bluuebunny/crossref_metadata_2025 huggingface dataset:
Central opioid mechanisms and cardiovascular control in hemorrhagic hypotension
Authors: Sandor P. , de Jong W. , Wiegant V. , de Wied D.
Published: December 2017

Bleeding volume during standardized hemorrhagic hypotension was studied in anesthetized, artificially ventilated rats after specific stimulation or blockade of opiate receptor systems. Hypotension was produced by stepwise bleeding to 80, 60, and 40 mmHg systemic arterial pressure. Subcutaneous administration of morphine 15 min before the bleeding resulted in a decrease, whereas subcutaneous administration of naloxone resulted in a significant increase in the required bleeding volume. Intracerebroventricularly administered met-enkephalin, dynorphin, or specific antisera against these peptides caused no characteristic alterations of the bleeding volume although met-enkephalin and dynorphin caused a significant decrease at the 40 mmHg level. Bleeding volume, however, was markedly reduced when beta-endorphin was intracerebroventricularly administered and significantly elevated by intracerebroventricular administration of a diluted beta-endorphin antiserum. These data suggest that 1) opioid mechanisms are participating in the control of blood pressure and of bleeding volume during blood loss, 2) these control mechanisms might be activated centrally, and 3) beta-endorphin or a closely related peptide plays a major role in these control mechanisms.
Effects of thyroid state on respiration of perfused rat and guinea pig hearts
Authors: Read L. C. , Wallace P. G. , Berry M. N.
Published: December 2017

The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses.
Effect of area postrema lesion on low-frequency arterial pressure oscillations in dogs
Authors: Pollick F. E. , Barnes K. L. , Ferrario C. M.
Published: December 2017

To explore the possibility that chronic inactivation of the area postrema (AP) may alter the frequency distribution of oscillations in blood pressure, the power spectra for mean arterial pressure (MAP) were evaluated in conscious dogs before and after heat coagulation (n = 4) or sham lesions (n = 6) of the AP. No significant changes in MAP were observed in either group of dogs after surgery. Tachycardia was seen in AP-lesioned animals after surgery; no consistent changes in heart rate were found in sham-lesioned dogs. Spectra were averaged to provide a group spectral estimate for the AP-lesioned and sham-lesioned groups, respectively, for each experimental period. In the sham-lesioned group a variance peak was observed at approximately 0.03 Hz both before and after surgery. The same peak was seen in the AP-lesioned group during the control period but disappeared following AP lesion, apparently because a greater proportion of the variance was shifted toward frequencies below 0.03 Hz. In addition, a peak related to respiratory rate was present in both groups before surgery but was selectively abolished by AP lesion. AP lesion also substantially reduced the power associated with frequencies between 0.1 and 0.4 Hz. The use of spectral analysis has allowed us to demonstrate that a low-frequency oscillation of MAP in conscious, resting dogs requires the integrity of the AP and that the 0.1- to 0.4-Hz components of the variability of MAP are attenuated after removal of the AP.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in adrenergic pressor responses by calcium channel modulation in conscious dogs
Authors: Wynsen J. C. , Gross G. J. , Brooks H. L. , Warltier D. C.
Published: December 2017

The influence of the slow channel calcium entry blocker, nifedipine, and the slow channel calcium entry promoter, BAY-K 8644, on receptor-mediated hemodynamic responses was studied in chronically instrumented, conscious dogs. Following ganglionic, cholinergic, and beta-adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg iv), a selective alpha 1-adrenoceptor agonist, and B-HT 933 (20 micrograms/kg iv), a selective alpha 2-adrenoceptor agonist, as well as a nonadrenergic vasoconstrictor, vasopressin (0.003 IU/kg) were administered before and after infusions of nifedipine or BAY-K 8644 (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X min-1). In doses producing minimal or no haemodynamic effects, nifedipine caused dose-related attenuation from control of phenylephrine- (from 26 +/- 3 to 8 +/- 1 mmHg), B-HT 933- (from 30 +/- 2 to 5 +/- 2 mmHg), and vasopressin- (24 +/- 1 to 2 +/- 2 mmHg) mediated changes in mean arterial pressure. In contrast, BAY-K 8644 produced dose-related potentiation from control of the same pressor responses (phenylephrine, 24 +/- 2 to 41 +/- 3 mmHg; B-HT 933, 28 +/- 3 to 46 +/- 2 mmHg; vasopressin, 25 +/- 3 to 45 +/- 5 mmHg). In addition, BAY-K 8644 produced a marked increase in the duration of the pressor response produced by all three agonists. Thus, in conscious dogs, alpha 1-, alpha 2-, and vasopressin-mediated pressor responses are strongly modulated by transmembrane calcium flux and can be influenced by dihydropyridine slow channel calcium agonists and antagonists.
Dexamethasone potentiates hypoxic vasoconstriction in salt solution-perfused rat lungs
Authors: Herget J. , McMurtry I. F.
Published: December 2017

