bluuebunny/crossref_metadata_2025 huggingface dataset:
Fade of cardiac responses during tonic vagal stimulation
Authors: Martin P. , Levy M. N. , Matsuda Y.
Published: December 2017

We applied trains of stimuli to the vagosympathetic trunks of anesthetized dogs and studied the time courses of the resultant chronotropic and inotropic responses. These responses were maximum soon after the onset of the test stimulus train but then declined over the next 1-5 min despite continued stimulation. The fade ratio was defined as the magnitude of this decline divided by the magnitude of the maximum response. For both inotropic and chronotropic responses, maximum increased with stimulation frequency, but the fade ratio did not change. In some experiments, conditioning stimulus trains of variable duration were applied before a standard rest period, after which the test stimulus train was applied. The longer the conditioning period, the lower was the subsequent fade ratio of the inotropic responses to the test stimulation train. In other experiments, a conditioning train of 2 min was applied, and then variable rest periods were interposed before the test train was applied. The longer the rest period, the greater were the subsequent maximum and fade ratios of the inotropic responses to the test stimulus train. These results indicate that some factor persists well after the cardiac responses to a given stimulus, and this factor affects the next response to an identical vagal stimulation. The chronotropic responses faded about three times faster than the inotropic responses. Thus different mechanisms may account for the fade of the inotropic and chronotropic responses.
Global cerebral vasodilation by stimulation of rat fastigial cerebellar nucleus
Authors: Nakai M. , Iadecola C. , Reis D. J.
Published: December 2017

The effects of electrical stimulation of the pressor area of the fastigial nucleus (FN) of cerebellum on regional cerebral blood flow (CBF) were examined in anesthetized, paralyzed rats. CBF was measured in tissue homogenates by the Kety principle using 14C-iodoantipyrine as an indicator during FN stimulation, during stimulation of the vermal cortex, or after placement of electrodes in FN (unstimulated controls). Blood gases and systemic arterial pressures were comparable in the three groups. FN stimulation elicited a widespread and significant (P less than 0.005) increase in CBF in 12 of 13 areas. Flow was maximally increased in cerebral cortex (up to 220% of control) but also rose in selected regions of telencephalon, diencephalon, mesencephalon, lower brain stem, and in white matter of the corpus callosum (172%). Flow was not increased in cerebellum. The increase in CBF persisted after transection of the spinal cord at C1 or cervical sympathectomy. In five rats, hypercarbia (PCO2 to 63 mmHg) increased CBF in all 13 regions but in a pattern differing from FN stimulation. Excitation of neurons originating in, projecting to, or passing through FN can elicit a potent and virtually global increase of CBF. The effect appears mediated by intrinsic pathways of the central nervous system.
Coronary dilator actions of adenosine and CO2 in experimental diabetes
Authors: Downing S. E. , Lee J. C. , Weinstein E. M.
Published: December 2017

We have previously shown that coronary regulation is altered in the diabetic lamb. In the present investigation the effects of hypercapnic acidosis (increases CO2) and adenosine on coronary sinus flow (CF; ml . min-1 . 100 g-1 LV) were assessed in 13 controls and 7 diabetic lambs (glucose 1,084 +/- 193 mg/dl) given alloxan (150 mg/kg) 2 days prior to study. All measurements were made under conditions of constant aortic pressures and cardiac output. Left ventricular (LV) performance was continuously recorded; O2 content, O2 and CO2 partial pressure, pH, and glucose concentrations were compared in simultaneous sinus and arterial samples. Dose-response curves (0.30 micrograms . min-1 . kg-1) indicated a linear relationship between adenosine and CF. At infusion rates of 30 (iv) or 3 (LV) micrograms . min-1 . kg-1 adenosine increased CF by 30 and 21 ml . min-1 . 100 g-1 LV, respectively in control (P less than 0.001) but not in diabetic lambs. With increases CO2 (80 mmHg; pH 6.95), CF increased substantially (control 60 ml; diabetic 45 ml) in both groups (P less than 0.001). The dilator action of adenosine was enhanced in control during increases CO2, and significant responses to adenosine appeared in the diabetic group. It is concluded that increases [H+] has a potent direct coronary dilator action in both control and diabetic lambs and enhances responsiveness to adenosine. Sensitivity to adenosine is reduced in diabetics, and this subsensitivity is largely reversed by hypercapnic acidosis.
Effect of myocardium at risk on outcome after coronary artery occlusion and release
Authors: Austin M. , Wenger T. L. , Harrell F. E. , Luzzi F. A. , Strauss H. C.
Published: December 2017

The relationship between the probability of sustaining ventricular fibrillation during occlusion or release of a canine coronary artery and the amount of myocardium made ischemic has never been carefully assessed. We occluded the left anterior descending coronary artery above or below the septal artery for 20 min and then released the ligation. The amount of left ventricle perfused by the ligated vessel was determined by injection of different color monastral dyes above and below the ligation. Despite careful ligature placement immediately proximal or distal to the septal artery, there was wide variation in the amount of left ventricle perfused by the ligated vessel, or myocardium "at risk." Myocardium at risk ranged between 24 and 51 g for ligations placed above the septal artery and 14 and 27 g for ligations placed below the septal artery. Ventricular fibrillation during occlusion and after release correlated significantly with the amount of myocardium at risk. This relationship was well described using the logistic risk regression model. The model predicts uniformly low and uniformly high probability of ventricular fibrillation with small and large amounts of myocardium at risk, respectively, and a direct correlation for midrange values of myocardium at risk. This relationship can account for a substantial portion of non-drug related variability in outcome of antiarrhythmic trials using the canine coronary occlusion or release model.
Impedance loading servo pump system for excised canine ventricle
Authors: Sunagawa K. , Burkhoff D. , Lim K. O. , Sagawa K.
Published: December 2017

