bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of decreased pressor responsiveness to ANG II, NE, and vasopressin in pregnant rats
Authors: Paller M. S.
Published: December 2017

The mechanism of decreased pressor responsiveness to pressor agents was examined serially throughout pregnancy in conscious rats. Rats, 15 and 20 days pregnant, showed marked blunting of the pressor response to graded doses of angiotensin, whereas after only 5 days of pregnancy there was a normal response and at 10 days an intermediate pressor response. A role for prior occupancy of vascular angiotensin II receptors for the blunted pressor response was made less likely by the observation that treatment with captopril to decrease endogenous angiotensin II did not improve the angiotensin II pressor response in 15-day pregnant rats. Studies of smooth muscle receptor binding of angiotensin II showed that, in pregnancy, receptor affinity and number was not changed. Inhibition of prostaglandin synthesis with meclofenamate increased the pressor response to angiotensin II toward normal in pregnant animals. The blunted vascular response in pregnancy was not specific for angiotensin since pregnant animals showed a similar decrease in the response to both norepinephrine and arginine vasopressin. Furthermore, meclofenamate increased the pressor response to norepinephrine and vasopressin in pregnant rats. We conclude that pressor hyporesponsiveness in pregnancy is not specific for angiotensin II and is not caused by alterations in vascular receptor occupancy or binding. In pregnancy there is a decreased pressor response to all three major pressor agents that is improved by inhibition of prostaglandin production.
Elastase, collagenase, and the biaxial elastic properties of dog carotid artery
Authors: Dobrin P. B. , Canfield T. R.
Published: December 2017

Segments of dog carotid artery were studied in vitro at four longitudinal extension ratios, lambda z = 1.2, 1.4, 1.6, and 1.8, in randomized order. At each length, the pressure was elevated in steps to 200 mmHg or until the vessels buckled. Vessels were studied under control conditions and after treatment with moderate doses of degradative enzymes: 80 U/ml elastase for 90 min or 640 U/ml collagenase for 120 min. These doses were selected, following pilot studies, to degrade vessels but not to destroy them. Treatment with elastase (n = 24) reduced both longitudinal and circumferential stresses at all vessel lengths. Circumferential stress was reduced at pressures greater than 15 mmHg, the magnitude of effect increasing with both longitudinal and circumferential deformations. Longitudinal stress was reduced by a constant amount, irrespective of vessel length. Treatment with collagenase (n = 24) reduced circumferential stress when the vessels were distended by at least 60 mmHg; it did not reduce longitudinal stress. These data suggest that in intact cylindrical segments of dog carotid artery, subjected to physiological levels of strain, elastin bears a portion of both circumferential and longitudinal loads, whereas collagen bears a portion of only circumferential loads.
Insulin treatment prevents vascular dysfunction in early juvenile alloxan-induced diabetes mellitus
Authors: Mueller S. M.
Published: December 2017

Microvascular pathology and sympathetic autonomic dysfunction have been described early in alloxan-induced diabetic juvenile rats. To determine the longitudinal development of these changes and whether insulin treatment can alter them, vascular and sympathetic function were studied in alloxan-induced (42.5 mg/kg) juvenile diabetic rats and saline-treated controls. The rats were examined 1 and 14 days after induction of diabetes. An insulin-treated group was studied with the 14-day group. Hindquarter perfusion with an artificial solution at constant flow/100 g hindquarter wt was used. After 14 days of diabetes mellitus, the diabetic group showed a significantly depressed response to central ischemia (P less than 0.001), maximal vasoconstriction (P less than 0.02), and maximal dilation (P less than 0.001) compared with both the control and insulin-treated group. The threshold response to norepinephrine did not differ. After 1 day of glucose elevation no differences were present between the control and diabetic animals during any of the testing procedures. These results suggest that severe vascular dysfunction develops early in juvenile-onset alloxan diabetes and that it can be prevented with insulin treatment.
Vasomotor projections from the anteroventral third ventricle (AV3V) region
Authors: Knuepfer M. M. , Johnson A. K. , Brody M. J.
Published: December 2017

The anteroventral third ventricle (AV3V) region is necessary for the development of a variety of models of experimental hypertension. Neuroanatomic studies have identified descending projections from this region to the mesencephalic central gray and tegmentum. This study was done to identify functionally the projections involved in cardiovascular regulation from the AV3V region to the mesencephalon. Regional hemodynamic responses to electrical stimulation of the AV3V region were compared with responses to stimulation of the rostral central gray, and these responses were compared before and after ablation of mesencephalic tissue. Stimulation of the AV3V region elicited hindquarter, vasodilation and renal and mesenteric vasoconstriction associated with a depressor response and bradycardia. These responses were partially dependent on adrenal catecholamines since adrenalectomy reduced hindquarter, mesenteric, and depressor responses. Regional hemodynamic responses to central gray stimulation were qualitatively similar and also demonstrated a partial dependence on adrenal catecholamines. After electrolyte ablation of central gray tissue, significant reductions in hindquarter, mesenteric, and depressor responses to AV3V stimulation were observed. These observations suggest that a cardiovascular control system important for the development of several models of hypertension may be dependent on neuronal projections from the rostral medial hypothalamus through the mesencephalic central gray.
Autonomic mechanisms in the ductus venosus of the lamb
Authors: Coceani F. , Adeagbo A. S. , Cutz E. , Olley P. M.
Published: December 2017

