bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal regulation of oxygen delivery: hematologic parameters of postnatal dogs
Authors: Mueggler P. A. , Peterson J. S. , Koler R. D. , Metcalfe J. , Black J. A.
Published: December 2017

Hematologic parameters influencing tissue oxygen delivery in dogs during the first 4 mo of life have been investigated. The rapid growth and increase in body temperature during this period imply an increased metabolic rate and increased tissue oxygen demand. Hemoglobin concentration and hematocrit decrease during the 1st mo following birth. The total red cell mass does not decrease during this period. The observed hemodilution can be attributed to an increasing plasma volume in the growing animal. The blood oxygen affinity decreases during this same period, resulting in a more effective tissue oxygen delivery. Erythropoiesis, as estimated from the percent circulating reticulocytes, decreases following birth and does not increase until 1 mo of postnatal life. The increase of erythropoietic activity during the 2nd mo of postnatal life coincides with an increase in red cell mass, hematocrit, and hemoglobin concentration.
Postnatal changes in response of canine neonatal pulmonary arteries to histamine
Authors: Newman J. H. , Souhrada J. F. , Reeves J. T. , Arroyave C. M. , Grover R. F.
Published: December 2017

Postnatal development of histamine receptors in the canine pulmonary circulation was examined utilizing histamine cumulative dose-response curves of pulmonary arteries isolated from neonatal and adult dogs. The maximal contractile response to histamine was relatively low at birth (avg 0.069 g) and increased with postnatal age, reaching a maximum in the adult (avg 1.10 g). H2-receptor blockade with metiamide increased the contractile response to histamine during the first 2 wk of life (avg 0.38 g), suggesting H2-receptor dominance over H1-receptors in the newborn. Maximal developed tension, in response to KCl, gradually increased with postnatal age, suggesting progressive maturation of the smooth muscle response. In contrast to pulmonary arteries, isolated tracheal segments from puppies aged 1-5 days demonstrated large contractile responses (avg 5 g). Histamine (in microgram/g of wet wt of lung tissue) was absent in the lungs from 3rd trimester fetal dogs and rapidly increased over the first 2 wk of life, reaching a maximum in the adult. It is concluded that 1) the response of pulmonary arteries to histamine changes during the first 2 wk of life; 2) this change may reflect a decrease in H2-receptors and an increase in H1-receptors; 3) the contractile ability of pulmonary vascular smooth muscle increases with postnatal age; and 4) histamine is unavailable for physiological responses in the fetal dog pulmonary circulation.
Renin response to hemorrhage and hypotension in the aglomerular toadfish Opsanus tau
Authors: Nishimura H. , Lunde L. G. , Zucker A.
Published: December 2017

Renal renin and the juxtaglomerular cells evolved in primitive bony fishes, whereas the macula densa emerged later in vertebrate phylogeny. We attempted to determine whether a renal arteriolar baroreceptor exists in the toadfish Opsanus tau, which possess renin and granulated cells in the kidneys, but lack glomeruli and macula densa. Cumulative hemorrhage of 1.5, 3, 6, 12, and 18 ml/kg, or a single massive bleeding from unanesthetized toadfish, kept in 50% seawater, caused an immediate and significant decrease in mean aortic pressure and stepwise increases (5-20 times) of plasma renin activity (PRA). Papaverine (10 mg/kg) caused hypotension and increased PRA. Minoxidil (6-12 mg/kg) neither decreased blood pressure nor increased PRA. The results suggest that toadfish respond to hemorrhage and acute hypotension with renin release despite the absence of a macula densa. It remains to be determined whether decreased renal perfusion pressure due to decreased dorsal aortic pressure stimulated the receptor in the granulated cells or whether the renal nerves may be involved.
Effect of sympathetic nerves on cerebral vessels during seizures
Authors: Mueller S. M. , Heistad D. D. , Marcus M. L.
Published: December 2017

The purpose of this study was to determine the effect of activation of sympathetic pathways during seizures on cerebral blood flow and integrity of the blood-brain barrier. We measured cerebral blood flow with microspheres and disruption of the blood-brain barrier with labeled albumin in cats. One cerebral hemisphere was denervated by cutting the superior cervical sympathetic trunk on one side. During bicuculline-induced seizures, superior cervical sympathetic nerve activity increased about threefold. Blood flow to the innervated hemibrain was significantly lower than flow to denervated hemibrain. However, in relation to the total increase in flow, this effect of nerves was minor. Blood-brain barrier permeability increased about sixfold during seizures, but there was no difference between the innervated and denervated sides of the brain. We conclude that sympathetic nerves attenuate the increase in cerebral blood flow during seizures, despite the increase in metabolism, but this effect is small. Activation of sympathetic nerves does not reduce disruption of the blood-brain barrier during seizures.
In vivo measurement of blood vessel wall thickness
Authors: L'italien G. J. , Kidson I. G. , Megerman J. , Abbott W. M.
Published: December 2017

To understand the mechanical properties of arteries and vascular grafts, it is crucial that the wall thickness in these vessels be known. Unfortunately, all availble methods for measuring this parameter require the removal of the vessel, which precludes the study of such vessels as a function of time. A new radiographic technique for measuring the wall thickness of arteries and vascular grafts in vivo, utilizing contrast materials injected into the vessel lumen and applied to the outer surface of the vessel, is described. Radiographs are obtained with a portable X-ray machine and analyzed using a calibrated microscope. The technique has been successfully applied to the in vivo measurement of wall thickness in canine arteries, veins, and experimental vascular grafts. It is concluded that the method provides better than 95% accuracy in a variety of vessels and that it can be used to study changes in vascular grafts after their implantation into the arterial circulation.
Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs
Authors: Wallick D. W. , Levy M. N. , Felder D. S. , Zieske H.
Published: December 2017

