bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial compliance and transcapillary Starling pressures in cat skin and skeletal muscle
Authors: Wiig H. , Reed R. K.
Published: December 2017

Interstitial compliance, defined as change in local interstitial fluid volume (delta IFV) divided by the corresponding change in local interstitial fluid pressure (delta IFP), has been measured in skin and muscle of pentobarbital-anesthetized cats. IFP was measured with micropipettes and IFV as the difference between 51Cr-ethylenediaminetetraacetic acid space and 125I-human serum albumin space. IFV was altered by overhydration (saline infusion, 10% of body wt, or by femoral vein ligation plus saline infusion, 20% of body wt) or by dehydration (peritoneal dialysis with 20% glucose). Control IFV in skin and muscle averaged 1.45 (SD 0.44, n = 22) and 0.37 (SD 0.04, n = 22) ml/g dry wt, respectively, with corresponding IFP of -1.9 (SD 0.4, n = 22) and -0.8 (SD 0.6, n = 22) mmHg. During dehydration, IFV fell by 5.5 and 10.4% per mmHg fall in IFP in skin and muscle, respectively. The maximal rise in IFP during overhydration was about 2 mmHg in both tissues. Analysis of covariance showed that compliance was lower in cats than in rats during dehydration (P less than 0.05). At subnormal IFV, IFP will therefore be more powerful in opposing capillary absorption of interstitial fluid in cats than in rats. IFP is, however, of similar importance in edema prevention in the two species.
Carotid sinus and blood pressure control during hindlimb and forelimb contractions
Authors: Beaty O.
Published: December 2017

Arterial blood pressure (ABP) regulation during exercise involves in part medullary interaction of afferent information from contracting skeletal muscles and the major baroreceptors. This study examined in chloralose-anesthetized dogs the role of the carotid sinus baroreceptors in modulating reflex changes in ABP, nonexercising hindlimb skeletal muscle vascular resistance, and heart rate (HR) evoked by two separately contracting (4, 16, and 48 Hz) groups of skeletal muscle, the right hindlimb and forelimb. When arterial and cardiopulmonary baroreceptor afferent information was interrupted, hindlimb contractions evoked a greater augmentation of ABP (16 and 48 Hz) and no further increase in nonexercising hindlimb perfusion pressure (HLPP). Forelimb contractions, which in the presence of baroreceptors had not affected ABP (4 and 16 Hz), now reduced it profoundly. Nonexercising HLPP, which increased independently of contraction frequency, now was decreased by 4 Hz, not affected by 16 Hz, and increased by 48 Hz. The increase in HR was abolished. Increasing carotid sinus pressure to 220 mmHg in vagotomized dogs abolished the reflex changes evoked by hindlimb skeletal muscle contractions. However, forelimb contractions continued to decrease ABP. Nonexercising HLPP and HR did not change from the precontraction values. These data indicate that the carotid sinus baroreceptor could buffer completely those changes in the selected cardiovascular variables evoked by hindlimb but not forelimb skeletal muscle contractions. Thus the role of the carotid sinus baroreceptors in controlling ABP during exercise depends on the group of skeletal muscle initiating the somatic afferent signal and its influence on the contraction-induced distribution of the efferent signals.
Pressure and tone dependence of coronary diastolic input impedance and capacitance
Authors: Canty J. M. , Klocke F. J. , Mates R. E.
Published: December 2017

To quantify reactive elements of the coronary circulation, we have characterized in vivo diastolic coronary input impedance by introducing sinusoidal pressure oscillations of constant amplitude and varying frequency at constant mean pressure levels during prolonged diastoles in heart-blocked dogs anesthetized with pentobarbital. The behavior of coronary input impedance is similar to that observed in other peripheral vascular beds and is a function of both mean distending pressure and vasomotor tone. The behavior of impedance modulus and phase at each pressure level could be described by a lumped resistive-capacitive (RC) parallel model over a frequency range of 1-5 Hz. At higher frequencies the phase angle response could be characterized by adding a Voigt viscoelastic element to the original RC model. Calculated coronary capacitances for both models were similar in magnitude and varied inversely with mean coronary distending pressure. Values for the RC and RC viscoelastic model in the maximally dilated coronary bed were 14.1 and 21.6 X 10(-3) ml X mmHg X 100 g-1 at 30 mmHg and 2.65 and 2.70 X 10(-3) ml X mmHg-1 X 100 g-1 at 110 mmHg. With vasomotor tone intact, calculated coronary capacitance at each pressure level was reduced by a factor of two. These results indicate that an RC parallel model with pressure- and vasomotor tone-dependent capacitance adequately describes diastolic coronary input impedance at frequencies encountered during ordinary diastoles. The addition of a viscoelastic element provides adequate fits up to frequencies of 10 Hz.
Adenosine inhibition of catecholamine-stimulated cardiac membrane adenylate cyclase
Authors: LaMonica D. A. , Frohloff N. , Dobson J. G.
Published: December 2017

