bluuebunny/crossref_metadata_2025 huggingface dataset:
Filling and arterial pressures as determinants of RV stroke volume in the sheep fetus
Authors: Thornburg K. L. , Morton M. J.
Published: December 2017

Right ventricular (RV) function was investigated in nine fetal lambs (125-130 days gestation) that were instrumented with pulmonary artery electromagnetic flow sensors and vascular catheters. Control arterial CO2 and O2 tension, pH, and hematocrit values were 46.1 +/- 1.6 (SD) Torr, 20.6 +/- 1.8 Torr, 7.39 +/- 0.02, and 31 +/- 5.3%, respectively. Control values for right ventricular output (247 +/- 75 ml X min-1 X kg-1), stroke volume (SV, 1.5 +/- 0.4 ml X kg-1), right atrial pressure (3.7 +/- 1.2 mmHg), heart rate (166 +/- 18 beats X min-1), and arterial pressure (AP, 43 +/- 4 mmHg) were unchanged by administration of atropine and propranolol. Withdrawal and infusion of fetal blood with or without concomitant infusion of nitroprusside or phenylephrine produced RV function curves at low, normal, and high arterial pressures. All function curves had a steep ascending limb and a plateau. The breakpoint joining the limbs of the control curve was right atrial pressure 3.4 +/- 1.2 mmHg and SV 1.5 +/- 0.4 ml X kg-1. Increased AP shifted the breakpoint downward. Linear regression of SV on AP from 15 to 95 mmHg at right atrial pressure greater than breakpoint was SV = -0.016 ml X kg-1 mmHg-1 X AP + 2.25 ml X kg-1.
Body fluid distribution in the maintenance of DOCA-salt hypertension in rats
Authors: Tajima Y. , Ichikawa S. , Sakamaki T. , Matsuo H. , Aizawa F. , Kogure M. , Yagi S. , Murata K.
Published: December 2017

Body fluid volumes and their relation to mean arterial pressure and plasma renin activity (PRA) were examined in heminephrectomized rats after 4 wk of treatment with deoxy-corticosterone acetate (DOCA) and placed on one of three levels of salt intake, either high (D-HS), normal (D-NS), or low (D-LS); sham-operated rats, which received heminephrectomy and no DOCA treatment, also received high (S-HS), normal (S-NS), or low (S-LS) intakes of salt. Body fluid volumes were measured as the distribution volumes of radioiodinated serum albumin, 35SO4, and tritiated water for plasma volume (PV), extracellular fluid volume (EFV), and total body water (TBW), respectively. Approximately the same degrees of hypertension occurred in the D-HS and D-NS rats, but the D-LS rats were normotensive. PV and EFV were increased only in the D-HS rats, with no prominent changes occurring in the D-NS rats. Intracellular fluid volume (ICF) was not changed in the D-NS rats when compared with the S-NS rats. The ratios of PV/EFV and EFV/TBW in the DOCA-treated groups on high or normal salt were not different from their controls. PRA was greatly suppressed in the D-HS and D-NS rats when compared with all other groups. In another group of D-HS rats, sodium was restricted for 2 wk; in this group the mean arterial pressure fell to control levels without significant changes in PV, but interstitial fluid volume was reduced to normal levels. These results demonstrated that 1) in DOCA-salt hypertensive rats there is expansion of body fluid volumes that are proportionally distributed among the PV, EFV, and ICF; 2) increases in body fluid volumes are not necessary for DOCA to maintain hypertension; 3) a certain minimal amount of dietary sodium is necessary for the development and maintenance of hypertension; and 4) following DOCA treatment the suppression of PRA is not due solely to expansion of body fluid volumes.
Force-length relations in cardiac muscle segments
Authors: Huntsman L. L. , Rondinone J. F. , Martyn D. A.
Published: December 2017

Using a new technique that measures the length of a segment in the central region of isolated papillaries, we have determined the force-segment length relation for ferret papillary muscles at 27 degrees C. The muscles contracted under muscle length isometric (auxotonic) and segment isometric conditions in physiological solutions containing 9.0, 4.5, 2.25, and 1.125 mM Ca2+. Force-segment length relations obtained from auxotonic and segment isometric contractions were identical in a given Ca2+ concentration. Calcium variations, however, changed the position, shape, and segment length intercept of the force-segment length relation. Force, at a given segment length, increased with increasing Ca2+ up to 9.0 mM Ca2+. The force-segment length relation changed shape from linear, in 4.5 mM Ca2+, to concave in 1.125 mM Ca2+. The segment length intercept was found by extrapolation to be 68, 69, and 74% SLmax in 4.5, 2.25, and 1.125 mM Ca2+, respectively. Two passive force corrections were used to calculate the developed force-segment length relations. Assuming passive force to be related primarily to segment length yields curves that change shape with Ca2+ concentration, suggesting length-dependent activation. On the other hand, assuming passive force to be related to muscle length results in curves for different Ca2+ concentrations that are nearly vertically shifted versions of each other, suggesting the influence of internal loads.
Vagal modulation of adrenergic effects on canine sinus and atrioventricular nodes
Authors: Takahashi N. , Zipes D. P.
Published: December 2017

