bluuebunny/crossref_metadata_2025 huggingface dataset:
Contractile responses to ouabain and K+-free solution in aorta from hypertensive rats
Authors: Moreland R. S. , Major T. C. , Webb R. C.
Published: December 2017

This study characterizes isometric force development in response to ouabain and K+-free solution in isolated aortic strips from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR aortas were more sensitive to ouabain than those from WKY (threshold: SHR, 3.1 X 10(-5) M; WKY, 25.6 X 10(-5) M), and force development in response to 10(-3) M ouabain was greater in SHR (SHR, 586 +/- 51 mg; WKY, 245 +/- 24 mg). Monensin, a Na+ ionophore, potentiated contractile responses to ouabain, whereas amiloride, a Na+ channel blocker, and low Na+ solutions depressed contractile responses to ouabain. Contractile responses of SHR aortic strips to K+-free solution were faster than those of WKY aortic strips [time to half-maximal response (t1/2): SHR, 24 +/- 5 min; WKY, 47 +/- 4 min]. Maximal force development by aortic strips from SHR in response to K+-free solution was not different from that of WKY aortic strips (SHR, 808 +/- 34 mg; WKY, 750 +/- 37 mg). Monensin (10(-5) M) increased the rate of force development to K+-free solution to a greater extent in WKY aortic strips than in those from SHR (t1/2: SHR, 3 +/- 1 min; WKY, 4 +/- 2 min). Amiloride and low Na+ solution depressed contractile responses to K+-free solution in both SHR and WKY aortic strips. These observations demonstrate that SHR aortas are more responsive to ouabain and K+-free solution compared with WKY aortas. Contractile responses to ouabain and K+-free solution were sensitive to experimental interventions that alter transmembrane Na+ movements.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular relaxation in the filling and nonfilling intact canine heart
Authors: Yellin E. L. , Hori M. , Yoran C. , Sonnenblick E. H. , Gabbay S. , Frater R. W.
Published: December 2017

We studied left ventricular relaxation in the filling and transiently nonfilling working hearts of seven open-chest pentobarbital-anesthetized dogs by totally occluding the mitral annulus during one systole. In the completely isovolumic nonfilling cycle, the ventricle relaxes to a lower pressure minimum (usually negative) than in the normal filling cycle. By clamping the ventricle at end systole, we determined the pressure asymptote (Poo) under dynamic conditions. With this information, we evaluated the validity of a monoexponential characterization of relaxation. P = (P0 - Poo) exp(-t/T) + Poo (T, time constant, P0, pressure at t = 0). Plots of In(P-Poo) versus t are nonlinear and concave to the origin, thereby revealing that late relaxation is more rapid than predicted by a monoexponential relation. Nevertheless, the monoexponential T remains a useful index of relaxation and correlates well with other temporal indexes (isovolumic relaxation time and relaxation half-time). When T is calculated from a filling cycle by assuming a zero pressure asymptote, i.e., the conventional way, there is no significant difference with the true value based on the nonfilling cycle.
Some consequences of capillary permeability to macromolecules: Starling's hypothesis reconsidered
Authors: Renkin E. M.
Published: December 2017

Starling's hypothesis ascribes fluid movements across capillary walls to the interaction of hydrostatic and colloid osmotic forces. For 90 years it has been recognized as the basis of plasma-to-interstitial fluid balance. Its original statement was based on the notion of capillary impermeability to plasma proteins. However, as knowledge of transcapillary exchange of plasma proteins developed, its formulation was progressively modified to allow for protein transport and for interaction of protein transport with volume flow. The most important aspects of the conceptual evolution of Starling's hypothesis are reviewed in the text of this lecture.
Acute resetting of baroreceptor reflex in rabbits: a central component
Authors: Kunze D. L.
Published: December 2017

Electrical stimulation of the aortic nerve of the anesthetized rabbit was used to determine whether there is a central nervous system component to acute resetting of the baroreceptor reflex. After stimulation of the aortic nerve for 5 min at 10 Hz, a ramp test stimulus to the nerve produced a reflex arterial pressure response that was attenuated as compared with that produced by the same ramp prior to the five-min stimulation period. Renal sympathetic nerve activity was recorded simultaneously to determine whether a reduction in the magnitude of the reflex inhibition of sympathetic activity produced by the depressor nerve stimulation could account for the attenuated arterial pressure response. Renal activity during the test ramp was reduced to the same value both before and after the constant stimulus period and thus did not correlate with the attenuated pressure response. There was, however, prolonged inhibition of tonic sympathetic activity after the 5-min stimulus period such that during the test stimulus there was less sympathetic activity to inhibit. The results were similar when sympathetic activity was recorded from branches of the sciatic nerve and from thoracic postganglionic nerves. In these nerves the period of prolonged inhibition after aortic nerve stimulation was up to 5 min. The attenuated pressure response to baroreceptor nerve stimulation after a constant stimulus appears to reflect the reduced change in sympathetic activity rather than the value to which the sympathetic activity falls.
Denervation increases myogenic tone in a resistance artery in the growing rabbit ear
Authors: Mangiarua E. I. , Joyce E. H. , Bevan R. D.
Published: December 2017

The effect of chronic sympathetic and sensory denervation of the growing rabbit ear vasculature on myogenic tone in a resistance artery was studied. Unilateral superior cervical ganglionectomy and section of greater and anterior auricular nerves were performed at 4 wk of age. Compared with the contralateral control, 2 and 6 wk later, the denervated artery developed greater stretch-dependent myogenic tone. This phenomenon may partially account for the return of tone described in the denervated ear vasculature.
Myocardial extraction and retention of 2-iododesmethylimipramine: a novel flow marker
Authors: Little S. E. , Link J. M. , Krohn K. A. , Bassingthwaighte J. B.
Published: December 2017

