bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo esterification of a synthetic 125I-labeled fatty acid into cardiac glycerolipids
Authors: Chien K. R. , Han A. , White J. , Kulkarni P.
Published: December 2017

Recent studies have demonstrated that fatty acids can be successfully utilized as myocardial imaging agents. 125I-paraphenylpentadecanoic acid (IPPA), a synthetic fatty acid, accumulates within the myocardium and can be visualized by conventional gamma scintigraphy. To determine if IPPA was incorporated into cardiac lipids in a pattern similar to palmitate, IPPA was purified by liquid chromatography, bound to fat-free albumin, and administered by intravenous injection to male Sprague-Dawley rats. After 2.5, 5, 10, and 30 min, the hearts were excised and the lipids were extracted in chloroform-methanol. The uptake of IPPA into the myocardium reached a maximal value after 2.5 min, and 95% of the 125I was found in the cardiac lipid fraction after chromatographic separation. Over 65% of the IPPA was found in cardiac triglycerides, whereas approximately 10% was present in membrane phospholipids (predominantly phosphatidylcholine and phosphatidylethanolamine). This pattern of IPPA incorporation is similar to that reported for intravenously administered [3H]palmitate. The rate of turnover of IPPA present in the triglyceride fraction was threefold faster than the rate of the IPPA which was incorporated into membrane lipids. At all time periods examined, the methanol-water soluble end products of IPPA oxidation did not account for more than 5% of the total IPPA present within the myocardium. The present study indicates that IPPA is incorporated primarily into triglycerides and other cardiac lipids in a pattern similar to palmitate.
Microvascular heparin-like species with anticoagulant activity
Authors: Marcum J. A. , Fritze L. , Galli S. J. , Karp G. , Rosenberg R. D.
Published: December 2017

Calf microvasculature was isolated from retina and cerebral gray matter. These preparations contained 0.048-0.060 U of heparin-like anticoagulant activity per gram of wet tissue. The retinal microvascular material contained no detectable mast cells. The anticoagulant potency of this product was associated solely with endothelial cells. This property appears to be due to a heparinlike proteoglycan since molecular species with biologic activity are precipitated with 10% (wt/vol) trichloroacetic acid and are destroyed by incubation with Flavobacterium heparinase. Furthermore, the above component functions in a manner virtually identical to heparin since approximately 60% of these species with anticoagulant activity bind to antithrombin-concanavalin A-Sepharose 4B, and only 15% of their biologic potency is expressed in the presence of antithrombin modified near the mucopolysaccharide binding domain. The cerebral microvascular tissue contained a trace subpopulation of mast cells (approximately 0.3%). The anticoagulant activity of this preparation is most probably associated with both endothelial cells and mast cells. However, complete separation of these two cellular elements has proven difficult with current methodology.
Sensitive and selective assay for adenosine using high-pressure liquid chromatography with fluorometry
Authors: Jacobson M. K. , Hemingway L. M. , Farrell T. A. , Jones C. E.
Published: December 2017

A new method for quantitation of adenosine was tested in canine myocardial extracts. The method involves incubation of the extract with chloroacetaldehyde to form the fluorescing adenosine derivative 1, N6-ethenoadenosine. The ethenoadenosine is separated by high-pressure liquid chromatography (HPLC) and quantitated by fluorometry. Experiments demonstrated that 1) the method is selective for adenosine, 2) fluorescence peak height is linearly related to the quantity of ethenoadenosine, and 3) adenosine in the extract is quantitatively converted to ethenoadenosine by the incubation procedure. Also, within the range of adenosine concentrations seen in five extracts, estimates of myocardial adenosine content with the fluorometric method were nearly identical to those using the more routine technique of HPLC with direct detection by ultraviolet (UV) absorption. A primary advantage of the fluorometric method is its greater sensitivity. As little as 0.50 pmol on the column could be quantitated by fluorescence, compared with approximately 20 pmol with UV absorption. Because of the greater sensitivity, the fluorometric method should be more easily applied to samples with smaller adenosine concentrations.
Calcium channels resistant to organic calcium entry blockers in a rabbit vein
Authors: Winquist R. J. , Baskin E. P.
Published: December 2017

We compared the effects of calcium entry blockers on myogenic tone with the effects of these compounds on agonist- and depolarization-induced mechanical responses in isolated rings of the rabbit facial vein. The development of intrinsic tone in response to distension of the vessel wall and its potentiation by increasing the ambient temperature were antagonized by MnCl2 (0.5 mM) but not verapamil, diltiazem, or nifedipine. Similarly, the contractile response to histamine was blocked by MnCl2 but was unaffected by moderate concentrations of the organic calcium entry blockers. The histamine contractile response elicited at 34 degrees C (a condition which abolishes intrinsic tone) was also refractory to verapamil (10(-6) M). Verapamil, diltiazem, and nifedipine antagonized the contractile response to calcium in depolarized facial vein rings. Thus both extrinsic and intrinsic contractile responses in the rabbit facial vein depend on an extracellular source of calcium. The distension-operated channels are unique in exhibiting a marked temperature sensitivity. However, receptor- and distension-operated calcium channels can be distinguished from the voltage-operated channels in their insensitivity to the organic calcium entry blockers.
Microvascular blood flow: evidence indicating a cubic dependence on arteriolar diameter
Authors: Mayrovitz H. N. , Roy J.
Published: December 2017