Vagal stimulation modulates adrenergic neurotransmission at pre- and postjunctional sites. The purpose of this study was to test whether such multilevel cholinergic inhibition depressed sinus nodal automaticity and atrioventricular (AV) nodal conduction (A-H interval) in open-chest dogs anesthetized with chloralose. We compared the inhibitory effects of vagal stimulation when sinus nodal automaticity and AV nodal conduction were enhanced by bilateral stellate ganglia stimulation with comparable degrees of enhanced automaticity and conduction achieved by infusing norepinephrine and isoproterenol. We found that vagal stimulation prolonged in a frequency-dependent fashion sinus nodal cycle length and A-H interval more during stellate ganglion stimulation than during norepinephrine or isoproterenol infusion. Atropine eliminated all effects of vagal stimulation. These data provide functional evidence to support the concept that muscarinic modulation of adrenergic effects on sinus nodal cycle length and AV nodal conduction occurs at site(s) in addition to the postjunctional effector cell.
Consistent substrate utilization despite reduced flow in hearts with maintained work
Authors: Fox K. A. , Nomura H. , Sobel B. E. , Bergmann S. R.
Published: December 2017

Assessments of myocardial metabolism based on external detection of accumulation of radiolabeled substrates may be influenced, as a result of alterations in flow, by altered substrate delivery as well as altered work (with concomitant changes in metabolic requirements). To determine whether reduced delivery limits substrate utilization under defined conditions of reduced perfusion, an isolated rabbit heart preparation was employed in which flow was reduced but myocardial oxygen consumption (MVo2) and work were kept constant by adjustment of left ventricular end-diastolic pressure and heart rate. Flow was reduced from 1.5 to 0.5 ml . g-1 . min-1, while work was maintained constant in hearts functioning at either low or high levels of MVo2. Consumption of palmitate remained constant (48.8 +/- 11.6 and 68.8 +/- 23.3 nmol . g-1 . min-1), because the proportion of palmitate extracted increased (8.8 +/- 4 to 29.1 +/- 7.2% and 10.3 +/- 3.4 to 21.0 +/- 6.1%). The results indicate that, despite reduction of flow, hearts at constant work loads can extract increasing proportions of delivered substrates such that net utilization remains constant until flow is reduced below the level required to maintain cellular function. They suggest that, under conditions of low flow, impaired extraction of substrates reflects either primarily or secondarily depressed myocardial metabolism rather than simply decreased delivery of substrate.
Temperature effects on dog hindpaw series and parallel vascular circuits
Authors: Baker C. H. , Davis D. L. , Lindsey B. G. , Sutton E. T.
Published: December 2017

The effect of environmental temperature (skin surface) on distribution of blood flow between the parallel vascular circuits has been assessed in vascularly and neurally isolated hindpaws perfused at constant pressure. The paw was sealed in a chamber filled with water at 10, 20, 30, or 40 degrees C. Peripheral resistance increased as the temperature decreased in both innervated and denervated paws. Resistance in the denervated paws was less than in the innervated paws at all temperatures. Recovery of 85Sr microspheres was less at 40 degrees C than at 10, 20, or 30 degrees C in the denervated paws but did not change in innervated paws. Capillary availability (diffusion capacity and filtration coefficient) increased with each elevation in temperature in both groups. At 10 degrees C both arteriovenous (AV) shunt and capillary flows were low in innervated paws with low capillary and high shunt flow in denervated paws. At 20 and 30 degrees C capillary flow increased with temperature and arteriovenous anastomosis (AVA) flow was unchanged in denervated paws. In innervated paws AV shunt flow fraction slightly increased, with capillary perfusion markedly increased as temperature was elevated. The increased capillary flow in both groups passed through an enlarged capillary bed, whereas the number and/or diameter of AVAs remained essentially unchanged.
Effect of changes in magnesium ion concentration on cat cerebral arterioles
Authors: Seelig J. M. , Wei E. P. , Kontos H. A. , Choi S. C. , Becker D. P.
Published: December 2017

The effect of changes in cerebrospinal fluid (CSF) concentration of magnesium ion ([Mg2+]) on pial arterioles was investigated in anesthetized cats equipped with acutely implanted cranial windows for the observation of the pial microcirculation. Increased [Mg2+] caused vasodilation, whereas decreased [Mg2+] caused vasoconstriction. The effect of [Mg2+] was dose dependent and was the same in small and larger arterioles. There was an interaction between CSF [Mg2+] and calcium ion concentration ([Ca2+]), such that the vasodilator effect of Mg2+ was greater when the [Ca2+] was lower, especially in larger vessels. The vasodilator effect of Mg2+ on pial arterioles was enhanced in the presence of the calcium antagonist verapamil (0.5 micrograms/ml), despite the fact that verapamil by itself caused a 12-13% arteriolar dilation. These results show that the vasodilator effect of Mg2+ is probably related to an interaction at the cell membrane resulting in reduction in the influx of Ca2+ into vascular smooth muscle.
Basal and maximal inotropic state in renal hypertensive dogs with cardiac hypertrophy
Authors: Broughton A. , Korner P. I.
Published: December 2017

We studied three isovolumic indexes of contractility, i.e., dP/dtmax, dP/dtDP40, and (dP/dt)/TPmax, in normal dogs and in a matched group of chronically hypertensive dogs with left ventricular hypertrophy (LVH) [DP40, developed LV pressure of 40 mmHg; TP, total LV pressure above atmospheric]. The LVH was moderate in degree with the LV-to-body weight ratio 50% greater than in normal dogs. The experiments were performed under pentobarbital with open chest, autonomic blockade, and independent control of mean left atrial pressure (LAP) and mean aortic pressure (MAP). We found that dP/dtmax provided the most consistent comparison of inotropic state in the two groups under both basal conditions and with norepinephrine (NE). The other indexes occurred too early in systole to reflect complete LV activation, particularly during the infusion with NE. Under controlled conditions basal dP/dtmax of LVH dogs was 1.28 times the value of normal dogs, with the increase accounted for by the amplifier effect of the increase in LV mass. But with moderate lowering of aortic pressure, inotropic state was more easily compromised in LVH than in normal dogs. With steady-state stimulation by infusing increasing amounts of NE, dP/dtmax rose by 10 times basal in both LVH and normal dogs at maximum stimulation. The absolute value of the index was 1.31 times higher in the LVH group, with the amplifier effect thus the same as under basal conditions. The results suggest that basal and maximal inotropic states are normal in LVH under optimum loading conditions.
Improved defibrillator waveform safety factor with biphasic waveforms
Authors: Jones J. L. , Jones R. E.
Published: December 2017

