bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrarenal vascular effects of angiotensin I and angiotensin II
Authors: Britton S. L.
Published: December 2017

The effects of angiotensin I (250 pmol) and angiotensin II (7.5 pmol) on total renal blood flow and its cortical distribution were examined in 25 dogs anesthetized with pentobarbital. These peptides were administered as bolus injections directly into the left renal artery. Right and left renal blood flows were measured with noncannulating electromagnetic flow probes. The distribution of renal cortical blood flow was measured with 15-micrometers radioactive microspheres. Because angiotensin I is converted to angiotensin II extrarenally as well as intrarenally, the distribution of renal blood flow in response to the bolus injection of angiotensin agonists was measured before these peptides could have recirculated through the kidney. This maneuver precluded the possibility that blood flow changes were due to the extrarenal formation of vasoactive metabolites of angiotensin I or angiotensin II. Control total renal blood flow averaged 3.0 +/- 0.1 ml.min-1.g kidney wt-1 and was decreased 25% by both angiotensin I and angiotensin II. Outer renal cortical flow (zone I) was 5.1 +/- 0.3 ml.min-1.g-1 and was decreased to 3.9 +/- 0.3 ml.min-1.g-1 by both angiotensin I and angiotensin II. On the average, angiotensin I decreased inner cortical renal blood flow from a control of 1.8 +/- 0.2 to 1.2 +/- 0.2 ml.min-1.g-1; angiotensin II decreased inner cortical renal blood flow from a control of 1.9 +/- 0.2 to 1.4 +/- 0.2 ml.min-1.g-1. Analysis on a per-experiment basis revealed that angiotensin I, compared with angiotensin II, produced a proportionally greater decrease in inner cortical renal blood flow relative to its effects on outer cortical blood flow.
The relative role of subendocardium and subepicardium in left ventricular mechanics
Authors: Sabbah H. N. , Marzilli M. , Stein P. D.
Published: December 2017

The purpose of this study was to determine whether differences of wall thickening and fiber shortening exist between the deep and superficial layers of the left ventricular (LV) wall during systole. By use of ultrasonic crystals, wall thickness and segment-length changes were studied in seven dogs, and changes of the internal and external diameter of the LV were studied in five dogs. Radiopaque markers were used in conjunction with ventriculograms to determine the changes of the internal and external volume of the LV in five additional dogs. The subendocardial portion of the LV wall accounted for 83% of wall thickening during diastole. Segments of the subendocardium shortened 18% during systole, whereas segments of the subepicardium shortened only 10%. A 22% reduction of the internal LV diameter occurred in comparison to only a 6% reduction of the external diameter during systole. Similar observations were made in relation to LV internal and external volumes. These results indicate that the subendocardium undergoes greater dimensional changes (both thickening and shortening) during systole than does the subepicardium.
Contractility of vascular smooth muscle: maximum ability to contract in response to a stimulus
Authors: Skaug N. , Detar R.
Published: December 2017

The reactivity of vascular smooth muscle observed under the usual steady-state conditions (termed the usual reactivity) is generally relatively labile to changes in the external environment (e.g., to changes in PO2 or [K]o). However, reactivity during brief exposure to ouabain is nearly always greater than the usual reactivity and is relatively stable. It is demonstrated that for any given stimulus (i.e., a given concentration of a particular agonist), this latter reactivity is always the maximum that can be produced under any given set of conditions. Accordingly, it is proposed that the usual reactivity may be expressed as the algebraic sum of two properties of vascular smooth muscle: contractility, relatively stable property, which is defined as the maximum ability to contract in response to a stimulus, and electrogenesis, a relatively labile property, which produces a sometimes dominating electrical influence that modulates reactivity by opposing contractility. It is further proposed that because of the fundamental importance of these two properties it is useful to categorize all changes in reactivity, depressing or enhancing, according to whether they involve changes in contractility or electrogenesis.
Chronic implantation of radiopaque beads on endocardium, midwall, and epicardium
Authors: Shoukas A. A. , Sagawa K. , Maughan W. L.
Published: December 2017

We have developed a method by which we can implant in chronic dog preparations over 200 radiopaque markers on the endocardial, midwall, and epicardial surfaces of the heart. The method is simple and fast and can allow for the determination of changes in local dimensions, shape, and volume in conscious dogs.
Platelets, von Willebrand factor, and prostaglandin I2
Authors: Moake J. L. , Tang S. S. , Olson J. D. , Troll J. H. , Cimo P. L. , Davies P. J.
Published: December 2017

Depending on the time of addition, prostaglandin I2 (PGI2; greater than or equal to 10(-9) M) either inhibits or reverses platelet agglutination mediated by human factor VIII-related von Willebrand factor activity (FVIIIvWF) and ristocetin, or bovine FVIIIvWF alone. 6-Keto-PGF1 alpha, the inactive metabolite of PGI2, is without effect, PGI2 inhibition is potentiated by the phosphodiesterase inhibitor, theophylline, and is not the result of PGI2 suppression of ADP release. PGI2 (+/- theophylline) does not inhibit ristocetin-induced binding of purified human 125I-FVIIIvWF multimers to washed platelets or to platelets treated with PGI2 and then formalin fixed (although subsequent agglutination of these platelets is impaired). Washed platelets treated previously with 2-aminoethylisothiouronium bromide (AET), an agent that reduces disulfide bonds and alters platelet membranes, also bind human 125I-FVIIIvWF multimers without agglutinating. We conclude that FVIIIvWF-mediated agglutination requires both functional platelet FVIIIvWF binding sites and platelet-platelet cohesion sites, and that platelet surface cohesion sites are altered by AET and PGI2. PGI2 from adjacent intact endothelial cells may prevent excessive platelet accumulation on exposed subendothelium without suppressing an essential hemostatic process--the binding of platelets to subendothelial FVIIIvWF.
Vascular volumes in isolated perfused guinea pig placenta
Authors: Schroder H. , Paul W. , Leichtweiss H. P.
Published: December 2017