A stable atrioventricular (AV) junctional rhythm was produced in open-chest dogs by injecting pentobarbital into the sinus node artery. When the cervical vagus nerves were stimulated repetitively, the junctional pacemaker cells tended to become synchronized with the vagal activity. During such synchronization, the junctional rate varied directly rather than inversely with the frequency of vagal stimulation. The magnitude of the chronotropic response depended on the timing of the vagal stimuli within the cardiac cycle. In 9 dogs, when the mean heart periods were plotted as a function of the R-st intervals (i.e., the time from the beginning of ventricular depolarization to the beginning of the stimulus burst), the mean heart periods varied from a maximum of 1,815 ms to a minimum of 1,160 ms, depending on the R-st interval. A small change in the R-st interval was capable of evoking a relatively large change in cycle length. Therefore, the impulses from various efferent vagal fibers to the AV junction must arrive almost synchronously, the released acetylcholine must be removed rapidly, and the sensitivity of the pacemaker cells to acetylcholine must change rapidly at some critical time during the cardiac cycle.
Inotropic responsiveness of atrial myocardium bathed in Tris- or bicarbonate-buffered solutions
Authors: Durrett L. R. , Adams H. R.
Published: December 2017

Atrial muscle of guinea pigs was used to study the inotropic influences of substituting a tris(hydroxymethyl)-aminomethane-buffered solution aerated with 100% O2 for a bicarbonate-buffered solution aerated with 95% O2-5% CO2 under otherwise equivalent in vitro conditions. Basal values of isometric contractile tension and its first derivative (dT/dt) were smaller and time to peak tension and time to 90% relaxation were longer in Tris- than in bicarbonate-bathed muscles. Both groups responded similarly to changes in stimulation frequently (0.1--2.2 Hz) and Ca2+ concentration (1.0--7.0 mM); however, maximal inotropic responses to these variables were smaller in the Tris-bathed atria. The negative inotropic effects of D600 and gentamicin were greater in the Tris group. Tris-bathed atria developed pulsus alternans when exposed to Mn2+ or a reduced Ca2+ concentration, whereas pulsus alternans did not occur in the bicarbonate group. A transient increase in contractility occurred in bicarbonate-bathed atria after treatment with 0.125 mM Mn2+, but only a negative response occurred in the Tris group. Thus important, and seemingly Ca2+-dependent, differences exist between the inotropic influences of Tris and bicarbonate solutions that may affect the utility of Tris-buffered (and/or bicarbonate deprived) heart muscle for studying certain inotropic interventions.
Ascending spinal pathways for the somatosympathetic A and C reflexes
Authors: Chung J. M. , Webber C. L. , Wurster R. D.
Published: December 2017

Sympathetic unit nerve activity was recorded from the cervical sympathetic trunk of anesthetized, vagotomized, and carotid sinus-denervated cats. Single pulses or short trains of pulses with suprathreshold intensity for afferent C fibers were applied to the common peroneal nerve to elicit somatosympathetic A or simultaneous A and C reflexes, respectively. Bilateral lesions of an ascending spinal pathway in the dorsolateral sulcus area (DLS) of the T12 spinal cord eliminated the sympathetic C reflex. The remaining somatosympathetic A reflex was abolished by the subsequent lesion of an ascending spinal pathway in the dorsolateral funiculus (DLF) bilaterally. The duration of the silent period was found to be mainly influenced by an ascending spinal pathway in the DLF. It was concluded that excitation of afferent A fibers activates ascending pathways mainly in the DLF and a smaller contribution in the DLS of the spinal cord. This produces a small reflex excitation (A reflex) followed by a long silent period in the sympathetic nerves resulting in a net decrease of total sympathetic nerve activity. On the other hand, excitation of afferent C fibers activates the ascending spinal pathway in the DLS. This produces a reflex excitation (C reflex) which exceeds the decreased activity due to the silent period resulting in a net increase of total sympathetic nerve activity.
Aortic nerve activation: effect of stimulus train composition on heart rate
Authors: Peterson D. F. , Meliza M. W. , Bishop V. S.
Published: December 2017

The central end of the sectioned left aortic nerve was stimulated within one heart cycle by a train of electrical pulses, producing a reflex reduction in heart rate in the anesthetized rabbit. Relative importance of the stimulation variables (train duration, pulse frequency, and pulse number) in producing bradycardia was investigated by maintaining one variable constant, while altering the other two over a wide range. At each fixed pulse frequency, maximal bradycardia was obtained by the longest train duration that corresponded with the greatest pulse number. At each fixed train duration, maximal bradycardia was achieved with pulse frequencies between 80--120 Hz and remained maximal up to 160 Hz. Stimulating over wide variations in train duration and pulse frequency at any fixed pulse number produced no significant differences in heart rate reduction at that pulse number. These results indicate the dominant importance of total pulse number per cardiac cycle in determining the magnitude of the heart rate response and reveal an apparent frequency limitation within the reflex.
On-line analysis of intracellular electrophysiological data using a microcomputer system
Authors: Elharrar V. , Lovelace D. E.
Published: December 2017

