bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of generation of body surface electrocardiographic P-waves in normal, middle, and lower sinus rhythms.
Authors: Eifler W J , Macchi E , Ritsema van Eck H J , Horacek B M , Rautaharju P M
Published: June 2012

We used comprehensive electrophysiological/anatomical digital computer models of atrial excitation and the human torso to study the mechanisms of generation of body surface P-waves in normal sinus rhythm, and in middle and lower sinus rhythm. Simulated atrial surface isochrone maps for normal sinus rhythm support the validity of the atrial excitation model. The results suggest that the presence of specialized internodal tracts containing fast-conducting fibers is not essential to account for propagation of excitation in apparent preferential directions from the sinoatrial (SA) node to the atrioventricular node. However, in the absence of fast conducting fibers, a slowly conducting segment in the intercaval region is necessary to achieve proper excitation of the interatrial septum. P-wave notches occur in the absence of specialized fast conducting atrial tracts and anisotropies due to fiber orientation. These notches are due to the atrial geometry and the separate contributions of the right atrium, left atrium, and interatrial septum to the P-waves, and become more pronounced as the pacemaker site shifts downward in the SA node. Thus, slight changes in the origin of excitation, which result in subtle changes in the atrial excitation isochrones, produce significant and complex changes in the simulated body surface P-waves.
Effects of angiotensin II on the blood flow and its distribution in fetal lambs.
Authors: Iwamoto H S , Rudolph A M
Published: June 2012

We studied the effects of intravenous infusion of angiotensin II on the circulation of the fetus in lambs in utero through chronically maintained intravascular catheters. Angiotensin II infused in doses of 29-280 ng/min per kg fetal weight resulted in an increase in plasma angiotensin II from a control value of 87 +/- 17 to 341 +/- 129 (mean +/- SE) pg/ml; these levels are similar to those observed following hemorrhage in fetal lambs. Fetal mean arterial blood pressure increased from 46 +/- 2.0 to 56 +/- 2.7 torr and fetal heart rate increased from 172 +/- 6 to 189 +/- 6 beats/min, an effect which was not altered by beta-adrenergic or cholinergic blockade. Fetal cardiac output and its distribution were measured before and during infusion of angiotensin II by the radionuclide-labeled microsphere technique. Combined ventricular output increased significantly from 526 +/- 32 to 616 +/- 24 ml/min per kg fetal body weight. Angiotensin constricted the umbilical-placental circulation as well as the gastrointestinal, renal, and thyroidal vascular beds. Angiotensin increased blood flow to the myocardium and markedly increased blood flow to the pulmonary circulation. These studies indicate that angiotensin II, at the plasma levels achieved with moderate hemorrhage, has marked influences on the circulation. The renin-angiotensin system may be important in the fetal response to stress.
Evidence that the velocity of sarcomere shortening in single frog atrial cardiac cells is load dependent.
Authors: Tarr M , Trank J W , Leiffer P , Shepherd N
Published: June 2012

Recent experiments using laser diffraction techniques to determine the time course and extent of sarcomere shortening in thin bundles of cardial tissue have given results which suggest that the velocity of sarcomere shortening in cardiac muscle is independent of the developed force (Nassar et al., 1974; Krueger and Pollack, 1975). However, the anatomical complexity of the intact tissue precludes a definite interpretation of the data, since the exact relationship between the force being borne by the total tissue to the force being borne by any observed group of sarcomeres is uncertain. The single frog atrial cell provides a simple cardiac preparation in which the relationship between sarcomere velocity and sarcomere force is well defined, since these cells are only 1-2 myofibrils wide. The purpose of the present investigation was to determine if sarcomere velocity in the single frog atrial cell is dependent on force by measuring the time course of sarcomere shortening in single cells under conditions in which the cell developed markedly different forces. The results presented in this paper give direct evidence that the velocity of sarcomere shortening in the single cardiac cell depends on the force being developed by the sarcomeres. Thus, cardiac sarcomeres have a type of force-velocity relationship, although the exact nature of this relationship could not be determined in these experiments.
Pressure-diameter relations during early diastole in dogs. Incompatibility with the concept of passive left ventricular filling.
Authors: Sabbah H N , Stein P D
Published: June 2012

We studied left ventricular (LV) pressure-diameter relations in 13 open-chest mongrel dogs to explore whether ventricular filling is passive, active, or a combination of both. Left ventricular internal diameter along the minor axis and thickness of the LV free wall were measured with ultrasonic dimension gauges. Pressures in the LV, left atrium (LA), and aorta were measured with catheter-tip micromanometers. Pressure in the LV during the rapid filling phase of diastole decreased from 13 +/- 1 mm Hg to 3 +/- 0.4 mm Hg (mean +/- SE). During this period, LV internal diameter increased from 32.6 +/- 1.5 to 36.7 +/- 1.5 mm, and this represented 49% of the total change of LV diameter that occurred during diastole. The pressure-diameter relation that we observed during the rapid phase of filling suggests that active enlargement rather than passive distension of the left ventricle occurred. Reduction of pressure within the left ventricle during rapid filling, while the ventricular diameter increased, appears to be due to forces within the LV wall that act to restore the LV to its diastolic dimensions. This allows the LV to draw blood from the atrium by creating a pressure in the LV that is lower than in the LA. On the other hand, during the latter part of diastole, following atrial contraction, the pressure-diameter relation suggests that the left ventricle undergoes passive distention.
The influence of circulating catecholamines and prostaglandins on canine renal hemodynamics during hemorrhage.
Authors: Henrich W L , Pettinger W A , Cronin R E
Published: June 2012