An ideal deposition marker for measuring regional flow is completely extracted during transcapillary passage and permanently retained. beta-Labeled desmethylimipramine ([3H]DMI) is a nearly ideal flow marker. To obtain gamma- and positron-emitting markers, DMI was iodinated to form 2-iododesmethylimipramine (IDMI). IDMI was more lipophilic than DMI. In isolated saline-perfused rabbit hearts its transorgan extraction was greater than 99%; and retention was greater than 98% at 5 min at mean flows of up to 3.5 ml X g-1 X min-1. During washout, the fractional escape rate was less than 0.1% X min-1 and was independent of flow. In isolated blood-perfused rabbit hearts, extraction was still 98%, but retention was as low as 86% after 5 min at a flow of 1.6 ml X g-1 X min-1. The fractional escape rate was up to 2% X min-1 but independent of flow. Despite this relatively rapid loss, regional IDMI deposition remains proportional to regional flow for many minutes. Therefore IDMI is useful as an externally detectable "molecular microsphere" for myocardial flow imaging in vivo.
Platelet activating factors alters calcium homeostasis in cultured vascular endothelial cells
Authors: Brock T. A. , Gimbrone M. A.
Published: December 2017

Platelet activating factor (1-O-alkyl-2-acetyl-sn-glycerol-3-phosphorylcholine; PAF), a potent in vivo mediator of allergic and inflammatory reactions, induced a rapid (onset less than 30 s), concentration-dependent (threshold approximately 10(-11) M, half-maximal approximately 10(-10) M, maximal approximately 10(-8)-10(-7) M) efflux of 45Ca2+ from preloaded cultured bovine aortic endothelial cells (BAEC). In contrast, deacetylated and other PAF analogues were essentially ineffective. PAF (10(-7) M) was also shown to increase cytosolic free calcium (49 +/- 5%) in suspensions of quin 2 (calcium-sensitive fluorescent dye)-loaded BAEC. PAF-stimulated 45Ca2+ efflux was not blocked by aspirin treatment (100 or 500 microM, 30 min). In the absence of external calcium, PAF was still highly effective in stimulating unidirectional 45Ca2+ efflux, thus suggesting that PAF mobilized a sequestered pool of intracellular calcium. CV-3988, a PAF antagonist, inhibited PAF-stimulated 45Ca2+ efflux in a dose-dependent manner. Pretreatment of BAEC with PAF (10(-8) M, 15 min), but not with other PAF analogues, resulted in a decrease in subsequent PAF-stimulated 45Ca2+ efflux, thus suggesting an agonist-specific desensitization. PAF also stimulated a 30% net decrease in the equilibrium 45Ca2+ content of BAEC within 1 min, which gradually recovered to prestimulus levels in 10-15 min. PAF-stimulated 45Ca2+ efflux was also observed in endothelial cells cultured from human umbilical vein and baboon cephalic vein but not from cultured human dermal fibroblasts or bovine aortic smooth muscle. These studies provide direct evidence for agonist- and cell-specific effects of PAF on vascular endothelium.
Prostaglandins do not mediate arteriolar oxygen reactivity
Authors: Jackson W. F.
Published: December 2017

The hypothesis that prostaglandins mediate arteriolar O2 reactivity was tested by assessing the effects of cyclooxygenase and phospholipase A2 inhibitors on the O2 responses of arterioles in superfused hamster cheek pouch and hamster and rat cremaster muscle preparations by use of intravital microscopy. Superfusion of these three preparations with the cyclooxygenase inhibitor indomethacin (50 microM) completely inhibited the response of the vessels to exogenous arachidonic acid but had no effect on the arteriolar constriction induced by elevation of superfusion solution PO2 from 15 to 150 mmHg. Similar results were obtained in the hamster cheek pouch with another cyclooxygenase inhibitor, meclofenamate, or when indomethacin (5-50 mg/kg) was administered systemically. Dexamethasone (12.7 microM) and quinacrine (10 microM), two reported inhibitors of phospholipase A2, also had no significant effect on arteriolar O2 reactivity in the cheek pouch. At 50 microM, quinacrine significantly depressed arteriolar reactivity to O2, adenosine, methacholine, and phenylephrine, suggesting nonspecific effects. These data do not support the hypothesis that prostaglandins mediate arteriolar O2 reactivity.
Alpha 1-adrenergic constriction limits coronary flow and cardiac function in running dogs
Authors: Gwirtz P. A. , Overn S. P. , Mass H. J. , Jones C. E.
Published: December 2017

Modulation of coronary blood flow and cardiac function by alpha 1-adrenergic receptors was examined in dogs during strenuous exercise. Fifteen dogs were chronically instrumented to measure left circumflex blood flow, heart rate, regional left ventricular function (systolic shortening, and rate of shortening), and global left ventricular function (left ventricular pressure, and dP/dt). The specific postsynaptic alpha 1-receptor blocker prazosin (0.5 mg) and nonselective alpha-receptor blocker phentolamine (1.0 mg) were injected through an indwelling circumflex artery catheter to produce local adrenergic blockade of the posterior left ventricular region during exercise. Exercise significantly increased heart rate, left ventricular systolic pressure, dP/dt, segment shortening and rate of shortening, and coronary blood flow. Both prazosin and phentolamine caused similar additional increases in dP/dt by 21 +/- 4%, in rate of shortening in the posterior region by 37 +/- 6%, and in myocardial O2 consumption by 26 +/- 11%, which were associated with a 21 +/- 3% increase in coronary flow during exercise but no change in O2 extraction. Similar results were obtained when dogs were beta-blocked with either atenolol (1.0 mg ic) or propranolol (1.0 mg ic) prior to exercise. These data suggest that an alpha 1-vasoconstriction modulates O2 delivery to myocardial tissue and limits both coronary vasodilation and cardiac function during exercise.
Adenosine regulates blood flow and glucose uptake in adipose tissue of dogs
Authors: Martin S. E. , Bockman E. L.
Published: December 2017