Automated analysis of intracellular action potentials from cardiac Purkinje fibers was implemented using a microcomputer system. A dual sampling rate was used during analog-to-digital conversion of action potentials recorded from stimulated fibers. The rapid phase of depolarization was sampled at 42.55 kHz. The repolarization and the diastolic phases were sampled at 1 kHz. The resting potential, action potential amplitude, conduction time, action potential duration measured at 50% and at 90% of repolarization, and the maximum upstroke velocity were obtained on-line. The digital form of the action potential was stored on cassette tape and a table containing the various measurements was assembled during the experiment. In unstimulated fibers, the time interval between consecutive action potentials was measured on-line along with the maximum diastolic potential, the action potential overshoot, and the slope of the diastolic depolarization.
Nature of load dependence of relaxation in cardiac muscle
Authors: Lecarpentier Y. C. , Chuck L. H. , Housmans P. R. , De Clerck N. M. , Brutsaert D. L.
Published: December 2017

Relaxation of spontaneously contracting single rat cardiac cells with an effective sarcoplasmic reticulum was shown to be sensitive to load, as previously described for intact mammalian ventricular cardiac muscle. Caffeine and tetanic stimulation could modify load-dependent relaxation in intact papillary muscle from cat or rat into a load-insensitive relaxation. Although such load dependence was demonstrated to be normally absent in frog ventricular cardiac muscle, in the present study it could also be made moderately manifest under specific conditions, e.g., high calcium, low sodium, or ouabain. The appearance of load dependence during relaxation in cardiac muscle thus emphasizes the presence of an effective sarcoplasmic reticulum.
Propagation velocity and reflection of pressure waves in the canine coronary artery
Authors: Arts T. , Kruger R. T. , van Gerven W. , Lambregts J. A. , Reneman R. S.
Published: December 2017

In this study the pressure wave velocity in the anterior descending branch of the left coronary artery (LADC) of the dog was measured by determining the delay time between pressure pulses along this artery. This method can only be applied if reflections of the pressure wave distal to the sites of pressure measurement are insignificant. From araldite casts of the coronary arteries the following relation between the diameter proximal to (dprox) and distal to (ddist 1, ddist 2) a bifurcation was found: dprox2.55 = ddist12.55 + ddist 22.55, indicating that reflections at a bifurcation areminimal. In dogs reflections were studied by inducing during diastole a pressure pulse in the aorta and measuring pressure and volume flow proximal to and pressure distal to a segment of the LADC at various levels of the coronary peripheral resistance. Reflection of high-frequency components (greater than 7 Hz) was found to be insignificant, allowing application of the above-mentioned method for measuring the wave-front velocity, which is insensitive to low-frequency reflection. At a pressure in the LADC of 13.3 kPa this velocity was 8.6 +/- 1.4 m.s-1 (mean +/- SD). The calculated dynamic cross-sectional stiffness (deltaP/(deltaA/A)) of the LADC was 97 +/- 11 kPa (mean +/- SE) at an arterial pressure of 13.3 kPa.
Experimental studies of the fibrinogen response to hemorrhage
Authors: Reeve E. B. , Stephens A. , Carlson T. H.
Published: December 2017

Rabbits were bled 20 ml/kg body wt over approximately 1 h, and the changes in hematocrit, plasma total protein, and fibrinogen concentrations, red cell and plasma volumes, and masses of total protein and fibrinogen in the plasma during and for 4 days after the hemorrhage were monitored. Ten percent of plasma fibrinogen was transferred from the interstitial fluids during the hemorrhage, and total plasma fibrinogen was raised to 140% of initial levels by 1 day later. 131I-labeled fibrinogen was given intravenously 1 day before a 20 ml/kg hemorrhage, and simulation methods described in the APPENDIX were used to define changes in the posthemorrhage fractional rates: transcapillary transfer rate (j1), lymphatic return rate (j2), and catabolic rate of fibrinogen (j3): j1 was unchanged but j2 increased and j3 briefly declined. In the day after hemorrhage fibrinogen synthetic rate increased approximately threefold to restore plasma fibrinogen concentrations to initial levels, but then returned to normal or subnormal levels. The alterations in j2 and j3 save about 20% of the synthetic work that would otherwise be required to restore plasma fibrinogen levels to normal.
Changes in the sensitivity of left atrial receptors following reversal of heart failure
Authors: Zucker I. H. , Earle A. M. , Gilmore J. P.
Published: December 2017

Recordings were made from left atrial type B receptors in six mongrel dogs after recovery from the cardiac effects of a chronic AV fistula. All animals showed hemodynamic and clinical signs of congestive heart failure after 44.5 +/- 3.6 days with a patent Dacron shunt between the aorta and inferior vena cava below the level of the renal arteries. The stimulus-response curves of the left atrial stretch receptors (change in spikes/cardiac cycle or in spikes/minute vs. change in left atrial pressure) after 45.2 +/- 7.2 days of shunt closure were similar to those seen in sham-operated dogs from a previous study. However, the slope of the stimulus-response curve of the dogs in which the AV fistula was closed was significantly greater than the slope of the curve from the AV fistula dogs with heart failure. Radiographs indicated that after shunt closure, cardiac dilatation had regressed. This study incidates that a decrease in the sensitivity of left atrial receptors in dogs with congestive heart failure is a reversible phenomenon and that the initial depression is most likely related to the concomitant cardiac dilatation that accompanies the failure state.
Left ventricular systolic pressure-volume area correlates with oxygen consumption
Authors: Khalafbeigui F. , Suga H. , Sagawa K.
Published: December 2017