The relationship between circulating catecholamines and prostaglandins and the independent contribution of circulating catecholamines to renal vasoconstriction during hemorrhage is unknown. The renal hemodynamic effects of a 30% decrease in blood pressure by hemorrhage were therefore studied in three groups of anesthetized dogs which had undergone prior bilateral renal denervation. A constant unilateral infusion of the catecholamine antagonist phenoxybenzamine (POB, 0.2 micrograms/kg per min) into the renal artery during hemorrhage was also performed. In the control (C) dogs (n = 6), hemorrhage was not associated with significant changes in glomerular filtration rate (GFR) or renal blood flow (RBF) in either POB-infused and denervated or noninfused, denervated kidneys. In the second group of dogs (n = 8), pretreated with the prostaglandin inhibitor indomethacin (IN, 10 mg/kg, iv), POB-infused and denervated kidneys had a significantly higher GFR (30 vs. 23 ml/min, P less than 0.05) and RBF (180 vs. 130 ml/min, P less than 0.0-5) than contralateral denervated kidneys during the hemorrhage period. Similar results were observed in the third group of dogs (n = 6) pretreated with the chemically dissimilar prostaglandin inhibitor meclofenemate (M). Circulating plasma catecholamines increased to a similar degree in C (116 to 530 pg/ml, P less than 0.005), IN (116 to 488 pg/ml, P less than 0.005), and M (75 to 315 pg/ml, P less than 0.01) groups; the major part of this increase was due to an increase in plasma norepinephrine (NE). These results indicate that, in this model of hemorrhage, plasma NE exerts a moderate but significant renal vasoconstrictor effect which is unmasked by prostaglandin inhibition.
Relationship between blood flow direction and endothelial cell orientation at arterial branch sites in rabbits and mice.
Authors: Langille B L , Adamson S L
Published: June 2012

The orientation of endothelial cells near arterial branch sites has been compared with flow streamlines near the arterial wall. We detected cell orientation by examining cell impressions in vascular casts of rabbit and mouse arterial branch sites. Flow streamlines were assessed in glass models with flow parameters approximating mean in vivo values. At high Reynolds numbers (large arteries), secondary flow develop near branch sites, and this was reflected in the pattern of streamlines near the vessel wall. At symmetrical Y bifurcations, streamlines originating near the inner wall of the branches are directed toward the lateral wall; thus they appear to wind around the daughter vessels and merge on the lateral wall. A similar phenomenon was observed on a 90 degree side branch. When flow conditions in the Y bifurcation and side branch models approximated those at the iliac bifurcation and renal artery origin, respectively, the streamlines near the walls were almost identical to the patterns of endothelial cell orientation. At very low Reynolds numbers, no secondary flow phenomena occurred and streamlines followed branch geometry. This mimicked endothelial cell orientation in very small vessels. Hence the influence of mean blood flow on endothelial cell was well predicted by the model studies.
Energy turnover and mechanical properties of resting and contracting aortas and portal veins from normotensive and spontaneously hypertensive rats.
Authors: Arner A , Hellstrand P
Published: June 2012

Aortas and portal veins from spontaneously hypertensive rats (SHR) and matched normotensive Wistar-Kyoto rats (WKY) were studied with respect to their energy turnover and mechanical properties. Relaxed aortas fom SHR 16--17 weeks and 20--25 weeks of age were stiffer, had smaller circumference, and greater maximal active wall tension compared to WKY aortas. Active stress (forced/areas) was not different. Passive and active length-force relations of portal veins from 16 to 17-week-old SHR and WKY were not different. O2 consumption (JO2) and lactate production (JLA) were studied in aortas and portal veins from 20- to 25-week-old rats. In relaxed aortas, JO2 was 0.63 +/- 0.03 (n = 1) and 0.54 +/- 0.03 (n = 10) mu mol/min per g dry wt in SHR and WKY, respectively (P less than 0.05). On activation by high-K+ solution, JO2 increased with tension in a similar way in both groups. In contrast, JLA, about 0.85 mu mol/min per g, did not differ, and decreased with tension development. JO2 of relaxed portal veins, about 1.5 mu mol/min per g dry wt, and the increase in JO2 with contraction were not different between SHR and WKY, but the JO2-active stress relation was steeper in spontaneous activity than in Kv+ contractures. JLA was similar in SHR and WKY portal veins, about 1 mu mol/min per g, and unlike behavior of the aortas, it increased with tension. Thus it is evident that SHR show increased arterial metabolism, which is not accounted for by an increased energy demand of the contractile system.
Vascular permeability and transvascular fluid and protein transport in the dog lung.
Authors: Parker J C , Parker R E , Granger D N , Taylor A E
Published: June 2012

