bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of gain of tachycardia and bradycardia responses of cardiac baroreflex
Authors: Kingwell B. A. , McPherson G. A. , Korner P. I.
Published: December 2017

The cardiac baroreflex was studied in humans by means of vasoactive drugs and in conscious rabbits by the drug and perivascular cuff methods, which provide somewhat different afferent drive. Mean arterial pressure (MAP)-heart rate (HR) curves were derived using 1) a single symmetric logistic function and 2) a compound function, where the two halves of separate logistic functions were centered on the resting value, one for the tachycardia response and the other for the bradycardia response. There were some differences in overall reflex parameters (plateaus, HR range, gain) between the two methods because of minor degrees of asymmetry. But the differences were small, and the single symmetric logistic adequately describes the overall properties. With the compound function, we assessed average gain, Gt and Gb, for the tachycardia and bradycardia responses and the corresponding normalized (range-independent) gains, Ct and Cb. The resting HR has a large effect on Gt/Gb, since it determines the HR range of each logistic. Moreover, Gt/Gb depends on both resting autonomic tone and reflex changes. However, Ct and Cb provide information about "intrinsic" differences in sensitivity; they are independent of resting HR but entirely dependent on reflex autonomic changes. In rabbits Ct and Cb tended to be larger with the cuff than with the drug method; in addition, with the former Ct less than Cb, whereas with the drug method Ct greater than or equal to Cb, which was consistent with differences in afferent drive. There were also differences between humans and rabbits in Ct/Cb of the vagal component of the reflex. The assessment of the normalized gains of the compound logistic function has substantial advantages over previous methods for assessing gain of the tachycardia and bradycardia responses.
Arousal responses to hypertension in lambs: effect of sinoaortic denervation
Authors: Horne R. S. , De Preu N. D. , Berger P. J. , Walker A. M.
Published: December 2017

Newborn lambs were subjected to hypertensive stimuli of 1-min duration to examine features of hypertension-induced arousal from sleep. Reflex mechanisms involved were studied by performing the same tests after sinoaortic denervation (SAD). In intact lambs, hypertension increased the probability of arousal from both quiet sleep (QS) and rapid-eye-movement (REM) sleep. Hypertension resulted in arousal in 51% (QS) and 50% (REM) of tests. Arousal time was significantly longer in REM (29.3 +/- 0.9 s, mean +/- SE) than in QS (22.6 +/- 0.6 s, P less than 0.01). Arterial oxygen saturation (So2) and partial pressure of oxygen (Po2) measured at the point of arousal, or after 60 s if arousal failed to occur, were unchanged from control values. After SAD hypertension did not increase the probability of arousal. Arousals significantly decreased (P less than 0.001) to 31% (QS) and 10% (REM). These findings indicate that acute hypertension, mediated via arterial baroreceptors, is a potent stimulus for arousal. In intact lambs, the arousal probability increased and arousal time decreased with increasing stimulus strength (1-30 mmHg), but the arousal time difference between QS and REM remained constant. Consideration of these findings in terms of a simple baroreflex threshold model suggests that the slower response in REM sleep is explained by slower neural processes after the achievement of a critical arousal input rather than by a higher threshold for baroreceptor input in this state.
Hyperoxemic reperfusion does not increase myocardial infarct size
Authors: Shnier C. B. , Cason B. A. , Horton A. F. , Hickey R. F.
Published: December 2017

We tested the hypothesis that arterial hyperoxia during myocardial reperfusion increases reperfusion injury and infarct size. The anterolateral marginal coronary artery of 35 anesthetized rabbits was occluded for 45 min, then reperfused for 3 h with either normoxic [arterial PO2 (PaO2) = 96.7 +/- 22.9 mmHg)] or hyperoxic (PaO2 = 554.8 +/- 61.7 mmHg) blood. In the hyperoxic group only, PaO2 was adjusted 10 s before the onset of reperfusion by raising inspired oxygen concentration to 100%. The area of infarction (AI) was defined by triphenyltetrazolium staining, and the area at risk (AR) by fluorescent microspheres. These areas were measured by planimetry. Heart rates and blood pressures did not differ between the two groups during occlusion or reperfusion. Infarct size (AI/AR) was 49.1 +/- 16.5% in the normoxic group (n = 17) and 40.8 +/- 16.1% in the hyperoxic group (n = 18). From these data, 90% confidence limits establish that the maximal true increase in AI/AR caused by hyperoxia would be 0%-1%. Hyperoxic reperfusion of ischemic myocardium compared with normoxic reperfusion does not significantly increase myocardial infarct size.
Sympathectomy stimulates capillary but not precapillary growth in hypertrophic hearts
Authors: Torry R. J. , Connell P. M. , O'Brien D. M. , Chilian W. M. , Tomanek R. J.
Published: December 2017

Sympathetic nerves are known to influence vascular growth, but their role in coronary vascular adaptations to pressure-overload left ventricular (LV) hypertrophy is unknown. Accordingly, regional sympathectomy (SYMX) was produced by painting a ring of phenol on the posterior third of the LV in seven renal hypertensive (Page: 1 kidney, 1 wrap) and seven normotensive (sham: 1 kidney, no wrap) rabbits. Two months later, maximal myocardial blood flow (MBF) following dipyridamole-induced coronary vasodilation was determined with microspheres in the intact anterior and the sympathectomized posterior regions of conscious rabbits. Histomorphometric methods were then utilized to evaluate capillary density (CD), intercapillary distance (ICD), and volume density (VD) of subepicardial and endocardial samples of each region of perfused-fixed hearts. The Page procedure significantly increased systolic blood pressure (+29%) and LV wt/body wt (+20%) above sham rabbits. In both sham and Page groups, MBF was not significantly different between intact and sympathectomized regions within either group. SYMX did not significantly alter CD, ICD, or VD between regions in the sham animals. In contrast, SYMX significantly increased CD (+30%) and VD (+26%) and decreased ICD (-21%) in the subendocardial region of Page animals. Regional SYMX did not alter myocyte cross-sectional area in Page animals. We conclude that SYMX neither 1) significantly increases resistance vessel cross-sectional lumen area in either normal or hypertrophic hearts, nor 2) significantly influences capillary growth in normal hearts, but SYMX does 3) promote capillary growth in hearts undergoing hypertrophy in response to hypertension.
Differential actions of albumin and plasma on capillary solute permeability
Authors: Huxley V. H. , Curry F. E.
Published: December 2017