In 13 excised, cross-circulated canine hearts, we studied the correlation between left ventricular oxygen consumption per beat (MVO2) and the magnitude of a specific pressure-volume (P-V) area circumscribed by the end-systolic and end-diastolic P-V relationship curves and the systolic segment of the P-V trajectory of a left ventricular contraction. The pressure and volume load of the ventricle were changed with a volume servo pump in order to alter the P-V area, and MVO2 was measured (after each change in the pressure and volume load). In the data collected from both isovolumic and ejecting contractions of each left ventricle contracting with a stable inotropic background, we found a linear correlation between MVO2 and the P-V area. The average correlation coefficient was 0.92 +/- 0.016 (SE). Linear regression analysis yielded the formula: MVO2 (ml/beat) = alpha[P-V area (mmHg.ml/beat)] + b, where alpha, the slope coefficient, was (1.53 +/- 0.14) x 10(-5) and b, which probably represents the basal O2 consumption, was 0.019 +/- 0.003 ml/beta. We propose that the P-V area as defined above may be a good index of ventricular oxygen consumption under a given inotropic background.
Permanent changes of ventricular contractility and compliance in chronic volume overload
Authors: Pinsky W. W. , Lewis R. M. , Hartley C. J. , Entman M. L.
Published: December 2017

Left ventricular volume overload (LVVO) has been created in 18 dogs by anastomosing a Dacron conduit between the infrarenal abdominal aorta and inferior vena cava. The dogs previously were instrumented so that in the awake state LV pressure, systemic arterial pressure, LV dP/dt, myocardial segment length and excursion, and coronary and renal artery velocities could be monitored. The animals were stressed with separate infusions of alpha-adrenergic and beta-adrenergic agonists. Both at rest and with stress, over a 12-wk period, preejection, ejection, and contractility indices decreased. Left ventricular compliance decreased as exemplified by the increased ratio of end-diastolic pressure to end-diastolic length. The shunt was ablated in 7 dogs, and monitoring in conjuction with alpha- and beta-adrenergic stress foan additional 12 wk demonstrated an initial improvement in the previous indices. However, the amelioration plateaued and values similar to the control state were not attained. This suggests that potentially permanent alterations in ventricular function and compliance have occurred.
Pressure and heart rate responses to raised carotid pressure in the toad
Authors: Segura E. T.
Published: December 2017

Neither transient nor steady occlusion of the bilateral carotid arterial trunks had noticeable effects on blood pressure or heart rate of the toad Bufo arenarum Hensel. Distension of isolated carotid labyrinths had no circulatory effects, whereas distension of unisolated carotid trunks by fluid infusion caused an increase in blood pressure proportional to the applied pressure. A simultaneous tachycardia was recorded. These circulatory effects seem to depend on the venous return to the heart because carotid distension was followed by a proportional rise in right atrial pressure. Consequently infusion of small volumes of saline into the right atrium also promoted tachycardia and hypertension. These responses seem not to depend on central nervous mechanisms because they persisted after complete deafferentation or removal of the bulbomesencephalic centers.
Changes in the diastolic pressure-diameter relation after ventricular function curves
Authors: Misbach G. A. , Glantz S. A.
Published: December 2017

Systolic performance depends on end-diastolic muscle fiber length, contractility, and afterload. Ventricular function curves are constructed using end-diastolic pressure instead of end-diastolic dimensions, on the assumption that end-diastolic pressure and end-diastolic dimensions (reflecting muscle fiber length) have a constant relation. That assumption has been rejected. Theorectically, ventricular function curves should change with changes in the diastolic pressure-dimension relation as well as with contractility or afterload. We measured pressures and dimensions in ventricles of six open-chest dogs before and after opening the pericardium to alter diastolic pressure-dimension relations with afterload constant. When an indicator of systolic performance (developed pressure times diameter change during systole) was plotted against end-diastolic pressure, data obtained with the pericardium closed and open resulted in two distinct curves, suggesting an increase in contractility with the pericardium open. However, when systolic performance was plotted against end-diastolic diameter, data obtained with the pericardiumclosed and open fell along one curve, indicating no change in contractility. Therefore, changes in the diastolic pressure-dimension relation to shift conventional ventricular function curves.
Interaction between the baroreceptor and Bezold-Jarisch reflexes
Authors: Chen H. I.
Published: December 2017

