bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct diastolic ventricular interaction gain measured with sudden hemodynamic transients
Authors: Slinker B. K. , Goto Y. , LeWinter M. M.
Published: December 2017

Changes in right ventricular volume affect left ventricular function via direct ventricular interaction mediated by the septum, common myocardial fibers in the free wall, and the pericardium, and also via series interaction mediated by changes in right ventricular output reaching the left ventricle through the pulmonary circulation. To study direct interaction, series interaction must be held constant or removed from the experimental preparation. Because there has been no way to directly measure direct ventricular interaction in the intact circulation, we developed a new method to experimentally separate these two components of ventricular interaction by combining abrupt occlusion of both venae cavae and quick withdrawal of 10-15 ml of blood from the right ventricle. This procedure decreased right ventricular end-diastolic pressure (RVEDP) on the next beat without changing pulmonary venous flow, left ventricular end-diastolic segment lengths, or left ventricular systolic function. The direct interaction gains, quantified as delta LVEDP/delta RVEDP, where LVEDP is left ventricular end-diastolic pressure, and delta refers to the change between the beats before and after reducing right ventricular volume, were (means +/- SD) 0.32 +/- 0.32 at steady-state LVEDP = 5 mmHg, 0.38 +/- 0.23 at LVEDP = 10 mmHg, and 0.28 +/- 0.32 at LVEDP = 15 mmHg. These gains were not significantly different (P greater than 0.50). Therefore, we calculated an overall average gain by pooling data from the three base-line LVEDP conditions. This value is 0.33 with 95% confidence interval 0.16-0.51. This 95% confidence interval indicates our data are consistent with many previous reports of diastolic direct interaction.
Analysis of regional responses to endothelin in hindquarters vascular bed of cats
Authors: Minkes R. K. , MacMillan L. A. , Bellan J. A. , Kerstein M. D. , McNamara D. B. , Kadowitz P. J.
Published: December 2017

Regional responses to endothelin, a peptide derived from endothelial cells in culture, were investigated in the hindquarters vascular bed of cats, when flow varied naturally and when flow was maintained constant with a pump. Intravenous injections of endothelin at doses of 0.03 and 0.1 nmol/kg caused dose-dependent decreases in systemic arterial pressure and increases in distal aortic blood flow. Injection of endothelin at a dose of 0.3 nmol/kg iv caused a biphasic response characterized by an initial decrease in arterial pressure and an increase in blood flow, which was followed by a secondary rise in pressure and a fall in blood flow. When blood flow to hindquarters was maintained constant with a pump, intra-arterial injection of 0.03 nmol endothelin caused a decrease in perfusion pressure, whereas 0.1-1 nmol doses elicited biphasic responses characterized by an initial decrease followed by a secondary increase in perfusion pressure. When compared with other vasoactive peptides, the pressor activity of endothelin was less than angiotensin II by an order of magnitude but was threefold greater than that of neuropeptide Y in the hindquarters vascular bed. The pressor component of the response to endothelin and the response to the calcium agonist BAY K 8644 were decreased in a reversible manner by nisoldipine, a dihydropyridine calcium entry blocking agent. The results of these studies indicate that porcine-human endothelin has both vasodilator and vasoconstrictor activity in the hindquarters vascular bed of cats. The predominant response at a low concentration is vasodilation, whereas at higher concentrations a vasoconstrictor response that was dependent in part on the influx of extracellular calcium could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic control of intrarenal arteries of rabbits
Authors: Owen M. P. , Taphorn M. C. , Walmsley J. G.
Published: December 2017

A comparative study of the adrenergic control of two sequential rabbit intrarenal arteries of differing diameter [intrarenal branch artery (IRBA)-unstretched lumen diameter (ULD) approximately 300 microns and interlobar artery (ILA)-ULD approximately 250 microns] has been conducted. The neurogenic contractile response of isolated segments in relation to the maximum response to l-norepinephrine (NE) was minimal (8 Hz response approximately 30% of maximum contraction) and similar in both types of arteries. Phentolamine (PTA) (10(-6) M) blocked neurally evoked contractions of the IRBAs at 2, 4, and 8 Hz and of the ILAs at 2 and 4 Hz. (8 Hz responses were not entirely blocked in 3 out of 8 ILAs.) The sensitivity to exogenous NE decreased with a decrease in intrarenal vessel diameter, whereas the maximum active smooth muscle cell stress to NE was greater than 3 X 10(5) N/m2 for each vessel. All arterial segments constricted in response to histamine (H) and NE with equal maximal effects; however, sensitivity to H was greater in the smaller artery (ILA). The comparative contractile responses to nerve stimulation and exogenous NE in sequential renal arteries contrasts to the pattern of these responses in sequential arteries in any other rabbit regional bed previously studied (pulmonary and ear vasculature).
Atrial wall function and plasma atriopeptin during volume expansion in conscious dogs
Authors: Hintze T. H. , McIntyre J. J. , Patel M. B. , Shapiro J. T. , DeLeonardis M. , Zeballos G. A. , Loud A. V.
Published: December 2017