Adenosine inhibition of hormone-sensitive adenylate cyclase activity was investigated using isolated myocardial membranes prepared from rat hearts. When cyclase activity was determined in membranes, using [alpha-32P]ATP as substrate, 10(-5) M adenosine inhibited isoproterenol-stimulated adenylate cyclase activity by 25% but did not inhibit basal activity or fluoride (5 mM) activation of the enzyme. The adenosine reduction of isoproterenol-sensitive cyclase activity was dependent on GTP but was not prevented by 10(-3) M theophylline. Adenosine neither appeared to compete with ATP for the substrate converting site of the enzyme nor reduced 5'-guanylyl imidodiphosphate activation of the enzyme. Inasmuch as lower concentrations of adenosine had no influence on enzyme activity, endogenous adenosine may be present in the adenylate cyclase assay. To obviate the effects of endogenous adenosine, the adenylate cyclase assay was then modified to a 2'-deoxy system with [alpha-32P]dATP used as the substrate in the presence of adenosine deaminase. With this assay system, the 15% inhibition of isoproterenol-stimulated adenylate cyclase activity produced by the adenosine receptor agonists, 10(-8) M 2-chloroadenosine or phenylisopropyladenosine, was prevented by 10(-4) M 8-phenyltheophylline or isobutylmethylxanthine (IBMX), respectively. While under these assay conditions, 10(-7) M 2',5'-dideoxyadenosine, a P-site analogue, did not influence the hormone-sensitive cyclase activity. The 35% reduction of the hormone-sensitive enzyme produced by this analogue at 10(-5) M was not prevented by IBMX. These results suggest that nanomolar concentrations of adenosine analogues interact with a methylxanthine-sensitive adenosine receptor that mediates the attention of membrane hormone-sensitive adenylate cyclase activity.
Functional modulation of cell coupling: evidence for a calmodulin-driven channel gate
Authors: Peracchia C. , Girsch S. J.
Published: December 2017

Much of the capacity of tissues to respond to signals as well integrated systems is due to the existence of direct cell-to-cell communication pathways. This type of communication, usually referred to as cell coupling, is based on the presence of cell-to-cell channels permeable to ions, metabolites, and regulatory compounds. The cell-to-cell channels are located at specialized regions of cell contact known as gap junctions or communicating junctions. An important aspect of cell coupling is channel permeability modulation. In recent years this feature of cell coupling has received a great deal of attention, most efforts being aimed at identifying uncoupling treatments and uncoupling agents and at determining the elements of the channel gating mechanism. This review focuses on recent studies suggesting the participation of calmodulin-like proteins in channel gating and on the application of in vitro approaches to cell coupling research-the study of permeability and gating of cell-to-cell channels incorporated into liposomes and the determination of conformational changes in isolated channel protein.
Intracoronary adenosine enhances myocardial reactive hyperemia after brief coronary occlusion
Authors: Saito D. , Hyodo T. , Takeda K. , Abe Y. , Tani H. , Yamada N. , Ueeda M. , Nakatsu T.
Published: December 2017

Adenosine is a prime candidate for the role of mediator between myocardial metabolic state and coronary blood flow. However, there are few reports concerning the direct effects of exogenously added adenosine on coronary autoregulation. The present investigation in the open-chest dog studied the effects of a threshold dose of intracoronary adenosine infusion on reactive hyperemia following brief coronary occlusions. The infused dose did not increase nonocclusive flow by greater than 10%. Adenosine enhanced total hyperemic flow at all occlusions tested (5, 10, 15, 20, and 30 s). Aminophylline pretreatment reduced reactive hyperemia below the control level even in the presence of an intracoronary infusion of adenosine. Adenosine injected into the left atrium and intracoronarily infused papaverine did not affect hyperemic response to 5- and 15-s coronary occlusions. The results suggest that a minimum dose of exogenously added adenosine enhances myocardial reactive hyperemia, possibly by potentiating the effects of endogenous adenosine released during ischemia.
Role of vessel wall in acute resetting of aortic baroreceptors
Authors: Munch P. A. , Brown A. M.
Published: December 2017

Previously we found that baroreceptor (BR) pressure-frequency (PF) curves rapidly (5 min) reset to changes in mean arterial pressure (MAP) exclusive of sympathetic efferents or circulating hormones. Since BRs are mechanically coupled to vessel wall structures, resetting may be due to changes in the wall. This was examined using an in vitro rat aortic arch-aortic nerve preparation and a photoelectric device to measure arch diameter. Pressure-diameter (PD) curves were constructed at selected MAPs following the resetting protocol used previously [Am. J. Physiol. 244 (Heart Circ. Physiol. 13): H672-H680, 1983]. Overall there was no consistent relationship between the PD curves and MAP, which was in sharp contrast to BR PF resetting. To determine if smooth muscle tone could affect aortic or BR function, the arch was constricted or relaxed with norepinephrine (NE) or sodium nitroprusside (NP), respectively. BR PF and aortic PD curves were constructed before and after drug treatment. NE reduced and NP increased discharge at given pressures. Diameter-frequency (DF) plots were not altered by either drug. PD and PF curves at constant MAP were stable after the initial responses to NP relaxation were completed. Subsequent MAP elevations in NP reset BRs to higher pressures, whereas PD curves shifted to lower pressures. Hence, DF plots shifted to higher diameters. These results show that neither smooth muscle activity nor mechanical changes in the whole wall can account for BR rapid resetting. The process probably occurs in the receptors.
Prostaglandins and fetal cardiac output distribution in the lamb
Authors: Sideris E. B. , Yokochi K. , Coceani F. , Olley P. M.
Published: December 2017