We tested the hypothesis that albumin regulates the solute permeability coefficients (Ps) of individually perfused exchange microvessels of the frog mesentery by mechanisms similar to those described for hydraulic conductivity. Using unbound Evans blue dye (T-1824, mol wt 960, 1.3 nm radius) as a test solute, we demonstrated a hysteresis of PT-1824s on luminal albumin content as perfusate albumin concentration was first reduced in three steps from 1 mg/ml to zero and then returned to 1 mg/ml. PT-1824 s did not return to initial control values. The same result was found with tetramethylrhodamine isothiocyanate-alpha-lactalbumin (mol wt 14,176; 2.0 nm radius) even when the perfusate albumin concentration was increased by 10-fold to 10 mg/ml. In contrast, frog plasma at the same total protein concentration restored P alpha-lactalbumin s to values below those measured with control albumin perfusates before Ringer perfusion. Our results conform to the hypothesis that a plasma factor (possibly orosomucoid) that modifies the charge selectivity of the microvessel wall is removed from the microvessel membrane during protein-free Ringer perfusion and is not restored by reperfusion with albumin alone.
Interactions between alpha-adrenoceptors and adenosine receptors on microvascular smooth muscle
Authors: Nishigaki K. , Faber J. E. , Ohyanagi M.
Published: December 2017

alpha 2-Adrenoceptor but not alpha 1-adrenoceptor constriction of arterioles is selectively inhibited by tissue acidosis, ischemia, and increased metabolic rate. To further examine neural-local interactions, we studied the effect of adenosine receptor stimulation on alpha 1- or alpha 2-adrenoceptor constriction. Intravital microscopy was used to study large arterioles (133 +/- 3 microns diam; mean +/- SE), small arterioles (16 +/- 1 microns), and large venules (178 +/- 3 microns) of rat cremaster skeletal muscle. Concentration-response (diameter change) curves were obtained for bath-added norepinephrine in the presence of either rauwolscine or prazosin to provide selective alpha 1- and alpha 2-constriction, respectively. The adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (2.24 x 10(-8) M) significantly attenuated both alpha 1- and alpha 2-constriction by 5- to 20-fold; alpha 1-constriction was three- to fourfold more sensitive than alpha 2-constriction. Similar inhibitory effects were obtained with adenosine (2.24 x 10(-6) M). The adenosine receptor antagonist 8-[4-[N(2-aminoethyl)carbamoylmethoxy]phenyl]-1,3-dipropylxanthine (0.7 microM) reversed the inhibitory effect of adenosine, which implicates extracellular A2 adenosine receptors. Intrinsic tone in large vessels was unaffected by adenosine receptor stimulation but was completely inhibited in small arterioles. These findings suggest that both alpha 2- and especially alpha 1-adrenoceptor constriction and intrinsic tone (of small but not large arterioles) are inhibited by physiologically relevant concentrations of adenosine.
Sulfated polysaccharides inhibit leukocyte rolling in rabbit mesentery venules
Authors: Ley K. , Cerrito M. , Arfors K. E.
Published: December 2017

Before firm adhesion, leukocytes roll slowly along the walls of small venules at velocities ranging from 0.7 to 36% of mean blood flow velocity. To investigate the nature of the adhesive process underlying leukocyte rolling, synthetic (dextran sulfate) and naturally occurring sulfated polysaccharides (heparin, chondroitin sulfates, keratan sulfate, and heparan sulfate) were infused via glass micropipettes into the lumen of small venules (20–60 microns diam) of the rabbit mesentery. Leukocyte rolling was observed and quantified using both transmitted light and incident fluorescence intravital microscopy. Rolling leukocytes accounted for 27–80% of total leukocyte flux, exhibiting a wide range of individual velocities (0.01–0.84 mm/s) with a mean value of 4% of centerline velocity. Dextran sulfate (Mr 500,000) inhibited leukocyte rolling very effectively [half-effective concentration (ED50) approximately 10 micrograms/ml] and was able to almost completely abolish rolling at 500 micrograms/ml. Heparin (ED50 approximately 50 micrograms/ml), chondroitin 6-sulfate C (ED50 approximately 500 micrograms/ml), and heparan sulfate (ED50 approximately 5 mg/ml) also reduced leukocyte rolling. At 5 mg/ml, chondroitin 4-sulfate B (dermatan sulfate) was marginally effective, but chondroitin 4-sulfate A and keratan sulfate were ineffective. The present data suggest that an adhesion receptor-ligand system distinct from the leukocyte integrins may be underlying transient leukocyte adhesion (rolling). Endothelial glycoproteins or proteoglycans containing sulfated side chains may be involved in mediating this adhesive process.
Endotoxin-induced alterations in contractility of isolated blood vessels from sheep
Authors: Nelson S. , Steward R. H. , Traber L. , Traber D.
Published: December 2017

