bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute inhibition of renin release during left circumflex coronary occlusion in dogs
Authors: Livnat A. , Zehr J. E.
Published: December 2017

We examined the reflex effect of brief left circumflex coronary artery occlusion (CAO) on renal blood flow (RBF) and renin secretion (RS). Studies were conducted in alpha-chloralose-anesthetized dogs maintained on a salt-free diet for at least 3 days. A snare was placed around the left circumflex artery near its origin. The left renal artery and vein were exposed via flank incision, a flow probe was placed around the artery, and a curved needle was inserted into the vein for collection of renal venous blood. Values of blood pressure (BP), RBF, and RS were obtained for a 30-min control period, 4 min after the completion of a 10-ml/kg hemorrhage, 1 and 5 min after CAO, and 15 min after reinfusion. The CAO consisted of two 1-min occlusions separated by a 1-min interval. The results indicate that CAO reflexively inhibits the RS response to nonhypotensive hemorrhage and prevents renal vasoconstriction (P less than 0.05, n = 7). Both effects were completely abolished after vagotomy (n = 5). Renal denervation also abolished the response (n = 5). No response was observed during identical time controls (n = 5). The response was more pronounced in dogs with carotid sinus denervation, even though CAO resulted in marked reductions in BP (20%) under these conditions. These results demonstrate the presence of a cardiorenal reflex that can be activated by myocardial hypoxia and that acutely suppresses RS. This response is more pronounced in the absence of carotid sinus buffering.
Noninvasive measurement of systolic and diastolic blood pressure in swine
Authors: Hodgkin B. C. , Burkett D. E. , Smith E. B.
Published: December 2017

Arterial blood pressure was measured noninvasively using Doppler ultrasound and an occluding cuff. The subjects were 28 domestic pigs (10-49 kg) anesthetized with pentobarbital sodium (25 mg/kg). Indirect pressure measurements were made with the Doppler unit placed over the radial or the ulnar artery proximal to the carpal joint. Comparison was made with directly measured pressure to determine the reliability and reproducibility of the indirect method. Direct systolic pressures between 73 and 230 mmHg and diastolic pressures between 52 and 165 mmHg were measured. There was no significant difference between directly and indirectly measured systolic pressure (P greater than 0.20). Indirectly measured diastolic pressure tended to be lower than direct diastolic pressure, the difference by the paired t test being significant to P = 0.06. For systolic pressure the sample correlation coefficient was 0.94, and for diastolic pressure, 0.88. Both systolic and diastolic blood pressure can be accurately measured in the anesthetized pig using Doppler ultrasound and an occluding cuff.
Interaction of verapamil with human platelet alpha-adrenergic receptors
Authors: Barnathan E. S. , Addonizio V. P. , Shattil S. J.
Published: December 2017

Platelet aggregation induced by epinephrine is an alpha-adrenergic event and is inhibited in vitro by the calcium-channel blocker, verapamil. We wondered whether this inhibition might be mediated by an interaction of verapamil with platelet alpha-adrenergic receptors. Verapamil inhibited the specific binding of [3H]dihydroergocryptine ([3H]DHE), a nonselective alpha-adrenergic antagonist, to intact platelets in a concentration-dependent and competitive manner. At 10 microM verapamil caused a fivefold decrease in the affinity of binding of [3H]DHE to platelet alpha-adrenergic receptors (P less than 0.001) with no change in the number of receptors per platelet. The inhibition of binding was not reversed by excess calcium. Verapamil also inhibited the binding of a selective alpha 2-adrenergic antagonist, [3H]yohimbine, to intact platelets, and inhibited the binding of an alpha 2-partial agonist, [3H]clonidine, to platelet membranes. Moreover there was a strong correlation between verapamil's effect on [3H]DHE binding and its effect on epinephrine-induced aggregation (r = 0.98). Although verapamil is commonly used as an inhibitor of calcium flux across cell membranes, the present studies demonstrate that verapamil also inhibits epinephrine-induced aggregation at the level of the platelet alpha-adrenergic receptor.
Acute interaction of vasopressin and neurogenic mechanisms in DOC-salt hypertension
Authors: Matsuguchi H. , Schmid P. G.
Published: December 2017

We investigated the relative role of vasopressin and neurogenic factors in the control of vascular resistance in rats treated with desoxycorticosterone (DOC) and salt and in control rats. DOC-salt-treated rats had elevated hindquarter vascular resistance (P less than 0.05). Vasopressin and neurogenic tone contributed significantly (P less than 0.05) to increased resistance. Vasodilator responses to a specific vasopressin antagonist, I-deaminopenicillamine, 4-valine, 8-D-arginine vasopressin (dPVDAVP), and lumbar sympathectomy in separate DOC-salt groups accounted for 40 +/- 5 (SE) and 43 +/- 6%, respectively, of the total vasodilator capacity. In contrast, corresponding responses to dPVDAVP and lumbar sympathectomy in control rats were smaller (P less than 0.01), were significantly different (P less than 0.05), and accounted for 8 +/- 3 and 20 +/- 3%, respectively, of the total vasodilator capacity. Effects of dPVDAVP compared in innervated hindquarters of DOC-salt-treated and control rats were greater in DOC-salt-treated rats (P less than 0.001); in the denervated hindquarters the effects of dPVDAVP were similar in DOC-salt-treated and control rats. Therefore, effects of vasopressin on vascular resistance were augmented in DOC-salt-treated hypertensive rats; furthermore this augmented effect was dependent on an intact innervation.
Fetal intestinal oxygen consumption at various levels of oxygenation
Authors: Edelstone D. I. , Holzman I. R.
Published: December 2017