Isolated rat lungs perfused with blood or plasma develop good hypoxic pressor reactivity, but those flushed of blood and perfused solely with physiological salt solution (PSS) show decreased or no hypoxic vasoconstriction. Because the handling of rats during collection of blood increases the plasma corticosterone levels, we wondered whether the difference between blood and PSS perfusion was due partly to higher glucocorticoid activity with blood than with PSS. Treatment of lung donors with the synthetic glucocorticoid dexamethasone (2 mg/kg im 3 h before isolation) or addition of dexamethasone (4.2 X 10(-6) M) to the perfusate increased markedly the hypoxic pressor reactivity of rat lungs perfused with PSS plus albumin (4 g/100 ml). In comparison, dexamethasone did not cause a significant increase in the already vigorous hypoxic pressor reactivity of blood-perfused lungs, but it reversed the blunted pressor reactivity of lungs perfused with blood collected from adrenalectomized rats. The potentiation of hypoxic vasoconstriction by dexamethasone required greater than 40 min to develop and was inhibited by a 100-fold higher concentration of progesterone, a glucocorticoid receptor antagonist. Although dexamethasone and the cyclooxygenase blocker meclofenamate (3.1 X 10(-5) M) caused similar decreases in perfusate levels of cyclooxygenase metabolites, the glucocorticoid was much more effective in inducing hypoxic vasoconstriction in PSS-perfused lungs. Thus a reduction of cyclooxygenase metabolism might have contributed to, but did not fully account for, the glucocorticoid effect. Dexamethasone also caused small increases in base-line perfusion pressure and in pressor reactivity to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Functional significance of alpha-adrenergic receptors in mature coronary collateral circulation of dogs
Authors: Maruoka Y. , McKirnan M. D. , Engler R. L. , Longhurst J. C.
Published: December 2017

There is little information on the functional significance of alpha-adrenergic receptors in the dog's coronary collateral circulation. Accordingly, we investigated the effects of infusion of either norepinephrine (NE) or B-HT 920 (BHT), an alpha 2-adrenergic agonist, on vascular resistance of coronary collaterals in chloralose-anesthetized dogs 2-3 mo after placement of an Ameroid constrictor around the left circumflex coronary (LCX) artery. To accomplish this, the vagotomized left ventricle was autoperfused through the left main coronary ostium using a servo-controlled constant-pressure pump. Pressures of the left anterior descending (LAD) and peripheral LCX arteries were measured, and regional blood flow in LAD and LCX regions were determined with radioactive microspheres before and during NE infusion in the unblocked condition, following beta-adrenergic and beta + alpha 1-adrenergic blockade with the use of propranolol and prazosin, respectively. The same parameters were also measured before and during BHT infusion following beta-adrenergic and beta + alpha 2-adrenergic blockade with the use of propranolol and idazoxan, respectively. In the unblocked condition, NE reduced LAD, LCX, and collateral resistance by 43, 50, and 31%, respectively. After beta-adrenergic blockade, NE increased LAD resistance (29%) but did not alter LCX or collateral resistance. The increase in LAD resistance was abolished following alpha 1-adrenergic blockade. BHT increased vascular resistance in LAD, LCX, and collateral circulations by 35, 29, and 45%, respectively. Selective alpha 2-adrenergic blockade significantly attenuated the vasoconstrictor response to BHT.(ABSTRACT TRUNCATED AT 250 WORDS)
Aortic arch reflex control of total systemic vascular capacity
Authors: Shoukas A. A. , Brunner M. J. , Greene A. S. , MacAnespie C. L.
Published: December 2017

The ability of the aortic arch baroreceptors to change vascular capacity was measured and, in the same animal, compared with carotid sinus reflex changes in capacity. Seven dogs were anesthetized with pentobarbital sodium and perfused with constant flow. Changes in external reservoir volume reflected reciprocal changes in total systemic vascular capacity and changes in arterial pressure parallel changes in total peripheral resistance. The aortic arch and carotid sinus baroreceptor areas were isolated, and the pressures were controlled separately. With carotid sinus pressure held constant at 125 mmHg, aortic arch pressure was increased and decreased between 225 and 50 mmHg, and the changes in reservoir volume and systemic arterial pressure were measured. Results from increasing and decreasing aortic arch or carotid sinus pressure were not significantly different and were averaged. The mean change in reservoir volume was 1.9 +/- 0.2 ml/kg and the change in mean arterial pressure was 18.7 +/- 3.7 mmHg. The changes in reservoir volume and arterial pressure caused by the aortic arch reflex were not influenced by the level of carotid sinus pressure. Carotid sinus pressure changes between 200 and 50 mmHg at a constant aortic arch pressure caused reservoir volume and arterial pressure to change by 7.2 +/- 0.9 ml/kg and 45.1 +/- 4.1 mmHg, respectively. The level of aortic arch pressure did not modify these responses.
Use of ultrasound for noninvasive study of blood vessel responsiveness
Authors: Stewart G. J. , Ziskin M. C. , Schaub R. G. , Cartee R. E. , Philips C. M. , Stone E. A. , Manuel D. W.
Published: December 2017

To provide a noninvasive means for studying individual macroscopic blood vessels, an ultrasound scanner was modified to provide a recording of blood vessel diameter. The instrument has A- and B-modes of signal display. The B-mode is used to position the probe and the A-mode to measure vessel diameter. The A-mode has two electronic gates for tracking the echo from each of two structures, i.e., near and far wall of vessel. The front gate was modified to pick up the falling rather than rising edge of a peak generated by the vessel wall. An analog signal proportional to the distance between gates was derived for recording with a strip-chart recorder. Probe holders were constructed to optimize positioning and holding of probe. Stability was excellent (reading varied 0.05 mm over 1 h). Axial resolution was between 0.3 and 0.73 mm. Discrepancy of measurements of plastic tubing made by ocular and ultrasound varied from 1.1 to 4.6%. Discrepancy with lightly fixed vessels was 2.7-8.2%. Ex vivo measurements on vessels with viable smooth muscle were more variable, perhaps because of actual change during measurements. Changes in vessel diameter induced by change in hydrostatic pressure and exposure to histamine were recorded.
Modeling mechanical alternans in the beating heart: advantages of a systems-oriented approach
Authors: Adler D. , Mahler Y.
Published: December 2017