Mean left atrial pressure is believed to be an accurate estimate of atrial stretch in vivo and is used to assess the stimulus for atriopeptin release in both animals and humans. However, for a number of years it has been known that atrial stretch receptor discharge occurs during specific phases of the atrial cycle and that B-receptor discharge correlates with the passive filling of the atrium, which occurs during the V wave. The purpose of this study was to develop the concept that phase-specific changes in atrial wall stress are responsible for atriopeptin secretion. In chronically instrumented conscious dogs, volume expansion (1,000 ml of saline in 5 min) increased left atrial pressure and dimensions and caused a 663 +/- 189% increase in plasma immunoreactive atriopeptin from 44 pg/ml. At this time, mean left atrial pressure increased only 202 +/- 36% (mean +/- SE), whereas A wave pressure increased 146 +/- 19% and V wave pressure increased 290 +/- 67%. A and V wave dimensions increased only a few percent. After developing atrial wall thickness constants for diastole (KCl fixation) and systole (BaCl2 fixation), calculated atrial A wave wall stress increased 163 +/- 25%, and V wave wall stress increased 346 +/- 85%. Minute wall stress (wall stress times heart rate) gave an even better correlation with changes in plasma atriopeptin. V wave minute wall stress increased 690 +/- 168%, whereas A wave wall stress increased 366 +/- 56%.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelium-associated vasodilators in rat skeletal muscle microcirculation
Authors: Kaley G. , Rodenburg J. M. , Messina E. J. , Wolin M. S.
Published: December 2017

Pharmacological probes were used to assess the possible roles of guanosine 3',5'-cyclic monophosphate (cGMP)-associated endothelium-derived relaxing factor (EDRF) in mediating microvascular responses to endogenous and exogenous agents in vivo. Pentobarbital-anesthetized rats (Wistar, 6 wk old) were prepared for in vivo microscopic observation and quantification of changes in diameter of third-order arterioles (15-25 microns) in the cremaster muscle to topical application of all agents. In indomethacin-pretreated preparations, cremasteric arteriolar dilator responses to acetylcholine, bradykinin, or ATP, but not to adenosine, histamine, or prostaglandin E2, were inhibited by hydroquinone (50 microM). Vasodilation to acetylcholine was also inhibited by methylene blue (5 microM), a blocker of guanylate cyclase activation. Constrictor responses to norepinephrine were not affected by hydroquinone or methylene blue. The inhibition of acetylcholine-induced vasodilation by hydroquinone and methylene blue was reversed by superoxide dismutase, suggesting that superoxide anion antagonized the response. On the other hand, basal arteriolar diameters or responses to acetylcholine were not affected by oxygen metabolite scavengers. Unlike in isolated arteries, vasodilator responses to the calcium ionophore A23187 or arachidonic acid were completely antagonized by cyclooxygenase inhibition. These data suggest that EDRF could be involved in the control of microvascular tone; however, significant differences exist in the stimuli that elicit dilation through this mediator in small and large blood vessels.
Effect of hematocrit on microvascular pressures in 3- to 5-wk-old rabbit lungs
Authors: Raj J. U. , Ramanathan R. , Chen P. , Anderson J.
Published: December 2017

To examine the effects of blood hematocrit (Hct) and apparent viscosity on the pulmonary microcirculation, we studied 30 isolated, perfused 3- to 5-wk-old rabbits with varying perfusate Hct. We partitioned total vascular resistance by measuring pulmonary artery and left atrial pressures and by micropuncture the pressures in the subpleural microcirculation in 20-40 microns diameter arterioles, 20-40 microns venules, and 250-300 microns venules. To prevent active vasomotion and changes in vessel geometry, we paralyzed the vasculature with papaverine hydrochloride. We studied four groups of lungs: group I (n = 7) with low Hct (17.8 +/- 2.4%); group II (n = 9) with medium Hct (46.8 +/- 8.2%); group III (n = 6) with high Hct (74.4 +/- 5.8%); and group IV (n = 8) with both low and high Hct perfusates. Lungs were perfused at constant flow (80 +/- 4 ml.kg body wt-1.min-1) in zone 3, airway and venous pressures being 6 and 8 cmH2O, respectively. We found that in lungs perfused with low Hct, approximately 52% of the total resistance was in arteries, approximately 25% in microvessels, and approximately 21% in small veins, with very little resistance in large veins. With an increase in perfusate hematocrit and apparent viscosity, total pulmonary vascular resistance increased mainly because of an increase in resistance in arteries and small veins, with little change in resistance in microvessels and large veins.
Influence of volume expansion on hemodynamic effects of atrial natriuretic factor in rabbits
Authors: Volpe M. , Cuocolo A. , Vecchione F. , Lembo G. , Pignalosa S. , Condorelli M. , Trimarco B.
Published: December 2017

We investigated the influence of acute volume expansion on the hemodynamic and renal responses to the constant infusion of atrial natriuretic factor (ANF) (alpha-human ANP, 2 micrograms/kg bolus, 0.2 microgram.kg-1.min-1) in rabbits anesthetized with ketamine and acepromazine. The effects of the peptide were evaluated in 12 euvolemic rabbits and in 15 rabbits during the steady-state phase of volume expansion (0.9% NaCl 4.5 ml/min for 60 min). In the euvolemic animals, ANF caused an increase in natriuresis and a reduction in blood pressure (BP), which was associated with a decrease in cardiac output (CO), stroke volume (SV), and no significant changes in central venous pressure (CVP), peripheral hematocrit (Hct), and heart rate (HR). When the peptide was infused in the volume-expanded animals, the effects of ANF on BP and HR were comparable with those observed in the euvolemic animals. However, in these animals the ANF-induced changes in CO, SV, CVP, and Hct were significantly greater than those observed in the euvolemic group. In addition, the percent increases in diuresis and natriuresis were significantly smaller than those obtained in the euvolemic animals. In conclusion, volume expansion with saline potentiates the effects of ANF on systemic hemodynamics and blood volume.
Mutual interaction of vasoconstriction and endothelial damage in stenotic arteries
Authors: Tulenko T. N. , Constantinescu D. , Kikuchi T. , Cox R. H. , Santamore W. P.
Published: December 2017

