bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dipyridamole on postischemic vasodilation and extracellular adenosine
Authors: Klabunde R. E.
Published: December 2017

Postischemic vasodilation (PIVD) was studied in pump-perfused dog gracilis muscles. The hemodynamic responses to 1, 3, and 5 min of ischemia were evaluated in the presence and absence of intraarterial infusions of dipyridamole in concentrations that inhibit cellular transport of adenosine. Dipyridamole infusion produced concentration-dependent reductions in vascular resistance and increased the time for 50% recovery (t0.5) in vascular resistance by 39% following 5 min of ischemia. The t0.5 for PIVD was unaffected by dipyridamole following 1 and 3 min of ischemia. Dipyridamole elevated tissue adenosine content two- to three-fold at 1, 3, and 5 min of ischemia compared with saline controls. Intra-arterial infusions of adenosine deaminase along with dipyridamole completely prevented the dipyridamole-induced increase in tissue adenosine, demonstrating that dipyridamole increases extracellular adenosine during muscle ischemia. The significance of these findings is analyzed using a two-compartment model for the distribution of adenosine. The data indicate that a severalfold increase in interstitial adenosine content does not alter PIVD and that the hemodynamic effects of dipyridamole following 5 min of ischemia may be due to some mechanism other than enhanced accumulation of adenosine.
Cardiac response of the fetal rat to carbon monoxide exposure
Authors: Penney D. G. , Baylerian M. S. , Thill J. E. , Yedavally S. , Fanning C. M.
Published: December 2017

Groups of pregnant rats were exposed to 200, 166, and 157 ppm CO for the last 17 out of 22 days of gestation. The number of fetuses per dam or live young per litter were unaffected. Neonatal red blood cell count was depressed, whereas mean corpuscular hemoglobin and volume were elevated. Birth weight was reduced; heart weight, heart weight-to-body weight ratio, placental weight, and placental weight-to-body weight ratio were elevated. Identical results were obtained in studies of fetuses examined daily during the final 4 days of gestation at 200 ppm. Cardiomegaly present at birth was not due to elevated myocardial water content, as dry heart weight and wet heart weight increased proportionately. Heart DNA content (microgram) was increased at both 157 and 200 ppm CO in neonates and fetuses, whereas DNA concentration (microgram/mg dry wt) was similar to the controls. Cardiac hydroxyproline concentration (microgram/mg dry wt) and content (microgram) were unaffected in neonates by fetal CO exposure at 157 and 200 ppm, although the hydroxyproline content was elevated in fetuses at 157 ppm CO. Cardiac lactate dehydrogenase (LDH) M subunit composition was elevated from 4 days before birth, until birth, at 200 ppm CO, whereas total LDH activity was unchanged. Although neonatal myocardial cytochrome c was unaltered by fetal CO exposure, myoglobin concentration (mg/g) and content (mg) were elevated. Prolonged maternal CO inhalation thus exerts significant effects on fetal body and placental weight, heart weight, enzyme constituents, and composition.
Chronic local infusion into the renal artery of unrestrained rats
Authors: Smits J. F. , Kasbergen C. M. , van Essen H. , Kleinjans J. C. , Struyker-Boudier H. A.
Published: December 2017

A method is described for providing chronic access to the right renal artery of unrestrained rats. It consists of insertion of a very thin (OD 0.2 mm) catheter into the right suprarenal artery of Wistar rats. The suprarenal artery originates from the right renal artery. After the cannula has been guided subcutaneously to the neck, it is connected to an Alzet osmotic minipump. The method has a success ratio of over 90% for periods up to 14 days. In the present study, we investigated the effects of catheter implantation on renal hemodynamics in uninephrectomized rats that were infused with saline for 2, 6, or 14 days. Values were compared with those obtained in control rats. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated from plasma clearances of 51Crethylenediaminetetraacetic acid and 125I-p-aminohippuric acid, respectively. Mean arterial pressure was between 107 +/- 2 and 116 +/- 2 mmHg in all animals. Neither GFR nor ERPF was influenced by catheter implantation. It is concluded that the method does not interfere with renal function.
Effects of SQ 20881 and captopril on mesenteric, renal, and iliac vasculatures
Authors: Fiksen-Olsen M. J. , Britton S. L. , Houck P. C. , Romero J. C.
Published: December 2017

The ability of two kininase II inhibitors, SQ 20881 and captopril, to inhibit conversion of angiotensin I to angiotensin II and to potentiate the vascular responsiveness to exogenous bradykinin were compared in the mesenteric, renal, and external iliac vasculatures of the dog. Basal rate of angiotensin I-to-angiotensin II conversion was found to be lower in the renal vasculature, average conversion being 4.7%, than in the mesenteric and iliac vasculatures, in which the average conversion was 30.7 and 26.3%, respectively. Inhibition of angiotensin I conversion by both kininase II inhibitors was independent of the basal angiotensin I conversion rate; however, SQ 20881 was a more potent inhibitor of angiotensin I conversion than captopril in all vascular beds tested. In the presence of equal molar doses of SQ 20881 and captopril, only 20-30% of the control bradykinin doses was needed to produce the same vascular effects in the mesenteric and iliac vasculatures. In the kidney, 70% of the control bradykinin doses was needed to produce the same vascular effects in the presence of SQ 20881; in contrast to SQ 20881, neither an equimolar nor 20 times an equimolar dose of captopril produced any change in the renal vascular responsiveness to bradykinin. In conclusion, 1) SQ 20881 is a more potent inhibitor of angiotensin conversion than captopril, and 2) captopril, unlike SQ 20881, does not alter renal vascular responsiveness to bradykinin.
Canine left ventricular performance during LD50 endotoxemia
Authors: Goldfarb R. D. , Tambolini W. , Wiener S. M. , Weber P. B.
Published: December 2017