Morphological and pharmacological studies were performed in the ductus venosus from near-term fetal and neonatal (1 day of age) lambs. Light and electron microscopic analysis demonstrated a concentration of circularly oriented muscle fibers at the junction of the ductus with the portal sinus (the sphincter region). With the use of histochemical methods, adrenergic and cholinergic fibers were visualized in both the sphincter and extrasphincter regions of the ductus. At either site, nerve fibers were confined to the adventitial layer and never formed a plexus. Norepinephrine and transmural electrical stimulation contracted the ductus sphincter in vitro, and their action was abolished by dibenzyline. In contrast, atropine had no effect on the transmural response. Moreover, acetylcholine contracted the vessel inconsistently. In the fetus, both the norepinephrine-induced and the electrically induced contractions increased on raising the O2 tension of the bathing fluid from 17-31 to 520-705 mmHg. In addition, the transmural response increased with advancing gestation. Norepinephrine and transmural stimulation relaxed dibenzyline-treated preparations in which the tone had been raised with indomethacin. Norepinephrine relaxation was antagonized by propranolol. We conclude that the ductus venosus sphincter contains functional adrenergic nerves, causing contraction and relaxation via, respectively, alpha- and beta-adrenoceptors. The alpha-adrenoceptor-mediated contraction may have a role in postnatal closure of the vessel.
Protective role of adenine nucleotide translocase in O2-deficient hearts
Authors: Pande S. V. , Goswami T. , Parvin R.
Published: December 2017

At subsaturating concentrations of palmitoyl-CoA, the carnitine-dependent oxidation of the palmitoyl portion by uncoupled rat heart mitochondria was stimulated by ADP or ATP. This effect was traced to the prevention of acyl-CoA binding to adenine nucleotide translocase and the consequent sparing of acyl-CoA for acylcarnitine formation. Palmitoyl-CoA oxidation was stimulated by ITP also although ITP served neither as a transportable substrate nor as an inhibitor of ADP transport. ITP and other nontransportable nucleoside di(tri)phosphates prevented octanoyl-CoA binding to mitochondria. ITP was bound to mitochondria, and this binding was reversed by ADP, octanoyl-CoA, and carboxyatractyloside. Thus, besides a substrate site, there is a site on the translocase that binds nucleoside di(tri)phosphates, CoA and its esters, and atractylosides; inhibition of the translocase results, however, only from the binding of CoA esters of fatty acids and of atractylosides. We suggest that in O2-deficient hearts, when nucleotides decline and fatty acyl-CoA rises, the binding of the latter to the translocase becomes operational to slow fatty acylcarnitine production. By retarding the rise in amphipathic burden, this mechanism could protect heart against irreversible damage during brief periods of ischemia or hypoxia.
Protein concentration of lymph and interstitial fluid in the rat tail
Authors: Aukland K. , Kramer G. C. , Renkin E. M.
Published: December 2017

Lymph was collected from tail lymphatics of anesthetized rats, subcutaneous interstitial fluid was obtained by implanting nylon wicks, and tendon interstitial fluid was obtained by centrifugation of pieces of tendon. Spontaneous lymph flow rates averaged 70 nl X min-1 X g skin-1. Protein concentrations and colloid osmotic pressures of sampled fluids differed significantly. Tail lymph had the highest protein concentration relative to plasma [lymph-to-plasma ratio 0.71 +/- 0.03 (SE) n = 10], followed by wick fluid (0.62 +/- 0.02, n = 9), with tendon fluid lowest (0.50 +/- 0.03, n = 10). Albumin and immunoglobulin G (IgG) concentrations in samples of tail skin and tendon were assayed by rocket immunoelectrophoresis. Comparison of their distribution volumes at lymph or tendon fluid concentrations, respectively, with interstitial fluid volumes measured as 2-h 51Cr-ethylenediaminetetraacetic acid space minus 5-min 125I-albumin space indicated that 50-60% of the interstitial volume in these tissues is not available for distribution of albumin or IgG. Low lymph flow and high interstitial protein content of rat tail indicate a slow turnover of interstitial protein. This suggests that interstitial washout of protein plays a role in limiting edema only after a sustained or chronic increase in fluid filtration.
Directional disparity of pulse reflection in the dog
Authors: Li J. K. , Melbin J. , Noordergraaf A.
Published: December 2017

Local reflection coefficients were experimentally determined in the dog for the first time at the aortoiliac junction using characteristic impedances derived from phase velocity, fluid density, and the vessels' cross-sectional areas. Reflection coefficients were determined for both the normal trifurcation and with the segment of aorta between external and internal iliacs occluded. For the normal case the coefficients were as follows: antegrade, 0.7; retrograde, -0.74. For the occlusion case the coefficients were as follows: antegrade, 0.33; retrograde, -0.67. These results provide experimental support for the concept that the vascular system, at least in this region, favors antegrade and suppresses retrograde pulse transmission. In addition, global reflection coefficients were determined in the femoral artery using a three-point pressure technique. Coefficient magnitudes varied from low (1.6 Hz) to high (9.6 Hz) frequencies, i.e., control, 0.42-0.22; vasoconstriction, 0.65-0.33; vasodilation, less than 0.1 for all frequencies. Discrepancies between results appearing in the literature are evaluated and shown to be associated with the method utilized as well as with system nonlinearities enhanced by tying branches.
Contractility and protein phosphorylation in cardiomyocytes: effects of isoproterenol and AR-L57
Authors: Hayes J. S. , Bowling N. , Boder G. B.
Published: December 2017

