2) in the right and left ventricles was made in 21 open-chest dogs. Simultaneous measurements were made of left anterior descending (LAD) and right coronary arterial blood flow and of O2 saturation in the coronary sinus and in from one to four anterior cardiac veins. Blood flow was greater in the LAD than in the right coronary artery, 87 +/- 5 vs. 46 +/- 3 ml.min-1.100 g-1. Similarly, the O2 saturation was 51 +/- 3% in the anterior cardiac veins and 40 +/- 1% in the coronary sinus. In a subset of seven dogs, the O2 saturation in blood from anterior cardiac veins varied substantially from vein to vein. The mean MVO2 was greater for the left than for the right ventricle, 8.6 +/- 1.4 vs. 4.0 +/- 0.3 ml O2.min-1,100 g-1. Increases in LAD flow with no increase in O2 extraction accounted for enhanced MVO2 of the left ventricle due to pacing, isoproterenol, or methoxamine. In contrast, pacing, isoproterenol, or constriction of the pulmonary artery increased MVO2 of the right ventricle by both augmented O2 extraction and a rise in right coronary blood flow. We conclude that right coronary arterial blood flow is lower per 100 g tissue and is less dependent on MVO2 than is LAD blood flow. The heterogeneity of O2 saturation in anterior cardiac veins suggests that regional differences in MVO2 may exist.
Different forms of spontaneous discharge induced by strophanthidin in cardiac Purkinje fibers
Authors: Ishikawa S. , Vassalle M.
Published: December 2017

The effect of strophanthidin on spontaneous discharge in canine cardiac Purkinje fibers perfused in vitro was studied during periodic interruptions (pauses) of the electrical drive. The results show that 1) strophanthidin initially increases the slope of diastolic depolarization and thereby induces a slow rhythm that accelerates progressively during the pause and becomes faster during the increasing strophanthidin inotropy; 2) oscillatory potentials appear only when strophanthidin inotropy reaches its peak (or actually declines) and may cause either a few fast action potentials during the pause or a fast rhythm that eventually overcomes the driven beats; 3) the slow rhythm is eliminated by cesium; 4) the fast rhythm is eliminated by tetrodotoxin; and 5) oscillatory potentials caused by high calcium, norepinephrine, or low potassium are similarly affected by cesium or tetrodotoxin. It is concluded that strophanthidin enhances diastolic depolarization, thereby causing the slow rhythm, and induces oscillatory potentials, thereby causing the fast rhythm. Only the oscillatory potentials are related to calcium overload as determined by several different procedures.
Fluid volumes and pressor responsiveness in two-kidney rabbits with renal artery stenosis
Authors: Johnson J. A. , Kurz K. D. , Siripaisarnpipat S. , Zeigler D. W. , Payne C. G.
Published: December 2017

This study examined body fluid volumes, the pressor responses to norepinephrine (NE), and the cardiovascular responses to NE before and during infusion of an angiotensin II (ANG II) antagonist in two-kidney rabbits with unilateral renal artery stenosis (RAS) of 3 and 30 day duration. Three separate experiments were performed. In the first experiment, plasma volume, extracellular fluid volume, and total body water were measured by the distribution volumes of radioiodinated serum albumin, 35SO4, and tritiated water, respectively. No differences were seen for any of these volumes between the 3- or 30-day RAS rabbits and their controls. In the second experiment, pressor responses to infusions of several doses of NE were examined; rabbits with 3- and 30-day RAS had exaggerated pressor responses to all doses of NE when compared with the control rabbits. In the third experiment, infusion of NE at 800 ng.min-1.kg body wt-1 resulted in more pronounced increases in mean arterial pressure and total peripheral resistance (TPR) in the 3- and 30-day RAS rabbits than in the controls; after infusion of [Sar1-Ile8] ANG II the increases in mean arterial pressure and TPR during NE infusion were blunted and were of the same magnitude as in the control group. In all experiments the 30-day RAS rabbits were hypertensive, whereas the 3-day RAS rabbits were normotensive; also, plasma renin activity (PRA) values were normal in both the 3- and 30-day RAS groups. These studies demonstrated that increases in body fluid volumes are not necessary for pressor and vascular hyperresponsiveness probably is mediated by ANG II, despite normal PRA values.
Sensitization of vagal cardiopulmonary baroreflex by chronic digoxin
Authors: Thames M. D. , Miller B. D. , Abboud F. M.
Published: December 2017