Previous reports of the effect of endotoxin shock on cardiac performance have not achieved uniform results. These discrepancies have possibly been caused by the use of indices of cardiac performance that may have been sensitive to altered heart rate or preconditions of cardiac contraction as well as altered cardiac performance. We tested the hypothesis that, following a median lethal dose (LD50) of E. coli endotoxin, cardiac performance would be diminished in nonsurviving animals and maintained in surviving animals. We elected to employ the analysis of the end-systolic pressure-diameter relationship (sigma ES) as well as other measurements of cardiac performance to test this hypothesis. We established that the sigma ES measurement was independent of increased and decreased afterload and relatively insensitive to altered heart rate. In the nonsurviving animals, sigma ES exhibited a marked depression following endotoxin a administration. In the surviving animals, sigma ES exhibited a nonsignificant decrease followed by a return toward preendotoxin values. All other cardiodynamic measurements were uninterpretable due to the marked changes in heart rate, peripheral vascular function, aortic pressure, and cardiac output. We conclude that, following endotoxin administration, those animals that exhibited a diminished myocardial contractility failed to survive more than 2.5 h postendotoxin, whereas the surviving animals were able to restore normal cardiac contractility. Thus survival of endotoxin administration is associated with the maintenance of normal cardiac contractility.
Effect of calcium antagonism on contractile behavior of canine hearts
Authors: Gelpi R. J. , Mosca S. M. , Rinaldi G. J. , Kosoglov A. , Cingolani H. E.
Published: December 2017

The cardiovascular effects of prenylamine (P), verapamil (V), and nifedipine (N) were studied in open-chest, anesthetized dogs and in isolated, isovolumic dog hearts perfused at constant coronary blood flow (CBF). These drugs significantly decreased left ventricular pressure (LVP) and its maximal rates of rise (+P) and fall (-P). The tension developed by an isometric segment of the left ventricle and its maximal rates of rise (+T) and fall (-T) also decreased, whereas heart rate (HR) did not show statistically significant differences. Maximal rates of fall (-P and -T) were proportionally more depressed than maximal rates of rise (+P and +T), producing significant increments in the ratios between both maximal velocities (+P/-P and +T/-T). The time constant of LVP isovolumic decay tau was significantly prolonged, either in the whole animal or in isolated perfused hearts. The afterload reduction produced by the compounds can account in part for the increase in +P/-P but not for the increase in +T/-T or for the prolongation of tau. These relaxation indices remained unchanged after comparable myocardial depressions elicited by d,l-propranolol or pentobarbital sodium. It is concluded that calcium antagonist compounds are characterized by an "antirelaxant" effect, not explained by changes in HR, CBF, or loading conditions, and independent from their negative inotropic action.
Mechanisms of protection against stroke in stroke-prone spontaneously hypertensive rats
Authors: Sadoshima S. , Busija D. W. , Heistad D. D.
Published: December 2017

The purpose of this study was to examine mechanisms by which sympathetic nerves protect against cerebral hemorrhage and ischemic infarction (i.e., "stroke") in stroke-prone spontaneously hypertensive rats (SHRSP). When unilateral superior cervical ganglionectomy was performed in SHRSP at 1 mo of age, development of cerebral vascular hypertrophy was inhibited and stroke developed only in the denervated hemisphere in 79% of the rats (P less than 0.05). Because "trophic" effects of sympathetic nerves on vascular growth may be less in older animals, unilateral sympathetic denervation was performed in SHRSP at 3 mo of age. The incidence of stroke was similar in the innervated and denervated hemispheres. In another group of rats that had unilateral ganglionectomy at 1 mo, we examined regulation of cerebral blood flow (CBF) when the rats were 4-5 mo of age, before neurologic signs of stroke. CBF, measured with microspheres, was similar in the innervated and denervated hemispheres during control conditions and during maximal vasodilatation produced by bicuculline. In contrast, when mean arterial pressure was raised acutely, CBF increased more in the denervated hemisphere than in the innervated hemisphere. We conclude that 1) in contrast to effects of denervation at 1 mo, sympathetic denervation at 3 mo of age (when trophic effects are less) does not lead to stroke, and 2) chronic denervation impairs the cerebral vasoconstrictor response to acute increases in arterial pressure.
Potentiation of slow action potentials with theophylline or "micro" adenosine deaminase
Authors: Knabb M. T. , Rubio R. , Berne R. M.
Published: December 2017

The effects of endogenous adenosine on rat atrial and ventricular slow action potentials (AP) were studied using theophylline, an adenosine receptor antagonist, or "micro" adenosine deaminase (mADA), small polypeptides having adenosine deaminase activity. Exogenous adenosine (10(-6) M) depressed slow APs at low and high isoproterenol concentrations and shifted the isoproterenol dose-response curve to the right in the atrium. In the ventricle, exogenous adenosine inhibited slow APs at low isoproterenol doses and only shifted the bottom of the dose-response relationship to the right. mADA (0.84 U) or theophylline (5 X 10(-5) M) potentiated the response to threshold concentrations of isoproterenol and caused a parallel shift of the curve to the left in the atrium but only shifted the bottom portion of the curve in the ventricle. This potentiation of slow APs in the presence of mADA or theophylline suggests that endogenous adenosine attenuates the response to isoproterenol in cardiac muscle.
Lack of interaction between a hypertonic NaCl stimulus and the brain renin-angiotensin system
Authors: Takishita S. , Ferrario C. M.
Published: December 2017

