bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrogenic sodium extrusion can stop triggered activity in the canine coronary sinus.
Authors: Wit A L , Cranefield P F , Gadsby D C
Published: June 2012

Soon after a burst of triggered activity in the canine coronary sinus begins, an initial fall in maximum diastolic potential and increase in rate gives way to an increase in maximum diastolic potential, reduction in rate, and eventual quiescence. This hyperpolarization, slowing, and subsequent quiescence might result from enhanced electrogenic sodium/potassium extrusion caused by the rise in intracellular sodium concentration ([Na+]i) associated with the high rate of firing. Triggered bursts can be terminated prematurely by a sudden increase in the rate of sodium extrusion, Brief exposure to K+- free fluid is known to cause [Na+]i to rise; reactivating the pump by switching back to K+-containing fluid causes immediate hyperpolarization, and within a few seconds, quiescence. Brief periods of overdrive, also thought to increase [Na+]i, are followed by hyperpolarization, slowing and, often, by premature termination of the burst. Inhibiting the sodium/potassium pump by exposure to 2 micrometer acetylstrophanthidin or to K+-free fluid (1) prevents or delays the hyperpolarization, (2) increases the rate of triggered activity and (3) prolongs bursts of activity when bursts last less than 2.5 minutes under control conditions. In the presence of 2 micrometer acetylstrophanthidine, neither brief exposures to K+- free fluid not overdrive causes sudden, premature termination of triggered bursts. Bursts do eventually stop in the presence of pump inhibitors; however, that termination is associated with an increase in rate and a decline in maximum diastolic potential and in action potential amplitude. We conclude that electrogenic Na+ extrusion plays an important role in the spontaneous termination of triggered activity.
Total circulatory capacity in the rat. Effects of epinephrine and vasopressin on compliance and unstressed volume.
Authors: Trippodo N C
Published: June 2012

In thoracic-spinal-cord-transected rats, mean circulatory pressure (Pmc) was measured during brief circulatory arrest by inflating an indwelling balloon in the right atrium and total blood volume (VB) was measured with 51Cr. The Pmc-VB relationship was determined over the range +/- 30% VB by rapid blood infusion or withdrawal. An infusion of 1.5 microgram/kg per min of epinephrine for 20-40 minutes caused the total circulatory compliance (Ctc) to decrease 18%, the extrapolated unstressed circulatory volume (V'o) and VB to decrease 8.6 and 7.3 ml/kg, respectively, and PMC to increase 41% (2.6 mm Hg). Total circulatory capacity (circulatory volume at a PMC of 8 mm Hg) was decreased 13.7 ml/kg by epinephrine at the above infusion rate. When vasopressin (20 ng/kg per min) and epinephrine (0.3 microgram/kg per min) were infused together for 20-40 minutes, compared to a 0.3 microgram/kg per min infusion of epinephrine alone, the net effect of vasopressin was a 4.8 ml per kg decrease in VB and a 5.9 ml/kg decrease in total circulatory capacity, with insignificant decreases in CTC and V'o. The results indicate that in rats both epinephrine and vasopressin act to decrease blood volume via transcapillary fluid shifts, and that vasopressin has a relatively small overall venoconstricting action.
Equal oxygen consumption rates of isovolumic and ejecting contractions with equal systolic pressure-volume areas in canine left ventricle.
Authors: Suga H , Hayashi T , Suehiro S , Hisano R , Shirahata M , Ninomiya I
Published: June 2012

Left ventricle systolic pressure-volume area (PVA) has been found to be highly linearly correlated with cardiac oxygen consumption rate per beat (VO2) in a given canine heart with a stable inotropic background. PVA is a specific area in the pressure-volume (P-V) diagram that is bounded by the end-systolic and end-diastolic P-V relationship lines and the systolic segment of the P-V loop, consisting of the sum of external mechanical work and what is considered the end-systolic elastic potential energy in the ventricular wall. In this study, we compared VO2's of steady state entirely isovolumic and variously ejecting contractions that were made to have equal PVA's in the canine left ventricle. We found that VO2's of these isovolumic and ejecting contractions with equal PVA's (isovolumic vs. ejecting = 1008 +/- 64 (SE) vs. 1022 +/- 62 mm Hg ml/beat, n = 32 pairs in 10 hearts) were equal to each other (0.0375 +/- 0.0021 vs. 0.0368 +/- 0.0021 ml O2/beat) regardless of the marked differences in stroke volume (0 vs. 9.8 +/- 0.6 ml), end-diastolic volume (20.3 +/- 0.8 vs. 23.7 +/- 0.9 ml), end-systolic volume (20.3 +/- 0.8 vs. 13.9 +/- 0.7 ml), peak pressure (123 +/- 5 vs. 88 +/- 5 mm Hg), stroke work (0 vs. 636 +/- 36 mm Hg ml/beat), and calculated peak total wall force (1588 +/- 77 vs. 1077 +/- 72 g). Therefore, we conclude that PVA can serve as a reliable predictor of VO2 in a given canine left ventricle with a stable inotropic background whether the contraction mode is isovolumic or ejecting.
Myocardial composition and function in diabetes. The effects of chronic insulin use.
Authors: Regan T J , Wu C F , Yeh C K , Oldewurtel H A , Haider B
Published: June 2012