Excitation thresholds and arrhythmias were studied in "adult-type" cultured chick embryo myocardial cells after electric field stimulation with biphasic, truncated, and rectified underdamped RLC (resistance-inductance-capacitance) type waveforms, to test the hypothesis that the negative phase of biphasic waveforms ameliorates membrane dysfunction induced by the initial positive portion. Photocell mechanograms and intracellular microelectrodes monitored extrasystoles and depolarization-induced arrhythmias. Rectifying or truncating biphasic waveforms did not alter the excitation threshold. However, shock intensities producing specific postshock arrhythmias or a specific severity of postshock prolonged depolarization differed significantly when biphasic waveforms were truncated or rectified. The voltage gradient producing a specific dysfunction was 12-14% lower for the truncated version than for the biphasic; that for the rectified version was 17-27% lower than for the biphasic version (although both contained the same energy). Safety factor, the ratio between shock intensity producing specific dysfunction and that producing excitation, was determined for each waveform. Biphasic waveforms had larger safety factors than truncated or rectified waveforms. Since safety factor, as measured in cultured myocardial cells, closely corresponds with in situ defibrillating effectiveness (14), the significantly higher safety factors of biphasic waveforms suggest that carefully shaped biphasic waveforms might improve the efficacy and safety of cardiac defibrillation procedures.
Blood flow and oxygen consumption in skeletal muscle during sympathetic stimulation
Authors: Thompson L. P. , Mohrman D. E.
Published: December 2017

We studied the effects of physiological rates (0-4 Hz) of sympathetic stimulation on blood flow and oxygen consumption of extensor digitorum longus muscles isolated from anesthetized dogs. Observations were made with the preparation at rest and during isometric twitch exercise at 1 and 4 Hz produced by somatic nerve stimulation. Graded increases in sympathetic stimulation rate resulted in graded and sustained reductions in muscle blood flow in all cases. A given rate of sympathetic stimulation reduced muscle blood flow by nearly the same absolute amount regardless of muscle exercise rate. Consequently the curve relating muscle blood flow to muscle oxygen consumption was progressively shifted downward in a parallel fashion with graded increases in sympathetic stimulation rate. Sympathetic stimulation at 0.5 and 1 Hz reduced muscle oxygen consumption during 4-Hz exercise but failed to do so during rest or 1-Hz exercise. Thus even during heavy exercise, local metabolic mechanisms do not override sympathetic vasoconstriction sufficiently to prevent the latter from limiting muscle oxygen consumption. In addition, the functional consequences of sympathetic activation appear to be greater for heavily exercising muscle than resting muscle.
Effects of epinephrine on resting potential in normal and hypertrophied cardiac muscles
Authors: Houser S. R. , Burgis V. , Martin F. , Weinberg D.
Published: December 2017

The role of the Na-K pump in the control of cellular ion balance has long been appreciated. Recent studies suggest that the manner in which this ion transport system functions in hypertrophied failing (HF) cardiac muscle is markedly different from that seen in normal muscles. The ability of the sympathetic neurohormone, epinephrine, to modulate membrane potential changes thought to reflect the activity of the Na-K pump in normal and HF cardiac muscle was examined in this study. Specifically rate-related changes in membrane potential (Emax) thought to be associated with the Na-K pump were measured in intact functioning cat papillary muscles. The results of these studies demonstrate that the rate-related changes in Emax thought to be associated with Na-K activity were markedly altered in HF cardiac muscles. Emax in these muscles responded to periods of transient stimulation by first depolarizing and then slowly returning to a new steady state which was depolarized with respect to the initial predrive Emax. Emax in normal muscles also depolarized on drive, but returned to a new steady state more rapidly and eventually hyperpolarized. Epinephrine significantly affected these rate-related changes in Emax in normal muscles by causing all the rates of change in Emax to be increased. In HF muscles, on the other hand, epinephrine had no significant effect on these parameters at the concentration tested. These results suggest that under certain conditions HF cardiac muscle may be incapable of maintaining normal resting membrane potentials. In addition the modulating influence of epinephrine is markedly blunted.
Hyaluronidase reversal of increased coronary vascular resistance in ischemic rat hearts
Authors: Sunnergren K. P. , Rovetto M. J.
Published: December 2017