Intravenous norepinephrine increases glycerol release and blood flow in adipose tissue. The vasodilation may be an indirect effect of norepinephrine through the production of adenosine. Adenosine increases glucose uptake and inhibits lipolysis in vitro. To test whether adenosine regulates blood flow and/or metabolism in vivo, adenosine deaminase (ADA) was infused intra-arterially into the inguinal fat pads of anesthetized dogs. In unstimulated tissues, ADA (n = 7) significantly increased vascular resistance and significantly decreased glucose uptake compared with the effects of a control (boiled deaminase, n = 6) infusion. ADA completely blocked the norepinephrine-induced vasodilation (n = 6). No potentiation of basal or catecholamine-stimulated lipolysis was observed with ADA. The presence of ADA in the interstitial space was verified by analysis of lymph effluents. Interstitial levels of ADA were inversely correlated with the tissue contents of adenosine. These data support the hypothesis that adenosine is a regulator of blood flow in basal and stimulated adipose tissue. Adenosine also appears to regulate glucose uptake, but not lipolysis, in vivo.
Factors regulating basal metabolism of the isolated perfused rabbit heart
Authors: Gibbs C. L. , Kotsanas G.
Published: December 2017

Basal metabolism has been measured in isolated whole hearts from rabbits and compared with myothermic and polarographic measurements on isolated papillary muscles. Hearts were perfused at constant pressure (Langendorff method) using a modified Krebs-Henseleit solution (KH) with glucose as substrate. Higher levels of basal O2 consumption (MVO2) and coronary flow (CF) were observed when arrest was induced by calcium depletion (low Ca; 0.1 mM CaCl2, 10.0 mM KCl) rather than by potassium excess (high K; 30.0 mM KCl). The metabolic rate of high K arrested hearts was close to earlier myothermic estimates (J. Mol. Cell. Cardiol. 16: 953-962, 1984); polarographic values, however, were about twofold higher, and somewhat higher than the value obtained in low Ca arrested hearts. The addition of erythrocytes, albumin, or dextran significantly reduced CF but did not substantially alter basal MVO2. Basal metabolic rate was substrate- and O2 tension-dependent, and under all experimental conditions there was linear relationship between MVO2 and CF. Extrapolations to zero flow showed that the basal MVO2 values so obtained were similar in low Ca or high K and were not altered by the presence of erythrocytes. Our results show that there are several factors regulating basal metabolism.
Age-related differences in effect of exercise training on cardiac muscle function in rats
Authors: Li Y. , Lincoln T. , Mendelowitz D. , Grossman W. , Wei J. Y.
Published: December 2017

To test the hypothesis that age may alter the effect of exercise training on myocardial function, we trained young adult (4-5 mo at study initiation) and old (21 mo at initiation) male Fischer 344 rats to run on a rodent treadmill 5 days/wk for 4.5 mo and compared their myocardial function with that of age-matched sedentary controls. Right ventricular papillary muscles were isolated from the young adult and aged animals and stimulated at the length at which developed isometric tension was maximal to contract isometrically at 12/min, bathed in oxygenated modified Krebs solution, and studied at 28 degrees, 32 degrees, 35 degrees, and 38 degrees C. In the absence of cardiac hypertrophy, exercise training significantly reversed the age-related prolongation of isometric contraction duration in the senescent rat (P less than 0.001). However, exercise training prolonged contraction duration in the young adult rat (P less than 0.05). The relaxation phase was more sensitive than the contraction phase to changes in temperature, especially in the aged rat (P less than 0.02). The ratio of developed tension to time-to-peak tension of the isometric twitch was not affected by exercise training. Because exercise training affects cardiac function in opposite directions from young adulthood to senescence, caution is advised in extrapolating results from exercise studies in young adult rats to populations of older animals.
Right heart pressures and blood-gas tensions in ponies during exercise and laryngeal hemiplegia
Authors: Manohar M.
Published: December 2017

Right atrial, right ventricular, and pulmonary artery pressures, along with change in pleural pressure, were determined with catheter-tipped micromanometers in two groups of ponies at rest, as well as during moderate (trot; heart rate = 180 beats . min-1) and severe (gallop; heart rate = 220 beats . min-1) exercise performed on a treadmill. Group A (n = 8) ponies served as controls, and group B ponies (n = 6) had laryngeal hemiplegia (LH) induced by sectioning the left recurrent laryngeal nerve 20-29 days before the study. It was observed that LH ponies could not gallop for more than 45-90 s. With both levels of exertion, pressures in the right atrium, right ventricle, and pulmonary artery increased very significantly in normal ponies. The change in pleural pressure of galloping ponies was 30.4 +/- 2.9 cmH2O, and the respiratory (and stride) frequency was 138 +/- 4 breaths . min-1. During severe exercise in normal ponies, the systolic, mean, and diastolic pressures in the pulmonary artery were 107 +/- 7, 63.5 +/- 4.2, and 46 +/- 4 mmHg, despite the fact that no alveolar hypoxia could be detected. In LH ponies pulmonary artery pressures rose to levels observed in normal ponies, but during galloping, the change in pleural pressure (delta Ppl) (92 +/- 6 cmH2O) was three times that in normal ponies, and there was no synchronization of respiratory (86 +/- 6 breaths . min-1) frequency to stride frequency (142 +/- 3 strides . min-1). Despite these respiratory adjustments (decreased frequency and increased delta Ppl), arterial PO2 decreased and arterial PCO2 increased in galloping LH ponies.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium effects on contractility and heat production in mammalian myocardium
Authors: Ponce-Hornos J. E. , Taquini A. C.
Published: December 2017

