bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary vasodilation during global myocardial hypoxia: effects of adenosine deaminase
Authors: Wei H. M. , Kang Y. H. , Merrill G. F.
Published: December 2017

Isolated, perfused guinea pig hearts were infused with intracoronary adenosine deaminase to investigate the contribution of endogenous adenosine to the coronary vasodilation of global myocardial hypoxia. Coronary perfusate pressure was held constant at 70 cmH2O throughout the experiment. We measured retrograde aortic inflow (assumed to equal total antegrade coronary flow) for 3-5 min of hypoxia before and 4 min after initiation of intracoronary adenosine deaminase infusion (4 U.g-1.min-1). In the absence of adenosine deaminase mild global hypoxia increased coronary perfusate flow 60%. In the presence of adenosine deaminase the response was limited to a 5% increment. Myocardial O2 consumption was significantly reduced during hypoxia in the presence of adenosine deaminase. In a second group of hearts, moderate global hypoxia increased coronary perfusate flow 125%. This was limited to a 53% increment in the presence of adenosine deaminase. Adenosine deaminase vehicle had no measurable effect on coronary perfusate flow responses to repeat mild hypoxia in a third group of hearts. We conclude that endogenous adenosine is singularly important in the coronary vasodilation of mild global myocardial hypoxia, but that other regulatory mechanisms might also contribute during moderate hypoxia.
Effects of asynchrony on myocardial relaxation at rest and during exercise in conscious dogs
Authors: Heyndrickx G. R. , Vantrimpont P. J. , Rousseau M. F. , Pouleur H.
Published: December 2017

The effect of left ventricular asynchrony induced by right ventricular pacing on relaxation indexes was studied at rest and during exercise in seven conscious dogs instrumented for chronic measurements of left ventricular pressure, coronary blood flow, and arterial pressure and with right atrial and ventricular pacing electrodes. Increasing heart rate with atrial pacing resulted in an increase in both left ventricular maximum and minimum rates of pressure development, LV dP/dtmax and LV dP/dtmin, respectively, as well as in a decrease in the relaxation constant T. In contrast, increasing heart rate with ventricular pacing resulted in a decrease in LV dP/dtmax, a small increase in LV dP/dtmin, and a significant decrease in T. During exercise with heart rate kept constant with atrial pacing, both LV dP/dtmax and LV dP/dtmin increased and T decreased to the same extent as during exercise in sinus rhythm. In contrast, exercising during right ventricular pacing resulted in a significant increase in T, expressing a slowing of relaxation. It is concluded that increasing heart rate alone in the presence of asynchrony of LV contraction induced by abnormal electrical activation results in a depressed contractile response, while the relaxation phase is not significantly affected. However, during sympathetic stimulation, a condition where synchronization should be improved, the relaxation phase is considerably lengthened.
Vasomotor activity of diadenosine triphosphate and diadenosine tetraphosphate in isolated arteries
Authors: Busse R. , Ogilvie A. , Pohl U.
Published: December 2017

Dinucleotides diadenosine triphosphate (AP3A) and diadenosine tetraphosphate (AP4A) are released from platelet-dense granules upon agonist-induced platelet aggregation. Since most platelet-derived compounds simultaneously affect aggregation and vascular tone, we investigated whether AP3A and AP4A have vasoactive properties. Experiments were performed in isolated, saline-perfused segments of rabbit mesenteric arteries precontracted with norepinephrine. In segments with intact endothelium, both dinucleotides (1-10 microM) induced vasodilation, with AP3A responses significantly greater. Vasodilator responses to AP3A in endothelium-denuded segments were not significantly different from those in segments with intact endothelium but those to AP4A in endothelium-intact segments were reversed to a pronounced contraction after endothelium removal. Likewise, pretreatment of endothelium-intact segments with gossypol (3 microM) reversed dilator responses to acetylcholine and to AP4A into contractions, whereas AP3A-induced dilation was not affected. In segments with intact endothelium but pretreated with reactive blue (10 microM), AP4A also induced a contraction. Dilator response to AP3A was not affected. High-performance liquid chromatographic analysis of effluent from vascular segments showed that neither AP3A nor AP4A was degraded during passage through segments. These results indicate that in rabbit mesenteric arteries both nucleotides act directly, and not through their hydrolysis products, on endothelial (AP4A) and/or smooth muscle receptors. The endothelium-dependent dilator effect of AP4A, is probably mediated by endothelial P2y-purinoceptors.
Serotonergic vasoconstriction in human fingers during reflex sympathetic response to cooling
Authors: Coffman J. D. , Cohen R. A.
Published: December 2017

The effect on finger blood flow (FBF) of 5-hydroxytryptamine (5-HT) in a 25 degrees C room and the S2-serotonergic receptor antagonist, ketanserin, during reflex sympathetic vasoconstriction was studied in normal subjects. Total FBF was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radioisotope from a fingertip injection. 5-HT in doses of 4 and 8 micrograms/min, given by constant infusion via a brachial artery catheter, significantly decreased FBF [32 +/- (SE) 10.4 to 12.8 +/- 6.6 for 4 micrograms/min and to 5.4 +/- 2.6 ml.min-1.100 ml-1 for 8 micrograms/min, P less than 0.05]. Ketanserin (50 micrograms/min) blocked the vasoconstriction caused by 5-HT. During reflex sympathetic vasoconstriction produced by body cooling, ketanserin increased FBF from 4.1 +/- 1.1 to 39.9 +/- 12.9 ml.min-1.100 ml-1 (P less than 0.025). The vasodilation caused by ketanserin was specific for serotonergic receptors, since it occurred during alpha 1-adrenoceptor blockade with prazosin. Furthermore, the decreases in FBF induced by clonidine and angiotensin II were not significantly different before and during ketanserin infusion. Also, ketanserin further increased FBF after vasodilation of reflexly vasoconstricted fingers by the alpha 2-adrenoceptor antagonist, yohimbine, and phentolamine increased FBF during ketanserin infusions. FCF decreased during 5-HT and increased during ketanserin infusions, demonstrating that both capillary and arteriovenous shunt flow were affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Baroreflex modulation by cardiopulmonary receptors during chronic sodium depletion
Authors: Echtenkamp S. F. , Anderson A. C.
Published: December 2017