In seven chronically catheterized fetal lambs, blood flow and oxygen consumption (VO2) in the combined small and large intestines were determined at various oxygen concentrations in fetal arterial blood (CaO2). Intestinal blood flow (Qi) was measured with the radioactive-microsphere technique; intestinal oxygen delivery (DO2 = Qi X CaO2), VO2 [Qi X C(a-v)O2, where oxygen extraction [C(a-v)O2/CaO2] were computed with the Fick equation. Compared with normally oxygenated fetuses (CaO2 greater than 6.6 ml/dl), moderately hypoxemic fetuses (CaO2 = 4.4-6.6 ml/dl) had decreased intestinal DO2, increased oxygen extraction, and no change in intestinal VO2, Qi, or mesenteric-venous pH and base excess. During severe fetal hypoxemia (CaO2 less than 4.4 ml/dl), DO2 decreased further while oxygen extraction increased substantially. Intestinal VO2 dropped, however, because the rise in oxygen extraction could no longer completely compensate for the reduced DO2. With severe hypoxemia, Qi and mesenteric-venous pH and base excess also fell. These data indicate that the fetal intestinal tract is able to meet its oxygen needs during hypoxemia until a critically low level of oxygenation is reached. Below this level intestinal oxygenation becomes inadequate, and anaerobic metabolism ensures.
Blood flow and ultrastructure in ischemic myocardium of cats given dexamethasone
Authors: Spath J. A. , Barsotti R. J.
Published: December 2017

Regional myocardial blood flow or myocardial creatine kinase activity and ultrastructure was studied in anesthetized cats subjected to sham operation, 5 h of circumflex-artery ligation, or 2 h of coronary-artery ligation with 3 h of reperfusion. Sham-operated cats were given dexamethasone sodium phosphate (8 mg/kg iv) at the beginning of the experiment. Cats subjected to coronary-artery ligation were given steroid or vehicle before ligation. In sham-operated cats the average blood flow in tissue of the anterior wall was 2.11 +/- 0.37 (SER) ml.g-1.min-1. The corresponding flow for tissue of the posterior wall was 2.22 +/- 0.42 ml.g-1.min-1. Ligation of the circumflex artery produced a range of average blood flow in the posterior basal myocardium that was 52-92% less than that of sham-operated cats. Within the tissue of the posterior left ventricular wall, steroid pretreatment did not prevent loss of creatine kinase activity after coronary-artery ligation. Moreover, steroid pretreatment was ineffective in maintaining myocardial structure in reperfused myocardial tissue. These results indicate that 1) dexamethasone does not effectively increase blood flow within ischemic or reperfused myocardial tissue, and 2) dexamethasone may stabilize ischemic myocardial tissue. However, upon reperfusion, dexamethasone is unable to maintain myocardial ultrastructure in moderately to severely ischemic tissue.
Direct measurement of sarcomere length from isolated cardiac cells
Authors: Roos K. P. , Brady A. J. , Tan S. T.
Published: December 2017

Isolated cardiac muscle cells enzymatically digested with collagenase and hyaluronidase from whole rat myocardium demonstrate the characteristics of an intact membrane in that they tolerate millimolar concentrations of free Ca2+ and exhibit phasic contractions with electrical excitation. These isolated cells maintain their characteristic A-I band striation patterns when at rest or during contraction. An apparatus has been developed to directly image these cells with phase-contrast micrography onto a 1,728-element charge-coupled device photodiode array for rapid data storage in a digital computer. The digitized striation pattern profile was analyzed for individual and average sarcomere spacing. In isotonic media the average resting sarcomere length ranged from 1.77 to 1.91 micrometers in 13 cells, with a mean length of 1.83 +/- 0.12 micrometers. Electrically stimulated phasic contractions in three cells demonstrated a synchronous 20% decrease in sarcomere spacing to a mean of 1.51 micrometers. Striation spacing decreased under hypertonic stress but elongated only up to 1.93 micrometers in hypotonic solutions, suggesting that some internal elastic constraint exists that limits elongation of the cell.
Responses to activation of cardiac sympathetic afferents with epicardial bradykinin
Authors: Felder R. B. , Thames M. D.
Published: December 2017

The cardiovascular reflex responses mediated by cardiac sympathetic afferent fibers (CSA) appear to differ depending on the nature of the activating stimulus. Although electrical stimulation of CSA may result in either excitatory of inhibitory reflex responses in both cats and dogs, topical application of bradykinin to these sensory endings elicits only excitatory reflex responses in cats. The present experiments were performed to determine whether CSA activated by epicardial bradykinin also mediate solely excitatory reflex responses in the dog. The changes in efferent cardiac or renal sympathetic nerve activity, mean arterial pressure, and heart rate resulting from application of bradykinin to the left ventricular epicardial surface were determined in 15 chloralose-anesthetized, sinoaortic-denervated vagotomized dogs. Activation of CSA with bradykinin (0.1—120 g/ml) elicited inhibitory responses in eight dogs, excitatory responses in four dogs, and biphasic responses in three dogs. Both excitatory and inhibitory reflexes were eliminated by cardiac sympathetic afferent denervation. The results show that, in the dog, cardiac receptors with sympathetic afferent fibers activated by epicardial bradykinin mediate nonuniform reflex responses that tend to be predominantly inhibitory.
Does normal pulmonary impedance constitute the optimum load for the right ventricle?
Authors: Piene H. , Sund T.
Published: December 2017