The effects of changing external Ca concentration ([Ca]o) on contractile parameters and heat production were investigated in the interventricular rabbit septa and the dog papillary muscle. Double reciprocal plots of tension development as a function of [Ca]o yielded half-maximal activation values of 1.04 +/- 0.17 and 2.8 +/- 0.7 mM Ca for the septum and papillary muscle, respectively. Resting heat rate was similar in both preparations, 1.9 +/- 0.08 mW . g-1 for the septum and 1.7 +/- 0.07 mW . g-1 for the papillary muscle, and it was not altered by changes in [Ca]o. Active heat production (Ha) normalized per unit of force developed (19 +/- 1.3 microJ . mN-1 . g-1) for the septum and the dimensionless ratio Ha/(To . lo), (0.30 +/- 0.02) for the papillary muscle, where To is the isometric tension and lo, the muscle length, remained unaltered with changes in [Ca]o. Total heat production per beat normalized per unit of force developed (Ht/T) for the septum and the ratio Ht/(To . lo) for the papillary muscle decreased hyperbolically with [Ca]o. Therefore, as a result of the unaltered economy of the contractile system and the unchanged resting heat rate, muscle economy improves as [Ca]o approaches physiological levels. Further increase in [Ca]o, over the physiological levels, can only slightly improve muscle economy.
Prostaglandins stimulate calcium-linked changes in heart mitochondrial respiration
Authors: Karmazyn M.
Published: December 2017

This study was done to determine the influence of prostaglandins (PGs) on oxidative phosphorylation and Ca-related changes in cardiac mitochondria. For most of the experiments mitochondria were isolated by using a nagarse-homogenization combination method that yields both subsarcolemmal and interfibrillar populations. When Ca (30-420 microM) was added a progressive stimulation in resting respiration was observed. Similarly, preaddition of Ca inhibited subsequent oxidative phosphorylation when ADP was added to the same preparation. The effect of calcium was enhanced by pretreating mitochondria with PGs E2, F2 alpha, and I2 (prostacyclin). Three PG concentrations, 100 pg/ml, 1 ng/ml, and 10 ng/ml were evaluated. For the most part the effect of PGs was concentration dependent with the exception of PGE2, which showed no effect at the highest concentration. The effects of PGs were observed when both NADH (pyruvate-malate) and succinate-linked respiratory substrates were used. Similar effects were evident when mitochondria were harvested using a non-nagarse homogenization method that yields a primarily subsarcolemmal population, although this preparation exhibited substantially higher sensitivity to Ca. None of the PGs had any direct effect on either resting respiration rate or oxidative phosphorylation in the absence of Ca, irrespective of isolation procedure or choice of substrate. The study demonstrates that PGs can augment Ca-related changes in cardiac mitochondrial respiration through an as yet unknown mechanism. The results may be important in understanding the role of endogenously synthesized PGs in cardiac pathology associated with defective intracellular Ca homeostasis.
Body fluid volumes in rats with mestranol-induced hypertension
Authors: Fowler W. L. , Johnson J. A. , Kurz K. D. , Zeigler D. W. , Dostal D. E. , Payne C. G.
Published: December 2017

Because estrogens have been reported to produce sodium retention, this study investigated the possibility that hypertension in rats resulting from the ingestion of an estrogen used as an oral contraceptive could be due to increases in body fluid volumes. Female rats were given feed containing mestranol for 1, 3, and 6 mo; control rats were given the feed without mestranol. The mestranol-treated rats had higher arterial pressures than the controls only after 6 mo of treatment. Plasma volume, extracellular fluid volume, and total body water were measured in each rat by the distribution volumes of radioiodinated serum albumin, 35SO4, and tritiated water, respectively. Values for blood volume, interstitial fluid volume, and intracellular fluid volume were derived from these measurements. These body fluid volumes, expressed per 100 g of body weight, were not different between the mestranol-treated rats and their controls at any of the three treatment times. Due to differences in body weight and lean body mass between the mestranol-treated and the control rats, these volumes also were expressed per 100 g of lean body mass. Again, no differences were observed between the mestranol-treated rats and the control rats for any of these body fluid compartments at any of the treatment times. These studies, therefore, were unable to provide evidence that increases in body fluid volumes contributed to the elevated arterial pressure in this rat model of oral contraceptive hypertension.
Evidence for a vasodilatory effect of vasopressin in the conscious rat
Authors: Walker B. R.
Published: December 2017