A model employing an original discrete method is proposed to explain mechanical alternans in the beating heart. This is compared with analysis using the difference-equation method, which has been utilized in some other areas of science and found to better represent the cardiac beat-to-beat behavior. The model shows the critical role of a slope with an exact value of 2 in the functional dependence between stroke volume (SV) and the end-diastolic volume (EDV). The implications of this model with respect to the factors causing sustained mechanical alternans (SMA) in the heart are shown. A criterion for determining whether SMA is caused by variations in EDV is described. However, this possibility is ruled out on the basis of experimental findings. It is further shown that SMA caused primarily by alterations in the contractile state leads to secondary variations in EDV. In this case the model predicts that the mean slope of SV as a function of EDV, as determined by the two alternating beats, has a value of 2 and is independent of the SV-EDV relation. This prediction concerning the relationship between SV and EDV is confirmed by available experimental data. The implications and advantages of the modeling approaches are explored.
Role of neutrophils in ischemia-reperfusion-induced microvascular injury
Authors: Hernandez L. A. , Grisham M. B. , Twohig B. , Arfors K. E. , Harlan J. M. , Granger D. N.
Published: December 2017

Recent studies indicate that polymorphonuclear neutrophils (PMNs) infiltrate the intestinal mucosa during ischemia and after reperfusion. To determine whether PMNs mediate the increased microvascular permeability produced by ischemia-reperfusion (I/R) we treated cats with either saline, antineutrophil serum (ANS), or a monoclonal antibody specific for the beta-chain of the CD18 complex (MoAb 60.3) that prevents neutrophil adherence and extravasation. Intestinal microvascular permeability to plasma proteins was measured in control preparations (0.08 +/- 0.007), in preparations subjected to 1 h of ischemia then reperfusion (I/R, 0.32 +/- 0.02), I/R preparations treated with ANS (0.13 +/- 0.01), and I/R preparations treated with MoAb (0.12 +/- 0.003). Our results indicate that both PMN depletion (to less than 10% control) and prevention of PMN adherence significantly attenuate the increased microvascular permeability induced by I/R. These findings, coupled to previous results obtained from this model, support the hypothesis that neutrophils, which accumulate in the mucosa in response to xanthine oxidase activation, mediate the oxyradical-dependent injury produced by reperfusion of the ischemic bowel.
Left ventricular O2 consumption and pressure-volume area in puppies
Authors: Suga H. , Yamada O. , Goto Y. , Igarashi Y. , Yasumura Y. , Nozawa T. , Futaki S.
Published: December 2017

We studied the relation between O2 consumption (VO2) and systolic pressure-volume (PV) area (PVA) in the left ventricles of eight puppies (2-4 mo old). PVA is the area circumscribed by the end-systolic and end-diastolic PV curves and systolic PV trajectory. We assumed PVA to represent the total mechanical energy generated by ventricular contraction. We produced isovolumic contractions at different volumes in the left ventricles isolated and cross-circulated with adult dogs. VO2 closely correlated with PVA in each of control contractile state, an enhanced contractile state with epinephrine, and a depressed contractile state with propranolol in each heart. The slope of the regression line of VO2 on PVA was not significantly affected by epinephrine and propranolol. The regression line shifted upward with epinephrine and downward with propranolol. These characteristics of the puppy's VO2-PVA relation were comparable to those of the adult dog. These results suggest that similar relations hold between myocardial mechanics and energetics in both the puppy and adult dog despite the differences in the heart size and contractile properties.
Depressor neurons in rabbit caudal medulla do not transmit the baroreceptor-vasomotor reflex
Authors: Blessing W. W. , Willoughby J. O.
Published: December 2017

Experiments to determine whether depressor neurons in the caudal ventrolateral medulla form an integral part of the central pathway transmitting the baroreceptor-vasomotor reflex were performed on rabbits anesthetized with urethan. The function of the depressor neurons was altered by intramedullary injections of agents that stimulate or block receptors for gamma-aminobutyric acid and by electrolytic lesions in the caudal ventrolateral medulla. Muscimol abolished both the depressor response and the inhibition of renal nerve activity normally observed after stimulation of the aortic depressor nerve and caused a paradoxical reversal of the depressor response. However, muscimol only partially impaired the inhibition of renal nerve activity produced by experimental elevation of arterial pressure, and it did not affect the increase in renal nerve activity normally produced by decreasing arterial pressure. Bicuculline methiodide amplified the depressor response and the inhibition of renal nerve activity and also restored baroreceptor-vasomotor reflexes abolished by muscimol. Bilateral electrolytic lesions did not alter any component of the baroreceptor-vasomotor reflex. Results indicate that the depressor neurons in the caudal ventrolateral medulla do not form an integral part of the central pathway mediating the baroreceptor-vasomotor reflex. However, output from the depressor neurons appears to inhibit sympathoexcitatory neurons, which also receive baroreceptor-derived inhibitory inputs.
Aging of modulation of heart rate
Authors: Shannon D. C. , Carley D. W. , Benson H.
Published: December 2017