The primary objectives of this study were 1) to determine the functional relationship between microvascular blood flow (Q) and arteriolar internal diameter (D) and 2) to determine whether this relationship conformed to a theoretical optimality prediction--that blood flow is proportional to the cube of the diameter (Q = kD3). Paired blood velocity and arteriolar diameter measurements in the cremaster muscle microvasculature of eight normotensive (WKY) and eight hypertensive (SHR) rats were made under control conditions and following maximal dilation of the microvasculature with topically applied adenosine. A total of 160 paired flow-diameter measurements were made in arteriolar vessels with diameters ranging from 6 to 108 micron. Analysis of this data showed that Q and D were functionally linked by Q = kDm with k = 417 and m = 3.01 with D expressed in centimeters. Confidence intervals at the 99.9% level were 331-503 and 2.86–3.14 for k and m, respectively. A theoretical development based on the minimization of the energy cost of blood volume and arteriolar wall volume led to a theoretical estimate for the range of k to be 92–132 and a value for m to be 3. Predicted pressure gradients in single vessels of the cat mesentery and shear rates in the rat cremaster based on Q = kD3 compared well with measured data reported in the literature and that determined in the present study. On the basis of the direct and predictive evidence, it is concluded that the relationship Q = kD3 represents a general average property of the microvasculature.
Computer registration of radioactive indicator-dilution curves
Authors: Shepherd A. P. , Perry M. A. , Alexander G. M. , Granger D. N. , Riedel G. L. , Kvietys P. R. , Franke C. P.
Published: December 2017

A system is described for recording indicator-dilution curves produced by gamma radiation-emitting tracers. The system consists of a flow-through cuvette in a well counter, appropriate commercially available gamma radiation-detecting equipment, an Apple II computer, and a two-channel pulse-counting interface of our own design. With the counting interface and the software described here, an investigator can simultaneously record two indicator-dilution curves produced by gamma emitters. Instead of having to wait hours or days for results, the investigator can watch the data being recorded and display the results in graphic form almost immediately after each injection.
Relaxation of canine saphenous vein following brief transmural nerve stimulation
Authors: Rooke T. W. , Rimele T. J. , Vanhoutte P. M.
Published: December 2017

The ability of electrical stimulation to cause relaxation in the canine saphenous vein was evaluated. Rings of vein were studied isometrically in organ chambers containing physiological salt solution. Prostaglandin F2 alpha produced stable contractions, during which brief periods of electrical stimulation caused further contraction. With cessation of the electrical stimulation, tension transiently decreased to a level below that observed prior to the stimulation (undershoot). This poststimulation undershoot was blocked by tetrodotoxin, phentolamine, ouabain, and potassium-free solution; it was not affected by atropine, cimetidine, indomethacin, ketanserin, methysergide, propranolol, pyrilamine, or removal of the endothelium. Undershoot did not occur following electrical stimulation during contractions evoked by norepinephrine. During superfusion with PGF2 alpha, a brief exposure to exogenous norepinephrine caused a transient contraction followed by a subsequent undershoot. These results suggest that 1) the interaction of norepinephrine with postjunctional alpha-adrenoceptors on vascular smooth muscle leads to an increase in the activity of Na+-K+-ATPase, and 2) increased activity of Na+-K+-ATPase is responsible for the poststimulation undershoot.
Effect of hypoxia and reoxygenation on mitochondrial function in neonatal myocardium
Authors: Young H. H. , Shimizu T. , Nishioka K. , Nakanishi T. , Jarmakani J. M.
Published: December 2017

he effect of hypoxia and reoxygenation on mitochondrial function was studied in the newborn and adult rabbit hearts. In control muscle, mitochondrial state 3 respiration (state 3 QO2), respiratory control index (RCI), energy-dependent calcium uptake, ATP content, and adenine nucleotide translocase in the newborn were significantly greater than in the adult. After 60 min hypoxia, both the newborn and adult showed significant decrease in 1) tissue glycogen, adenine nucleotides, and creatine phosphates and 2) mitochondrial adenine nucleotides, adenine nucleotide translocase, and glutamate-supported state 3 respiration. In the adult, reoxygenation following 60 min hypoxia was not associated with significant recovery in any of the variables described above, and there was significant decrease in the rate of calcium uptake. In the newborn, the values of all variables returned to control except for tissue glycogen and adenine nucleotide translocase. The data suggest that the effect of hypoxia on mitochondrial function in the newborn is less than in the adult. This occurs because of 1) the lower energy demand in the newborn, 2) higher tissue glycogen and higher rates of glycolysis in the newborn, 3) increased degradation and/or efflux of ATP and ADP in the adult, and 4) possibly a difference in the sarcolemmal resistance to hypoxia in the two age groups.
Arterial and microvascular contributions to cerebral cortical autoregulation in rats
Authors: Harper S. L. , Bohlen H. G. , Rubin M. J.
Published: December 2017

The responsiveness of the microvasculature and arteries during cerebral cortical autoregulation in rats was determined from measurements of microvascular pressures and blood flow as the systemic arterial pressure was altered. At systemic arterial pressures from 65 to 155 mmHg, cortical blood flow was essentially constant. Arterioles with a resting internal diameter of 20-70 microns responded by nearly equal proportional changes in diameter over this pressure range, but microvascular pressures were a linear function of arterial pressure. The percent of control changes in arterial and microvascular resistances at systemic pressures from 80 to 180 mmHg were nearly identical. Therefore, the microvasculature and arterial vasculature were approximately equally responsive to changes in arterial pressure over most of the autoregulatory pressure range. In addition, the arterial vasculature controlled 45-50% of the total vascular resistance at systemic arterial pressures from 40 to 180 mmHg. These data indicate that the cerebral vascular autoregulation in the rat depended substantially on the approximately equal responsiveness of the arterial vasculature and microvasculature. Similar results have been reported in cats and may indicate a common form of cerebral vascular control, which involves both the microvasculature and brain arteries among different species.
Exercise blood flow patterns within and among rat muscles after training
Authors: Armstrong R. B. , Laughlin M. H.
Published: December 2017