This study was undertaken in an animal model of mild diabetes to determine if provision of chronic insulin replacement during postprandial hyperglycemia may modify the abnormalities of myocardium. Group 1 served as controls with normal glucose tolerance by intravenous testing. Two additional groups were made diabetic with low doses of alloxan. Diabetic animals of Group 2 were untreated (n = 6). Group 3 animals (n = 6) received regular insulin daily to reduce postprandial hyperglycemia. After one year with maintained body weight, the animals were studied in the intact anesthetized state using the indicator dilution technique for left ventricular volume determinations. Basal left ventricular function and contractility were similar to normals in both diabetic groups. During intraventricular infusion of saline, end-diastolic pressure rose to higher levels in untreated diabetes (14.8 +/- 2 mm Hg) than normals (8.8 +/- 0.84), despite similar basal levels. Insulin treatment was associated with higher filling pressures than in group 1 as well as reduced end-diastolic volume response. Collagen concentrations were enhanced an average of 50% in layers from the inner to outer myocardium in both untreated and treated diabetics, associated with sodium and water accumulation. Since hypertrophy was not present, the diminished compliance appeared related to increased collagen levels. On electron microscopy, the subcellular organelles of the cardiac cell appeared normal in both diabetic groups. Thus, collagen accumulation and abnormal myocardial function in this model of diabetes is not affected by control of postprandial hyperglycemia, but a potential role for sustained hormone replacement is not excluded.
Cardiac Fibrinoid Lesions Produced by Cross Circulation or Temporary A-V Shunts
Authors: DAVIS RICHARD L. , BRUNSON JOEL G. , FEHR PETER E.
Published: June 2012

Localized acute cardiac lesions containing fibrinoid were produced in rabbits by carotid-jugular cross circulation or temporary arteriovenous shunts, using small amounts of heparin as anticoagulant. Excessive amounts of heparin markedly reduced the incidence of fibrinoid in the lesions, which suggests that the formation of fibrinoid was inhibited or its deposition in the heart prevented. The results of the experiments suggest that the shunting procedures not only produce mechanical damage to the heart, but also participate in the production of fibrinoid or its precursors, which is deposited in localized sites of cardiac damage.
Effect of Dihydrocholesterol and β-Sitosterol on Cholesterol Atherosclerosis in Rabbits
Authors: BEHER W. T. , BAKER G. D. , ANTHONY W. L.
Published: June 2012

While dihydrocholesterol lowered total plasma cholesterol in the rabbit, it did not promote the regression of either the aorta lipid fractions or plaque areas in atherosclerotic animals. A comparative study of the toxicities of β-sitosterol and dihydrocholesterol disclosed that dihydrocholesterol, fed for a 7 month period, resulted in aorta plaque formation and caused the development of liver cirrhosis. On the other hand, β-sitosterol produced no toxic effects.
Effect of Epinephrine, Norepinephrine and Serotonin Upon Systemic Small and Large Vessel Resistance
Authors: HADDY F. J. , FLEISHMAN M. , EMANUEL D. A. , Scott J. B.
Published: June 2012

Locally injected epinephrine and norepinephrine elevate dog foreleg total vascular resistance primarily through small vessel constriction. Serotonin does not significantly change total resistance, constricts large arteries and veins and dilates small vessels.
Cationic Shifts and Blood Pressure Regulation
Authors: FRIEDMAN SYDNEY M. , FRIEDMAN CONSTANCE L. , NAKASHIMA MIYOSHI
Published: June 2012

The effects of Pitressin and norepinephrine on movements of sodium, potassium, and water into and out of the intracellular compartment were measured in bilaterally nephrectomized rats using inulin as a measure of extracellular fluid volume. Observations were made from 0.5 to 7 min. following injection of the test substances. Pitressin causes a movement of sodium and water into cells and the extrusion of potassium during the pressor plase of its action. These effects were observed at 0.75 and 1.5 min. after the injection of 30 or 60 mU. The reverse movements were observed during the subsequent return of the blood pressure towards normal. A secondary shift of sodium into cells was observed at 5 min. Norepinephrine caused similar shifts in sodium, water, and potassium in relation to its blood pressure effects. These were more rapid in onset than those induced by Pitressin. Our operational theory is that the regulation of the blood pressure depends, inter alia, on the "sodium transfer systems" broadly defined, which govern the rate of entrance and extrusion of sodium, water and potassium in smooth muscle cells.
Factors Influencing Collateral Blood Flow to the Dog's Lung
Authors: SALISBURY PETER F. , WEIL PETER , STATE DAVID
Published: June 2012

The collateral circulation of the lung, i.e., that part of the bronchial flow which drains into the pulmonary veins, was studied by a heart-lung arrangement in which the lesser and systemic circuits of dogs could be perfused separately. In this preparation the collateral supply amounted to 0.5 to 1 per cent of the total arterial flow under approximately normal conditions. The changes in this collateral flow under a variety of experimental conditions were studied. These included variable systemic, venous and pulmonar pressures, lung collapse, air embolism, and actions of CO
2
and serotonin.
Effects of Low Temperatures on Transmembrane Potentials of Single Fibers of the Rabbit Atrium
Authors: MARSHALL JEAN M.
Published: June 2012