Right ventricular performance of isolated supported cat hearts was experimentally characterized by a relationship among ventricular pressure (P), volume (V), and time after onset of systole. This characterization was combined with a hypothetical load network consisting of lumped central and peripheral lung vascular resistances (Rc and Rp), inertance (L), and compliance (C). We calculated ventricular and load pressure, flow, external ventricular work (Wext), static ventricular P-V energy (Wstat), and pump efficiency Q = Wext/Wstat over a broad range of load conditions. Magnitudes of load network variables resulting in a maximum value of Q would define the load impedance matching the ventricle. A practical optimum magnitude of lumped vascular compliance was obtained at C = 150 x 10(-6) g-1 . cm4, above which no substantial change in Q took place. We obtained maximum Q at approximately 4 ml stroke volume (heart rate = 2 Hz) and at characteristic impedance between 0.75 and 1.1 x 10(3)g . cm-1 . s-1. As these values are quite close to those encountered in the intact animal, we conclude that the right ventricular and the pulmonary arterial tree appear to constitute a matched pump-load system.
Sinusal afferents supplying superior cervical ganglion
Authors: Tuttle R. S. , McCleary M.
Published: December 2017

Sinusal distension can evoke activity in nerves supplying the superior cervical ganglion. These nerves, which have been shown to have little depressor influence, may carry an inhibitory input from the carotid sinus to the superior cervical ganglion (SCG). They have the morphological characteristics of the nerve of Hering and show cardiac pulse-related activity that may reach a maximum of 50 impulses/s during distension of the sinus. Electrical stimulation of the ascending preganglionic sympathetic trunk supplying the SCG may evoke discreet bursts of activity in these fibers, which do not summate with continued stimulation.
Influence of carotid sinus pressure on atrial receptors and renal blood flow
Authors: Karim F. , Mackay D. U. , Kappagoda C. T.
Published: December 2017

Stimulation of the atrial receptors results in an increase in renal blood flow. The present investigation was undertaken to determine whether this response was modulated by the input from the baroceptors in the carotid sinus. The experiments were performed on dogs anesthetized with chloralose. The systemic arterial pressure was held constant. The carotid sinuses were perfused at 62 +/- 1.3, 95 +/- 2.7, and 145 +/- 8.3 mmHg. The atrial receptors were stimulated by distension of small balloons positioned at the left pulmonary vein-atrial junctions and the left atrial appendage. At a carotid sinus pressure of 62 +/- 1.3 mmHg, the blood flow increased from 182 +/- 8.5 to 199 +/- 8.9 ml . min-1 . 100 g-1 renal mass. At a carotid sinus pressure of 95 +/- 2.7 mmHg, the blood flow increased from 202 +/- 9.6 to 209 +/- 10.4 ml . min-1 . 100 g-1 renal mass. At a carotid sinus pressure of 145 +/- 8.3 mmHg, the blood flow increased from 237 +/- 13.0 to 239 +/- 12.5 ml . min-1 . 100 g-1 renal mass. The first two responses alone were statistically significant. The response at a carotid sinus pressure of 62 +/- 1.3 mmHg was abolished by cutting or cooling the cervical vagi to 8--10 degrees C. It is concluded that stimulation of the left atrial receptors produces a reflex increase in blood flow to the kidney, and this response is modulated by the input from the carotid sinus baroceptors.
Regulation of norepinephrine levels in synaptic clefts of dog vascular tissue
Authors: Rorie D. K. , Tyce G. M.
Published: December 2017

The overflow of endogenous norepinephrine (NE) from superfused dog pulmonary artery and saphenous vein in response to electrical stimulation and the content of NE remaining in the tissue after stimulation were measured using liquid chromatography with electrochemical detection. Overflow of NE was 0.15-0.22 and 0.14 to 0.30 ng/min in pulmonary artery and saphenous vein, respectively, during stimulation. Release of NE (measured in the presence of cocaine and corticosterone to block removal of NE from the synaptic cleft) was greater in the pulmonary artery (0.50-0.87 ng/min) than in saphenous vein (0.39-0.51 ng/min). NE overflow decreased after the first 4 min of continuous stimulation in saphenous vein but not in pulmonary artery. As only 2.26% of the NE content of vein overflowed during stimulation, depletion of NE or deterioration of the preparation seemed unlikely. Presynaptic alpha- or beta-receptor blockade did not change the pattern of NE overflow. Thus in the saphenous vein, but not in the pulmonary artery, removal of NE from the synaptic cleft appears to be facilitated during electric stimulation. This suggests the existence of a new mechanism, possibly related to enhanced catechol methyltransferase activity, which regulates NE levels in the synaptic cleft in saphenous vein but not in pulmonary artery.
Comparison of mechanical and chemical properties of extra- and intralobar canine pulmonary arteries
Authors: Cox R. H.
Published: December 2017

Segments of pulmonary arteries from five extralobar and intralobar sites in the form of circumferential rings were used for the determination of active and passive mechanics, analysis of connective tissue, and determination of water and electrolyte content. Measurements of ring length and tension were made under conditions of active (145 mM K+) and passive (Ca2+ free and 2 mM EGTA) smooth muscle and were used to compute values of segment stress and strain. Passive stress-strain relations among the various sites studied were not significantly different. Collagen and total connective tissue content increased from the largest extralobar to the smallest intralobar sites studied. This suggests differences in the organization of the connective tissue proteins at the secondary and tertiary levels in the various sites studied. The maximum active stress (force/area) developed in response to high K+ was largest in the intralobar arteries and lower in the larger extralobar arteries. The K+ content of these arteries decreased significantly with distance from the heart. The extracellular water content decreased with distance from the heart, whereas total water content was unchanged. These results suggest that relative cell volume decreased with distance from the heart in pulmonary arteries. Thus differences in the relative cell content per se were not responsible for the differences in maximum active stress development among the various arteries.
Mitochondrial cholesterol content and membrane properties in porcine myocardial ischemia
Authors: Rouslin W. , MacGee J. , Gupte S. , Wesselman A. , Epps D. E.
Published: December 2017

