bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal aortic growth in lambs: relation to blood flow changes at birth
Authors: Langille B. L. , Brownlee R. D. , Adamson S. L.
Published: December 2017

We have examined aortic growth and aortic hemodynamics in lambs in the perinatal period. Morphometry of histological cross sections indicated that abdominal aortic circumference decreased by 31% between 131 days of gestation and 2-3 wk postpartum. In contrast, the internal circumference of the thoracic aorta increased by 34% over the same time interval; thus size reduction of the abdominal aorta was not part of a generalized arterial response to ex utero life. We also determined medial cross-sectional area as an index of medial tissue mass. In the perinatal period (120 days gestation to 21 days postpartum), this index increased by 144% for the thoracic aorta but only by 69% in the abdominal aorta. Differences in rate of medial tissue accumulation were much greater postpartum than in utero. The relationship between abdominal aortic growth and hemodynamic changes was examined by instrumenting fetal lambs with blood pressure catheters, abdominal aortic blood velocity transducers, and sonomicrometer diameter crystals mounted on the abdominal aorta. Parturition, and the consequent loss of the placental circulation, caused a 73% reduction in abdominal aortic blood velocity. Abdominal aortic external diameter in the period between 4 and 14 days postpartum was reduced significantly compared with in utero values. These data are consistent with the hypothesis that blood flow changes at birth significantly influence arterial growth postpartum.
Neutrophil-mediated vascular leakage is not suppressed by leukocyte elastase inhibitors
Authors: Rosengren S. , Arfors K. E.
Published: December 2017

Application of leukotriene B4 (LTB4) to hamster cheek pouches induces neutrophil-dependent vascular leakage of macromolecules as well as leukocyte intravascular adherence and emigration. The effect of inhibitors of neutrophil elastase on these reactions was studied with intravital microscopy. Anesthetized hamsters were pretreated with the elastase inhibitors L 658,758, Eglin C, or dextran sulfate, and LTB4 (10 nM) was superfused over the cheek pouches. Neither Eglin C nor L 658,758 had any effect on the resulting vascular leakage of a macromolecular marker; in contrast, dextran sulfate suppressed this leakage by 85%. None of the compounds affected LTB4-induced leukocyte adherence or neutrophil diapedesis. The inhibitors were able to inhibit both hamster and human neutrophil elastase as estimated in crude neutrophil extracts. These results suggest that neutrophils extravasate and generate vascular leakage without the use of their elastase activity. The inhibitory effect of dextran sulfate on macromolecular leakage may be due to interaction with cationic proteins released from the neutrophils.
Responses of isolated pulmonary arteries to the C5a anaphylatoxin
Authors: Crowell R. E. , Van Epps D. E. , Reed W. P.
Published: December 2017

The anaphylatoxin C5a possesses spasmogenic activity in smooth muscle tissues. In this study, we examined the effect of C5a on isolated rabbit pulmonary artery (PA) ring segments under a variety of experimental conditions. C5a (1-100 nM) caused transient constriction of PA at resting tension. C5a-induced PA constriction was not affected by the histamine H1-receptor antagonist pyrilamine (1 microM) but was significantly decreased by the cyclooxygenase inhibitor indomethacin (1 microM). Disruption of the endothelial layer of the vessel had no effect on C5a activity in resting PA. PA, which had been preconstricted with norepinephrine (5 microM), exhibited a different response to C5a than PA at resting tension, however. C5a (1-10 nM) induced a biphasic response in preconstricted PA, initially causing further constriction followed by a greater degree of relaxation resulting in an overall decrease in PA tension. All responses of preconstricted PA to C5a were completely eliminated by indomethacin and significantly depressed by endothelial disruption. These data indicate that C5a interacts directly with isolated rabbit PA, but the nature of the PA response to this peptide depends on several variables including the presence or absence of active PA tension and cyclooxygenase metabolites, and the presence of intact endothelium.
Pertussis toxin abolishes the effect of neuropeptide Y on rat resistance arteriole contraction
Authors: Andriantsitohaina R. , Andre P. , Stoclet J. C.
Published: December 2017

Pertussis toxin (PTX) was used to investigate the possible involvement of a G protein in the mechanism of action of neuropeptide Y (NPY) on rat mesenteric arterioles. ADP ribosylation of membrane protein was assessed by gel electrophoresis followed by autoradiography. The effect of NPY was studied on contractions elicited either by addition of calcium to depolarized vessels or by the calcium agonist BAY K 8644. Under conditions in which PTX ADP-ribosylated a 40-41 kDa protein, the potentiation of contractions induced by NPY in both protocols was abolished. In contrast, the contraction induced by norepinephrine was unaffected by PTX. It is concluded that a G protein mediates the potentiating effect of NPY on external calcium-dependent contractions in rat mesenteric arterioles.
Antibiotics versus cardiovascular support in a canine model of human septic shock
Authors: Natanson C. , Danner R. L. , Reilly J. M. , Doerfler M. L. , Hoffman W. D. , Akin G. L. , Hosseini J. M. , Banks S. M. , Elin R. J. , MacVittie T. J. , et al.
Published: December 2017