With the use of a triple thermodilution technique in 17 fetal lambs, combined with microsphere estimations in 7, the effects of indomethacin prostaglandin (PG) I2 and PGE2 on cardiac output and its distribution were measured. Indomethacin (0.2 mg/kg) induced a main pulmonary artery-to-aorta pressure gradient, which peaked within 45–60 min and persisted for 2–3 h. PGE2 abolished this gradient (threshold 50 ng X kg-1 X min-1), while PGI2 in doses up to 100 ng X kg-1 X min-1 increased it. Indomethacin did not change total cardiac output but altered its distribution (right ventricular output, left ventricular output) and increased the percentage of right ventricular output flowing to the lungs. Ductal flow decreased concomitantly. After indomethacin, PGI2 further decreased ductal flow, increased pulmonary flow, and decreased pulmonary vascular resistance. PGE2 restored the original right ventricular-to-total cardiac output ratio, although ductus flow did not return to base-line levels. Pulmonary resistance increased slightly, reflecting decreased pulmonary flow, associated with decreased right ventricular output. Thus PGE2 was more effective on the ductus than on the pulmonary circulation. PGI2 did not relax the ductus but was a potent pulmonary vasodilator. Neither PGI2 nor PGE2 nor indomethacin changed total cardiac output but all altered its distribution.
Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy
Authors: Anversa P. , Loud A. V. , Levicky V. , Guideri G.
Published: December 2017

To determine whether left ventricular failure after acute myocardial infarction is associated with a growth response of the myocytes that tends to compensate for the loss of muscle mass and function, the left coronary artery in rats was ligated near its origin, and the animals were killed 3 days later. Elevated left ventricular end-diastolic pressure and decreased first derivative of left ventricular pressure and systolic arterial pressure indicated significant impairment of ventricular function. Absolute infarct size, determined morphometrically by measurement of the fraction of myocyte nuclei lost, averaged 57%. Hypertrophy of surviving left ventricular myocytes was 28%, involving a 14% increase in cell length and a 6% increase in diameter. Right ventricular myocyte volume per nucleus increased 21% by a 10% enlargement of cellular diameter with no change in length. These results show on a cellular basis that myocardial hypertrophy in the left ventricle is accomplished by cellular shape changes characteristic of a combination of pressure and volume overload hypertrophy, whereas cellular growth in the right ventricle is consistent with pressure overload hypertrophy.
Effects of physiological beating on the contractility of cat ventricular muscle
Authors: Hanck D. A. , Jewell B. R.
Published: December 2017

Force and length changes corresponding to those undergone by muscle fibers in the ventricular wall of the heart during systole and diastole were generated in isolated cat ventricular muscles contracting at 30 degrees C. The effect on contractility of such cycles of force and length changes (“physiological” contractions) was assessed by measuring force production in isometric test beats. Contractility rose over the 1st min of physiological beating but then fell over the next 7–10 min. These changes in contractility were compared with those occurring during a series of isotonic contractions or modified isotonic contractions in which muscles were held at the short length during relaxation (reversed relaxation contractions). In all cases contractility increased to the same extent over the 1st min, but over the next 10 min it fell significantly more when the contractions were physiological than when they were isotonic (normal or reversed relaxation). This difference could be accounted for experimentally by the diastolic length changes that occur in physiological contractions. This study demonstrates 1) that contractility depends on length changes occurring in the muscle during both systole and diastole, and 2) that length-dependent changes in contractility contain both positive and negative components.
Restoration of coronary dilator action of adenosine in experimental diabetes
Authors: Downing S. E.
Published: December 2017

We have recently shown that the coronary dilator action of adenosine is reduced in animals with experimental diabetes mellitus. Effects of insulin replacement are reported in the present study. Lambs, age 6-17 days, were studied 1-2 days after induction of diabetes with alloxan (150 mg/kg; n = 6). These were compared with nondiabetic controls, age 4-15 days (n = 5). A third group was studied after 8-15 days of diabetes (n = 3). In the acute diabetics blood glucose was 362 +/- 48 mg/dl. Heart rate, dP/dtmax, and myocardial O2 consumption did not differ from controls, but pH tended to be lower (7.29 +/- 0.03). Adenosine was given by left ventricular infusion. Coronary flow changes were significantly lower at all infusion rates (3-15 micrograms X min-1 X kg-1) in the untreated diabetics. Dose-response curves before and after insulin (10 U/kg) were identical in controls. However, in the diabetics, insulin enhanced the dilator response to adenosine, and changes in coronary flow at each infusion rate did not differ from controls. Aminophylline (6 mg/kg) abolished or sharply reduced the dilator responses to adenosine in both controls and diabetics (P less than 0.01). Animals diabetic 1-2 wk were unresponsive to adenosine. But after insulin, the nucleoside elicited vigorous coronary dilatation. It is concluded that insulinopenic diabetes is accompanied by sharply reduced adenosine sensitivity of coronary resistance vessels. Sensitivity is restored by giving insulin. This hormone may modulate adenosine receptor properties of vascular smooth muscle.
Slow inward current may produce many results attributed to IX1 in cardiac Purkinje fibers
Authors: Jaeger J. M. , Gibbons W. R.
Published: December 2017