The interaction between the carotid baroreflex and Bezold-Jarisch (BJ) reflex (intravenously administered veratridine) was studied in anesthetized rabbits after aortic nerve section. The carotid sinuses were vascularly isolated to regulate the intrasinus pressure (ISP). The extent of BJ reflex bradycardia and hypotension was progressively diminished as the ISP was elevated stepwise. When the carotid baroreflex was not operative by holding the ISP constant at control, the BJ reflex changes in heart rate (HR) and systemic arterial pressure (SAP) were not significantly different from those induced at the normal condition. Thus the calculated baroreflex static loop gain was greatly decreased during the BJ reflex. However, sinus denervation, analogous to keeping ISP below 50 mmHg, significantly enhanced the BJ reflex effects. A steady-state infusion of veratridine remarkably reduced the slope of the baroreflex function ISP-SAP and ISP-HR curves. The results indicate that the BJ reflex effects are affected by the prevailing arterial baroreceptor input, varying inversely with the ISP level. An attenuation in the baroreflex sinsitivity, in terms of the loop gain or slope of the transfer function curve, was observed during the BJ reflex. The presence of tonic cardiovascular inhibitions exerted by the arterial baroreceptors tends to reduce the BJ reflex bradycardia and hypotension, but the baroreceptors do not function adequately in buffering the cardiovascular inhibition produced by the cardiogenic reflex.
Analysis of oxygen diffusion from arteriolar networks
Authors: Popel A. S. , Gross J. F.
Published: December 2017

A mathematical model of oxygen transport in the precapillary microcirculation is presented. The theory is then used to simulate oxygen distribution in the arteriolar network of the hamster cheek pouch. Theoretical prediction of transmural and longitudinal oxygen tension (PO2) gradients is in qualitative agreement with available experimental data. The effect of the variation of inlet network PO2, blood flow rate, blood hematocrit, and other parameters on the transport characteristics is studied. The calculations predict that the luminal PO2 in small arterioles is practically independent of the inlet network PO2 leve if the latter is sufficiently high; when this inlet PO2 level is low, then the longitudinal gradients of luminal PO2 vanish. It is further shown that retardation of blood flow may cause a significant increase in precapillary oxygen losses.
Preservation of ischemic myocardium by pinane thromboxane A2
Authors: Schror K. , Smith E. F. , Bickerton M. , Smith J. B. , Nicolaou K. C. , Magolda R. , Lefer A. M.
Published: December 2017

Pinane thromboxane A2 (PTA2), a thromboxane A2 analog has been shown to antagonize the vasoconstriction and platelet aggregation induced by thromboxane A2, in addition to specifically inhibiting thromboxane synthetase. Because thromboxane A2 generation would be detrimental in acute myocardial ischemia (MI) by both decreasing coronary blood flow and increasing platelet aggregation, inhibition of thromboxane production and action may be beneficial in myocardial ischemia. In pentobarbital-anesthetized cats, the left anterior descending coronary artery was ligated, and PTA2 (0.5 mumol . kg-1 . h-1) or a Na2CO3 vehicle was infused 30 min post-MI for 270 min. Compared to vehicle-treated MI cats, PTA2 prevented the increase in plasma thromboxane levels seen at 2 through 5 h (P less than 0.005 at 2 through 5 h) and prevented the large increase in plasma CK activities at 4 and 5 h (P less than 0.025). In addition, PTA2 treatment abolished the differences in myocardial CK activities between ischemic and nonischemic regions and prevented the decrease in percent-bound cathepsin D in the ischemic region. Moreover, ECG analysis revealed a decreased incidence of premature beats in PTA2-treated MI cats as compared to MI-vehicle cats. In summary, these data indicate that PTA2 protects the ischemic myocardium and provide further evidence that inhibition of thromboxane formation, in addition to antagonism of its activity, is beneficial during the early stages of acute myocardial ischemia.
Adenosine release during early and sustained exercise of canine skeletal muscle
Authors: Tominaga S. , Curnish R. R. , Belardinelli L. , Rubio R. , Berne R. M.
Published: December 2017

During contraction of skeletal muscle in the isolated dog hindlimb under constant-flow perfusion, the specific activity of infused [8- 14C]adenosine (nonvasoactive concn) in venous effluents decreased to 7% of the resting level in 1.25 min and was associated with a concomitant decrease in vascular resistance to 39% of the resting value. Since this decrease in specific activity of labeled adenosine could have been due to 1) an enhanced adenosine release by parenchymal tissue, 2) an exercise-induced increase in the number of open capillaries (greater surface area) in the absence of increased adenosine production 3) some degree of tissue hypoxia, or 4) a combination of these factors, experiments with maximally dilated vessels were performed. Acetylcholine and a nonvasoactive concentration of [8- 14C]adenosine were continuously infused into an isolated dog hindlimb which was perfused at constant flow during periods of rest, contraction, and recovery while arterial oxygenation was maintained at normoxic levels. Approximately 2.75 min after the onset of contraction with the vascular bed maximally dilated, the specific activity of [8- 14C]adenosine in venous effluents decreased to 38% of the resting level while the venous Po2 decreased from 78 to 42 mmHg; the value of 42 mmHg indicates apparent absence of hypoxia in the muscle. These observations are consistent with the concept that adenosine release is involved in the vasodilation observed in contraction of skeletal muscle.
Method for morphophysiological study of specific pial microvessels
Authors: Dietrich W. D. , Wei E. P. , Povlishock J. T. , Kontos H. A.
Published: December 2017

A method is described whereby specific segments of the pial vasculature of cats can be both physiologically and morphologically studied. This is accomplished by the insertion of a cranial window through which specific pial vessels can be visualized, illustrated, numbered in a simple sketch, and physiologically evaluated under both control and experimental conditions. Following these procedures, perfusion of aldehydes is initiated and the pia and associated vasculature are stripped from the cortical mantle. The thin velum of pia so obtained permits the direct visualization of the pial vasculature whose unchanged configuration can be matched to the appropriate previously sketched vessels whose individual physiological status is known. In turn these vessels are divided into alternate segments and are prepared for either scanning or transmission electron microscopy. The advantages of this methodology is exemplified by the fact that it provides the physiological status and morphological characteristics of the same microvascular segment. Although designed for the pial vasculature, this protocol may also prove of use in the study of other superficially coursing microvascular beds.
Cytoprotective actions of prostacyclin during hypoxia in the isolated perfused cat liver
Authors: Araki H. , Lefer A. M.
Published: December 2017