This study compares the efficacy of antibiotics (cefoxitin and gentamicin), cardiovascular support (fluids and dopamine titrated by intravascular monitoring to hemodynamic end points), and a combination of these two therapies in dogs with septic shock induced by an intraperitoneal clot containing Escherichia coli. Survival rates were 0, 13, 13, and 43% in groups receiving no therapy (controls), antibiotics alone, cardiovascular support alone, or combined therapy (P less than 0.01), respectively. The improved survival observed in the group receiving combined therapy considerably exceeded that in the groups receiving either therapy alone (i.e., a synergistic increase P less than 0.05). Compared with antibiotics alone, cardiovascular support alone prolonged survival time (P less than 0.006). All groups developed similar and significant (P less than 0.01) increases in endotoxin levels; however, in the combined therapy group, nonsurvivors (compared with survivors) had higher levels of endotoxemia (P less than 0.05). Although survivors and nonsurvivors in the combined therapy group required similar (P = 0.10) quantities of fluid therapy, nonsurvivors gained more weight (P less than 0.05), suggesting abnormal vascular permeability with extravascular retention of fluids in the nonsurvivors. This study demonstrates that antibiotics alone and cardiovascular support alone are relatively ineffective in the treatment of septic shock. When combined, however, these two therapies provide moderately successful treatment for this highly lethal disorder.
Metabolic and functional consequences of barium-induced contracture in rabbit myocardium
Authors: Shibata T. , Berman M. R. , Hunter W. C. , Jacobus W. E.
Published: December 2017

Barium contracture tonically activates myocardium while preserving cellular integrity. We studied the metabolic and mechanical consequences of sustained Ba2+ contracture. We measured the time course of phosphocreatine (PCr), ATP, Pi, total phosphate, and intracellular pH via 31P nuclear magnetic resonance (NMR) in isolated, isovolumic rabbit hearts. For mechanical studies, we measured force transients and dynamic stiffness in excised rabbit right ventricular papillary muscles at different elapsed times in Ba2+ contracture. In the perfused hearts, PCr fell steadily to 20% of control after 60 min. ATP remained constant for approximately 25 min then fell to 25% by 60 min. Pi rose to 200% within 15 min and then remained unchanged, whereas total phosphate dropped steadily to 50% of control by 60 min. Myocardial O2 consumption remained near control for 30 min and then declined to 50% by 60 min. Consistent with ATP and O2 consumption measurements, mechanical responses were unchanged for approximately the first half hour. Because of the elevated Pi, however, myofilament kinetics may have been accelerated compared with the control metabolic state. After the initial period of stable contracture, the gradual alteration of mechanical behavior exhibited a progressive trend toward more rigor-like characteristics. In summary, myocardium in Ba2+ contracture is metabolically and mechanically stable for approximately 30 min but begins to degrade thereafter. When compared with other tonic states of activation, Ba2+ contracture appears to be less demanding energetically.
Influence of atrial natriuretic factor on intravascular volume displacement in pigs
Authors: Rutlen D. L. , Christensen G. , Helgesen K. G. , Ilebekk A.
Published: December 2017

The present study was undertaken to quantitate the influences of transcapillary fluid loss, urine output, and the capacity vessels on volume displacement toward and away from the right heart during atrial natriuretic factor (ANF) administration. In eight anesthetized pigs undergoing carotid denervation, cervical vagotomy, and splenectomy, blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that volume displacement toward and away from the heart could be recorded as change in reservoir volume. Human ANF-(99-126) (0.1 micrograms.kg-1.min-1) for 15 min was associated with a decrease in reservoir volume of 2.7 +/- 0.4 ml/kg (P less than 0.05), which resulted from a decrease in total blood volume of 8.6 +/- 1.0 ml/kg (P less than 0.05) and a displacement from the capacitance vasculature of 5.9 +/- 1.3 ml/kg (P less than 0.05). Since urine output increased only slightly, virtually all of the total blood volume decrement was due to a displacement of fluid into the extravascular space. Thus ANF acts to displace volume away from the right heart. The displacement is due almost entirely to an increase in transcapillary fluid loss; however, volume displacement from the capacity vessels to the right heart partially counteracts this transcapillary influence.
Effects of neuropeptide Y on regulation of blood flow rate in canine myocardium
Authors: Svendsen J. H. , Sheikh S. P. , Jorgensen J. , Mikkelsen J. D. , Paaske W. P. , Sejrsen P. , Haunso S.
Published: December 2017