Coronary artery vasomotion may be important in the pathogenesis of angina pectoris. Numerous experimental studies demonstrated accentuated arterial vasomotion in endothelium-damaged vessels. We examined interactions of stenosis, arterial vasoconstriction, and endothelium denudation in a stenosed artery preparation in vitro. Canine carotid arteries and porcine coronary arteries were perfused with a physiological salt solution under constant pressure and a fixed distal resistance. Pressures at the proximal and distal ends of the artery, as well as the flow, were continuously recorded. Hemodynamic responses to serotonin, norepinephrine, and angiotensin II were separately studied. In intact arteries without stenosis, the agonists produced a 30-40% reduction in lumen diameter without altering flow or distal pressure. After a luminal stenosis was created, vasoconstriction produced by the agonists decreased flow and increased the pressure gradient across the stenosis. Flow decreased to (or near) zero, indicating occlusion at the stenotic site. After endothelial loss, this effect was amplified, demonstrating occlusion of the artery and suppression of the flow at significantly (P less than 0.05) lower concentrations of agonist (0.1-0.3) compared with endothelial intact arteries. These studies illustrate 1) the necessity for the presence of stenosis in large arteries for vasoconstriction to impair flow and 2) the protecting effect of intact endothelium in blunting the effects of arterial vasoconstriction in stenosed vessels. Through the reciprocal interaction of arterial stenosis, vasoconstriction, and endothelial damage, ischemic events associated with certain types of vasomotion can be explained.
Effects of dextran-induced hyperviscosity on regional blood flow and hemodynamics in dogs
Authors: Chen R. Y. , Carlin R. D. , Simchon S. , Jan K. M. , Chien S.
Published: December 2017

In 10 pentobarbitalized dogs, plasma viscosity (Ep) was raised fourfold while apparent blood viscosity (Ea) increased about twofold by two steps of exchange transfusion of 200 ml of plasma with plasma containing high molecular weight dextran (mol wt 500,000, 20% wt/vol). Elevation of Ea was primarily caused by an increase of Ep but not red cell aggregation. As Ea increased, regional blood flow (by 15-microns microspheres) remained constant in most organs but reduced in the small intestine, spleen, and thyroid gland. Vascular hindrance (Z), which reflects the state of vascular geometry, was calculated as flow resistance per Ea. Among various organs, a reduction in Z was noted in the heart, liver, pancreas, kidney, brain, and adrenal gland. In myocardium, there was a progressive reduction of the endocardial-to-epicardial flow ratio, indicating a less profound vasodilation in endocardium than epicardium. These results indicate that dextran-induced hyperviscosity leads to a compensatory vasodilation in several vital organs thus serving to maintain blood flow and nutrient transport.
Coronary sinus pressure and arterial flow during intermittent coronary sinus occlusion
Authors: Neumann F. , Mohl W. , Schreiner W.
Published: December 2017

The relationship between coronary artery flow and coronary venous pressure during intermittent coronary sinus occlusion was studied in dogs at normal perfusion, left anterior descending artery occlusion, and reperfusion. Coronary sinus occlusion and release phases were varied systematically. The periodicity of the data and the assumption of a linear relationship between pressure and flow suggested Fourier analysis as a methodological approach. To show the systematic slow oscillations of coronary venous pressure and arterial flow induced by intermittent occlusion of the coronary sinus, the data were smoothed by superimposing consecutive cycles of identical occlusion-release timing and filtering the higher frequencies. A small number of Fourier components, corresponding to the time scale of the respective occlusion-release cycle, was sufficient to study the long wavelength behavior. The effect of arbitrarily varying the occlusion-to-release ratio at a given total cycle length was investigated in hypothetical pressure and flow curves based on interpolation of experimental Fourier coefficients. By means of a transfer function relating pressure and flow in the frequency domain, it was possible to predict the arterial flow curve using coronary venous pressure measurements only. Because at zero frequency the pressure-flow relationship cannot be assumed to be linear, the mean value of flow could not be obtained in this way. However, the deviation of flow from the mean, i.e., the shape of the flow curve, was reproduced satisfactorily.
Sarcoplasmic reticulum function in skinned fibers of hypertrophied rat ventricle
Authors: Kimura S. , Bassett A. L. , Saida K. , Shimizu M. , Myerburg R. J.
Published: December 2017

This study was designed to examine the Ca2+ sensitivity of the contractile system and the ability of the sarcoplasmic reticulum (SR) to accumulate and release Ca2+ in chemically (saponin) skinned cardiac fibers obtained from normal and pressure-overloaded hypertrophied rat left ventricles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 6-8 wk before study. Age- and weight-matched normal rats served as controls. Pressure over-load increased the left ventricular weight-to-body weight ratio by 51%. There were no differences in the Ca2+-tension relationship between normal and hypertrophied preparations at Ca2+ concentrations of 10(-7) to 10(-4) M. Caffeine-induced Ca2+ release from the maximally Ca2+ -loaded SR was also not different between the two groups at caffeine concentrations of 0.5-30 mM. However, when the relative amount of Ca2+ accumulated in the SR with 10(-6), 3 x 10(-6), or 10(-5) M Ca2+ loading solutions for various loading periods was estimated by the area under the 25 mM caffeine-induced contraction, the accumulation of Ca2+ was significantly slower in hypertrophied fibers than in normal fibers. We conclude that depressed Ca2+ accumulation by the SR plays a role in modulation of contractile performance in this model of chronic pressure overload in rats.
Stenotic amplification of vasoconstriction responses
Authors: Li K. , Santamore W. P. , Morley D. L. , Tulenko T. N.
Published: December 2017