Experiments were performed on conscious, chronically instrumented rats to determine the cardiovascular effects of intravenous arginine vasopressin (AVP) with and without V1-vasopressinergic antagonist administration. This design allowed the assessment of the cardiovascular effects of high circulating levels of AVP in the absence of the direct vasoconstrictor properties of the hormone. One group of rats (n = 10) were administered a constant infusion of AVP (2.5 mU/min iv) for 40 min and demonstrated increased mean arterial blood pressure (MABP) and total peripheral resistance (TPR), while heart rate (HR) and cardiac output (CO) fell. Another group of animals (n = 7) also received AVP for 40 min; however, at 25 min of the infusion, 10 micrograms/kg of d(CH2)5Tyr(Me)AVP was given intravenously. Administration of this V1-vasopressinergic antagonist caused MABP and TPR to fall below pre-infusion levels, although AVP infusion continued. HR and CO returned to control. Additional experiments showed no effect of the antagonist (n = 8) or AVP vehicle (n = 7) alone on the measured hemodynamic variables. In addition, pretreatment with the cyclooxygenase inhibitor meclofenamate did not affect the observed vasodilation in AVP-treated animals given the antagonist. A final group of animals (n = 6) was pretreated with d(CH2)5Tyr(Me)AVP prior to AVP infusion. On AVP administration, TPR fell in all animals. These data suggest that AVP exerts a vasodilatory effect unrelated to stimulation of V1-vasopressinergic receptors or arterial baroreceptors, which may partially offset the potent vasoconstrictor properties of this peptide.
Effect of hematocrit on cerebral blood flow
Authors: Hudak M. L. , Koehler R. C. , Rosenberg A. A. , Traystman R. J. , Jones M. D.
Published: December 2017

Cerebral blood flow (CBF) falls as hematocrit (Hct) rises. Investigators have differed on the relative importance of the increases in arterial O2 content (CaO2) and red blood cell concentration in mediating the fall. Our experimental protocol attempted to determine the independent effects of these two variables. In 13 unanesthetized lambs (less than 7 days old) we measured arterial and sagittal sinus blood gases, and O2 contents, and CBF (microsphere technique) at oxyhemoglobin Hcts of approximately 20 and 40% and after an isovolemic exchange transfusion with a mixture of normal and pure methemoglobin (MHb) containing red cells. Following MHb exchange, Hct rose (19.7 +/- 0.3 vs. 38.2 +/- 0.4%, mean +/- SEM) with little change in CaO2 (9.3 +/- 0.2 vs. 10.0 +/- 0.3 vol%). Arterial PCO2, pH, mean arterial blood pressure, and cerebral O2 consumption (CMRO2) did not change. However, CBF fell (153 +/- 11 vs. 110 +/- 7 ml . 100 g-1 . min-1). CBF declined further when CaO2 rose (17.3 +/- 0.5 vol%) at the higher oxyhemoglobin Hct (36.9 +/- 0.8%). We calculated that the increase in red cell concentration accounted for 56% of the decrease in CBF that ordinarily occurs as Hct rises from 20 to 40%. The effect of red cell concentration on CBF varied among individual animals. It correlated closely (r = -0.77) with the initial cerebral fractional O2 extraction [E = CMRO2/(CBF X CaO2)]. Animals with the most luxuriant O2 supply (CBF X CaO2) relative to demand (CMRO2) had the greatest decrements in CBF as red blood cell concentration rose.
Technique with lock-in amplifier for real-time measurement of tricuspid valve annulus area
Authors: Tamiya K. , Higashidate M. , Kikkawa S.
Published: December 2017

A new measuring system that permits real-time registration of the tricuspid valve annular area (TVA) using lock-in amplifier is devised and applied in open-chest anesthetized dogs. The tricuspid valve annulus was stitched with a fine, pliable, metal thread made of 10 30-micron urethane resin-coated copper wires during inflow occlusion. Both ends of the thread were guided out from the right atrium through a single pinhole in the right atrial wall. The signal intensity induced in the sense loop is linearly related to the area encircled by the thread, i.e., the area of the tricuspid annulus. During control state, TVA varied by an average of 24.5% (3.8-46.5%) of its maximum. Presystolic peak and valley of TVA due to atrial contraction and a decrease in TVA during ventricular ejection were generally observed. An increase in TVA during the initial portion of isovolumic contraction phase was prominent in dogs with filariasis, whereas in the other dogs it was not.
Functional interdependence of discrete vagal projections to SA and AV nodes
Authors: O'Toole M. F. , Ardell J. L. , Randall W. C.
Published: December 2017

Dynamic modulation of chronotropic and dromotropic function was evaluated in anesthetized dogs before and after selective parasympathectomy of the atrioventricular (AV) node. Vagal and cardiac sympathetic efferent nerves were decentralized, and the distal cut ends of the cervical vagi were stimulated at frequencies from 1 to 25 Hz with step-wise voltage changes. To investigate parasympathetic modulation of AV conduction, stimulations were performed with and without atrial pacing. After determination of chronotropic and dromotropic responses, in the intact state, selective AV node parasympathectomy was performed as previously described [Am. J. Physiol. 248 (Heart Circ. Physiol. 17): H61-H68, 1985]. Stimulation protocols were then repeated. Control results in intact animals reveal a parallel and finely balanced vagal regulation of chronotropic and dromotropic responses over a wide range of frequency stimulations. Conversely, selective parasympathectomy of the AV node interrupts extrinsic vagal modulation of AV conduction without affecting parasympathetic control of chronotropic function. The dynamic balance of chronotropic and dromotropic function, modulated by extrinsic vagal input, reflects the parallel activation of functionally and anatomically distinct parasympathetic projections to the sinoatrial (SA) and AV nodal tissue. Thus present experiments allow a more detailed examination of vagal innervation of the SA and AV nodes, the importance of their balance through neuroregulation, and progress toward understanding the pathophysiology of disturbances to this balance.
Meclofenamate potentiates vasoreactivity to alpha-adrenergic stimulation in chronically hypoxic guinea pigs
Authors: Harrison G. L. , McMurtry I. F. , Moore L. G.
Published: December 2017