Sodium and the renin-angiotensin system (RAS) participate in the regulation of cardiovascular function, in part via activation of central nervous system (CNS) mechanisms. Because intraventricular (IVT) administration of either hypertonic sodium chloride (NaCl) or angiotensin II (ANG II) elicits similar effects (i.e., natriuresis, hypertension, increased drinking, and enhanced vasopressin release) a common and final pathway may be involved. With this in mind, we measured the effect of an IVT injection (third or lateral ventricle) of 0.6 M NaCl on postganglionic renal nerve activity (RNA) and blood pressure in morphine-pentobarbital-anesthetized dogs before and after blockade of the brain RAS with either captopril or [Sar1,Ile8]ANG II. Both vagus and carotid sinus nerves were cut to avoid impingement of the baroreceptor reflex on the measured variables. IVT injection of 0.6 M NaCl produced a prominent hypertensive response and tachycardia associated with a 59 +/- 9% increase in RNA. These changes were statistically significant (P less than 0.001), correlated with each other, and were abolished by administration of hexamethonium chloride (10 mg/kg iv). Blockade of central ANG II receptors with [Sar1,Ile8]ANG II was without effect. However, in dogs given IVT SQ 14,225, there was a slight increase in baseline RNA before injection of 0.6 M NaCl; in addition, both the pressor and heart rate responses to the stimulus of hypertonic NaCl were further augmented. These results demonstrate that central administration of hypertonic NaCl in baroreceptor-denervated dogs produces marked activation of sympathetic nerve activity via mechanisms other than activation of the brain RAS.
Effect of norepinephrine on contractility of isolated mesenteric lymphatics
Authors: Allen J. M. , McHale N. G. , Rooney B. M.
Published: December 2017

Norepinephrine increases the spontaneous contraction frequency of isolated bovine lymphatic vessels but, paradoxically, reduces contraction force. In this investigation contractions were elicited by electrical stimulation, applied as field stimulation or across a sucrose gap. Evoked contractions were not reduced in force by concentrations of norepinephrine that have previously been shown to dramatically reduce contractility in spontaneously active vessels. However, at higher concentrations a beta-inhibitory component of the norepinephrine effect was often observed. Simultaneous recordings of electrical and mechanical activity from spontaneously active vessels showed that each spontaneous contraction was initiated by a single action potential. Norepinephrine significantly disrupted electrical activity causing increased action potential frequency, reduction in action potential amplitude, and frequent failure of full action potential development. We conclude that norepinephrine depresses the force of spontaneous contractions by disruption of spontaneous pacemaking rather than by any direct effect on vessel contractility.
Blood flow and oxygen consumption in active soleus and gracilis muscles in cats
Authors: Bockman E. L.
Published: December 2017

The results of the present study indicate that, although there are quantitative differences, there are no fundamental, qualitative differences in the vascular and metabolic responses to muscle contraction between slow-twitch soleus muscle and fast-twitch gracilis muscle in cats. Vascularly isolated muscles were perfused under free-flow conditions and were stimulated to contract isometrically for 12 min. Venous outflow was measured with a drop counter. Resting blood flow (6.3 +/- 1.3 ml . min-1 . 100 g-1) and oxygen consumption (0.27 +/- 0.04 ml O2 . min-1 . 100g-1) in soleus muscle did not differ significantly from the respective values in gracilis muscle. Blood flow increased by as much as sixfold above control values in both soleus and gracilis muscles in response to muscle contraction. Oxygen consumption increased linearly as a function of muscle performance in both muscles. However, the oxygen cost per kilogram of force developed was about threefold greater in gracilis compared with soleus muscle. The lower oxygen cost of contraction, coupled with an apparent maximal oxygen consumption twice that of gracilis muscle, enabled soleus muscle to maintain a greater level of muscle performance.
Extravascular distribution of albumin and IgG during high-permeability edema in skin
Authors: Bell D. R. , Mullins R. J. , Powers M. R.
Published: December 2017

The effects of local intra-arterial infusions of bradykinin on the interstitial distribution of albumin and gamma-immunoglobulin G (IgG) was studied in hind paw skin of anesthetized rabbits. After 4 h of a continuous bradykinin infusion, lymph flow in a prenodal popliteal lymphatic was five times base line. The lymph-to-plasma concentration ratio for total protein was increased by 34%. Samples of heel skin were taken at the end of the experiment. The extracellular and plasma spaces in the tissue samples were measured using 51Cr-labeled ethylenediaminetetraacetic acid and 125I-labeled human serum albumin, respectively. The protein spaces were calculated from measurements of endogenous albumin and IgG concentrations using rocket electroimmunoassay. After bradykinin, the interstitial volume was 28% greater than control, whereas the extravascular masses of albumin and IgG were twice as great as the control values. Based on lymph concentration, both proteins distributed in 50% of the interstitial volume during control. Following bradykinin, both proteins distributed in a greater fraction of the interstitium. However, the excluded volume, equal to 0.9 ml/g dry wt, was not altered after bradykinin. This may indicate an increase in free-fluid channels with no hydration of the interstitial gel matrix.
Neurohumoral mechanisms in acute aortic coarctation in conscious and anesthetized dogs
Authors: Whitlow P. L. , Katholi R. E.
Published: December 2017