Lowering the temperature caused a fall in the diastolic membrane potential and action potential and an increase in the duration of the action potential in both pacemaker and nonpacemaker fibers of the rabbit atrium. Pacemaker fibers were the most resistant to cooling and continued to discharge at a temperature where all conducted action potentials and mechanical contractions had ceased. Acetylcholine (10
-7
Gm./ml.) administered at a low temperature when only pacemaker fibers were discharging, elicited propagated action potentials and contractions. This effect was associated with an increase in diastolic membrane potential towards that existing at a temperature of 30 C.
Effect of Alterations in Vasomotor Tone on Pressure-Flow Relationships in the Totally Perfused Dog
Authors: READ RAYMOND C. , KUIDA HIROSHI , JOHNSON JOHN A.
Published: June 2012

The technic of total body perfusion with a pump oxygenator system has been used to extend pressure flow studies to the circulation as a whole. The effect of alterations in vasomotor tone on both total peripheral resistance and pressure flow relationships has been investigated by surgical ablation of the central nervous system or administration of vasoactive drugs. Certain aspects of the results obtained are discussed in relation to the concept of critical closing pressures.
Effects of the discrete pattern of electrical coupling on propagation through an electrical syncytium.
Authors: Joyner R W
Published: June 2012

We used numerical integration techniques to simulate action potential propagation along one-dimensional strands of cells coupled with electrical junctions. We considered the standard case to be a series of cardiac cells (20 micrometer in diameter, 50 micrometers long) with intercellular coupling such that the effective longitudinal resistance was 200 omega cm. The membrane properties were represented by the model of Beeler and Reuter (1977) (Sharp and Joyner, 1980). By increasing Ri (and thus decreasing the space constant, L), we showed that effects due to the discrete cell length, delta X, became apparent when delta X/L was greater than about 0.2, producing an increased maximal dV/dt but a decrease in peak inward current. We also simulated the effects of a periodic spatial variation in Ri, representing a structure with groups of well-coupled cells but with minimal coupling between the groups. Even with a constant membrane model and cell size, variations in the spatial pattern of interconnection produced significant changes in action potential shape and velocity, with some patterns producing decremental conduction or propagation failure.
Effect of tissue anisotropy on extracellular potential fields in canine myocardium in situ.
Authors: Roberts D E , Scher A M
Published: June 2012

The extracellular epicardial potential fields produced by simple depolarization waves in the in situ canine left ventricular myocardium were analyzed. A mathematical model that included tissue anisotrophy was developed to explain the observed fields. Values of intracellular (i), extracellular (o), longitudinal (l), and transverse (t) resistivity which gave the best fit between the model and experimental data were (in ohm-cm, mean +/- SD): rol = 852 +/- 232, rot = 1247 +/- 210, ril = 291 +/- 38, rit = 1677 +/- 331. The potential fields around simple stimulated waves on the epicardium can best be explained if the extracellular wavefront voltage is (mean +/- SD) 74 +/- 7 mV for a wave propagating parallel to the local muscle fibers, and 43 +/- 6 mV for a wave propagating perpendicular to these fibers. We conclude that the anisotrophy of the electrical conductivity of cardiac muscle has important effects on he propagation of waves of depolarization and on the potential fields produced by depolarization in the intact heart.
Distribution of choline acetyltransferase in cerebral and extracerebral cranial arteries of the cat. Its relationship to neurogenic atropine-sensitive dilation.
Authors: Bevan J A , Buga G M , Florence V M , Gonsalves A , Snowden A
Published: June 2012

Choline-acetyltransferase (ChAT) activity was surveyed in segments of cranial arteries--both cerebral and extracerebral--from the cat. High levels were found in pial arteries, both cerebral and cerebellar, and in the arteries to salivary glands, tongue, and nose. Intermediate levels were found in the external and internal maxillary arteries and many of their branches. Enzyme levels in the arteries supplying the head--common carotid, vertebral, and in several systemic arteries and veins and also the lingual vein--were probably not significant. Only those vessels that have higher ChAT contents show capacity for neurogenic vasodilation. The dilation of segments of a number of these arteries, the basilar, middle cerebral, lingual, and internal maxillary, is reduced significantly by atropine (5 X 10(-7) M). ChAT activity did not correlate with vessel norepinephrine content. The data may be interpreted as defining a functional vasodilator system to the head encompassing both cerebral and extracerebral arteries that depends in part on a functional cholinergic link involving a muscarinic receptor. It is separate from the adrenergic outflow. The tissues supplied by vasculature receiving this type of innervation are of ectodermal origin.
Alterations in local cerebral glucose utilization during hemorrhagic hypotension in the rat.
Authors: Savaki H E , Macpherson H , McCulloch J
Published: June 2012