The effect of neuropeptide Y (NPY) on tension development was examined in isolated canine coronary arteries, and the effects on local myocardial blood flow rate were studied in open-chest anesthetized dogs by the local 133Xe washout technique. By immunohistochemistry, numerous NPY-like immunoreactive nerve fibers were identified in the adventitia of canine coronary arteries. NPY (10(-9)-10(-6) M) supplied to isolated epicardial segments of the left anterior descending coronary artery induced a modest vasoconstriction, with a maximum tension of 0.95 mN, that was only 6.9% of the response to K+. In contrast, intracoronary NPY (0.01-10 micrograms) induced a considerable degree of vasoconstriction; the reduction of blood flow rate was dose related, with a maximum reduction to 52% of control values. The effect of intracoronary NPY (1 microgram) on maximally relaxed arterioles elicited by 30 s of ischemia was studied in separate experiments during reactive hyperemia. NPY induced a decrease in maximum blood flow during reactive hyperemia (166.6 vs. 214.6% of preocclusive blood flow rate, mean values; P = 0.05), an increase in the cumulative excess blood flow (61.0 vs. 35.3 ml/100 g; P = 0.02), and an increase in the duration of reactive hyperemia compared with control values (66 vs. 41 s; P = 0.02). Thus we conclude that in the heart NPY is a potent vasoconstrictor that seems to act preferentially on smaller intramyocardial arterioles. Furthermore, NPY inhibits vascular relaxation of myocardial resistance vessels after ischemia, suggesting that this peptide may participate in the regulation of myocardial blood flow not only during physiological conditions but also after ischemia.
Nicotine-induced skeletal muscle vasodilation is mediated by release of epinephrine from nerve terminals
Authors: Diana J. N. , Qian S. F. , Heesch C. M. , Barron K. W. , Chien C. Y.
Published: December 2017

To determine the role of sympathetic innervation on nicotine-induced alterations in peripheral (hindlimb) blood flow in the pentobarbital-anesthetized dog, one hindlimb was acutely denervated and remained attached to the body by only the femoral artery and vein, whereas the contralateral limb remained innervated and intact. Measurements were made of aortic pressure, femoral artery and venous pressures, femoral artery flow, and plasma catecholamine levels during intravenous systemic infusion of nicotine. The response to nicotine (9-36 micrograms.kg-1.min-1) on the denervated side was a transient increase followed by a persistent decrease in flow and increase in vascular resistance. The response in the innervated limb was a large increase in blood flow and decrease in vascular resistance. The vasoconstrictor and vasodilator responses could be abolished by pretreatment with both propranolol and phentolamine. The vasodilator response could not be abolished by cholinergic or histaminergic receptor antagonism. Hexamethonium abolished all systemic and peripheral responses to nicotine. Desipramine selectively abolished the vasodilator response in the innervated hindlimb. The vasodilator and vasoconstrictor responses could be mimicked with systemic or local administration of epinephrine. We conclude that, in the hindlimbs of dogs, nicotine stimulates the release of epinephrine from nerve terminals and/or tissue stores to activate beta 2-adrenoceptors and promote vasodilation in skeletal muscle of innervated preparations.
Proliferation in vivo and in culture of differentiated adult atrial cardiomyocytes from transgenic mice
Authors: Steinhelper M. E. , Lanson N. A. , Dresdner K. P. , Delcarpio J. B. , Wit A. L. , Claycomb W. C. , Field L. J.
Published: December 2017

Transgenic mice expressing atrial natriuretic factor-SV40 T-antigen fusion genes (ANF-TAG) developed unilateral right atrial tumors composed of differentiated dividing cardiomyocytes. The atrial tumors could be propagated as transplantable tumor lineages in syngeneic animals. Cardiomyocytes derived from ANF-TAG atrial tumors did not proliferate in tissue culture. However, cardiomyocytes derived from the transplantable tumor lines proliferated in culture, and these proliferating cardiomyocytes could be passaged in culture and recovered from frozen stocks. Cardiomyocytes from either tumor source were highly differentiated as determined by diverse functional and structural criteria. The cells continued to express numerous cardiac-specific proteins and retained ultrastructural features characteristic of cardiomyocytes including well-formed myofibrils, transverse tubules, and intercalated disks. In addition, the cultured cells displayed spontaneous electrical and contractile activities. These atrial tumor cardiomyocytes are a novel experimental resource for the identification of genes regulating the cardiomyocyte cell cycle.
Perfused prenodal lymphatics are constricted by prostaglandins
Authors: Dabney J. M. , Buehn M. J. , Dobbins D. E.
Published: December 2017

Prostaglandins may contribute to the control of lymph flow by affecting lymphatic vessel contractility. We measured the pressure in perfused prenodal lymphatic vessel in the paw of the anesthetized dog as affected by administration of prostaglandins E1, E2, F2 alpha or arachidonic acid. The forelimb was perfused at constant flow with blood obtained from a femoral artery. Systemic arterial, central venous, and forelimb vascular pressures were measured. When added to the lymphatic perfusate, all of the prostaglandins and arachidonic acid caused constriction of lymphatic vessels. Perfusion of prenodal lymphatics separated from downstream nodes and vessels showed that this constriction occurred primarily in prenodal vessels. However, only prostaglandin F2 alpha caused lymphatic constriction when infused into the blood to the forelimb. Because prostaglandins are a common component of the lymph leaving an area of tissue damage, these results are compatible with the possibility that prostaglandins, by directly affecting lymphatics, help modulate lymph flow following local injury.
Spinal NMDA receptors mediate pressor responses evoked from the rostral ventrolateral medulla
Authors: Bazil M. K. , Gordon F. J.
Published: December 2017