The cardiotonic drugs AR-L57 [2-(2,4-dimethoxyphenyl)-1H-imidazo(4,5b)-pyridine] and isoproterenol stimulated contractility in cultured heart cells in concentration-dependent manners; only the effects of isoproterenol were blocked by propranolol. Isoproterenol, but not AR-L57, enhanced the phosphorylation state of seven protein bands [relative molecular weights (MrS) 155,000, 96,000, 27,000, 24,000, 20,000, 16,000, 12,000] and resulted in the dephosphorylation of one protein band (Mr 21,000). Also, only isoproterenol increased the activation states of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase and glycogen phosphorylase. The eight protein bands resolved by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and detected by autoradiography were altered by isoproterenol in time- and concentration-dependent manners. The 24,000-Mr protein substrate phosphorylated in response to isoproterenol was converted to a 12,000-Mr species by heating in the presence of SDS prior to electrophoresis, suggesting that the two substrates were in fact identical proteins. A comparison of the 2-min responses to varying concentrations of isoproterenol resulted in excellent correlations between the phosphorylation states of individual protein bands and contractility. This was true even for the 21,000-Mr species that was dephosphorylated. However, only the 27,000-, 24-12,000-, and 16,000-Mr substrates were phosphorylated rapidly enough to be associated with the onset of the inotropic response. Cultured myocytes are an important feature of these studies as they are 84% pure ventricular cells that remain 100% viable throughout an experiment. Because this system is suitable for biochemical measurements and the effects of agents on heart cell contractility can be determined, it is possible to correlate changes in biochemical parameters with alterations in physiological state.
Effects of nimodipine on cerebral vasoconstrictor responses
Authors: Haws C. W. , Heistad D. D.
Published: December 2017

The purpose of this study was to examine effects of nimodipine (Bay e 9736), a calcium blocker, on constrictor responses of cerebral vessels in vivo. Pial artery diameter was measured in anesthetized cats. In the control state, sympathetic nerve stimulation, acute hypertension, and hypocapnia produced maximal decreases in pial artery diameter of 13.7 +/- 1.4, 12.1 +/- 2.7, and 13.3 +/- 2.7% (SE), respectively. Low doses of nimodipine (0.1-0.25 microgram X kg-1 X min-1) decreased the vasoconstrictor response to all three stimuli, and higher doses (0.5-1.0) virtually abolished the response (P less than 0.05 vs. control). In other experiments in cats and monkeys, cerebral blood flow (CBF) was measured with microspheres during acute increases in arterial pressure. Elevation of arterial pressure by approximately 40 mmHg in cats produced only a modest increase in CBF from 48 +/- 3 to 57 +/- 3 ml X min-1 X 100 g-1 in the control state and a larger increase in CBF from 53 +/- 6 to 87 +/- 9 ml X min-1 X 100 g-1 during nimodipine (P less than 0.05, control vs. nimodipine). Nimodipine also inhibited autoregulatory vasoconstriction in monkeys. Nimodipine, in the doses used, had only modest effects on resting vessel diameter, CBF, or arterial pressure. We conclude that nimodipine inhibits cerebral vasoconstrictor responses to several physiological stimuli in vivo.
Mechanisms of central prostaglandin E2 hypertension in conscious dogs, sheep, and calves
Authors: Hull S. S. , Chimoskey J. E.
Published: December 2017

Intracarotid prostaglandin E2 (PGE2) infusions (10 ng X kg-1 X min-1) increased arterial pressure in conscious dogs, sheep, and calves. Total and regional peripheral resistances (renal, superior mesenteric, and iliac) increased in conscious calves. Arterial pH and CO2 tension did not change, implying no activation of the chemoreflex. The arterial baro-reflex was reset upward during intracarotid PGE2 infusion; arterial pressure increased with little heart rate change, but baroreflex sensitivity was unchanged. In contrast, equipotent intracarotid angiotensin II infusions (10 ng X kg-1 X min-1) both reset the baroreflex upward and decreased baroreflex sensitivity. Pretreatment with alpha-, but not beta-, adrenoceptor blocking agents attenuated the intracarotid PGE2 pressor effect. Increasing PGE2 infusions (10-200 ng X kg-1 X min-1) caused dose-related arterial pressure increases; plasma renin activity was increased only at the largest infusion rate. Pretreatment with captopril, an inhibitor of the angiotensin-converting enzyme, attenuated the PGE2 pressor effect. During barbiturate-halothane and chlorolose-urethan anesthesia, no pressor effect was observed during intracarotid PGE2. We conclude that intracarotid PGE2 acts centrally to augment sympathetic vasomotor outflow. The central action of PGE2 is not affected by activation of the arterial chemoreflex or alteration of baroreflex sensitivity and has a small renin-angiotensin component.
Accumulation of nonesterified fatty acids in ischemic canine myocardium
Authors: Prinzen F. W. , Van der Vusse G. J. , Arts T. , Roemen T. H. , Coumans W. A. , Reneman R. S.
Published: December 2017