Regional myocardial ischemia was produced in anesthetized pigs by occluding the left anterior descending coronary artery. Mitochondria were prepared from both normally perfused and ischemic myocardium after 2 h of occlusion. Mitochondria from the ischemic area exhibited an 89% increase in cholesterol content from 32.7 +/- 1.9 (control) to 62.0 +/- 0.47 (ischemic) nmol/mg protein with no change in either total phospholipid content or in membrane fatty acid composition. This increase in mitochondrial membrane cholesterol was accompanied by an increase in membrane microviscosity as indicated by increased fluorescence polarization using the fluorescent membrane probe, 1,6-diphenyl-1,3,5-hexatriene. In these same experiments the Arrhenius plot discontinuity temperature of oligomycin-sensitive adenosinetriphosphatase (ATPase) activity fell from 20.0 to 14.2 degrees C. Our results suggest that, during the myocardial ischemic process in pigs, there is an intracellular redistribution of free cholesterol that produces a marked increase in mitochondrial membrane cholesterol content. This appears to produce an altered mitochondrial membrane lipid bilayer packing, resulting in increased membrane microviscosity and, possibly, altered inner membrane ATPase function. Intracellular cholesterol redistribution may thus contribute to the cell membrane damage that occurs during the myocardial ischemic process.
Fluid exchange across single capillaries in rat intestinal muscle
Authors: Gore R. W.
Published: December 2017

Previous studies suggest that large differences exist among fluid exchange parameters in the mesenteric, muscle, and mucosal regions of the small intestine. However, few quantitative data from the separate regions, with the exception of the mesentery, are available for comparison. In this study, quantitative measurements of hydraulic conductivities (LP) and occluded effective pressures (P'e) were made on single capillaries in rat intestinal muscle. The microcirculation of longitudinal intestinal muscle was viewed through a microscope using the method of Bohlen and Gore. The single-occlusion method of Lee, Smaje, and Zweifach was used to estimate LP and P'e in single capillaries. Details of the procedures for analyzing the experimental data using the Lee analytical model are included in an APPENDIX. Measurements were made at four different sites in each capillary studied so gradients in LP could be quantitated and variations in P'e could be detected. The average LP at the venous end of the capillaries was nearly seven times greater than LP at the arterial end. The average LP at the arterial end [18.6 +/- 2.3(SE)% of the distance (%L/Lo) from the fifth-order arterioles] was 1.32 +/- 0.4 X 10(-2) micrometers.s-1.cmH2O-1. The average LP at the venous end (%L/Lo = 81.7 +/- 2.2%) was 9.15 +/- 0.34 X 10(-2) micrometers.s-1.cmH2O-1. Values of LP at intermediate capillary locations 39.9 +/- 2.3 and 61.3 +/- 3.2% were 2.17 +/- 0.34 and 4.48 +/- 0.62 X 10(-2) micrometers.s-1.cmH2O-1, respectively. The total mean LP for all the data (132 samples, 33 capillaries, 10 rats) was 4.19 +/- 0.61 X 10(-2) micrometers.s-1.cmH2O-1. Comparison of these data with results from other tissues indicates that LP of intestinal muscle capillaries is 1.7 times greater than LP of omental capillaries and three times greater than LP of mesenteric capillaries. Values of P'e were corrected for the unoccluded state and were used to calculate total transcapillary pressures (delta P). The results suggested that the intestinal muscle layers were well hydrated and that tissue hydrostatic pressures were positive. Transcapillary fluid fluxes (JVo) at different sites on the capillaries were estimated from the relationship, JVo = LP X delta P. The results imply that intestinal muscle capillaries are primarily an absorptive network when systemic arterial pressure and capillary pressures are normal.
A model for studying chronic reduction in uterine blood flow in pregnant sheep
Authors: Clark K. E. , Durnwald M. , Austin J. E.
Published: December 2017

A model is described for the investigation of the effects of acute and chronic reduction in uterine blood flow in unanesthetized pregnant sheep. An externally adjustable vascular occluder has been designed to utilize the principles of a modified Goldblatt clamp. This occluder is made of nonbreakable plastic and is adjusted via a flexible cable encased in a sheath. The occluder has been tested in 17 pregnant sheep and has remained functional for periods up to 36 days, the length of implantation. This occluder has allowed graded reductions in uterine blood flow, which can be accurately and consistently reproduced. An example of flow reduction is shown in which uterine blood flow has been reduced by 24, 47, and 82% in late-term pregnant sheep. This method will allow the investigation of the effects of uterine hypoperfusion and fetal hypoxia in a precisely controlled unanesthetized pregnant sheep preparation.
Decrease in myocardial oxygen extraction with aortic constriction in the dog
Authors: Saito D. , Kusachi S. , Nishiyama O. , Yasuhara K. , Haraoka S. , Nagashima H. , Olsson R. A.
Published: December 2017

In the open-chest dog constriction of the descending thoracic aorta, which raises central aortic pressure by 30-80 mmHg, increases cardiac oxygen usage (MVO2) and coronary blood flow (CBF) but reduces heart rate and myocardial oxygen extraction [(A-V)O2]. Pacing tachycardia superimposed on aortic constriction further increases MVO2 and CBF but does not alter (A-V)O2. Atropine or vagotomy abolishes the effect of aortic constriction on (A-V)O2, whereas vagal stimulation in the presence of alpha- and beta-adrenergic blockade reduces (A-V)O2. L-propranolol and phenoxybenzamine fail to modify the effect of aortic constriction on (A-V)O2. These results indicate that aortic constriction reduces (A-V)O2 by eliciting parasympathetically-mediated coronary vasodilation.
Vasopressor and depressor actions of angiotensin in the anesthetized fowl
Authors: Nishimura H. , Nakamura Y. , Sumner R. P. , Khosla M. C.
Published: December 2017