These studies investigated the role of spinal N-methyl-D-aspartic acid (NMDA) receptors in the mediation of cardiovascular responses evoked by L-glutamate (L-Glu) stimulation of the rostral ventrolateral medulla (RVM). Microinjections of L-Glu into the RVM of urethan-anesthetized rats increased mean arterial pressure (MAP) and heart rate. Intrathecal administration of the NMDA receptor antagonists D-(-)-2-amino-7-phosphonoheptanoic acid (D-AP-7) or 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) reduced MAP and heart rate. Blockade of NMDA receptors by D-AP-7 or CPP in the caudal thoracic spinal cord markedly reduced RVM pressor responses with little effect on evoked tachycardia. Administration of D-AP-7 to the rostral thoracic spinal cord had no effect on RVM pressor or tachycardic responses. Intrathecal D-AP-7 and CPP abolished the cardiovascular effects of intrathecal NMDA without reducing those produced by intrathecal kainic acid or the quisqualate agonist DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). These results indicate that 1) tonic activation of spinal NMDA receptors participates in the maintenance of sympathetic outflow to the heart and blood vessels, 2) pressor responses evoked from the RVM require synaptic activation of spinal NMDA receptors, and 3) an excitatory amino acid may be the neurotransmitter of pressor pathways descending from the RVM to the spinal cord.
Protein kinase C is not involved in alpha 1-adrenoceptor-mediated positive inotropic effect
Authors: Endou M. , Hattori Y. , Tohse N. , Kanno M.
Published: December 2017

This study was performed to determine whether activation of protein kinase C is responsible for the positive inotropic effect of alpha 1-adrenoceptor stimulation in rat papillary muscle. In the presence of 1 microM propranolol, phenylephrine (10 microM) produced triphasic inotropic response that was accompanied by prolongation of action potential duration (APD) and hyperpolarization of membrane potential. Phorbol 12,13-dibutyrate (PDBu, 0.1 microM) abolished the negative inotropic effect of phenylephrine and apparently resulted in enhancement of the positive inotropic effect. PDBu also attenuated the phenylephrine-induced hyperpolarization without affecting the APD prolongation. However, such changes were not observed with 12-O-tetradecanoylphorbol-13-acetate (TPA, 0.1 microM). Neither PDBu nor TPA increased the force of contraction or prolonged APD similar to phenylephrine. The protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H 7, 10 microM) did not suppress the changes induced by PDBu, and more importantly H 7 did not affect the inotropic and electrophysiological effects of phenylephrine. Both TPA and PDBu significantly inhibited the phenylephrine-induced phosphoinositide hydrolysis as measured by [3H]inositol monophosphate, and these inhibitory effects were eliminated in the presence of H 7. Our results provide an argument against a role of protein kinase C activation in the alpha 1-adrenoceptor-mediated inotropic and electrophysiological effects.
Baroreflex-induced vasoconstriction in active skeletal muscle of conscious dogs
Authors: O'Leary D. S. , Rowell L. B. , Scher A. M.
Published: December 2017

We investigated the magnitude of baroreflex-mediated vasoconstriction in the hindlimbs of six conscious dogs at rest and during four levels of treadmill exercise ranging in intensity from mild (2 mph, 0% grade) to heavy (6 mph, 10% grade). Dogs were instrumented with vascular occluders on both common carotid arteries, an electromagnetic flow probe and vascular occluder on the terminal aorta, and a catheter in a branch of the femoral artery; aortic baroreceptors were intact. The responses to a 2-min carotid occlusion were observed at rest and after 3-5 min of exercise at each work rate. The increases in mean arterial pressure during carotid occlusion were similar at rest and at each level of exercise (26 +/- 4 to 35 +/- 3 mmHg; no significant difference). At rest, carotid occlusion caused only a small but significant decrease in terminal aortic vascular conductance (TAC) (-0.89 +/- 0.21 ml.min-1.mmHg-1, P less than 0.05). During mild exercise, baseline terminal aortic blood flow (TAQ) and TAC increased, and the reduction in TAC during carotid occlusion exceeded that observed at rest (-1.85 +/- 0.42 ml.min-1.mmHg-1, P less than 0.05). As exercise intensity increased, the magnitude of the reduction in TAC during carotid occlusion increased linearly with the baseline TAQ. At the highest work rate, approximately 59% of the increase in mean arterial pressure during carotid occlusion was due to the large decrease in TAC (-6.35 +/- 0.50 ml.min-1.mmHg-1). We conclude that the vasoconstriction of active skeletal muscle during the pressor response to bilateral carotid occlusion increased with exercise intensity.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution volumes and macromolecular mobility in rat tail tendon interstitium
Authors: Aukland K.
Published: December 2017