The present study examined reactivity to norepinephrine (NE) and KCl in isolated, suffused blood vessels from the systemic and pulmonary circulations of endotoxin-treated and control sheep. A possible mechanism underlying an endotoxin-induced alteration in vascular reactivity was also investigated. Chronically instrumented sheep were given Escherichia coli endotoxin (1.5 micrograms/kg). Eight to 12 h later these endotoxin-treated animals exhibited a significantly increased cardiac output and decreased systemic vascular pressure and resistance. The pulmonary vascular pressure and resistance were not changed. The isolated superficial femoral artery from the endotoxin sheep exhibited depressed contractions in response to KCl (75 mM) and to NE (10(-7)-10(-5) M), whereas the pulmonary artery (tertiary branch) did not exhibit altered reactivity. The decreased sensitivity to NE in the femoral artery from endotoxin sheep did not appear to involve an alteration of alpha- or beta-adrenoceptors, or an increased release of vasodilator prostanoids, or endothelium-derived relaxing factor.
Coronary input impedance is constant during systole and diastole
Authors: Judd R. M. , Mates R. E.
Published: December 2017

Although it is well known that coronary inflow decreases substantially during systole, the mechanism responsible for this decrease remains controversial. Knowledge of how coronary input impedance is affected by contraction can differentiate between some of the proposed mechanisms. In open-chest dogs, we have measured coronary inflow in the beating heart both during constant-pressure perfusion and during 10-Hz sinusoidal pressure oscillations around the same constant pressure. By exploiting the principle of superposition, we have shown that coronary input impedance remains unchanged between systole and diastole. Using this result, we have shown that a simple lumped-parameter model with constant resistance and compliance can describe coronary inflow at heart rates of 60, 90, 120, and 150 beats/min both with vasomotor tone intact and during maximal coronary vasodilation. Coronary resistance and compliance determined using the model are comparable to those obtained in our laboratory and by others during normal diastoles and in the arrested heart. The results suggest that, despite large increases in myocardial tissue stresses during systole, coronary resistance and compliance as determined using inflow measurements are constant during systole and diastole.
Convergence of sympathetic, vagal, and other sensory inputs onto neurons in feline ventrolateral medulla
Authors: Blair R. W.
Published: December 2017

Responses of 80 neurons in rostral and caudal ventrolateral medulla to multiple sources of sensory input were assessed in cats anesthetized with alpha-chloralose. Sixty-one of eighty-one neurons (76%) were excited by stimulation of the stellate ganglion, and one neuron exhibited inhibition followed by excitation. In response to vagal stimulation, 12% of the neurons were excited and 29% inhibited. Vagal stimulation reduced the responses of 13 of 39 (33%) neurons to sympathetic stimulation. Overall, one-third of the neurons responded to both sympathetic and vagal stimulation. There was no difference in proportion of responsive neurons in rostral versus caudal ventrolateral reticular formation. Cells were also tested for auditory, visual, and natural somatic stimuli. Ten percent of the neurons responded to all five stimuli, and another 25% responded to four stimuli. Twelve percent of neurons were unresponsive to any stimulus. Twenty cells were tested for responses to changes in blood pressure elicited with phenylephrine and nitroglycerin. Seven neurons were inhibited by increases or excited by decreases in pressure, four had the opposite responses, and nine were unresponsive. In general, blood pressure-sensitive cells exhibited comparable convergence of other inputs as the overall cell population. However, three times as many pressure-insensitive neurons received vagal input as did pressure sensitive neurons. In conclusion, neurons in the ventrolateral medulla, including the vasopressor and vasodepressor regions, receive and integrate convergent input from multiple sensory origins. Since the regions of the reticular formation studied are functionally heterogeneous, the precise functions of these neurons are not known.
Microvascular development during normal growth and reduced blood flow: introduction of a new model
Authors: Wang D. H. , Prewitt R. L.
Published: December 2017

The purpose of this study was to evaluate microvascular development during normal skeletal muscle maturation and to determine the alterations associated with decreased blood flow caused by a decrease in demand. Unilateral orchidectomy was performed on 4-wk-old rats to reduce muscle tension and growth of one cremaster muscle. Three weeks later, total blood flow was reduced to 58 +/- 9% measured by the dual-slit velocity technique and 55 +/- 9% by radioactive microspheres, and the muscle was smaller when compared with the intact contralateral muscle. Blood flow per gram of tissue was not significantly different. Measured by closed-circuit television microscopy, the internal diameters and wall cross-sectional areas of all orders of arterioles (1A-4A), and the number of 4As per 3A had increased with age in the control muscle. The arcading arterioles increased in length by 35% as the intact muscle grew, but the number of 3As remained unchanged. Arteriolar length increased but not in proportion to muscle mass. As a result, large and small arteriolar density decreased with age. Thus, during normal skeletal muscle maturation, preexisting arterioles became elongated and only precapillary arterioles increased in number, resulting in a decreased ratio of arteriolar number to tissue mass. Unilateral orchidectomy inhibited the growth of arterioles in both size and number. A reduced diameter of the 1A in the orchidectomy muscle resulted in unchanged wall shear rate. Flow-induced shear stress and/or local changes in growth factors are suggested as possible mechanisms mediating the alterations.
Microvascular recruitment in hamster striated muscle: role for conducted vasodilation
Authors: Segal S. S.
Published: December 2017