Vasopressor and depressor properties of angiotensins (ANG) were characterized in the anesthetized, adult female chicken Gallus gallus. [Asp1,Val5,Ser9]ANG I and [Asp1,Val5]ANG II (native fowl angiotensins) increased blood pressure, and removal or replacement of the amino acid in position 1 decreased pressor potency. The pressor effect of [Asp1,Val5]ANG II was inhibited nearly completely with [Sar1,Ile8]ANG II (5 micrograms.kg-1.min-1) and partially with [Sar1,Thr8]ANG II, [Ile8]ANG III, and [Ile8]ANG I. Phenoxybenzamine, reserpine, or 6-hydroxydopamine reduced the pressor action to one-third. After administration of these compounds [Asp1,Val5]ANG II caused biphasic responses, a depressor followed by a small pressor response. [Sar1,Ile8]ANG II completely, and meclofenamate partially, blocked the depressor response, whereas propranolol, methysergide, vasopressin antagonists, or atropine did not. These results suggest that in fowl 1) the first (Asp) and eighth (Phe) amino acids are important for receptor binding and action, 2) vasopressor action of angiotensin may be primarily caused by release of catecholamines, and 3) angiotensin may exert depressor action possibly by acting directly on the vascular smooth muscle.
Interstitial fluid dynamics in conscious renal hypertensive rats
Authors: Trippodo N. C.
Published: December 2017

Interstitial fluid pressure (IFP) was measured in conscious rats with one-kidney one-clip Goldblatt hypertension using implanted capsules. No significant differences in IFP were found between rats with hypertension of 3, 28, or 56 days duration and the one-kidney controls. To estimate interstitial compliance in the 28-day hypertensive and control rats, hyperosmotic albumin solution was infused intravenously. The subsequent transfer of tissue fluid into the intravascular space was associated with increased diuresis and decreased IFP. The changes in tissue fluid volume (TFV) were estimated from the changes in plasma volume and urine output. In the hypertensive rats 3 h postinfusion, TFV decreased by 36.3 +/- 2.9 ml/kg, and IFP decreased from -1.2 +/- 0.2 to -4.7 +/- 0.6 mmHg. In the normotensive rats TFV decreased by 36.7 +/- 2.7 ml/kg, and IFP decreased from -1.2 +/- 0.2 to -4.3 +/- 0.4 mmHg. Interstitial compliance, estimated from the regression of delta IFP and delta TFV, averaged 7.3 +/- 1.2 and 8.1 +/- 0.7 ml.kg-1.mmHg-1 (P greater than 0.5) in the hypertensive and normotensive rats, respectively. These results suggested that the rats with one-kidney one-clip Goldblatt hypertension had normal interstitial fluid dynamics.
Acute and chronic microsphere loss from canine left ventricular myocardium
Authors: Consigny P. M. , Verrier E. D. , Payne B. D. , Edelist G. , Jester J. , Baer R. W. , Vlahakes G. J. , Hoffman J. I.
Published: December 2017

We determined the effects of time, type of anesthesia, and myocardial infarction on loss of radioactive microspheres averaging 9 or 15 micrometers diameter from left ventricular myocardium. The principle used to compute losses was comparison of the number of microspheres injected directly into coronary arteries to the numbers remaining in myocardium, appearing within 2-4 min in the coronary sinus, or trapped in the lungs. Losses of 9-micrometers microspheres within 2 min of injection were significantly greater for halothane (mean 6.3%) than nitrous oxide anesthesia (mean 3.3%), and in the next 2 h increased to 11.7 and 7.9%, respectively. Over 5 wk in conscious dogs losses were as high as 40 and 11% for 9 and 15 micrometers microspheres, respectively. Losses were not greater for infarcted than normal muscle, and negligible radioactivity appeared in paracardiac lymph nodes. Microspheres leaving the heart were almost all below 10.3 micrometers diameter, so that microspheres with diameters 10-14 (mean 12) micrometers might be the best size to use for myocardial studies.
Sarcomere length control in striated muscle
Authors: van Heuningen R. , Rijnsburger W. H. , ter Keurs H. E.
Published: December 2017

A system that makes control of muscle length (ML), sarcomere length (SL), and force (F) possible in striated muscle preparations is described. SL was measured by light diffraction techniques and two diffractometers. Control was performed by influencing ML with a penmotor system with a frequency response of 190 Hz. SL or F could be controlled by interrupting the internal position (i.e., ML) feedback of the motor and by closing the respective loop. Velocity feedback of the motor through an internal velocity coil was maintained in all cases for optimal damping. Steady-state error of the system was minimized by an integrating loop filter. The feedback path was selected by means of potentiometers or analog switches. Electronic stops in the circuit protected the muscle against excessive stretch and load. A microprocessor-based average-response computer could be used for feedforward control to eliminate noise or to analyze longitudinal uniformity of the muscle. Responses of rat cardiac trabeculae during SL and F control are shown. Transient behavior of SL and F during control and measures to eliminate the transients are discussed.
Placental transfer as a function of uterine blood flow
Authors: Wilkening R. B. , Anderson S. , Martensson L. , Meschia G.
Published: December 2017