We used steady state lymph-to-plasma concentration ratios of six endogenous protein fractions (effective hydrodynamic radii of 37, 40, 44, 53, 100, and 120 A) to estimate pulmonary capillary permeability characteristics. Pulmonary lymph was collected from an afferent lymphatic to the left tracheobronchial lymph node, and left atrial pressure was elevated in steps until the lymphatic protein concentration obtained a constant value. Lymph flow and transvascular protein flux increased with each increase in left atrial pressure. Convective flux was the predominant mode of transport for the smaller fractions, and solvent-drag reflection coefficients increased as lymph flow increased. This dependency on lymph flow (capillary filtration) indicates a heteroporous membrane system. For lymph flows greater than five times control, the solvent-drag reflection coefficients were: 0.59 +/- 0.11, 0.52 +/- 0.06, 0.66 +/- 0.05, 0.70 +/- 0.05, 1.01 +/- 0.04, and 1.05 +/- 0.03 for the six fractions. Osmotic reflection coefficients estimated from the minimal lymph-to-plasma concentration ratios were: 0.50 +/- 0.03, 0.59 +/- 0.02, 0.67 +/- 0.04, 0.72 +/- 0.03, 0.94 +/- 0.01, and 0.96 +/- 0.01 for the six protein fractions. The osmotic reflection coefficients are consistent with a two- "pore" exchange model possessing equivalent pore radii of 80 and 200 A. Theoretical considerations indicate that only the two largest protein fractions (100 A and 120 A radii) achieved filtration-independent concentrations in pulmonary lymph, even at the highest filtration rates. This suggests that the reported osmotic reflection coefficients of the four small protein fractions underestimate their true values.
Effects of nitroglycerin on regional myocardial ischemia induced by atrial pacing in dogs.
Authors: Gerry J L , Schaff H V , Kallman C H , Flaherty J T
Published: June 2012

The exact mechanism or mechanisms by which nitroglycerin exerts its beneficial effect on pacing-induced regional myocardial ischemia has not been ellucidated previously. In an open-chest, anesthetized canine preparation a fixed, flow limiting stenosis was applied to the left anterior descending (LAD) coronary artery and heart rate was increased by atrial pacing. Mass spectrometry was used to measure myocardial oxygen (PmO2) and carbon dioxide (PmCO2) tensions. Myocardial blood flow was measured by the radioactive microsphere technique. Application of the stenosis resulted in regional decreases in PmO2 and increases in PmCO2 of greater magnitude in the subendocardial than in the subepicardial layer. Atrial pacing resulted in a further decrease in PmO2 and increase in PmCO2 as well as a reduction in subendocardial blood flow. Nitroglycerin (TNG) infusion reduced mean arterial pressure 20 mm Hg, resulting in a 14 mm Hg reduction in PmCO2 in the more ischemic subendocardial layer (P less than 0.05). Myocardial blood flow decreased in all regions; however, the magnitude of this decrease was less in the ischemic region. Addition of aortic constriction abolished both the afterload and preload lowering effects of nitroglycerin but improved ischemic zone blood flow. These data demonstrate that nitroglycerin reduces the severity of pacing-induced regional myocardial ischemia primarily by reducing the determinants of myocardial oxygen demand. We found that when these effects are counteracted, improvement in myocardial oxygen supply becomes the dominant mechanism.
Hypertension following arterial baroreceptor denervation in the unanesthetized dog.
Authors: Ito C S , Scher A M
Published: June 2012

Studies were conducted on unanesthetized dogs (1) in the control state, (2) after carotid sinus denervation plus section of the cervical aortic nerves (SCAD), and (3) after carotid sinus denervation plus section of intrathoracic vegal branches which innervate arterial and cardiopulmonary baroreceptors, the heart, lungs, and other structures (STD). Mean values and standard deviations of blood pressure and heart rate were measured during many 75-minute recording sessions. The control mean arterial pressure was 94.8 +/- 8.9 mm Hg. The mean pressure after SCAD was 105.5 +/- 9.5 mm Hg, 10.0 mm Hg higher (P less than 0.05) than in the control state, whereas after STD, the mean pressure was 119.5 +/- 16.8 mm Hg, 25.3 mm Hg higher (P less than 0.001) than in the control state. The standard deviation of pressure was increased (P less than 0.01) by either denervation procedure. The mean pressure after STD was higher than after SCAD (P less than 0.05). Ten of 12 animals with SCAD showed residual baroreceptor reflexes (seven from intrathoracic receptors) whereas, after STD, six of 11 animals showed reflexes (one from intrathoracic receptors). SCAD only occasionally produces denervation as complete as that produced by STD. A larger increase in arterial pressure follows a more complete denervation of vagally innervated baroreceptors. We believe that our procedures do not denervate all arterial baroreceptors. Chronic denervation of arterial baroreceptors leads to a widely varying, elevated arterial pressure. The increase in pressure has persisted more than 1 1/2 years.
The utilization by rabbit aorta of carbohydrates, fatty acids, ketone bodies, and amino acids as substrates for energy production.
Authors: Chace K V , Odessey R
Published: June 2012

The ability of rabbit aorta to oxidize various substrates was studied to determine which of these compounds may be energy substrates for vascular smooth muscle (VSM). Glucose, ketone bodies, medium-chain length fatty acids, branched-chain amino acids, and glutamine all are oxidized at comparable rates on a molar basis. Some other amino acids, long chain fatty acids, pyruvate and glycerol also are oxidized, but at lower rates. The oxidation of 6 amino acids could not be detected. VSM was found to release ketone bodies when incubated in leucine beta-hydroxybutyrate or octanoate. This suggests that the acetoacetyl CoA and/or acetoacetate derived from these substrates is not completely oxidized. The oxidation rate of several substrates when measured individually is inhibited by 50-80% by the presence of a combination of other substrates in the medium. Under these conditions, glucose is a minor substrate for oxidative metabolism accounting for only 5% of O2 consumption. The oxidation rate of all the exogenous substrates together is calculated to account for less than half of the oxygen consumption; this finding indicates that an endogenous substrate must also be utilized.
Characterization of [3H](+/-)carazolol binding to beta-adrenergic receptors. Application to study of beta-adrenergic receptor subtypes in canine ventricular myocardium and lung.
Authors: Manalan A S , Besch H R , Watanabe A M
Published: June 2012