The cytoprotective effect of prostacyclin (PGI2) was examined using hypoxic cat livers perfused with Krebs-Henseleit buffer at constant flow. PGI2 infusion (10 ng . g-1 . min-1) showed no direct vasodilator effect on the hepatic circulation under conditions of normoxia or hypoxia, as studied by changes in perfusion pressure. Hypoxia induced a marked decline in hepatic oxygen consumption, an increase in perfusion pressure, and in perfusate cathepsin D and LDH activity in the hepatic effluent indicating lysosomal and cytoplasmic leakage. Tissue samples, obtained 150 min after hypoxic perfusion, showed higher percent-free cathepsin values (82 +/- 4%, mean +/- SE, 7 livers, P less than 0.025) compared to that of normoxia (58 +/- 4). Phagocytic activity, measured by the clearance rate of colloidal carbon particles, was also depressed by hypoxia. PGI2 infusion significantly inhibited the posthypoxia leakage of liver cathepsin D and LDH into the recirculating perfusate, restored the percent-free cathepsin D to 64 +/- 3%, and preserved the phagocytic activity during hypoxia, indicating preservation of lysosomal and cytoplasmic membrane integrity and Kupffer cell phagocytic function. The preservation of lysosomal integrity by PGI2 was further confirmed by electron microscopy. It is evident that PGI2 has a significant protective effect in hypoxic hepatocytes that may not be related to its vasodilation and inhibition of platelet aggregation.
Role of prostaglandins in pial arteriolar response to CO2 and hypoxia
Authors: Wei E. P. , Ellis E. F. , Kontos H. A.
Published: December 2017

The effect of inhibition of prostaglandin synthesis on the pial arteriolar responses to arterial hypercapnia, hypocapnia, and hypoxia was studied in anesthetized cats equipped with a cranial window for the observation of the pial microcirculation of the parietal cortex. Inhibition of prostaglandin synthesis was achieved by intravenous administration of indomethacin (3 mg/kg) or AHR-5850 (2-amino-3-benzoylbenzeneacetic acid, 50 mg/kg). It was shown that the administration of these agents inhibited substantially the vasodilation in response to topical application of arachidonic acid (100--200 micrograms/ml). Inhibition of prostaglandin synthesis did not modify significantly the vasodilator responses to arterial hypercapnia or arterial hypoxia, nor the vasoconstrictor response to arterial hypocapnia. We conclude that endogenous prostaglandins are not mediators of these vascular responses in the pial microcirculation.
Acetylcholine lengthens action potentials of sheep cardiac Purkinje fibers
Authors: Lipsius S. L. , Gibbons W. R.
Published: December 2017

The effect of acetylcholine (ACh) on the electrical activity of sheep cardiac Purkinje fibers was studied using standard microelectrode techniques. Most fibers showed a definite sequence of changes when exposed to ACh. Initially, action potential duration (APD) increased markedly. After about 20 s, the maximum diastolic potential (MDP) started to become more negative and, at the same time, the rate of increase in APD slowed. Once the MDP stabilized at a more negative level, the APD usually resumed its rapid increase. ACh also increased the slope of diastolic depolarization and made the plateau voltage more positive. APD was increased by ACh concentrations as low as 10(-7) M, and it increased with concentrations up to 10(-5) M (the highest concentration tested). ACh-induced increases in APD depended on the stimulation frequency; 2-min exposures to 10(-6) M ACh increased APD by 76.8 +/- 14.7% at 6 min-1 and 17.7 +/- 4.2% at 60 min-1. Atropine blocked all the effects of ACh. Hexamethonium did not prevent the ACh effects. It is concluded that ACh acts via muscarinic receptors. The changes in APD and MDP appear to be separate events, and it is difficult to see how the former effect may be explained by known actions of ACh.
Implication of renal perfusion pressure in stroke of spontaneously hypertensive rats
Authors: Nagaoka A. , Shino A. , Shibota M.
Published: December 2017

To elucidate the significance of hypertension associated with cerebrovascular lesions (CVL), renal perfusion pressure (RPP) was controlled by aortic clips of two different sizes in stroke-prone spontaneously hypertensive rats kept under normal or salt-loaded conditions. Tail and femoral arterial pressures (RPPs) in the mildly and severely clamped animals were reduced in proportion to the severity of the clamping. In contrast, carotid pressures in both clamped groups were significantly higher than that in the controls. Proteinuria and hyperreninemia accompanied by arteriolar changes in the renal cortex were observed in the controls prior to the onset of CVL. The renal changes were inhibited by both types of clamping. The onset of CVL was delayed by the mild clamping in salt-loaded animals, but accelerated by the severe clamping in both the normal and salt-loaded animals. Renal cortical blood flow was decreased only by the severe clamping. The results suggest that reduction in RPP and/or renal ischemia, which seems to be due to the hypertensive arteriolar changes in the renal cortex, may be related to the pathogenesis of CVL in the stroke-prone rats with or without hyperreninemia.
Responses of peak ear-pulse derivative to changing left ventricular function
Authors: Nakamura Y. , Haffty B. G. , Spodick D. H. , Paladino D. , Moreau K. , Flessas A. P.
Published: December 2017