This study was designed to determine the influence of a long-term, moderate-intensity treadmill training program on the distribution of blood flow within and among muscles of rats during exercise. One group (T) of male Sprague-Dawley rats trained for 1 h/day for 13-17 wk at 30 m/min on a motor-driven treadmill. A second group (UT) of rats was conditioned for 10 min/day for 4 wk at the same speed. Muscle succinate dehydrogenase activities were higher in T than UT rats indicating a significant training effect. Blood flows (BFs) in 32 hindlimb muscles or muscle parts and other selected organs were measured in the two groups with radiolabeled microspheres during preexercise and while the rats ran for 30 s, 5 min, or 15 min at 30 m/min on the treadmill. The data indicate 1) there were no differences in total hindlimb muscle BF between UT and T rats at any time; however, 2) T rats had higher preexercise heart rates and higher muscle BFs in the deep red extensor muscles, suggesting a greater anticipatory response to the impending exercise; 3) T rats demonstrated more rapid elevations in BF in the red extensor muscles at the commencement of exercise; 4) T rats had higher BFs in red extensor muscles during exercise, whereas UT rats had higher BFs in white muscles; and 5) T rats maintained higher BFs in the visceral organs during exercise. These findings demonstrate that exercise training results in changes in the distribution of BF within and among muscles and among organs during exercise. Specifically, data indicate the high-oxidative motor units that are primarily recruited in the muscles during the initial stages of moderate treadmill exercise receive higher blood flows in the trained rats; this presumably contributes to increased resistance to fatigue.
Viscoelastic properties of canine pulmonary arteries
Authors: Cox R. H.
Published: December 2017

Ring segments of extralobar and intralobar canine pulmonary arteries were used in vitro to study their frequency-dependent viscoelastic properties. Measurements of force in response to sinusoidal perturbations of length were made over the frequency range of 0.002-10 Hz. These measurements were made under three conditions: 1) passive smooth muscle at a physiological value of wall circumference (passive), 2) active smooth muscle at the same circumference (active), and 3) passive smooth muscle at a higher force (circumference) approximating the active value (high strain). Most of the frequency dependence of the dynamic modulus occurred over the range of 0.002-0.1 Hz. Variations in dynamic modulus for frequencies between 0.1 and 10 Hz were smaller in comparison. Larger variations in dynamic modulus were found 1) under conditions of active smooth muscle than under passive or high strain conditions, 2) at high strain compared with low strain (passive) conditions, and 3) for the intralobar compared with extralobar arteries under equivalent conditions. Values of modulus ratio were computed by dividing dynamic modulus by a low-frequency value (f = 0.002 Hz). Values of modulus ratio were similar at high and low wall strain under passive conditions and were higher for intralobar than for extralobar arteries. Values of modulus ratio with active muscle were larger than for passive conditions, but no differences were found between extralobar and intralobar arteries. The "amount" of viscoelasticity correlated with the amount of muscle at the two sites but not with the force-generating capacity of the muscle, so that viscoelasticity and force development may represent different manifestations of muscle properties.
Effects of chronic cigarette smoking on canine arteries
Authors: Cox R. H. , Tulenko T. , Santamore W. P.
Published: December 2017

Segments of carotid and femoral arteries were obtained from beagles subjected to cigarette smoking (12/day for 2 yr) and from unexposed controls. The segments were used for in vitro studies of active and passive mechanics, dose responses to norepinephrine (NE) and K+, connective tissue content, and water and electrolyte content and distribution. No significant differences in passive arterial wall mechanics or geometry at 100 mmHg were found, but a small (significant) increase in passive stiffness was found at wall loads corresponding to higher values of pressure for arteries from smokers. No significant changes in connective tissue composition were found at either site. No significant differences in maximum active force development were found at either site between the two groups. However, values of active force near the middle of the active force-length curve were lower (P less than 0.05) for smoker's arteries when expressed as a fraction of the maximum developed force. No differences in cell volume were found in arteries from the two groups. Mg2+ and K+ content of the femoral and Ca2+ content of both arteries were greater in the smokers. No difference in NE dose-response relations were found for either site. A statistically significant decrease in responsiveness to K+ was found for femoral arteries from smokers, but not for the carotids. The results of these studies demonstrate that some significant changes in arterial wall properties occur in beagle dogs exposed to chronic cigarette smoke.
Role of AVP in maintenance of circulatory homeostasis during hemorrhagic shock
Authors: Hock C. E. , Su J. Y. , Lefer A. M.
Published: December 2017