[3H](+/-)Carazolol, a newly available beta-adrenergic receptor antagonist, can be used to characterize beta-adrenergic receptor subtypes present in membrane vesicles derived from canine ventricular myocardium and canine lung. [3H](+/-)Carazolol binding is saturable, of high affinity, and is displaceable by beta-adrenergic agents in accordance with their known pharmacological potencies. The interaction of carazolol with beta-adrenergic receptors is stereospecific; the (-) stereoisomer demonstrates greater potency than the (+) stereoisomer. Kinetic analysis of [3H](+/-)carazolol interaction with beta-adrenergic receptors suggests that presence of two phases of interaction, consistent with initial rapidly reversible "low" affinity association of ligand with receptor, followed by isomerization to form a high affinity, slowly reversible complex. Through use of a [3H](+/-)carazolol binding assay based on the high affinity complex, pharmacological specificities of beta-adrenergic receptor populations of canine myocardium and lung were quantified. Analysis using computer-assisted techniques suggests a beta 1/beta 2 receptor ratio of approximately 85%/15% for canine myocardium and 5%/95% for canine lung. In the absence of added guanine nucleotides, comparison of potencies of beta-adrenergic agonists in the two membrane systems suggests significant beta 2 selectivity of l-isoproterenol and l-epinephrine, and non-selectivity of norepinephrine. In the presence of saturating levels of guanine nucleotides, comparison of agonist potencies confirms the non-selectivity of l-isoproterenol and l-epinephrine, and beta 1 selectivity of norepinephrine. These results demonstrate that the state of guanine nucleotide regulation of receptors should be defined when examining agonist selectivities for beta-adrenergic receptor subtypes in vitro.
"Pressure-volume" relations in isolated cat trabecula.
Authors: Elzinga G , Westerhof N
Published: June 2012

We studied isolated cat trabecula under conditions closely resembling those present for muscle fibers in the left ventricular wall. The purpose of the study was to see if muscle contraction under those circumstances could be described by a time-varying compliance as reported for intact canine left ventricle. We found the time of the end of systole to depend on the history of contraction. This time varied between 100 and 160 msec as measured from the onset of contraction. Similar dependency, although less percentage-wise, was found by reanalysis for intact feline left ventricles. We conclude that the behavior of the canine left ventricle as a time-varying compliance may be related to the complex organization of the cardiac muscle fibers in the wall of the heart rather than to muscle properties.
Liposome concentration in canine ischemic myocardium and depolarized myocardial cells.
Authors: Mueller T M , Marcus M L , Mayer H E , Williams J K , Hermsmeyer K
Published: June 2012

To determine whether liposomes (microscopic phospholipid vesicles) may be useful in delivering drugs to a region of myocardial ischemia, we studied the concentration of positively charged and neutral liposomes containing 131I-albumin and horseradish peroxidase in ischemic myocardium of 20 dogs during the first 4 hours of experimental myocardial infarction. We studied the interaction of liposomes containing fluorescent dyes and horseradish peroxidase with isolated contracting cardiac myocytes. We found that positively charged and neutral liposomes accumulated in poorly perfused myocardium and that positively charged liposomes accumulated in the ischemic region to a greater extent than neutral liposomes [138 +/- 21 vs. 81 +/- 9% (mean +/- SE) of the concentration of liposomes in uninvolved myocardium]. Electron microscopic examination of this myocardium showed liposome contents to be located in the vascular space, in endothelial cells, and in ischemic myocytes. We found high potassium environment and that liposomal contents were scattered throughout the interior of the cells in the electron micrographs of some of the isolated myocytes. Anoxia alone for 20-30 minutes did not modify the liposome-isolated myocyte interaction or cause depolarization of the cells. We conclude that liposomes may be useful as drug carriers to depolarized ischemic myocardium, although significant uptake by normal myocardial cells cannot be expected with lecithin, cholesterol, and octadecylamine liposomes we used.
Effect of initial sarcomere length on sarcomere kinetics and force development in single frog atrial cardiac cells.
Authors: Tarr M , Trank J W , Goertz K K , Leiffer P
Published: June 2012

We studied sarcomere performance in single isolated intact frog atrial cells using techniques that allow direct measurement of sarcomere length and force. The purpose of this investigation was to determine whether length-dependent alterations in contractile activation occur in the single isolated cardiac cell. This was accomplished by determining the effect of initial sarcomere length on the time course of sarcomere shortening and force development during auxotonic twitch contractions. The results presented in this paper demonstrate that the velocity of sarcomere shortening, the rate of force development, and the magnitude of force development during auxotonic twitch contractions all increase as initial sarcomere length increases over the range of about 2 micrometers to greater than 3 micrometers. These results indicate that the level of contractile activation increases as initial sarcomere length increases. Also, results are presented that indicate that the rate of increase of contractile activation during a twitch contraction also increases as initial sarcomere length increases. These length-dependent effects on contractile activation in conjunction with the slow time course of contractile activation cause the force-velocity-length relationship to be time-dependent: i.e., the velocity of sarcomere shortening at a given sarcomere length and load depends on the time during the contraction when the sarcomere reaches that length. The results suggest that length-dependent alterations in contractile activation may play a major role in the improved contractile performance that accompanies an increase in initial sarcomere length in cardiac muscle.
Prostaglandin synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure.
Authors: Sraer J D , Moulonguet-Doleris L , Delarue F , Sraer J , Ardaillou R
Published: June 2012