The alterations in local cerebral glucose utilization in 58 anatomically discrete regions which occur during a period of hemorrhagic hypotension have been investigated in conscious rats, using the quantitative autoradiographic 14C-deoxyglucose technique. Hemorrhagic hypotension (mean arterial pressure reduced by approximately 50 mm Hg) effected significant increases in glucose utilization in eight areas of the central nervous system, namely, the nucleus of the tractus solitarius (glucose utilization increased by 38%), the dorsal motor nucleus of the vagus (by 36%), locus coeruleus (by 38%), lateral habenular nucleus (by 40%), periventricular nucleus of the hypothalamus (by 41%), paraventricular nucleus of the hypothalamus (by 97%), supraoptic nucleus (by 86%), and the interstitial nucleus of the stria terminalis (by 84%). In five of these eight areas (nucleus of the tractus solitarius, dorsal motor nucleus of the vagus, paraventricular and supraoptic nuclei, and the interstitial nucleus of the stria terminalis), a significant relationship could be demonstrated between the level of glucose utilization and mean arterial blood pressure. In the majority of the CNS regions examined (neocortex, hippocampus, thalamus, extrapyramidal and motor areas), hemorrhagic hypotension was without significant effect upon local cerebral glucose utilization. The results provide direct evidence of the functional involvement of specific brain areas of conscious rats (thus obviating complicating anesthetic influences) in the response of the CNS to hemorrhagic hypotension.
Phasic coronary blood flow velocity in intramural and epicardial coronary arteries.
Authors: Chilian W M , Marcus M L
Published: June 2012

Knowledge concerning phasic coronary blood flow is based primarily on measurements obtained from epicardial coronary arteries, which, in part, function as capacitors. If present, epicardial capacitance effects could obscure the dynamic nature of phasic intramyocardial perfusion. To analyze this effect of epicardial capacitance, we simultaneously measured coronary blood flow velocity in an epicardial artery (left anterior descending) and an intramural artery (septal) in open-chest, anesthetized dogs. During control conditions, the percentage of total coronary blood flow velocity occurring during diastole per cardiac cycle was significantly greater (P less than 0.05) in the septal artery (92%) than in the left anterior descending artery (75%). Furthermore, blood flow velocity during mid-systole in the septal artery was retrograde (-7.2%), whereas blood flow velocity at this time was antegrade in the left anterior descending artery (+3.5%). Blood flow velocity measurements from small epicardial arteries just before they penetrated into the myocardium revealed a phasic pattern similar to that of the septal artery. This suggests that the phasic blood velocity pattern in penetrating coronary arteries, in general, is different than that in large epicardial arteries. During vasodilation following nitroglycerin, dipyridamole, or a 20-second occlusion of the left main coronary artery, the retrograde component of mid-systolic blood velocity persisted in the septal artery, despite large increases (300-400%) in the mid-systolic antegrade component of blood flow velocity in the left anterior descending artery. These qualitative and quantitative differences in phasic blood flow velocity between intramural and large epicardial arteries are best reconciled by postulating the existence of a significant coronary capacitor.
Testosterone-mediated sexual dimorphism of the rodent heart. Ventricular lysosomes, mitochondria, and cell growth are modulated by androgens.
Authors: Koenig H , Goldstone A , Lu C Y
Published: June 2012

The ventricular myocardium was studied in A/J mice and in Sprague-Dawley rats. In male mice, the ventricles were slightly larger and the specific activities of the lysosomal hydrolases, beta-glucuronidase, hexosaminidase, beta-galactosidase, and arylsulphatase, and the inner mitochondrial enzyme cytochrome c oxidase were substantially higher than in female mice. Orchiectomy abolished this sex difference. Testosterone administration induced myocardial hypertrophy and accretion of RNA and protein without altering the DNA, and substantial increases in the activities of the lysosomal hydrolases and cytochrome c oxidase. However, the mitochondrial membrane enzyme monoamine oxidase was unaffected by sex, orchiectomy, and testosterone administration. Heart lysosomes from male mice showed a smaller structure-linked latency of the lysosomal enzymes and a greater fragility of the lysosomal membrane to osmotic and mechanical stress than those from female mice. This sex difference was also abolished by orchiectomy and restored by testosterone replacement. Similar sex differences were observed in the rat with respect to heart size, acid hydrolase activities, and lysosomal enzyme latency and membrane stability. These findings indicate that endogenous androgens regulate myocardial cell growth, the activity of enzymes associated with lysosomes and the inner mitochondrial membrane, and some physiochemical properties of lysosomes.
Juxtaglomerular cells grown as monolayer cell culture contain renin, angiotensin I-converting enzyme, and angiotensin I and II/III.
Authors: Rightsel W A , Okamura T , Inagami T , Pitcock J A , Takii Y , Brooks B , Brown P , Muirhead E E
Published: June 2012