Testicular hyaluronidase prevents increased coronary vascular resistance (CVR) during prolonged myocardial ischemia. The mechanism is unknown, but edema and contracture both have been suggested to increase CVR. Additionally, the extent of contracture has been inversely related to ATP levels. Therefore, isolated perfused ischemic rat hearts were treated with hyaluronidase, following a 25% increase in CVR, to determine whether 1) increased CVR was reversed, 2) edema or contracture was reduced, and 3) tissue ATP levels were increased. Three hours of low-flow ischemia decreased coronary flow (CF) from 17.4 +/- 0.13 to 12.6 +/- 0.2 ml X min-1 X g dry tissue-1. During the subsequent 2 h of ischemia, CF of vehicle-treated hearts continued to decline to 8.0 +/- 0.76 ml X min-1 X g dry tissue-1, whereas CF of hyaluronidase-treated hearts increased to 15.6 +/- 1.17 ml X min-1 X g dry tissue-1. These changes in CF persisted during postischemic perfusion. Furthermore, restoration of coronary vascular resistance by hyaluronidase was associated with a 19% reduction in tissue water compared with control ischemic hearts but not with a reduction in cardiac contracture or an increase in tissue ATP. These results suggest that treatment of ischemic hearts with hyaluronidase reverses increased CVR through a reduction in tissue edema.
Action of an opiate receptor blocker on ovine cardiopulmonary responses to endotoxin
Authors: Traber D. L. , Thomson P. D. , Blalock J. E. , Smith E. M. , Adams T. , Sziebert L. A. , Traber L. D.
Published: December 2017

The involvement of endorphins in the ovine cardiopulmonary response to endotoxin was evaluated by measuring blood levels of opiate receptor binding substances and administering the opiate receptor blocking agent naloxone prior to and after the administration of lipopolysaccharide. The animals were prepared for chronic study by placement of cardiovascular catheters and cannulation of the lung lymphatic at least 1 wk prior to study. The sheep were given endotoxin (0.75 micrograms/kg) and studied for 6 h. This was accomplished twice in the same animal. Naloxone (2 mg/kg bolus + 2 mg X kg-1 X h-1) was given with one of the two doses of the lipopolysaccharide. The response to endotoxin could be divided into two phases. In phase 1, there was an increase in protein-poor lung lymph and a marked increase in pulmonary artery pressure. In phase 2, the pulmonary lymph flow was elevated but the lymph protein level was higher than in phase 1. The pulmonary artery pressure, however, was near normal. During both phases leukocytes and cardiac output were reduced and the hematocrit was elevated. There was an increase in opiatelike materials in the plasma of these animals, and the response to endotoxin was partially blocked by naloxone. This suggested that endorphin-like materials were involved in the response to endotoxin.
Blood pressure maintenance in awake dehydrated rats: renin, vasopressin, and sympathetic activity
Authors: Burnier M. , Biollaz J. , Brunner D. B. , Brunner H. R.
Published: December 2017

The role of vasopressin, the renin system, and sympathetic activity in sustaining blood pressure in the dehydrated state was investigated in normotensive nonanesthetized male Wistar rats. After 48-h dehydration, plasma arginine vasopressin was 14.0 +/- 1.7 pg/ml and plasma norepinephrine 0.46 +/- 0.05 ng/ml. In another group of rats in which the angiotensin converting enzyme inhibitor (MK 421, 5 mg po twice daily) was administered throughout the dehydration period, blood pressure was reduced by more than 20% (P less than 0.001), and both plasma arginine vasopressin and norepinephrine were higher at 23.4 +/- 3.9 pg/ml (P less than 0.01) and 0.83 +/- 0.07 ng/ml (P less than 0.01), respectively. Taken together, in rats with or without converting enzyme blockade, there was an inverse correlation between mean blood pressure and plasma arginine vasopressin (r = 0.67, P less than 0.01) as well as plasma norepinephrine (r = 0.82, P less than 0.01) levels. The acute administration of a specific vasopressin pressor inhibitor (dPVDAVP) reduced mean blood pressure in the rats with a blocked renin system by 16.9 mmHg (P less than 0.001). In rats without converting enzyme inhibition, the induced fall was only 6.4 mmHg. These results indicate that following 48-h dehydration the renin angiotensin system interacts with the vasopressin secretory mechanism to sustain blood pressure, with renin playing a predominant role. They further suggest that, following blockade of the renin system, activation of the sympathetic nervous system probably also contributes to blood pressure maintenance.
Effects of chronic volume overload on left ventricular response to tachycardia
Authors: Pouleur H. , Rousseau M. F. , Petein M. , Van Mechelen H. , Charlier A. A.
Published: December 2017

The aim of the study was to determine the effects of chronic volume overload on the inotropic response of the left ventricle to a change in frequency of stimulation. Ten normal dogs (normal) and eight dogs with a chronic left ventricular (LV) volume overload (aortocaval fistula) were studied by cardiac catheterization after sedation with morphine (1 mg/kg). In normal dogs, increasing heart rate from 122 to 172 beats/min produced insignificant changes in peak +dP/dt (+2%; NS) or (dP/dt)/DP40 (+6%; NS). In volume overload, these indexes increased by 16% (P less than 0.01) and 31% (P less than 0.01), respectively, when heart rate increased from 135 to 173 beats/min. Conversely, the poststimulation potentiation appeared greater in normal than in volume overload; (dP/dt)/DP40 increased by 40% in normal vs. 1% in volume overload (P less than 0.01). These differences between normal and volume overload persisted after propranolol (1 mg/kg) and atropine (0.25 mg) administration. In both groups, AR-L115 BS, a nonsympathomimetic positive inotrope with caffeinelike properties, reduced the inotropic response to tachycardia, thereby normalizing the peak +dP/dt changes in volume overload. We conclude that the positive inotropic effects of tachycardia are enhanced in LV volume overload. Changes in LV compliance or alterations in the cellular mechanisms responsible for the force-frequency phenomenon might explain these findings.
Myoglobin oxygenation remains constant during the cardiac cycle
Authors: Makino N. , Kanaide H. , Yoshimura R. , Nakamura M.
Published: December 2017