Based on simple hemodynamic principles, arterial stenoses could accentuate the effects of arterial vasoconstriction by reducing intraluminal pressure. To examine this mechanism we employed an in vitro stenotic carotid artery preparation. Eight carotid arteries, obtained from anesthetized heartworm-positive dogs, were isolated and perfused with a physiological salt solution under constant pressure (100 mmHg) and with a fixed distal resistance. After creating an intraluminal stenosis, proximal pressure, distal pressure, and flow were continuously recorded as norepinephrine was incrementally added to the perfusion reservoir. At each norepinephrine concentration, arterial dimensions were recorded on 35-mm film and measured by quantitative dimensional analysis. These data were approximated by a four-parameter logistic equation. The proximal diameter data were considered to represent solely the effects of arterial vasoconstriction, while the stenotic diameter data were considered to be affected both by arterial vasoconstriction and by stenotic pressures. The stenotic diameters shortened significantly more than the proximal diameter (1.2 +/- 2 vs. 0.5 +/- 0.1 mm, P less than 0.01). The shape of the stenotic diameter dose-response curve was similar to the distal pressure curve and was significantly (P less than 0.05; - 3.4 +/- 0.7) steeper than the proximal diameter curve (-0.7 +/- 0.1). Furthermore, the half maximum effective doses (ED50) were significantly interrelated for distal pressure and stenotic diameter data and unrelated for proximal diameter data. In five additional experiments, to eliminate the stenotic pressure changes, the flow was maintained constant. Maintaining stenotic vasoconstriction response (0.6 +/- 2 mm). The results of the present study show exaggerated stenotic vasoconstriction caused by a stenotic pressure decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
Ca2+-dependent heterometric and homeometric autoregulation in hypertrophied rat heart
Authors: Pawlush D. G. , Musch T. I. , Moore R. L.
Published: December 2017

There is evidence to suggest that the alterations in cardiac function that accompany several forms of myocardial hypertrophy are due in part to desensitization of the heart to the positive inotropic effect of extracellular Ca2+ (Cae2+). In this study the heterometric and homeometric functional responsiveness of normal (SH) and hypertrophied (HYP) isolated working rat hearts was examined as a function of extracellular Ca2+ concentration [( Ca2+]e). Surgically induced renovascular hypertension was used to produce a 39% increase in left ventricular (LV) weight in HYP hearts relative to LV weights of SH hearts. The Cae2+ dependence of heterometric autoregulation was examined in SH and HYP hearts. At high left atrial filling pressures, HYP hearts were functionally less sensitive to changes in [Ca2+]e than were SH hearts; this difference appeared to be due to a preload-dependent increase in the functional sensitivity of SH hearts but not HYP hearts to changes in [Ca2+]e. In both SH and HYP hearts, a step increase in afterload resulted in a beat-by-beat increase in peak aortic outflow systolic pressure (AoP) independent of changes in LV diastolic pressure. Under our experimental conditions, the magnitude of this homeometric AoP increase (the Anrep effect) was similar in both SH and HYP hearts. The AoP increase occurred at a monoexponential rate (kHA) and was much faster in SH than in HYP hearts. Furthermore, KHA varied directly as a function of [Ca2+]e only in the SH hearts.
Left ventricular function in experimental volume overload hypertrophy
Authors: Carabello B. A. , Nakano K. , Corin W. , Biederman R. , Spann J. F.
Published: December 2017

Left ventricular function in volume overload hypertrophy is controversial. In humans, chronic severe volume overload eventually results in left ventricular dysfunction; paradoxically, experimental volume overload hypertrophy has nearly always been associated with normal left ventricular function. However, in most cases, experimental volume overload hypertrophy has either been mild or only present for a short duration. To help resolve the issue of contractile function in volume overload hypertrophy, we examined ventricular function in a recently described model of severe chronic experimental mitral regurgitation. Left ventricular function was measured before and 3 mo after the creation of severe mitral regurgitation (averaged regurgitant fraction 0.64 +/- 0.04). At 3 mo end-diastolic volume had increased from 78 +/- 5 to 114 +/- 7 ml (P less than 0.01). Significant left ventricular hypertrophy had occurred with an increase in the left ventricular weight-to-body weight ratio from 3.84 +/- 0.2 to 5.22 +/- 0.2 (P less than 0.01). All indicators of left ventricular function (ejection fraction, the end ejection stress-volume relationship, this relationship corrected for eccentric hypertrophy, and mean velocity of circumferential fiber shortening at a common stress) were reduced at 3 mo. Our study produced 64% volume overload which was maintained for 3 mo at which time there was a 36% increase in left ventricular mass. This amount of volume overload of this duration produced significant left ventricular dysfunction.
Multiple tracer studies of bone uptake of 99mTc-MDP and 85Sr
Authors: McCarthy I. D. , Hughes S. P.
Published: December 2017