To investigate ventricular-arterial system interaction, we have developed a hybrid-computer-controlled impedance loading servo pump system that enables us to impose a simulated arterial hydraulic impedance on an excised canine ventricle. An analog computer programmed to simulate a three-element Windkessel model of the arterial system computes instantaneous aortic flow from the instantaneous ventricular pressure. The time integral of this flow is used to command a volume servo pump system that controls the instantaneous ventricular volume. All parameter values in the loading system are controlled by a digital computer. The actual impedance spectrum generated by the system was reasonably close to that expected from the arterial model. The unique features of this system are the following. 1) The instantaneous volume of the ventricle, which is crucial information, can be measured. 2) If needed, the arterial impedance model can easily be reprogrammed to generate more complex impedance spectra. 3) The vascular parameters can be made nonlinear or time varying through the digital computer control.
Quantitation of changes in lymph protein concentration during lymph node transit
Authors: Adair T. H. , Moffatt D. S. , Paulsen A. W. , Guyton A. C.
Published: December 2017

Many investigators assume the protein concentration and colloid osmotic pressure of interstitial fluid and lymph to be identical even after the lymph has passed through a lymph node. We quantitated the degree of modification of lymph by the dog popliteal lymph node by perfusing isolated lymph nodes in situ at physiological flow rates with homologous plasma or plasma diluted to low protein concentration. This enabled us to compare directly prenodal and postnodal lymph flows and protein concentrations. When undiluted plasma was infused into the node, fluid filtered from the blood into the lymph, diluting the lymph. When diluted plasma was infused, fluid was absorbed from the lymph, concentrating the lymph. Nearly all (98%) of the change in lymph protein concentration could be explained by transfer of protein-free fluid either into or out of the lymph. However, when the nodes were perfused with lymph having a colloid osmotic pressure that exactly balanced the hydrostatic and osmotic forces acting across the lymph node blood-lymph barrier, the lymph was not modified during nodal transit. This "equilibrium colloid osmotic pressure" averaged 60% of that of plasma. The concentrating-diluting mechanism became more significant as the perfusion rate decreased and/or as the colloid osmotic pressure of the afferent lymph was made progressively greater than or less than the equilibrium colloid osmotic pressure. We conclude that lymph nodes modify lymph protein concentration and colloid osmotic pressure except when these are already at equilibrium values for given lymph node conditions. Therefore, the assumption that postnodal lymph is representative of interstitial fluid, especially at low but still physiological lymph flows, is likely to be incorrect.
Salt loading augments vascular responses to indomethacin in stroke-prone SHR
Authors: Imaizumi T. , Takeshita A. , Ashihara T. , Nakamura M.
Published: December 2017

We examined whether endogenous prostaglandins (PGs) participated in control of hindquarters vascular resistance during salt loading in stroke-prone spontaneously hypertensive rates (SHR-SP). SHR-SP and Wistar-Kyoto rats (WKY) were fed either a normal (0.3% NaCl) or high (8% NaCl) salt diet for 5 wk. High salt increased blood pressure and hindquarter vascular resistance (VR) in SHR-SP (P less than 0.01) but not in WKY. Indomethacin given intravenously increased hindquarter VR in SHR-SP during high salt as well as during normal salt (P less than 0.01) but not in either group of WKY. In SHR-SP the increase in hindquarter VR by PG synthesis inhibitors were two times greater during high salt than during normal salt (P less than 0.01). In addition, hindquarter vasodilatation by bradykinin was greater (P less than 0.05) in SHR-SP during high salt than that during normal salt, but vasodilatation by prostaglandin E1 or nitroglycerin was not different between the two groups. These results suggest that vascular synthesis of endogenous PGs was greater in SHR-SP during high salt than that during normal salt. Increased endogenous PGs may play an important role in the regulation of hindquarter VR during high salt intake in SHR-SP.
Concentrations of ionic and total calcium in plasma of four models of hypertension
Authors: Wright G. L. , Rankin G. O.
Published: December 2017

The levels of ionic calcium in whole blood obtained from female Sprague-Dawley (SDR). Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rate tended to decrease between 5 and 13 wk of age. During this interval the plasma total calcium levels of each strain remained stable, indicating an increase in the binding or complexing of endogenous calcium with maturation. The ionic calcium levels of WKY were lower than those of SDR, while SHR levels were below those of the WKY and SDR strains. Neither the one-kidney, one-clip (1KHT) nor the two-kidney one-clip (2KHT) renovascular models of hypertension showed evidence of an alteration in blood ionic or total calcium concentrations compared with sham-operated controls. The ionic calcium levels of blood from deoxycorticosterone-treated (DOCA/saline) hypertensive rats were significantly reduced from those of sham-operated controls but were similar to values recorded for normotensive uninephrectomized controls. Each of the four models of hypertension studied and the normotensive uninephrectomized control group demonstrated some degree of reduction in the in vitro binding or complexing of exogenous calcium. The results indicate that the spontaneous, renovascular, and mineralocorticoid forms of hypertension examined were accompanied by some disturbance in extracellular calcium homeostasis. It is unlikely, however, that the alterations observed are primary causal factors in the maintenance of high blood pressure.
Epicardial deformation and left ventricular wall mechanisms during ejection in the dog
Authors: Arts T. , Veenstra P. C. , Reneman R. S.
Published: December 2017