In ischemic myocardium the time course of nonesterified fatty acid (NEFA) accumulation was studied in relation to changes in regional metabolism and mechanics. In open-chest dogs a coronary artery was partially occluded for 120 min. In the ischemic myocardium no increase was observed in NEFA content within 10 min, whereas changes were found in regional shortening, high-energy phosphate content, and glucose arteriologcal venous difference. During prolonged ischemia NEFA content increased, the highest values being found in the inner and middle layers after 120 min (112 and 85 nmol X g-1, respectively; control values 30); the value in the outer layers after 60 min was 93 nmol X g-1. After 120 min of ischemia, accumulation of NEFA generally occurred when myocardial blood flow was below 0.3 ml X min-1 X g-1 and ATP content was below 10 mumol X g dry wt-1. Under these circumstances the individual NEFA with the highest relative increase was arachidonic acid. The present findings indicate that the changes in mechanical function and metabolism, as observed in myocardium rendered ischemic for 10 min, are not caused by increased NEFA content and that NEFA accumulation may partly result from hydrolysis of glycerophospholipids.
Perturbations in the membrane potential of cultured heart cells: role of calcium
Authors: Nathan R. D. , Bhattacharyya M. L.
Published: December 2017

Intracellular recordings were obtained from spheroidal aggregates of 7-day embryonic chick heart cells after 3 days in gyratory culture. Three types of perturbations in the membrane potential were observed under experimental conditions expected to increase intracellular calcium: 1) multiple oscillations (of 5-20 mV peak-to-peak amplitude) during diastole in aggregates exposed to 10-15 mM Ca, 5 microM strophanthidin, or K-free solutions; 2) less periodic spontaneous voltage fluctuations (of less than 1.5 mV peak-to-peak amplitude) in aggregates exposed to solutions containing 22% of the normal [Na], and 3) depolarizing afterpotentials (DAPs), following repolarization of the action potential, in aggregates treated with 20-50 microM A23187, a Ca ionophore, or 5-10 mM caffeine. The oscillations were reduced markedly by 0.03-3.0 microM tetrodotoxin (TTX) and were blocked by 5-10 mM caffeine. Spontaneous voltage fluctuations were increased by raising external Ca, were unaffected by 30 microM TTX, and were blocked by 5 mM caffeine. DAPs were not blocked by 5 mM caffeine or by 0.1 microM TTX and 1 microgram/ml D 600, concentrations that greatly reduced the action potential upstroke velocity and plateau, respectively. Two intracellular electrodes were employed to test for electrotonic coupling between cells within an aggregate. An electrotonic response in one cell could be recorded when current was injected into another cell during recordings of each of the perturbations but was somewhat less during spontaneous voltage fluctuations. Possible ionic mechanisms for the perturbations and for concomitant changes in the configuration of the action potential are discussed.
Heat transport in the canine left ventricular wall
Authors: ten Velden G. H. , Westerhof N. , Elzinga G.
Published: December 2017

The rate of rise of local myocardial temperature (dT/dt) evoked by left coronary artery main stem occlusion has been proposed in the literature as a measure of local metabolic heat production, assuming heat loss due to diffusion to be negligible. In a previous study (ten Velden, G. H. M., G. Elzinga, and N. Westerhof. Circ. Res. 50: 63-73, 1982), we showed that this assumption was not valid. With this information in mind, in an attempt to study local metabolism, we compared, in anesthetized dogs, the dT/dt with the temperature distribution over the left ventricular wall. We found the value of dT/dt to be reproducible in time and to reproducibly depend on location. Negative values as well as positive values were measured; values even higher than the maximal possible temperature slope, calculated from the energy equivalent of left ventricular oxygen consumption and the specific heat of cardiac tissue, were found. Transmural distribution of the dT/dt showed positive values epicardially and negative values endocardially, while, as previously shown, a parabola-like shape of the transmyocardial temperature distribution existed. Our findings demonstrate that dT/dt by left coronary main stem occlusion cannot be used as a measure of local myocardial heat production.
Adrenergic potentiation on spontaneous activity of canine paranodal fibers
Authors: Tse W. W.
Published: December 2017

The present study, using in vitro preparations, was designed to determine the anatomic, histological, and automatic properties of canine paranodal fibers. This tissue, together with the atrioventricular (AV) node and His bundle, constituted the three major tissues in the AV junction. The fascicles of the paranodal fibers ran parallel and adjacent to the base of the septal cusp of the tricuspid valve. The distal end of the paranodal fibers joined the lower half of the compact AV node on its convex side. Paranodal fibers when isolated were able to initiate spontaneous activity. Action potentials of many of these fibers showed primary pacemaker characteristics, i.e., a prominent phase 4 depolarization and smooth transition from phases 4 to 0. In 14 preparations, epinephrine (2.0 micrograms injected into the tissue bath) potentiated spontaneous rates to 144 +/- 6.0 beats/min from 61 +/- 5.0, an increase of 136%. Also, under the influence of epinephrine, paranodal fibers consistently generated a spontaneous rate higher than that of the AV node or His bundle, whether they were functionally connected or separated. These findings provide a basis for explaining the junctional tachycardia that occurs under adrenergic influence and demonstrate the presence of three major automatic tissues: the paranodal fibers, AV node, and His bundle in the canine AV junction.
Some consequences of body size
Authors: Ford L. E.
Published: December 2017

The question of the proper size denominator for metabolic indices is addressed. Metabolic rate among different species is proportional to the 3/4 power of body weight, not surface area. Muscle power also varies with the 3/4 power of weight, suggesting that metabolic rate is determined mainly by muscle power. Power-to-weight ratio, specific metabolic rate, and a number of metabolic periods, including heart rate, all vary inversely with the 1/4 power of body weight. Thus the relative times required for physiological and pathological processes in different species may be estimated from the average resting heart rate for the species. There are not many small humans among athletic record holders in events involving acceleration and hill climbing, as would be expected if they had higher power-to-weight ratios. Thus the relationship between size and metabolic rate in different species should not be applied within the single species of humans. Evidence is reviewed showing that basal metabolic rate in humans is determined mainly by lean body mass.
Left ventricle-aortic coupling: prediction of contraction pattern
Authors: Piene H. , Myhre E. S.
Published: December 2017