The aim of this study was to examine the effect of chronic hypoxia on systemic vascular reactivity and the role of prostaglandins in modulating the vascular response to chronic hypoxia. Meclofenamate, a prostaglandin synthesis inhibitor, increased the systemic vascular resistance response to the alpha-adrenergic agonist, phenylephrine, in awake, unrestrained guinea pigs exposed for 6 wk to high altitude (3,900 m), but it did not alter the response in animals kept at low altitude (1,600 m). The systemic vascular resistance response to phenylephrine before treatment with meclofenamate was the same in high- and low-altitude animals. Meclofenamate also increased the contractile response to phenylephrine in aortic rings isolated from high- but not low-altitude animals. The systemic vascular resistance response to angiotensin II was the same in high- and low-altitude animals, and meclofenamate increased this response to the same extent in both groups. Thus chronic hypoxia appeared to enhance vascular production of dilator prostaglandins during beta-adrenergic stimulation.
Effects of calcium entry blockade on left ventricular dynamics in exercising dogs
Authors: Walsh R. A. , Cleary F. X. , O'Rourke R. A.
Published: December 2017

To study the previously undefined effects of calcium entry blockade on left ventricular (LV) function and coronary blood flow during dynamic exercise we gave intravenous equihypotensive infusions of nifedipine (10 +/- 4 SE micrograms X kg-1 X min-1), diltiazem (60 +/- 8 micrograms X kg-1 X min-1), and verapamil (52 +/- 7 micrograms X kg-1 X min-1) before and after intravenous propranolol (2 mg/kg) to chronically instrumented dogs at rest and while running on a treadmill at 4 and 10 km/h. Prior to beta-blockade, each agent significantly and equivalently (P = NS among drugs) reduced mean arterial pressure during exercise (-13% nifedipine, -8% diltiazem, -15% verapamil at 4 km/h, each P less than or equal to 0.01 vs. exercise alone) but did not significantly alter LV end-diastolic dimension (EDD), heart rate, or cardiac output compared with exercise alone. Only verapamil blunted the positive inotropic response to exercise (LV dP/dtmax decreased 20% at 4 km/h, P less than 0.01 vs. exercise alone). Coronary blood flow was significantly and equivalently increased at rest and during submaximal exercise with each calcium blocker, but this effect was largely offset by propranolol. During exercise after beta-blockade each agent produced significant additional reductions in mean arterial pressure and dP/dtmax at peak exercise but did not alter LVEDD or heart rate compared with results obtained with propranolol alone. Combined beta-blockade and verapamil uniquely diminished myocardial contractility to a greater extent at peak exercise than at rest (dP/dtmax 1,260 +/- 410 peak exercise vs. 1,775 +/- 431 mmHg/s rest, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Fluorescent microspheres: a new tool for visualization of ischemic myocardium in rats
Authors: Hale S. L. , Vivaldi M. T. , Kloner R. A.
Published: December 2017

Fluorescent microspheres (FM) were used in vivo to visualize and quantify an ischemic risk zone after experimental coronary artery occlusion (CAO). Anesthetized rats were subjected to CAO. After 5 min, FM were injected into the left ventricular cavity of seven rats. Six control rats received no FM. When examined with magnification under ultraviolet light, heart slices with FM showed a white-green particulate fluorescence in the nonischemic septum and a well-delineated transmural zone of nonfluorescence in the ischemic free wall. In hearts without FM, this fluorescence was not apparent nor was any perfusion defect observed. In other rats, relative regional myocardial blood flow in the nonfluorescent ischemic zone outlined by FM was measured using plastic radioactive microspheres and found to be approximately 12% of regional flow in normal areas where fluorescence was present. A close correlation (r = 0.92) existed between the amount of ischemic myocardium at risk as outlined by FM and that of necrotic myocardium as defined by tetrazolium staining after both 6 and 24 h of coronary occlusion. We conclude that FM is a promising technique in a small-animal model in which an ischemic risk zone can be established shortly after CAO and can be preserved for later quantification and analysis.
Evaluation of photometric methods for quantifying convective mass transport in microvessels
Authors: Ellsworth M. L. , Pittman R. N.
Published: December 2017

We evaluated the accuracy of blood (Qb), hemoglobin (QHb) and O2 (QO2) flow determinations in arterioles (30-89 micron ID) and venules (30-140 micron ID) of the hamster retractor muscle by testing flow conservation in straight segments (for Qb and QHb) and at bifurcations (for Qb, QHb, and QO2). We found absolute values of relative discrepancies in flow conservation of greater than 30% in straight sections and of greater than 20% at bifurcations. To understand these results, we evaluated the assumptions implicit in the flow calculations by determining the intraluminal profiles of red blood cell velocity, hemoglobin concentration, and O2 saturation. We found that these assumptions were not generally satisfied since only 59% of velocity profiles, 70% of hemoglobin concentration profiles, and 70% of O2 saturation profiles were symmetric about the vessel axis with the velocity profiles more blunt than would be expected for Poiseuille flow. We reevaluated flow conservation by taking into account the bluntness of the velocity profiles. By selecting vessels that had symmetric velocity and hemoglobin concentration profiles and by including the bluntness of the velocity profile, we obtained a significant improvement in the demonstration of flow conservation.
Pulmonary vasoactive effects of exogenous and endogenous AVP in conscious dogs
Authors: Nyhan D. P. , Geller H. S. , Goll H. M. , Murray P. A.
Published: December 2017