Maternal and fetal vascular volumes were determined in 13 isolated artificially perfused guinea pig placentas by measuring mean transit times of an intravascular indicator (Evan's blue dye) at constant flow rates. When both maternal and fetal flow rates were 3.1 ml/min, the average maternal volume of the placenta was 1.85 +/- 0.54 (SD) ml, and the mean fetal volume was 0.92 +/- 0.2 (SD) ml. If calculated maternal volumes were corrected for the myometrial vascular volume and for the interlobium volume, the remaining volume attributable largely to the labyrinth averaged approximately 1.2 ml. When flow rates were changed on the fetal or the maternal side between 0 and 6.2 ml/min, vascular volumes also changed. For example, volumes increased directly with flow rates on that side of the placenta in which the flow change was introduced; in most cases, it decreased on the opposite side where the flow rates had not been altered. This intraplacental volume shift may be regarded as the basic event for the sluice flow phenomenon in placentas.
Cerebral blood flow during elevation of intracranial pressure: role of sympathetic nerves
Authors: Sadoshima S. , Thames M. , Heistad D.
Published: December 2017

This study was performed to examine effects of increased intracranial pressure on cerebral blood flow (CBF) and to determine if sympathetic nerves modulate this response. Intracranial pressure was raised by infusion of artificial cerebrospinal fluid into a lateral ventricle of rabbits. Increases in intracranial pressure were similar in the lateral ventricles and cisterna magna. Graded increases in intracranial pressure from base line of 7 to 96 mmHg produced graded reductions in CBF (measured with microspheres). Reductions in blood flow were heterogeneous: elevation of intracranial pressure from 7 +/- 1 to 46 +/- 3 (SE) mmHg reduced blood flow to the cerebrum by 33 +/- 5% and blood flow to the medulla by only 5 +/- 2% (P less than 0.05). Reduction of intracranial pressure to normal levels produced marked reactive hyperemia in all areas of the brain. Although sympathetic nerve traffic increased fivefold during intracranial hypertension, superior cervical ganglionectomy did not affect CBF. In other experiments, electrical stimulation of sympathetic nerves at 4 Hz reduced blood flow to skeletal muscle by 80% but did not affect CBF; stimulation at 15 Hz produced a modest reduction in CBF. We conclude that 1) during increases in intracranial pressure, blood flow is better preserved to the medulla than to the cerebrum despite similar intracranial pressure in the two areas and 2) intense reflex activation of sympathetic nerves during intracranial hypertension does not affect CBF.
Carotid sinus reflex vasoconstriction in right coronary circulation of dog and pig
Authors: Ely S. W. , Sawyer D. C. , Anderson D. L. , Scott J. B.
Published: December 2017

This study was designed to evaluate the effects of the sympathetic nervous system on right ventricular and right coronary hemodynamics in the anesthetized vagotomized dog and pig during constant-pressure coronary perfusion. Carotid occlusion in the dog resulted in an increase in heart rate, aortic pressure, right ventricular dP/dt, and a sustained 13% decrease in right coronary artery blood flow and a 14% increase in coronary vascular resistance. This coronary vasoconstriction was not modified during beta-blockade with propranolol but was prevented by alpha- blockade with phentolamine. Similar hemodynamic data was obtained in the pig and, in addition, it was found that the O2 consumption of the right ventricle is low (4.8 +/- 0.4 ml O2.min-1.100 g-1) and is only slightly increased (5.l5 +/- 0.8 ml.min-1.100 g-1) during carotid occlusion. These data suggest that baroreflex-mediated sympathetic stimulation to the heart evokes only a minor increase in metabolic activity in the right ventricular myocardium so that the direct neural (alpha-vasoconstrictor) effect predominates over the metabolic vasodilator mechanism.
Perturbation measurements of papillary muscle elasticity
Authors: Brady A. J. , Tan S. T. , Ricchiuti N. V.
Published: December 2017

Small step-length perturbations (less than 0.5% Lmax) have been applied to rabbit papillary muscle for the purpose of measuring muscle stiffness at rest and during isometric twitch-force development. These stiffness-force measurements were fitted to four mechanical analogs to evaluate whether any of the models adequately predict the mechanical properties of papillary muscle. Stiffness-force relations have been measured at varied initial muscle lengths so that a broad range of applicability of an analog could be evaluated. This study shows that none of the four experimentally definable analogs predicts the stiffness-force responses of the muscle over a physiological range of initial muscle lengths. A two-segment nonhomogeneous analog has the same stiffness-force characteristics as a six-parameter lumped model but cannot be differentiated from the lumped model without a measurement of segmental variations. It is concluded that the passive elastic elements of papillary muscle cannot be controlled only by the manipulation of total muscle length so as to deduce cross-bridge mechanical properties from whole-muscle measurements.
Small vessel and total coronary blood volume during intracoronary adenosine
Authors: Crystal G. J. , Downey H. F. , Bashour F. A.
Published: December 2017