A monolayer cell culture of juxtaglomerular cells (JGC) was derived from the renal cortex of neonatal rats. The JGC had the characteristics of those within the kidney, including peripheral dense bodies and myofibrils indicating a smooth muscle origin; rough ER containing fluffy material consistent with protein synthesis; a prominent Golgi apparatus for packaging granules, and granules having the characteristics of secretory granules and lysosomes. Transplants of the cultured cells into syngeneic recipients survived for 2 weeks or longer and retained the features of JGC. The JGC granules fluoresced when treated with a rabbit antibody against pure rat renin, followed by fluorescein isothyocyanate conjugated F(ab')2 fragment of goat antirabbit IgG (Fc fragment) heavy chain specific. The latter indicated the presence of renin. The JGC were lysed in the presence of DFP, captopril, leupeptin, and EDTA, and were extracted in the presence of pepstatin. The lysate contained renin activity that was inhibited by a specific renin antibody. Nonspecific proteases were excluded by the antibody and its pH optimum. Angiotensin I-converting enzyme was detected in the lysate prepared without the use of EDTA and captopril. Angiotensins I and II/III were derived from the extract by additional extractions, TLC, and RIA, using highly specific antibodies. The angiotensins were confirmed by chromatography monitored by authentic angiotensins. We concluded that the cultured JGC contained renin, angiotensin I-converting enzyme, and angiotensin I and II/III.
Active modulation of electrical coupling between cardiac cells of the dog. A mechanism for transient and steady state variations in conduction velocity.
Authors: Spach M S , Kootsey J M , Sloan J D
Published: June 2012

Propagation velocities of action potentials were measured simultaneously along the longitudinal and transverse axes of cardiac fibers in ventricular muscle. The anisotropic distribution of propagation velocities was found to be altered transiently and in the steady state by the rate and pattern of stimulation and by ouabain. The relative amount of velocity change varied with the direction of propagation and was greatest in the direction perpendicular to the long fiber axis. None of the variables usually associated with the membrane ionic mechanism of depolarization--resting potential, Vmax, and taufoot--showed enough variation to account for the observed changes in velocity. A simplified anisotropic propagation model representing the internal current pathway as an alternating sequence of cytoplasmic and junctional resistance is presented, taking into account the larger contribution to the internal resistance made by the cell couplings in the transverse direction than in the longitudinal direction. On the basis of this model, it was concluded that the observed changes in velocity were due to changes in cell coupling. Both transient and steady state velocity changes were found to correspond to changes in the action potential duration, suggesting that there is a common factor, such as the internal calcium and/or sodium concentrations, linking the control of the action potential duration and the coupling resistance between cardiac cells.
Further evidence for a muscarinic component to the neural vasodilator innervation of cerebral and cranial extracerebral arteries of the cat.
Authors: Bevan J A , Buga G M , Jope C A , Jope R S , Moritoki H
Published: June 2012

Transmural electrical stimulation of segments of lingual and cerebral (basilar, middle and posterior cerebral) and also other cranial arteries of the cat results after a long latency in a dilator response. The response may be resolved into two components--an initial transient atropine-sensitive component and a slower more ponderous one that is atropine-resistant. The variability in pattern of dilation responses from segments of different vessels or even those from the same segment of different cats is considerable. Some responses are entirely atropine-sensitive and others atropine-resistant; however the vast majority show a dilation that can be considered to be made up of both components. The latencies of the atropine-sensitive and atropine-resistant components are not different. The effect of atropine on the lingual but not the cerebral arteries is frequency dependent, being proportionately greater at low than at high frequencies. In both vessels, the effect of atropine is independent of train length at 1 Hz. Physostigmine potentiates significantly the dilation of the lingual artery but not that of the cerebral arteries. The potentiation is reversed by atropine. The endogenous acetylcholine level was measured in a series of vessels. It can be correlated with the activity of choline acetyltransferase and the presence of neurogenic dilation. It is proposed that there are two transmitters released in parallel from nerve(s) in the walls of cerebral, lingual, and possibly, other cranial arteries to cause vasodilation. It seems that one of these is acetylcholine.
Isolated cat trabeculae in a simulated feline heart and arterial system. Contractile basis of cardiac pump function.
Authors: Elzinga G , Westerhof N
Published: June 2012

Isolated cat trabeculae were studied under conditions resembling those present for the muscle fibers in the wall of the left ventricle. To obtain such a situation experimental animals, perfusion fluid, temperature, stimulation frequency, peak stress values, contraction sequence, length, and force control were chosen with respect to that criterion. Results were compared with those described for the intact feline heart in previous studies. Special emphasis was placed on determinants of the pump function graph, i.e., the relationship between mean ventricular pressure and output. It was found that peak isometric stress values measured in the trabeculae were about twice as high as those existing on average at the base of the intact left ventricle in the circumferential direction. However, the duration of the mechanical activity, as measured in iso(volu)metric contractions, was in the isolated trabeculae (206 msec) significantly less (P less than 0.01) than found in intact right (292 msec) or intact left ventricle (344 msec). Furthermore the (maximum) output of the intact left ventricle at end-diastolic pressure could not be accounted for in a simple manner by the maximum amount of shortening found in isolated trabeculae. The points of the pump function graph obtained by varying the input impedance of the loading arterial system over a wide range of compliance and resistance values in the steady state deviated only little from the graph obtained from a series of constant pressure levels applied in a beat-to-beat fashion. Therefore, the insensitivity of the pump function graph to the nature of the arterial load is found in the intact heart as well as in isolated cardiac muscle.
Potentiating and depressive effects of ouabain and potassium-free solutions on rat mesenteric resistance vessels.
Authors: Mulvany M J , Nilsson H , Flatman J A , Korsgaard N
Published: June 2012