Significant differences between epicardial and endocardial systolic stress in the wall of the left ventricle (LV) have been predicted by various models of LV mechanics. Yet a model incorporating transmural differences in fiber orientation and torsion, defined as a rotation of the apex with respect to the base around the long axis of the LV, predicts transmural equalization of stress and shortening along the fiber direction during the ejection phase. this equalization is due to an interplay between torsion and myocardial contraction. To assess the model hypothesis, predicted epicardial deformation during the ejection phase was compared with that measured experimentally. For this purpose 45 sets of measurements were performed in four open-chest dogs using a triangular array of inductive gauges for the assessment of epicardial circumferential strain (epsilon c), base-to-apex strain (epsilon z), and shear angle (gamma). Changes in shear angle are directly related to LV torsion. LV end-diastolic pressure was varied over a wide range (0-15 mmHg) by volume loading and bleeding. In the control state, the slope of the shear angle vs. volume strain curve (volume strain = 2 epsilon c + epsilon z), which is related to contraction, was found to be 0.74 +/- 0.10 (mean +/- SD). This compares reasonably wih the mathematical model prediction of a slope of 0.67. Due to an interplay between torsion and contraction, left ventricular fiber stress and fiber shortening might be uniformly distributed across the wall.
Elevated arteriolar adenosine 3',5'-cyclic monophosphate production by SHR
Authors: Dusseau J. W. , Hutchins P. M.
Published: December 2017

Adenosine 3',5'-cyclic monophosphate (cAMP) metabolism was studied in the microcirculation (100- to 150-micrometers arterioles) of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at different stages of hypertension. Mesenteric arterioles from animals 4, 6, 12, and 18 wk old were incubated in Krebs-Ringer bicarbonate buffer for 30 min at 37 degrees C, pH 7.4, with and without the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX). cAMP was assayed by radioimmunoassay. Arteriolar production of cAMP was age related in both WKY and SHR rats although the temporal patterns were different. At 6 wk (developmental stage of hypertension in SHR) cAMP accumulation in the presence or absence of MIX by SHR arterioles was higher than in the WKY before falling to normotensive levels at 12 wk. Salbutamol (a beta 2-agonist) stimulated dose-dependent increases in cAMP in both WKY and SHR at 6 wk. Stimulation of cAMP by salbutamol or by isoproterenol was blocked by propranolol. Neither agonist increased guanosine 3',5'-cyclic monophosphate. These data indicate that differences in cAMP metabolism are evident at the arteriolar level during the developmental stage of SHR hypertension. These differences may contribute to the morphological and physiological changes occurring at this time.
Relationship between placental blood flow and placental and fetal size in guinea pig
Authors: Myers S. A. , Sparks J. W. , Makowski E. L. , Meschia G. , Battaglia F. C.
Published: December 2017

Blood flow measurements were made using radioactive microspheres in 14 unstressed, conscious, pregnant guinea pigs with gestational age ranging between 34 and 67 days. Within each litter placental blood flow (PBF) was positively correlated to fetal weight (FW), even after correcting for placental weight differences. Although the largest littermate was, on the average, only 30% larger than the smallest, its material placental blood flow was 95% greater. The PBF vs. FW relationship could be described by the allometric equation: PBF = Ai FW2.89 where Ai is a litter-specific coefficient. This study demonstrates that the placenta of the largest littermate is "hyperperfused" compared with its smaller siblings.
Ca2+-tolerant adult canine myocytes: preparation and response to anoxia/acidosis
Authors: Spanier A. M. , Weglicki W. B.
Published: December 2017

A procedure is described for the production of large numbers of Ca2+-tolerant adult canine ventricular myocytes. Gentle tissue dissociation is achieved in Spinner flasks using 320 mosM enzyme buffer containing collagenase hyaluronidase, and trypsin in the presence of millimolar levels of Ca2+. The technique allows for the complete removal of erythrocytes, the gentle removal of closely adhering nonmuscle cells (less than 3% contamination), and the selective removal of damaged from nondamaged myocytes. Total myocyte yields averaged 4-6 x 10(6)/g wet wt; 61.0 +/- 6.5% of the cells have rod-shaped morphology and are "viable" based on trypan blue exclusion. Only 3.9 +/- 1.1% of the rod-shaped cells beat spontaneously when challenged with 2 mM Ca2+. Exposure to 2 mM Ca2+ at 37 degrees C results in minimal loss of viability (2.1 +/- 1.3%/h) based on both trypan blue uptake and creatine kinase release. Simulation of cellular (i.e., membrane) injury in vitro is performed by the separate application of the perturbations of anoxia, acidosis, and low glucose to the canine myocyte suspensions; the data suggest that these myocytes are affected independently by these perturbations and are in good agreement with the results obtained by others using the isolated rat myocyte system.
A comparison of capillary hydraulic conductivities in postural and locomotor muscle
Authors: McDonagh P. F. , Gore R. W.
Published: December 2017