The effect of a maximally dilating dose of intracoronary adenosine on total (CBV) and small-vessel blood volume (MSVBV, an index of open-capillary density), hematocrit (MSVHct), and related parameters of O2 supply-demand ratio was examined in left ventricular myocardium of anesthetized open-chest dogs. CBV was measured from washout of 51Cr-labeled red blood cells (RBC) and MSVBV and MSVHct from contents of 51Cr-RBC and plasma label, either 131I-serum albumin or 59Fe-siderophilin, in samples of myocardium and blood. Coronary blood flow (CBF) was measured by electromagnetic flowmeter. Myocardial oxygen consumption (MVO2) was computed with the Fick equation. Myocardial oxygen tension (MPO2) was measured with bare-tipped platinum electrodes. Adenosine raised CBV 75%, CBF, 574%, and MPO2 122%, but did not affect significantly MSVBV, MSVHct, or MVO2. These results indicate that infusion of adenosine into a coronary artery perfused at constant pressure causes relaxation of smooth muscle of arteriolar resistance vessels and of other vessels larger than 100 micrometers diam, but not that of the precapillary sphincters. This may be explained by the opposing action of increased MPO2 on the sphincters when flow increases. MSVHct was consistently much less than large-vessel Hct. This warrants combined use of red blood cell and plasma labels for accurate measurements of MSVBV.
Steady-state effects of extracellular potassium concentration on vascular smooth muscle reactivity
Authors: Skaug N. , Detar R.
Published: December 2017

Helical strips cut from small arteries taken from rabbit skeletal muscle were used to determine the steady-state effects of extracellular potassium concentration ([K]o) on the reactivity to epinephrine or norepinephrine. It was found that reactivity observed under the usual steady-state conditions (termed "usual reactivity") was depressed as steady-state [K]o was reduced from 8 to 1 mM. This depression reflected concurrent changes in two components of contraction: 1) a positive component (evaluated as reactivity during brief exposure to 10(-6) M ouabain) decreased when steady-state [K]o was reduced below approximately 5 mM, and 2) a negative component (evaluated indirectly as enhancement of reactivity produced by 10(-6) M ouabain) increased to a peak when steady-state [K]o was reduced from 8 to approximately 4-5 mM and decreased below this peak when steady-state [K]o was reduced below approximately 4-5 mM. It was also found that the magnitude of a reserve ouabain-sensitive negative component (demonstrated by abruptly increasing [K]o to 10.18 mM) increased from a minimum to a maximum level when steady-state [K]o was reduced from 6 to 3 mM. It is suggested that the effects of [K]o on the positive component of contraction, defined earlier as contractility, primarily involve some factor(s) other than transmembrane potential, whereas the effects on the negative component involve transmembrane potential exclusively and, in particular, the electrogenic potential. The latter suggestion constitutes the basis for use of the term electrogenesis in reference to this negative component.
Continuous measurement of cerebral blood flow in anesthetized cats and dogs
Authors: Busija D. W. , Heistad D. D. , Marcus M. L.
Published: December 2017

We have developed a method for virtually continuous measurement of changes in cerebral blood flow (CBF) in cats and dogs. CBF was computed by multiplying cross-sectional area (CSA) and mean blood velocity in a pial artery. CSA was determined by measuring pial artery diameter with an electronic micrometer every 2-4 s through a cranial window. Velocity was measured continuously with a pulsed Doppler crystal positioned under a pial artery. CBF was determined in 12 anesthetized cats during 1) control, 2) hypocapnia, 3) hypercapnia, and 4) hypercapnia plus hypertension. Microspheres were injected under steady-state conditions to compare the two methods. During control, the diameter of the cerebral arteries observed was 388 +/- 28 (SE) micrometers, and CBF measured with microspheres was 40 +/- 4 ml.min-1.100 g-1. CBF decreased 18 +/- 2% during hypocapnia and increased 152 +/- 36% during hypercapnia. During steady-state conditions, the correlation coefficient between changes in CBF (CSA X velocity and microspheres) was 0.94, and the slope of the regression line was 1.02. In similar studies on seven anesthetized dogs, the correlation coefficient between CSA X velocity and microspheres was 0.98, and the slope of the regression line was 0.94. We conclude that the product of CSA and blood velocity of a pial artery provides accurate on-line measurement of changes in CBF.
Brain adenosine concentration during hypoxia in rats
Authors: Winn H. R. , Rubio R. , Berne R. M.
Published: December 2017

We analyzed brain tissue for adenosine and its metabolites, inosine and hypoxanthine, in rats during acute (30 s) hypoxia and during sustained (5 min) hypoxia and hypocarbia. Within 30 s of the onset of hypoxia, adenosine levels were increased from 0.34 +/- 0.08 (SE) to 1.65 +/- 0.33 nmol/g (P less than 0.005), paralleling temporally the changes in cerebral blood flow. During sustained hypoxia and hypocarbia, brain tissue was sampled by a fast (freeze-blow) or slow (in situ) freezing method. With the freeze-blow technique, adenosine concentrations remained stable between arterial partial pressure of O2 (PaO2) greater than 200 and 100 mmHg, doubled at PaO2 = 50 mmHg, and increased sevenfold (P less than 0.005) when PaO2 reached 30 mmHg. No increases in adenosine or its metabolites were noted with the in situ technique. During hypocarbia (arterial CO2 partial pressure less than 20 mmHg), adenosine concentrations increased with both sampling techniques. Freezing times in brain were measured during in situ freezing and were increased during hypoxia and decreased during hypocarbia. In conclusion, 1) adenosine concentrations in brain are increased during hypoxia, and 2) the in situ technique in rat does not appear to be optimal for sampling brain tissue for subsequent measurement of adenosine under conditions where cerebral blood flow is increased.
Exercise plasma catecholamines in dogs: role of adrenals and cardiac nerve endings
Authors: Peronnet F. , Nadeau R. A. , de Champlain J. , Magrassi P. , Chatrand C.
Published: December 2017