To study the interactions of the renin-angiotensin system, sodium balance, and the sympathetic nervous system in the development of coarctation hypertension, an aortic gradient was created with a pneumatic cuff in 11 chronically instrumented conscious dogs. Significant hypertension associated with a significant rise in plasma renin activity and sodium retention occurred within 48 h. Competitive angiotensin II blockade caused a greater decrease in arterial pressure after coarctation than before coarctation. In contrast, plasma norepinephrine decreased significantly from control levels after coarctation, and alpha-adrenergic blockade with phentolamine caused less of a decrease in arterial pressure than before coarctation. This decrease in sympathetic activity was also accompanied by a decreased blood pressure response to pressor doses of angiotensin II and methoxamine after coarctation. To assess carotid baroreceptor influence on acute coarctation hypertension, aortic blood pressure responses to pressor agents were determined in 12 chlorolose-urethan-anesthetized dogs while carotid sinus pressure was independently varied. Maintaining carotid pressure at control levels after aortic constriction restored blood pressure responses to pressor agents to before-coarctation levels. These results suggest that 1) activation of the renin-angiotensin system and sodium retention contribute to the development of coarctation hypertension, and 2) there is a carotid sinus baroreceptor-mediated decrease in alpha-adrenergic activity with acute coarctation hypertension.
Ratio of cells and plasma in blood flowing past branches in small plastic channels
Authors: Dellimore J. W. , Dunlop M. J. , Canham P. B.
Published: December 2017

Red cell concentrations related to flow were studied by measuring delivered cell fractions from branching channels. A branched channel in a plastic block was cast by pouring setting plastic into a mold containing two 0.18 mm steel wires; one was beveled and touching, at 60 degrees, the side of the other wire, which extended across the mold. The wires were later withdrawn. Two of these flow chambers were perfused (flow of 0.14 ml/min) with human blood or blood diluted with host plasma (anticoagulant ethylenediaminetetra-acetic acid), and the percent cell volume was measured in the collecting tubes. The difference in hematocrit from the two outflow channels was a linear function of the proportional flow in the side branch, and the average slope for 29 experiments was 32.0 +/- 9.7 (SD)% with a negative dependence on inflow hematocrit (correlation coefficient -0.63, P less than 1%). When analyzed as cell flux ratio vs. flow ratio the data show a significant deviation from the line of identity, which is most marked for the lowest values of hematocrit that we studied (approximately equal to 20%). We concluded that if the model branching channels are representative of arteriolar-sized blood vessels, then there is the potential for wide variations in hematocrit in the microcirculation, especially in blood with a low cellular fraction.
Body fluid volumes in prehypertensive spontaneously hypertensive rats
Authors: Mullins M. M.
Published: December 2017

To ascertain the effect of aldosterone on body fluid volumes in neonatal, prehypertensive spontaneously hypertensive rats (SHR), we studied these animals at 12 days using age-matched Wistar-Kyoto (WKY) as normotensive controls. Some pups of each strain were treated with spironolactone (1.5 micrograms/g body wt) on days 10-12. Total body water (TBW, by dessication) and extracellular fluid (ECF, Na2 35SO4 space) volumes were significantly larger in SHR than in WKY, whereas plasma volumes (125I-serum albumin space) were not different. Thus the enlarged ECF was due to preferential expansion of the interstitial fluid (ISF) space. Treatment of SHR with spironolactone reduced TBW and ISF to values not different from untreated WKY and also reduced plasma volume to some extent. These results indicate 1) significant ISF volume expansion occurs in SHR prior to elevation of blood pressure, and 2) the previously observed elevation in plasma aldosterone in SHR at this age probably mediates the volume expansion.
Rapid resetting of aortic baroreceptors in vitro
Authors: Munch P. A. , Andresen M. C. , Brown A. M.
Published: December 2017

Pressure-response characteristics of arterial baroreceptors (BR) were shown recently to be reset following a 15- to 20-min change in mean arterial pressure (MAP); the curves shifted in the direction of the MAP change. To characterize this rapid BR resetting process more precisely than in vitro studies allow, we utilized an in vitro aortic arch-aortic nerve preparation from Wistar-Kyoto rats. Pressure ramps were used to determine the discharge response curves of single BRs following exposure to precisely controlled conditioning pressures. Rapid resetting occurred in all BRs and followed an exponential time course with a 3- to 5-min time constant. The reset curves were stable for 1 h and were completely reversible. The curves were shifted along the pressure axis in a parallel manner, i.e., pressure threshold (Pth) changed but slope and mean asymptotic discharge were unaltered. In experiments lasting as long as 7 h in which more than two MAP steps were possible, in vitro rapid resetting was a very consistent and reproducible process. Quantitatively, the extent of resetting (delta Pth/delta MAP) averaged 0.33 over an MAP range of 40-160 mmHg. In vitro resetting therefore appears very similar to that observed in vivo, suggesting that the conditioning pressure is the primary, perhaps the sole, determinant of resetting. Resetting occurred at subthreshold MAPs, demonstrating action potentials are not a prerequisite. Efferent neural or hormonal influences are also not required.
Myocardial segment velocity at a low load: time, length, and calcium dependence
Authors: Martyn D. A. , Rondinone J. F. , Huntsman L. L.
Published: December 2017