In a comparative skeletal muscle study Folkow and Halicka (Microvasc. Res. 1: 1-14, 1968) reported that the capillary filtration coefficient (CFC) of postural (red) muscle was two times the CFC of locomotor (white) muscle. It was concluded that the twofold difference in CFC was due solely to a difference in the perfused capillary surface areas (Sf) of red vs. white muscle. However, CFC is the product of capillary hydraulic conductivity (LP) and Sf. Hence their conclusion assumed that the average LP of red muscle capillaries is exactly equal to the average LP of white muscle capillaries. The following study was undertaken to test the validity of this assumption. The microocclusion procedures and analytical model described by Lee et al. (Circ. Res. 28: 358-370, 1971) and Gore [Am. J. Physiol. 242 (Heart Circ. Physiol. 11): H268-H287, 1982] were used to determine LP. Independent measurements of LP were recorded from single capillaries in red, anterior latissimus dorsi (ALD) and white, posterior latissimus dorsi (PLD) muscles of chickens anesthetized with L.A. Thesia. We found that the mean capillary hydraulic conductivity in postural muscle [(LP)ALD = 0.20 +/- 0.06 (SE) micrometers . s-1 . cmH2O-1 (n = 11)] was significantly different from the mean capillary hydraulic conductivity in locomotor muscle [(LP)PLD = 0.061 +/- 0.01 micrometers . s-1 . cmH2O-1 (n = 14)] (P less than 0.05). These results provide direct evidence that observed differences in red vs. white muscle CFC's may not be due solely to different perfused capillary surface areas but may also be due to differences in capillary hydraulic conductivity.
Effects of autonomic activity and changes in heart rate on atrioventricular conduction
Authors: Wallick D. W. , Martin P. J. , Masuda Y. , Levy M. N.
Published: December 2017

The effects of autonomic neural stimulation and changes in atrial pacing frequency on atrioventricular (AV) conduction were determined in anesthetized open-chest dogs. Increases in vagal stimulation frequency and in pacing rate significantly increased the AV interval, whereas increases in sympathetic stimulation frequency reduced the AV interval. Vagal stimulation (1.4 Hz) prolonged the AV interval by 17 ms when the atrial pacing rate was 2 Hz. On the other hand, the same vagal stimulation increased the AV interval by 29 ms when the pacing rate was 2.73 Hz. In addition, sympathetic stimulation (1.2 Hz) reduced the AV interval by 29 ms when the pacing rate was 2 Hz. In contrast, the same sympathetic stimulation reduced the AV interval 54 ms when the pacing rate was 2.73 Hz. However, the increase in vagal stimulation did not significantly alter the positive dromotropic response of the AV node to sympathetic stimulation. Therefore, the response of AV conduction to combined sympathetic and vagal stimulation was essentially the algebraic sum of the responses to the individual stimulations. Furthermore, the level of activity in one autonomic division did not alter appreciably the interaction between the pacing rate and the activity in the other autonomic division; i.e., the interaction between pacing rate, sympathetic stimulation, and vagal stimulation was not significant.
Early changes in fiber profile and capillary density in long-term stimulated muscles
Authors: Hudlicka O. , Dodd L. , Renkin E. M. , Gray S. D.
Published: December 2017

Predominantly fast skeletal muscles of rabbits [tibialis anterior (TA), extensor digitorum longus (EDL)] were stimulated at a frequency naturally occurring in nerves to slow muscles (10 Hz continuously) for 8 h/day for 2--4 days. Such stimulation is known to convert all glycolytic fibers to oxidative and to increase capillary density. Our aim was to study early stages of conversion to investigate the factors responsible for the changes. Staining of quick-frozen sections for myosin ATPase, succinic dehydrogenase, and alkaline phosphatase was used to study the distribution of different fiber types and to measure fiber cross-sectional areas, capillaries per square millimeter, and capillary-to-fiber ratios in each fiber category. TA but not EDL showed conversion of fast glycolytic to fast oxidative fibers after 2 days, more after 4 days of stimulation. In both muscles, the largest fast glycolytic fibers were diminished in number after stimulation. There was significant increase in total capillaries per square millimeter after 4 days and some increase after 2 days of stimulation. The increase in capillaries per square millimeter exceeded the increase in the number of fibers per square millimeter, and since there was no change in mean fiber area, the increase is attributed to capillary growth. In EDL, there was an increase in the number of capillaries supplying both fast glycolytic and fast oxidative fibers, suggesting that capillary growth precedes fiber type conversion. In TA, the number of capillaries supplying fast oxidative fibers was increased but that to fast glycolytic fibers, was not. This is consistent with capillary growth simultaneous with or following fiber conversion. In both TA and EDL the number of capillaries perfused after contraction was higher in stimulated muscles, suggesting that increased capillary flow contributed to capillary growth.
Adenosine's role in coronary vasodilation induced by atrial pacing and norepinephrine
Authors: Manfredi J. P. , Sparks H. V.
Published: December 2017