Our objectives were to investigate the extent to which both exogenously administered and endogenously released arginine vasopressin (AVP) exert a direct, vasoactive influence on the pulmonary circulation of conscious dogs. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava (IVC) to reduce Q. In intact dogs, AVP infusion (7.6 ng X kg-1 X min-1 iv) increased (P less than 0.01) plasma AVP from 2.3 +/- 0.4 to 280 +/- 23 pg/ml, and increased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure minus pulmonary capillary wedge pressure, PAP-PCWP) over the entire range of Q studied. Following administration of autonomic nervous system antagonists and a converting-enzyme inhibitor, exogenous AVP again increased (P less than 0.01) PAP-PCWP over the entire range of Q. Generation of P/Q plots via IVC constriction resulted in systemic hypotension (58 +/- 4 mmHg) and a concomitant increase (P less than 0.01) in endogenous AVP release from 2.1 +/- 0.2 to 109 +/- 22 pg/ml. Following administration of the specific AVP receptor antagonist [d(CH2)5]AVP (10 micrograms/kg iv), systemic arterial pressure, but not PAP - PCWP, was decreased to significantly lower levels as Q was reduced during IVC constriction. A similar response was observed in dogs pretreated with the neurohumoral blockers. Thus exogenous administration of AVP results in active, non-flow-dependent pulmonary vasoconstriction. This effect is not dependent on reflex activation of the autonomic nervous system or on the increased production of angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Serial analysis of renal blood flow by positron tomography with rubidium-82
Authors: Tamaki N. , Rabito C. A. , Alpert N. M. , Yasuda T. , Correia J. A. , Barlai-Kovach M. , Kanke M. , Dragotakes S. C. , Strauss H. W.
Published: December 2017

To determine whether renal blood flow can be measured by positron-emission tomography (PET) during constant infusion of rubidium-82 (82Rb) using a steady-state kinetic model, studies were performed in 10 dogs at control (n = 10), during mild flow reduction (n = 7), during severe flow reduction (n = 10), and after reperfusion of the kidney (n = 3). PET data were quantified to determine mean concentration of 82Rb (Ct) in each transverse section of the kidney. The arterial concentration (Ca) of 82Rb was measured by well counting of arterial blood samples during the equilibrium scan. 82Rb renal uptake (Ct/Ca) correlated nonlinearly with microsphere renal blood flow according to a steady-state kinetic model (r = 0.90). 82Rb estimated flow was 3.16 +/- 1.36 ml X min-1 X g-1 at control and 1.56 +/- 0.57 and 0.37 +/- 0.59 during mild and severe flow reductions, respectively. Microsphere determined flow was 2.89 +/- 0.77 ml X min-1 X g-1 at control, 1.58 +/- 0.42 at mild reduction, and 0.27 +/- 0.49 at severe reduction. In the occlusion and reperfusion model, the 82Rb estimated flow during occlusion was 0.21 +/- 0.15 ml X min-1 X g-1 and on reperfusion went up to 2.13 +/- 1.08. The contralateral kidney demonstrated reductions in the 82Rb estimated flow of 3.02 +/- 1.62 ml X min-1 X g-1 (63%) and 2.92 +/- 0.89 (61%) during mild and severe flow reductions, respectively. We conclude that PET with 82Rb permits serial quantitative assessment of renal flood flow.
Effect of atrial contraction frequency on atrial natriuretic peptide secretion
Authors: Schiebinger R. J. , Linden J.
Published: December 2017

Paroxysms of atrial tachycardia are oftentimes associated with polyuria. The plasma levels of the potent diuretic hormone, atrial natriuretic peptide (ANP), are elevated during episodes of atrial tachycardia, suggesting that ANP may play a role in mediating the diuresis. The mechanism of enhanced ANP secretion associated with atrial tachycardia is not known. We examined the effect of altering the pacing frequency of isolated left rat atria on ANP secretion. Atria were suspended between an electrode and hook connected to a force transducer and superfused with medium 199. The ANP content of the superfusate was measured by radioimmunoassay. Increasing the frequency of pacing from 2 to 4 Hz resulted in a 46 +/- 5% (means +/- SE, n = 9) rise in immunoreactive ANP secretion above base line (P less than 0.01). Lowering the frequency from 4 to 2 Hz lowered immunoreactive ANP secretion by 36 +/- 3% (n = 6) relative to base line (P less than 0.02). Incremental increases in the pacing frequency from 2 to 8 Hz resulted in a continual rise in immunoreactive ANP with a peak increase of 191 +/- 6% of base line (n = 8) at 8 Hz. To examine the possibility that release of norepinephrine or acetylcholine from endogenous nerves mediated this effect, the atria were superfused with the combination of 0.1 microM propranolol, 1.0 microM phentolamine, and 10 microM atropine. The concentrations of the antagonists were 125-fold or higher than the dissociation constant for binding to receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial recruitment during ANF mRNA increase with volume overload in the rat
Authors: Lattion A. L. , Michel J. B. , Arnauld E. , Corvol P. , Soubrier F.
Published: December 2017

A synthetic oligonucleotide probe complementary to messenger ribonucleic acid (mRNA) encoding for the C-terminal portion of atrial natriuretic factor (ANF) has been used to study the expression of the ANF gene in rat myocardium. Four experimental models were studied: binephrectomy (for 48 h); ligature of both ureters (for 48 h); deoxycorticosterone acetate-salt (for 3 wk); and aortocaval fistula (for 2 wk). Analysis of atrial RNA by gel-blot hybridization detected a single band, corresponding in length to that of mRNA coding for ANF. Such an mRNA was also detected in ventricular RNA but was 1/50th as abundant. In the four experimental groups ANF mRNA was increased significantly as compared with controls. In all rats there was no significant difference in the ANF mRNA content between the left and the right atrium. Each experimental condition was accompanied by a highly significant increase in ANF gene expression in the left ventricle, where all of the ventricular tissue could be recruited and with a negative gradient from the base to the apex of the left ventricle. These data were confirmed by in situ hybridization. Thus all of the atrial and ventricular myocardium can express the ANF gene. Recruitment increases in response to passive stretch of the cardiac chambers.
Peripheral circulatory alterations in canine anaphylactic shock
Authors: Wagner E. M. , Mitzner W. A. , Bleecker E. R.
Published: December 2017