Oxygen saturation of myoglobin (Mb) during the cardiac cycle was recorded spectrophotometrically by incorporating fiber optics in the isolated rat heart perfused using the Langendorff procedure. Oxygen saturation of Mb was continuously measured from absorbancy increments at 581-592 nm of transmitted light through the left ventricular free wall. In addition, quantification in the Mb oxygen saturation induced by the change of wall thickness during cardiac cycle was assessed from the absorbance change at 568-592 nm, namely, dual wavelengths of two isosbestic points. The results show that to obtain actual Mb oxygen saturation the absorbance change induced by the change in the wall thickness has to be subtracted from the absorbance change of 581-592 nm and that the Mb oxygen saturation in a steady state determines the amount of subtraction. On the basis of these procedures, it was found that the myocardial Mb oxygen saturation and hence myocardial oxygen tension during pulsation in aerobic and anaerobic steady state did not vary during the cardiac cycle.
Effects of hypoproteinemia on fluid volumes and arterial pressure
Authors: Manning R. D. , Guyton A. C.
Published: December 2017

The effects of both moderate and large decreases in plasma protein concentration on arterial pressure and fluid volumes were studied in 23 conscious dogs. In experiment 1, plasma protein concentration decreased 33% during a 5-day plasmapheresis period. During this time sodium space increased 11%, mean arterial pressure decreased slightly, and neither blood volume nor plasma volume decreased. Experiment 2 was performed to see if blockade of the alpha-sympathetic and angiotensin systems could prevent the blood volume homeostasis during moderate hypoproteinemia. Sodium space increased; however, blood volume was unchanged. During experiment 3 plasma protein concentration decreased 68% over a 12-day plasmapheresis period. By the last day of plasmapheresis, plasma protein concentration was 2.4 g/100 ml, mean arterial pressure had decreased 26 mmHg, sodium space had increased 12%, plasma renin activity had increased 11-fold, and blood volume and plasma volume were 63.9 +/- 4.0 and 66.9 +/- 2.5% of control, respectively. We conclude that the maintenance of a normal blood volume during moderate hypoproteinemia does not require active participation of the renin-angiotensin and alpha-sympathetic systems and large decreases in plasma protein concentration are accompanied by marked hypovolemia, hypotension, and hyperreninemia.
Susceptibilities of cardiac myofibrillar proteins to cathepsin D-catalyzed degradation
Authors: Jones T. L. , Ogunro E. A. , Samarel A. M. , Ferguson A. G. , Lesch M.
Published: December 2017

The binding of various myofibrillar proteins to cathepsin D and consequent susceptibility to degradation was assessed by determination of apparent Michaelis constant (Km) values for the purified enzyme using myosin, alpha-actinin, actin, and tropomyosin as substrates. Cathepsin D, purified 1,000-fold to homogeneity from canine cardiac tissue, was incubated (0-100 min at 37 degrees C) with myofibrillar proteins isolated from homologous tissue and labeled radioactively with 14C by reductive alkylation. The reaction was terminated by addition of trichloroacetic acid (10% wt/vol), and radioactivity in the supernatant fraction was determined after centrifugation (5 min) at 100,000 g. Double reciprocal graphs (1/reaction velocity vs. 1/substrate concn) were constructed for each substrate from the linear portion of graphs of disintegrations. min-1 X ml-1 100,000-g supernatant vs. time (min). Apparent Km values (+/- SD) calculated for myosin, alpha-actinin, actin, and tropomyosin were found to be 2.7 +/- 0.3 X 10(-6) (n = 6), 10.0 +/- 2.3 X 10(-6) (n = 13), 13.0 +/- 1.3 X 10(-6) (n = 7), and 45.5 +/- 9.0 X 10(-6) (n = 6) mol/l, respectively. The results show that myofibrillar proteins differ in their binding and thus susceptibility to hydrolysis by cathepsin D in order of molecular weight (i.e., myosin greater than alpha-actinin greater than actin greater than tropomyosin). Because the relative turnover rates of myofibrillar proteins are known to be independent of molecular weight, our results suggest that the degradation of these proteins by cathepsin D is not rate limiting and that other factors including lysosomal or nonlysosomal enzymes must determine the rate-limiting steps of myofibrillar protein degradation in cardiac tissue.
Pulmonary hypertension and ECG changes from monocrotaline pyrrole in the rat
Authors: Bruner L. H. , Hilliker K. S. , Roth R. A.
Published: December 2017

Chemically synthesized monocrotaline pyrrole (MCTP) was administered to adult male rats at a dose of 5 mg/kg in the tail vein. Controls received an equivalent volume of dimethylformamide vehicle. Rats were killed at 3, 5, 7, 10, and 14 days after treatment. Bronchopulmonary lavage fluid lactate dehydrogenase activity and lung weight were significantly elevated at 4 and 7 days, respectively, after MCTP, indicating that pulmonary damage had occurred. White blood cell count was elevated 7 days after treatment. Mean pulmonary arterial pressure was also first elevated in treated (22 +/- 3 mmHg) compared with control (16 +/- 1 mmHg) animals 7 days after treatment. Right ventricle-to-left ventricle plus septum weight ratios were significantly increased in treated (0.429 +/- 0.015) vs. control (0.320 +/- 0.015) animals 14 days after treatment. Development of right heart enlargement correlated with a shift in the QRS complex mean electrical axis in the frontal plane of the electrocardiogram. These results indicate that MCTP produces effects similar to that caused by monocrotaline, that pulmonary arterial pressure increases from control levels between 5 and 7 days after treatment, and that measurement of mean electrical axis of the electrocardiogram may be a useful, noninvasive method to monitor MCTP-induced cardiac changes in vivo.
Intrarenal flow of microspheres and red blood cells: skimming in slit and tube models
Authors: Ofjord E. S. , Clausen G.
Published: December 2017