It has been recently reported that intracoronary acetylstrophanthidin injection acutely sensitizes the cardiac baroreflex (vagal afferents). We wondered whether chronic administration of digoxin also augmented the gain of this reflex. We treated seven dogs with digoxin intravenously (40 micrograms/kg loading dose followed by 15 micrograms.kg-1.day-1) for 7 days; eight additional dogs received vehicle for 7 days. With the dogs under chloralose anesthesia, we assessed the changes in renal nerve activity that resulted from stimulation of cardiopulmonary receptors with volume expansion (15 ml/kg of 6% dextran in saline) in digoxin- and vehicle-treated groups under control conditions, after sinoaortic denervation (SAD), and after SAD plus vagotomy. Under control conditions volume expansion resulted in decreases of renal nerve activity of 13.5 +/- 3.5%/mmHg increase in pulmonary artery wedge pressure in digoxin-treated dogs. This tended to be greater than the response of sham-treated dogs (-9.5 +/- 1.5%/mmHg increase). After SAD, renal nerve activity decreased 19 +/- 5%/mmHg increase in pulmonary artery wedge pressure in the digoxin group compared with only 8 +/- 1%/mmHg increase in the vehicle group. These responses were significantly different. The plasma digoxin level in the digoxin-treated group was in the therapeutic range (1.9 +/- 0.4 ng/ml). Vagotomy abolished the responses to volume expansion in both groups. Thus chronic digoxin treatment resulting in therapeutic plasma levels of digoxin sensitizes vagal afferents mediating the cardiopulmonary baroreflex influence on renal nerve activity.
NAD/NADH: redox state changes on cat brain cortex during stimulation and hypercapnia
Authors: Gyulai Laszlo , Dora Eörs , Kovach Arisztid G. B.
Published: December 2017

Page H619: Laszlo Gyulai, Eörs Dora, and Arisztid G. B. Kovach. “NAD/NADH: redox state changes on cat brain cortex during stimulation and hypercapnia.” Authors' affiliation line should read: Experimental Research Department and Second Institute of Physiology, Semmelweis Medical University, Budapest, Üllöi ut 78/a, Hungary. Address for reprint requests: L. Gyulai, Johnson Research Foundation, University of Pennsylvania, 37th and Hamilton Walk, Richards Bldg.Ü5th Floor, Philadelphia, PA 19104.
Estimation of rabbit myocardial metabolic rate for glucose using fluorodeoxyglucose
Authors: Krivokapich J. , Huang S. C. , Phelps M. E. , Barrio J. R. , Watanabe C. R. , Selin C. E. , Shine K. I.
Published: December 2017