In control heart beats of six open-chest dogs we established a relationship between ventricular diameter and change in volume during systolic ejection, described ventricular mechanical performance by a time-dependent pressure-diameter relationship, and represented ventricular afterload in subsequent variably loaded test beats by aortic input impedance calculated from aortic flow and pressure. Impedance was manipulated by means of an inflatable balloon in the aorta. A computational procedure was developed which combined the independent and general descriptions of ventricle (1 and 2 above) and load (3 above) to predict the time course and mean values of aortic pressure, flow, ventricular pressure, and diameter over a broad range of aortic impedance. Predicted data were compared with those directly observed at identical impedance. High degree of accordance between predicted and observed data of stroke volume, mean aortic and mean ventricular pressure was found, but diameter shortening was less accurately predicted. Previously assessed dependency of the ventricular pressure-volume-time relationship on aortic flow and "ejection history" was also incorporated in the calculations. This caused improved prediction of the flow pulse configuration, but the quality of predictions of mean values of pressures and flow was not enhanced.
Reduced transcoronary exchange and prostaglandin synthesis in diabetic rat heart
Authors: Rosen P. , Rosen R. , Hohl C. , Reinauer H. , Klaus W.
Published: December 2017

In perfused hearts of streptozotocin-diabetic rats the kinetics of a fluoresce indicator transit was measured after pulse injection of FITC-dextran 3. The fluorescence changes on the left ventricle could be described by two pseudo first-order processes with half times in the range of seconds (t/2) corresponding to the intravascular washout and a slow process (T/2) corresponding to the exchange between the extra- and the intravascular space. In diabetes both half times became prolonged, and the amount of FITC-dextran 3 exchanged between the two compartments was reduced, indicating an impaired transcoronary transport in diabetic hearts. There was a time-dependent reduction in the basal release of prostacyclin in hearts of control and diabetic rats. However, studied hearts of diabetic rats released less 6-keto-prostaglandin F1 alpha (PGF1 alpha) than controls. This impaired release of 6-oxo-PGF1 alpha could be prevented partly by adrenalectomy. Because diabetic hearts release more 6-oxo-PGF1 alpha than controls after application of arachidonic acid, these data suggest that the supply of arachidonic acid for the synthesis of prostaglandins is impaired in diabetes, but not the cyclooxygenase pathway itself. The reduced transcoronary transport and the impaired synthesis of prostacyclin might be early steps in the development of microangiopathic myocardial alterations in diabetes.
Propagation through electrically coupled cells: two inhomogeneously coupled cardiac tissue layers
Authors: Joyner R. W. , Overholt E. D. , Ramza B. , Veenstra R. D.
Published: December 2017

Most of the ventricular endocardial surface is covered with a layer of Purkinje (P) cells which provide a rapid spread of activation into the underlying ventricular (V) cells. We have shown experimentally that the P-V junctional region of papillary muscles is spatially inhomogeneous with different regions showing bidirectional conduction, bidirectional block, or unidirectional block between the P and V layers. We have now extended our one-dimensional simulations to a double layer of excitable cells with spatially inhomogeneous electrical coupling between the two layers. Our simulations show that a partial uncoupling can actually increase the common conduction velocity of the two layers and can produce successful P-to-V conduction at regions that would otherwise show P-to-V block, and inhomogeneous spatial distributions of coupling resistivity between two excitable layers can simulate the observed spatial distribution of spatially variable conduction block in papillary muscles. Our simulations indicate that a partial regional electrical coupling may be a useful design feature of the heart to enhance the velocity and safety factor of ventricular activation, but the further increases in uncoupling that may be associated with ischemia may provide a structural basis for the occurrence of arrhythmias.
Sympathetic effects on spontaneous activity in bovine mesenteric lymphatics
Authors: Ohhashi T. , Azuma T.
Published: December 2017

To investigate the effects of autonomic nerves on the spontaneous activity, responses of valvular and intervalvular segments of isolated bovine mesenteric lymphatics to 60-strains of pulses (50 V for 0.5 ms at 2 Hz) have been studied under the influence of various drugs. There was a marked difference in response to transmural stimulation between the valvular and intervalvular segments. In the valvular segment, the stimulation arrested the spontaneous activity. However, the rhythm of spontaneous contractions was markedly accelerated during the stimulation in the intervalvular segment. Both inhibitory and excitatory effects were completely blocked by tetrodotoxin and guanethidine, potentiated by cocaine, and unaffected by hexamethonium and atropine. Propranolol blocked the inhibitory effect of the stimulation in the valvular segment. Pretreatment of the intervalvular segment with phentolamine converted the normal excitatory effect of the stimulation into an inhibitory influence. No change in rhythm was brought about by the stimulation in the presence of propranolol and phentolamine in either segment. These results suggest that transmural electrical stimulation causes the release of norepinephrine from postganglionic sympathetic nerve terminals in the vicinity of pacemaker cells and that beta-adrenoceptors are predominant in the valvular region of the lymph vessel.
Load sensitivity of ventricular force-interval relations in conscious dogs
Authors: Caillet D. , Crozatier B.
Published: December 2017