The length and time dependence of shortening velocity (VL) at a very light load (1 mN) was determined for central segments of ferret papillary muscle at 27 degrees C. A recently developed technique that measures the cross-sectional area of the chosen segment was used to assess segment length. Segment length (SL) or force could be used as a feedback control signal. VL was determined by releasing the muscle to a 1-mN load (less than or equal to 3% maximum force) at various times during a segment isometric twitch. Segment isometric twitches were typically performed at 95-98% SLmax, SLmax being the longest segment length attainable in the preparation. VL, as a function of time and SL, was determined from SL shortening during the load clamp. Muscle responses were sampled, stored, and analyzed with an on-line digital computer. The data indicate that 1) at a given SL, VL declines from 20 to 50% of its peak value by the time of peak force production, 2) VL declines linearly with SL below 90% SLmax in 1.125, 2.25, and 4.5 mM extracellular Ca2+, 3) VL exhibits a dependence on extracellular Ca2+, having peak values at 90% SLmax of 3.32 +/- 0.33, 2.66 +/- 0.17, and 1.89 +/- 0.17 SL/s in 4.5, 2.25, and 1.125 mM extracellular Ca2+, respectively.
A reproducible model of chronic hypoxemia
Authors: Erath H. G. , Graham T. P. , Hammon J. W. , Bender H. W.
Published: December 2017

This report presents our experience with producing a stable chronic hypoxemia preparation in the dog without the disadvantages of prosthetic graft insertion or sacrifice of pulmonary tissue. In 28 adult dogs, the intrapericardial inferior vena cava and the area of junction of the right and left inferior pulmonary veins were exposed through a right thoracotomy. The cava was clamped at the diaphragm and at the right atrium, divided at the atrial clamp, and quickly anastomosed to the inferior pulmonary veins. The mean arterial O2 tension (PaO2) decreased from 83.2 +/- 1.6 mmHg preoperatively in mechanically ventilated (room air) animals to 35.3 +/- 1.5 mmHg postoperatively in awake animals spontaneously breathing room air (P less than 0.001). There was persistent depression of the PaO2 (49.1 +/- 1.8 mmHg) and elevation of the hematocrit (64.8 +/- 2.0%) in six animals tested at 18.5 mo postoperatively. Shunt patency without significant stenosis was confirmed in each animal at autopsy. This method attains predictable and persistent hypoxemia and polycythemia and is simple to perform. It may be useful in studying various aspects of ventricular function and ventricular histological and biochemical changes with chronic cyanosis.
Effect of hypoxia on ouabain inhibition of sodium pump in newborn rabbit myocardium
Authors: Shimizu T. , Nakanishi T. , Uemura S. , Jarmakani J. M.
Published: December 2017

The effects of hypoxia and reoxygenation on the inotropic effect of ouabain and sodium pump were studied in the isolated, arterially perfused newborn rabbit heart. Myocardial 86Rb+ active uptake was used as a marker of the sodium pump activity. During reoxygenation after mild hypoxia, 86Rb+ active uptake and ouabain effect were not significantly different from control. After severe hypoxia (with glucose) and reoxygenation, the inotropic effect of ouabain was not different from control, but mechanical toxicity occurred sooner. Severe hypoxia (with glucose-free solution) and reoxygenation caused an increase in tissue calcium, an attenuated inotropic effect of ouabain, and earlier mechanical toxicity. 86Rb+ active uptake was similar in all severe hypoxia groups and was significantly less than control values. Ouabain inhibition of 86Rb+ uptake in the severe hypoxia groups was not significantly different from control. These data indicate that severe hypoxia and reoxygenation depress the sodium pump but the effect of ouabain on the sodium pump in these muscles is similar to control. The decreased inotropic effect and increased toxicity of ouabain during reoxygenation after severe hypoxia may be due to an increase in cytoplasmic calcium and decreased tissue ATP.
Effect of Escherichia coli endotoxin on dog lung fluid balance
Authors: Scott R. L. , Adcock D. K. , Drake R. E. , Gabel J. C.
Published: December 2017

Endotoxin may cause an increase in pulmonary capillary permeability and thus promote edema formation. We used a gravimetric technique to estimate the pulmonary capillary filtration coefficient (KF) and the maximum capillary pressure at which the lung could maintain a constant weight (Pccritical) in dogs after intravenous administration of Escherichia coli (E. coli) endotoxin. KF should be increased and Pccritical should be decreased by an increase in permeability. Four groups of three to four dogs were given 1, 10, 1,000, or 3,000 micrograms/kg of endotoxin. A fifth group of five dogs, which served as controls, was given no endotoxin. KF was significantly (P less than 0.05) greater than control [0.049 +/- 0.031 (SD) ml . min-1 . mmHg-1] in only the 1-micrograms/kg group (0.100 +/- 0.027), indicating a possible increase in permeability. However, changes in capillary surface area may have affected KF. Pccritical was not significantly different from control (20.7 +/- 2.4 mmHg) in any of the E. coli groups. We conclude from these results that E. coli endotoxin may have caused a slight increase in permeability; however, the lung retained its ability to resist edema formation.
Central catecholamine depletion, vasopressin, and blood pressure in the DOCA/NaCl rat
Authors: Okuno T. , Winternitz S. R. , Lindheimer M. D. , Oparil S.
Published: December 2017