Chronic sodium to depletion is associated with a reduced baroreflex responsiveness to carotid sinus hypotension. One hypothesis to explain the mechanism of the reduced baroreflex responsiveness involves a redistribution of blood volume toward the cardiopulmonary circulation during sodium depletion. This volume redistribution may result in enhanced discharge of cardiopulmonary volume-sensing mechanoreceptors, which tonically inhibit the expression of the carotid baroreflex. In this study, when the pressor and tachycardic responses to carotid occlusion were tested, the baroreflex responses were significantly smaller in sodium-depleted dogs (P less than 0.05). When the vagal and aortic depressor nerves were removed, the baroreflex responses to carotid occlusion were increased in both sodium-replete and sodium-depleted animals. However, the pressor and tachycardic responses were still attenuated in the sodium-depleted animals after vagotomy (P less than 0.05). Thus the results of this study indicate that cardiopulmonary volume receptor discharge is not increased in the sodium-depleted state, and removal of cardiopulmonary vagal afferent influences does not normalize the impaired baroreflex responsiveness of sodium-depleted animals.
Two components of coupling calcium in single ventricular cell of rabbits and rats
Authors: Rich T. L. , Langer G. A. , Klassen M. G.
Published: December 2017

A system for rapid superfusion with simultaneous measurement of contractile amplitude of single adult rat and rabbit ventricular cells is used to measure cellular response to alterations of the superfusate achieved in less than 0.3 s. The time course of contractile response of the cells to extracellular Ca concentration [( Ca]o) depletion and repletion identifies "fast" and "slow" cellular pools of Ca that contribute to contraction. The fast pool can be totally depleted or repleted within a single diastolic period. Depletion of this pool completely eliminates contraction in both rat and rabbit cell. Experiments using dimethonium to investigate the effect of Ca in the diffuse double layer and dodecyl sulfate to specifically augment sarcolemmal fixed-negative charge indicate that sarcolemmal binding sites may represent a major fraction of the fast pool. At 1 mM [Ca]o, this pool is functionally saturated in the rat but not nearly saturated in the rabbit. After 10 min Ca depletion more than 60 s of Ca repletion are required to restore full contraction amplitude. This indicates the presence of a slow pool of Ca that contributes to contraction. This pool, at 1 mM [Ca]o, is nearly functionally saturated in the rabbit but not nearly so in the rat. The responses to Ca depletion and repletion, Na depletion and repletion, and 1 microM ryanodine indicate that the contribution of Ca to contraction from the slow pool is much greater in the rat than in the rabbit and that its cellular locus is probably the sarcoplasmic reticulum.
Cardiovascular and hormonal response to hemorrhage in conscious rats
Authors: Fejes-Toth G. , Brinck-Johnsen T. , Naray-Fejes-Toth A.
Published: December 2017

The effect of arginine vasopressin (AVP) pressor blockade on the response to graded hemorrhage was investigated on conscious, unstressed, freely moving rats. The parameters studied were mean arterial pressure (MAP), heart rate (HR), blood velocity in the ascending aorta (ABV), and plasma concentrations of AVP (pAVP), renin (PRC), corticosterone (pCS), and catecholamines. After the first hemorrhage (0.75% of body wt over 5 min), MAP remained unchanged while ABV declined and HR increased. The two subsequent hemorrhages brought about significant reduction in MAP, HR, and ABV. pAVP, pCS, and PRC increased gradually during the experiment, while plasma catecholamine levels remained unchanged except for epinephrine, which increased after the third hemorrhage. After pretreatment with the AVP-pressor antagonist, [d(CH2)5Tyr(Me)]AVP, the hemorrhage-induced cardiovascular changes were practically identical to those seen in control animals. Results with AVP blockade performed after the third hemorrhage were also negative. A pressor role of AVP after hypotensive hemorrhage could only be revealed in the presence of converting-enzyme inhibition and alpha-adrenergic blockade. In addition, [d(CH2)5Tyr(Me)]AVP did not modify the effect of hemorrhage on pCS and catecholamines and caused only a slight enhancement of the increase in PRC. It is concluded that conscious, nonstressed rats, if all compensatory mechanisms are allowed full expression, exhibit a normal cardiovascular compensatory response to hemorrhage in the absence of functional AVP pressor receptors.
Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents
Authors: Longhurst J. C. , Dittman L. E.
Published: December 2017

Page H556: J. C. Longhurst and L. E. Dittman. “Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents.” Replace Figs. 2 B, 5 B, and 8 with the following.