The influence of the interval between beats on myocardial contractility was examined in conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular major and minor diameters and parietal wall thickness during control state and after inflation of an aortic cuff. Ventricular contraction was measured during variations of diastolic intervals (DI) produced by respiratory arrhythmia or atrial pacing. During control before aortic stenosis, minor equator shortening (% delta L) increased slightly after long (L) DI compared with short (S) DI with a corresponding decrease of end-systolic stress. During aortic stenosis, LDI were associated with a significant increase of % delta L compared with SDI although end-systolic stress was larger. Thus end-systolic stress-diameter relations were not modified during control but they were significantly shifted to the left after LDI during aortic stenosis. Inotropic state is thus increased after LDI during acute pressure overload but not during control, suggesting that the restitution phenomenon is load sensitive.
Reduced effectiveness of the carotid baroreflex during arterial hypoxia in dogs
Authors: Pisarri T. E. , Kendrick J. E.
Published: December 2017

The ability of the carotid baroreflex to produce cardiac slowing during arterial hypoxia was investigated in dogs anesthetized with morphine-chloralose. The heart rate response to baroreflex stimulation decreased by about 20% at an arterial O2 tension (PaO2) of 65-70 Torr and by over 60% at a PaO2 of 15-20 Torr. After the aortic nerves were cut bilaterally, baroreflex stimulation produced greater cardiac slowing (P less than 0.001) during arterial hypoxia (PaO2 20 Torr) than at the same PaO2 with intact aortic nerves. The systemic depressor response to baroreflex stimulation was reduced in a qualitatively similar manner but with greater variability. After atropine (0.2 mg/kg iv) or vagal transection the heart rate response to baroreflex stimulation during hypoxia was not suppressed from its control. Perfusion of the head with hypoxic blood in carotid-denervated animals also reduced the baroreflex bradycardia. The results suggest that the vagal component of the baroreflex bradycardia is suppressed during arterial hypoxia both by a reflex mediated by the aortic chemoreceptors and by a direct effect of hypoxia on the central nervous system.
An array of microelectrodes to stimulate and record from cardiac cells in culture
Authors: Israel D. A. , Barry W. H. , Edell D. J. , Mark R. G.
Published: December 2017

An array of extracellular microelectrodes containing 25 recording and 6 stimulating electrodes was fabricated using microelectronics technology. Ventricular myocardial cells from 8- to 10-day chick embryos were cultured on the surface of the microelectrode array. Extracellular potentials were recorded simultaneously from multiple sites. Simultaneous recordings of extracellular and transmembrane potentials were made from single sites. Extracellular potentials were also recorded simultaneously with cell motion from single sites. Cells were paced by means of electrical stimuli applied via the stimulating electrodes. Conduction velocity in a strip of cells varied linearly as a function of temperature from 0.21 m/s at 26 degrees C to 0.38 m/s at 36.5 degrees C.
Systemic and pulmonary hemodynamic responses to intracranial hypertension
Authors: Chen H. I. , Wang D. J.
Published: December 2017

Experiments were conducted in anesthetized, vagotomized, and open-chest dogs. Total heart bypass was performed to perfuse the systemic and pulmonary circulations with constant flow. The venous outflows were diverted into reservoirs. We studied the simultaneous changes in systemic vascular resistance (SVR) and capacity (SVC) as well as pulmonary vascular resistance (PVR) and capacity (PVC) during a period of intracranial hypertension (ICH). In 20 dogs with an intracranial pressure of 164 +/- 12 mmHg, SVR increased by 110% and SVC decreased by 8.4 +/- 1.2 ml/kg. The increase in PVR reached 69%, and the decrease in PVC amounted to 1.24 +/- 0.40 ml/kg body wt or 9.7 +/- 3.9 ml/100 g lung wt. The results indicate that ICH exerts profound effects on both systemic and pulmonary resistance and capacitance vessels. An analysis from the pulmonary blood volume change suggested that the pulmonary vascular compliance was significantly reduced by ICH from a control value of 0.33 +/- 0.06 to 0.26 +/- 0.05 ml X mmHg-1 X kg-1. In the pulmonary circulation, an elevation of left atrial pressure with lung volume expansion attenuated the resistance response, while it increased the capacity reduction. When pulmonary blood volume was kept constant by a constant venous outflow equal to the arterial inflow, the response of capacitance vessels to ICH increased both pulmonary arterial and venous pressures associated with a slight change in PVR. These findings suggest that an increase in pulmonary venous pressure with a constant or increased blood volume reduced the ICH-induced change in resistance.
Regional myocardial perfusion and wall thickening during ischemia in conscious dogs
Authors: Gallagher K. P. , Matsuzaki M. , Koziol J. A. , Kemper W. S. , Ross J.
Published: December 2017