The influence of conducted vasodilation upon arteriolar diameter and capillary red blood cell (rbc) perfusion was investigated in the cremaster muscle of male hamsters anesthetized with pentobarbital. The muscle was surgically exposed, superfused with physiological saline solution (pH 7.4; 34 degrees C), and transilluminated for observation of microvessels using intravital video microscopy. The tip (2 microns ID) of a glass micropipette filled with acetylcholine (ACh; 1.0 M) was positioned adjacent to an arteriole. Microiontophoretic delivery of an ACh stimulus (200-1,000 nA; 200-750 ms) caused vasodilation at the pipette tip, which conducted rapidly along the arteriole and decayed with distance; this was characterized by length constants of 2.1 and 2.4 mm (P greater than 0.05) for arterioles with maximal diameters of 32 +/- 2 (means +/- SE; n = 8) and 63 +/- 2 microns (n = 5), respectively. When applied to the distal end of a terminal arteriole (TA) devoid of flow, ACh triggered a dilation that was conducted proximally (greater than 1,000 microns upstream) into the parent vessel (terminal arteriole feed, TAF) containing rbc flow, thereby inducing flow into the TA; stimulation of the TAF also induced rbc flow into TA. In capillaries fed by TA, rbc flux (rbc/s) increased from zero at rest to 23 +/- 6 during the peak of the TA dilation (n = 9); calculated tube hematocrit increased from 4 +/- 2 to 28 +/- 3%. Findings demonstrate that conduction of vasodilation can coordinate vasomotor responses between terminal and parent arterioles and promote rbc delivery to capillaries supplying striated muscle fibers.
Lack of cardiovascular and vasopressin responses to human relaxin in conscious, late-pregnant rats
Authors: Ward D. G. , Cronin M. J. , Baertschi A. J.
Published: December 2017

Measurements of arterial pressure, heart rate, and plasma vasopressin were obtained in unanesthetized late-pregnant rats after administration of human relaxin (hRlx) alone or in conjunction with hemorrhage. Forty-two timed-pregnant rats were prepared with chronic femoral cannulas on the 17th day of pregnancy for measurements on the 19th day. In three separate sets of experiments, mean arterial pressure and heart rate were measured for 10 min before administration of 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle and for 20 h thereafter; plasma vasopressin was determined 20 min before and 3 min after administration of hRlx or vehicle and 20 min after performing a 15-ml/kg 3-min hemorrhage. Neither mean arterial pressure nor heart rate was significantly different among rats administered 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle. Plasma vasopressin was not significantly different among rats administered 2 mg/kg hRlx, 100 micrograms/kg hRlx, or vehicle. The decreases and subsequent compensatory changes in mean arterial pressure and heart rate after hemorrhage and the increases in plasma vasopressin were not significantly different among rats administered vehicle or hRlx.
Endothelin stimulates Na(+)-K(+)-ATPase activity by a protein kinase C-dependent pathway in rabbit aorta
Authors: Gupta S. , Ruderman N. B. , Cragoe E. J. , Sussman I.
Published: December 2017

Incubation with endothelin (Endo) caused a time- and concentration-dependent increase in both ouabain-sensitive (OS) and ouabain-insensitive (OI) 86Rb+ uptake [half-maximal effective concentration (EC50) for OS component = 11 nM] in the rabbit aorta. Increase in the OS component [Na(+)-K(+)-adenosine triphosphatase (ATPase) activity] accounted for 70% of the 110% increase in total 86Rb+ uptake at a maximally effective concentration of Endo (100 nM). Protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBU; 100 nM) increased total 86Rb+ uptake by 69%, with 42% of the increase in the OS component. Stimulation by Endo and PDBU was not additive. Staurosporine (STA; 100 nM) inhibited stimulation of total 86Rb+ uptake by Endo and PDBU by approximately 60%. With ouabain and STA added together, inhibition of Endo-stimulated total 86Rb+ uptake (90%) was greater than with either agent alone, suggesting that STA inhibits an OS as well as an OI component of 86Rb+ uptake. Stimulation of total 86Rb+ uptake by both Endo and PDBU were also inhibited by approximately 60% by the Na(+)-H+ exchange inhibitor 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Endo-stimulated total 86Rb+ uptake was not further inhibited when ouabain was added together with EIPA, suggesting that Na(+)-H+ exchange is primarily linked to the OS component of 86Rb+ uptake. In contrast, Na(+)-K(+)-Cl- cotransport inhibitor bumetanide inhibited increases in total 86Rb+ uptake caused by Endo (30%) and PDBU (56%) due solely to its effects on OI 86Rb+ uptake. Results suggest that Endo stimulates Na(+)-K(+)-ATPase activity in rabbit aorta by activating PKC and Na(+)-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Cortical blood flow changes during spreading depression in cats
Authors: Piper R. D. , Lambert G. A. , Duckworth J. W.
Published: December 2017

Changes in cortical blood flow and cerebrovascular activity occurring during and after cortical spreading depression (CSD) were studied in alpha-chloralose-urethan-anesthetized cats. CSD was induced by superficial cortical pinprick, and laser-Doppler velocimetry (LDV) was used to measure cerebral blood flow (CBFLD). CSD resulted in a wave of cortical hyperemia during which there was a 215 +/- 48% peak increase in cortical blood flow that lasted for 2.7 +/- 0.4 min. This hyperemic phase was followed by prolonged cortical oligemia, with a reduction in flow of 20 +/- 4% at 1 h and 28 +/- 4% at 2 h. After CSD, cerebrovascular reactivity to the inhalation of CO2 was abolished and did not fully recover for at least 10 h. Spontaneous vasomotor activity in the cerebral microcirculation was significantly decreased after CSD, and autoregulation of cortical blood flow in response to hypotension was preserved. The abnormal cerebrovascular reactivity seen after CSD in the gyrencephalic cortex of the cat has possible significance for human migraine with aura.
Effect of blood flow rate and blood flow history on newborn pulmonary microcirculation
Authors: Fike C. D. , Kaplowitz M. R.
Published: December 2017