The ear densitograph displacement pulse derivative (dD/dtear) is the analog of the arterial pressure derivative (dP/dt) and behaves comparably under a variety of cardiocirculatory challenges. Technical reliability and uniform application of the transducer are advantages that make it ideal for intrasubject monitoring. With atrial fibrillation as a model of functional variability in eight subjects, peak dD/dtear (P) tracked echocardiographic stroke volume, ejection fraction, ejection rate, and velocity of circumferential fiber shortening quite closely with the exception of some values in three subjects, two of whom had mitral regurgitation and one paradoxic septal movement. In all subjects, P showed good to excellent correlations with cycle length, preejection period (PEP), LVET (left ventricular ejection time), and PEP/LVET. The method appears to be ideally suited to intrasubject monitoring for changing ventricular function.
Effect of hemorrhage on blood flow to marrow and osseous tissue in conscious rabbits
Authors: Syftestad G. T. , Boelkins J. N.
Published: December 2017

The effect of hemorrhage on blood flow to marrow and osseous tissue was determined in conscious rabbits by injecting radioactive microspheres (15 micron diam) at three time intervals: pretreatment control; 15 min after nonfatal hemorrhage (20 ml/kg body wt), and 16 h posthemorrhage. Cardiac output (CO), blood pressure, heart rate, resistance, arterial PCO2, PO2, and pH, and hematocrit were measured at each time interval. Tissues analyzed included heart, spleen, kidney, and femur with marrow and osseous tissue separated. At 15 min posthemorrhage, CO decreased to all tissues measured except the heart, where it increased. Sixteen hours later, CO returned to normal, and blood flow increased significantly to heart and marrow, while osseous tissue flow returned to control levels. The results show no immediate shunting of blood from bone to marrow; however, after 16 h there is a selective increase in marrow blood flow. This response is only detected by separating marrow and osseous tissue and it may reflect a preparatory mechanism for increased erythropoietic activity.
Myocardial oxygen and carbohydrate consumption in fetal lambs in utero and in adult sheep
Authors: Fisher D. J. , Heymann M. A. , Rudolph A. M.
Published: December 2017

We measured myocardial oxygen, glucose, lactate, and pyruvate consumption in chronically instrumented fetal and adult sheep. Although ascending aortic blood concentration of oxygen was significantly lower in fetuses, myocardial consumption of oxygen was similar in the two groups. This was accomplished by a significantly greater myocardial blood flow in the fetuses. Although ascending aortic blood glucose concentration was significantly lower in fetuses, myocardial consumption of glucose was significantly greater in fetuses. Complete oxidative combustion of all glucose consumed by the fetal heart would supply only one-third of myocardial energy demands, as measured by oxygen consumption. Ascending aortic blood concentration of lactate was similar in fetuses and adults, but myocardial consumption of lactate was significantly greater in fetuses. Complete oxidative combustion of all lactate consumed by fetal hearts would supply almost 60% of myocardial energy demands. Small, but significant, amounts of pyruvate are consumed by both fetuses and adults. Our data indicate that fetal lamb myocardium requires substrates other than glucose alone. The large amount of lactate consumed indicates that there is oxidative metabolism in addition to glycolysis and that lactate is of equal, or perhaps greater, importance as a myocardial energy substrate.
Indices of sympathetic activity in the sinoaortic-denervated hypertensive rat
Authors: Alexander N. , Velasquez M. T. , Decuir M. , Maronde R. F.
Published: December 2017

Blood pressure and circulating levels of norepinephrine (NE), epinephrine (Epi), and dopamine-beta-hydroxylase (DBH) were measured sequentially in sinoaortic-denervated (SAD) Wistar rats and in sham-operated (SO) rats. Systolic tail pressure, plasma NE and E, and plasma DBH all increased significantly within 2 days in SAD rats. In separate studies of rats with indwelling arterial catheters, arterial pressure and plasma NE and DBH were increased in SAD rats in home cages; restraint caused similar increases of pressure and catecholamines in both groups. Systolic pressure remained increased up to 4 mo and plasma DBH for 10 wk in SAD rats; plasma NE and E, however, declined by 3 wk and thereafter remained close to values of SO rats. Additionally, DBH was increased in heart, mesenteric blood vessels and adrenal glands of SAD rats up to 6 wk; tissue monoamine oxidase activity was also increased up to 4 mo. These findings suggest that activation of the sympathetic nervous system initiates and probably sustains hypertension in SAD rats up to 6 wk after operation; thereafter some other mechanism(s) sustains the hypertension.
Volumetric properties of intracellular compartments in canine cardiac Purkinje cells
Authors: Houser S. R. , Freeman A. R.
Published: December 2017