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Tachycardia of carotid chemoreceptors originates in apneic asphyxia in dogs
Authors: Gupta P. G. , Singh M.
Published: December 2017

Page H591: P. G. Gupta and M. Singh. “Tachycardia of carotid chemoreceptors originates in apneic asphyxia in dogs.” The title should read: “Tachycardia originating from carotid chemoreceptors in apneic asphyxia in dogs.”
Histamine dilates pial arterioles of newborn pigs through prostanoid production
Authors: Mirro R. , Busija D. W. , Armstead W. M. , Leffler C. W.
Published: December 2017

To test the hypothesis that histamine would dilate pial arterioles via a prostanoid mechanism, histamine was placed on the brain surface of anesthetized newborn pigs via a closed cranial window. Pial arteriolar diameters were measured after topical application of 10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) M histamine. In addition, cortical cerebrospinal fluid (CSF) was collected for radioimmunoassay of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and prostaglandin F2 alpha (PGF2 alpha). The animals were then randomized to receive either indomethacin trihydrate (5 mg/kg, iv) or an equal volume of saline (vehicle). The protocol then was repeated. Histamine (before indomethacin or vehicle infusion) caused concentration-dependent vasodilation. This vasodilation was accompanied by a significant increase in cortical CSF 6-keto-PGF1 alpha and PGE2. Concentrations of TxB2, PGD2, and PGF2 alpha were not altered significantly by histamine application. Pretreatment with indomethacin blocked the histamine-induced cerebral vasodilation, but vasodilation after vehicle was intact. These data imply that histamine dilates the pial arterioles of newborn pigs by stimulating the synthesis of vasodilator prostanoids.
Pulsatile vs. mean component of baroreflex compensation for posthemorrhage hypotension
Authors: Yamazaki T. , Brunner M. J. , Sagawa K.
Published: December 2017

We studied the influence of pulsatile pressure and mean arterial pressure signals on the restoration of arterial pressure after 10% hemorrhage in seven anesthetized dogs. After transection of the aortic nerve, a quick 10% hemorrhage was repeated under four different sinus conditions: condition 1, carotid sinus pressure depulsated and fixed at a level equal to the prehemorrhage level (no feedback); condition 2, pulsatile component of aortic pressure fed back to the carotid sinus with a fixed mean pressure (pulsatile feedback); condition 3, depulsated mean aortic pressure fed back (mean pressure feedback); condition 4, both pulsatile and mean pressure fed back (pulsatile plus mean component feedback). The restoration of arterial pressure in condition 2 was not significantly different from that in condition 1, but there was greater restoration in conditions 3 and 4. At 1.5 min posthemorrhage, the open-loop gains calculated from the restoration values were nearly zero for the pulsatile feedback only, 2.8 +/- 0.8 for mean arterial pressure feedback, and 1.5 +/- 0.3 for pulsatile and mean pressure feedback. These results indicate that the pulsatile component of the carotid baroreflex contributes minimally to the restoration of arterial pressure after 10% hemorrhage in the anesthetized dog.
Functional and anatomical recovery of endothelium after denudation of coronary artery
Authors: Hayashi Y. , Tomoike H. , Nagasawa K. , Yamada A. , Nishijima H. , Adachi H. , Nakamura M.
Published: December 2017

Endothelium-related coronary dilation after balloon denudation was compared with the extent of luminal lining of the regenerated endothelial cells. Under conditions of asepsis, a pair of 10-MHz piezoelectric crystals, an electromagnetic flow probe, and a cuff occluder were placed on the left circumflex coronary artery. Seven to 10 days after this instrumentation, the dogs were anesthetized and the endothelium was removed with the use of a balloon catheter. Immediately after balloon denudation, coronary dilations following reactive hyperemia (reactive dilation) and acetylcholine 3 micrograms/kg iv were reduced to 19 +/- 5 (P less than 0.01) and 10 +/- 4% (P less than 0.01) of control, respectively. In 2, 5, and 7–10 days after denudation, reactive dilation in the conscious dogs was 24 +/- 7 (n = 16), 71 +/- 10 (n = 11), and 75 +/- 9% (n = 5) of control, respectively. Acetylcholine-induced coronary dilation in conscious state was 52 +/- 12 (n = 9), 116 +/- 17 (n = 7), and 94 +/- 24% (n = 2) of control in 2, 5, and 7-10 days after denudation, respectively. There was a positive linear relation between the extent of reactive dilation and acetylcholine-induced dilation from 2 to 10 days after denudation (r = 0.734). The amount of reactive hyperemia, nitroglycerin-induced coronary dilation, and ergonovine-induced coronary constriction remained constant during the experimental period. The area covered by the endothelial cells at the denuded site was 8 +/- 3 (n = 5), 18 +/- 9 (n = 6), 64 +/- 9 (n = 6), and 81 +/- 11% (n = 3) of the denuded area in 0, 2, 5, and 7-10 days after denudation, respectively, which linearly related to the percent recovery of reactive dilation (r = 0.912). Thus reactive dilation or acetylcholine-induced coronary dilation depended on the presence of endothelium, irrespective of the shape or alignment of the regenerated tissues. These findings may be clinically relevant because anatomical integrity of the endothelium might be assessed in vivo by reactive dilation or acetylcholine-induced coronary dilation.
Right ventricular hypertrophy long after reversal of severe pressure overload in cats
Authors: Wisenbaugh T. , O'Connor W. N.
Published: December 2017