We postulated that measurements of autonomically mediated fluctuations in heart rate might provide a quantitative probe of biological aging. We used power spectrum analysis of instantaneous heart rate while 33 male subjects matched their breathing to a metronome at 15 breaths/min. Measurements were made in supine and standing position. Total power and its two major components, high- and low-frequency power, declined with age in both positions but at different rates. High-frequency power that represents parasympathetically mediated respiratory sinus arrhythmia declined linearly in supine position only in subjects 9-28 yr with a slope of -0.796, which was significantly different from zero at P = 0.0007. The absolute value of high-frequency power in standing position was approximately 60% of that in supine, a difference that was statistically significant (P = 0.01). Low-frequency power that represents beta-adrenergically mediated heart rate fluctuations, especially in standing position, declined linearly to 62 yr of age (P = 0.0001). Mean heart rate increased 17.2 beats/min, and diastolic blood pressure increased 8 mmHg in the entire group in the standing compared with supine position. There were no significant differences in these changes above and below 30 yr of age. We conclude that the influence of the two major mechanisms that modulate heart rate decline at significantly different rates with aging.
Relaxation of canine coronary artery to electrical stimulation: limited role of free radicals
Authors: Feletou M. , Vanhoutte P. M.
Published: December 2017

Electrical stimulation induces tetrodotoxin-insensitive relaxation of the canine coronary artery. The present study was designed to verify whether this relaxation involves the production of oxygen-derived free radicals. Isolated rings of canine coronary arteries were suspended for isometric tension recording in organ chambers filled with Krebs-Ringer bicarbonate solution. They were stimulated electrically (9 V, 3 Hz, 2 ms for 2 min) by means of two platinum electrodes during contractions evoked by various vasoactive agonists. Under control conditions, electrical stimulation caused rapid, reversible relaxations. Superoxide dismutase in association with catalase or mannitol, sodium ascorbate, dimethyl sulfoxide, and glutathione did not inhibit the relaxation caused by stimulation applied for only 2 min; neither did the removal of chloride ions from the salt solution nor the association of Cl-free solution in the presence of mannitol, superoxide dismutase, and catalase. Prolonging the electrical stimulation (9 V, 3 Hz, 2 ms) for up to 20 min produced a secondary relaxation. This second phase was inhibited by sodium ascorbate. These experiments indicate that the rapid relaxation induced by short-lasting electrical stimulation is probably not due to the generation of oxygen-derived free radicals. However, prolonged stimulation causes the production of such radicals, which then evoke irreversible inhibition of the vascular smooth muscle of the canine coronary artery.
Rapidly recovered transient flow resistance: a newly discovered property of blood
Authors: McMillan D. E. , Strigberger J. , Utterback N. G.
Published: December 2017

Although blood flows in a pulsatile fashion, little consideration has been given in past studies to its instantaneous resistance to motion when onset and cessation of flow occur abruptly. Hemorheological studies have documented three kinds of blood flow properties. 1) Shear thinning is a fall in viscolity as shear rate rises. 2) Viscoelasticity is a transient shear stress variation due to elastic deformation of erythrocytes. Dilatancy is a viscoelasticity-modifying property attributed to high shear rate erythrocyte rigidity; viscoelasticity is prominent only at low shear rate. 3) Thixotropy is an initial extra flow resistance linked to developing orientation and disaggregation of erythrocytes. Thixotropy returns fully to blood over a period longer than 1 min. Measurements utilizing a fast response Couette viscometer have revealed an extra 10% transient flow resistance after a flow cessation shorter than that between heart beats. The rapidly recovered transient flow resistance has a temporal pattern similar to thixotropy. Its peak and duration are directly related to total shear strain (shear rate x time) over the 8-30 s-1 shear rate range studied. Transient behavior was essentially identical in analyses carried out using three different viscometer gaps. Numerical simulation to test the effect of the newly observed transient behavior on sudden onset tube flow shows that the developing pattern of pulsatile arterial flow can be affected by its presence.
Persistent fetal pulmonary hypoperfusion after acute hypoxia
Authors: Abman S. H. , Accurso F. J. , Wilkening R. B. , Meschia G.
Published: December 2017

To determine the effects of duration of hypoxia on fetal pulmonary blood flow and vasoreactivity, we studied the response of the fetal pulmonary vascular bed before, during, and after prolonged (2-h) and more brief (30-min) exposures to acute hypoxia in 19 chronically instrumented unanesthetized fetal lambs. Left pulmonary arterial blood flow was measured by an electromagnetic flow transducer. Fetal PO2 was lowered by delivering 10-12% O2 to the ewe. During 2-h periods of hypoxia left pulmonary arterial blood flow decreased, and main pulmonary arterial and pulmonary vascular resistance increased. The increase in pulmonary vascular resistance was sustained throughout the 2-h period of hypoxia. After the return of the ewe to room air breathing, pulmonary vascular resistance remained elevated for at least 1 h despite the rapid correction of hypoxemia and in the absence of acidemia. In contrast, after 30 min of hypoxia, left pulmonary arterial blood flow, pulmonary arterial pressure, and pulmonary vascular resistance returned to base-line values rapidly with the termination of hypoxia. The persistent pulmonary hypoperfusion after 2 h of hypoxia was attenuated by alpha-adrenergic blockade and was characterized by a blunted vasodilatory response to increases in fetal PO2. When fetal PO2 was elevated during the posthypoxia period in the presence of alpha-blockade, pulmonary blood flow still remained unresponsive to increases in fetal PO2. We conclude that 2-h periods of acute hypoxia can decrease fetal pulmonary vasoreactivity, and we speculate that related mechanisms may contribute to the failure of the normal adaptation of the pulmonary circulation at birth.
Release of atrial natriuretic factor from heart-lung preparations of inbred Dahl rats
Authors: Onwochei M. O. , Snajdar R. M. , Rapp J. P.
Published: December 2017