We have investigated the in vitro effects of ouabain and K-free solutions on some pharmacological and electrophysiological properties of rat mesenteric resistance vessels (internal diameter approximately 190 micrometers). Vessels were mounted as ring preparations on a myograph capable of measuring their isometric wall tension. In normal saline solutions, vessels did not exhibit any tone and had a membrane potential of -54 mV. Both 1 mM ouabain and K-free solutions caused a transient depolarization of 5-8 mV; thereafter the membrane slowly depolarized to about -45 mV after 30 minutes. There was no mechanical response to ouabain, but K-free solutions caused a transient development of tension which could be inhibited by phentolamine (1 microM). In norepinephrine-activated vessels, exposure to ouabain or K-free solutions caused a small depolarization and an increase in tension. Long-term (30-minute) exposure to 1 mM ouabain or K-free solutions reduced the amplitude of norepinephrine responses and, for the lower (but not the higher) norepinephrine concentrations, the membranes were about 14 mV more depolarized than control. The mechanical responses to a cocktail of norepinephrine in a high potassium solution were, however, unaffected. Re-exposure to normal saline solution produced a transient hyperpolarization and transiently eliminated the norepinephrine response, but thereafter the membrane potential and response returned to normal. The results indicate that ouabain and K-free solutions can have both short-term potentiating and long-term depressive effects on the mechanical response of rat mesenteric resistance vessels to norepinephrine.
Arteriosclerosis in normal and von Willebrand pigs: long-term prospective study and aortic transplantation study.
Authors: Fuster V , Fass D N , Kaye M P , Josa M , Zinsmeister A R , Bowie E J
Published: June 2012

In a long-term prospective study, five normal control pigs and five pigs with homozygous von Willebrand's disease received a nonfatty diet from age 3 months to 4 years; then the aortas were analyzed. The fibrous arteriosclerotic plaques in the distal abdominal aortic region involved an average of 28% of the surface area in control pigs and only 7% of the surface area in pigs with von Willebrand's disease (P less than 0.01). In a subsequent study of 3-month-old pigs, the distal abdominal aortic segments from nine normal pigs were cross-transplanted with segments from nine other normal pigs (control study), and aortic segments from four normal pigs were transplanted into four host pigs with von Willebrand's disease (exchange study). All pigs received a 2% cholesterol diet for up to 6 months; then the transplanted aortic segments were analyzed. The donor normal aortic segments in the host normal pigs developed arteriosclerosis that involved an average of 20% of the surface; the endothelial fluorescent pattern of von Willebrand factor was identified. In contrast, the donor normal aortic segments in the host pigs with von Willebrand's disease had arteriosclerosis that involved an average of only 4% of the surface (P less than 0.01); the endothelial cell von Willebrand factor was not identified. The long-term prospective study indicates that pigs with von Willebrand's disease are resistant to the development of spontaneous arteriosclerosis. The aortic transplantation data are compatible with the hypothesis that the absence of von Willebrand factor in pigs with von Willebrand's disease may cause impairment of platelet-arterial wall interaction and resistance to arteriosclerosis.
Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle.
Authors: Kagiyama Y , Hill J L , Gettes L S
Published: June 2012

We studied the individual and combined effects of extracellular acidosis and increases in extracellular potassium on action potential characteristics and conduction in order to gain a better understanding of the effects of acute ischemia. At each level of potassium between 2.7 and 17 mm, acidosis induced by increasing Pco2 (respiratory acidosis) and by decreasing HCO3- (metabolic acidosis) decreased resting membrane potential, the maximum rate of rise of the action potential upstroke (Vmax), and slowed conduction. Metabolic acidosis consistently and significantly lengthened the steady state action potential duration whereas respiratory acidosis did not. Respiratory acidosis caused changes in resting membrane potential, Vmax, and conduction velocity; which occurred more rapidly and were of greater magnitude than the changes induced by metabolic acidosis. The changes in Vmax induced both types of acidosis were due to a change in the resting membrane potential-Vmax relationship as well as to the changes in the resting membrane potential. The conduction slowing induced by acidosis was greater when potassium was 9 and 13 mM than when potassium was 5.4 mm. Our results suggest that acidosis causes important changes in the electrophysiological properties of ventricular fibers and that many of the known electrophysiological effects of acute ischemia can be mimicked by the combined effects of extracellular acidosis and an increase in extracellular potassium.
Relaxation to transmural nerve stimulation and exogenously added norepinephrine in porcine cerebral vessels. A study utilizing cerebrovascular intrinsic tone.
Authors: Winquist R J , Webb R C , Bohr D F
Published: June 2012