The purpose of this study was to determine whether increased pulmonary blood flow and/or the history of pulmonary blood flow alters microvascular pressures in lungs of newborns. Using the direct micropuncture technique, we measured pressures in 20- to 60-microns-diameter arterioles and venules in isolated lungs of newborn rabbits at consecutive blood flow rates of 50 (baseline), 100, and/or 200 ml.min-1.kg-1. Then in some lungs we returned blood flow rate to baseline and repeated microvascular pressure measurements. We kept left atrial pressure the same at all blood flow rates. When blood flow rate increased and left atrial pressure was maintained constant, pulmonary arterial, 20- to 60-microns-diameter arteriolar, and 20- to 60-microns-diameter venular pressures increased such that the percentage of total pressure drop that occurred across veins increased. When we returned blood flow to baseline, venular pressure returned to baseline, but arteriolar and pulmonary arterial pressures returned to values less than baseline so that the percentage of the total pressure drop that occurred across microvessels decreased. Thus both blood flow rate and blood flow history are important determinants of the longitudinal distribution of pulmonary vascular pressures across newborn lungs. These findings also suggest that in newborn lungs venules greater than 60 microns diameter are poorly distensible such that higher blood flow rates result in increased microvascular pressures. Hence, under conditions of increased pulmonary blood flow, such as occurs with left to right shunts, the tendency for edema formation will increase in newborn lungs even if left atrial pressure does not increase.
Ischemia and reperfusion-induced arrhythmias in rabbits with chronic heart failure
Authors: Bril A. , Forest M. C. , Gout B.
Published: December 2017

The incidence of ventricular arrhythmias occurring during acute myocardial ischemia and reperfusion was studied in anesthetized rabbits with chronic heart failure. Cardiac failure was induced by volume and pressure overload and was characterized by marked hypertrophy (84%) and lower systolic aortic blood pressure (112 +/- 3 mmHg) than in controls (124 +/- 2 mmHg, P less than 0.01). During the first 20 min postcoronary artery ligation, the incidence and duration of ventricular fibrillation were greater in the heart failure group (76% and 485 +/- 77 s, respectively) compared with the control group (27% and 86 +/- 37 s, respectively, P less than 0.01). Reperfusion-induced arrhythmias after various ischemic durations were also more frequent in the heart failure group than in the control group. Papillary muscles taken from rabbits with heart failure showed a reduced diastolic potential and a prolonged action potential duration (APD90) compared with the control group (by 7 and 46%, respectively), but there was no change in maximum upstroke velocity. The present study established that rabbits with pronounced morphological signs of chronic heart failure have an enhanced susceptibility to ischemia and reperfusion-induced arrhythmias. As already described in situations of uncomplicated cardiac hypertrophy, a delay in the repolarization process could represent an arrhythmogenic mechanism in this model.
Lack of coupling between adrenal cortical metabolic activity and blood flow in anesthetized dogs
Authors: Sakima N. T. , Breslow M. J. , Raff H. , Traystman R. J.
Published: December 2017

To determine whether adrenal O2 consumption and cortical blood flow (CBF) increase during stimulation of cortical secretory activity, exogenous adrenocorticotrophic hormone (ACTH) was infused at 0, 2, and 10 ng.kg-1.min-1 (groups 1, 2, and 3, respectively) into dexamethasone-pretreated, pentobarbital-fentanyl-anesthetized, ventilated dogs. ACTH levels of approximately 20, 100, and 500 pg/ml were obtained in groups 1, 2, and 3, respectively. Cortisol secretion increased after 20 min in groups 2 and 3 (from 0.016 +/- 0.004 to 2.25 +/- 1.36 and from 0.02 +/- 0.01 to 5.32 +/- 1.23 microgram.min-1.g cortex-1, respectively) while adenosine 3',5'-cyclic monophosphate (cAMP) secretion increased after 20 min only in group 3 (from 5.7 +/- 2.8 to 61.3 +/- 18.6 micrograms.min-1.g cortex-1). Whole adrenal gland O2 consumption increased after 20 min in group 3 animals (from 0.89 +/- 0.16 to 1.77 +/- 0.27 ml O2.min-1.100 g tissue-1) but not in the other two groups. CBF measured with radiolabeled microspheres was unaffected by ACTH infusion while O2 extraction increased from a baseline of 5.9 +/- 1.4 to 13.0 +/- 2.4% after 30 min in group 3. These data demonstrate that in anesthetized dogs increases in adrenal cortical secretory activity are associated with increases in O2 consumption, and this increase in O2 consumption is met by increasing O2 extraction, not by increasing cortical blood flow.
Subendocardial coronary compression in beating dog hearts is independent of pressure in the ventricular lumen
Authors: Van Winkle D. M. , Swafford A. N. , Downey J. M.
Published: December 2017

Ventricular decompression has been shown to have little effect on either the magnitude or transmural distribution of the extravascular resistance in the small hearts of the cat or rabbit. This study tests whether that independence from ventricular pressure also occurs in the large heart of the dog, which should be more representative of the human. We measured regional myocardial flow in each in situ dog heart during three conditions: normally beating, vented beating, and arrest. Hearts were perfused at constant pressure and maximally dilated with 0.4-1.0 mg/min ic adenosine. Total coronary blood flow was measured with an electromagnetic flowmeter, and regional flow was assessed with radiolabeled microspheres. Although arrest resulted in more than a doubling of flow to the inner layer, greatly reducing ventricular pressure by venting had no significant effect on subendocardial flow. Subepicardial flow was minimally affected by either venting or arrest. We conclude that both the magnitude and the transmural distribution of extravascular resistance in the large heart of the dog is unrelated to the pressure in the ventricular lumen.
Segmental vascular resistance during pulsatile and steady perfusion in 3- to 5-wk-old rabbit lungs
Authors: Kaapa P. , Usha Raj J. , Hillyard R. , Anderson J.
Published: December 2017