Multiple tracer outflow dilution studies were performed on the normal canine tibia. In all cases 125I-labeled albumin was used as a vascular tracer. In one series of experiments 99mTc-labeled methylene diphosphonate and [14C]sucrose were used as test tracers, and in a second series 85Sr and 22Na were used. A bolus of three tracers was injected into the tibial nutrient artery, and fractional concentrations appearing in the ipsilateral femoral vein were measured for a period of 5 min. A distributed model, containing parameters for capillary and bone permeability and apparent volumes of distribution of interstitial fluid, was fitted to these data. It was found that there was no discrimination between movement of 85Sr or 22Na from interstitial fluid space into bone. Transcapillary exchange does not appear to be a significant barrier to exchange between blood and bone surfaces.
Effects of hypoxia on atrioventricular node of adult and neonatal rabbit hearts
Authors: Young M. L. , Tan R. C. , Ramza B. M. , Joyner R. W.
Published: December 2017

We used an isolated perfused heart model to assess the effects of graded hypoxia (95, 45, 20, 10, or 0% O2, exposure for 5 min) on the adult and neonatal (0-3 days) rabbit atrioventricular (AV) node. The AV nodal function was assessed by measuring the A-H interval at a constant atrial pacing cycle length, the longest pacing cycle length resulting in Wenckebach periodicity [Wenckebach cycle length (WCL)] and the AV nodal effective refractory period (AVNERP). The A-H intervals remained stable in neonatal hearts until O2 saturation was decreased to 10%. On the other hand, the A-H intervals began to increase in adult rabbit hearts at 20% O2. In 95% O2, the AV nodal WCL was longer in adult hearts than in the neonatal hearts (165 +/- 8 ms vs. 142 +/- 7 ms). The effect of hypoxia on the AV nodal WCL was significantly greater in adult hearts than in neonatal hearts when the O2 saturation was decreased to 20% (a 54% increase in adults vs. a 14% increase in neonates, P = 0.02). The difference was greater at lower levels of O2. In 95% O2 at comparable basis driving cycle length (240 ms), the A-H intervals were equal in neonatal and adult hearts (43 +/- 3 vs. 43 +/- 7 ms), but the AVNERP of the neonates was significantly longer than that of the adults (133 +/- 21 vs. 97 +/- 19 ms, P = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
Reperfusion arrhythmias: dose-related protection by anti-free radical interventions
Authors: Bernier M. , Manning A. S. , Hearse D. J.
Published: December 2017

Isolated rat hearts (n = 15 per group) were subjected to regional ischemia (10 min) and reperfusion. Superoxide dismutase (SOD; 8 X 10(3), 2 X 10(4), 4 X 10(4), 6 X 10(4), 8 X 10(4), 1.2 X 10(5), or 1.6 X 10(5) IU/l) given early (i.e., throughout the experiment) reduced the incidence of reperfusion-induced ventricular fibrillation (VF), the dose-response characteristics describing an asymmetric U-shaped curve. The optimal dose of SOD (8 X 10(4) IU/l) reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Given late (i.e., 2 min before reperfusion), this dose of SOD exerted a reduced but nonetheless significant antifibrillatory effect. Early administration of catalase (1 X 10(3), 1 X 10(4), 2.5 X 10(4), 5 X 10(4), 1 X 10(5), 1.5 X 10(5), or 1 X 10(6) IU/l) reduced VF incidence in a linear dose-dependent manner, from its control value of 87 to 7% with 1 X 10(6) IU/l (P less than 0.05). Late administration of this dose reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Allopurinol (0.07, 0.15, 0.37, 0.73, 1.10, or 1.47 mM added to the perfusate throughout the experiment) significantly reduced VF incidence over a wide range of doses, but low and high doses were ineffective. Pretreatment with allopurinol (0, 0.01, 0.02, 0.05, 0.10, 0.20, or 0.50 g.kg-1.day-1 per os 48, 24, and 1 h before study) reduced VF incidence from its control value of 93 to less than 50% at several doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of age on mechanical and structural properties of myocardium of Fischer 344 rats
Authors: Anversa P. , Puntillo E. , Nikitin P. , Olivetti G. , Capasso J. M. , Sonnenblick E. H.
Published: December 2017

To determine whether the mechanical and structural characteristics of the myocardium from the left and right ventricles are comparable in the adult rat and whether aging affects the two ventricles in a similar manner, the left and right posterior papillary muscles of rats at 10-11 and 19-20 mo of age were studied in terms of function and quantitative morphology. At 10-11 mo of age, the duration of isometric contraction was shorter and resting tension higher in the right muscle than in the left muscle. Isotonic velocity of shortening and relengthening were quicker in the left, but time-to-peak shortening was faster in the right. With aging (19-20 mo), velocity of shortening fell in the left ventricle while duration of contraction became prolonged. No such age-related effects were found in the right papillary muscle. On a structural basis, myocardial damage in the form of replacement scarring was present in the left and right muscles at 10-11 mo of age. However, the left muscle was more severely injured, and this difference persisted with age because a comparable increase in replacement fibrosis occurred in both muscles. It was concluded that cardiac performance is distinctly different in the left and right papillary muscles and aging exerts its detrimental impact on the left more than in the right myocardium, an observation that is further supported by the magnitude of tissue injury.
Outward currents in normal and hypertrophied feline ventricular myocytes
Authors: Kleiman R. B. , Houser S. R.
Published: December 2017