The large arteries at the base of the brain in the pig were studied in vitro for their responsiveness to neurogenic and humoral stimuli. Helical strips of these cerebral vessels tonically contracted consistently following application of resting force. The development and maintenance of this tone were not influenced by prior treatment of strips with tetrodotoxin (5 x 10(-7) M), 6-hydroxydopamine (300 micrograms/ml) guanethidine (5 x 10(-6) M), or antagonists of known vasoactive autacoids (i.e., phentolamine, propranolol, atropine). Once tone reached an equilibrated plateau, transmural nerve stimulation and exogenously applied norepinephrine evoked a relaxation. The relative potency of beta-adrenergic agonists in producing a relaxation was isoproterenol greater than norepinephrine greater than epinephrine much greater than terbutaline. The response to norepinephrine, but not that to transmural nerve stimulation, was abolished by beta-adrenoceptor antagonists. The neurogenic response, but not the relaxation to exogenous catecholamines, was blocked by tetrodotoxin and 6-hydroxydopamine and diminished by guanethidine. Vasoactive intestinal polypeptide and adenosine were also potent relaxant agents. These responses, but not the response to transmural nerve stimulation were blocked by alpha-chymotrypsin (1.5 U/ml) and aminophylline (3 x 10(-5) M), respectively. These results suggest that porcine cerebral vessels develop myogenic tone which allows one to examine neural and/or humoral dilator responses without prior spasmogen addition. The vascular beta-receptors appear to be of the beta 1-subtype which is consistent with that found in other species. The nature of the dilator neurotransmitter is unknown, but the functional integrity of the adrenergic nerve terminals appears important for the neurogenic relaxation.
Right ventricular performance during increased afterload impaired by hypercapnic acidosis in conscious dogs.
Authors: Rose C E , Van Benthuysen K , Jackson J T , Tucker C E , Kaiser D L , Grover R F , Weil J V
Published: June 2012

Since heart failure may occur in the setting of lung dysfunction and CO2 retention with only modest increases in cardiac work load, we questioned whether myocardial function is impaired by hypercapnic acidosis. To determine the influence of hypercapnic acidosis on right ventricular function, we measured the effects of acute (2 hours) and chronic (2 weeks) hypercapnic acidosis on right ventricular performance during normal and increased right ventricular afterload in five conscious dogs. Systemic hemodynamic and right ventricular functions were unaltered during normal right ventricular afterload by acute hypercapnic acidosis (PaCO2 = 49 +/- 3 mm Hg, pH = 7.27 +/- 0.003). As right ventricular afterload was increased by progressive balloon occlusion of the right ventricular outflow tract during acute hypercapnic acidosis, the rise (slope) in right ventricular end-diastolic pressure was increased 4-fold (P less than 0.01) over that observed in normocapnic control. Maximum isovolumic right ventricular dP/dt rose (P less than 0.05) comparably with increasing right ventricular afterload during normocapnic control and acute hypercapnic acidosis. Chronic hypercapnic acidosis (PaCO2 = 55 +/- 2 mm Hg, pH = 7.28 +/- 0.01) resulted in systemic vasodilation and increased (P less than 0.05) heart rate and cardiac output during normal right ventricular afterload. As right ventricular afterload was increased during chronic hypercapnic acidosis, the rate of rise in right ventricular end-diastolic pressure was 2-fold (P less than 0.01) above normocapnic control but maximum isovolumic right ventricular dP/dt was unchanged in contrast to normocapnic control and acute hypercapnic acidosis. Moreover, cardiac output fell and stroke work was unchanged with increasing afterload during chronic hypercapnic acidosis. beta-Adrenergic blockade resulted in an increased (P less than 0.01) rate of rise in right ventricular end-diastolic pressure with afterload during normocapnic control and chronic hypercapnic acidosis. We conclude that hypercapnic acidosis results in diminished right ventricular performance during increased right ventricular afterload, evidenced by accentuated rise in right ventricular end-diastolic pressure, and may contribute to the congestive heart failure and edema observed in patients with pulmonary hypertension and CO2 retention.
External detection of early microvascular dysfunction after no-flow ischemia followed by reperfusion in isolated rabbit hearts.
Authors: Tilton R G , Larson K B , Udell J R , Sobel B E , Williamson J R
Published: June 2012

To define relationships better between the duration of severe ischemia and microvascular functional integrity with an approach potentially applicable to studies in vivo, the effects of 30 and 60 minutes of global, no-flow ischemia on the coronary vasculature of isolated, perfused rabbit hearts were determined. Residue-detection data, analyzed with a two-compartment model, were used to estimate indices of microvascular function, including the mean-transit time (tBSA) of radiolabeled bovine serum albumin (125I-BSA), vascular into extravascular space clearance, and vascular and extravascular space volumes. It was shown that the Central Volume Principle of tracer kinetics does not hold when transport of label between vascular and extravascular spaces takes place convectively by solvent drag, and a more general expression for tBSA was derived and applied. Left ventricular end-diastolic pressure and left ventricular developed pressure were monitored with an isovolumic balloon. Aortic perfusion pressure, left ventricular end-diastolic pressure, left ventricular developed pressure and vascular space volume remained constant, while mean transit time, vascular into extravascular space clearance and extravascular space volumes increased gradually during 3-hour control perfusions. Perfusion pressure, mean transit time and extravascular space clearance increased significantly with reperfusion after 30 minutes of ischemia even though left ventricular end-diastolic and left ventricular-developed pressures returned to control levels. Vascular space volumes increased minimally, whereas extravascular space volumes increased 5-fold during reperfusion. These changes in 125I-BSA washout and permeation across endothelium with reperfusion after no-flow ischemia indicate that compromised vascular integrity is an early manifestation of ischemia with functional consequences that persist even after ischemia sufficiently brief to permit restoration of left ventricular performance.
A mathematical analysis of the myogenic hypothesis with special reference to autoregulation of renal blood flow.
Authors: Oien A H , Aukland K
Published: June 2012