Microspheres (MS) provide somewhat erroneous estimates of intrarenal blood flow distribution due to a variable MS skimming. The errors were computed from two sets of model experiments. Skimming of 3.5-, 10-, and 15-micron MS and normal and hardened red blood cells (RBC and HRBC, respectively) were studied in a slit model simulating an interlobular artery (ila) with variable diameter from 40 to 160 micron, having as a side branch of constant diameter one afferent arteriole with variable fractional flow. The corresponding afferent arteriole capture zones in the ila were determined in a tube model. All particles except 3.5-micron MS were skimmed, RBC having an effective diameter of 5 micron compared with 8 micron for HRBC. Skimming was greater in tubes than in slits at a given afferent arteriole flow fraction and was predominantly determined by the particle-to-ila diameter ratio. Intrarenal MS and RBC skimming in dog and rat kidneys was predicted on the basis of the number of afferent arterioles along the ila, ila diameter and tapering. The predictions agreed fairly well with available in vivo data. In conclusion, previously observed redistribution of MS, induced by vasodilation and vasoconstriction in the dog kidney, may be quantitatively ascribed to changes in the ila diameters and MS skimming in the inner cortex without redistribution of fractional blood flow between deep and superficial renal zones.
Determinants of systemic zero-flow arterial pressure
Authors: Brunner M. J. , Greene A. S. , Sagawa K. , Shoukas A. A.
Published: December 2017

Thirteen pentobarbital-anesthetized dogs whose carotid sinuses were isolated and perfused at a constant pressure were placed on total cardiac bypass. With systemic venous pressure held at 0 mmHg (condition 1), arterial inflow was stopped for 20 s at intrasinus pressures of 50, 125, and 200 mmHg. Zero-flow arterial pressures under condition 1 were 16.2 +/- 1.3 (SE), 13.8 +/- 1.1, and 12.5 +/- 0.8 mmHg, respectively. In condition 2, the venous outflow tube was clamped at the instant of stopping the inflow, causing venous pressure to rise. The zero-flow arterial pressures were 19.7 +/- 1.3, 18.5 +/- 1.4, and 16.4 +/- 1.2 mmHg for intrasinus pressures of 50, 125, and 200 mmHg, respectively. At all levels of intrasinus pressure, the zero-flow arterial pressure in condition 2 was higher (P less than 0.005) than in condition 1. In seven dogs, at an intrasinus pressure of 125 mmHg, epinephrine increased the zero-flow arterial pressure by 3.0 mmHg, whereas hexamethonium and papaverine decreased the zero-flow arterial pressure by 2 mmHg. Reductions in the hematocrit from 52 to 11% resulted in statistically significant changes (P less than 0.01) in zero-flow arterial pressures. Thus zero-flow arterial pressure was found to be affected by changes in venous pressure, hematocrit, and vasomotor tone. The evidence does not support the literally interpreted concept of the vascular waterfall as the model for the finite arteriovenous pressure difference at zero flow.
Effects of histamine receptor stimulation on regional myocardial blood flow
Authors: Christensen C. W. , Gross G. J. , Hardman H. F. , Brooks H. L. , Warltier D. C.
Published: December 2017

The effect of histamine (H) and specific H1 and H2 agonists and antagonists on regional myocardial blood flow was studied in anesthetized dogs by use of tracer microspheres. Intracoronary infusion of histamine (15 and 34 micrograms/min) produced a dose-related increase in transmural myocardial blood flow (from 0.82 to 1.36 and 2.25 ml X min-1 X g-1) without alteration of heart rate or blood pressure. Infusion of the H1 agonist 2-(2-thiazolyl)ethylamine (135 and 442 micrograms/min) produced an increase in transmural perfusion (from 0.69 to 1.22 and 1.65 ml X min-1 X g-1) and a significant (P less than 0.05) increase in the ratio of flow between subendocardium and subepicardium (endo/epi from 0.97 to 1.31 and 1.54). Infusion of the H2 agonist dimaprit (195 and 390 micrograms/min) produced an increase in transmural myocardial blood flow (from 0.97 to 1.49 and 2.00 ml X min-1 X g-1) without a change in endo/epi. The H1-mediated increase in regional myocardial perfusion and endo/epi was blocked by the H1 antagonist diphenhydramine but not by the H2 antagonist cimetidine. These results suggest that stimulation of H1 coronary receptors preferentially distributes flow to the subendocardium, whereas H2 receptors mediate vasodilation in subepicardium as well as subendocardium.
Cardiovascular responses to graded reductions in hindlimb perfusion in exercising dogs
Authors: Wyss C. R. , Ardell J. L. , Scher A. M. , Rowell L. B.
Published: December 2017

In six dogs trained to run at 2, 4, and 6 mph, we caused graded reductions in hindlimb perfusion by compressing the terminal aorta. Our goal was to examine the relationship between hindlimb perfusion [terminal aortic flow (TAQ) and femoral arterial pressure (FP)] and cardiovascular responses [aortic pressure (AP), heart rate, and ascending aortic flow (CO)]. Small reductions in TAQ and FP produced bradycardia, small decreases in CO, and small increases in AP. Further reductions in TAQ and FP produced tachycardia, increased CO, and large increases in AP. AP rose by about 1 mmHg for each 1-mmHg fall in FP. The response was similar at all speeds, but as work load increased it required smaller reductions in FP and TAQ to cause a pressor response (e.g., at 6 mph we could not demonstrate a nonlinear relationship between TAQ and AP). At low work loads the cardiovascular responses to exercise were most likely set by signals other than feedback from exercising muscle because substantial reductions in hindlimb perfusion caused no significant cardiovascular responses. At moderate-to-high work loads or where muscle perfusion is restricted, metabolic feedback from muscle may play a role in cardiovascular responses to exercise.
A method for evaluation of blood substitutes in the conscious animal
Authors: Goodin T. H. , Clarke W. P. , Taylor K. , Eccles R. , Geyer R. P. , McCoy L. E.
Published: December 2017