Isolated heart-lung preparations from hypertensive inbred Dahl salt-hypertension sensitive (S) and normotensive inbred Dahl salt-hypertension resistant (R) rats were perfused using 15% washed rat red blood cells in Krebs-Ringer bicarbonate buffer. Atrial pressures were increased by increasing venous return (preload) or by increasing the arterial resistance (afterload). Increases in preload at a constant afterload produced increases in the right and left atrial pressures equivalent between S and R strains. Atrial natriuretic factor (ANF) release was linearly related to right atrial pressure (RAP) or left atrial pressure (LAP) in either strain, but S released more ANF at each level of preload, and the slope of the line relating ANF release to RAP was significantly greater in S than R. When the heart-lung preparations were subjected to changes in afterload at a constant preload, LAP was significantly increased in R but not in S rats, and concomitantly ANF increased in R but not in S. In the afterload experiments, as in the preload studies, S released more ANF than R for comparable LAP. It is concluded that 1) at any atrial pressure, hearts of hypertensive S rats release more ANF than hearts of normotensive R rats, 2) this strain difference is probably a consequence of hypertension, and 3) the observed relationships between ANF release and atrial pressures support the contention that atrial distention stimulates the release of ANF.
Mechanisms of endothelium-dependent vascular smooth muscle relaxation elicited by bradykinin and VIP
Authors: Ignarro L. J. , Byrns R. E. , Buga G. M. , Wood K. S.
Published: December 2017

The objective of this study was to elucidate the mechanisms by which bradykinin and vasoactive intestinal polypeptide (VIP) relax bovine intrapulmonary artery and bradykinin, but not VIP, relaxes intrapulmonary vein. Bradykinin and VIP elicited entirely endothelium-dependent relaxation of phenylephrine-precontracted arterial rings, and this was associated with arterial accumulation of both guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). Bradykinin, but not VIP, relaxed precontracted venous rings and increased cGMP, but not cAMP levels, by endothelium-dependent mechanisms. Neither arteries nor veins relaxed in response to substance P, thrombin, bombesin, arginine vasopressin, or angiotensin II. Methylene blue or indomethacin each partially antagonized, whereas both, when together, abolished arterial relaxant responses to bradykinin and VIP. Methylene blue or indomethacin, respectively, abolished arterial cGMP or cAMP accumulation elicited by bradykinin and VIP. Venous relaxation and cGMP accumulation elicited by bradykinin was abolished by methylene blue but was unaltered by indomethacin. Thus bradykinin and VIP relaxed bovine intrapulmonary artery by endothelium-dependent mechanisms involving the actions of cGMP and cAMP whose formation may be stimulated by endothelium-derived relaxing factor and prostacyclin, respectively. In contrast, bradykinin relaxed intrapulmonary vein by endothelium-dependent mechanisms involving only cGMP.
Neuropeptide Y is a potent vasoconstrictor and a cardiodepressant in rat
Authors: Zukowska-Grojec Z. , Marks E. S. , Haass M.
Published: December 2017

Neuropeptide Y (NPY) is contained in and coreleased with norepinephrine (NE) from sympathetic nerves innervating vascular and cardiac tissues. The effects of NPY infusion on systemic hemodynamics and cardiac performance were compared with those of NE in conscious and pentobarbital sodium-anesthetized rats. A 10-min infusion of NPY (2 nmol.kg-1.min-1) decreased cardiac index (CI) 20% and stroke volume index (SVI) 9% with increases of 20% in mean arterial pressure (MAP) and 48% in total peripheral resistance (TPR). Conversely, NE (1.0 microgram.kg-1.min-1) increased SVI 14%, MAP 29%, and TRP 26%, with no change in CI. Heart rates decreased similarly (approximately 60 beats/min) but only NE-induced bradycardia was reversible by methylatropine nitrate. In anesthetized rats NPY (0.1 nmol.kg-1.min-1) increased left ventricular end-diastolic pressure (LVEDP) 20 +/- 10 mmHg (means +/- SD, n = 7) and decreased dP/dt by 8 +/- 6%. NE (0.07 microgram.kg-1.min-1) produced an equivalent pressor response, however, dP/dt rose 22 +/- 10% whereas LVEDP increased significantly less than with NPY. Thus NPY is a potent vasoconstrictor exerting similar effects to NE on MAP and TPR but, unlike NE, possesses negative inotropic and chronotropic activity.
Factors influencing myocardial response to metabolic acidosis in isolated rat hearts
Authors: Watters T. A. , Wendland M. F. , Parmley W. W. , James T. L. , Botvinick E. H. , Wu S. T. , Sievers R. , Wikman-Coffelt J.
Published: December 2017