Hemorrhagic hypotension produces significantly increased plasma arginine vasopression (AVP) concentrations. We have utilized a specific antagonist (AVP-A) of the pressor effects of endogenous AVP to investigate the role of this neurohypophyseal hormone on the pathogenesis of hemorrhagic shock. Infusion of the AVP-A (2 micrograms/kg bolus + 2 micrograms X kg-1 X h-1 infusion) into sham-shocked animals produced no significant changes in any of the observed experimental variables. Cats subjected to hemorrhagic shock given AVP-A had final superior mesenteric artery flow (SMAF) values significantly (P less than 0.05) higher than shock cats given vehicle (7.7 +/- 1.1 vs. 4.5 +/- 0.8 ml X kg-1 X min-1, respectively). Increases in postreinfusion plasma cathepsin D activities were significantly blunted in hemorrhaged animals treated with AVP-A (10.4 +/- 2.0 vs. 24.8 +/- 5.5 U/mg protein; P less than 0.05). Plasma proteolysis as well as the plasma accumulation of myocardial depressant factor (MDF) were also significantly modulated by AVP-A treatment in hemorrhaged animals. MDF activities were 75 +/- 6 and 53 +/- 4 U/ml (P less than 0.02) for shock cats given vehicle or AVP-A, respectively. However, these beneficial actions were not reflected in any significant improvement in postreinfusion mean arterial blood pressure (MABP). These findings suggest that endogenous AVP functions not only as a potent splanchnic vasoconstrictor but also as a key humoral factor in the maintenance of postreinfusion MABP, a profile that is different from the role of angiotensin II, the other major splanchnic vasoconstrictor, in shock.
Kinetic characterization of 13NH3 and [13N]glutamine metabolism in rabbit heart
Authors: Krivokapich J. , Barrio J. R. , Phelps M. E. , Watanabe C. R. , Keen R. E. , Padgett H. C. , Douglas A. , Shine K. I.
Published: December 2017

The isolated arterially perfused rabbit interventricular septum was used to study the effects of methionine sulfoximine (MSO) on 13N-labeled ammonia (13NH3) and 13N-labeled glutamine [( 13N]gln) metabolism. Tissue time-activity curves were generated from bolus injections of 13NH3 or [13N]gln delivered interarterially during control conditions and in the presence of MSO. The fraction of 13N label retained in the tissue [EF(3)] was significantly (P less than 0.01) less after a bolus of [13N]gln than 13NH3. MSO significantly (P less than 0.05) decreased the EF(3) after a bolus of 13NH3 or [13N]gln. Chemical analyses using high-pressure liquid chromatography on tissue and effluent samples obtained after bolus injections of 13NH3 and [13N]gln with or without MSO present showed the following: 1) after a bolus of 13NH3 or [13N]gln the tissue 13N label is predominantly in [13N]gln at 6 min after injection, and 2) MSO significantly decreases the synthesis of [13N]gln after an 13NH3 bolus. Thus it would appear that the glutamine synthetase reaction is primarily responsible for the retention of the 13N label from 13NH3 as [13N]gln in rabbit myocardium.
A new technique for producing pure aortic stenosis in animals
Authors: Su-Fan Q. , Brum J. M. , Kaye M. P. , Bove A. A.
Published: December 2017

To date, techniques used to produce an animal model of valvular aortic stenosis have been unsuccessful. We have developed a new technique for producing pure subcoronary aortic valvular stenosis, which results in left ventricular hypertrophy in a short time. Five adult mongrel dogs weighing 18-24 kg were anesthetized with Brevital (0.5 mg/kg), intubated, and mechanically ventilated with halothane-oxygen. The chest was opened through the right 4th intercostal space, and cardiopulmonary bypass was established between the right atrium and femoral artery. When the esophageal temperature was reduced to about 25 degrees C, the aorta was cross clamped and incised. A piece of Teflon felt covered by pericardium was sutured into each of the sinuses of Valsalva below the coronary orifices. Two to four weeks after the operation, the animals were catheterized. The average pressure gradient between left ventricle (LV) and aorta was 52 +/- 15 mmHg. Mean LV mass-to-body weight ratio was 6.16 +/- 0.28 g/kg vs. 4.24 +/- 0.27 for controls. End-diastolic volume and ejection fraction remained normal, and no aortic regurgitation was seen on aortic root angiography. This preparation creates a hemodynamic representation of valvular aortic stenosis and produces a useful model for examining the myocardial response to this disease. Although hypertrophy develops rapidly, slowly developing hypertrophy may also be possible with this technique.
Anoxia and capillary filtration coefficient in the isolated cat hindlimb
Authors: Watson P. D. , Scott D. R. , Wolf M. B.
Published: December 2017

Isolated cat hindlimbs were perfused from a reservoir with an albumin-blood mixture at a constant flow of 20 ml X min-1 X 100 g muscle-1 while alternately bubbling the perfusate with either 95% O2-5% CO2 gas mixture or a 95% N2-5% CO2 mixture for 50- to 60-min periods. Capillary filtration coefficient (CFC), vascular resistance (R), and perfusate O2 content were measured in each period. The arterial O2 content fell from fully equilibrated to 0.25 vol% during the use of N2. R fell from about 6 mmHg X min X 100 g X ml-1 during O2 bubbling to approximately 1.0 with N2. CFC averaged 0.012 +/- 0.002 ml X min-1 X mmHg-1 X 100 g muscle-1 (SD, n = 6) during the 1st O2 period, rising to 0.016 +/- 0.002 (n = 4) in the 3rd O2 period 4 h later. CFC fell by 5% (P less than 0.001) during the periods of N2 bubbling. Papaverine was present in two experiments without effect on the CFC data. It was concluded that CFC was not meaningfully influenced by vascular resistance or anoxia, a finding that is inconsistent with the concept of local metabolic control of CFC by precapillary resistance vessels.
Sustained interruption of the aortic baroreflex by left cervical vagotomy in dogs
Authors: Walgenbach S. C.
Published: December 2017