To test the hypothesis that alterations in ventricular size and function may persist long after reversal of a severe pressure overload, right ventricular (RV) hypertrophy was produced in cats by abrupt, severe constriction of the pulmonary artery (PA) for 8 wk, after which pressure overload was completely reversed by surgical removal of the PA band (group III). Despite debanding and recovery from pressure overload (RV peak systolic pressure = 22 +/- 4 vs. 66 +/- 20 mmHg before debanding and 25 +/- 4 mmHg in controls), parameters of hypertrophy 8–10 mo later remained substantially increased: e.g., RV/LV (left ventricular) mass ratio was 0.36 +/- 0.06 in group III vs. 0.24 +/- 0.03 in controls (group I) and 0.43 +/- 0.07 in a separate cohort (group II) studied after 8 wk of banding. Maximum RV stroke work during volume loading was computed from RV micromanometry and PA electromagnetic flow: 20 +/- 8 g-cm/g for group III vs. 51 +/- 14 for group I, P less than 0.05, and 21 +/- 7 for group II. Thus severe pressure overload of the RV may produce changes in size and function that are not fully reversed by complete removal of the overload.
Albumin improves stability and longevity of perfluorochemical-perfused hearts
Authors: Segel L. D. , Ensunsa J. L.
Published: December 2017

We determined the effect of protein and nonprotein oncotic agents on physiological function and substructural integrity of perfluorochemical emulsion-perfused isolated working rabbit hearts. We used four media that contained Fluosol-43 (FL) emulsion and either 3.4% hydroxyethylstarch (HES), 2.9% albumin, 0.8% HES, or neither HES nor albumin (n = 5 hearts/group). All four groups of hearts had stable function for the first 5.5 h of perfusion; the FL plus albumin hearts continued to exhibit stability in most indexes of function until 9.5 h. The FL plus albumin hearts had a longer total period of ejecting function (12.5 +/- 0.5 h) compared with the other groups (mean longevities = 7.4-8.4 h). Functional stability and longevity correlated with maintenance of coronary flow and coronary vascular resistance. The rates of excess fluid accumulation and creatine kinase leakage were lower in the FL plus albumin hearts than in the other groups. We conclude that: 1) albumin maintained function, coronary flow, and myocardial cell integrity of FL-perfused hearts better than did HES; 2) albumin may exert its effect by preserving capillary permeability, thereby reducing the rate of interstitial fluid accumulation and preventing edema-induced vascular compression; and 3) HES had no effect on cardiac function or integrity and was ineffective in preventing interstitial fluid accumulation when it was used in FL-perfused isolated hearts in the absence of protein.
Interstitial transudate concentration of adenosine and inosine in rat and guinea pig hearts
Authors: Decking U. K. , Juengling E. , Kammermeier H.
Published: December 2017

Interstitial transudate (IT) was sampled from the surface of isolated constant pressure-perfused guinea pig and rat hearts. With endogenous adenosine (AR) formation, IT concentrations (Crr) of AR and inosine (IR) were 4- to 6.5-fold higher than those in the venous effluent. The AR-to-IR ratio varied between 0.5 and 0.1. During normoxic perfusion, CIT-AR reached a basal level of 0.18 microM. During maintained hypoxia, CIT-AR was elevated only initially up to 0.63 microM. Subsequently, it decreased to basal values, whereas coronary flow remained elevated. With repetitive hypoxia, CIT-AR decreased to basal values, with little alteration in the coronary flow response. Addition of 1,000 U/l adenosine deaminase reduced CIT-AR below 0.2 microM, with no change in coronary flow response to hypoxia. High concentrations of coformycin (Streptomyces antibioticus), an adenosine deaminase inhibitor (greater than 1 microM), were necessary to increase the AR-to-IR ratio to unity, indicating an intracellular site of action. During administration of 0.1 microM dipyridamole, no close correlation between CIT-AR and coronary flow was found. Administration of 1 microM AR did not induce a detectable change in Crr-AR despite a distinct coronary flow response. We conclude that at least in our heart preparation, interstitial adenosine seems to play no primary role in coronary flow regulation.
Nonadrenergic and noncholinergic excitatory neurotransmission in rat intrapulmonary artery
Authors: Inoue T. , Kannan M. S.
Published: December 2017

Electrical responses evoked by perivascular nerve stimulation were recorded from rat small intrapulmonary artery with the microelectrode technique. Nerve stimulation with a single pulse produced an excitatory junction potential that was insensitive to phentolamine, propranolol, atropine, ketanserin, mepyramine, and guanethidine but was abolished by tetrodotoxin. Treatment with reserpine in vivo or with 6-hydroxydopamine in vitro had no significant effect on the amplitude of the junction potentials. In the mesenteric arteries from the same rats, these procedures led to the inhibition of the junction potentials, confirming adequate functional sympathectomy. Low concentrations of alpha, beta-methylene ATP attenuated the amplitude of the excitatory junction potential without changing the membrane potential. The membrane depolarization induced by norepinephrine or serotonin were not. It is concluded that the excitatory junction potential in rat pulmonary artery results from the release of a nonadrenergic, noncholinergic neurotransmitter from perivascular nerves that are not sympathetic and that the most likely transmitter is ATP. Such neurotransmission may play a role in the regulation of regional pulmonary blood flow.
Alpha-subunit of Gk activates atrial K+ channels of chick, rat, and guinea pig
Authors: Kirsch G. E. , Yatani A. , Codina J. , Birnbaumer L. , Brown A. M.
Published: December 2017