To determine whether impaired arginine vasopressin (AVP) release occurs when DOCA-NaCl hypertension is prevented following chemical sympathectomy with 6-hydroxydopamine (6-OHDA), male Sprague-Dawley rats treated with intraventricular injections of 6-OHDA (250 micrograms X 2) or Merlis solution received deoxycorticosterone acetate (DOCA) implants (100 mg/kg) and drank 0.5% saline. Systolic blood pressure in the 6-OHDA-treated DOCA/NaCl group (139 +/- 4 mmHg) was lower (P less than 0.001) than in the Merlis-DOCA/NaCl group (183 +/- 7 mmHg). 6-OHDA treatment produced widespread catecholamine depletion throughout the central nervous system, including the supraoptic and paraventricular nuclei, the cells of which are known to produce AVP, but hypothalamic, pituitary, and plasma AVP levels were similar in both experimental groups, the latter values averaging 1.5–2 times those of controls. Both groups of rats suppressed AVP secretion appropriately when water loaded. Such suppression, however, had no effect on blood pressure in the hypertensive animals and, furthermore, administration of the AVP antagonist d(CH2)5Tyr(Me)AVP produced small decrements in mean blood pressure of both groups that were not significantly different from responses seen in control normotensive rats. These data demonstrate that 6-OHDA does not prevent DOCA-NaCl hypertension by decreasing AVP levels and suggest that AVP is not necessary for the maintenance of hypertension in this model.
Rat muscle blood flows as a function of time during prolonged slow treadmill exercise
Authors: Laughlin M. H. , Armstrong R. B.
Published: December 2017

The purpose of these experiments was to follow blood flows (BF) within and among rat hindlimb skeletal muscles as a function of time during prolonged low-speed treadmill locomotion. Male Sprague-Dawley rats were chronically instrumented with two Silastic catheters, one in the ascending aorta via the right carotid artery for microsphere infusion and one in the left renal artery for arterial reference blood sample withdrawal. BFs were measured, using the radio-labeled microsphere technique, within and among 23 major skeletal muscles of rats before exercise and during treadmill locomotion at 15 m/min at 0.5, 1, 5, 15, 30, 54, and 71 min of exercise. During preexercise, BF was highest to deeply situated slow-twitch muscles (210 ml . min-1 . 100 g-1 in vastus intermedius) in the antigravity extensor muscle groups. During the 1st min of exercise each of the hindlimb muscles displayed one of four general BF patterns. 1) Many muscles had an “overshoot” in BF during the first 30 s of exercise; 2) some muscles attained steady-state exercise levels in the first 30 s of exercise; 3) others showed a decrease below preexercise levels; and 4) some muscles showed no change from preexercise. Most muscles showed a gradual increase in BF from 5 min through 54 min of exercise. The elevations in BF over preexercise were primarily directed to fast-twitch oxidative muscle fibers in the antigravity extensor muscles, and BFs to extensor muscle groups were generally higher than those to flexor muscle groups. The data demonstrate that BFs within and among rat muscles are heterogeneous, both before exercise and during prolonged low-intensity treadmill walking to fatigue. Mechanisms regulating the distribution of flow to the muscles remain to be elucidated.
Altered coenzyme A and carnitine metabolism in pressure-overload hypertrophied hearts
Authors: Reibel D. K. , Uboh C. E. , Kent R. L.
Published: December 2017

Changes in the total content and acylation state of coenzyme A (CoA) and carnitine in the heart result in alterations in fatty acid metabolism that may be associated with ventricular dysfunction. The present study was undertaken to determine whether abnormal myocardial CoA and carnitine metabolism occur in pressure-overload hypertrophy and congestive heart failure. Right ventricular hypertrophy was induced in cats by pulmonary artery (PA) banding. Total tissue CoA was reduced by 50% in the hypertrophied right ventricle and 25% in the nonhypertrophied left ventricle of PA-banded cats in the presence or absence of heart failure. No alterations were observed in long-chain fatty acyl CoA levels in either ventricle of PA-banded cats. In addition, a 20% reduction in total CoA was also observed in hypertrophied hearts of rats subjected to aortic banding. Although the CoA content was reduced in hypertrophied cat hearts, myocardial tissue levels of its precursor, pantothenic acid, were unaltered. Total tissue carnitine and long-chain fatty acyl-carnitine levels were unchanged in both ventricles of PA-banded cats; however, total carnitine was reduced by 25% in hypertrophied rat hearts. This study establishes a marked reduction in myocardial CoA content in pressure-overload hypertrophy.
Evidence for a central role for vasopressin in cardiovascular regulation
Authors: Berecek K. H. , Webb R. L. , Brody M. J.
Published: December 2017