The plasma norepinephrine concentration (NE, ng . ml-1) in the pulmonary artery of dogs increased above resting values (0.22 +/- 0.04) for moderate (0.53 +/- 0.06) and severe exercise (1.45 +/- 0.23) and during prolonged exercise of moderate intensity (2.06 +/- 0.14). The plasma epinephrine concentration (E) increased above resting values (0.14 +/- 0.04) for severe exercise only (0.76 +/- 0.10) or when moderate exercise was prolonged (1.81 +/- 0.24). The E response, which appeared greater than that found in humans, is probably related to the species difference in the vasomotor response to exercise between humans and dogs, the latter not being subjected to compensatory vasoconstriction in nonworking areas. The activity of the adrenal medulla is confirmed by the plasma catecholamine (CA) gradient between proximal and distal posterior vena cava at rest (0.20 +/- 0.09) and during short- (0.35 +/- 0.08) and long-duration exercise (1.37 +/- 0.23). On the contrary, the heart is not a source of plasma CA in dogs: coronary sinus CA did not exceed aortic CA at rest and for moderate exercise and was lower than aortic CA for severe exercise (4.80 +/- 0.25 vs. 6.55 +/- 0.76 ng . ml-1).. The sources of plasma NE remain unclear in exercising dogs. Significant amounts of NE may be released by the adrenal medulla.
Neurogenic suppression of carotid sinus reflexes by vagal afferents in sodium-depleted dogs
Authors: Szilagyi J. E. , Masaki Z. , Brosnihan K. B. , Ferrario C. M.
Published: December 2017

Reduction of sodium intake affects both the renin-angiotensin and sympathetic nervous systems, but the effects on the latter are less well understood. To clarify this relationship, the responsiveness of the baroreceptor reflex was compared in groups of normal and sodium-depleted dogs prepared with a single innervated carotid sinus and left vagus nerve after anesthesia with morphine-chloralose. Three weeks of sodium depletion did not affect the mean arterial blood pressure, but cardiac output (-50%) and stroke volume (-38%) were reduced, whereas there was a large compensatory increase in total peripheral resistance (115%). The pressor response to carotid occlusion in sodium-depleted dogs was significantly less (35 +/- 4 mmHg) than that obtained in normal dogs (61 +/- 5 mmHg). In the dogs treated with cholinergic blockade with atropine, this difference (-51%) persisted. In contrast, the pressor response to carotid occlusion in sodium-depleted dogs was significantly potentiated (112%) and restored in magnitude to that found in normal dogs after severing the only remaining vagus nerve. These data suggest that the cardiopulmonary and/or aortic vagal afferents are responsible for the blunting of baroreceptor reflexes during sodium depletion.
Contractile proteins and sarcoplasmic reticulum in physiologic cardiac hypertrophy
Authors: Malhotra A. , Penpargkul S. , Schaible T. , Scheuer J.
Published: December 2017

To study effects of physiologic hypertrophy on contractile protein ATPases and sarcoplasmic reticulum, hypertrophy was caused in female Wistar rats by a chronic swimming program. Nonhypertrophied hearts of female control sedentary rats and rats made to run on a treadmill program were also examined. The swimming program, but not the running program, resulted in a significant increase in heart weight. Actomyosin ATPase activity was also increased by 15% in the hearts of swimmers but not runners. Similar increases were observed for Ca2+-activated myosin ATPase activity and actin-activated ATPase of myosin. Sarcoplasmic reticulum from the hearts of swimmers showed increased calcium binding and calcium uptake as a function of time and of calcium concentration. Sarcoplasmic reticulum ATPase activities were not altered by hypertrophy. These findings in physiologic hypertrophy contrast with those of pathologic hypertrophy in which ATPase activity of contractile proteins and calcium binding and uptake of sarcoplasmic reticulum have generally been found to be depressed.
Continuous blood pressure measurement in rats with aortic baroreceptor deafferentation
Authors: Fink G. D. , Bryan W. J. , Mann M. , Osborn J. , Werber A.
Published: December 2017