If adenosine (ADO) mediates metabolic vasodilation in the heart, increases in interstitial ADO (ISF[ADO]) must accompany increases in coronary vascular conductance. We tested this using ADO release, defined as the difference in [ADO] in coronary venous and arterial plasma multiplied by coronary plasma flow, as an index of ISF[ADO]. Pentobarbital-anesthetized dogs received intravenous norepinephrine or left atrial pacing, and the resulting changes in coronary blood flow (delta CBF), conductance (delta C), myocardial oxygen consumption (delta VO2), and ADO release (delta RADO) were measured. If ISF[ADO] and C are coupled, the ratio delta RADO/delta C should be greater than zero. For dogs receiving atrial pacing, the ratios delta RADO/delta C, delta RADO/delta CBF, and delta RADO/delta VO2 equal -2.4 +/- 2.2 nmol . mmHg-1 . ml-1, -0.022 +/- 0.020 nmol/ml, and -0.13 +/- 0.12 nmol/ml, respectively. These values do not differ from zero. For dogs receiving norepinephrine, delta RADO/delta C, delta RADO/delta CBF, and delta RADO/delta VO2 equal 9.7 +/- 1.8, 0.051 +/- 0.017, and 0.44 +/- 0.13, respectively. These values are greater than zero (P less than 0.05). These differences between atrial pacing and norepinephrine infusion rate observed despite similar changes in C, CBF, and VO2. We conclude that ADO may mediate the vasodilation induced by norepinephrine, but not atrial pacing.
Effect of norepinephrine on lymph flow and edema formation in the canine forelimb
Authors: O'Neill J. T. , Haddy F. J. , Grega G. J.
Published: December 2017

In the present study we sought evidence for the hypothesis that norepinephrine (NE) can cause constriction of lymph vessels in the canine forelimb perfused at constant flow. Mechanical venous compression (small-vein pressure approximately equal to 45 mmHg), intra-arterial infusion of histamine (16 micrograms base/min), and intra-arterial infusion of NE (16 micrograms base/min) caused the limbs to gain weight at similar rates due to edema formation; the first two maneuvers caused a sustained increase in skin lymph flow, but the increase in lymph flow with NE was only transient. Similar changes were seen during infusion of NE at 1 and 2 micrograms/min, and studies with radioactive microspheres indicated that NE increased capillary blood flow. When venous pressure was elevated and held constant at 45 mmHg. NE (4 micrograms base/min ia) antagonized and phentolamine (400 micrograms/min ia) potentiated the increase in skin lymph flow. Finally, NE (16 micrograms base/min ia) caused a reduction in histamine (16 micrograms base/min)-elevated skin lymph flow, despite the fact that capillary pressure was greatly increased due to active venous constriction. We conclude that intra-arterial infusion of norepinephrine in the dog forelimb perfused at constant flow causes constriction of lymphatic trunk vessels in skin, resulting in increased resistance to the flow of lymph.
Inhibition of baroreflex bradycardia by aortic nerve excitatory afferents in dogs
Authors: Pisarri T. E. , Matson G. L. , Kendrick J. E.
Published: December 2017

In dogs anesthetized with morphine-chloralose, low-frequency high-intensity stimulation of the aortic nerve (AN) causes a modest reflex tachycardia and a rise in systemic pressure. Stimulation of the carotid sinus nerve or raising pressure in the isolated carotid sinus causes reflex bradycardia and a fall in systemic pressure. Combined stimulation of these reflexes resulted in less bradycardia and a smaller decrease in systemic pressure than the sum of the responses to separate stimulation (P less than 0.001). This suggests that the opposing reflexes interact in a manner whereby the carotid baroreflex responses are inhibited by the AN stimulation. This interaction occurs in the medullary centers and appears to involve primarily suppression of the vagal efferents to the heart. Baroreflex inhibition of sympathetic vasomotor activity also appears to be suppressed by AN stimulation. It is concluded that aortic cardiac sympathetic activity and in part by suppressing baroreflex-induced bradycardia.
Adenosine and coronary blood flow in conscious dogs during normal physiological stimuli
Authors: Bacchus A. N. , Ely S. W. , Knabb R. M. , Rubio R. , Berne R. M.
Published: December 2017

The role of adenosine in matching myocardial oxygen supply to demand by regulating coronary blood flow has been the subject of intensive study. The present experiments were designed to determine the relationship among myocardial oxygen consumption, coronary blood flow, and adenosine production as estimated by pericardial adenosine accumulation under several physiological conditions in the same animal. Conscious chronically instrumented dogs were used to measure changes in coronary blood flow, myocardial oxygen consumption, and pericardial adenosine accumulation during two levels of treadmill exercise, excitement caused by loud noises, and feeding (the presentation and consumption of a meal). The results show significant increases in the adenosine production with all experimental procedures and significant linear correlations between myocardial oxygen consumption and coronary blood flow (r = 0.78), myocardial oxygen consumption and adenosine production (r = 0.73), and adenosine production and coronary blood flow (r = 0.88). These data show that increases in adenosine production by the normally oxygenated myocardium can be the physiological mechanism for matching oxygen supply to increased oxygen demand in the conscious dog.
Metabolic and mechanical effects using L- and D-carnitine in working swine hearts
Authors: Liedtke A. J. , Nellis S. H. , Whitesell L. F. , Mahar C. Q.
Published: December 2017