A specific guanine nucleotide-binding protein, Gk, is the link by which muscarinic receptors activate atrial potassium channels (Science Wash. DC 235: 207-211, 1987). In adult guinea pigs, the alpha-subunit at picomolar concentrations mediates the holo-G protein effect (Science Wash. DC 236: 442-445, 1987), but in chick embryo it has been reported that the beta gamma-dimer at nanomolar concentrations rather than the alpha-subunit is the effective mediator (Nature Lond. 325: 321-326, 1987). This difference might have a phylogenetic or ontogenetic basis, and the present experiments tested these possibilities. Preactivated alpha k derived from human red blood cell Gk, when applied to the intracellular surface of inside-out membrane patches from the atria of embryonic chick, neonatal rat, and adult guinea pig activated single K+ channel currents. In each case, the alpha k-activated channels had the same single-channel conductance and mean open time as the muscarinic agonist-activated channels. Half-maximal activation was achieved at alpha k-concentrations of 2.4-13.8 pM. Hence, alpha k-activation of these K+ channels is independent of differences in age or species. The detergent 3-[3-cholamidopropyl)-dimethyammoniol]-1-propanesulfonate (CHAPS), which was used by Logothetis et al. (Nature Lond. 325: 321-326, 1987) at 184 microM to suspend the hydrophobic beta gamma-dimers, activated the same currents. We conclude that the effects of the beta gamma-dimer on these K+ channels is unknown and that as we had proposed earlier (Science Wash. DC 236: 442-445, 1987) it is the alpha-subunit that mediates the Gk effect.
Inotropic agents modulate gap junctional conductance between cardiac myocytes
Authors: Burt J. M. , Spray D. C.
Published: December 2017

Cardiac gap junction channels mediate the intercellular exchange of second messenger and small molecules. Through effects on conduction velocity, enhanced junctional conductance (gj) facilitates rapid and synchronous activation of the contractile myocardium, whereas reduced gj slows activation and could contribute to arrhythmogenesis. We report here that gj is enhanced by agents that elevate intracellular adenosine 3',5'-cyclic monophosphate (cAMP; 8-bromo-cAMP or isoproterenol) and is depressed by agents that elevate intracellular guanosine 3',5'-cyclic monophosphate (cGMP; 8-bromo-cGMP or carbachol). Both effects occur with a time course comparable to the inotropic events mediated by these agents. The effect of cAMP on gj is not dependent on simultaneous changes in intracellular calcium; however, during calcium-overload conditions cAMP can precipitate calcium-dependent uncoupling. These results indicate that cyclic nucleotide-dependent changes in gj may contribute to the inotropic effects of these agents. Furthermore, the results suggest that the inotropic effect of cAMP includes a calcium-independent component.
Trigeminalectomy modifies pial arteriolar responses to hypertension or norepinephrine
Authors: Moskowitz M. A. , Wei E. P. , Saito K. , Kontos H. A.
Published: December 2017

The responses of pial precapillary vessels were examined bilaterally using a closed cranial-window preparation in 11 anesthetized cats after chronic unilateral section of the trigeminal ganglia. During increases or decreases in arterial PCO2 or hypoxia, vasoconstrictor and vasodilator responses were symmetrical and appropriate on the two sides. The superfusion of vessels with norepinephrine (10 micrograms/ml) constricted large and small pial arterioles to a greater extent on the denervated side, and this difference persisted even after washing (P less than 0.02). After severe hypertension, small and large arterioles dilated on both sides, although to a greater extent on the innervated side. In 8 of 10 acutely hypertensive animals, extravasation of intravenously administered iodinated albumin was greater in the intact than deafferented hemisphere. These results suggest that the trigeminal nerve can modify the responses of cerebral arterioles and participate in the regulation of the cerebral vasculature.
Age-related changes in composition and Ca2+-binding capacity of canine cortical bone extracts
Authors: Pinto M. R. , Gorski J. P. , Penniston J. T. , Kelly P. J.
Published: December 2017

The variable of age was used to study macromolecules in bone that may mediate in part the in vivo readily exchangeable calcium-binding capacity (VCa2+D). Organic components were extracted from nonmineralized bone with 4 M guanidine-HCl and from both nonmineralized and mineralized bone with 0.1 M EDTA. The composition of pup bone extracts demonstrated an enrichment in protein, hexuronate, sialic acid, organic phosphorus, and bound sulfate when compared with other age groups. In vitro calcium-binding studies identified low-affinity (Kd congruent to 10(-3) M) sites in both types of extracts; high-affinity sites (Kd congruent to 10(-5) M) were only evident in EDTA extracts of bone. Readily exchangeable calcium-binding capacity in vivo was found to decrease from pup (40.7 mM) to adolescent (11.1 mM) to the mature/old groups (2.6/1.2 mM); however, a large difference in low-affinity site number was only observed between pup and adolescent bone extracts. The overall organic composition of EDTA and guanidine-HCl extracts generally reflected the composition of total bone, which dropped dramatically on a dry weight basis from pup to adolescent groups. A similar pattern was observed with the number of low-affinity binding sites measured in vitro. In vitro binding data indicate that nonmineralized matrix of pup bone, extractable by 4 M guanidine-HCl, possesses enough capacity to accommodate approximately 40% of the readily exchangeable pool. As age progresses, other components of the blood-bone exchange process, such as vascularity, may reduce the readily exchangeable calcium pool size below the amount of low-affinity sites measured in vitro.
Contractile force of single heart cells compared with muscle strips of frog ventricle
Authors: Tung L. , Morad M.
Published: December 2017

Single heart cells were obtained from frog ventricle with an enzymatic dispersion technique. Isometric contractile force was measured in these cells by an ultrasensitive force transducer and compared with that generated by multicellular muscle strips under similar conditions. The shape of the single-cell twitch was qualitatively similar to that obtained in intact tissue; however, the time to peak was generally shorter, and the falling phase was prolonged in the single cell compared with the muscle strip. The single-cell contractile force was measured in response to alterations in stimulus rate, resting length, and extracellular Ca2+ concentration [Ca2+]o or by addition of epinephrine; in all cases, the force response resembled the physiological response seen in the muscle strip. However, at a constant stimulation rate, the steady-state amplitude of the single-cell twitch exhibited beat-to-beat variations under all conditions tested, whereas that of the muscle strip was essentially constant. These results may prove to be useful in assessing the suitability of the single-cell preparation as a model for the intact tissue.
Quantitative identification of superoxide anion as a negative inotropic species
Authors: Schrier G. M. , Hess M. L.
Published: December 2017