In vitro PG synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure (ARF) was measured by radiometric high performance liquid chromatography after incubation with [14C]arachidonic acid and radioimmunoassay (RIA). The four PGs, 6-keto-PGF1 alpha, TXB2, PGF2 alpha, and PGE2 were each synthesized by glomeruli from both control and treated rats but the synthesis rates were greater after glycerol. This increase was not apparent 1 hour after injection but, at 24 hours, all PGs were produced in greater amounts by glomeruli of treated rats. Thus, we studied PGE2, PGE2 alpha, and TXB2 synthesis by glomeruli at various time intervals after induction of ARF using direct RIA, PGF 2 alpha and TXB2 synthesis were greater only at 24 hours and only in the presence of arachidonic acid, whereas PGE2 synthesis was greater at 24 hours, irrespective of arachidonic acid, but at 48 hours only with arachidonic acid. The stimulatory effect of arachidonic acid was always greater in glycerol-treated than in control rats for these three PGs in the later period, whereas a significant decrease for PGE2 was observed at 1 hour. The late increase in PG synthesis may be due to stimulation of the renin-angiotensin system since it was abolished in rats pretreated for 48 hours with captopril. A late increase in PG synthesis by the papilla of the treated rats also was observed. We concluded that any increase in the glomerular production of vasoconstrictor PGs could contribute to the maintenance of acute renal failure, whereas the early fall in the stimulatory effect of arachidonic acid on PGE2 synthesis could play a role in its initiation.
Decreased intercellular coupling after prolonged rapid stimulation in rabbit atrial muscle.
Authors: Bredikis J , Bukauskas F , Veteikis R
Published: June 2012

Driving rabbit atrial trabeculae at a rapid rate for 15 minutes resulted in a decrease in the space constant for electrotonic decay from an average of 670 to 440 micrometers. Input resistance, Rin, as measured by use of a double-barrelled microelectrode, increased from a mean value of 380 kOhms to one of 600 kOhms. The time to return to control values after the end of rapid driving was 20-60 minutes. Similar effects of rapid driving were observed in the presence of atropine, propranolol, and atropine plus propranolol and phentolamine. According to the theory of current spread in a three-dimensional syncytium, a rise of input resistance should be interpreted mainly as an increase of cell-to-cell resistance. We advance the hypothesis that, when driven at their maximal possible rate (or when fibrillating), cardiac cells gain Na+ ad Ca2+, and that this results in partial but reversible uncoupling.
Preferential sensitivity of the left canine purkinje system to cardiac glycosides.
Authors: Reiser J , Anderson G J
Published: June 2012

Previous studies have shown that the toxic effects of cardiac glycosides are not manifested uniformly throughout the myocardium. The purpose of our study was to determine whether cardiac glycosides exert different effects on the right vs. left peripheral Purkinje systems and to ascertain mechanisms involved. Control in vitro measurements of paired right and left canine Purkinje fibers showed higher spontaneous rates in left (24.2 +/- 1.75 beats/min) than in right (11.6 +/- 1.55 beats/min, P less than 0.01, n = 81) Purkinje fiber bundles. Following overdrive stimulation, left Purkinje fiber bundles also showed earlier escape beats. After ouabain exposure (2 X 10-7 M), left Purkinje fiber bundles showed earlier signs of toxicity in 20 of 28 experiments, as determined by changes in the maximum diastolic potential, the degree of diastolic depolarization, spontaneous escape intervals, and the magnitude of delayed after-depolarizations. The enhanced sensitivity of left Purkinje fiber bundles was independent of the extracellular potassium concentration and glycoside polarity, and was also observed in situ. We conclude that distal Purkinje fibers are functionally dissimilar and that the left Purkinje system shows greater sensitivity to cardiac glycosides than the right Purkinje system. These data also support the observation that digitalis-induced dysrhythmias arise in the left ventricle.
The coronary pressure-flow determinants left ventricular compliance in dogs.
Authors: Olsen C O , Attarian D E , Jones R N , Hill R C , Sink J D , Lee K L , Wechsler A S
Published: June 2012

Displacement of the left ventricular diastolic pressure-dimension relationship (change in compliance) has been observed with alterations in coronary perfusion pressure. The relative contribution of coronary (myocardial) blood flow, as compared with the perfusion pressure at which flow occurs, was studied in 10 dogs during diastolic relaxation potassium arrest during cardiopulmonary bypass. The normalized left ventricular pressure-dimension relationships, obtained during passive, gradual filling of the left ventricle (0-20 mm Hg) were shifted progressively to the left as coronary perfusion pressure was increased. Myocardial blood flow was 0.06 ml/mg per min +/- 0.02 ml/mg per min (mean +/- SEM) at a coronary perfusion pressure of 40 mm Hg and increased to 0.38 ml/mg per min +/- 0.11 ml/mg per min as the coronary perfusion pressure was raised to 120 mm Hg. Addition of adenosine significantly increased myocardial blood flow by 109% at a coronary perfusion pressure of 80 and by 147% at a coronary perfusion pressure of 120 mm Hg, but caused no additional significant shifts in the pressure-dimension relationships, compared to the same coronary perfusion pressures without adenosine. Coronary perfusion pressure, and not coronary blood flow, is a more direct determinant of cardiac diastolic properties.
Ultrastructural features of the innervation and smooth muscle of the rabbit facial vein, and their relationship to function.
Authors: Rowan R A , Bevan R D , Bevan J A
Published: June 2012