The properties of the inward rectifier K current (IK1) and the delayed rectifier K current (IK) were studied in single feline myocytes isolated from the right ventricle of normal cats and cats with experimentally induced right ventricular hypertrophy (RVH). IK1 demonstrated time-dependent decay during hyperpolarizations and showed inward rectification with a prominent negative-slope region between -30 and -10 mV. Both IK1 and IK was carried primarily by K ions. The activation of IK during depolarizations followed a monoexponential time course, whereas the deactivation of IK tail currents was either mono- or biexponential depending on the repolarization potential. IK showed marked rectification at positive potentials. A comparison of these currents in normal and hypertrophy myocytes revealed that in RVH the magnitude of IK1 is increased, whereas the magnitude of IK is decreased. IK showed steeper rectification, had slower activation, and had more rapid deactivation in RVH. These abnormalities of the IK may contribute to the prolongation of action potential duration, which characterizes pressure-overload cardiac hypertrophy.
Role of iron in postischemic microvascular injury
Authors: Smith J. K. , Carden D. L. , Grisham M. B. , Granger D. N. , Korthuis R. J.
Published: December 2017

Iron-catalyzed formation of hydroxyl radicals has been postulated to occur during reperfusion of ischemic tissues. To assess the role of iron-catalyzed oxidant production in ischemia/reperfusion (I/R) injury to skeletal muscle, we examined the effects of deferoxamine (an iron chelator) and apotransferrin (an iron-binding protein) on the increased vascular permeability produced by I/R in isolated, pump-perfused rat hindquarters. Solvent drag reflection coefficients (sigma) were measured in hindquarters subjected to 2 h of ischemia and 30 min of reperfusion with either no pretreatment, pretreatment with 50 mg/kg deferoxamine, 200 mg/kg apotransferrin, or iron-loaded deferoxamine (50 mg/kg). I/R alone was associated with an increase in vascular permeability as indicated by the significantly lower estimates of sigma obtained after I/R (0.68 +/- 0.03) compared with those obtained in nonischemic preparations (0.82 +/- 0.02). Pretreatment with deferoxamine or apotransferrin attenuated this permeability increase (sigma = 0.83 +/- 0.03 and 0.86 +/- 0.02, respectively), whereas pretreatment with iron-loaded deferoxamine afforded no protection (sigma = 0.71 +/- 0.02). These findings are consistent with the hypothesis that iron-catalyzed oxidant production is important in the genesis of microvascular injury following I/R. Since the enzyme xanthine oxidase has been implicated as a major source of oxidants generated during reperfusion, we also measured tissue levels of xanthine oxidase and xanthine dehydrogenase in muscle samples obtained from the same hindquarters in which we measured permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)
An unusual receptor mediates adenosine-induced SA nodal bradycardia in dogs
Authors: Belloni F. L. , Belardinelli L. , Halperin C. , Hintze T. H.
Published: December 2017

To characterize the receptor mediating the negative chronotropic effect of adenosine in dogs, experiments were performed on conscious dogs with chronically implanted cardiovascular instrumentation. Autonomic blockade was used to eliminate any reflex influences on heart rate. Intravenous bolus injections of various adenosine analogues caused dose-dependent, aminophylline-blockable reductions in heart rate with a potency order of 5'-(N-ethylcarboxyamido)-adenosine (NECA)-78:2-chloroadenosine-17:adenosine-1. Dipyridamole enhanced the potency of adenosine to equal that of 2-chloroadenosine. Moderately selective A1-receptor agonists N6-(L-2-phenylisopropyl)-adenosine (R-PIA) and N6-cyclohexyladenosine and an A2-selective agonist 2-phenylaminoadenosine (200 nmol/kg) had no negative chronotropic effect in the conscious dog. Adenosine and its analogues, including R-PIA, caused coronary vasodilatation at smaller doses than were required to slow the heart rate. The selective A1-adenosine receptor blocker xanthine amine congener (XAC) antagonized the negative chronotropic action of adenosine but did so nonselectively, as the coronary vasodilative and negative chronotropic actions of adenosine were antagonized equally well. The spontaneous contraction rate of isolated perfused dog right atrial preparations, which included the sinoatrial node, was reduced by intrasinoatrial node artery infusions of adenosine analogues with a potency ratio of NECA-100:adenosine-15:N6-cyclopentyladenosine-2.3:R-PIA-1. We conclude that the adenosine receptor mediating the negative chronotropic action of adenosine in the dog does not display the pharmacological characteristics of either typical A1- or A2-adenosine receptors. Instead, either a novel adenosine receptor or an A1-receptor with unusual agonist and antagonist binding properties appears to exist in the dog's sinoatrial node.
Effect of diltiazem on aortic pressure-diameter relationship in dogs
Authors: Yano M. , Kumada T. , Matsuzaki M. , Kohno M. , Hiro T. , Kohtoku S. , Miura T. , Katayama K. , Ozaki M. , Kusukawa R.
Published: December 2017

To study the effects of diltiazem (Dz) on aortic (Ao) pressure-diameter (P-D) relationships, the external diameter (D) of the thoracic Ao (sonomicrometry) and Ao pressure (AoP, micromanometer) were simultaneously measured in 10 anesthetized dogs. The P-D relationship from 80 ms after the dicrotic notch of AoP (t80) to 20 ms after the peak of the next R wave on the electrocardiogram (ECG) (t20) was plotted at 30-ms intervals. To depict the P-D relationship in a wide range of AoP, Ao occlusion immediately after the release of inferior vena caval (IVC) occlusion was performed both before and after a Dz (0.03 mg.kg-1.min-1, over 10 min) infusion. The P-D relationship so obtained was a sigmoid curve under both conditions and was reasonably described by a cubic curve (P = aD3 + bD2 + cD + d, where a, b, c, and d are constants and r greater than 0.99). The first derivative of cubic regression equation (dP/dD) value of the cubic curve was used as an index of Ao stiffness. In all dogs, the dP/dD-D relationship, which was parabolic, was similar to the delta P/delta D-D relationship measured from the actual P-D relationship (delta P/delta D is the ratio of the change in AoP to that in AoD), suggesting that it corresponded to a cubic curve.(ABSTRACT TRUNCATED AT 250 WORDS)
Peripheral vasodilatation induced by a vasopressin analogue with selective V2-agonism in dogs
Authors: Liard J. F.
Published: December 2017