The purpose of this study was to determine if once-daily arterial pressure measurements are a reliable estimate of actual time-averaged arterial pressure in neurogenic hypertensive rats. Male rats were subjected to either aortic baroreceptor deafferentation (ABD, n = 10) or sham operation (SO, n = 10). One to 3 mo later, arterial pressure (AP) was recorded from a chronic indwelling catheter in each rat for 72 continuous hours. Subsequently, AP was determined once a day (10- to 30-min recording periods) in each rat for an additional 3 consecutive days. Continuous recording yielded an average mean arterial pressure (MAP) of 104 +/- 2 mmHg in SO rats and an average mean MAP of 120 +/- 3 mmHg in ABD rats. Standard deviation of MAP measured every 5 min for 24 consecutive hours (as an index of pressure lability) was 8.0 +/- 0.4 mmHg in SO rats and 14.4 +/- 1.3 mmHg in ABD rats. Both of the above differences were statistically significant (P less than 0.05). The average MAP from daily measurements in the same rats was 107 +/- 3 mmHg in SO rats and 124 +/- 3 mmHg in ABD rats. Average pressure values were not statistically different for the two measurement techniques in either group of rats. Overall, there existed a significant correlation (r = 0.64, P less than 0.01) between MAP measured continuously and daily in the 20 rats studied. We conclude that daily direct measurement of MAP in conscious ABD rats yields a satisfactory estimate of actual time-averaged MAP in these rats despite their markedly increased MAP lability.
Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat
Authors: Haywood J. R. , Shaffer R. A. , Fastenow C. , Fink G. D. , Brody M. J.
Published: December 2017

Development of techniques for the continuous measurement of regional blood flow and vascular resistance in intact small animals has been impeded primarily by the bulkiness of flow probes. The availability of an ultrasonic pulsed Doppler flowmeter system enabled us to construct miniaturized probes using 1-mm-diameter piezoelectric crystals that emit a 20-mHz signal and receive the reflected sound waves from passing blood cells. The finished flow probe is approximately 2.5-4 mm long and 2 mm in cross-sectional diameter with lumen diameters appropriate for the rat, ranging from 0.7 to 1.2 mm. This report describes the materials and methods involved in constructing and implanting the probes in rats to monitor renal, mesenteric, and hindquarter blood flow velocity. The accuracy of the pulsed Doppler method in detecting changes in regional blood flow and vascular resistance was established by the demonstration of a highly significant correlation between velocity recorded from the Doppler unit and volume flow recorded simultaneously. These data indicate that the ultrasonic pulsed Doppler flowmeter provides the opportunity to measure changes in regional blood flow and vascular resistance in a conscious freely moving rat.
Microvascular rarefaction in spontaneously hypertensive rat cremaster muscle
Authors: Chen I. I. , Prewitt R. L. , Dowell R. F.
Published: December 2017

We have investigated the neural and local vascular effects on vessel length and surface area per unit volume in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) by quantitative stereology. Fourteen SHR and 14 KWY (70-130 g) were anesthetized with chloralose-urethan, and the cremaster muscle was exposed for microscopic observation. The large arterioles entering the muscle were termed the first order, and consecutive branches were termed second-, third-, and fourth-order arterioles. The data were collected in three consecutive states: innervated, denervated, and vasodilated with nitroprusside. The third- and fourth-order arteriole and capillary lengths per unit volume in the SHR were less than those of the WKY in all three states. The vessel surface area per unit volume was also reduced in the SHR. Denervation and sodium nitroprusside (Nipride) resulted in larger percent increases in vessel length and surface area in the SHR than in the WKY. We conclude that in the SHR cremaster muscle there are fewer terminal arterioles and capillaries anatomically present, and, under resting conditions, a greater percentage but similar absolute number of them are closed to flow.
Bimodal relationship between sinus node arterial distension and sinus nodal automaticity
Authors: Musgrave G. E.
Published: December 2017

In the isolated buffer perfused canine sinus node the effect of either an increase or decrease in perfusion rate (PR), and hence sinus node (SN) arterial pressure (PSNA), on the frequency of sinus nodal depolarization (SDF) is bimodal. SDF decreased from 121.9 +/- 6.1 to 101.4 +/- 6.0 depolarizations/min as PR and PSNA increased from 1 to 4 ml/min and from 18.7 +/- 3.8 to 45.1 +/- 7.3 mmHg, respectively. Further increasing PR from 4 to 10 ml/mn (PSNA increasing from 45.1 +/- 7.3 to 94.0 +/- 14.1 mmHg) caused SDF to increase from 101.4 +/- 6.0 to 121.0 +/- 7.4 depolarizations/min. With respect to the PR, SDF is logarithmically related to the relative degree to which the SN artery is distended, the degree of SN arterial distension being determined by the change in SN arterial resistance (R) with respect to PR (dR/dPR). This relationship is defined by the equation: SDF = 9.23 1n(—dR/dPR) + 99.7. While these results support the existence of a mechanism for autoregulation of sinus nodal automaticity, they indicate that it is considerably more complex than previously envisioned.
Detection of delayed ventricular activation on the body surface in dogs
Authors: Simson M. B. , Euler D. , Michelson E. L. , Falcone R. A. , Spear J. F. , Moore E. N.
Published: December 2017