To test the hypothesis that autoregulation of renal blood flow could result from myogenic regulation of arterial/arteriolar wall tension, we have explored a model based on the assumptions that (1) each preglomerular vessel segment reacts to a change in transmural pressure by altering its internal radius until the initial change in wall tension is reduced by a gain factor, (2) postglomerular structural resistance remains unchanged, (3) extravascular tissue pressure equals intrarenal venous pressure, and (4) the renal vascular system can be represented by one unbranched tube. General equations were obtained for flow and segmental radii and pressure as functions of aortic pressure. With a gain factor of 1 and a glomerular capillary pressure of 50% of aortic pressure under control conditions, the model predictions agree well with experimental data in dogs. Increasing aortic pressure from about 60% of control level causes only slight increase of blood flow. A rise in tissue pressure up to 40% of aortic pressure causes only moderate reduction. Changes in vessel radii begin in proximal vessel segments and spread distally toward glomerulus at increasing changes in aortic and tissue pressures from their control levels. Glomerular capillary pressure is autoregulated in proportion to blood flow. The degree of autoregulation is only moderately dependent on the gain factor: A moderate impairment caused by reducing the gain factor from 1 to 0.7 may be compensated by locating the myogenically responsive wall layer a distance 0.2 times the internal radius from the vessel lumen. "Superautoregulation," i.e., a rise in flow at reduced aortic pressure, is not possible. An upper limit of autoregulation is obtained only with the additional assumption of a fall in contractile force at extreme shortening of the muscle fibers. No definitive biological proof has yet been provided for a segmental wall tension-regulating mechanism in the preglomerular vessels, and obviously its existence cannot be proved by a mathematical model. However, if such a mechanism does exist, it can explain most of the renal resistance changes at varying arterial and intrarenal pressures, as well as the observed autoregulation of terminal interlobular arterial pressure.
Overperfusion, hypoxia, and increased pressure cause only hydrostatic pulmonary edema in anesthetized sheep.
Authors: Landolt C C , Matthay M A , Albertine K H , Roos P J , Wiener-Kronish J P , Staub N C
Published: June 2012

Overperfusion (high pressure and flow through a restricted microvascular bed) has been suggested as the mechanism for both microembolic and high altitude pulmonary edema. In eighteen anesthetized, ventilated sheep, we measured pulmonary hemodynamics, lung lymph flow, and lymph:plasma protein concentration ratio. After a 2-hour stable baseline, we resected 65% of lung mass (right lung and left upper lobe) and gave whole blood transfusions to maintain cardiac output. During overperfusion of the left lower lobe, lymph flow increased moderately (5.8 +/- 2.3 to 7.7 +/- 3.8 ml/hr) and lymph:plasma protein concentration decreased (0.73 +/- 0.08 to 0.64 +/- 0.08). After a 2-hour stable period, we decreased inspired oxygen in 10 sheep (Pao2 = 40 +/- 3 mm Hg). With added alveolar hypoxia, pulmonary artery pressure increased modestly, but lymph flow and the lymph:plasma protein concentration ratio did not change. In eight sheep (four hypoxic, four normoxic), we raised left atrial pressure approximately 12 cm H2O for 2 hours. Lymph flow rose (10.8 +/- 3.8 ml/h) and lymph:plasma protein concentration decreased further (0.52 +/- 0.07). At each step, lymph:plasma protein concentration decreased, as predicted for the calculated rise in microvascular pressure. There was no evidence that overperfusion, with or without alveolar hypoxia, increased lung endothelial barrier protein permeability.
Coronary artery spasm in intact dogs induced by potassium and serotonin.
Authors: Pérez J E , Saffitz J E , Gutiérrez F A , Henry P D
Published: June 2012

Although coronary artery spasm has been implicated as an important cause of myocardial ischemia in humans, an animal model of reversible segmental coronary constriction has not been described. To provoke coronary spasm in open-chest dogs, selected vasoconstricting agents adsorbed to viscous ion exchange gels were applied topically to the surface of epicardial coronary arteries. The procedure provided a sustained localized release of drug, and minimized effects on contiguous myocardium or on the systemic circulation. Segmental arterial constrictor responses were evaluated by sonomicrometry, arteriography, and electromagnetic flow measurements. Potassium evoked sustained constrictions or spasms, and concomitantly reduced flow by -42 +/- 4% (SE; n = 34). Serotonin likewise produced sustained decreases in flow of -22 +/- 6% (SE; n = 5). Other constrictors, including norepinephrine and angiotensin, failed to evoke sustained constrictions. Spasms nearly abolished reactive hyperemic responses elicited by temporary complete occlusion of the artery. Intravenous nitroglycerin and dihydropyridine calcium antagonists promptly relieved the spasms. Scanning electronmicroscopic examination of the intimal surface of arteries undergoing sustained spasm revealed no platelet thrombi. Thus, nonthrombotic, vasodilator-sensitive segmental coronary spasms were elicited by endogenous constrictors which may play a role in regulating flow to ischemic myocardium.