We have tried to answer two fundamental questions concerning the outward current IX1 of cardiac Purkinje fibers. 1) Is it possible that current changes identified as arising from IX1 in voltage-clamp experiments are actually manifestations of changes in the slow inward current (Isi); and 2) is IX1 in fact required to produce the electrical phenomena attributed to it? Isi behavior and the role of IX1 were explored using computer simulation. The Isi model produced current changes during depolarizations and hyperpolarizations from depolarized resting potentials like those attributed to IX1. It also produced a component of "tail currents" that behaved like IX1. If these current changes were analyzed, assuming that an outward current is responsible, the resulting kinetics and current voltage relation would be very similar to the kinetics and current voltage relation reported for IX1. Using the McAllister, Noble, and Tsien formulation of the Purkinje fiber action potential, we found that IX1 is not essential for repolarization of the reconstructed action potential nor is it needed to reproduce interval duration effects and the effects of applied current in that model. Data suggesting that calcium channel blockers reduce IX1 and that catecholamines increase IX1 may be explained as arising from changes in Isi. Thus many manifestations of IX1 can be explained as arising from unanticipated behavior of Isi, and IX1 does not necessarily play a key role in generating Purkinje fiber electrical activity.
Differential responses accompanying sequential stimulation and ablation of vagal branches to dog heart
Authors: Randall W. C. , Ardell J. L. , Becker D. M.
Published: December 2017

Electrical excitation of small thoracic vagal branches elicited highly localized responses in the canine heart. Specific pathways to the sinoatrial nodal (SAN) regions were identified from negative chronotropic responses to stimulation (20 Hz, 5.0 ms, 3.0-5.0 V) of these branches. Pathways to the atrioventricular nodal (AVN) region were determined from changes in A-H interval (His bundle electrogram) and incidence of heart block as vagal branches were stimulated during concurrent atrial pacing. A few small branches influenced a single cardiac function (atrial rate, contractile force, or AV conduction). More commonly, activation of such branches elicited simultaneous chronotropic and dromotropic effects. However, many branches failed to elicit any detectable cardiac change. The major outflow from the left vagus to SAN and AVN regions is by way of cardiac branches from the recurrent laryngeal nerve at its reflection around the aorta. Activation of the left recurrent nerve reduced atrial rate by 43% and doubled A-H interval 84 to 167 ms. The right thoracic vagus or its branches induced A-H prolongation from 78 to 131 ms. H-V intervals remained constant at a mean of 35 ms. Outflows from the right thoracic vagus to SAN and/or AVN regions originated just below the middle cervical ganglion and at all levels down to the azygos vein.
Effects of anesthetics on regional hemodynamics in normovolemic and hemorrhaged rats
Authors: Seyde W. C. , McGowan L. , Lund N. , Duling B. , Longnecker D. E.
Published: December 2017

Twenty-nine male Sprague-Dawley rats were divided into four groups based on anesthetic exposure, i.e., awake animals and those receiving anesthesia produced by chloralose-urethan, pentobarbital, or by midcollicular brain stem transsection. Before and after hemorrhage (30% of the estimated blood volume), cardiac output (CO) and regional blood flows were measured by the microsphere method. Arterial blood gases and lactate (L) and pyruvate (P) were also determined. CO and regional blood flows were greatest and the L/P ratio was least in awake animals both before and after hemorrhage. In normovolemic rats, the frequency of altered values (as compared with those in awake animals) was similar for all anesthetic techniques, whereas the CO and regional blood flow responses to hemorrhage were altered less frequently in decerebrated animals. Decerebration may be the preferable procedure if the intent is to produce responses in anesthetized animals similar to those in awake rats. If the intent is to study hemodynamics in a specific organ, the selection of an anesthetic technique should be guided by the individual anesthetic effects on that particular tissue.
Vasopressin withdrawal produces hypotension in the spontaneously hypertensive rat
Authors: Chiu E. K. , McNeill J. R.
Published: December 2017

In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous infusions of either arginine vasopressin (AVP, 8 mU X kg-1 X min-1) or phenylephrine (PE, 20 nmol X kg-1 X min-1) resulted in similar rises in arterial pressure. Heart rate fell greatly in the WKY but not in the SHR. Withdrawal of the PE infusion resulted in moderate decreases in blood pressure and increases in heart rate; these responses were similar in SHR and WKY. At 5 h after PE withdrawal, blood pressure and heart rate returned to basal values. In contrast, withdrawal of the AVP infusion was associated with greater falls in blood pressure and rises in heart rate. Blood pressure and heart rate in both the SHR and the WKY at 5 h after AVP were significantly different from their respective basal values. The effects of AVP withdrawal on either blood pressure or heart rate were significantly greater in the SHR than in the WKY. At 5 h after the withdrawal of AVP, blood pressure in the SHR was reduced to normotensive levels. These results suggest that the withdrawal effect was specific to AVP, was more marked in the SHR, and might not result from only the rise in blood pressure seen during the intravenous infusion of the pressor agent.
Response of canine cardiocyte lysosomes to ATP
Authors: Spanier A. M. , Dickens B. F. , Weglicki W. B.
Published: December 2017

The present study was designed to evaluate the relationship of adenosine triphosphate (ATP) to maintenance of cardiac lysosome latency. Highly latent lysosomes were isolated from adult canine ventricular myocytes or cardiocytes and exhibited latency values (based on % free N-acetyl-beta-glucosaminidase, NAGA) of 29.3 +/- 4.7% (SE), minimal cross contamination by mitochondria (less than 2% cardiolipin by weight) and only 1.68% of the total cytochrome c oxidase activity; enzymatic enrichments ranged from 10-fold for NAGA to almost 50-fold for cathepsin B. Incubations of cardiocyte lysosomes at pH 7.0 and 25 degrees C for up to 1 h resulted in changes in the rate of loss in lysosomal latency when ATP levels were adjusted from 0.0 to 5.0 mM; under these conditions as ED50 of 0.62 mM ATP was determined. The protection afforded by ATP was reversed by addition of the H+ ionophore m-chlorocarbonylcyanide phenylhydrazone (CCCP) at 10 microM to the lysosomal suspensions. A significant increase in lysosomal membrane fluidity, measured by fluorescent polarization of diphenylhexatriene, was also seen in the absence of ATP. Adenosine diphosphate (ADP) afforded significant protection only at the very highest concentration (5.0 mM); inorganic pyrophosphate (PPi) did not protect against loss of latency at any concentration. Thus ATP exerts a significant stabilizing effect on cardio(myo)cyte lysosomes in vitro and may be one of the metabolites regulating lysosomal integrity in vivo.
Prostaglandin involvement in hypersensitivity of ischemic hearts to arrhythmogenic influence of ouabain
Authors: Moffat M. P. , Karmazyn M. , Ferrier G. R.
Published: December 2017