This study explores a centrifugation technique for estimating interstitial fluid composition and macromolecular transport. Rat tail tendon supported by a nylon net was subjected to three consecutive 15-min centrifugations at 3,000, 6,000, and 14,000 revolutions per minute (rpm) or 3, 10, and 20 min at 6,000 rpm. Colloid osmotic pressure (COP) and concentrations of albumin, total protein, and hyaluronan in subsequent centrifugate fell as exponential functions of accumulated centrifuged volume, reaching 10-30% of initial level at an accumulated volume corresponding to 8% of tendon volume. Intercepts for zero centrifugation were 11 mmHg (COP), 22 mg/ml (albumin), and 39 mg/ml (total protein), probably reflecting concentrations in protein-accessible interstitial volume. Corresponding serum values were 19 mmHg, 34 mg/ml, and 63 mg/ml. Tendon distribution spaces were 0.62 (H2O), 0.57 (51Cr-labeled-EDTA), and 0.22 ml/g wet wt (albumin). The progressive fall in centrifugate concentrations probably reflects increasing resistance to macromolecular transport, with a sieving coefficient for albumin falling from 1 to 0.35, or increasing contribution of fluid from protein-excluded space. The effect was reversed by rehydration, which caused increased concentrations in centrifugate. Low hyaluronan concentrations in centrifugate (0.25 mg/ml) compared with that of whole tendon (0.4 mg/g wet wt) reflect either a large "bound" fraction in tissue or marked sieving of hyaluronan in normohydration.
Intravascular chemoattractants inhibit diapedesis by selective receptor occupancy
Authors: Goldman G. , Welbourn R. , Klausner J. M. , Kobzik L. , Valeri C. R. , Shepro D. , Hechtman H. B.
Published: December 2017

An extravascular chemoattractant leads to migration of polymorphonuclear neutrophils (PMN) to that site, whereas intravascular administration leads to PMN oxidative activity and sequestration in microvessels but no diapedesis. This study examines the inhibitory role of intravascular chemoattractants. Rabbits (n = 37) were pretreated with zymosan-activated plasma (ZAP), leukotriene (LT) B4, or thromboxane (Tx) mimic. These agents were given intra-arterially, topically into plastic chambers taped atop sites of dermabrasion on the back, or into a lobar bronchus (n = 35). Intra-arterial injection of each chemoattractant resulted, 10 min later, in a 29-42% increase in intracellular PMN H2O2. In saline-infused animals, topical administration of the chemoattractants into dermabrasion chambers resulted in PMN accumulation per cubic millimeter after 3 h of 600 with ZAP, 536 with LTB4, and 643 with Tx mimic; all values higher than 46 with saline and 63 with normal plasma (all P less than 0.05). In other saline-infused animals, lobar lung aspiration of chemoattractants led to diapedesis as measured in bronchoalveolar lavage (BAL) fluid (PMN x 10(4)/ml) after 3 h: 19.0 with ZAP, 11.2 with LTB4 and 14.5 with Tx mimic, all greater than aspiration with saline or normal plasma 4.0 and 4.9, respectively (all P less than 0.05). Intra-arterial chemotactic administration inhibited subsequent PMN diapedesis in response to that same chemoattractant, both in dermabrasion chambers and in BAL fluid. When different intra- and extra-vascular chemoattractants were used diapedesis was promoted. Thus Tx infused intra-arterially and ZAP applied to a blister or lobar bronchus led to rapid cell migration and increased cell numbers.(ABSTRACT TRUNCATED AT 250 WORDS)
Intracellular free Ca2+ is elevated in hypertrophic aortic muscle from hypertensive rats
Authors: Papageorgiou P. , Morgan K. G.
Published: December 2017

Vessels from hypertensive animals have been shown to have increased medial thickness and also to exhibit increased sensitivity to agonists. We tested the hypothesis that changes in intracellular Ca2+ concentration [( Ca2+]i) may be associated with the growth response and the altered contractility of the aortic smooth muscle of modified coarctation-hypertensive rats. Freshly isolated single cells, loaded with fura-2, showed significantly higher [Ca2+]i both at rest and after depolarization compared with normal rat aortic cells. These cells also exhibited at rest a significant nuclear-cytoplasmic [Ca2+] gradient. Furthermore, the increased [Ca2+]i was associated with increased nuclear volumes, suggesting the presence of polyploid nuclei, as determined by ethidium dimer fluorescence imaging. Intact vascular rings from hypertrophic rat aortas, loaded with aequorin, also showed significantly higher [Ca2+]i at rest and after depolarization compared with normal rat aortas. In addition, the maximal force per cross-sectional area generated by the hypertrophic muscle was less than normal, consistent with a change in the contractile phenotype of the growing smooth muscle cells. This is the first report to directly indicate an increase in [Ca2+]i in hypertrophic vascular smooth muscle in hypertensive animals.
Method for studying arterial wave transmission effects on left ventricular function
Authors: Kirkpatrick R. D. , Campbell K. B. , Bell D. L. , Taheri H.
Published: December 2017