Physiological evaluation of new and potential blood replacement agents has not kept pace with the development of such agents. Current procedures involve partial or total blood replacement in the anesthetized animal. This introduces the variable of anesthesia and eliminates the ability to observe behavior changes during blood replacement. Clinically, many patients receive blood or will receive artificial agents while sedated or under anesthesia, whereas others will be conscious. It is essential that evaluative studies be performed on the awake animal using procedures that are nontraumatic and nonrestrictive. A technique for isovolumic exchange perfusion utilizing an indwelling, heparin-coated, double-lumen catheter in the right atrium of a conscious rat is described. This animal model system permits continuous pre- and postperfusion monitoring. Nearly total blood replacement with perfluorochemical blood substitutes causes no discerniable discomfort or adverse reactions in the animal. Such animals thrive and replace missing hematologic components in 1-3 wk. The technique described can, with minimal modification, be used for isovolumic exchange perfusion of larger animals.
Control of cardiac contractility at the cellular level
Authors: Chapman R. A.
Published: December 2017

Recent experiments involving the measurement of intracellular activities in Na+ and Ca2+; functional studies; descriptions of the Na+ and Ca2+ fluxes from intact cardiac tissue; studies of isolated cardiac sarcolemmal vesicles, isolated sarcoplasmic reticulum (SR) vesicles, and isolated mitochondria; and investigations of the behavior of cardiac contractile proteins have revealed a plurality of processes associated with the activation and control of the contraction and relaxation of cardiac muscle. Which of these processes predominates, even in intact cardiac muscle, would seem to depend critically on the experimental conditions. As the cycle of contraction and relaxation essentially involves the reversible binding of Ca2+ to the contractile proteins as a final step, if a number of processes influence this binding they must interact. Quantitative consideration of available information suggests that in the beating mammalian heart the bulk of the activating Ca2+ cycles between the SR and the contractile proteins with the sarcolemmal Ca2+ pump and Na+-Ca2+ exchange operating to maintain the Ca2+ economy of the heart and affecting contraction only by influencing the filling of the SR with Ca2+ and possibly its release. In amphibian heart the sarcolemmal Na+-Ca2+ exchange would seem to be more directly involved, adding or subtracting from the Ca2+ liberated from the SR. The Ca2+ uptake by mitochondria may become particularly important when the intracellular sodium concentration alters.
Allometric relations of cardiovascular function in birds
Authors: Grubb B. R.
Published: December 2017

The avian cardiovascular system is interesting because birds have larger hearts and lower heart rates than mammals of the same size. This study defines how cardiovascular function is related to body size in nine species of birds encompassing a 1,000-fold size range. Heart mass (HM, g) was related to body mass (M, kg) by the following equation: HM = 8.76 M0.92, and the heart rate (HR, beats X min-1) to body mass by HR = 178.5 M-0.282. Cardiac output (Q, ml X min-1) was related to body mass as Q = 290.7 M0.69. Birds also had a greater cardiac output for a given body mass than mammals. Cardiac output was directly proportional to the rate of O2 consumption (VO2, ml X min-1): Q = 17.5 VO2(1.04), with birds having a greater cardiac output for a given VO2 than mammals. (Variables are considered directly proportional if the exponent does not differ significantly from one). As in mammals, stroke volume (SV, ml) was also directly proportional to body mass: SV = 1.72 M0.97, but for a given body size stroke volume was larger in birds than in mammals. However, as bird hearts are disproportionately large in comparison with body size, when stroke volume is expressed per gram of heart (SV = 0.177 HM1.05) birds have a significantly lower stroke volume-to-heart weight ratio than mammals.(ABSTRACT TRUNCATED AT 250 WORDS)
Ouabain binding, Na+-K+-ATPase activity, and 86Rb uptake of canine arteries
Authors: Bukoski R. D. , Seidel C. L. , Allen J. C.
Published: December 2017

In a previous report [Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H598-H603, 1983] we measured potassium-induced relaxation of canine femoral and renal arteries as an index of sodium pump function and concluded that it may not be an accurate measure. In this report, the sodium pumps of femoral and renal arteries were examined using three separate approaches to compare sodium pump function more directly. The number of pump sites in subcellular fractions was measured using [3H]ouabain binding. No differences were observed (femoral artery 14.5 +/- 4.8 pmol/g wet wt; renal artery 17.4 +/- 6.5). Similarly, there was no difference in ouabain-inhibitable Na+-K+-ATPase activity in NaI-treated microsomal fractions of these arteries (femoral artery 3.10 +/- 0.65 mumol Pi X mg-1 X h-1; renal artery 3.42 +/- 0.23). Finally, sodium pump function was measured using the ouabain-inhibitable 86Rb uptake method. The rate of ouabain-inhibitable 86Rb uptake was found to be identical for the two arteries, as were the dissociation constants of the two arteries for rubidium. However, in the presence of 3.5 microM norepinephrine, the rate of 86Rb uptake in the renal artery was greater than that of the femoral artery. We conclude that, under resting conditions, the sodium pumps of femoral and renal arteries are identical, whereas in the presence of norepinephrine, the renal artery sodium pump is not rate limiting with respect to contractility. These data have significant implications with regard to the use of potassium-induced relaxation as an index of sodium pump activity.
Modification of lymph by lymph nodes. II. Effect of increased lymph node venous blood pressure
Authors: Adair T. H. , Guyton A. C.
Published: December 2017