Previous experiments demonstrated that acute left vagotomy interrupted 90% of the aortic baroreflex. The present study determined whether or not this interruption was sustained over a period of weeks. Bilateral carotid occlusions (BCO) were performed in conscious dogs before and for 3 wk after left vagotomy and immediately after subsequent right vagotomy. Prior to left vagotomy, BCO induced a rise in arterial pressure of 28 +/- 8 mmHg but no change in heart rate. After left vagotomy, BCO resulted in a rise in arterial pressure of 71 +/- 7 mmHg and a rise in heart rate of 43 +/- 6 beats/min. The BCO-induced elevations in arterial pressure and heart rate did not change significantly during the next 3 wk. Subsequent right vagotomy did not alter the rise in arterial pressure to BCO. These data indicate that left cervical vagotomy interrupts the aortic baroreflex for at least a 3-wk period and suggest that this procedure, when combined with reversible vascular isolation of the carotid sinuses, provides a method for studying cardiovascular adaptation to the acute loss of sinoaortic reflexes in the conscious dog.
Evidence for the role of PO4 deficiency in antihypertensive action of a high-Ca diet
Authors: Lau K. , Chen S. , Eby B.
Published: December 2017

Previous studies indicated a salutary effect of a high-Ca diet on high blood pressure (BP). The mechanism, however, is obscure. With balance and clearance techniques, the role of parathyroid hormone (PTH), volume contraction, hypercalcemia, and PO4 deficiency was evaluated in female spontaneous hypertensive rats (SHR). The antihypertensive effects of a high (4.3%) Ca diet in intact animals (groups I and II) could be reproduced in both 9- and 22-wk-old chronic stable parathyroidectomized (PTX) rats (groups III and IV), when compared with a low (0.22%) or normal (1.2%) CA diet. In both short (7 days) and long (12 wk) term exposure to the high-Ca diet, evidence for volume contraction could not be documented despite hypercalcemia sustained through the 12th wk (10.8 vs. 9.7 mg/100 ml, group I control, P less than 0.02). When produced by ip injections, chronic hypercalcemia of similar magnitudes as oral Ca supplements failed to reduce BP in either intact (group VI) or PTX (group IV) rats. Rats in group IV fed the high-Ca diet displayed marked hypophosphatemia (3.2 vs. 6.9 mg/100 ml), hypophosphaturia (0.15 vs. 15 mg/day), hypermagnesiuria (11 vs. 7.7 mg/day), and drastically reduced net intestinal PO4 absorption (13.3 +/- 7.5 vs. 66.8 +/- 7.5 mg/day) compared with rats fed 1.2% Ca diet. To test the PO4-deficiency hypothesis, additional SHR (group V) were fed either 1.2% Ca diet and injected ip with NaCl or fed 4.3% Ca diet, with half of these animals injected with neutral NaPO4 and half with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)
Nutritional modification of rat heart postnatal development
Authors: Dowell R. T.
Published: December 2017

Postnatal development of the mammalian myocardium encompasses increases in cellularity, energy producing and energy utilizing systems, and concurrent augmentation of heart contractile performance. The present study disrupted normal developmental sequences by adjusting the number of newborn rats per litter at 4 days postbirth. Fast-growing (4 rats/litter), normal (8 rats/litter), or slow-growing (16 rats/litter) animals were studied when 21 days old. Left ventricular cellularity (total DNA) increased as a function of the nutritionally modified growth of the heart, having values of 562 +/- 27, 625 +/- 33, and 791 +/- 20 (SE) micrograms in 16, 8, and 4 rats/litter groups, respectively. Low levels of systolic pressure (55 + 5 mmHg) and rate of pressure development (dP/dt, 2,670 +/- 130 mmHg/s) were noted in the slow-growing rats. Growth-related augmentation of pressure and dP/dt occurred such that adult levels (104 +/- 4 mmHg; 5,810 +/- 290 mmHg/s) were observed in 21-day-old, fast-growing rats. An enzymatic marker for aerobic metabolism (malate dehydrogenase) indicated mitochondrial accumulation in excess of ventricular tissue, thereby establishing progressive increases in aerobic capacity. Myofibrillar ATPase activity was not significantly different among all groups. Thus heart contractile function during nutritionally induced changes in postnatal development is augmented in proportion to increases in heart DNA content. A positive relationship also exists between dP/dt and number of mitochondria; however, enhanced contractile function is achieved independently of myofibrillar ATPase activity level.
Beta 2-adrenergic vascular control in hemorrhage and its influence on cardiac performance
Authors: Gustafsson D. , Lundvall J.
Published: December 2017

Cardiac output (CO), heart rate, stroke volume (SV), and total peripheral resistance (TPR) were followed in anesthetized cats with intact and selectively blocked beta 2-adrenoceptors. SV and CO decreased and TPR increased initially after bleeding in both groups. After this, animals with intact beta 2-adrenoceptors showed gradual recovery of SV and CO and gradual restoration to control of the initially raised TPR. In beta 2-blocked animals SV and CO instead remained low and TPR high. These patterns of response occurred after mild, moderate, and severe bleeding. Separate experiments indicated that the restoration of TPR with intact beta 2-adrenoceptors mainly can be attributed to beta 2-adrenergic dilator interaction with the vasoconstrictor influences. The previously described beta 2-adrenergic control of plasma volume in hemorrhage (Acta Physiol. Scand. 116: 175-180, 1982) suggests that the increases in SV and CO with intact beta 2-adrenoceptors, in turn, probably are indirect effects on cardiac performance due to improved cardiac filling. A synthesis of present and previous findings thus suggests the existence of a beta 2-adrenergic vascular control in hemorrhage favoring tissue perfusion via decreased resistance and via increased plasma volume and hence SV and CO.
Effect of norepinephrine on penetrating arterioles of rat cerebral cortex
Authors: Dacey R. G. , Duling B. R.
Published: December 2017