A technique for studying the real-time effects of arterial wave reflections on the performance of the isolated left ventricle was investigated. Real-time arterial loading of an isolated ferret heart with an asymmetric T-tube wave transmission model was obtained with the use of a multiprocessor computer control system and a volume control linear motor pump. The multiprocessor computer system was programmed to compute the instantaneous aortic flow from the instantaneous ventricular pressure. The time integral of the flow was used as a command to the linear motor pump to control the instantaneous ventricular volume. This loading system allowed the imposition of a wide variety of vascular impedances on the ventricle by changing the parameters of the asymmetric T-tube model.
Diastolic stiffness impairs left ventricular function during hypovolemic shock in pigs
Authors: Walley K. R. , Cooper D. J.
Published: December 2017

To determine the causes of impaired left ventricular function during hypovolemic shock we measured diastolic and end-systolic pressure-volume relationships and hemodynamics. Left ventricular pressure (Millar catheter) and volume (3 ultrasonic crystal pairs) were measured in six open-chest, chloralose-morphine anesthetized, juvenile pigs. After baseline measurements, the pigs were bled and maintained at a mean aortic pressure of 50 cmH2O for 7 +/- 1 h. After resuscitation with all shed blood, left ventricular function was markedly impaired as indicated by increased end-diastolic pressure (20.3 vs. 8.7 cmH2O at baseline, P less than 0.05), decreased aortic pressure (36% of baseline, P less than 0.01), and decreased stroke volume (50% of baseline, P less than 0.01). Systolic contractility was increased (P less than 0.05), but diastolic compliance was greatly reduced due to decreased diastolic maximum (52% of baseline, P less than 0.01) and equilibrium volumes (57% of baseline, P less than 0.01). We conclude that impaired left ventricular function during hypovolemic shock is due entirely to increased diastolic stiffness. These results can theoretically be accounted for by a 20% reduction in myocardial muscle length with no change in muscle stress-strain characteristics. This may be the physiological expression of morphologically observed myocardial "zonal lesions" of hypovolemic shock.
Pressure segment length analysis of right ventricular function: influence of loading conditions
Authors: Calvin J. E.
Published: December 2017

The purpose of this study was to determine whether segment lengths measured from the right ventricular inflow and outflow tract regions of the right ventricle would accurately reflect true volume changes of the right ventricle and to determine the response of the right ventricle to afterload increases induced by both constricting the pulmonary artery (PAC) and embolizing the pulmonary circulation with glass beads (GBE). Three excised hearts were instrumented with segment-length crystals attached to the inflow and outflow tract regions, and saline was instilled into a balloon implanted inside the right ventricular cavity. The experiments showed a high correlation (r greater than or equal to 0.90 in all cases) between static segment lengths and volume instilled. In open chest, open pericardial canine experiments, vena caval occlusion reduced end-diastolic segments lengths and right ventricular systolic pressure consistent with a reduction in right ventricular end-diastolic volume. In a separate group of animals, volume loading with dextran increased inflow and outflow end-diastolic segment lengths and increased cardiac output. In two further groups of animals, one of which was pretreated intravenously with propranolol (Inderal), both forms of pressure overload increased end-diastolic lengths in both regions. However, GBE increased right ventricular stroke work compared with PAC. We conclude that end-diastolic segment lengths reflect true volume changes of the right ventricle. Furthermore, during acute pressure overload, the right ventricle dilates to compensate for the afterload change. However, ventricular function is better maintained after GBE.
Intestinal microvascular responsiveness to norepinephrine in chronic portal hypertension
Authors: Joh T. , Granger D. N. , Benoit J. N.
Published: December 2017

Effects of chronic prehepatic portal hypertension on intestinal microvascular sensitivity to norepinephrine (NE) were studied. Normal and portal hypertensive rats were anesthetized, and the intestine was prepared for in vivo microscopic observation. The preparation was transferred to a video microscope and a first-, second-, or third-order submucosal arteriole (i.e., 1A, 2A, or 3A, respectively) selected for study. Microvascular diameter and arteriolar erythrocyte velocity were measured on-line, and arteriolar blood flow was subsequently calculated as the product of velocity and vessel cross-sectional area. Once steady-state conditions were reached, the preparation was exposed to incremental doses of NE and microvessel responses were recorded. Cumulative log dose-response curves relating the change in arteriolar blood flow and vessel diameter to NE concentration were constructed for each group of arterioles and the ED50 for maximal response obtained from each dose-response relationship. NE ED50 for 1A blood flow was significantly higher in portal hypertensive rats (2.57 +/- 0.25 microM) compared with control rats (1.48 +/- 0.19 microM). Analysis of the diameter responses of 1A, 2A, and 3A indicated that the loss of vascular NE sensitivity in chronic portal hypertension was localized to the terminal submucosal arterioles (2A and 3A). No differences in the diameter response of 1A were observed between normal and portal hypertensive rats. Separate experiments were conducted to test if glucagon, a known mediator of the hyperdynamic intestinal circulation in portal hypertension, could acutely alter NE responsiveness in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Heart rate response to hemorrhage-induced 0.05-Hz oscillations in arterial pressure in conscious dogs
Authors: Madwed J. B. , Cohen R. J.
Published: December 2017