The purpose of this study was to determine to what extent the ultrastructure of the intramedial plexus of autonomic nerves and the smooth muscle of the rabbit facial vein could be correlated with the functional properties of this vessel. The mean observed widths of neuromuscular clefts were 250 nm in untreated control vessels, 260 in the dilated vein, and 390 in the contracted vein. Variation in the plane of section and in cell surface contours may lead to overestimation of cleft width, particularly in contracted vessels; the conclusion was reached, therefore, that the actual mean cleft width in this vessel, which may be closer to 200 nm, is relatively narrow in comparison with other blood vessels. There is probably little significant variation in cleft width with changes in vessel diameter. This narrow cleft correlates with the pronounced neurogenic response of this vessel. The smooth muscle cells of the facial vein appear to contain a relatively small amount of sarcoplasmic reticulum, which may be related to the dependence of maintained tone on extracellular calcium. Areas of close apposition of cell surfaces, with gaps of approximately 15 nm, may be related to propagation of electrical activity from one smooth muscle cell to another.
Heterogeneity of intracellular potassium activity and membrane potential in hypoxic guinea pig ventricle.
Authors: Baumgarten C M , Cohen C J , McDonald T F
Published: June 2012

The relationship between membrane potential (Em) and the potassium equilibrium potential (EK) was investigated in hypoxic guinea pig papillary muscle. After more than 8 hours of hypoxia, cells with near normal Em (-86.2 +/- 0.9 mV) and action potentials were observed. However, the intracellular potassium concentration ([K+]i) based on chemical analysis and the assumption that potassium was homogeneously distributed was 41.8 +/- 4.3 mM; the apparent EK was -55.7 +/- 2.9 mV, significantly positive to Em. Measurements with potassium ion-selective microelectrodes revealed that prolonged hypoxia results in at least two populations of cells with different characteristics. The first population had an intracellular potassium activity (aiK) of 101.5 +/- 1.9 mM, and EK was 4.7 mV negative to Em. In contrast, EK was 33.4 +/- 1.3 mV negative to Em in the second population. These cells also exhibited a reduced sensitivity to changes in bath potassium, and calculations suggest aiK was about 18 mM. The existence of cell populations with a near normal and very low aiK can explain the intermediate value of [K+]i calculated assuming a homogenous potassium distribution. Cells with near normal Em and action potentials represent the population with near normal aiK. Hypoxia may also cause non-uniform changes in other cellular characteristics.
Intracoronary adenosine deaminase reduces canine myocardial reactive hyperemia.
Authors: Saito D , Steinhart C R , Nixon D G , Olsson R A
Published: June 2012

We employed intracoronary infusions of calf intestine adenosine deaminase (ADA) to test the hypothesis that adenosine regulates coronary blood flow during myocardial reactive hyperemia (RH). Infusions of 4.5 U ADA/min per kg body weight into the left circumflex coronary artery of 10 open-chest dogs reversibly reduced repayment of flow debt by 30-39% (P less than 0.05) following 5-, 10-, 15-, 20-, and 30-second coronary occlusions, the percentage reduction being independent of occlusion length. ADA reduced peak RH flow rate (17%, P less than 0.05) only after 5-second occlusions. Intracoronary infusions of [131]ADA in seven dogs produced interstitial ADA concentrations between 1.2 and 13.1 U/ml in perfused myocardium and, in five of these dogs, 131I activity in the cardiac node was 1.8-35 times that of contiguous mediastinal tissue. Theophylline, a specific adenosine antagonist, reduced repayment of flow debt by 27-36% (P less than 0.02) in eight dogs, an effect similar to that of ADA. In six other dogs, ADA plus theophylline did not reduce RH flow debt repayment below that produced by ADA alone. This experiment confirms the contribution of adenosine to myocardial RH but shows that this nucleoside accounts for but a third of volume flow. Other, as yet unidentified, factors are collectively more important.
Postnatal age-related renal responses to hypoxemia in lambs.
Authors: Weismann D N , Clarke W R
Published: June 2012

The role of normocapnic hypoxemia (arterial PO2 33 +/- 7 torr for 30 minutes) in asphyxial renal failure and its modification by maturation of renal function was studied in 50 chronically catheterized, unanesthetized lambs of 2-38 days postnatal age. Arterial pH and PCO2 did not change significantly in response to hypoxemia in these lambs. Normocapnic hypoxemia was associated with (1) significant percent increases in arterial serum osmolality (1.82 +/- 2.96%, P = 0.0001), arterial blood lactate concentration (1009 +/- 2092%, P = 0.0018), arterial blood hematocrit (6 +/- 12%, P = 0.0016), arterial hemoglobin concentration (4.6 +/- 6.5%, P = 0.0004), arterial plasma vasopressin (2370 +/- 3340%, P = 0.0001), arterial plasma renin activity (153 +/- 230%, P = 0.0001), arterial plasma aldosterone (91.3 +/- 143%, P = 0.0001), and fractional sodium excretion rate (120 +/- 240%, P = 0.007); and (2) significant percent decline in glomerular filtration rate (-22.6 +/- 32.6%, P = 0.0003). Several responses to hypoxemia correlated significantly with postnatal age, including (1) positive correlation of postnatal age with percent change in blood osmolality (r = 0.36, P = 0.010), hematocrit (r = 0.48, P = 0.0005), hemoglobin (r = 0.59, P = 0.0004), and lactate (r = 0.72, P = 0.0001), suggesting greater water movement from the intravascular compartment in response to hypoxemia in more mature lambs; and (2) positive correlation of postnatal age with change in urinary flow rate (r = 0.66, P = 0.0001), urinary sodium excretion rate (r = 0.65, P = 0.0001), and osmolar clearance rate (r = 0.60, P = 0.0002), suggesting a greater effect of hypoxemia on the renal tubules to decrease sodium reabsorption in more mature kidneys. Thus, normocapnic hypoxemia may play a role in asphyxial renal failure, and the immature kidney does not have increased susceptibility to this condition.
Calcium ion-insensitive contraction of glycerinated porcine cardiac muscle fibers by Mg-inosine triphosphate. ITP as a tool to dissociate the contraction mechanism from the regulatory mechanism.
Authors: Toyo-oka T
Published: June 2012