Penetrating intracerebral arterioles from the rat with mean resting diameters of 26.3 +/- 2.8 micron and maximal diameters of 37.4 +/- 2.5 (SE) micron were isolated, cannulated, and perfused in vitro. Spontaneous tone development and hydrogen ion reactivity indicated that vessels were relatively undamaged and viable. The norepinephrine (NE) reactivity of intracerebral penetrating arterioles is pH dependent. Vessels studied at extraluminal pH 7.30 were unresponsive to NE up to concentrations of 10(-6) M. At NE concentrations above 10(-6) M, vessels dilated to diameters approximately 110% of control. At pH 7.80, vessels contracted to diameters between 75 and 80% of control in response to extraluminal NE concentrations between 10(-11) and 10(-6) M. Vessels in 10(-6) M phentolamine failed to respond to 10(-8) M NE at pH 7.30 and pH 7.80. An aliquot of 10(-8) M NE solution made up at pH 7.80 failed to induce vessel contraction when the pH was readjusted to 7.30, indicating that a NE breakdown product was not responsible for the contraction. These data suggest that adrenergic mechanisms in penetrating cerebral arterioles are significantly different from those seen in peripheral arterioles of similar size.
Mechanical determinants of transient changes in stroke volume
Authors: Slinker B. K. , Campbell K. B. , Ringo J. A. , Klavano P. A. , Robinette J. D. , Alexander J. E.
Published: December 2017

To better define beat-to-beat regulation of stroke volume (SV), the several-beat transient response of the left ventricle (LV) to sudden changes in hydraulic loading impedance was studied. Data were collected from eight canine isolated heart-lung preparations with controlled LV loading impedance. At a selected diastolic interval, a sudden increase in hydraulic loading resistance was induced. The resulting transient response in SV, end-diastolic pressure (EDP), and end-systolic pressure (ESP) was analyzed by comparing the relative predictive capability of six competing models, each incorporating different degrees of complexity in the relationship between SV and EDP and ESP. The basic model assumed linear LV pressure-volume relationships at both end diastole and end systole. Incorporation of nonlinear, end-state interaction or coronary perfusion pressure effects into the basic model did not improve predictive performance. Models incorporating SV and ESP of the preceding beat as well as ejecting beat ESP and EDP were consistently superior to all other models. The ranking of the relative influence of the determinants of SV was 1) ejecting beat ESP, 2) preceding beat ESP, 3) ejecting beat EDP, and 4) preceding beat SV.
Cardiac adrenergic innervation after instrumentation of the coronary artery in dog
Authors: Dolezel S. , Gerova M. , Hartmannova B. , Dostal M. , Janeckova H. , Vasku J.
Published: December 2017

A fine methacrylate ring (not constricting the artery) was placed around the ramus interventricularis anterior (RIA) of the left coronary artery in dogs. By means of Falck's histochemical technique an extensive degeneration of the vasomotor and cardiomotor adrenergic innervation of ventricles was detected 14 days after the procedure. The innervation of atria remained intact. The surgical intervention as well as the scarring process (which compressed the conducting parts of axons composing the perivascular nerves) induced the degeneration. The results have important implications for experiments with instrumented arteries.
Glutamic dehydrogenase activity in rat heart: demonstration of two forms of enzyme activity
Authors: McDaniel H. G. , Yeh M. , Jenkins R. , Freeman B. , Simmons J.
Published: December 2017

Glutamic dehydrogenase (GDH) activity in rat heart was found to be 2.1 U/g of heart (wet wt). The mitochondrial glutamic dehydrogenase activity accounted for only 18% of the total. This percentage of the total activity in heart mitochondria was not altered by nagarse treatment, acetone extraction, sonication in Triton X-100, and extraction with buffer containing a protease inhibitor. The remainder of the activity was present in the cytosol. Cytosolic GDH activity differed from mitochondrial GDH activity by its pH curve, stability to heat, Arrhenius plot, and the effect of different nucleotides. Acetone extraction of the mitochondria resulted in GDH that was stable to heat and had a shallow temperature activation curve resembling cytosolic GDH. Acetone extraction of cytosolic GDH inactivated it. The cytosolic activity was purified 288-fold and the mitochondrial activity 100-fold. Purified cytosolic and mitochondrial GDH enzymes had different monomeric molecular weights on sucrose density gradient centrifugation. Gel filtration of cytosolic and mitochondrial GDH also showed different monomeric molecular weights. We conclude that rat heart GDH exists in two forms with different physical and kinetic characteristics. The majority of GDH activity in rat heart is cytosolic. The mitochondrial enzyme has a lipid-soluble component that can be removed with acetone without destroying its activity.
Developmental changes in myocardial mechanical function and subcellular organelles
Authors: Nakanishi T. , Jarmakani J. M.
Published: December 2017