Central vasopressin (VP) may modulate the functional activity of specific neuronal systems involved in cardiovascular regulation. To test this hypothesis we compared cardiovascular (CV) responses to electrical stimulation of the anteroventral region of the third ventricle (AV3V) in Brattleboro rats homozygous for diabetes insipidus (DI), in heterozygous DI rats (DI-HZ) and in normal Long-Evans rats (LE). We also studied the effects of peripheral and intracerebroventricular (ivt) treatment of DI rats with VP and treatment of LE rats with an antipressor blocker of VP on cardiovascular responses to AV3V stimulation. Stimulation of the AV3V region in anesthetized LE rats produced a frequency-dependent increase in renal (RVR) and mesenteric vascular resistance (MVR), a decrease in hindquarter vascular resistance (HQVR), and a decrease in arterial pressure (AP) and heart rate (HR). DI and DI-HZ rats showed significantly greater decreases in AP and HR and lesser changes in RVR, MVR, and HQVR. The deficiency in vasoconstriction in DI rats appeared to be centrally mediated inasmuch as vascular responses to peripherally administered phenylephrine and nerve stimulation were comparable in LE and DI rats. Treatment of DI rats with VP peripherally improved CV responses to AV3V stimulation. An even greater improvement in CV responses to AV3V stimulation was obtained when DI were given ivt infusion of VP. Finally, following intravenous administration of an antipressor VP blocker LE rats showed a greater decrease in AP and HR and lesser resistance changes in response to AV3V stimulation. Our data suggest that cardiovascular responses elicited from stimulation of the AV3V region may depend, in part, on a central vasopressin mechanism.
Renal blood flow autoregulation in developing swine
Authors: Buckley N. M. , Brazeau P. , Frasier I. D.
Published: December 2017

Pressure-flow relationships (P/F) in the renal circulation were determined in 62 swine, aged 1 day-2 mo, anesthetized with pentobarbital sodium. Aortic and inferior vena caval pressures and renal and femoral arterial flows were recorded. Blood gas composition and pH and body temperature were monitored. The P/F was first determined while perfusion pressure was decreased for 2 min at each pressure by suprarenal aortic occlusion. The left renal artery in 38 of these animals was then cannulated for in situ perfusion of the kidney with blood withdrawn from a carotid artery by a Masterflex pump. The P/F was subsequently determined by changing pump flow for 2 min at each flow while recording perfusion pressure. Records were analyzed for transient and steady-state effects. Readjustments in renal vascular resistance (RVR) were apparent within 5 s after changing pressure or flow. The RVR stabilized at a new level within 2 min. Graphs of steady-state data delineated an autoregulatory range in the P/F for animals as young as 2 wk of age. We conclude that renal blood flow autoregulation in this mammal is negligible at birth and develops progressively during the first postnatal month.
Left ventricular systolic dynamics in terms of its chamber mechanical properties
Authors: Shroff S. G. , Janicki J. S. , Weber K. T.
Published: December 2017

To determine the mechanical properties of the left ventricle (LV) as a pump, a mathematical model of its systolic dynamics was developed. Initially the model consisted of three elements, i.e., elastance, resistance, and inertance. Results from three experiments, however, indicated that the inertial component was negligible compared with the other two components. The functional forms of elastance and resistance were determined by applying the flow-pulse response technique to an isovolumetrically beating, isolated canine heart. Results from three experiments indicated that the systolic elastance and resistance can be represented by a third-order polynomial in time and a linear function of instantaneous ventricular pressure (LVP), respectively. The simplified model was then tested by calculating the systolic elastance and resistance from LVP, volume, and flow data of an ejecting LV obtained over a single cardiac cycle. A total of 225 combinations (10 expts) of end-diastolic volume (EDV), ejection pressure (EP), heart rate (HR), and contractile state (CS) were evaluated. The results indicated that 1) the elastance function was insensitive to variations in EDV and EP but was a function of CS and HR; 2) the linear resistance-pressure relationship was insensitive to variations in EDV, EP, HR, and CS; and 3) the model could "prospectively" predict the LV isovolumetric pressure from the data of an ejecting beat. Thus a model of LV systolic dynamics has been established that can be used to calculate the intrinsic chamber mechanical properties, i.e., elastance and resistance, of an ejecting LV.
A compartmental analysis of the splenic circulation in rat
Authors: Stock R. J. , Cilento E. V. , Reilly F. D. , McCuskey R. S.
Published: December 2017

Isolated, acellular washout experiments of 125I-labeled bovine serum albumin (BSA) from control, anemic, and polycythemic rat spleens were used to develop a model of the splenic plasma circulation. The results indicated that the plasma circulation can be described adequately by two compartments. As in red blood cell (RBC) washouts [Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H272-H277, 1980] the fast compartment represents intrasplenic vessels that bypass the red pulp, whereas the intermediate/slow compartment represents plasma flow through the red pulp (filter). The combined plasma and RBC parameters suggest the rat spleen is not an RBC reservoir and that splenic RBC filtration capacity decreases during polycythemia and anemia. The ratio of fast compartment to systemic hematocrit indicates hemodilution occurs, supporting the concept of plasma skimming. A small plasma holdup occurs in the red pulp of anemic and polycythemic spleens probably due to RBC congestion. This congestion, in turn, might be due to reticulocyte sequestration and/or erythropoiesis in anemic spleens and RBC sequestration and/or destruction in polycythemic spleens. There is plasma redistribution in polycythemic spleens possibly to meet the increased metabolic demand.
Continuous measurement of arteriovenous oxygen difference and VO2 by microcomputer
Authors: Kiel J. W. , Shepherd A. P.
Published: December 2017