We have previously reported that oscillations at 0.05 Hz can be generated by a simple computer model incorporating a negative-feedback reflex mechanism and an effector mechanism with a time delay. Computer simulations by inhibiting the vagal effector mechanism and activating the adrenergic effector mechanism elicited low-frequency oscillations at a frequency of 0.05 Hz in heart rate. We have observed that the cardiovascular system of the conscious dog, when stressed by the loss of blood, generates oscillations in arterial pressure and heart rate at a frequency of 0.05 Hz. We investigated in six conscious dogs the role of the sympathetic and parasympathetic nervous systems in generating these heart rate oscillations. During baseline conditions, the predominant peak in the arterial pressure and heart rate power spectra was located at the respiratory frequency, while the low-frequency oscillations were small. After a 30-ml/kg hemorrhage or after an 8-, 15-, or 30-ml/kg hemorrhage with glycopyrrolate, a muscarinic-blocking agent, low-frequency oscillations at a frequency of 0.05 Hz predominated, while the respiratory frequency oscillations were negligible. Since respiratory frequency oscillations have been reported to reflect vagal activity, and since the low-frequency oscillations were present after vagal blockade, these hemorrhage-induced low-frequency oscillations in heart rate may be primarily mediated by the cardiac sympathetic nerves. Also cross-correlation analysis between arterial pressure and heart rate showed that a change in arterial pressure caused an opposite change in heart rate with a delay of 2-5 s. We conclude that hemorrhage-induced oscillations in heart rate at 0.05 Hz represent the arterial baroreceptor-beta-sympathetic reflex response to underlying arterial pressure oscillations.
Effects of autonomic nerve stimulation, asynchrony, and load on dP/dtmax and on dP/dtmin
Authors: Henning R. J. , Levy M. N.
Published: December 2017

We studied asynchronous depolarization effects on mechanical responses to autonomic nerve stimulation (ANS) in 21 dogs with AV nodal block. In 11 of these dogs, we kept mean aortic pressure (AoP) at 85 mmHg and paced the hearts at 120 beats/min. We paced, in random order, either the LV apex or the RV anterior or lateral wall to increase the asynchrony of ventricular contraction and relaxation. During pacing at each site, we determined maximum rate of LVP rise (dP/dtmax) and fall (dP/dtmin) before and during stimulation of cardiac sympathetic and vagal nerves and during combined nerve stimulation. Changing the pacing site from LV to RV decreased dP/dtmax and also dP/dtmin (P less than 0.001); the decrease was most pronounced when we shifted pacing from LV apex to RV anterior wall. Sympathetic stimulation increased (P less than 0.0001) and vagal stimulation decreased (P less than 0.001) dP/dtmax and dP/dtmin during pacing at each site. Effect of vagal stimulation was substantially enhanced during concomitant sympathetic stimulation. However, the magnitude of changes in dP/dtmax and also in dP/dtmin due to nerve stimulations during pacing at each ventricular site was similar. In 10 additional dog experiments, we also varied AoP from a mean value of 74 to 113 mmHg during pacing at each site. An increase in AoP augmented dP/dtmax by a mean value of 582 mmHg/s and increased dP/dtmin by a mean value of 617 mmHg/s (both P less than 0.0001). Sympathetic stimulation increased, whereas vagal stimulation decreased, dP/dtmax and dP/dtmin at each afterload (P less than 0.001).
Effect of dexamethasone on cerebral prostanoid formation and pial arteriolar reactivity to CO2 in newborn pigs
Authors: Wagerle L. C. , DeGiulio P. A. , Mishra O. P. , Delivoria-Papadopoulos M.
Published: December 2017

This study investigates the effect of glucocorticoid treatment on the relationship between arteriolar PCO2 and cortical prostanoid production and on cerebrovascular responsiveness to elevated CO2 in newborn piglets. The response of pial arteries to hypercapnia (fractional inspired CO2 = 0.035 and 0.07) was studied in 18 anesthetized newborn piglets, 9 of which were pretreated with dexamethasone (2 mg.kg-1.day-1 for 36-48 h). Pial arterioles (77-122 microns diam) were monitored using a closed cranial window and intravital microscopy. Perivascular cerebrospinal fluid (CSF) was sampled from the cortical surface and analyzed for 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) using radioimmunoassay. In the dexamethasone-treated animals the increase in arteriolar diameter to CO2 was diminished by approximately 50% for each respective CO2 concentration vs. the control group. Acute sympathetic denervation did not restore the CO2 dilator response. Dexamethasone did not alter baseline cortical CSF prostanoid concentrations but abolished the CO2-induced increase in CSF prostanoids. The dilator response to exogenously applied prostaglandin E2 was inhibited in dexamethasone-treated animals. However, the dilator response to exogenous adenosine and the contractile response to prostaglandin F2 alpha were not altered in the dexamethasone-treated piglets. The data support the concept that metabolites of arachidonic acid participate in the cerebrovascular response to CO2 and suggest that glucocorticoid treatment may influence cerebrovascular tone via this mechanism.
Glycine microinjected into nucleus tractus solitarii of rat acts through cholinergic mechanisms
Authors: Talman W. T. , Colling J. M. , Robertson S. C.
Published: December 2017