The purpose of the present studies was to contrast the differences in mechanical and metabolic functions between treatments of L- and D-carnitine as measured in intact, regionally ischemic swine hearts. Coronary flows were decreased in the anterior descending circulation (-53% delta) after an equilibration period of 30 min during which hearts in both treatment groups were supplemented with trace-labeled [U14-C]palmitate. Nine hearts were selectively treated with L-carnitine (avg serum concentration 804 nmol/ml) and were compared with eight hearts treated with D-carnitine (same dosage schedule). No differences in fatty acid metabolism or regional shortening were observed between treatment groups in the heart muscle rendered moderate-to-severely ischemic. L-Carnitine did effect a significant reduction in fatty acid uptake and labeled CO2 production as compared with D-carnitine in aerobic tissue. This resulted in a secondary improvement in global mechanical efficiency (expressed as a ratio of either left ventricular developed pressure or work/global oxygen consumption) in L-treated hearts. Higher levels of high-energy phosphate stores were also noted in both ischemic and aerobic tissue of L-treated hearts. Thus differences in fatty acid metabolism occurred in working swine hearts based on the structural specificity of carnitine treatment. L-Carnitine favorably modified oxygen consumption and global mechanical efficiency.
Myocardial blood flow and function with critical coronary stenosis in exercising dogs
Authors: Gallagher K. P. , Osakada G. , Matsuzaki M. , Kemper W. S. , Ross J.
Published: December 2017

Critical stenosis of coronary arteries does not alter myocardial blood flow (MBF) at rest, but eliminates hyperemia and corresponds to a degree of arterial narrowing that expends subendocardial vasodilator reserve. Because subepicardial vasodilator reserve remains with critical stenosis at rest, we tested the significance of this reserve in six exercising dogs chronically instrumented to measure MBF (microspheres), regional function (systolic wall thickening with sonomicrometers), and coronary blood flow velocity (CBFV, pulsed Doppler). Critical stenosis produced with a hydraulic occluder limited CBFV and mean MBF to the resting level during treadmill exercise, but MBF was maldistributed. Subendocardial MBF decreased 50% (P less than 0.05) and subepicardial MBF increased 104% (P less than 0.01) compared with resting control conditions, suggesting that a transmural "steal" phenomenon had occurred, with augmented MBF in the subepicardial region at the expense of subendocardial MBF. Systolic wall thickening decreased markedly from 31.5 +/- 6.8 to 9.4 +/- 2.0% (P less than 0.01) during exercise, indicating that use of subepicardial vasodilator reserve with critical stenosis had little sustaining effect on regional contractile performance. Rather, subepicardial vasodilator reserve is potentially deleterious, inasmuch as a steal effect could contribute to reduced subendocardial perfusion, the primary determinant of systolic wall thickening.
Effect of serum and stirring on diffusive 125I-albumin and Evans blue dye uptake
Authors: Fry D. L. , Melchior G. W. , Mitschelen J.
Published: December 2017

The diffusive in vitro uptake of homologous 125I-albumin (MA, nmol.cm-2) and Evans blue dye (EBD) (ME, nmol.cm-2) by the deendothelialized canine aorta from serum and from a simple albumin solution with and without EBD and with and without vigorous stirring was measured in 18 preparations. The results show that 1) MA and ME were significantly smaller from serum than from a simple albumin solution, 2) vigorous stirring of the liquid phase caused a slight decrease (approximately 5%) in MA and increase (approximately 9%) in ME, 3) MA was not influenced by the presence of EBD, and 4) at least 90% of the radioactivity in the tissue was free 125I-albumin with an electrophoretic mobility identical to its nonlabeled cohort molecules and albumin in the original reagent. These observations confirm the identity of the tissue radioactivity with the labeled protein in the reagent, show that less than 10% of the labeled protein is irreversibly bound in the tissue, indicate that significant concentration gradients do not occur in the reagent phase, and indicate that albumin appears to interact with other plasma components in the reagent phase.
Regional myocardial blood flow and oxygen delivery in fetal, newborn, and adult sheep
Authors: Fisher D. J. , Heymann M. A. , Rudolph A. M.
Published: December 2017

We measured and calculated their product, regional myocardial oxygen delivery, in unanesthetized, previously instrumented fetal, newborn, and adult sheep. In the fetus, blood flow and oxygen delivery were greater to the right ventricular free wall than to the left ventricular free wall. In the left ventricular free wall oxygen delivery increased significantly after birth and later decreased to a level in the adult that was similar to that of the fetus. There was a progressive decrease in oxygen delivery to the right ventricular free wall during the developmental period that we studied. Although the inner-to-outer blood flow ratio was significantly lower for the left and right ventricular free walls of the fetuses as compared with the newborns and adults, the ratio was greater than one in all three groups for both of the ventricular free walls. These data demonstrate that the changes that occur in the circulation after birth are associated with significant alterations in right and left ventricular myocardial blood flow and oxygen delivery, which most likely reflect changes in regional myocardial metabolic demands. In addition, there are further significant changes in regional myocardial blood flow during the transition from the newborn to adult hemodynamics.
Atrioventricular nodal conduction during atrial fibrillation in rabbit heart
Authors: Mazgalev T. , Dreifus L. S. , Bianchi J. , Michelson E. L.
Published: December 2017