Volumetric properties of canine cardiac Purkinje fibers were examined. Purkinje cells were superfused with anisosmolar solutions, and changes in extracellular space and relative cell volume were determined. The relationship between cellular volume and the osmolarity of the bathing medium was shown to be linear except in solutions of very low osmolarity. A linear regression line crossed the volume axis at 38%, suggesting an osmometric dead space of 38% and correspondingly an osmometric compartment comprising about 62% of the cell interior. To determine the volumetric properties of the "electrophysiological compartment," Purkinje cells were impaled with voltage-sensitive microelectrodes, and cellular resting potentials were recorded. When log K was plotted against resting potential (Em) in preparations bathed in normal and hyperosmotic solutions, it was shown that Em was increased in hyperosmotic solutions (13.5 and 21 mV in 600 and 850 mosM solutions, respectively). Calculations using the Nernst equation showed that the compartment containing the intracellular K involved in membrane electrical events behaves as a near-perfect osmometer in hyperosmotic solutions. Changes in the osmometric compartment were well correlated with K changes in the electrophysiological compartment, thus suggesting that the K is homogeneously distributed intracellularly.
Nonmetabolically coupled coronary vasodilatation during inosine infusion in dogs
Authors: Jones C. E. , Mayer L. R.
Published: December 2017

Left ventricular contractile force (LVCF), dP/dt, arteriovenous oxygen difference [(a-v)O2], circumflex blood flow (CBF), and myocardial oxygen consumption (MVo2) were determined in dogs during intravenous infusion of inosine at various rates. LCVF and maximal dP/dt increased progressively with increasing infusion rates. CBF increased by 100% at the highest infusion rate, but (a-v)O2 was reduced by 30%. At each infusion rate the increase in MVo2 was only 40% the increase in CBF (P less than 0.05), indicating a nonmetabolically coupled vasodilatation. To further demonstrate this action, the effects of isoproterenol on CBF and (a-v)O2 were compared with those of inosine. During isoproterenol infusion, the increase in CB paralleled the increase in MVo2, and (a-v)O2 showed no change. Intracoronary infusion experiments showed that a 100% increase in flow was caused by an arterial inosine level of about 150 micro M. At inosine levels over 400 micro M, the increase in flow was equal to the maximal increase seen with adenosine infusion.
Effect of body hypothermia on transventricular simple-capacitor-discharge defibrillation thresholds
Authors: Arredondo M. T. , Armayor M. R. , Clavin O. E. , Valentinuzzi M. E. , Scida E. E.
Published: December 2017

In 260 successful transventricular simple capacitor-discharge defibrillations performed on 20 mongrel dogs under conditions of body hypothermia, an overall average peak current threshold of 69.5 mA/g of heart (SD 30.4) was found. This value, when compared by means of the unpaired t test with previous data obtained under conditions of relative normothermia (89.5 mA/g of heart, SD 32.8, 346 defibrillations, 20 dogs) yielded a highly significant difference (P less than 0.1%). When comparing the deviation of the regression equation (current vs. temperature) from the horizontal line, the Snedecor F test gave also a high level of significance (P less than 1%). These results led to the conclusion that body hypothermia significantly reduces transventricular defibrillation thresholds. After normalizing the regression equations, this reduction was found to be on the average equal to 4.1%/degrees C (SD 1.4) for current and to 5.9%/degrees C (SD 1.4) for energy over the 20 dogs. In all animals, the coefficient of variation was greater for energy than for current (about twice as much), suggesting that current is a better descriptor of what is needed for electrical defibrillation. The transventricular impedance was rather constant, yielding an overall average of 28.5 omega (SD 6.0).
Thermodynamic technique for the quantification of regional blood flow
Authors: Adams T. , Heisey S. R. , Smith M. C. , Steinmetz M. A. , Hartman J. C. , Fry H. K.
Published: December 2017

A method is described to quantify regional blood flow by thermal analysis. A weak temperature field is established in a tissue and for a thermal steady state, unidirectional heat flux and the associated temperature gradient are measured simultaneously across a small fixed segment of the tissue. This information is evaluated with probe calibrations for homogeneous isotropic fluids, with data from ancillary measurements in the nonperfused tissue and with values of specific heat and density of blood to express local blood flow in heat transfer [effective thermal conductivity (W. degrees C-1 . cm-1 x 10(-3) and/or in perfusion (ml . min-1 . cm-3)] terms. The technique measures local perfusion in small tissue volumes and is usable in acute or chronic experiments. Its accuracy is not a function of the absolute steady-state temperature of the tissue or of its metabolic heat production.
Microvessel mean transit time and blood flow velocity of sulfhemoglobin-RBC
Authors: Baker C. H. , Sutton E. T. , Davis D. L.
Published: December 2017

An indicator dilution technique is described for obtaining time-concentration curves subsequent to bolus injections of sulfhemoglobin red blood cells (SH-RBC), which have a deep greenish-brown color (absorption peak 620 nm vs. 542 and 564 nm for normal red cells). The series- and parallel-coupled microvessels of cat mesentery were studied. This is accomplished by means of video microscopy with a two-window intensity-sensitive video sampler system. The relationship between SH-RBC concentration in blood and optical measurement is linear. Blood flow velocities were calculated from the difference in mean transit times between two points along a vessel. When this technique is used in association with the previously reported method for determining time-concentration curves for the plasma indicator FITC-dextran the mean transit time (t) for red blood cells was less than for plasma in arterioles. The reproducibility of t and flow velocity for both SH-RBC and FITC-dextran from successive injections were reported. The mean transit time ratio of arteriolar SH-RBC to FITC-dextran averages 0.89. Blood flow velocity calculated from SH-RBC is greater than that calculated from FITC-dextran in these same arterioles. The ratio of the velocities averages 1.29.