The selective V2-agonist 4-valine-8-D-arginine vasopressin (VDAVP) increases cardiac output and heart rate and decreases total peripheral resistance in dogs. The mechanism of these hemodynamic effects was examined in the present studies. When infused into the left coronary artery of six conscious dogs for 1 h, VDAVP (10 ng.kg-1.min-1) increased cardiac output and decreased total peripheral resistance more than when given intravenously in the same animals. Administration of VDAVP into the carotid circulation elicited effects that did not differ significantly from those after intravenous infusion at the same rate in six conscious dogs. After destruction of the central nervous system in five dogs anesthetized with pentobarbital, VDAVP failed to increase cardiac output and heart rate but lowered mean arterial pressure and total peripheral resistance. Finally, infusion of VDAVP into the femoral artery of six anesthetized dogs increased femoral blood flow at rates of 1, 5, and 10 ng.kg-1.min-1, whereas none of these rates increased femoral blood flow when given intravenously. Thus the hemodynamic effects of VDAVP appear to result primarily from a peripheral vasodilatory action, with possible contribution from a positive inotropic effect. We found no evidence that central effects of VDAVP were importantly involved in its cardiovascular action.
Central effect of endothelin on blood pressure in conscious rats
Authors: Ouchi Y. , Kim S. , Souza A. C. , Iijima S. , Hattori A. , Orimo H. , Yoshizumi M. , Kurihara H. , Yazaki Y.
Published: December 2017

This study was conducted to investigate the effect of intracerebroventricular administration of endothelin (EDT), a novel potent vasoconstricting peptide, on blood pressure in conscious rats. The lateral cerebral ventricle of male Wistar rats was cannulated, and the femoral artery was also cannulated to measure the mean arterial blood pressure (MABP) and heart rate (HR). EDT dissolved in 10 microliters of artificial cerebrospinal fluid (ACSF) (8.25-66 pmol icv) provoked a dose-dependent increase in MABP. EDT also increased HR, although the effect of 66 pmol was variable. Intracerebroventricular ACSF did not provoke any effects on MABP and HR. Intracerebroventricular EDT also provoked contralateral rotational behavior. Pretreatment with 2 mg/kg iv phenoxybenzamine significantly suppressed the 16.5 pmol icv EDT-induced increase in MABP. Moreover, 16.5 pmol icv EDT markedly increased plasma epinephrine and norepinephrine concentration. These results indicate that EDT has a central pressor action, and the action might be mediated, at least in part, by catecholamine release to the periphery. EDT might play a role in the central control of blood pressure, although the physiological implications have not yet been determined.
Characteristics of regional myocardial stunning after exercise in dogs with chronic coronary stenosis
Authors: Thaulow E. , Guth B. D. , Heusch G. , Gilpin E. , Schulz R. , Kroeger K. , Ross J.
Published: December 2017

Persistent impairment of regional contraction of the left ventricle after restoration of blood flow following transient coronary occlusion has been termed “stunning,” and reversible regional dysfunction has also been observed during recovery from exercise-induced regional ischemia. To determine whether limitation of subendocardial blood flow after exercise is a determinant of such dysfunction in the presence of chronic coronary stenosis, nine conscious chronically instrumented dogs having an Ameroid constrictor were studied before, during, and after treadmill runs that induced regional ischemia. During exercise, systolic wall thickening (%WTh, sonomicrometers) in the ischemic region decreased from a normal level of 22.1 +/- 9.1% at rest to 8.8 +/- 5.2% (+/- SD, P less than 0.01), whereas subendocardial blood flow (microspheres) in the ischemic region decreased from 0.75 +/- 0.25 to 0.45 +/- 0.27 ml.min-1.g-1 (P less than 0.05). %WTh in the ischemic region gradually improved after exercise but remained depressed (75% of control) at 30 min after the run (P less than 0.05). Postexercise dysfunction was not related to simultaneous regional hypoperfusion, since at 5 and 10 min after running there was a tendency toward subendocardial hyperemia (control 0.75 vs. 1.33 and 1.30 ml.min-1.g-1, NS) with a return to control by 30 min. Thus persistent regional dysfunction after exercise-induced regional ischemia in the conscious dog is not due to sustained subendocardial ischemia in the presence of chronic coronary stenosis and represents an example of myocardial stunning.
Vascular responses of dura mater
Authors: Faraci F. M. , Kadel K. A. , Heistad D. D.
Published: December 2017