This study describes a noninvasive method for detecting delayed ventricular activation, caused by ischemia, on the body surface. Signal averaging and a newly developed high-pass digital filter were used. The filter has the property that it does not create an artifact or ring after the QRS complex ends, thereby allowing the detection of microvolt-level potentials that occur immediately after the QRS complex. Eleven dogs were studied before and during acute ischemia induced by coronary artery ligation and latex embolization. The ischemic region was mapped with bipolar electrodes and, after the chest was rapidly closed, signal-averaged recordings were made from the body surface. Repeated cycles of ventricular mapping and signal averaging were performed. In each dog, delayed and fractionated electrograms were recorded directly from the ischemic epicardium that lasted a maximum of 118 +/- 18 ms after QRS onset. The duration of the ventricular electrograms varied with time. Whenever delayed epicardial electrograms were recorded, filtered signal-averaged leads showed microvolt-level potentials early in the S-T segment that were continuous with the QRS complex. The duration of ventricular activation, as measured from the bipolar electrograms and from the filtered signal-averaged leads, correlated well (r = 0.93, P less than 0.001). Because of the absence of filter ringing, low-level potentials could be detected less than 40 ms after the QRS complex ended. This study demonstrates that microvolt-level potentials arising from delayed ventricular activation can be reliably detected on the body surface, even when they occur just after the QRS complex.
Effect of inotropic interventions on rate of change of ventricular diastolic dimensions
Authors: Sabbah H. N. , Stein P. D.
Published: December 2017

The effects of inotropic interventions upon the maximal rate of change of left ventricular (LV) wall thickness and internal diameter during early diastole were measured in nine open-chest dogs by ultrasonic-dimension gauges. Isoproterenol increased the maximal rate of wall thickening during systole from 28 +/- 3 to 48 +/- 5 (SE) mm/s (P less than 0.001), whereas it had no effect on the maximal rate of wall thinning during early diastole, 40 +/- 4 vs. 42 +/- 4 mm/s [not significant (NS)]. Isoproterenol also increased the maximal rate of reduction of the LV diameter during systole from 87 +/- 6 to 125 +/- 8 mm/s (P less than 0.001), whereas it had little effect on the maximal rate of increase of the diameter during early diastole, 79 +/- 6 vs. 87 +/- 4 mm/s (NS). Similarly, propranolol had a direct effect on the maximal rate of wall thickening and LV diameter reduction during systole, but it had little or no effect on their counterparts during early diastole. These observations support the concept that alterations of the contractile state need not be accompanied by a concomitant effect on relaxation.
Mechanisms of mitral valve motion during diastole
Authors: Yellin E. L. , Peskin C. , Yoran C. , Koenigsberg M. , Matsumoto M. , Laniado S. , McQueen D. , Shore D. , Frater R. W.
Published: December 2017

To examine the mechanisms of mitral valve motion in mid diastole and at closure, we simultaneously measured mitral flow (electromagnetic), valve motion (echo), and atrioventricular pressures (micromanometer). Peak valve excursion (E point) occurs early 46 +/- 7 ms) after opening and always precedes peak flow; therefore, mid-diastolic closing motion (EF slope) is not due to flow deceleration or vortex formation. Large variations in peak flow are accompanied by small variations in valve excursion (coefficient of variation 41 vs. 12%, respectively). We conclude that the valve overshoots its equilibrium position and that the chordae produce tension on the valve during diastole. This approach is supported by data from papillary muscle rupture, prolonged P-R interval, and mathematical modeling. We offer a valve-closure theory unifying chordal tension, flow deceleration, and vortices, with chordal tension as a necessary condition for the proper function of the other two. Nevertheless, prolonged periods of diastasis and ventricular premature contractions indicate that competent valve closure may occur in the absence of vortices and flow deceleration.
Effects of antenatal glucocorticoid administration on ductus arteriosus of preterm lambs
Authors: Clyman R. I. , Mauray F. , Roman C. , Heymann M. A. , Ballard P. L. , Rudolph A. M. , Payne B.
Published: December 2017

We have previously shown that the incidence of patent ductus arteriosus (PDA) in premature infants whose mothers received prenatal glucocorticoid therapy was significantly lower than that of an untreated group. In addition, the incidence of respiratory distress syndrome was lower in the treated than in the untreated group. To determine whether glucocorticoids affect the ductus arteriosus itself, we studied the effects of a 48-h intravenous infusion of 1 mg/h hydrocortisone in prematurely born lambs (120-129 days, 0.84 gestation). Estimations of ductus patency were made on 1-h-old lambs by radioactive microsphere injections. We found that hydrocortisone infusions facilitate the closure of the ductus without altering the severity of respiratory distress in premature lambs. In the lamb, prostaglandin E2 (PGE2) inhibits the ability of the ductus to contract in response to O2. Because production of PGE2 has been shown to be inhibited by hydrocortisone in several isolated organ systems, we measured PGE2 plasma concentrations in treated and untreated animals. We found circulating PGE2 concentrations to be similar in the two groups; furthermore, release of PGE2 by isolated ductal rings in vitro was similar in treated and untreated animals. This contradicts the hypothesis that diminished PGE2 concentrations, either circulating or in the tissue, are the cause for ductus arteriosus closure in hydrocortisone-treated animals. However, hydrocortisone treatment decreases the sensitivity of the ductus arteriosus in vitro to the relaxing action of PGE2. These findings suggest that glucocorticoid treatment decreases the incidence of PDA in premature infants by affecting the interaction of PGE2 with ductal tissue.
Effect of sympathectomy on arterial and venous changes in renal hypertensive rats
Authors: Simon G.
Published: December 2017