Atrial fibrillation was induced in 15 superfused rabbit atrial-atrioventricular nodal preparations in which surface bipolar electrograms were recorded simultaneously from the crista terminalis, interatrial septum, and His bundle along with microelectrode action potentials from cells in the atrionodal (AN), nodal (N), and nodal-His (NH) regions of the atrioventricular node. Effective engagement of the atrioventricular node with propagation to the His bundle was critically dependent on the relative timing of activation at the crista terminalis and interatrial septal input regions of the atrioventricular node. Conduction through the AN and N regions appeared dependent on the relative timing of activation wave fronts emerging from the two input regions. Asynchronous engagement of AN and N regions resulted in both distortion of action potentials and concealed conduction, with delayed conduction and block to the NH region and His bundle. Successful engagement of the NH region always produced a 1:1 NH-to-His bundle relationship. It is concluded that during atrial fibrillation 1) activation of the AN region occurs as a result of the variable interaction of inputs from the crista terminalis and interatrial septum; 2) predictably, effective synchronous engagement of the AN and consequently the N region is responsible for conduction to the NH and His bundle regions; 3) conversely, asynchronous activation inputs from the crista terminalis and interatrial septum result in fragmented, asynchronous as well as concealed conduction within the AN and N regions with block in the atrioventricular node and variable conduction to the His bundle.
Tyrosine hydroxylase and choline acetyltransferase activities in ischemic canine heart
Authors: Schmid P. G. , Greif B. J. , Lund D. D. , Roskoski R.
Published: December 2017

After coronary artery occlusion, enzymes involved in the synthesis of sympathetic and parasympathetic neurotransmitters may change disparately. We investigated this in the canine heart by measuring the activity of tyrosine hydroxylase (TH) and choline acetyltransferase (CAT) in normal and ischemic tissue. Myocardial blood flow in selected regions was measured by the microsphere technique. Dogs had either ligation of the anterior descending coronary artery (LAD) or sham ligation (S). In the ischemic zone 5 h after LAD ligation, TH activity was lower than in corresponding anterior apical zones of S dogs (5.1 +/- 1.7 vs. 13.5 +/- 2.3 nmol.g-1.h-1) (P less than 0.05) with a tendency for greater decreases in endocardium than in epicardium. In contrast, there were insignificant changes in CAT activity 2.5 and 5 h after LAD ligation. Thereafter, progressive and significant (P less than 0.05) decreases occurred in CAT activity at 25 and 170 h after LAD ligation. Thus there are early heterogeneous decreases in TH activity that correlate directly with heterogeneous deficits in blood flow. Although decreases in CAT are also heterogeneous and correlate with deficits in perfusion, these changes occur later. These results indicate differences in the effects of infarction on these biochemical indices of sympathetic and parasympathetic innervation in canine heart.
Mechanisms for redistribution of plasma protein following acute protein depletion
Authors: Kramer G. C. , Harms B. A. , Bodai B. I. , Demling R. H. , Renkin E. M.
Published: December 2017

Acute plasma protein depletion is followed by a rapid and substantial replenishment of the protein deficit. We studied the effects of plasmapheresis on flow and composition of peripheral lymph in 11 unanesthetized sheep. Whole blood was replaced with red blood cells and lactated Ringer solution to reduce plasma protein concentration ([P]) 26-54%. At 24 h after plasmapheresis, [P] had returned halfway to base line. Lymph flow (L) increased immediately after plasma protein reduction, was maximal 3 h later, and remained elevated for more than 3 days. The increase in L was coupled with a decrease more than 3 days. The increase in L was coupled with a decrease in lymph-to-plasma protein concentration ratio ([L/P]). The plasma-to-lymph oncotic gradient was reestablished by 24 h due to the reduction in lymph protein and the partial return of [P]. After 24 h, L remained elevated despite base-line levels for all measured vascular pressures and plasma-to-lymph oncotic gradients. Although lymph flow was increased, the permeability-surface area product for protein was decreased below base line. The data confirm that the partial return of [P] in the first day after plasmapheresis is due largely to a shift of extravascular protein mass into the vascular compartment and show that redistribution is initiated by increased lymphatic return and maintained by a sustained increase in L and a decrease in protein permeability of the plasma-lymph barrier.
beta-Adrenergic dilator effects in consecutive vascular sections of skeletal muscle
Authors: Lundvall J. , Hillman J. , Gustafsson D.
Published: December 2017

Humoral and neurogenic beta-adrenergic dilatation that influenced the resistance function, the capillary exchange function, and to some extent the capacitance function was demonstrated in the vascular bed of cat skeletal muscle. The beta-adrenergic effects were mainly confined to the microcirculation, causing dilatation of the precapillary sphincters and the resistance vessels of small calibre. The microcirculatory effects were pronounced in response to epinephrine, but blood-borne and nerve-released norepinephrine also evoked marked effects. The beta-adrenergic inhibition of vascular tone in the microcirculation may serve in the intact organism to improve tissue nutrition by facilitating capillary diffusion exchange. It further seems to regulate transcapillary hydrodynamic exchange, partly by controlling the precapillary sphincters and the capillary hydrostatic pressure. The blood-borne catecholamines, especially epinephrine, also markedly affected total regional vascular resistance and thereby blood flow by dilator interaction with the concomitant alpha-adrenergic vasoconstrictor response.
Persistence of myocardial failure following removal of chronic volume overload
Authors: Newman W. H. , Webb J. G. , Privitera P. J.
Published: December 2017