We have developed a microcomputer-based system to measure the arteriovenous oxygen difference [(a-v)O2] continuously in whole blood and to compute the oxygen consumption rate of an organ. The system consists of a pair of flow-through cuvettes perfused with arterial and venous blood, a simple electronic circuit to illuminate the cuvettes and to measure the intensity of the transmitted light, an analog-to-digital converter, and an Apple II+ computer. The computer samples the intensities of the light transmitted through the arterial and venous cuvettes, digitizes an electromagnetic blood flow signal, and computes both the arteriovenous oxygen difference and the oxygen consumption rate. The computed variables are sent via a digital-to-analog converter to a multichannel recorder. By comparing our spectrophotometric determinations of the (a-v)O2 with conventional O2 content measurements, we found our (a-v)O2 computer to yield an accurate, linear measurement of the (a-v)O2. This spectrophotometric method for determining the (a-v)O2 offers the advantages of a rapid, continuous measurement. It eliminates the labor and errors involved in multiple, discontinuous sampling, thus freeing the investigator for other tasks, and it provides the investigator almost immediate feedback regarding the oxygen consumption rate of his preparation. Furthermore, the system could also be used (with minor modifications to the program) for the continuous measurement of cardiac output if whole-body oxygen consumption were determined from expired gases.
Altered nicotinic sensitivity of AV node in surgically denervated canine hearts
Authors: Priola D. V. , Curtis M. B. , Anagnostelis C. , Martinez E.
Published: December 2017

The responses of normal and cardiac-denervated (DNV) dogs to acetylcholine (ACh) and nicotine (NIC) were examined to determine if the intrinsic cardiac nerves (ICN) that modulate electrical conduction display denervation supersensitivity. Control (n = 18) and DNV (n = 18) animals were placed on cardiopulmonary bypass. Recording of intra-atrial (P-A), intraventricular (H-V), and atrioventricular (AV) nodal (A-H) conduction times were made from the region of the His bundle. ACh (0.1-10 micrograms) was used to produce muscarinic stimulation, whereas NIC (0.1-400 micrograms) was employed to stimulate the ICN. All drugs were administered intracoronary. No supersensitivity to either ACh or NIC was seen in the data from the P-A or H-V intervals of the His electrogram in the DNV animals. However, this group displayed approximately a 10-fold increase in the negative dromotropic effect of NIC on the AV node compared with control. No significant change in muscarinic sensitivity of the AV node was observed in the DNV animals. We conclude that 1) no denervation supersensitivity of the ICN mediating effects on intra-atrial and intraventricular conduction occurs; 2) the AV node itself does not show muscarinic supersensitivity following extrinsic denervation; 3) the ICN do display denervation supersensitivity as shown by a 10-fold increase in the effects of NIC on AV nodal conduction time.
Electrotonic inhibition and summation of impulse conduction in mammalian Purkinje fibers
Authors: Antzelevitch C. , Moe G. K.
Published: December 2017

Models of electrotonically mediated transmission were created by superfusion of the central fiber segment of a three-compartment Purkinje fiber preparation with either an "ion-free" or "ischemic" solution or by localized application of pressure. The frequency-dependent impairment of impulse conduction across such inexcitable gaps was found to be the result of influences exerted not only by impulses transmitted across the area of block but also by impulses blocked at the proximal border of the inexcitable zone. The electrotonic image of a nonconducted response was observed to exert an important inhibitory effect on the electronically mediated transmission of a subsequent impulse, thus causing block or delay. This phenomenon, which we have termed electrotonic inhibition, shows both time and voltage dependence. The related phenomenon of electrotonic summation describes the facilitation of conduction that occurs when two subthreshold potentials occur close enough in time to fuse. These data provide a demonstration of Wedensky inhibition in heart tissues and point to electrotonic inhibition as a mechanism of concealed conduction. Electrotonically mediated phenomena may explain both temporal and spatial inhibition and summation previously described in nodal or depressed tissues and ascribed to partial active invasion of intermediary tissue.
Baroreflex open-loop gain and arterial pressure compensation in hemorrhagic hypotension
Authors: Chen H. I. , Bishop V. S.
Published: December 2017

The loop gain (G) of the carotid baroreceptor was determined using open- and closed-loop approach in anesthetized rabbits after aortic denervation and vagotomy. The open-loop relationship between the intrasinus pressure (ISP) and systemic arterial pressure (SAP) was nonlinear. The slope (delta SAP/delta ISP) or G was maximal (about 1.5) near the control arterial pressure and decreased toward the saturation pressures. We examined how this nonlinearity relates to the arterial pressure compensation following hemorrhage. Because the baroreflex attenuation of the posthemorrhagic hypotension depends on the SAP responses to an input perturbation, we first demonstrated that the open-loop responses in SAP to a specific delta ISP was not altered during various amounts of hemorrhage, despite different operating range for the responses. In the open-loop condition when ISP was fixed at the control level, hemorrhage of 10, 20, and 30 ml produced a SAP disturbance (D) of 23.3, 43.5, and 62.4 mmHg, respectively. The figures were minimized to 9.8, 19.8, and 34.4 mmHg (D'), respectively through the baroreflex compensation in the closed-loop condition. The calculated G (D/D' - 1) from the closed-loop data were 1.38, 1.20, and 0.82 for 10, 20, and 30 ml hemorrhage. For a given input signal (delta ISP = D'), the values of G were essentially the same as those obtained from the open-loop ISP-SAP curve. The G values decreased as the degree of hemorrhagic hypotension increased, being in agreement with the sigmoid characteristics of the nonlinear ISP-SAP curve.