Arterial pressure-flow and venous pressure-volume relationships were measured at maximal vasodilatation in the denervated pump-perfused hindquarters of four groups of rats: 1) neonatally sympathectomized (guanethidine-injected and adrenal-demedullated), one-kidney, one-clip hypertensive (n = 9); 2) sympathectomized, sham-operated, unilaterally nephrectomized control (n = 10); 3) sham-sympathectomized, one-kidney, one-clip hypertensive (n = 8); and 4) sham-sympathectomized, sham-operated, unilaterally nephrectomized control (n = 9). Dry defatted weight of anatomically defined segments of the aorta and vena cava in the four groups of rats also was measured. Significant rises in arterial pressure developed in sympathectomized rats after clipping of the renal artery and contralateral nephrectomy. Arterial pressure-flow curves were shifted toward the pressure axis (P less than 0.01) in clipped rats whether sympathectomized or not. In sympathectomized clipped rats, there was also a shift of the venous pressure-volume curves toward the pressure axis (P less than 0.05). The same degree of hypertrophy of the aorta was found in sympathectomized and sham-sympathectomized clipped rats. The findings indicate that in renal hypertensive rats structural changes of both large arteries and veins may develop in the absence of an intact sympathoadrenergic system.
A circuit for measuring peak potential
Authors: McGillivray R. , Wald R. W.
Published: December 2017

The measurement of maximal potential is an integral part of several biological signal analyzers. We designed a circuit, which, unlike previously described devices that perform this function, is capable of picking a positive peak at below ground potentials or a negative peak above ground. Other features include user-selected decay characteristics, allowing beta-to-beat following and rejection of base-line noise. The circuit was implemented and tested with intracellular signals recorded from cardiac Purkinje fibers.
Ionic activities in cardiac muscle cells and application of ion-selective microelectrodes
Authors: Lee C. O.
Published: December 2017

Intracellular activities of K, Na, H, Cl, and Ca ions are kept at an optimal level for maintenance of normal cellular functions. Furthermore, many cellular functions are regulated directly or indirectly by these ion activities in cells. The use of ion-selective microelectrodes has emerged as the only method for measuring directly and continuously intracellular ion activities of intact cells. In recent years, they have been extensively used for measurements of intracellular ion activities in cardiac muscle and other tissues. This article concerns both intracellular ion activities of cardiac muscle and intracellular application of ion-selective microelectrodes. Intracellular ion activities in cardiac muscle cells have been measured under several experimental conditions, such as changes in ion composition of bathing fluid and exposure to certain drugs. This approach has provided significant information about electrochemical potentials of ions, membrane transport, and cellular functions related to ion activities. Relevant data and information is presented for K+, Na+, H+, Cl-, and Ca2+. Although ion-selective microelectrodes are widely used, this technique has certain assumptions, problems, and limitations that vary with the types of microelectrodes. The appendix of this article reviews basic principles for intracellular application of ion-selective microelectrodes and examines pertinent assumptions, problems, and issues. Particular features of K+-, Na+-, H+-, Cl--, and Ca2+-selective microelectrodes are described.
Hypophysectomy alters cardiorespiratory variables: central effects of pituitary endorphins in shock
Authors: Holaday J. W. , O'Hara M. , Faden A. I.
Published: December 2017

The possible involvement of pituitary endorphins in the pathophysiology of shock was evaluated by measuring cardiorespiratory variables after naloxone injection in conscious hypophysectomized and sham-hypophysectomized rats subjected to controlled hemorrhage. Additionally, the role of the central nervous system (CNS) in mediating the cardiodepressant effects of endorphins in shock was studied. After the induction of hypovolemic shock (20 min at below 40 mmHg), hypophysectomized and sham-hypophysectomized rats received intraventricular (ivt) injections of naloxone HCl (10 micrograms) or an equivalent volume of saline (20 microliters over 20 s). In sham-hypophysectomized rats, both injections significantly elevated mean arterial pressure and pulse pressure; however, the increase produced by naloxone was significantly greater than that produced by saline. By contrast, hypophysectomized rats showed no response to naloxone or saline. Intravenous (iv) administration of naloxone HCl (3 mg/kg) or saline to these same hypophysectomized rats 15 min after ivt administration had no additional cardiovascular effects; as before, only animals with intact pituitaries responded to naloxone. Heart rate and respiration rate were unaffected by ivt or iv naloxone. From these data we suggest that pituitary endorphins contribute to the pathophysiology of hypovolemic shock, at least in part through actions within the CNS.
Distribution of maternal and fetal blood flow within cotyledons of the sheep placenta
Authors: Power G. G. , Dale P. S. , Nelson P. S.
Published: December 2017

These studies explore the distribution of blood flow among small samples of placental tissue. Labeled microspheres (14 +/- 1 micrometers, SD) were injected into the left ventricle of six unanesthetized ewes and into the jugular vein of the fetuses in utero. A total of 3,576 samples weighing 31 +/- 11 (SD) mg were taken from 17 cotyledons and counted for flow labels. Maternal and fetal blood flow within the cotyledons were both normally distributed with standard deviations of 44%. The maternal-fetal blood flow ratio was less than 0.5 in 9% of the cotyledon, between 0.5 and 1.5 in 70%, and greater than 1.5 in 21%. Errors caused by the method were estimated to contribute less than 10% of the flow variances. Maternal and fetal blood flows were significantly correlated (r = 0.57, P less than 0.001), and both exhibited spatial organization. Calculations based on mathematical models suggested that the observed distribution of the ratio of maternal to fetal blood flow may explain about 50% of the uterine-umbilical venous oxygen tension difference. It was concluded that the samples studied were small in comparison with the dimensions of placental oxygen exchange but may have been similar in size to the dimensions of blood flow control.
Effects of increased plasma viscosity and red blood cell aggregation on blood viscosity in vivo
Authors: Gustafsson L. , Appelgren L. , Myrvold H. E.
Published: December 2017