To determine the mechanisms by which pulsatile perfusion reduces vascular resistance in isolated lungs, we compared the effects of pulsatile versus steady perfusion on total and segmental vascular resistance in isolated lungs of 3- to 5-wk-old rabbits. Lungs were perfused alternately with steady and pulsatile flow for 45-min periods at a constant total arteriovenous pressure drop. Blood flow was adjusted to keep mean pulmonary arterial pressure at 20 cmH2O, when left atrial and airway pressures were 8 and 6 cmH2O, respectively. We partitioned the pulmonary circulation into three longitudinal vascular segments, i.e., arteries, microvessels, and veins, by measuring pressures in 20- to 50-microns-diameter subpleural arterioles and venules by the micropipette servo-nulling method. We found that in the isolated, perfused 3- to 5-wk-old rabbit lung, in which arteries and veins are the main sites of resistance, pulsatile flow results in a 20-36% reduction in total vascular resistance, mainly due to a reduction in arterial and venous resistances. The decrease in total vascular resistance was similar in lungs that were untreated or treated with papaverine, indicating that the effect of pulsatile flow was not due to active vasomotion. The reduction in arterial resistance was greater than that in veins (31-55 vs. 19-22%), especially when pulse amplitude was high (5-10 vs. 20-30 cmH2O). Total vascular resistance was also lower after 45 min of pulsatile perfusion with a pulse rate of 200 pulses/min than 80 pulses/min (0.126 +/- 0.04 vs. 0.154 +/- 0.059 cmH2O.min.ml-1.kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypothermic cerebral reperfusion and recovery from ischemia
Authors: Baldwin W. A. , Kirsch J. R. , Hurn P. D. , Toung W. S. , Traystman R. J.
Published: December 2017

The effect of transient postischemic hypothermia (30 degrees C) on recovery of cerebral blood flow (CBF), oxygen consumption (CMRO2) and somatosensory-evoked potentials (SEPs) was determined in anesthetized dogs. Ischemia was produced for 20 min by intracranial pressure (ICP) elevation while core temperature was lowered by cooling externalized blood. Epidural temperature was controlled at 37.6 +/- 0.2 degrees C during ischemia, lowered to 30.0 +/- 0.1 degrees C during the first hour of reperfusion, and then rewarmed to 38.0 +/- 0.1 degrees C in experimental dogs (n = 8) and maintained at 38.0 +/- 0.1 degrees C in control dogs (n = 8). ICP was lower throughout reperfusion in experimental as compared with control animals. By 240 min of reperfusion, CBF was approximately 70% of control in both groups. CMRO2 was 60% of preischemic values in control animals and 74% in experimental animals (P = 0.077). A persistent uncoupling of CBF and CMRO2 was observed throughout reperfusion only in the control group. Recovery of SEP amplitude was significantly improved in the experimental group (26 vs. 11% of preischemic values). These data suggest that transient hypothermia reduces ICP and facilitates recovery of electrophysiological function after cerebral ischemia.
Specific proteins synthesized in human lymphocytes during hypoxia
Authors: Aldashev A. A. , Agibetov K. A. , Yugai A. A. , Shamshiev A. T.
Published: December 2017

Hypoxia is a severe stress factor to which man and most other mammalian species are capable of adapting. However, the cellular mechanisms that enable cells to tolerate decreases in ambient oxygen tension are still unknown. We have previously shown that hypoxia induces the synthesis of unique proteins (molecular mass 38, 52, 74, 76 kDa) in human aortic endothelial cells and lymphocytes. In this study we investigated the specificity of hypoxia on the upregulation of these hypoxic stress proteins (HYP) in human peripheral blood lymphocytes and the role of calcium in this response. 35S-methionine pulse-labeling studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis and autoradiography demonstrated that normobaric hypoxia (4% O2–5% CO2–91% N2) enhanced synthesis of HYP, whereas heat-shock protein synthesis was not affected. Heat shock (42°C) and cold stress (4°C) did, however, induce synthesis of heat-shock protein but not HYP. The 38-kDa HYP is the major protein for which synthesis is upregulated by hypoxia. Its isoelectric point (pI) is 3.5–4.0, and it is localized in the cytosol. The 52-kDa HYP has a pI of >6.5, and it is also localized in the cytosol. The 74- and 76-kDa HYPs appear to be membrane bound. In addition to hypoxia, an increase in calcium concentration in the culture media (25–50 mM) enhanced synthesis of HYP. An ethylene glycol-bis(-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)/Ca2+ binding complex, when added to blood lymphocytes during exposure to hypoxia, significantly inhibited HYP synthesis. On the basis of the similarity of molecular masses, pI, localization in the cytosol, and Ca2+ dependence of HYP expression, we suggest that HYP 38 and 52 may be isoenzymes of inositol 1,4,5-triphosphate 3-kinase, an enzyme that regulates phosphoinositol turnover and intracellular calcium concentration in cells.

calcium; internal localization; stress
Interaction of nitric oxide and cGMP with signal transduction in activated platelets
Authors: Nguyen B. L. , Saitoh M. , Ware J. A.
Published: December 2017