The effect of variations of uterine blood flow (F) on placental transfer was examined in six chronic sheep preparations by measuring the placental clearances of ethanol (CE) and antipyrine (CA) at different levels of F. Norepinephrine infusion, hemorrhage, and occlusion of the terminal aorta were used to reduce F below normal. The reduction of F had no appreciable effect on umbilical blood flow (f). In each ewe, CE significantly correlated with F. The CE vs. F relationship at constant f was curvilinear with convexity toward the clearance axis. Regression analysis showed that the equation 1/CE = 1/.911 F + 1/.831 f could account for most of the CE variance (r2 = 0.97). Implicit in this relation is the concept that, given a certain level of placental perfusion, an F/f ratio congruent to 1 is optimal for the exchange of highly diffusible inert molecules between mother and fetus [CE/(F + f) was maximum at F/f = 0.955]. CA was not significantly different from CE at low clearance level but became smaller than CE at clearance values greater than 300 ml/min. This suggests that a high rates of perfusion placental permeability was a factor in limiting CA.
Postnatal regulation of canine oxygen delivery: control of erythrocyte 2,3-DPG levels
Authors: Mueggler P. A. , Black J. A.
Published: December 2017

The oxygen affinity of canine blood changes markedly following birth. These changes are correlated with alterations in the intracellular concentration of 2,3-diphosphoglycerate (2,3-DPG). We have examined the control of erythrocyte glycolysis by measurements of intracellular enzymes and intermediates, and we have identified the component responsible for regulation of 2,3-DPG concentration and hence blood oxygen affinity during canine postnatal development. The concentration of 2,3-DPG could be regulated entirely by the enzymes of the Rapoport-Luebering shunt. We have not detected any alterations in the levels or intracellular activity of 2,3-DPG mutase or 2,3-DPG phosphatase during development; therefore postnatal changes of 2,3-DPG must be a result of changes in the intracellular concentrations of 1,3-diphosphoglycerate (1,3-DPG) that are controlled by other reactions in the glycolytic pathway. Neither low intracellular concentrations of glucose, the glycolytic substrate, nor an inherently low glycolytic rate can account for the low 2,3-DPG levels at birth. 1,3-DPG concentrations and hence 2,3-DPG concentrations are controlled by the activity of pyruvate kinase, which acts as a glycolytic sink reaction. The intracellular activity of pyruvate kinase decreases during the first 50-60 days of age and causes the accumulation of 2,3-DPG. There is a subsequent change in the in vivo kinetic properties of the enzyme, giving increased intracellular activity and resulting in the slow decline of 2,3-DPG concentrations toward normal adult values.
Responses of aortic baroreceptors to changes of aortic blood flow and pressure in rat
Authors: Charlton J. D. , Baertschi A. J.
Published: December 2017

To test the hypothesis that aortic baroreceptors may respond not only to changes of aortic pressure but also to changes of aortic flow, sinusoidal flow waves were applied at 1 Hz to the aorta of urethan-anesthetized rats by infusion and withdrawal of 90 microliters blood with a pump while aortic blood pressure and single baroreceptor fiber activity were monitored. Averages from 20 to 30 pressure wave forms and nerve impulse histograms were established by computer for each single fiber during control (no pump), pump instroke (I), and outstroke (O). Fiber activity increased 20 +/- 3% (mean +/- SEM, n = 28 fibers) and decreased 23 +/- 4% with respect to control during I and O, respectively, whereas estimated changes of aortic flow were +/- 21%. The number of nerve impulses increased (I) and decreased (O) mainly during late systolic pressure rise did not change significantly, but the rate of late systolic pressure fall decreased 42 +/- 7 mmHg/s (I) and increased 39 +/- 11 mmHg/s (O). These results suggest that, because of the rate sensitivity of aortic baroreceptors, changes in aortic flow are reflected in changes of nerve impulse firing patterns during the blood pressure decrease in late systole, even in the absence of significant changes in systolic, diastolic, and pulse pressure.
Fibronectin deficiency and intestinal transvascular fluid balance during bacteremia
Authors: Dillon B. C. , Saba T. M.
Published: December 2017

Reticuloendothelial (RE) clearance dysfunction, which can be induced by opsonic fibronectin deficiency, has been correlated with organ failure during sepsis. We investigate the role of opsonic fibronectin deficiency and RE blockade in modulating alterations in intestinal transvascular fluid balance induced by Pseudomonas bacteremia using an isolated, innervated, and autoperfused canine small intestinal segment. Intravenous infusion of gelatin-coated particles was used to induce fibronectin deficiency and RE blockade. Lymph flow and lymph/plasma (L/P) protein concentration ratios were stable following intravenous challenge with bacteria or gelatin-coated particles. In contrast, lymph flow increased and L/P ratio decreased significantly when bacteremia coexisted with particle-induced opsonic fibronectin deficiency and RE blockade. This elevation in lymph flow and decline in L/P ratio was associated with normal vascular permeability to albumin, IgG, and IgM. The increase in intestinal fluid flux during bacteremia with RE blockade appears to be due to an increase in microvascular hydrostatic pressure and not to an increase in vascular permeability. These findings emphasize a potentially important role for fibronectin and associated RE system function as determinants of fluid filtration during sepsis.
Evidence for a neurotransmitter role for epinephrine derived from the adrenal medulla
Authors: Berecek K. H. , Brody M. J.
Published: December 2017