We examined in conscious dogs the effects of reductions in myocardial blood flow (MBF) in three different layers across the wall on regional myocardial contractile function in the ischemic zone, measured as systolic wall thickening (%WT). In 16 dogs, %WT was measured with sonomicrometry and MBF was determined with microspheres (10- to 12-microns diam) during coronary stenosis of the left circumflex coronary artery. The stenoses were categorized into six groups by the effect on %WT (each group representing progressive 20% decrements in %WT from control), and individual and pooled regression analyses were performed on data from six of the dogs having multiple data points to evaluate the shape (linear or curvilinear) of the relationships between MBF and changes in %WT. Transmural contractile function was highly sensitive to acute reductions in MBF, especially reductions in the subendocardium. The shape of the normalized subendocardial MBF-%WT relation was mildly curvilinear by regression analysis (quadratic equation, gamma = -0.75x2 + 2.15x -0.39, r2 = 0.92). Likewise, mean transmural and midmyocardial MBF correlated well and closely with changes in %WT. Subepicardial MBF, however, correlated poorly with changes in %WT, there being no change in subepicardial MBF until %WT had been reduced more than 50%.
Red blood cell deformability and protein adsorption on red blood cell surface
Authors: Kikuchi Y. , Koyama T.
Published: December 2017

Effects of protein and NaCl concentrations in plasma on red blood cell (RBC) deformability were studied using fresh human blood and a 5-microns Nuclepore filtration test. The protein and salt concentrations were varied by diluting the plasma with saline and adding crystalline NaCl to the fluids, respectively. The mean pore passage time of the RBCs, which was measured as an index of the deformability, increased with increasing plasma protein and NaCl concentrations. A marked interdependence was observed; the relation of RBC deformability with plasma protein was accentuated by an increase in plasma NaCl, whereas the effect of increasing plasma NaCl was diminished by a decrease in plasma protein. It is suggested that the RBC-protein interaction which is modified by the fluid ionic strength plays a dominant role in producing these characteristic changes in RBC deformability with protein and salt contents in the plasma. An analysis is made of the cell-protein interaction; the electric repulsive and van der Waals attractive forces are calculated with a result that the protein adsorption on a RBC increases with increasing fluid ionic strength above normal. This analysis, furthermore, provides information on the surface charge distribution on a RBC.
Direct action of norepinephrine on aortic baroreceptors of rat adventitia
Authors: Kunze D. L. , Krauhs J. M. , Orlea C. J.
Published: December 2017

The adventitia of the rat aortic arch, with the depressor nerve intact, was separated from the underlying media to obtain a preparation in which the direct effects of norepinephrine on baroreceptor discharge could be examined free of smooth muscle effects. Cyclic stretch was applied to the adventitia to evoke discharge in single aortic baroreceptor fibers. Norepinephrine and phenylephrine in concentrations of 10(-7) to 10(-5) M increased baroreceptor discharge. No effect on discharge was seen with isoproterenol. Phentolamine but not propranolol blocked the increase in discharge produced by norepinephrine. An alpha-adrenergic modulation of baroreceptor discharge that is not dependent on smooth muscle tension has been demonstrated.
Diabetic cardiomyopathy in rats: mechanical and biochemical response to different insulin doses
Authors: Fein F. S. , Malhotra A. , Miller-Green B. , Scheuer J. , Sonnenblick E. H.
Published: December 2017

Diabetes mellitus causes congestive heart failure in humans, independent of atherosclerosis. The present study extends previous work on the reversibility, with insulin, of the alterations in myocardial function and contractile protein biochemistry observed in diabetic rats. The response of these alterations to different fixed doses of insulin was explored. Diabetic rats were given 0, 0.5, 1, 1.5, 2, or 2.5 U of insulin daily for 6 wk. Papillary muscle function, actomyosin ATPase, and myosin isoenzyme distribution showed progressive normalization with increasing insulin dose as blood glucose concentration returned to normal. Thus insulin therapy in diabetic rats on a normal diet produces continuous improvement in cardiac function and biochemistry as euglycemia is approached. This study also suggests that mild diabetes results in qualitatively identical, although quantitatively less pronounced, myocardial changes compared with those observed in severely diabetic rats.
Effects of palmitoyl carnitine and LPC on cardiac sarcolemmal Na+-K+-ATPase
Authors: Pitts B. J. , Okhuysen C. H.
Published: December 2017

We have previously reported that palmitoyl carnitine is a potent inhibitor of Na+-K+-ATPase. Recently, Owens et al. [Am. J. Physiol. 242 (Heart Circ. Physiol. 11): H456-H461, 1983] reported that palmitoyl carnitine did not inhibit Na+-K+-ATPase activity of their cardiac sarcolemmal preparation that had been isolated without the use of detergents. We have investigated this using a similar preparation. Palmitoyl carnitine appears to be a much less effective inhibitor of the sarcolemmal preparation at lower concentrations because it simultaneously stimulates Na+-K+-ATPase by unmasking latent activity. When this latent activity is exposed by pretreatment with sodium dodecyl sulfate, a marked inhibition by palmitoyl carnitine is then observed. Similar results were obtained with lysophosphatidylcholine (LPC). The concentrations of palmitoyl carnitine and LPC required to inhibit Na+-K+-ATPase are, however, higher than those that cause sarcolemmal permeability changes; consequently, it is improbable that inhibition of the enzyme by these metabolites occurs to any significant extent in vivo.
Inhibition of myocardial rotenone-insensitive NADH cytochrome c reductase by amphiphilic compounds
Authors: Kennett F. F. , Knauer T. E. , Owens K. , Weglicki W. B.
Published: December 2017