A previous study from this laboratory demonstrated that lymph nodes can change the protein concentration and colloid osmotic pressure of lymph by transfer of protein-free fluid between the blood and lymph compartments. In that study a Starling force disequilibrium across the blood-lymph barrier caused fluid to transfer through the barrier in the direction required to establish equilibrium of Starling forces. In the present study we examined the effect of increased lymph node venous blood pressure on efferent lymph protein concentration and efferent lymph flow. We utilized an isolated dog popliteal lymph node preparation in which afferent lymph having various protein concentrations was perfused into the node at an average flow rate of 19.1 +/- 0.3 (SD) microliter/min. We compared steady-state values of prenodal and postnodal lymph flows and protein concentrations during various steady-state levels of lymph node venous blood pressure. When venous pressure was increased, the protein concentration of the efferent lymph invariably decreased and the efferent flow rate invariably increased. Measurements showed that an average of 96% of the change in lymph protein concentration was caused by transfer of protein-free fluid through the lymph node blood-lymph barrier. The results of this study indicate again that the lymph node functions as a fluid exchange chamber in which fluid is transferred between the blood and lymph compartments in the direction required to establish equilibrium of the Starling forces across the blood-lymph barrier.
Release of norepinephrine from sympathetic nerve efferents by bilateral carotid occlusion
Authors: Reison D. S. , Oliver J. A. , Sciacca R. R. , Cannon P. J.
Published: December 2017

To investigate the response of the efferent sympathetic nervous system to carotid sinus hypotension, norepinephrine and epinephrine were measured in the dog during control and following bilateral carotid occlusion in arterial, coronary sinus, renal vein, hepatic vein, femoral vein, and pulmonary artery plasma. Mean arterial pressure increased from 109 mmHg during control to 144 and 143 at 1 and 5 min after carotid occlusion, respectively (P less than 0.01). This was associated with an increase in arterial norepinephrine, which could be prevented by the ganglionic blocking agent mecamylamine. While the concentration of norepinephrine rose in all venous effluents, the venous minus arterial norepinephrine difference increased only in the coronary and renal circulations. The results indicate that bilateral carotid occlusion increases the arterial norepinephrine concentration and the overflow of this neurotransmitter from the heart and kidney. The data thus suggest that norepinephrine release from sympathetic axon terminals in the heart and kidney is increased by carotid sinus hypotension. The magnitude of the increase in sympathetic activity evoked by carotid occlusion may have little effect on renal hemodynamics but may have a significant influence on cardiac contractility and coronary blood flow.
Elevated sympathetic response of epicardium proximal to healed myocardial infarction
Authors: Gaide M. S. , Myerburg R. J. , Kozlovskis P. L. , Bassett A. L.
Published: December 2017

Sympathetic nerve interaction with cardiac electrophysiology was evaluated in healed myocardial infarction by monitoring the effects of sympathetic nerve stimulation on local epicardial refractoriness in cats. Single-stage distal coronary artery ligation was used to induce myocardial infarction. Regions overlying and surrounding infarcts 3 mo after healing and comparable regions in sham-operated and normal unoperated hearts were studied. Local ventricular muscle refractory periods were measured by the extrastimulus technique from 1) the epicardium overlying the infarct, 2) the area bordering the infarct, and 3) a normal area proximal to the infarct on the anterior free wall of the left ventricle. Bilateral stimulation of the ansa subclavia induced significant and disparate refractory period shortening (P less than or equal to 0.01) in hearts with healed myocardial infarction. Shortening was greatest in the normal area [-26 +/- 8 (+/-SD) ms], less in the border area (-15 +/- 6), and least in the infarct area (-7 +/- 2). In contrast, refractory periods measured in noninfarcted hearts shortened significantly (P less than or equal to 0.01) but uniformly and to a lesser extent during sympathetic stimulation. We conclude 1) the effects of sympathetic nerve stimulation are more pronounced in the areas proximal to healed infarction than in similar areas of noninfarcted hearts and 2) a marked disparity in sympathetic responsiveness occurs in hearts with healed myocardial infarction.
Prevention of two-kidney, one-clip renal hypertension in rat by ablation of AV3V tissue
Authors: Haywood J. R. , Fink G. D. , Buggy J. , Boutelle S. , Johnson A. K. , Brody M. J.
Published: December 2017

This study examined the role of the anteroventral third ventricle (AV3V) in the renin-dependent two-kidney, one-clip model of renal hypertension. AV3V lesion and sham lesion rats were subjected to the placement of a clip on one renal artery or a sham operation. The sham lesion-renal artery clip rats experienced an increase in systolic blood pressure; however, AV3V lesioned animals experienced only a transient rise in arterial pressure during the 1st wk after clip. Body fluid regulation studies during the course of the hypertension revealed that there were no differences in water intake and urine volume between the lesion- and sham lesion-renal artery clip animals. Although significantly greater plasma and blood volumes were demonstrated in the AV3V lesion-sham clip rats compared with sham lesion animals, no differences in vascular volumes were detected in the renal artery clip rats. Finally, the rats were water deprived for 3 days to maximally stimulate vasopressin release. Urine osmolality increased significantly in all groups of rats except the AV3V lesion-renal artery clip animals protected against the hypertension.