We assessed the effects of metabolic acidosis in Langendorff rat hearts to identify factors influencing myocardial response to metabolic acidosis. Intracellular pH (pHi), beta-ATP, phosphocreatine, and inorganic phosphate (Pi) content were measured by 31P nuclear magnetic resonance spectroscopy along with simultaneous measurements of coronary flow and developed pressure during 30 min of perfusion at pH = 6.8, followed by 15 min of reequilibration at pH = 7.4. Under high work-load conditions, pHi, high-energy phosphates, coronary flow, and developed pressure were severely reduced during metabolic acidosis. Each of these hearts exhibited a progressive decline in developed pressure and stopped beating during reequilibration. Lowering work load prevented severe biochemical or mechanical deterioration, allowing complete recovery during reequilibration. In the presence of high work load, factors found to improve myocardial tolerance to metabolic acidosis included maintaining base-line or higher levels of coronary flow with vasodilators or substitution of pyruvate for glucose as the energy-producing substrate. Raising perfusate osmolality did not prevent severe decreases in coronary flow and developed pressure during acidosis, but did allow a dramatic recovery during reequilibration. Recovery of biochemical and mechanical performance after 30 min of metabolic acidosis was directly related to 1) ln[ATP]/[ADP]f[Pi] greater than or equal to 4.1, where [ADP]f is the concentration of free ADP; 2) pHi greater than 6.40; and 3) ATP level greater than or equal to 75% of control.
Cardiac output in adult and neonatal rats utilizing impedance cardiography
Authors: Gotshall R. W. , Breay-Pilcher J. C. , Boelcskevy B. D.
Published: December 2017

Impedance cardiography (IC) has the potential to be applied to very small animals for the measurement of cardiac output (Q). To evaluate this, Q measured by impedance (ZQ) and thermal dilution (TDQ) were compared in adult Sprague-Dawley rats. Absolute values for TDQ were comparable with ZQ (e.g., 29.7 vs. 26.0 ml.min-1.100 g-1), and both equally followed the change in Q caused by hemorrhage and reinfusion of blood. IC was also evaluated in neonatal rats (1 and 7 day old). Control ZQ values were 113 ml.min-1.100 g-1 for the 1-day-old rats, and 104 ml.min-1.100 g-1 for 7-day-old rats. Both stroke volume and Q decreased with head-up tilt and increased with head-down tilt for both ages. Therefore, in the neonate, ZQ decreased appropriately with age and with preload reduction. From these results, it is concluded that IC can be utilized to evaluate cardiac function in neonatal and adult rats.
Altered endothelial cell-mediated arterial dilation in dogs with D. immitis infection
Authors: Kaiser L. , Williams J. F. , Meade E. A. , Sparks H. V.
Published: December 2017

Vascular endothelial cells regulate arterial diameter in vivo and in vitro. Stimulation of endothelial cell muscarinic receptors by acetylcholine results in the production and release of a nonprostaglandin metabolite of arachidonic acid that causes vascular smooth muscle relaxation. We examined femoral artery endothelium-dependent vasodilator responses in normal dogs and dogs with heartworm (Dirofilaria immitis) infection. Endothelium-dependent vascular reactivity was attenuated in dogs with D. immitis infection studied in the spring but not in the fall. The dilator response was inversely related to the number of female worms but not related to the presence of circulating microfilariae. Indomethacin markedly depressed responses to acetylcholine in dogs with D. immitis but did not alter acetylcholine-induced dilation in normal dogs. These data suggest that D. immitis releases substances that alter distal arterial endothelial cell arachidonic acid metabolism. The seasonal pattern may reflect the onset of maximal reproductive activity in the spring and its decline as the vector season ends in the fall.
Cerebral blood flow autoregulation during intracranial hypertension in hypoxic lambs
Authors: Borel C. O. , Backofen J. E. , Koehler R. C. , Jones M. D. , Traystman R. J.
Published: December 2017

We tested the hypothesis that hypoxic hypoxia interferes with cerebral blood flow (CBF) autoregulation when intracranial pressure (ICP) is elevated in pentobarbital-anesthetized lambs (3 to 9 days old). Cerebral perfusion pressure (CPP) was lowered stepwise from 73 to 23 mmHg in eight normoxic lambs and from 65 to 31 mmHg in eight other hypoxic lambs by ventricular infusion of artificial cerebrospinal fluid. In normoxic lambs, CBF measured by microspheres was not significantly changed over this range of CPP. In animals made hypoxic [arterial O2 tension (PaO2) of 28 Torr; 47% arterial O2 saturation], base-line CBF was twice that of normoxic lambs. CBF was unchanged as CPP was reduced to 31 mmHg. Lower levels of CPP were not attained because a pressor response occurred with further elevations of ICP. No regional decrements in blood flow to cortical arterial watershed areas or to more caudal regions, such as cerebellum, brain stem, or thalamus, were detected with elevated ICP. Cerebral O2 uptake was similar in both groups and did not decrease when CPP was reduced. These results demonstrate that normoxic lambs have a considerable capacity for effective autoregulation of CBF when ICP is elevated. Moreover, cerebral vasodilation in response to a level of hypoxia approximating that normally seen prenatally does not abolish CBF autoregulation when ICP is elevated during the first postnatal week.
Intracellular calcium levels in phorbol ester-induced contractions of vascular muscle
Authors: Jiang M. J. , Morgan K. G.
Published: December 2017