Because myocardial ischemia is correlated with both an elevation of intracellular levels of amphiphilic lipid metabolites and a decrease in the rotenone-insensitive NADH cytochrome c reductase (RINCR), we investigated the effects in vitro of some amphiphilic lipid metabolites and synthetic detergents on the activity of RINCR-enriched subfractions of microsomes from isolated cardiac myocytes. RINCR activity was unaffected in vitro by the addition of lysophosphatidylethanolamine (up to 0.5 mM) but was inhibited (maximum 63%) by lysophosphatidylcholine (8 microM). Palmitoyl carnitine (up to 2 mM) was ineffective, but the coenzyme A thioesters of palmitate, stearate, oleate, and arachidonate were inhibitory at concentrations (less than 3 microM) below their critical micellar concentrations. Arachidonyl CoA was approximately one order of magnitude more inhibitory than the other long-chain acyl CoA thioesters. Kinetic analyses revealed the effect of arachidonyl CoA on RINCR activity to be exclusively an alteration of the Vmax with no change in the Km for cytochrome c. The inhibition of myocytic RINCR activity by long-chain acyl CoA may be unrelated to the bulk-phase detergency of this lipid amphiphile since the effects were observed at concentrations below the critical micellar concentration, and other lipid amphiphiles had no effect on RINCR activity. Inhibition of microsomal RINCR activity may result from localized disruption of the membrane microenvironment of the enzyme complex by penetration or dissolution of long-chain acyl CoA into the membrane. The pronounced sensitivity of myocytic RINCR activity to long-chain acyl CoA suggests a relationship between the decreased RINCR activity and the increased levels of this class of lipid metabolites observed in the ischemic myocardium.
Extracellular pH and tension during ischemia in the isolated rabbit ventricle
Authors: Couper G. S. , Weiss J. , Hiltbrand B. , Shine K. I.
Published: December 2017

To investigate the factors determining the rate of H+ accumulation during early ischemia, miniature intramyocardial pH electrodes (tip diam 0.2–0.5 mm) were used to record extracellular pH (pHo) in the isolated arterially perfused rabbit interventricular septum. Changes in pHo and the rate of fall of tension during global ischemia were compared under control conditions (37 degrees C, heart rate 75 beats/min) and after exposure to the following interventions: reduced heart rate (36 beats/min), hypothermia (27 degrees C), verapamil (0.5 microM), reduced extracellular Ca2+ concentration [( Ca2+]o 0.5 mM), norepinephrine (0.5 microM) in normal and catecholamine-depleted preparations, norepinephrine and reduced [Ca2+]o, and theophylline (4 mM). Under control conditions pHo declined by 0.61-0.73 pH units after 10 min of ischemia. The negative inotropic interventions and reduced temperature significantly decreased [H+]o accumulation during ischemia. Positive inotropic interventions did not affect the rate of [H+]o accumulation during ischemia except in reserpinized preparations. All of the interventions except for reduced temperature significantly altered the relationship between tension and pHo during ischemia.
Amino acids induce renal vasodilatation in isolated perfused kidney: coupling to oxidative metabolism
Authors: Brezis M. , Silva P. , Epstein F. H.
Published: December 2017

Renal vasodilatation regularly accompanies protein feeding and amino acid infusions, but the mechanism is unknown. The effects of several different amino acids on renal hemodynamics were studied in the isolated rat kidney, perfused with glucose as the only other substrate. Addition of amino acids produced a dose-dependent, brisk, and sustained decrease in renal vascular resistance (by 5–35%) without change in glomerular filtration rate (GFR). The vasodilatation was associated with a parallel increase in O2 consumption (increases QO2). The effect was most marked with amino acids actively metabolized by the kidney, such as glutamine (at 2 mM), but was seen with most amino acids at 8 mM. The amino acid analogues alpha-aminobutyrate, taurine, and cycloleucine, cotransported with sodium but not metabolized, did not cause significant vasodilatation or increases QO2. Blocking active transport with ouabain blunted the amino acid-induced vasodilatation and increases QO2. Similar resistance to amino acids was produced by halting GFR with hyperoncotic medium. Restoration of GFR by increasing perfusion pressure in the presence of hyperoncotic medium reestablished amino acid-induced vasodilatation and increases QO2. Furosemide did not block the vasodilatory response. Inhibition of mitochondrial respiration by antimycin blocked both vasodilatation and increases QO2, but rotenone blockade could be bypassed by succinate or glutamine. Amino acids have a direct vasodilating action on isolated kidneys probably related to their role as metabolic substrates and linked to an increase in renal O2 consumption.
Exchange of macromolecules between peritoneal cavity and plasma
Authors: Flessner M. F. , Dedrick R. L. , Schultz J. S.
Published: December 2017

The exchange of fluorescein isothiocyanate-labeled dextrans ranging in weight-averaged molecular weight from 19,400 to 160,000 and 125I-bovine serum albumin (BSA) between dialysis fluid (5% BSA in Krebs-Ringer solution) in the peritoneal cavity and the plasma was studied in anesthetized female Sprague-Dawley rats. Plasma and peritoneal samples were collected for 3-4 h after either 1) an intraperitoneal injection of dialysis fluid with tracer or 2) an intravenous injection of tracer material simultaneously with an intraperitoneal injection of dialysis solution without tracer. Analysis of the data by means of a mathematical model of the transport process suggests a functional asymmetry in transport of large molecules across the blood capillary wall. Substances injected intravenously have a net transport from the blood capillaries to the peritoneal cavity. Substances of molecular weight greater than or equal to 39,000 transport from the cavity to the plasma via peritoneal lymphatics; 19,400 molecular-weight dextran transports from the cavity to the plasma primarily via lymphatics with some blood capillary uptake. Tissue diffusivities and capillary mass transport coefficients are derived for the substances tested.