Length-contractile force curves and dose-response curves of heart rate, blood pressure, and contractile force were recorded from the left ventricle of six anesthetized dogs in a control state. These measurements were repeated at an average of 56 days following creation of an atrioventricular fistula when signs of heart failure were present. The fistula was then closed and the dogs restudied after an additional 57 days. Heart failure was associated with a shift up the ascending limb of a depressed length-contractile force curve and a depressed contractile response to isoproterenol. For instance, 0.1 micrograms/kg of isoproterenol produced a 173 +/- 8% increase in contractile force in control and 42 +/- 7% in failure. The contractile response to ouabain (30 micrograms/kg) was unchanged in heart failure, i.e., 36 +/- 5% in control vs. 39 +/- 4% in heart failure. When the dogs were restudied following fistula closure, the length-contractile force curve was still depressed as was the contractile response to isoproterenol, whereas the response to ouabain was again unchanged from control. Plasma norepinephrine and renin levels increased 5- and 10-fold, respectively, during heart failure and then returned to control following closure of the fistula. The data support the view that myocardial dysfunction associated with volume-overload heart failure is not reversible within the same time frame as its onset.
Response of vasopressin and norepinephrine to lower body negative pressure in humans
Authors: Goldsmith S. R. , Francis G. S. , Cowley A. W. , Cohn J. N.
Published: December 2017

To examine the contributions of cardiopulmonary and sinoaortic baroreceptors to the nonosmotic release of arginine vasopressin (AVP) in normal humans, we subjected nine individuals without evidence of hypertension or heart disease to graded, lower body negative pressure (LBNP). We also studied the effects of this maneuver on sympathetic nervous system activity using plasma norepinephrine (NE) as an index. Heart rate (HR), mean arterial pressure (MAP), pulse pressure (PP), and central venous pressure (CVP) were measured in the control state and during two consecutive levels of increasingly intense LBNP. At each stage blood was sampled for AVP and NE. AVP was analyzed by radioimmunoassay, NE by a radioenzymatic method. During the first level of LBNP, CVP decreased with no change in HR, MAP, or PP. NE increased from 147 +/- 47 to 212 +/- 53 (SD) pg/ml, P less than 0.01, whereas AVP (5.0 +/- 1.0 pg/ml) did not change. With increased suction CVP fell further, HR increased, and PP narrowed, but MAP did not change. NE further increased to 291 +/- 58 pg/ml (P less than 0.01), but AVP still did not change significantly. One subject became markedly hypotensive, and his AVP increased from 2.6 to 81 pg/ml. A fall in CVP that results in sympathetic activation presumably via cardiopulmonary receptors does not therefore increase AVP levels; a further fall in CVP that leads to modest unloading of the sinoaortic baroreceptor and further increased sympathetic activity also fails to stimulate AVP. Hypotension, however, is accompanied by a rapid and profound increase in circulating AVP.
Stability of 8-, 15-, and 26-micron microspheres entrapped in feline myocardium
Authors: Andersen K. S. , Skjerven R. , Lekven J.
Published: December 2017

The stability of 8-, 15-, and 26-micron radioactive microspheres entrapped in ischemic and nonischemic myocardium and possible mechanisms for microsphere loss were investigated. Anesthetized cats were given microspheres prior to left anterior descending coronary artery occlusion (or sham operation) and 8 h later. Eight-micron microspheres, compared with 15-micron spheres, underestimated preocclusion myocardial blood flow in ischemic and nonischemic tissue by 30%. With 26-micron spheres, endocardial-to-epicardial blood flow ratio was 1.28. In nonischemic tissue, no loss of 15- and 26-micron microspheres occurred during 8 h. In ischemic myocardium, however, 15% apparent loss of 15- and 26-micron preocclusion spheres took place. In endocardial ischemic tissue, edema could account for 50% of the 15-micron microsphere loss and almost completely for loss of 26-micron spheres. In epicardial ischemic tissue, microsphere loss was not influenced by edema. We found no hemodynamic variable that could predict the magnitude of microsphere loss. Only weak evidence for migration of 15- and 26-micron microspheres through lymphatic pathways was found. Most likely the spheres migrated through venous pathways to embolize in the lungs. We conclude that 15-micron microspheres provide the most reliable tissue blood flow estimates in normal myocardium, but even for these spheres significant loss occurs during 8 h of ischemia.
Intrarenal blood flow distribution during adenosine-mediated vasoconstriction
Authors: Macias J. F. , Fiksen-Olsen M. , Romero J. C. , Knox F. G.
Published: December 2017

Intrarenal infusion of adenosine induces an initial vasoconstriction followed by a subsequent vasodilation. The intrarenal distribution of blood flow in the vasoconstriction phase is unknown. The present study was undertaken to assess the effect of intrarenal infusion of adenosine on intracortical distribution of renal blood flow during both the vasoconstriction and vasodilation phases. Renal blood flow distribution was measured with radiolabeled microspheres in anesthetized sodium-depleted dogs before and during the early vasoconstriction phase and the late vasodilation phase of intrarenal infusion of adenosine. During the vasoconstriction phase, there was a uniform decrease in blood flow in each renal cortical zone. In the late phase of adenosine infusion, there was a significant increase in deep cortical flow without significant changes in superficial cortical flow compared with control. The effects of adenosine were also compared with those exerted by norepinephrine in which decreased blood flow was demonstrated in all zones. We conclude that the vasoconstrictor phase of adenosine infusion is characterized by a uniform reduction of renal blood flow to all cortical zones, whereas the vasodilator phase is characterized by a selective deep cortical vasodilation.