Intracellular calcium concentration ([Ca2+]i) was measured with aequorin in ferret and rat aortic strips contracted with phorbol esters. In ferret aorta, 12-deoxyphorbol 13-isobutyrate 20-acetate (DPBA, 1 microM) induced contractions without significantly increasing [Ca2+]i, whereas 21 mM K+ induced smaller contractions with a significant rise in [Ca2+]i. Ca2+-free 2.5 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA)-physiological saline solution (PSS) had no effect on DPBA-induced tension, whereas it abolished contractions induced by 66 mM K+. The alpha 1-adrenergic agonist phenylephrine (10(-5) M) induced less than 10% of the tension with no initial [Ca2+]i spike under Ca-free conditions. In rat aorta, both phorbol 12-myristate 13-acetate (PMA, 2 microM) and DPBA (1 microM) induced contractions without increasing [Ca2+]i; Ca2+-free EGTA-PSS or the addition of the calcium channel blocker gallopamil (D600, 1 microM), however, abolished greater than 50% of the tension induced by either phorbol ester with a decrease in [Ca2+]i. These results are consistent with the idea that 1) resting [Ca2+]i is both sufficient and required to support phorbol ester-induced contractions in two vascular smooth muscles, suggesting an increased sensitivity of the contractile apparatus for Ca2+, and 2) there are differences in the mechanisms by which phorbol esters and alpha 1-agonists may activate vascular smooth muscle.
Improved cardiac cell excitation with symmetrical biphasic defibrillator waveforms
Authors: Jones J. L. , Jones R. E. , Balasky G.
Published: December 2017

According to the most commonly accepted hypothesis, ventricular defibrillation is produced by exciting cells in a critical mass of the ventricle. For monophasic defibrillator waveforms, this hypothesis correctly predicts a direct correlation between defibrillation threshold in the transthoracic calf model and excitation threshold for extracellular field stimulation in the cultured cell model. To further test the hypothesis, we determined whether symmetrical biphasic waveforms, which reduce defibrillation threshold in the calf to approximately 65% of that of the corresponding monophasic waveform (14), decrease excitation threshold in the cultured cell model. Experiments were performed on 100- to 250-microns aggregates from 10- to 12-day-old chick embryos. Excitation threshold strength-duration curves obtained at extracellular potassium (Ko) = 6.5 mM and pacing interval of 1,000 ms showed a significant reduction for symmetrical biphasic rectangular waveforms, when compared with the corresponding monophasic waveforms for durations greater than 3 ms. At the rheobase, the threshold ratio between the biphasic and monophasic waveforms was 0.63 (SE = 0.02). Transmembrane potentials during stimulation showed that excitation takes place during the second portion of the biphasic waveform for intensities that are subthreshold for the monophasic waveform. The relative effectiveness of the biphasic waveform (5-ms duration) increases under "fibrillation conditions" of short pacing interval (300 ms) and high extracellular potassium (10.5 mM). These results show that symmetrical biphasic waveforms decrease excitation threshold in the cultured cell model and that the degree of threshold reduction is dependent on Ko and beat rate.
Effects of left circumflex Ameroid constrictor placement on adrenergic innervation of myocardium
Authors: Roth D. M. , White F. C. , Mathieu-Costello O. , Guth B. D. , Heusch G. , Bloor C. M. , Longhurst J. C.
Published: December 2017

We evaluated the adrenergic innervation of the swine and canine myocardium after placement of an Ameroid constrictor around the left circumflex coronary artery (LCX). Fluorescent histochemistry was used to identify adrenergic nerve terminals in the myocardium and coronary vasculature. Ameroid occlusion of the proximal LCX in 10 pigs for 3 wk resulted in 6 +/- 1% infarction as well as myocardial ischemia in the left circumflex region of pigs studied during exercise. However, placement of the Ameroid constrictor did not significantly alter the surface density of the nerve terminals in the LCX region of myocardium when compared with innervation of control hearts. Histological examination of the coronary arterial adrenergic innervation in Ameroid-occluded pigs revealed that coronary vessels in the circumflex region of the heart were innervated. Similarly, in seven LCX Ameroid-occluded dogs, no significant decrease in adrenergic innervation of the LCX region of myocardium was observed when compared with control dogs. In contrast LCX Ameroid-occluded pigs demonstrated significant (P less than 0.01) denervation of the left anterior descending (LAD) region of myocardium when compared with control animals. The close proximity of adrenergic nerve bundles in the proximal LAD region indicates that denervation of the myocardium supplied by the LAD may result from the dissection and/or fibrosis associated with placement of the Ameroid constrictor on the proximal LCX. Our results suggest that placement of an Ameroid constrictor on the proximal LCX does not significantly alter the adrenergic innervation of the LCX-perfused myocardium or its associated coronary vasculature. However, denervation of LAD-perfused myocardium and its vasculature may result.
Influence of acidosis on inotropic effect of catecholamines in newborn rabbit hearts
Authors: Nakanishi T. , Okuda H. , Kamata K. , Seguchi M. , Nakazawa M. , Takao A.
Published: December 2017