Arrhythmias were produced by ouabain (2.7 X 10(-7) M) in isolated perfused guinea pig hearts. In control hearts the average time to onset of arrhythmias following exposure to ouabain was approximately 35 min. Ligation of the left anterior descending coronary artery significantly shortened the time to arrhythmias to about 15 min. This effect of ligation was attenuated significantly by pretreating the hearts with acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs. In contrast, the protective influence of ASA was reversed by either prostaglandin (PG) E2, PGF2 alpha, or PGI2 (2.8 X 10(-9) M). When PGE2 or PGI2 were present in the absence of ASA, the time to arrhythmias following ouabain administration was significantly shortened. PGF2 alpha had no effect in these experiments. The sensitivity was enhanced significantly by treatment with arachidonic acid. This effect was reduced by treatment with ASA or indomethacin. Prostaglandin production during the experiments was estimated by monitoring release of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin. Abbreviation of time to arrhythmias by ligation was greatest in hearts that released large amounts of 6-keto-PGF1 alpha and least in those that released low amounts. These results suggest that coronary ligation potentiates the arrhythmogenic effects of ouabain by a mechanism probably mediated by prostaglandin(s).
Enhanced depressor effect of bromocriptine in the DOCA/NaCl hypertensive rat
Authors: Nagahama S. , Chen Y. F. , Oparil S.
Published: December 2017

To elucidate the role of the dopaminergic system in the maintenance of hypertension in the deoxycorticosterone acetate (DOCA)/NaCl hypertensive rat, the responses of mean arterial pressure (MAP), plasma norepinephrine (NE), epinephrine (E), and prolactin (PRL) to intravenous (iv) administration of bromocriptine, a dopamine agonist, and hexamethonium bromide, a ganglion blocker, were examined in conscious, unrestrained 4-wk DOCA/NaCl hypertensive rats. Bromocriptine was administered to adrenomedullectomized (ADMX) rats to assess the role of the adrenal medulla in its depressor effect. Bromocriptine (50, 250, and 500 micrograms/kg) and hexamethonium (3 and 30 mg/kg) caused dose-dependent decreases in MAP that were greater in DOCA/NaCl rats than in uninephrectomized controls. Basal plasma NE, E, and PRL were significantly higher in DOCA/NaCl rats than in controls. Bromocriptine (500 micrograms/kg iv) decreased plasma PRL to undetectable levels and increased plasma E significantly without changing NE levels in DOCA/NaCl and uninephrectomized control rats. In ADMX rats bromocriptine (500 micrograms/kg iv) decreased MAP, PRL, and NE without affecting E levels. These results suggest that the depressor response to bromocriptine could be related to inhibition of sympathetic outflow without participation of the adrenal medulla. The hyperprolactinemia and enhanced depressor response to bromocriptine observed in DOCA/NaCl animals suggest that the dopaminergic system might be altered in this model of hypertension.
Chronic infarction decreases maximum cardiac work and sensitivity of heart to extracellular calcium
Authors: Fellenius E. , Hansen C. A. , Mjos O. , Neely J. R.
Published: December 2017

Rat hearts were infarcted in vivo by ligation of the left ventricular coronary artery to cause an initial 40% loss of viable tissue by weight. Due to compensatory hypertrophy of the surviving myocardium and progression of the infarct to scar tissue, the infarct represented approximately 25% by weight of the whole heart after 1 wk. After 1 or 3 wk, these infarcted hearts were removed and perfused in vitro by the working hearts technique. Ventricular pressure development and positive dP/dt were lower in infarcted hearts compared with sham-operated ones. O2 consumption and glucose utilization by viable tissue per unit pressure development was the same in normal and infarcted hearts. Levels of creatine phosphate and free creatine were decreased, but ATP and total adenine nucleotides were well maintained. The inotropic response to decreases in extracellular [Ca2+] was much greater in infarcted hearts than in sham controls. Prenalterol increased ventricular function proportionally more in infarcted than in the sham-operated hearts, suggesting that down regulation of beta receptors was not a problem. The infarcted hearts were much more sensitive to verapamil than control hearts. It is concluded that the depressed function of the noninfarcted tissue of chronically infarcted hearts is due in part to loss of functioning tissue mass and in part to decreased sensitivity to extracellular Ca2+.
Dietary salt loading produces baroreflex impairment and mild hypertension in rats
Authors: Miyajima E. , Bunag R. D.
Published: December 2017