The contraction of cardiac muscle that has been treated with glycerol requires Ca2+ (pCa 8-5), when MgATP is used as a substrate. In contrast, this preparation contracts, even in the absence of Ca2+ (pCa 8-10), when ATP is replaced by ITP. Ca2+ dependency was not observed after increasing free Ca2+ concentrations from pCa 8.0 to 5.0, or after increasing MgITP concentration from 5 to 80 mM. On the other hand, rabbit skeletal muscle fiber treated by the same method as cardiac muscle demonstrates Ca2+ dependency in the presence of both MgITP and MgATP, although this Ca2+ regulation is less in the presence of MgITP. Loss of Ca2+ dependency was confirmed by the finding that, in contrast to ATPase, the ITPase activity of cardiac myofibrils was not dependent on Ca2+ concentrations. Furthermore, the very fast tension responses (quick phases) following quick stretch and quick release were missing in MgITP, and the contractions were similar to rigor. These were not rigor however, because phosphate liberation from ITP continued, and muscle shortening occurred in MgITP. These findings suggest that MgITP dissociates the contraction mechanism from the regulatory mechanism, modulating the regulatory properties of cardiac muscle fiber.
Effect of Change in Air Temperature Upon Systemic Small and Large Vessel Resistance
Authors: HADDY F. J. , FLEISHMAN MALCOLM , SCOTT JERRY B.
Published: June 2012

Direct resistance measurements in the foreleg of the anesthetized dog show that the rise in total resistance following reduction of air temperature is due predominately to small vessel constriction and is based upon at least three different mechanisms. The large arteries and veins also constrict and evidence is presented which suggests that the venous and possibly the arterial resistance responses are predominately due to changing levels of circulating epinephrine, norepinephrine or both.
Influence of L-Norepinephrine Upon Cardiac Output in Anesthetized Dogs
Authors: LEVY MATTHEW N. , BRIND SHIRLEY H.
Published: June 2012

It was the purpose of this investigation to test again the general conclusion that norepinephrine augments cardiac output during experimental hemorrhagic hypotension but has no such effect on normal animals or man. Results are presented which fail to support this differential action in normal and hypotensive dogs and an explanation is offered for failure of the drug to increase cardiac output in human subjects.
Reflex Peripheral Venoconstriction Induced by Carotid Occlusion
Authors: SALZMAN EDWIN W.
Published: June 2012

The present investigation was designed to obtain additional evidence for the effect of carotid sinus reflexes on venous tone. It was found that occlusion of one or both common carotid arteries increases tension in a miniature balloon inserted into a peripheral vein. Deafferentation of the aortic arch by cervical vagotomy enhanced the venous response. The time course and magnitude of the venous reactions paralleled the increase in arterial pressure. It appears that the homeostatic increase in peripheral resistance as a result of reflex arteriolar constriction is complemented by a decrease in size of the peripheral venous reservoir.
Relation Between Work and Labile Phosphate Content in the Isolated Dog Heart
Authors: WOLLENBERGER ALBERT
Published: June 2012

Starling heart-lung preparations of the dog (with only minor differences in heart rate) were subjected to changes in work load to study their effect on the amount of labile phosphate in the left ventricle. While increasing the work load three to fourfold by increasing output caused no change, doubling the work load by increasing the resistance was accompanied by a marked reduction in labile phosphate. The data suggest that the heart expends phosphate bond energy chiefly in overcoming resistance rather than in systolic emptying.
A Humoral Influence on Cardiovascular Adjustments to Acute and Chronic Posthemorrhagic Anemia in Dogs
Authors: JUSTUS D. W. , CORNETT R. W. , HATCHER J. D.
Published: June 2012

The possibility that the increased cardiac output observed in severe anemia is due to a humoral mechanism was investigated by an assay procedure in which blood from anemic donor dogs was infused into normal assay dogs. Blood removed from anemic donors during the period of augmented cardiac output and infused into assay dogs produced cardiovascular changes which were statistically different from the changes observed with infusions of normal blood or blood removed from anemic donors when the cardiac output was not elevated.
Role of Autonomic Hormones on Left Ventricular Performance Continuously Analyzed by Electronic Computers
Authors: RUSHMER ROBERT F. , WEST THEODORE C. , Lobb Allan C. , Franklin Dean L. , Moss Robert W.
Published: June 2012