Although nitric oxide (NO), one of the endothelium-derived relaxing factors, prevents formation of platelet aggregates, the mechanism by which this occurs is not fully understood. Accordingly, the effect of NO on signal transduction of gel-filtered human platelets was measured and compared with that of a cell-permeant guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cGMP (8-BrcGMP). NO inhibited the rise in intracellular Ca2+ concentration ([Ca2+]i), phosphorylation of the 47-kDa substrate (p47) of protein kinase C (PKC), serotonin secretion, and phosphatidic acid production induced by thrombin or the endoperoxide analogue U-46619. Similar effects were seen with 8-BrcGMP, and NO induced a concentration-related rise in cGMP. Neither NO nor 8-BrcGMP inhibited platelet aggregation, [Ca2+]i mobilization, or serotonin secretion induced by the Ca2+ ionophores A23187 or ionomycin or directly activated PKC purified from platelets. However, both NO and 8-BrcGMP enhanced p47 phosphorylation induced by the Ca2+ ionophores without augmenting phosphatidic acid production. Thus, if [Ca2+]i is elevated, a rise in cGMP enhances PKC activation. Both NO and 8-BrcGMP, however, prevent Ca2+ mobilization and platelet aggregation induced by receptor-mediated agonists by interfering with signal transduction at a point proximal to phospholipase C activation.
Slope of human left ventricular end-systolic force-length relation is independent of myocardial length
Authors: Takeda K. , Tamano K. , Okamura A. , Kobayashi N. , Shimizu T. , Kadota R. , Yamamoto H. , Yagi S.
Published: December 2017

We have introduced a new contractility index (Ec), i.e., the slope of the left ventricular (LV) end-systolic force-length (Fes-Les) relation. To examine whether Ec was dependent on the LV wall myocardial length, 16 normal hearts of human subjects were evaluated to determine the LV end-systolic force-dimension (Fes-Des) and pressure-dimension (Pes-Des) relations (dimension denotes the distance between the LV septum and posterior wall). LV end-systolic pressures and dimensions were estimated simultaneously by intra-arterial cannulation and LV echocardiography. In seven subjects, the effect of a dobutamine infusion was also assessed. The Fes-Des relation was found to be nearly linear. Slopes and extrapolated dimension intercepts were obtained for the LV Fes-Des and Pes-Des relations [Ec, slope of LV Pes-Des relation (Es), and extrapolated dimension intercept of LV Fes-Des (Do), and of Pes-Des relation (D'o), respectively]. Es showed a hyperbolic relation to the baseline LV Des, whereas Ec was unrelated to it. The average variation for Ec (9.5%) was smaller than that for Es (22.5%). Dobutamine infusion increased Ec, Es, and D'o, whereas Do was not changed. Thus the assumption of linearity of the LV Fes-Les relation was found to be reasonable in normal human hearts. Do appears to provide a more accurate parameter than D'o for estimating the actual unstressed myocardial length, whereas Ec could possibly serve as an index of LV wall performance in the normal human heart that is independent of myocardial length and nearly constant between individuals.
Measurement of mitochondrial free Ca2+ concentration in living single rat cardiac myocytes
Authors: Miyata H. , Silverman H. S. , Sollott S. J. , Lakatta E. G. , Stern M. D. , Hansford R. G.
Published: December 2017

A technique that allows the continuous measurement of mitochondrial free Ca2+ ([Ca2+]m) in a single living cardiac myocyte is described. It involves the introduction of the fluorescent chelating agent indo-1 into the cell by exposure to the acetoxymethyl ester, followed by selective quenching of the fluorescence of indo-1 in the cytosol by Mn2+. The identity of the remaining fluorescence due to intramitochondrial indo-1 is established by its resistance to treatment of the cell with digitonin at concentrations that release cytosolic but not mitochondrial enzymes and by the finding that ruthenium red and carbonyl cyanide p-trifluoromethoxyphenylhydrazone prevent its response to elevated cytosolic free Ca2+ ([Ca2+]c). [Ca2+]m is found to be low (less than 100 nM) in unstimulated cells and to rise in procedures that chronically elevate [Ca2+]c, such as Na+ replacement. The gradient [Ca2+]m/[Ca2+]c is less than unity at values of [Ca2+]c of less than 500 nM but rapidly increases at higher values of [Ca2+]c. Although there is no detectable increase in [Ca2+]m during a single electrical stimulation, [Ca2+]m increases up to 600 nM as the pacing frequency is raised to 4 Hz in the presence of norepinephrine; this increase occurs over the course of many contractions. It is concluded that these findings are consistent with an increase in [Ca2+]m acting as a signal to increase dehydrogenase activity, and hence flux through oxidative phosphorylation, in response to increased work loads.
Splanchnic vasoconstriction and bacterial translocation after thermal injury
Authors: Jones W. G. , Minei J. P. , Barber A. E. , Fahey T. J. , Shires G. T. , Shires G. T.
Published: December 2017

Gut barrier failure and bacterial translocation (BT) after thermal injury may result from splanchnic vasoconstriction and intestinal ischemia. The role of the renin-angiotensin system in intestinal blood flow and BT after thermal injury was studied by pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in Wistar rats before sham or 30% scald burn. Adequacy of ACE inhibition was documented by the absence of a hypertensive response to angiotensin I, and intestinal blood flow was determined using 51Cr-labeled microspheres. Small bowel blood flow was decreased by 46% at 4-h postburn (P less than 0.05) in untreated burned animals despite maintenance of normal cardiac index but returned to baseline levels by 24 h after injury. Enalapril pretreatment resulted in maintenance of small bowel blood flow after thermal injury and was associated with a significantly reduced incidence of BT (20% vs. 75% in untreated burned animals, P less than 0.01). These findings further implicate intestinal ischemia in the etiology of gut barrier dysfunction after thermal injury, mediated in part by activation of the renin-angiotensin system.
Neutrophil passage through isolated perfused rabbit lungs
Authors: Schutte H. , Rosseau S. , Walmrath D. , Grimminger F. , Ernst C. , Seeger W.
Published: December 2017