We have examined peripheral circulatory variables that might contribute to the decrease in cardiac output and arterial pressure characteristic of anaphylactic shock. In six dogs instrumented with a right heart bypass, the intravenous administration of Ascaris suum antigen caused a 53% decrease in cardiac output and a 58% decrease in arterial pressure. Resistance to venous return increased from 0.0038 +/- 0.0004 to 0.0056 +/- 0.0006 mmHg X ml-1 X min (P less than 0.05), mean systemic pressure decreased from 7.0 +/- 0.6 to 4.4 +/- mmHg (P less than 0.005), and vascular compliance did not change. Assuming a constant vascular volume, the decrease in mean systemic pressure could be explained by a rightward shift of the systemic pressure volume curve. This constant-volume assumption was tested in intact (n = 6) and splenectomized dogs (n = 7). Serial measurements of protein oncotic pressure and hematocrit were used to estimate plasma volume changes during anaphylaxis. Both methods for estimating volume showed small increases in plasma volume at the time of the largest decrease in arterial pressure in both groups of animals. These results suggest that the primary circulatory mechanisms responsible for anaphylactic shock are an increase in resistance to venous return and a shift of the systemic pressure volume curve and not an acute loss of plasma volume.
Effect of hypertensive rat plasma on ion transport of cultured vascular smooth muscle
Authors: Magargal W. W. , Overbeck H. W.
Published: December 2017

We layered fresh, unprocessed plasma from healthy rats with early (less than or equal to 7 days) or benign, chronic (greater than 3 wk) one-kidney, one-clip hypertension and from paired one-kidney normotensive control rats over confluent primary-cultured rat aortic smooth muscle cells. Plasma from all rats increased cellular ouabain-sensitive 86Rb+ uptake and sodium content and decreased ouabain-insensitive 86Rb+ uptake compared with uptakes and content in the presence of balanced salt solution (P less than 0.01). Cells incubated in the presence of plasma from rats with early (P less than 0.02) or chronic hypertension (P less than 0.01) had significantly reduced ouabain-sensitive 86Rb+ uptake when compared with cells incubated in normotensive plasma, but their intracellular Na+ contents were not lower. We no longer detected this uptake difference when chronic hypertensives drank 0.9% NaCl instead of water. Plasma from hypertensive rats also altered ouabain-insensitive 86Rb+ uptake by the cultured cells. These findings of this new, reproducible, and specific assay system support the hypothesis that plasma factors inhibit the membrane sodium-potassium pump in vascular smooth muscle cells in this form of hypertension. The abnormality occurs in both early and chronic stages, but may not be related to sodium intake. The data also provide evidence for plasma factors in hypertension altering membrane K+ permeability.
Blood pressure and baroreflex sensitivity in conscious hypertensive rats of Lyon strain
Authors: Su D. F. , Cerutti C. , Barres C. , Vincent M. , Sassard J.
Published: December 2017

The evolution with age of blood pressure (BP), heart rate (HR), and baroreflex sensitivity was studied in hypertensive (LH), normotensive (LN), and low blood pressure (LL) male rats of the Lyon strains. Intra-arterial BP was continuously recorded for 48 h in freely moving animals. On-line computer analysis of the BP curve allowed calculation of systolic (SBP), mean (MAP), and diastolic (DBP) blood pressure, HR, and their variability. At 5 wk of age, LH rats exhibited a higher BP than LN and LL controls, which, at 21 wk of age, was associated with significant bradycardia and a greater variability in DBP and HR. LL rats had a MAP similar to LN, which confirms that both strains are, in terms of BP, valid controls for LH animals. The baroreflex sensitivity measured after phenylephrine injections increased with age more markedly in LN and LL than in LH rats, whereas in the latter, it was significantly lower at the age of 9 and 21 wk. When measured after nitroglycerin injections, the baroreflex sensitivity was higher and more stable than that observed after phenylephrine administration. In addition, the baroreflex sensitivity in the different strains was inversely related to the level and the variability of DBP but not of HR.
Estimation of left ventricular mass in conscious dogs
Authors: Coleman B. , Cothran L. N. , Ison-Franklin E. L. , Hawthorne E. W.
Published: December 2017

The short-axis area-length method for the estimation of left ventricular mass (LVM) and volume was validated in 24 formaldehyde-fixed canine hearts, using the truncated ellipsoid model. Estimates of the short-axis muscle area were highly correlated with directly measured values (R = 0.92; P less than 0.001). Similarly, LVM calculated using the area-length method showed good correlation with the actual weight of the left ventricle (LVW) (R = 0.85; P less than 0.001). When the regression equation was used, retrospectively, to correct the LVM estimates, the correlation between the actual LVW and the calculated LVM was markedly improved (R = 0.96; P less than 0.001). In awake dogs instrumented for measuring transverse and long axis ventricular dimensions using sonomicrometry, short-axis two-dimensional echocardiograms were used to convert the sonar external transverse dimensions to true diameters. The combined use of the corrected diameters and the regression equation to calculate LVM in the intact dog resulted in values that were highly correlated with the actual LVW (R = 0.95; P less than 0.001). Application of this technique for monitoring LVM in awake instrumented dogs demonstrated the method to be reproducible from day to day and to be sensitive enough to detect serial changes in mass such as during the development of left ventricular hypertrophy.