This study investigates the developmental changes in myocardial mechanical function and the function of subcellular organelles. Mechanical function was determined at various Ca2+ concentrations ( [Ca2+]0) in the isolated, arterially perfused heart of the fetus (28th day of gestation), newborn (3-5 day old), and adult rabbit. Maximal force of contraction in the fetus (observed at 7.5 mM [Ca2+]0) was significantly less than that in the newborn (observed at 30 mM ( [Ca2+]0), and both the fetus and newborn values were significantly less than that in the adult (observed at 15 mM [Ca2+]0). The myofibrillar content in the fetus and ATPase activity in the fetus and newborn were significantly less than in the adult at pCa 4 and 5 where this enzyme was maximally activated. Both the amount of sarcoplasmic reticulum (SR) and SR Ca2+ uptake per gram of muscle increased with age. Mitochondrial Ca2+ uptake was not observed at pCa more than 6 (physiological range) in all age groups. At pCa less than 6, mitochondrial Ca2+ uptake (per g muscle) in the newborn was significantly greater than in the fetus and adult. Ca2+ uptake by crude homogenate in the newborn was also greater than in the fetus and adult. These data suggest that the age-related change in myocardial contractility is due to the differences in intracellular Ca2+ concentration and myofibrillar content as well as ATPase activity. Intracellular Ca2+ concentration may vary with development depending on the relative capability of Ca2+-releasing system and Ca2+-sequestering system.
Injection of protein kinase inhibitor into cultured heart cells blocks calcium slow channels
Authors: Bkaily G. , Sperelakis N.
Published: December 2017

An inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase was injected into cultured heart cells (reaggregates) by the phosphatidylcholine liposome method. The inhibitor blocked both the isoproterenol-induced slow action potentials and the spontaneously occurring slow action potentials of these cells. The inhibitory effect of protein kinase inhibitor was prevented by denaturation or reversed by the injection of the catalytic subunit of cAMP-dependent protein kinase. These findings support the phosphorylation hypothesis for the myocardial slow channels, namely that the slow channel protein must be phosphorylated for the channel to be available for voltage activation.
Loss of hepatic venous responsiveness after endotoxin in anesthetized cats
Authors: Seaman K. L. , Greenway C. V.
Published: December 2017

Endotoxin (from Salmonella enteriditis ) was administered either as an intravenous bolus injection after administration of indomethacin to prevent the acute anaphylactoid response or as a slow intravenous infusion to cats anesthetized with pentobarbital. Within 30 min, hepatic blood volume measured by plethysmography increased by 30%. However, unlike the outflow block seen in dogs after endotoxin, this increase in blood volume was associated with a fall in portal and hepatic lobar venous pressures. Responses to hepatic nerve stimulation (1-8 Hz), to intravenous infusions of norepinephrine (0.2-1.0 microgram X kg-1 X min-1), and to infusions into the hepatic artery of norepinephrine (0.1-0.5 microgram X kg-1 X min-1) and angiotensin II (0.1-0.5 microgram X kg-1 X min-1) were compared before and 150 min after endotoxin administration. Both portal pressure and hepatic blood volume responses to these stimuli were markedly depressed by 150 min after endotoxin. We conclude that in cats endotoxin causes a markedly depressed responsiveness of hepatic venous smooth muscle to agonists and a modest pooling of blood in the liver probably due to impairment of preexisting sympathetic tone. Although these hepatic venous effects were observed at a time when cardiac output was not markedly depressed, it is suggested that they may play a significant role in the later development of reduced cardiac output and shock.
Rabbit carotid sinus reflex under pentobarbital, urethan, and chloralose anesthesia
Authors: Ishikawa N. , Kallman C. H. , Sagawa K.
Published: December 2017

To determine the effects of different anesthesias on the performance of the arterial baro-reflex, the open-loop characteristic of the carotid sinus reflex was analyzed in 24 rabbits under anesthesia with pentobarbital (30 mg/kg), urethan (800 mg/kg), alpha-chloralose (80 mg/kg), or a mixture of alpha-chloralose (40 mg/kg) and urethan (0.4 g/kg). For each rabbit and anesthesia, mean systemic arterial pressure and heart rate were measured as carotid sinus pressure was changed in 10-mmHg steps between 40 and 150 mmHg. This set of measurements was repeated four times at 1-h intervals. A logistic function curve was fitted to the carotid sinus pressure-arterial pressure relationship. The parameters of this curve were then analyzed to delineate the specific effects of the anesthesias on the relationship. The main finding was that the response range and the slope parameters under alpha-chloralose anesthesia were significantly smaller than those obtained under the other anesthesias. Propylene glycol, used as the solvent for chloralose, did not affect the reflex control of arterial pressure or heart rate. The reflex under chloralose-urethan anesthesia showed characteristics similar to those under urethan anesthesia. We conclude that although alpha-chloralose has traditionally been used in the dog to obtain strong reflex responses, it weakens the reflex control of arterial pressure in the rabbit.
Pulmonary vascular effects of vasoactive intestinal peptide in conscious newborn lambs
Authors: Kulik T. J. , Johnson D. E. , Elde R. P. , Lock J. E.
Published: December 2017

Vasoactive intestinal peptide (VIP) may be a neurotransmitter in a peptidergic nervous system and is found in nerves in pulmonary blood vessels. Information regarding its pulmonary vascular effects is limited. We therefore studied VIP's effect on pulmonary vascular tone in the immature lung. Normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around the right and left pulmonary arteries were used. VIP was injected into one pulmonary artery only, and direct effects of this peptide on the pulmonary vessels were determined by comparing the flow changes in the injected vs. the uninjected lung. VIP was a powerful pulmonary vasodilator with a threshold of 0.3 microgram/kg. It also was a systemic vasodilator (after 1 microgram/kg, aortic pressure fell 27% and cardiac output increased 29%, both P less than 0.01), with a threshold of 0.1 microgram/kg. Pretreatment with propranolol (1 mg/kg iv) did not abolish pulmonary or systemic vasodilation after VIP. On the other hand, pretreatment with indomethacin (3 mg/kg per day for 3 days) abolished VIP-induced pulmonary vasodilation but probably did not affect systemic vasodilation. We conclude that VIP is a powerful pulmonary vasodilator in the newborn lamb and that this dilation can be blocked by the cyclooxygenase inhibitor indomethacin. VIP is also a powerful systemic vasodilator in the newborn lamb but this effect is not blocked by either propranolol or indomethacin.
Impaired central mediation of the arterial baroreflex in chronic renal hypertension
Authors: Guo G. B. , Abboud F. M.
Published: December 2017