Kinetics of polymorphonuclear leukocyte (PMN) lung passage were investigated in ex vivo isolated and ventilated left rabbit lungs, perfused with buffer solution at physiological flow rate. 111In-labeled PMNs of rabbit or human origin were injected into the pulmonary artery, and the first fraction of PMNs that rapidly passed the lung together with coinjected erythrocytes, was collected separately for external radioactivity counting. Washout of initially retained PMNs from the lung was monitored by use of a sodium-iodide detector. Recirculation of cells was avoided by insertion of a filter in the perfusion circuit. A fraction of 16.6 +/- 1.3% of rabbit PMNs rapidly passed the lung vasculature, followed by an exponential washout of initially retained PMNs [half-time (t50) of lung transit 8.1 +/- 0.6 min]. Slightly higher t50 (12.2 +/- 1.0 min) was obtained upon use of human PMNs. Reduction in flow by 50% caused a marked prolongation of PMN transit (t50 = 27.8 +/- 5.1 min), whereas increase in flow to 150% only insignificantly decreased t50. Rise in pulmonary venous pressure to 5 and 8 mmHg caused retardation of PMN lung transit (t50 = 15.3 +/- 0.6 and 31.6 +/- 3.6 min). Preincubation of PMNs with 2 ng/ml endotoxin for 1 h induced marked delay in PMN washout (t50 = 26.1 +/- 2.8 min). In conclusion, single-pass PMN kinetics in isolated lungs correspond to in vivo studies previously reported, thus allowing elucidation of PMN-endothelial interactions in an intact lung vasculature under standardized conditions.
Simultaneous measurement of contraction and oxygen consumption in cardiac myocytes
Authors: Rose H. , Strotmann K. H. , Popping S. , Fischer Y. , Kulsch D. , Kammermeier H.
Published: December 2017

A setup has been developed that simultaneously measures the mechanics and the energetics of electrically induced contractions at physiological frequencies of isolated cardiac myocytes. The core of the setup is a self-manufactured stimulation chamber in which most of the myocytes are in suspension while some are attached to a plastic cover slip prepared from culture Petri dishes. The analysis of the contractile behavior of the attached myocytes is based on an image-processing system with digitized frames of a charge-coupled device camera. Thirty-six frames illuminated by a stroboscope are taken at increasing time intervals between stimulus and flash (snap), allowing one to resolve the contraction cycle with a very high time resolution (down to 1 ms). The number of pixels that differ between each of these frames and a “reference” frame of the cells in the relaxed state (slack cell length) are used to quantify the contractions. An oxygen electrode in the chamber registers the drop of oxygen tension resulting from the consumption by the myocytes, which exhibit a strictly aerobic metabolism. The resulting data are also stored and analyzed in an IBM-AT-compatible computer.
Rate-dependent differences in dog epi- and endocardial monophasic action potential configuration in vivo
Authors: Tande P. M. , Mortensen E. , Refsum H.
Published: December 2017

A transient outward current (Ito), long considered to be a unique feature of Purkinje fiber tissue, has recently been demonstrated in dog ventricular tissue in vitro and most prominently in the epicardium. To investigate its possible contribution to ventricular repolarization in vivo, we recorded right ventricular endocardial and epicardial monophasic action potentials (MAP) simultaneously in pentobarbital-anesthetized open-chest dogs. Epicardial MAP had lower phase 1 than phase 2 amplitude at both spontaneous heart rate and paced cycle length of 300 and 400 ms. This "spike-and-dome" morphology of the epicardial MAP, possibly attributable to Ito, progressively disappeared at shorter extrastimulus intervals. In endocardium the phase 1 amplitude was always higher or equal to phase 2 amplitude and was not affected by shorter extrastimulus intervals. The action potential duration (APD) was shorter in epicardium than in endocardium. Both endocardial and epicardial APD shortened as the premature intervals were reduced, but the shortening was not parallel. The restitution curves converged so that, at the shortest intervals (160 ms), there were no longer any significant differences in APD between endocardium and epicardium. This study indicates that Ito contributes to ventricular repolarization in vivo, and most prominently in the epicardium. Unequal shortening of APD between endocardium and epicardium after progressively shorter diastolic intervals may thus partly result from uneven distribution of Ito across the ventricular wall.
Significant left ventricular contribution to right ventricular systolic function
Authors: Damiano R. J. , La Follette P. , Cox J. L. , Lowe J. E. , Santamore W. P.
Published: December 2017

To examine the importance of systolic ventricular interdependence on right ventricular function, we used a unique electrically isolated right ventricular free wall preparation. Double-peaked waveforms for right ventricular pressure and pulmonary arterial blood flow occurred over a wide range of pacing intervals between the left and right ventricles. One component of the waveforms could be directly related to right ventricular free wall contraction, whereas the other component was directly related to left ventricular and septal contraction. For left ventricular pressure, the left ventricular component was significantly larger than the right ventricular free wall component (92.7 +/- 3.2 vs. 7.3 +/- 3.2% peak-to-peak value, P less than 0.01). For right ventricular pressure, the left ventricular and septal component was significantly greater than the right ventricular component (63.5 +/- 10.9 vs. 36.5 +/- 10.9% peak-to-peak value, P less than 0.05). Similarly, for pulmonary arterial blood flow, the left ventricular component was significantly greater than the right ventricular component. When right ventricular free wall pacing stopped in diastole, 68 +/- 4% of right ventricular systolic pressure and 80 +/- 4% of pulmonary flow were obtained in the subsequent beat. The results of this study indicate that left ventricular contraction is very important for right ventricular developed pressure and volume outflow.