The effects of increased plasma viscosity and induced red blood cell (RBC) aggregation on apparent viscosity of blood in vivo in the skeletal muscle of the dog were studied. Apparent viscosity in vivo was determined in the isolated and vasodilated calf muscles of one hindlimb by comparing pressure-flow relationships for RBC suspensions with pressure-flow relationships for a Newtonian solution of known viscosity. RBC suspensions of increased plasma viscosity with and without RBC aggregation were obtained by substituting plasma with isoviscous solutions of high- and low-molecular-weight dextran in saline. Hematocrits of the suspensions were adjusted to either 45 or 60%. The viscosities of the suspensions in vitro were determined in a Wells-Brookfield viscometer. Apparent viscosity of blood in vivo was found to be mainly dependent on the viscosity of plasma. RBC aggregation had no significant influence on the viscosity in vivo.
Functional evaluation of coronary collateral development in conscious dogs
Authors: Tomoike H. , Franklin D. , Kemper W. S. , McKown D. , Ross J.
Published: December 2017

Gradual coronary constriction was elicited in conscious dogs by means of an implanted ameroid coronary constrictor. The functional state of the coronary collateral circulation was serially evaluated by means of regional contractile responses, using brief occlusions of the left circumflex coronary artery and strenuous running in the field. Although resting regional myocardial function was unchanged throughout the study, regional myocardial shortening during coronary occlusion decreased to 9% of control at 3-4 days after the operation; it then recovered progressively to 24% at 7-9 days, 45% at 15-18 days, and 94% at 20-24 days. Concomitantly, reactive hyperemia measured with a flowmeter declined from 300% at 3-4 days to 228, 88, and 0% at 7-9, 15-18, and 20-24 days, respectively. A bout of running held 21 days after the ameroid implant when resting regional function was well maintained induced severe regional and global dysfunction. These findings indicate the usefulness of regional myocardial contractile responses in assessing coronary collateral reserve.
Effect of oxygen on arteriolar dimensions and blood flow in cat sartorius muscle
Authors: Sullivan S. M. , Johnson P. C.
Published: December 2017

The effect of O2 on arteriolar internal diameter, dual-slit velocity, and volume flow was studied by intravital microscopy in isolated autoperfused cat sartorius muscle. The muscle surface was covered with silicone oil, and gas mixtures containing 0, 5, 10, or 20% O2 in N2 were introduced over the muscle. When the O2 concentration was increased from 0 to 10%, arteriolar diameter, dual-slit velocity, and volume flow decreased on the average by 11 +/- 4, 30 +/- 29, and 37 +/- 13%, respectively. Under 20% O2, these parameters decrease by an additional 9 +/- 5, 29 +/- 10, and 30 +/- 14%, respectively. Percentage reduction in the diameter of large and small arterioles located at the same depth in the muscle were not significantly different. Conversely, the fall in volume flow was significantly greater in small arterioles. The lesser flow decrease in large vessels may reflect the fact that large vessels also feed deep muscle layers where the change in tissue O2 tension (PO2) is less. Our results do not support the hypothesis that small arterioles are intrinsically more sensitive to changes in tissue PO2.
Lack of a direct metabolic effect of fructose, 1,6-diphosphate in ischemic myocardium
Authors: Eddy L. J. , Chambers D. , Honig S. , Downey J. M.
Published: December 2017

Fructose 1,6-diphosphate (FdP) reportedly protects ischemic myocardium. To determine whether this is a direct action on the heart, we used a canine model in which two coronary arteries were perfused at identical but reduced rates. Into one artery we infused FdP (total doses of 400 mg or 1.8 g) while the other received 0.9% NaCl. After 1 h, biopsies were taken from a normal region and the two ischemic regions and were analyzed for ATP, phosphocreatine (PC), and lactate content. In the 0.9% NaCl-treated ischemic tissue, ATP and PC fell to half the nonischemic levels. The FdP-treated tissue exhibited high-energy phosphate levels similar to the 0.9% NaCl-treated tissue with no significant differences between the two ischemic areas. Lactate levels in both ischemic areas were elevated threefold above nonischemic levels. Contractility studies showed that infusion of FdP directly into the coronary artery depressed contractility in both nonischemic and ischemic conditions. Our data show that, if FdP does have a protective action in ischemia, it is not through a direct action on the heart.
Twitch potentiation by rest in canine ventricular muscle: effects of theophylline
Authors: Endoh M. , Iijima T.
Published: December 2017

Short rest of the regular stimulation of the isolated canine right ventricular muscle induced a large transient increase of subsequent twitch tension (rest-twitch potentiation, RTP). This RTP attained the maximum level when the rest period was 120 s and decayed progressively at longer rest periods. The rate of regular stimulation prior to rest affected the degree of RTP but not the time course of RTP. The action potential duration was prolonged progressively after rest until 120 s and maintained this level at longer rest periods. Under the same experimental condition, RTP was not induced in the rabbit papillary muscle. Theophylline, caffeine, and epinephrine increased the strength of steady-state contraction, whereas RTP was inhibited by theophylline and caffeine and unaffected by epinephrine. Manganese and D 600 significantly reduced the strength of steady-state contraction but did not affect the degree of RTP. These results indicate that RTP is induced via a mechanism different from that regulating the steady-state contraction.