After 6 wk of renal hypertension in rabbits, the arterial baroreflex control of heart rate (HR) is impaired but the baroreflex control of lumbar sympathetic nerve activity ( LSNA ) is preserved. This selective impairment may reflect a predominant abnormality in the baroreceptors. In this study, we tested the hypothesis that renal hypertension of longer duration may impair baroreflex control of LSNA through a defect in the central nervous system mediation of the reflex. Four months after induction of renal hypertension, baroreflex responses were determined during increases in arterial pressure with intravenous phenylephrine or decreases in pressure with vena caval occlusion under chloralose-urethan anesthesia. Reflex control of LSNA and HR was impaired markedly in hypertensive rabbits. Reflex inhibition of LSNA and HR in response to afferent electrical stimulation of the left aortic depressor nerve (all arterial baroreceptor afferents cut) was attenuated in hypertensive in contrast to normotensive rabbits. This attenuation was noted when the medullated fibers only were stimulated or when both medullated and nonmedullated fibers were stimulated. We conclude that baroreflex control of LSNA that is preserved after 6 wk of hypertension is impaired after 4 mo of hypertension. The impairment reflects an abnormality in the central nervous system mediation of the reflex.
Microvascular alterations in the one-kidney, one-clip renal hypertensive rat
Authors: Prewitt R. L. , Chen I. I. , Dowell R. F.
Published: December 2017

The microcirculation was studied in one-kidney, one-clip renal hypertensive rats ( 1KG ) and uninephrectomized controls at 4-6 and 8-10 wk postoperation. Under chloralose-urethan anesthesia the gracilis muscle was transilluminated in situ with a light pipe. Measurements of arteriolar and capillary density and arteriolar diameter were made in three consecutive states: innervated, denervated, and vasodilated with nitroprusside. Arteriolar wall-to-lumen ratio was measured after vasodilation. At 4-6 wk vasoconstriction was significantly greater in 1KG and vasodilated arteriolar diameter was significantly smaller, partially because of an elevated wall-to-lumen ratio. Capillary density in 1KG was reduced in the innervated and denervated states compared with controls. At 8-10 wk in the 1KG , arteriolar vasoconstriction was no longer significantly elevated. However, the vasodilated arteriolar diameter was smaller, wall-to-lumen ratio had increased further, and rarefaction of arterioles and capillaries was present. Thus, with time, structural mechanisms for increasing vascular resistance were seen to displace the active mechanism of vasoconstriction.
Myocardial alterations due to free-radical generation
Authors: Burton K. P. , McCord J. M. , Ghai G.
Published: December 2017

Oxygen-derived free radicals have been proposed as general mediators of tissue injury in a variety of disease states. Recent interest has focused on the possibility that free radicals may be involved in ischemic myocardial damage. However, the exact types of damage that result from myocardial exposure to free radicals remains to be established. The purpose of this study was to evaluate the effects of superoxide and hydroxyl radicals on myocardial structure and function in an isolated perfused rabbit interventricular septal preparation. Superoxide was generated by adding purine (2.3 mM) and xanthine oxidase (0.01 U/ml) to the physiological solutions perfusing the septa. Hydroxyl radical generation was catalyzed by the addition of 2.4 microM Fe3+-loaded transferrin to the system. Exposure of normal septa to superoxide-generating solutions resulted in the development of structural alterations in the vascular endothelium including the development of vacuoles. Membranous cellular debris was evident in the extracellular space and within the vessels. Cardiac myocytes showed evidence of mild alterations. Exposure of septa to solutions capable of generating hydroxyl radicals resulted in more extensive and severe damage. Vascular endothelial cells showed evidence of vacuoles or blebs and edema. Severe swelling of mitochondria was evident in cardiac myocytes and vascular endothelial cells. In addition, myocytes often showed blebbing of the basement membrane. Normal septa exposed to superoxide showed no significant decrease in developed tension, whereas hydroxyl radical exposure resulted in a significant decrease in myocardial function.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of plasma and red blood cells on water permeability in cat hindlimb
Authors: Watson P. D.
Published: December 2017

Capillary filtration coefficient (CFC) was measured to investigate the effect of blood in the perfusate of an isolated, maximally vasodilated cat hindlimb. CFC was measured during perfusion with several different perfusates: a blood-albumin mixture, albumin alone, a plasma-albumin mixture, and a plasma-albumin mixture containing varying volumes of red blood cells. In some experiments the plasma was ultrafiltered to remove low-molecular-weight components. It was found that perfusion with albumin alone usually raised CFC above the level found with the blood-albumin mixture, plasma could reduce the CFC when CFC was elevated above that value obtained with the blood-albumin mixture, ultrafiltered plasma failed to reduce CFC when CFC was elevated, and the red cell content of the perfusate had no influence on CFC over the hematocrit range of 0-20% when the plasma solute concentrations were kept constant. It was concluded that the reduction of CFC by blood was caused by a small molecule (less than 10,000 mol wt) present in plasma.