We examined the neurohumoral mechanisms underlying the hindlimb vasodilator response produced by electrical stimulation of the anteroventral region of the third ventricle (AV3V). Hindlimb blood flow velocity was recorded using a pulsed Doppler flow probe. The vasodilator response to AV3V stimulation was greater than that obtained after inhibition of neurogenic vasoconstrictor tone with sympathectomy and was, therefore, in part an active process. The hindlimb vasodilator response was not affected by cholinergic or histaminergic receptor blockade but was reduced by bilateral adrenalectomy (ADX) or adrenal demedullation (ADM) and was further reduced by beta-adrenergic receptor blockade with propranolol in ADX rats. In ADX or ADM rats the vasodilator response was attenuated by repeated AV3V stimulations and restored by epinephrine infusion. Moreover, restoration of the response after epinephrine infusion was completely blocked by the neuronal uptake blocker desmethylimipramine. As was observed with vasodilation, constrictor responses to AV3V stimulation in the renal and mesenteric vascular beds were also attenuated by adrenal demedullation and were restored by epinephrine infusion. These data suggest that circulating epinephrine, originating in the adrenal medulla, is taken up by sympathetic nerve terminals innervating blood vessels. The catecholamine is then released from these nerves and acts like a classical neurotransmitter, producing vasodilation in skeletal muscle and vasoconstriction in splanchnic and renal vascular beds.
Hemodynamic studies in spontaneously hypertensive rats with congenital arteriovenous shunts
Authors: Sesoko S. , Pegram B. L. , Kuwajima I. , Frohlich E. D.
Published: December 2017

Previous studies have demonstrated a subset of normotensive rats (Wistar-Kyoto, WKY) that has arteriovenous shunts and biventricular hypertrophy. In this study, using the combined radioactive reference sample and microsphere techniques, spontaneously hypertensive (SHR) and WKY rats were found to have arteriovenous fistulas, and the magnitude of this shunting was quantified. In both groups with shunts (WKY and SHR, respectively) mean arterial pressure was lower (117 +/- 3 vs. 125 +/- 2 mmHg, NS; 164 +/- 4 vs. 184 +/- 7 mmHg, P less than 0.001) and cardiac index was higher (518 +/- 52 vs. 259 +/- 10 ml.min-1.kg-1, P less than 0.001: 416 +/- 18 vs. 239 +/- 8 ml.min-1.kg-1, P less than 0.001) than in rats without shunts. Both groups demonstrated sizable shunts, with microsphere trapping in 55 +/- 6 and 47 +/- 5% in WKY and SHR, respectively, and reduced blood flow to every organ. These data demonstrate the need for caution in evaluating hemodynamic and myocardial functional data as well as endocrinologic or metabolic functions in WKY and SHR unless shunting is excluded. Moreover, since these subsets seem to have had arteriovenous shunts from birth, it may be inferred that the development of the arterial hypertension in SHR did not result from tissue hyperperfusion.
Adverse effects of prostacyclin used to perfuse isolated lung lobes
Authors: Krausz M. M. , Utsunomiya T. , Levine L. L. , Dunham B. , Shepro D. , Hechtman H. B.
Published: December 2017

To test the hypothesis that preservation of circulating platelets would prolong the function of an isolated perfused canine lung lobe, prostacyclin (PGI2) was added to the perfusate. Platelet count in heparinized controls (n = 7) fell to 44,500 platelets/mm3, lower than 136,000 platelets/mm3 seen with 1 microgram/min PGI2 (n = 7, P less than 0.005). Surprisingly, with PGI2, thromboxane B2 (TXB2) the stable product of thromboxane A2 (TXA2), rose from 0.07 to 0.25 ng/ml, a level higher than controls (P less than 0.005). PGI2, in comparison to controls, also led to higher pulmonary arterial pressure, an increase in lobe weight, an increase in wet weight-dry weight ratio, an increase in physiological shunt, and a decrease in compliance (P less than 0.005). Further, with PGI2 there was hemorrhagic edema. Infusion of the PGI2 hydrolysis product 6-keto-prostaglandin F1 alpha (n = 2) led to results similar to controls. Adverse PGI2 effects were eliminated by pretreatment with ibuprofen (12.5 mg/kg, n = 5) or an antiplatelet antibody (n = 6). Infusion of PGI2 into a lobar pulmonary artery of an intact animal was without effect on the lung (n = 2). These results show that platelets exposed to a foreign surface will aggregate and be lost from the circulation. PGI2 prevents platelet loss but not the synthesis of TXA2. This vasoconstrictor is likely to be the cause of pulmonary hypertension and hemorrhagic pulmonary edema.
Favorable effects of therapy on cardiac performance in spontaneously hypertensive rats
Authors: Pfeffer J. M. , Pfeffer M. A. , Fletcher P. , Fishbein M. C. , Braunwald E.
Published: December 2017

To determine whether chronic antihypertensive therapy reduces cardiac mass and improves performance in spontaneously hypertensive rats (SHR) with marked left ventricular hypertrophy and evidence of cardiac dysfunction, 12-mo-old male and female SHR and age- and sex-matched normotensive rats (NORM) were treated for 6 mo with either tap water or tap water containing hydralazine or guanethidine. Cardiac performance was assessed by the peak stroke volume and cardiac indices attained during volume loading and by the maximum left ventricular pressure developed during an aortic occlusion. Passive diastolic pressure-volume curves were obtained in the potassium-arrested heart. Treatment prevented the progression of left ventricular hypertrophy in SHR and the marked deterioration in peak pumping ability observed in untreated male SHR and the modest impairment observed in female SHR. The peak developed pressure of both the male and female treated SHR was reduced toward that of NORM and was associated with a reduction in the left ventricular mass-to-volume ratio toward that of NORM. Thus chronic therapy with either hydralazine or guanethidine reduced cardiac mass and prevented the deterioration in cardiac pumping performance observed in SHR with sustained hypertension and marked cardiac hypertrophy.
Reflex cardiovascular changes with veratridine in the conscious dog
Authors: Barron K. W. , Bishop V. S.
Published: December 2017