Mild hypertension with reduced chronotropic baroreflex sensitivity to phenylephrine occurred in Sprague-Dawley rats fed a high-salt diet for 5 wk. Progressive elevation of systolic and mean pressures, detected initially by indirect tail-cuff measurement, was later verified by direct recording of phasic pressures from indwelling aortic catheters in the same rats. Reflex bradycardia during pressor responses to phenylephrine was consistently less pronounced in salt-loaded than in control rats, whether tested while rats were awake or anesthetized. However, attendant decreases in renal nerve activity were not appreciably altered. Neither central nor carotid baroreceptor mechanisms were considered likely but aortic baroreceptors must have somehow been depressed because increases in afferent aortic nerve activity elicited during intravenous infusion of phenylephrine were invariably smaller in salt-loaded than in control rats. Whatever the underlying mechanisms may be, our results show that when hypertension develops during dietary salt loading, baroreflex chronotropic responses are selectively inhibited while attendant decreases in renal nerve activity are preserved.
Saxitoxin binding and "fast" sodium channel inhibition in sheep heart plasma membrane
Authors: Doyle D. D. , Brill D. M. , Wasserstrom J. A. , Karrison T. , Page E.
Published: December 2017

We compared specific [3H]saxitoxin (STX) binding to isolated sheep ventricular sarcolemmal vesicles with inhibition of maximal action potential upstroke velocity (V max) by STX and tetrodotoxin (TTX) in sheep trabeculae carneae. In sarcolemmal vesicles purified 30 to 40 times over cardiac homogenate, STX binding at 0 degrees C in Na-free solution exhibited both high-affinity sites (KD = 0.22 +/- 0.05 nM, n = 85 +/- 13 fmol/mg protein) and low-affinity sites (KD = 11 +/- 4 nM, n = 360 +/- 42). The STX-inhibition constant for V max in Tyrode solution at 37 degrees C was 280 nM. TTX was approximately 10% as effective as STX in displacing bound [3H]STX and inhibiting V max. Allowing for different experimental conditions during [3H]STX binding and V max measurements, we suggest that the low-affinity sites are physiologically relevant "fast" Na+ channels of myocardial cells. Combining morphometric data for plasmalemmal area of mammalian cardiac myocytes with n for low-affinity sites, we estimate 3.6-7.6 fast Na+ channels/micron2 plasmalemma.
Effects of peptide leukotrienes on cardiac dynamics in rat, cat, and guinea pig hearts
Authors: Roth D. M. , Lefer D. J. , Hock C. E. , Lefer A. M.
Published: December 2017

The purpose of the present investigation was to examine potential inotropic effects of leukotrienes C4 (LTC4) and D4 (LTD4) in relation to their potent coronary constricting effects. The experiments were carried out in isolated Langendorff perfused hearts and isolated electrically driven isometrically contracting papillary muscle preparations. Tissues from cat, rat, and guinea pig were used in the study. Both LTC4 and LTD4 at 50 ng/ml had no effect on papillary muscles isolated from the rat, guinea pig, or cat. These papillary muscles responded to known negative inotropic agents including pentobarbital sodium and methanol. In isolated hearts perfused under constant flow, both LTC4 and LTD4 at 50 ng/ml increased coronary perfusion pressure and decreased contractile force of the heart in all three species. In hearts perfused under constant pressure perfusion, both LTC4 and LTD4 decreased coronary flow with concomitant decreases in contractile force. The leukotriene antagonist, FPL 55712, blocked both the coronary constrictor and the cardiodepressant effects of both leukotrienes. Pentobarbital (100 micrograms/ml) significantly decreased cardiac contractile force without inducing coronary vasoconstriction. These findings demonstrate that LTC4 and LTD4 do not possess direct negative inotropic activity in cardiac muscles of these three species. However, LTC4 and LTD4 are potent coronary constrictors that can secondarily decrease myocardial contractile force via their coronary constrictor action.
Age-related changes in regional blood flow in the rat
Authors: Tuma R. F. , Irion G. L. , Vasthare U. S. , Heinel L. A.
Published: December 2017

The purpose of this investigation was to characterize the changes in regional blood flow and central hemodynamic measures that occur in the rat as a result of the aging process. The isotope-labeled microsphere technique was used to measure cardiac output and regional blood flows in conscious and anesthetized adult (12 mo) and senescent (24 mo) Fischer 344 virgin female rats. No significant changes were observed in central hemodynamic measurements or regional blood flows in conscious rats with the exception of a 25% reduction in splenic blood flow. Pentobarbital anesthesia significantly reduced cardiac index and heart rate but elevated total peripheral resistance and mean arterial blood pressure. There was a decrease in blood flow to skeletal muscle, spleen, duodenum, stomach, and brain tissue samples and increased hepatic arterial blood flow in both age groups. The use of anesthesia caused a greater reduction in the cardiac index and brain blood flow in the senescent anesthetized rats than in the adult rats. Heart and kidney blood flows were decreased by anesthesia in the senescent rats but not in the adult rats. Skeletal muscle blood flow, however, was significantly greater in the senescent anesthetized rats than in the younger anesthetized animals. Although body weight and organ weights of the liver, spleen, kidneys, stomach, heart, and brain were significantly greater for the senescent rats, no differences could be demonstrated in tibial length or lean body mass.
Relationship between caffeine effects and calcium in canine cardiac Purkinje fibers
Authors: Di Gennaro M. , Vassalle M.
Published: December 2017