The influence of acidosis on the inotropic effect of isoproterenol was studied in the isolated arterially perfused heart of the newborn rabbits. Baseline mechanical function during acidosis (pH 6.8) was not different from control (pH 7.4). However, the inotropic effect of isoproterenol was significantly suppressed in the acidotic muscles. The increment of myocardial adenosine 3',5'-cyclic monophosphate (cAMP) content during isoproterenol infusion was also reduced in acidosis. Inotropic effects of Ca and dibutyryl cAMP in the acidotic muscles were not significantly different from those in the control muscles. beta-Receptor number and affinity in the respiratory acidotic muscle was similar to those in the control muscle. Effects of pH on myocardial beta-receptor and adenylate cyclase activity were further determined in the membrane fraction by changing the pH of the reaction medium from 7.4 (control) to 6.8 or 6.0. beta-Receptor numbers were significantly decreased at pH 6.0 but not at pH 6.8. Adenylate cyclase activity was depressed at pH 6.8 and 6.0. These data suggest that the inotropic effect of isoproterenol is diminished in the acidotic muscle. This may be due to the decreased activation of cAMP production, which in turn most likely results from depressed adenylate cyclase activity.
Increased skin lymph protein clearance after a 6-h arterial bradykinin infusion
Authors: Mullins R. J. , Hudgens R. W.
Published: December 2017

When bradykinin (0.15-0.28 micrograms.kg-1.min-1) was infused into both femoral arteries of 11 anesthetized dogs, skin lymph flows increased by 25-371% within 2 h, and mean lymph protein concentrations increased by one-third. To determine whether, in addition to the initial increase in permeability, a 6.5- to 10-h bradykinin infusion caused a sustained effect, the bradykinin infusion into one hindpaw was stopped after 2 h (2HR), whereas the contralateral hindpaw was infused continuously (CONT). Two hours after the bradykinin infusion was stopped, Ringer lactate equal to 10% of the dog's body weight was given intravenously to further increase lymph flow. After Ringer lactate infusion, increase in lymph protein clearance from the CONT hindpaws was greater than that from the 2HR hindpaws (change in clearance from before Ringer lactate infusion to final: 2HR, 6.9 +/- 1.4 to 8.8 +/- 1.1; CONT, 23.4 +/- 2.5 to 40.2 +/- 4.8 microliters/min). In the final lymph samples of the CONT, but not 2HR, hindpaws, the lymph-to-plasma ratio for immunoglobulin G and immunoglobulin M divided by the albumin lymph-to-plasma ratio exceeded the value of these ratios in the base-line samples. An intravenous bolus of Evans blue dye was given less than 2 h before the end of the experiment. The concentrations of dye in the final lymph samples were greater in CONT hindpaws (12.6 +/- 3.7% plasma equivalents) than in the 2HR hindpaws (1.1 +/- 0.5%). A continuous 6.5- to 10-h intra-arterial bradykinin infusion produced a sustained increase of transvascular protein clearance in skin that is consistent with a sustained increase in microvascular membrane permeability.
Effect of pressure and intimal damage on 131I-albumin and [14C]sucrose spaces in aorta
Authors: Tedgui A. , Lever M. J.
Published: December 2017

To measure the distribution volume for sucrose and albumin in the media of the rabbit thoracic aorta, we studied the uptake of tracers in vitro. In most cases the tracers were applied to both luminal and adventitial surfaces at the same concentration. When transmural convection was prevented by pressurization of the arteries with air, there was a decrease in sucrose space (19% at 70 mmHg and 28% at 180 mmHg) and in albumin space (60% at 70 mmHg and 66% at 180 mmHg), compared with the respective spaces in relaxed arteries (0.42 for sucrose and 0.08 for albumin). Much smaller changes were found when intact vessels were pressurized with liquid (insignificant for sucrose, decreases of 24% at 70 mmHg and 14% at 180 mmHg for albumin). Removal of the endothelium, which increases transmural fluid flux, increased the space for sucrose (not significantly at 70 mmHg and 17% at 180 mmHg) and particularly for albumin (100% at 70 mmHg and 250% at 180 mmHg). We conclude that the interstitial volume and consequently the protein space within the media can be modified both by distending stresses applied to the vessel and by transmural fluid flux.
Carnitine-acylcarnitine translocase in ischemia: evidence for sulfhydryl modification
Authors: Pauly D. F. , Yoon S. B. , McMillin J. B.
Published: December 2017

After coronary occlusion and reflow, carbohydrate catabolism is enhanced, whereas fatty acid utilization is delayed. To test the hypothesis that "stunning" of fatty acid use by ischemic heart reflects reduced fatty acid transport into the mitochondria, two activities involved in the transport were examined: carnitine-acylcarnitine translocase and carnitine palmitoyltransferase II (CPT II). The maximal velocity for carnitine exchange of the translocase is reduced 55% in mitochondria isolated from ischemic canine heart (60-min left circumflex occlusion). Mitochondria from ischemic heart show 50% depletion in total matrix glutathione, a 200% increase in glutathione disulfide (GSSG), and an 80% decrease in the ratio of reduced glutathione (GSH) to GSSG, suggesting that the loss of translocase activity may be a consequence of protein sulfhydryl modifications. In support of this, treatment of these mitochondria with the sulfhydryl-reducing agents, GSH or dithiothreitol, restores carnitine exchange to control. Partial return of mitochondrial GSH and a decrease in GSSG are observed with a 20-min reperfusion of the ischemic myocardium. Continued depression in carnitine exchange with reperfusion suggests that other mechanisms may prevent restoration of activity. Import of palmitoylcarnitine on the translocase is coupled to palmitoyl-CoA production by CPT II. Mitochondria from ischemic heart with decreased coupling activity also have the lowest palmitoylcarnitine-supported respiratory rates, suggesting that in severely ischemic tissue the translocation-transesterification sequence may become rate limiting to fatty acid oxidation.