Reduced oxygen intermediates have been shown to directly depress cardiac muscle function at the subcellular, tissue, and whole animal levels. The exact species of reduced oxygen intermediate [superoxide anion radical (O2-.), H2O2, hydroxyl free radical (HO.)] and the concentrations necessary to depress cardiac muscle function have not been quantified. To better understand the role of O2-. and H2O2, we have studied rabbit right ventricular papillary muscle function in the presence of these reduced oxygen intermediates generated by a xanthine-xanthine oxidase system at 37 degrees C. In the presence of xanthine (0.1 mM) and xanthine oxidase (0.02 U/ml), 57.5 +/- 0.85 nmol.l-1.s-1 O2-. and 69.25 +/- 5.3 nmol.l-1.s-1 H2O2 were produced. In the presence of superoxide dismutase (SOD), O2-. was eliminated and H2O2 concentration increased. Catalase effectively eliminated the accumulation of H2O2 without significantly changing the rate of O2-. generation. When applied to isometrically contracting right ventricular papillary muscles, this system, with or without SOD and catalase, had no effect on peak developed tension or +/- dT/dt derived either from length-tension or force-frequency studies. However, when the xanthine oxidase concentration was increased to 0.112 U/ml, the rate of O2-. generation increased to 196.67 +/- 3.26 nmol.l-1.s-1 and H2O2 production increased to 142.19 +/- 9.3 nmol.l-1.s-1 with significant depression of papillary muscle tension development. SOD virtually eliminated O2-. production, whereas H2O2 production increased to 199.48 +/- 9.8 nmol.l-1.s-1 with no effect on papillary muscle tension development.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of cholesterol metabolism in fetal rabbit aorta: role of amniotic fluid factors
Authors: Rymaszewski Z. , Yunker R. L. , Ashraf M. , Park M. , Subbiah M. T.
Published: December 2017

This study shows that amniotic fluid enhances cholesterol esterification in arterial wall, as measured by in vitro assay of acyl-CoA:cholesterol acyltransferase (ACAT) activity and by incorporation of oleic acid to cholesteryl esters in cultured fetal aortas and smooth muscle cells. This property is mostly evident in the fraction of molecular weight greater than 100,000, and it is abolished by delipidation, indicating that stimulating factor is probably lipoprotein in nature. Despite an increased cholesterol esterification by the presence of amniotic fluid in medium of cultured fetal aortas, the content of cholesterol and cholesteryl esters was much lower. The cellular structures are better preserved in explants cultured with amniotic fluid than in control animals. This study indicates that amniotic fluid contains factors that may have a pronounced effect on arterial wall during development.
Activation of dehydrogenase activity and cardiac respiration: a 31P-NMR study
Authors: Katz L. A. , Koretsky A. P. , Balaban R. S.
Published: December 2017

31P-NMR studies were performed to determine the tissue phosphate and oxygen consumption effects of known maneuvers on the activation of pyruvate dehydrogenase during work jumps in the perfused rat heart. In control studies of the glucose-perfused heart, work jumps, with pacing, resulted in a 32% increase in oxygen consumption (QO2) from 1.72 +/- 0.09 to 2.29 +/- 0.12 mmol O2.h-1.g dry wt-1. During this transition no significant change in the high energy phosphates were detected. In contrast, work jumps did cause changes in the phosphates when the activation of pyruvate dehydrogenase was blocked with 2.5 micrograms of ruthenium red per milliliter or maximally stimulated with 11 mM pyruvate before the increase in work. The observed increase in QO2 and inorganic phosphate and calculated increase in ADP are consistent with these phosphates controlling mitochondrial respiration under these conditions. These results suggest that the activation of pyruvate dehydrogenase and/or other dehydrogenases may be an important step in the orchestration of work and QO2.
Ventricular ejection fractions of linear transformation and ellipsoid models
Authors: Wattenbarger J. M. , Templeton G. H. , Seibert G. B. , Ramanathan M. , Cassidy S. S. , Johnson R. L.
Published: December 2017

Eigenvolumes calculated from a linear transformation model were found previously to be linearly related to balloon volumes in excised hearts. The present study analyzed endocardial marker kinematics in intact, contracting left ventricles by biplane cinefluorography. Ejection fractions of the linear transformation model were compared by linear regression analysis with those of an ellipsoidal model, whose ejection fractions had been documented previously in closed and open-chest dog preparations. Data from 10 dogs indicated a correlation coefficient of 0.98 and a regression equation with close similarity to the line of identity. Ejection fractions calculated from the linear transformation model are concluded to be proportional to actual ejection fractions in intact, beating left ventricles.
Effects of ischemia on cardiac afferent sympathetic and vagal reflexes in dog
Authors: Inoue H. , Skale B. T. , Zipes D. P.
Published: December 2017