The goal of this study was to examine vascular responses of the dura mater. Microspheres were used to measure blood flow to the dura and brain in anesthetized dogs. Under control conditions, blood flow to the dura was 38 +/- 3 (SE) ml.min-1.100 g-1. Values for blood flow to the dura obtained with simultaneous injection of 15- and 50-microns microspheres were similar, which suggests that shunting of 15-microns spheres was minimal. Left atrial infusion of substance P (100 ng.kg-1.min-1) and serotonin (40 micrograms.kg-1.min-1), two agonists that have been reported to increase vascular permeability in the dura, increased blood flow to the dura two- to threefold. Adenosine (iv) produced vasodilatation in the dura. Adenosine and serotonin did not affect cerebral blood flow, but substance P increased blood flow to the brain by approximately 40%. Seizures, which produce pronounced dilatation of cerebral vessels despite activation of sympathetic nerves, produced vasoconstriction in the dura. Thus 1) the dura is perfused at a relatively high level of blood flow under normal conditions and is very responsive to vasoactive stimuli, and 2) substance P and serotonin, which have been implicated in the pathogenesis of vascular headache, produce pronounced vasodilator responses in the dura mater.
Adenosine-induced hyperemia attenuates myocardial ischemia in coronary microembolization in dogs
Authors: Hori M. , Tamai J. , Kitakaze M. , Iwakura K. , Gotoh K. , Iwai K. , Koretsune Y. , Kagiya T. , Kitabatake A. , Kamada T.
Published: December 2017

We have recently reported that coronary microembolization sustains myocardial ischemia with hyperemic response of coronary blood flow (CBF) induced by massive release of adenosine from the ischemic myocardium. In this study, we tested the hypothesis that this hyperemic flow caused by released adenosine improves myocardial ischemia. In eight dogs (control), microspheres (5.0 X 10(4)/ml of base-line CBF) were repetitively injected until CBF decreased toward zero, and the changes in CBF, fractional shortening, lactate extraction ratio (LER), and adenosine release were studied. In 15 other dogs, an identical procedure was done with an intracoronary infusion of prazosin (4 micrograms.kg-1.min-1, n = 8) or theophylline (0.1 mg.kg-1.min, n = 7) to elucidate the effect of adenosine, since prazosin inhibits release of adenosine from ischemic myocardium and theophylline blocks adenosine receptors. In 16 other dogs, hemodynamic and metabolic parameters were examined with and without these drugs after a single injection of microspheres (1.0 X 10(5)/ml of base-line CBF). In the control group, CBF increased to 170 +/- (SE) 14% of the base-line CBF at 16-30% of maximal embolization. In contrast, intracoronary infusion of prazosin markedly attenuated adenosine release and hyperemic response and significantly deteriorated both fractional shortening and LER. Theophylline also significantly attenuated the hyperemic response and tended to decrease both fractional shortening and LER. A salutary effect of adenosine release was further confirmed by the improvement of ischemic changes in the same dog after withdrawal of prazosin and theophylline associated with an increase in CBF. Thus we conclude that adenosine released from ischemic myocardium improves ischemia in microembolization through the hyperemic response.
Effects of ANP on venous pressures and microvascular protein permeability in dog forelimb
Authors: Eliades D. , Swindall B. , Johnston J. , Pamnani M. , Haddy F. J.
Published: December 2017

Intravenous administration of alpha-atrial natriuretic peptide (ANP) produces a decrease in arterial blood pressure due to a decrease in cardiac output. The mechanism of the decrease in cardiac output is unknown but has been suggested to result from transcapillary fluid efflux caused by venoconstriction and/or increased permeability of the microvascular membrane to plasma proteins. We investigated these possibilities in the dog forelimb perfused at constant flow and prepared to measure 1) large and small vessel pressures in the two parallel skin and skeletal muscle vascular beds, and limb weight; or 2) skin lymph flow and skin lymph protein concentration. In both preparations, human ANP was injected and infused into the brachial artery. Bolus injections of ANP (0.1–0.4 micrograms) depressed perfusion pressure much less than acetylcholine or an isotonic solution of potassium chloride and did not raise small vein pressures. ANP infused at nine different rates ranging from 0.1 ng to 38.8 micrograms/min failed to influence skin and muscle small and large vein pressures, limb weight, skin lymph flow, and skin lymph protein concentration. It also failed to affect perfusion pressure and skin and muscle small artery pressures until the infusion was shut off, at which time they increased above control levels. These studies suggest that human alpha-ANP is neither a direct venous constrictor nor a potent arteriolar dilator and does not directly influence the permeability of the microvascular membrane to plasma proteins in the skin and skeletal muscle of the dog forelimb.
Quantitating error in blood flow measurements with radioactive microspheres
Authors: Austin R. E. , Hauck W. W. , Aldea G. S. , Flynn A. E. , Coggins D. L. , Hoffman J. I.
Published: December 2017

Accurate determination of the reproducibility of measurements using the microsphere technique is important in assessing differences in blood flow to different organs or regions within organs, as well as changes in perfusion under various experimental conditions. The sources of error of the technique are briefly reviewed. In addition, we derived a method for combining quantifiable sources of error into a single estimate that was evaluated experimentally by simultaneously injecting eight or nine sets of microspheres (each with a different radionuclide label) into four anesthetized dogs. Each nuclide was used to calculate blood flow in 145–190 myocardial regions. We compared each flow determination (using a single nuclide label) with a weighted mean for the piece (based on the remaining nuclides). The difference was defined as “measured” error. In all, there were a total of 5,975 flow observations. We compared measured error with theoretical estimates based on the Poisson error of radioactive disintegration and microsphere entrapment, nuclide separation error, and reference flow error. We found that combined estimates based on these sources completely accounted for measured error in the relative distribution of microspheres. In addition, our estimates of the error in measuring absolute flows (which were established using microsphere reference samples) slightly, but significantly, underestimated measured error in absolute flow.