The actions of caffeine (1-9 mM) on electrical and mechanical events were studied under conditions known to change the intracellular calcium in canine cardiac Purkinje fibers perfused in vitro. It was found that caffeine in a dose-dependent manner 1) shifts the early repolarization to more positive values, 2) shifts the plateau to more negative values, 3) prolongs the terminal phase 3 (induction of a "tail"), 4) transiently increases and then decreases the force of contraction with respect to control values, 5) causes a smaller tail in the presence of agents (local anesthetics, tetrodotoxin, high potassium) that have been shown to diminish the force of contraction, presumably by decreasing cellular calcium, 6) causes the oscillatory potentials in high calcium to peak sooner after the action potential and eventually to disappear as the tail develops, 7) induces a tail at lower concentrations when cellular calcium is enhanced by lowering the external sodium concentration or in the presence of veratridine, and 8) fails to induce a marked tail in the presence of metabolic inhibitors. It is concluded that in Purkinje fibers caffeine induces a marked delay in the final repolarization through a process modulated by calcium. This process may be related to an electrogenic sodium-calcium exchange.
Standardization of end-systolic pressure-volume relation in the dog
Authors: Belcher P. , Boerboom L. E. , Olinger G. N.
Published: December 2017

Left ventricular (LV) volume elastance (Emax) and its volume intercept (Vo) are subject to considerable intersubject and interspecies variation. In humans, indexing with body surface area does not decrease variance. Because these are volume indexes, it was considered they would better standardize against body or LV weight. Fifteen open-chest mongrel dogs (mean wt 25.9 +/- 8.0 kg, range 15.6-42.5) were studied under 1% halothane anesthesia. Emax, derived by caval occlusion, averaged 9.0 +/- 4.4 mmHg X ml-1 (range 4.1-16.1) with a coefficient of variation (CV) of 48%. Average Vo was 19.6 +/- 10.5 ml (range 8.3-40.3) with a CV of 53%. LV weight was 110 +/- 21 g (range 78-147). Vo correlated best with LV weight: Y = 0.47 X - 31.78, r = 0.93, and adjustment of Vo by regression reduced CV to 20%. Emax was closely correlated with either 1/dog wt [Y = 313.02 (1/X) - 4.16, r = 0.88, CV = 23% after adjustment by regression] or 1/LV wt [Y = 2088.63 (1/X) - 10.72, r = 0.86, CV = 25% after adjustment]. Indexing of Emax by dog weight (CV = 29%) or LV weight (CV = 35%) reduced variation but by less than adjustment by regression. A subset of eight dogs had inotropic state varied, which had no effect on the relation between Vo and LV weight, but which resulted in an appropriate change (P less than 0.025) in the relation between Emax and 1/LV wt.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevention of fatal hemorrhagic shock in dog by pretreatment with chronic high-salt diet
Authors: Rocchini A. P. , Gallagher K. P. , Botham M. J. , Lemmer J. H. , Szpunar C. A. , Behrendt D.
Published: December 2017

The ability of a chronic high-salt diet to prevent fatal hemorrhagic shock was examined in 36 mongrel dogs. Twenty-one dogs received a dietary supplement of 9 g sodium chloride/day for 6 wk, and 15 dogs received the same basic diet for 6 wk but without the sodium chloride supplement. Hemorrhagic shock was induced in all dogs by bleeding into an overhanging sealed reservoir. After 3 h of shock, salt-pretreated dogs had a lower systemic vascular resistance of 0.70 +/- 0.02 versus 1.44 +/- 0.04 mmHg X ml-1 X min X kg (P less than 0.01) and a higher cardiac output of 53 +/- 3 versus 26 +/- 3 ml X min-1 X kg-1 (P less than 0.01) than was observed in controls. At 2.5 h of shock, the salt-pretreated dogs also experienced an increase in gastrointestinal (P less than 0.01), hepatic arterial, (P less than 0.05), kidney (P less than 0.05), brain (P less than 0.01), and heart blood flows (P less than 0.001) compared with 0.5 h of shock, whereas the control dogs experienced no increased flow during this same period. We also observed that after 3 h of hypotension there was a significantly smaller increase in plasma renin activity in the salt-pretreated dogs. Administration of 0.1 U X kg-1 X min-1 of hog renin eliminated the differences in systemic vascular resistance, cardiac output, and survival in five salt-pretreated dogs.
Influence of buffers on dV/dtmax recovery kinetics with lidocaine in myocardium
Authors: Stambler B. S. , Grant A. O. , Broughton A. , Strauss H. C.
Published: December 2017

Buffers are reported to modify electrical function of heart tissue. Since electrophysiological actions of antiarrhythmic drugs are examined in different buffer systems, we set out to examine the influence of buffers on lidocaine's electrophysiological actions by measuring recovery kinetics of maximum upstroke velocity (dV/dtmax) in lidocaine solutions buffered with HCO-3-CO2, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), and tris(hydroxymethyl)aminomethane (Tris) at extracellular pH 7.4. Transmembrane potential and dV/dtmax were recorded from guinea pig papillary muscle. Recovery kinetics were determined by introducing progressively earlier test stimuli during diastole. During lidocaine (1.5 X 10(-5) M) exposure, the time constant (Tr) of dV/dtmax recovery significantly increased when 21 mM HCO-3-5% CO2 was replaced by either 5 mM HEPES (38 +/- 8%, mean, +/- SED) or 5 mM Tris (41 +/- 6%). This potentiation of Tr was 1) reversed by increasing Tris to 20 mM, and 2) also abolished by restoring HCO-3-CO2 to HEPES or Tris solutions. Decreasing HCO-3 (21-4 mM) and CO2 (5-1%) increased Tr by 27 +/- 1%. We propose that the mechanism for the potentiation of Tr is therefore related to buffer concentration rather than to the lack of HCO-3-CO2. We speculate that, by reducing surface pH, lowered buffer capacity can slow the rate of dV/dtmax recovery.
BAY K 8644 potentiates and A23187 inhibits hypoxic vasoconstriction in rat lungs
Authors: McMurtry I. F.
Published: December 2017