To determine the time course of afferent sympathetic and vagal denervation after coronary occlusion and that of neural recovery after reperfusion, we measured the vasopressor responses to bradykinin and the vasodepressor responses to nicotine applied in a felt pad to the left ventricular epicardium of open-chest dogs. Shortly after latex injection of a diagonal branch of the left anterior descending coronary artery (LAD), the vasopressor response to bradykinin applied to the transmural ischemic area (n = 7) or apically to it (n = 6) was interrupted or attenuated. In contrast, nontransmural ischemia produced by ligation of the diagonal branch did not attenuate the response to bradykinin applied to the ischemic region (n = 6) or apically to it (n = 7). Transmural ischemia produced by occlusion of a diagonal branch of the LAD and a lateral marginal branch of the left circumflex coronary artery (n = 8) or by intraluminal balloon occlusion of the LAD (n = 7) decreased the vasopressor response to bradykinin applied within or apically to the ischemic area in less than 13 min. The vasopressor response to bradykinin became attenuated when the myocardial blood flow in the epicardial test site decreased to approximately 40% or less of the control value. Nontransmural ischemia produced by occlusion of a diagonal branch (n = 7) attenuated the vasodepressor response to nicotine applied to the nonischemic area apically to the occlusion in less than 13 min. A 15-min coronary occlusion followed by reperfusion produced reversible attenuation of afferent neural responses. We conclude that ischemia interrupts afferent sympathetic and vagal cardiac reflex responses to bradykinin and nicotine and that these alterations are reversible after reperfusion.
Evaluation of whole body autoregulation in conscious dogs
Authors: Metting P. J. , Strader J. R. , Britton S. L.
Published: December 2017

The ability of the systemic circulation to maintain cardiac output during decreases in arterial pressure was evaluated in conscious dogs with intact reflexes (n = 8) and during pharmacological blockade of the autonomic nervous system, angiotensin II formation, and arginine vasopressin (n = 6). Cardiac output was measured electromagnetically, and aortic pressure was controlled via a gravity reservoir connected to a carotid artery. When aortic pressure was decreased in either small steps to approximately 60% of control, or decreased in a single square-wave step to 75% of control and maintained for 2 h, cardiac output decreased to the same or a greater extent in both control and areflexic dogs. Thus total peripheral resistance did not decrease, and autoregulation of the cardiac output did not occur in response to short-term (less than or equal to 2 h) decreases in arterial pressure, even in the absence of the major pressor systems. After long-term (greater than 8 h) decreases in arterial pressure to 75% of control in five dogs with all reflexes intact, significant autoregulation of the cardiac output occurred. The relationship between the gain of blood flow autoregulation and the corresponding values of mixed venous oxygen tension suggests that whole body autoregulation results when oxygen extraction reserve becomes limited.
The stunned myocardium: effect of electrical and mechanical arrest and osmolarity
Authors: Nayler W. G. , Elz J. S. , Buckley D. J.
Published: December 2017

After relatively short periods of ischemia, reperfusion for several hours, or even days, is required to facilitate complete recovery of the ATP stores and mechanical function. The term "stunned" has been applied to these hearts. In the present experiments, isolated, spontaneously beating and electrically paced rat hearts were made ischemic for 10 min and then reperfused with Krebs-Henseleit buffer (KH) for up to 30 min. On reperfusion, functional recovery was impaired and the inotropic effect of Ca2+ blunted. In these experiments, the effect of a period of electrical and/or mechanical quiescence before the ischemic episode was investigated. Electrical quiescence was obtained by raising the KH K+ concentration, whereas mechanical without electrical quiescence was obtained by lowering the KH Ca2+ concentration or adding 2,3-butanedione monoxime (BDM). Mechanical arrest caused by low Ca2+ perfusion before ischemia failed to improve functional recovery on reperfusion. However, introducing a high K+ perfusate or BDM for a few minutes before ischemia significantly improved the recovery during reperfusion. This improvement was neither caused by energy preservation nor an altered "reflow area". The improvement may be caused by the increased osmolarity of KH containing high K+ or BDM, since adding 10 mM sucrose to KH for an equivalent time before ischemia improved recovery and abolished the blunted inotropic effect of Ca2+.
Circulatory and metabolic responses to carbon monoxide hypoxia during beta-adrenergic blockade
Authors: Melinyshyn M. J. , Cain S. M. , Villeneuve S. M. , Chapler C. K.
Published: December 2017

The role(s) of beta-adrenoceptors in whole body and hindlimb skeletal muscle cardiovascular and metabolic responses during carbon monoxide hypoxia (COH) was studied in anesthetized dogs. One group of animals was beta-blocked with propranolol (beta 1- and beta 2-blockade), a second was given ICI 118,551 (beta 2-blockade), and a third served as a time control. Immediately after a control-sampling period, COH was induced (about a 63% decrease in arterial O2 content), and additional measurements were then obtained at 30 and 60 min of hypoxia. Cardiac output values were not different between the three series at control; an increase (P less than 0.05) occurred in all groups during COH. This rise was greatest in the COH group; the values for the propranolol- and ICI 118,551-blocked groups were not different from each other during COH. Hindlimb blood flow rose (P less than 0.05) during COH only in the control group. Both whole body (30 min) and hindlimb (30 and 60 min) resistance values were greater during hypoxia in the beta-blocked groups (P less than 0.05) than in the control series. Furthermore, whole body oxygen uptake decreased (P less than 0.05) in both beta-blocked groups during COH. We conclude that approximately 35% of the rise in cardiac output occurring during COH depended on peripheral vasodilation mediated through beta 2-adrenoceptors.
OBSERVATIONS ON THE ACCURACY OF THE THERMOSTROMUHR
Authors: Gregg D. E. , Pritchard W. H. , Eckstein R. W. , Shipley R. E. , Rotta A. , Dingle J. , Steege T. W. , Wearn J. T.
Published: December 2017

The authors of the paper "Observations on the Accuracy of the Thermostromuhr" beginning on page 250 of no. 2 of this volume (136) desire to record the following corrections:

p. 256. Delete sentence beginning line 9 and substitute: "In the right coronary flow is frequently always forward but the appearance of back flow components is not uncommon."