Ventricular responses during spontaneous activity by intact dogs have been studied by using electronic computors to continuously analyze ventricular function in terms of various parameters, including effective ventricular pressure, changes in left ventricular circumference or diameter, rate of change in ventricular dimensions, myocardial "power," myocardial "stroke work," "eumulative work" per unit time and heart rate. Simultaneous recordings of these various factors permit characterization and direct comparison of the nature and sequence of left ventricular responses during infusion of autonomic hormones, spontaneous activity or exercise. Intravenous infusion of catechol amines in "physiologic doses’ produces changes in ventricular performance which differ significantly from those observed during exercise, particularly with reference to heart rate. The left ventricle appears to be directly influenced by neural reflexes, some of which are probably initiated by higher centers of the nervous system.
Effect of Acute Cardiac Tamponade on Red Cell Volume, Total Plasma Protein and Plasma Volume
Authors: UNDERWOOD REX J. , GRISWOLD HERBERT E. , HURST WILLIAM A.
Published: June 2012

Acute heart failure was produced by cardiac tamponade in unsplenectomized and splencetomized dogs. The results indicate that splenic contraction was entirely responsible for the rise in hematocrit observed following tamponade in the unsplenectomized dogs. A fall in the hematocrit values of the splenectomized dogs and a reduction in total plasma proteins of both groups indicates an increase in plasma volume following tamponade. There was no evidence of sequestration of red cells.
Lipoprotein Patterns by Starch Electrophoresis in Idiopathic Hyperlipemia and Hypercholesteremia
Authors: PARONETTO FIORENZO , WANG CHUN-I , ADLERSBERG DAVID
Published: June 2012

Starch electrophoresis was employed for the study of the lipoprotein patterns in inborn errors of lipid metabolism. Idiopathic hyperlipemia was characterized by marked increases of cholesterol and phospholipid in the alpha-2-lipoprotein fraction of the serum whereas idiopathic hypercholesteremia showed an increase of these lipids in the beta-lipoprotein fraction. The cholesterol and phospholipid contents in the alpha-1-lipoprotein fractions were diminished in both metabolic errors.
Studies of Vitamin B Depletion in Perfused Hearts
Authors: ROBB JANE SANDS , CHANG IRENE C. L.
Published: June 2012

A progress report stated that perfused hearts could be maintained over a longer period if vitamin B complex were added to the perfusate. The present study comprises analyses of four of the B vitamins in muscle of control hearts, of hearts perfused with oxygenated Locke's solution and of hearts perfused with the same solution plus dihydropaveril. Statistically significant amounts of B vitamins disappear from the muscle during perfusion in comparison to values for control hearts.
Effect of Acute Fat Loads on Serum Lipids in Atherosclerosis
Authors: HORLICK Louis
Published: June 2012

Since the imposition of a lipid load might uncover latent defects in lipid absorption or transport, "normal" individuals, and those with atherosclerosis, were subjected to test meals of butter fat, and qualitative and quantitative aspects of serum lipids and lipoproteins were measured. In contrast to the metabolic defects in diabetes mellitus which can be uncovered by a glucose load, the metabolic faults in atherosclerosis are not readily infuenced by single or repeated high fat meals.
Role of Magnesium Ion in the Initiation of Ventricular Fibrillation Produced by Acute Coronary Occlusion
Authors: GARDEN NORMAN L. , STEINHAUS JOHN E.
Published: June 2012

The incidence of ventricular fibrillation following acute coronary occlusion in dogs was reduced by perfusing the ischemic area of the myocardium with Locke-Ringer's solution and solutions of magnesium ion in physiological saline. In contrast, normal serum concentrations of magnesium in 5 per cent dextrose appeared to induce ventricular fibrillation in these circumstances. The results suggest that changes in the concentration of magnesium and sodium ion in extracellular fluid may initiate ventricular fibrillation in the ischemic heart.
Ventricular Arrhythmias Induced by Sympathomimetic Amines in Unanesthetized Dogs Following Coronary Artery Occlusion
Authors: MALING HARRIET M. , MORAN NEIL C. , Williams Martha A.
Published: June 2012

Epinephrine and norepinephrine, in doses which cause little ectopic activity in unanesthetized normal dogs, produce exaggerated ectopic responses about the fourth day after coronary ligation, when the arrhythmias caused by the ligation per se have subsided. These responses persist for approximately 12 days after ligation and suggest reactivation of latent ectopic foci. Observations with methoxamine, isoproterenol, and atropine indicate that ventricular tachycardia is easily induced after occlusion by drugs which simultaneously stimulate the myocardium and slow the sinus node rate.
A Preliminary Reaction of Coagulation Factors Found in Plasama and Serum
Authors: MANN FRANK D.
Published: June 2012

This paper is concerned with the question of whether the coagulation factors in plasma and serum may react with each other before reacting with thromboplastin. The observation reported suggest an association between stable and labile factors.
Effect of Hydrocortisone on Acidotic Failure of the Isolated Heart
Authors: NAHAS GABRIEL G.
Published: June 2012

Acute myocardial failure observed when the denervated heart-lung preparation is rendered acidotic is mitigated if 5 to 10 mg. of hydrocortisone are administered to the preparation 12 to 15 min. before the onset of ventilation with high CO
2
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Chromatography Studies of the Excretion Products after Meralluride Administration in Normal Subjects and Cardiac Patients
Authors: MOYER JOHN H. , SEIBERT RICHARD A. , HANDLEY CARROLL A.
Published: June 2012

Separation of the urinary excretory products of the organomercurial diuretic, meralluride (Mercuhydrin) has been possible using adsorption chromatography. Practically all of the mercury is excreted in a form closely resembling the administered meralluride. Most of the excretion occurs within the first 6 hours in both cardiac patients and normal subjects. The amount of mercury excreted as degradation products is insufficient to produce diuresis. Therefore, it is concluded that the diuretic action of meralluride depends on the specific organic mercurial molecule.