The susceptibility of hypoxic pulmonary vasoconstriction to inhibition by Ca2+ channel antagonists suggests that membrane depolarization and Ca2+ influx are components of the hypoxic mechanism. Recent characterization of BAY K 8644 as a 1,4-dihydropyridine that facilitates Ca2+ influx through partially activated voltage-dependent Ca2+ channels provides a new pharmacological tool to further test this idea. Effects of BAY K 8644 on normoxic vascular tone and on hypoxic and angiotensin II-induced vasoconstriction were examined in isolated rat lungs perfused with either blood or physiological salt solution (PSS) containing meclofenamate. Parallel experiments were performed with the Ca2+ ionophore A23187 for comparison with a Ca2+-active agent that does not act selectively on the voltage-dependent Ca2+ channel. Addition of BAY K 8644 (10(-7) to 10(-5) M) to the perfusate did not alter base-line vascular tone of the normoxic lung, but it potentiated hypoxic and angiotensin II pressor responses. For example, addition of 10(-7) M BAY K 8644 to five PSS-perfused lungs increased the hypoxic (5% O2) pressor response from 8.7 +/- 2.1 to 19.5 +/- 4.2 Torr and the angiotensin II (0.1 micrograms) response from 2.1 +/- 0.4 to 6.5 +/- 2.0 Torr. In contrast, addition of A23187 (10(-7) to 10(-6) M) to the perfusate increased normoxic perfusion pressure and inhibited hypoxic vasoconstriction. The respective effects of BAY K 8644 and A23187 were essentially the same in both blood- and PSS-perfused lungs. These results indicate that a Ca2+ channel facilitator and a Ca2+ ionophore have diametric effects on pulmonary vasoreactivity. The marked potentiation of hypoxic vasoconstriction by BAY K 8644 supports the idea that activation of voltage-dependent Ca2+ channels is an important component of the mechanism of hypoxic pulmonary vasoconstriction.
Renal hypertension impairs inotropic isoproterenol effect without beta-receptor changes
Authors: Gende O. A. , Mattiazzi A. , Camilion M. C. , Pedroni P. , Taquini C. , Gomez Llambi H. , Cingolani H. E.
Published: December 2017

Experiments were performed in male Wistar rats with renovascular hypertension (167 +/- 4.2 mmHg) produced by clipping the renal artery for a 3-wk period (2-kidney, 1-clip Goldblatt). The results were compared with those obtained in age-matched normotensive controls. Hypertension of 3-wk duration elicited a significant increase in ventricular weight (1.01 +/- 0.02 g) with respect to the controls (0.82 +/- 0.01 g) but had no significant effect on body weight. The inotropic responsiveness to beta-adrenergic stimulation was diminished in papillary muscles from renal hypertensive rats: the maximum increase in the maximal rate of rise of tension produced by isoproterenol was 27.39 +/- 5.4 and 11.77 +/- 2.91 g X mm-2 X s-1 (P less than 0.05) in control and hypertensive animals, respectively. Similar results were obtained when the estimated maximal velocity of shortening of the contractile element (Vmax) was used to assess myocardial contractility. The inotropic response to CaCl2 was also significantly depressed in the 2-kidney, 1-clip rats. However, the relaxant and the chronotropic responses to isoproterenol were not significantly modified in the Goldblatt rats. Assays of beta-adrenergic receptors to l-[3H]dihydroalprenolol binding, showed no significant changes in the number (expressed per mg of membrane protein) or in the affinity of the beta-receptors. These results suggest that at an early stage of the renal hypertensive model the impaired inotropic response to isoproterenol is not mediated by an alteration of the beta-receptors and should be searched at a postreceptor adenyl cyclase level.
Phosphate-induced efflux of adenine nucleotides from heart mitochondria
Authors: Asimakis G. K. , Conti V. R.
Published: December 2017

Adenine nucleotide efflux from isolated rat heart mitochondria was studied. Inorganic phosphate induced efflux of adenine nucleotides from the mitochondria. This efflux was inhibited by carboxyatractyloside and atractyloside. The rate of efflux showed saturation kinetics with respect to extramitochondrial phosphate (Km, 9.5 mM). Lowering the pH from 7.4 to 6.8 had little or no effect on the rate of efflux. Deenergizing the mitochondria enhanced carboxyatractyloside-insensitive efflux, but it did not affect carboxyatractyloside-sensitive efflux. Extramitochondrial ATP (200 microM) or AMP (200 microM) prevented efflux when the phosphate concentration was 10 mM. AMP (200 microM) did not inhibit efflux when the phosphate concentration was 40 mM. Atractyloside inhibited efflux noncompetitively with respect to inorganic phosphate. Mersalyl (10 nmol/mg protein) did not inhibit efflux. Phenylsuccinate (20 mM) totally inhibited phosphate-induced efflux. The results of this study indicate that under conditions found in the ischemic heart cell (low ATP, high phosphate), adenine nucleotides may be lost from the mitochondria via the adenine nucleotide translocase. Phosphate does not induce this efflux by interacting with the translocase or the phosphate-hydroxyl carrier. The site of action of phosphate may be the dicarboxylate carrier.