In line 13 after the words "can appear" insert reference (5).

p. 261. Under "References" correct to read as follows:

(2) Gregg, D. E., A. Rotta, R. W. Eckstein, R. E. Shipley and J. T. Wearn. Proc. Soc. Exper. Biol. and Med. 49: 267, 1942.

(4) Eckstein, R. W., D. Book and D. E. Gregg. This Journal 135: 772, 1942.

(5) Pritchard, W. H., A. S. Weisberger, E. F. Schroeder, R. E. Shipley and D. E. Gregg. To be published.
THE EFFECT OF CARBON MONOXIDE ON THE OXYHEMOGLOBIN DISSOCIATION CURVE
Authors: Roughton F. J. W. , Darling R. C.
Published: December 2017

On page 19 of the current volume (Vol. 141) figures 1 and 2 for the paper "The Effect of Carbon Monoxide on the Oxyhemoglobin Dissociation Curve" by F. J. W. Roughton and R. C. Darling were inadequately reproduced. Below these figures are again reproduced with satisfactory legibility.

(See PDF)
SPECTROPHOTOMETRIC MEASUREMENT OF TRACES OF THE DYE T-1824 BY EXTRACTION WITH CELLOPHANE FROM BOTH BLOOD SERUM AND URINE OF NORMAL DOGS
Authors: Allen Thomas H. , Orahovats Peter D.
Published: December 2017

Volume 154, page 37. Insert the following paragraph before Summary and Conclusions: Finally, in connection with a discussion of T-1824 clearance, it is interesting and informative to note the tabulated data of electrophoretic studies on T-1824 and protein in urine of human nephrosis (17). Although it is not stated how dye was measured in nephrotic urine, the T-1824 clearance was 0.37 ml. per minute per square meter of body surface, the albumin clearance was 0.39 while total protein clearance was 0.09. The globulin clearance of 0.03 was very small indeed. Luetscher (17) preferred in 1944 to compare dye with total protein clearance, but since the clearances for T-1824 and serum albumin were nearly equal and considerably greater than that of globulin it is probable that the dye was excreted in the form of dye albumin. In nephrosis, then, the kidney behaves as though injected dye combined selectively with serum albumin leaving vanishingly small amounts of free dye in the blood. On the basis of body surface area a human nephrotic can have a dye clearance 100 times greater than that of a normal dog. This again suggests that dye clearance when analyzed by a sensitive method is a measure of normally occurring albumin clearance.
CAPILLARY PERMEABILITY: RATE OF TRANSCAPILLARY EXCHANGE OF IRON ADDED TO PLASMA AS RADIOACTIVE FERRIC BETA1-GLOBULINATE
Authors: Flexner Louis B. , Vosburgh Gilbert J. , Cowie Dean B.
Published: December 2017

Volume 153, page 508. Line 5: The designation C+0 should read C*0.

Line 10: The equation should read C*t = C*0e–Rt.
COMBINATION OF TOLUIDINE DYE ISOMERS WITH PLASMA ALBUMIN
Authors: Allen T. H. , Orahovats P. D.
Published: December 2017

Page 473. Allen, T. H. and P. D. Orahovats, "Combination of Toluidine Dye Isomers with Plasma Albumin": The word "toluidine" should read "tolidine" throughout the article.
INDIVIDUAL AND AGE VARIATION IN METHEMOGLOBIN FORMATION AND REDUCTION IN RABBIT ERYTHROCYTES
Authors: Spicer S. S. , Reynolds Helen
Published: December 2017

Page 50. S. S. Spicer and Helen Reynolds, "Individual and Age Variations in Methemoglobin Formation and Reduction in Rabbit Erythrocytes." In the first column of table 3, the fourth item, which now reads "8 weeks," should read "2 weeks."
PHYSIOLOGIC RESPONSES OF CERTAIN ANIMALS AND ISOLATED PREPARATIONS TO MIXTURES OF SNAKE VENOM AND EGG YOLK
Authors: Boquet Paul , Dworetzky Murray , Essex Hiram E.
Published: December 2017

Page 566. P. Boquet, M. Dworetzky and H. E. Essex, "Physiologic Responses of Certain Animals and Isolated Preparations to Mixtures of Snake Venom and Egg Yolk." The last 2 sentences of the legend for figure 5 belong at the end of the legend for figure 4. These sentences read as follows: "Material in 2 syringes was injected simultaneously. Note return to base line in 2 minutes and stepwise return to normal contractility in 4 to 5 minutes."

Page 571. The third sentence under Summary and Conclusions should read, "The D-L substance is heat stable."
Permeability of the Bladder to Water Studied by Means of Isotopes
Authors: Johnson John A. , Cavert H. Mead , Lifson Nathan , Visscher Maurice B.
Published: December 2017

Page 89. J. A. Johnson, H. M. Cavert, N. Lifson and M. B. Visscher, "Permeability of the Bladder to Water Studied by Means of Isotopes." The sentence which begins under table 1 should read: "Upon integration the above equation yields, In (See PDF), where S0 is the isotope concentration at t = 0, and k can be obtained from plotting log (See PDF) against time."
Glomerular and Tubular Influences on Sodium and Water Excretion
Authors: Mueller C. Barber , Surtshin A. , Carlin M. Richard , White H. L.
Published: December 2017

Page 418. C. B. Mueller, A. Surtshin, M. R. Carlin and H. L. White, "Glomerular and Tubular Influences on Sodium and Water Excretion." In footnote 4 "table 2" should read "table 1 B."