The present study was undertaken to examine the reflex responses of activation of cardiac sensory receptors in the conscious dog. Intracoronary (left circumflex coronary artery) injection of veratridine (0.10 micrograms/kg) reduced mean arterial pressure (-40 mmHg, P less than 0.05), heart rate (-34 beats/min, P less than 0.05), and maximum rate of rise of left ventricular pressure (LV dP/dtmax) (-419 mmHg/s, P less than 0.05). Bilateral cervical vagal cold block (BVB) eliminated the depressor and bradycardic responses of veratridine. BVB not only eliminated the negative inotropic response to veratridine but reversed it to a positive inotropic response (LV dP/dtmax increased 313 +/- 76 mmHg/s). Ganglionic blockade abolished all effects of veratridine. The bradycardia and negative inotropic effects caused by veratridine were attenuated by either atropine or metoprolol and completely eliminated by the combination of the two antagonists. Veratridine also produced a decrease in renal artery blood flow but had no effect on renal vascular resistance. In contrast, iliac blood flow was increased with veratridine, and this, combined with the depressor effect, resulted in a decrease in iliac vascular resistance (-37%), P less than 0.05). BVB abolished the changes in renal and iliac blood flow or resistance caused by veratridine. The results indicate that activation of cardiac receptors in the conscious dog elicits inhibitory reflexes to the heart and peripheral circulation that are mediated by vagal afferents. After vagotomy, veratridine elicited a reflex positive inotropic response, which may have resulted from activation of cardiac sympathetic afferent fibers.
Prolonged myocardial nucleotide depletion after brief ischemia in the open-chest dog
Authors: Swain J. L. , Sabina R. L. , McHale P. A. , Greenfield J. C. , Holmes E. W.
Published: December 2017

Purine and pyrimidine nucleotides are essential energy sources for basic metabolic reactions and play important roles in protein, glycogen, and nucleic acid synthesis, cyclic nucleotide metabolism, and energy transfer reactions. Brief coronary occlusions (12 min) were produced in seven open-chest dogs, and repetitive myocardial samples were taken in order to determine the response of the nucleotide pool to ischemia and reperfusion. During ischemia adenosine 5'-triphosphate (ATP) decreased to 57% of control, and similar decreases occurred in the guanosine 5'-triphosphate (GTP), cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP), and nicotinamide adenine dinucleotide (NAD+) pools. The decrease in nucleotides was accompanied by an increase in nucleosides and bases. After 60 min of reperfusion the content of all nucleotides had increased but was still significantly less than nonischemic values. The content of nucleosides and bases decreased immediately upon reperfusion. In contrast, creatine phosphate (CP) fell to 10% of control during ischemia but rebounded to above control values immediately upon reperfusion. Thus depletion of all nucleotide pools occurs during ischemia, and with reperfusion nucleotide content is restored only slowly. Delayed repletion is not caused by a defect in mitochondrial synthesis of ATP because CP content is restored rapidly. The slow repletion of nucleotides may be secondary to loss of nucleotide precursors during reperfusion and may result in widespread alterations in myocardial metabolism.
Excitation-contraction coupling in neonatal and adult myocardium of cat
Authors: Maylie J. G.
Published: December 2017

Neonatal cardiac cells were smaller in diameter, having a lower concentration of myofilaments than cardiac cells of the adult cat. The sarcoplasmic reticulum-content in 1-day-old neonates was less than in the adult, and there were no transverse tubules in the neonatal myocardium. Postextrasystolic potentiation and post-voltage clamp potentiation were significantly greater in the adult than in the neonate. Rate inotropisms consisted of a fast component (1st 6-8 beats) and a slow component (50-100 beats). The beat constants for the decay of postextrasystolic potentiation and of the fast component of a negative frequency staircase were the same in both neonate and adult. The restitution of contractility was much faster in the neonate than in the adult. Shortening of the action potential plateau suppressed twitch tension in the first beat with little further effect on subsequent shortened beats in the neonate. The structural and functional differences between the neonate and adult lead to the conclusion that two sources of activator calcium contribute to the development of tension in mammalian ventricle.
Transmural variation in the relationship between myocardial infarct size and risk area
Authors: Koyanagi S. , Eastham C. L. , Harrison D. G. , Marcus M. L.
Published: December 2017

To test the hypothesis that the relationship between infarct area (IA) and area at risk (AR) varies in different layers of the left ventricle (LV), we occluded the circumflex coronary artery for 48 h in 20 conscious dogs. AR was determined by postmortem coronary stereoarteriography, and infarct area by pathological examination. Both AR and IA were divided into four layers: posterior papillary muscle (PPM), subendocardium (Endo), midwall, and subepicardium (Epi) and quantified with planimetry. Hemodynamics and regional myocardial flow with tracer microspheres (7-10 micrometers diam) were measured before and after coronary occlusion. IA was closely correlated with AR for PPM (r = 0.96), Endo (r = 0.97), and Epi (r = 0.92). However, the slope of IA/AR for Endo (1.30 +/- 0.08) was significantly steeper (P less than 0.05) than that for Epi (0.89 +/- 0.11); furthermore, the intercepts at zero infarction for PPM (0.5 +/- 0.1% of LV), Endo (4.2 +/- 0.4%), and Epi (0.1 +/- 0.7%) were significantly different from each other. Regional blood flow measurements indicate that the differences in IA/AR in various layers reflected earlier and greater total collateral flow to the noninfarcted AR in the epicardium. Thus IA/AR for the entire LV is a composite representing separate IA/AR specific to various transmural layers of the LV. In addition, this study demonstrates that the lateral border zone between the IA and the AR is minimal (less than 3-5 mm) in the subendocardium and midwall layers of the left ventricle.