The isolated arterially perfused rabbit interventricular septum was used to determine the feasibility of using the glucose analogue 18F-2-deoxy-2-fluoro-d-glucose (DG) with a tracer kinetic model to estimate the rate of exogenous glucose utilization. FDG was delivered to the septum by constant infusion, and tissue 18F radioactivity was measured as a function of time by external coincidence counting. The following four conditions were studied: flow rates of 0.5, 1.0, and 1.5 ml/min with a heart rate of 72 beats/min and flow at 1.5 ml/min with 96 beats/min. The rate constants for FDG forward and reverse transport between the vascular and extravascular compartments (k*1, k*2, respectively), phosphorylation of FDG (k*3), and dephosphorylation of FDG-6-phosphate (FDG-6-P) (k*4) were determined from the tissue curves using a tracer kinetic model. The lumped constant (LC) of the deoxyglucose model calculated using Fick-derived myocardial metabolic rates of glucose (MMRGlc), was 0.60 +/- 0.10 and was stable over the range of conditions studied. Average k*'s and LC were used to calculate MMRGlc's employing the model and were not significantly (P greater than 0.05) different from those determined by the Fick method. Tissue analyses using high-pressure liquid chromatography documented that tissue 18F radioactivity wa due to FDG and FDG-6-P, and their relative fractions agreed well with the values predicted from the tracer kinetic model. Only FDG was detected in the effluent. These studies also indicate the presence of a myocardial enzyme that can hydrolyze FDG-6-P to FDG. Thus our results support the use of the FDG method with positron-computed tomography for the in vivo determination of the myocardial rate of exogenous glucose utilization.
Passive electrical properties of normal and hypertrophied rat myocardium
Authors: Keung E. C. , Keung C. S. , Aronson R. S.
Published: December 2017

We determined the electrical constants of epicardial and endocardial preparations from both normal and hypertrophied rat hearts. This was done by comparative analysis of the spatial decay of steady-state electronic voltage deflection produced by injection of a hyperpolarizing constant-current pulse. We used a two-dimensional finite disk model to obtain the apparent membrane resistance, (Rm)app, and internal longitudinal resistivity (Ri), (Rm)app was significantly larger in epicardial (565 +/- 222 omega . cm2) than endocardial (375 +/- 137) preparations from normal hearts. This regional difference disappeared in hypertrophied hearts (epicardium 421 +/- 138, endocardium 383 +/- 121 omega . cm2). Ri was similar for normal endocardial (272 +/- 169 omega . cm) and epicardial (326 +/- 152) preparations, as well as for hypertrophied endocardial (251 +/- 108) and epicardial (312 +/- 59) preparations. We determined the effective membrane capacity (Ceff) by measuring the ratio of applied charge to the displacement of membrane potential. Ceff was larger for normal hearts (epicardium 9.7 +/- 2.5 micro F/cm2, endocardium 7.5 +/- 3.0) than for hypertrophied hearts (epicardium 4.1 +/- 1.4, endocardium 4.7 +/- 1.2). From the values for Ceff we calculated the effective membrane resistance, (Rm)eff. (Rm)eff was larger for normal (epicardium 5,392 +/- 2,613 omega . cm2, endocardium 3,013 +/- 2,096) than for hypertrophied (epicardium 1,552 +/- 633, endocardium 1,838 +/- 826) preparations. Our results show that the amount of electrically effective membrane area is decreased in hypertrophied myocardium, despite the increased total area per hypertrophied cell. One functional implication of this finding is that activation of contraction by spread of surface electrical depolarization into the T-tubules may be impaired in hypertrophied cardiac muscle.
Postextrasystolic potentiation and contractile reserve: requirements and restrictions
Authors: Lust R. M. , Lutherer L. O. , Gardner M. E. , Cooper M. W.
Published: December 2017

These studies were conducted to examine the basic characteristics of postextrasystolic potentiation (PESP) and the relationship of loading effects to PESP. Measurements of left ventricular (LV) and aortic pressures, the rate of pressure rise, and echocardiographically determined LV dimensions were made in anesthetized open-chest dogs. The hearts were paced, and timed extrasystoles were introduced that were followed by postextrasystoles (PES). PES's were elicited after an interval equal to either a full compensatory pause or a time when the diastolic properties of the LV could not be distinguished from control (isolength). Potentiation of contraction for the PES's introduced after an isolength pause was dependent on both the heart rate and the extrasystolic interval, whereas the PES's that occurred after a full pause showed no dependence on either of these intervals. PESP elicited during the isolength period was not dependent on either preload and afterload. It is concluded that PESP depends on the combination of heart rate and extrasystolic and postextrasystolic intervals. Further, PESP may be inaccurate in assessing contractile reserve unless the heart rate and extrasystolic interval are known and the PES is introduced after an isolength pause.