Previous studies have demonstrated the release of glycine from neurotransmitter pools in the region of the nucleus tractus solitarii (NTS) where cardiovascular afferents terminate. Microinjection of glycine into NTS elicits decreases in arterial pressure and heart rate; these effects are also produced by glutamate or acetylcholine. As glycine may act both at the N-methyl-D-aspartate (NMDA)-receptor complex and centrally to release acetylcholine, we have sought to determine whether the cardiovascular responses to exogenous glycine are mediated through glutamatergic or cholinergic mechanisms. Responses to glycine microinjected into the NTS of anesthetized rats were not affected by blockade of the NMDA receptor complex but, like acetylcholine, were blocked by muscarinic receptor blockade. Physostigmine prolonged responses to glycine. Subthreshold doses of glycine, which augmented responses to acetylcholine microinjected into NTS, either decreased or had no effect on glutamate or NMDA. This study supports a role for glycine in cardiovascular regulation by the NTS and suggests that the actions of glycine may be effected, at least in part, through cholinergic mechanisms.
A canine model of chronic heart failure produced by multiple sequential coronary microembolizations
Authors: Sabbah H. N. , Stein P. D. , Kono T. , Gheorghiade M. , Levine T. B. , Jafri S. , Hawkins E. T. , Goldstein S.
Published: December 2017

A canine model of chronic heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Twenty closed-chest dogs underwent three to nine intracoronary embolizations performed 1-3 wk apart. Embolizations were discontinued when left ventricular (LV) ejection fraction was less than 35%. LV ejection fraction was 64 +/- 2% at baseline and decreased to 21 +/- 1% at 3 mo after the last embolization (P less than 0.001). During the same period, LV end-diastolic pressure increased from 6 +/- 1 to 22 +/- 3 mmHg (P less than 0.001); LV end-diastolic volume increased from 64 +/- 3 to 101 +/- 6 6 ml (P less than 0.001), and cardiac output decreased from 2.9 +/- 0.2 to 2.3 +/- 0.1 l/min (P less than 0.01). These changes were accompanied by significant increases of pulmonary artery wedge pressure and systemic vascular resistance. Plasma norepinephrine increased from 332 +/- 17 pg/ml at baseline to 791 +/- 131 pg/ml at 3 mo after the last embolization (P less than 0.01); plasma levels of atrial natriuretic factor increased from 12.7 +/- 10.0 to 28.8 +/- 8.6 pmol/l (P less than 0.01), whereas plasma renin activity remained unchanged. Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy. We conclude that multiple intracoronary embolizations with microspheres, separated in time, can lead to chronic heart failure in dogs. The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.
Microvascular pressure distribution in the hamster testis
Authors: Sweeney T. E. , Rozum J. S. , Desjardins C. , Gore R. W.
Published: December 2017

Convective transport is a critical element in the regulation of steroidogenesis and spermatogenesis in the testis. Steroid hormones are distributed to their target cells within seminiferous tubules via interstitial fluid. The movement of interstitial fluid and lymph, which transports protein hormones and many of the substrates required for spermatogenesis and steroidogenesis, is driven by capillary filtration. Despite the importance of convective transport in testicular function, however, the mechanisms regulating transvascular exchange in the testis are unknown. As a first step in understanding this process, we measured directly the microvascular hydrostatic pressure distribution in the hamster testis (pentobarbital sodium, 70 mg/kg ip). Using a servo-null transducer, intravascular pressure was measured in all vessel types accessible beneath the surface of the testis of 19 animals. Systemic arterial pressure averaged 89 +/- 2 (SE) mmHg. The most significant observations were that mean capillary pressure was extremely low (10.1 +/- 0.8 mmHg) and remarkably constant (range 8.2–13.3 mmHg), despite a 45 mmHg range in systemic mean arterial pressure among the animals observed. The maintenance of a low hydrostatic pressure in testicular capillaries may serve to sustain fluid filtration at a rate that prevents washout of essential solutes while preserving convective transport. Unfortunately, the anatomical and functional characteristics that determine this unique microvascular environment may also expose the testis to significant pathological risks. For example, the large pre- to postcapillary resistance ratio observed suggests that testicular capillaries must be highly susceptible to increases in venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Physical and physiological determinants of transmitral velocity: numerical analysis
Authors: Thomas J. D. , Newell J. B. , Choong C. Y. , Weyman A. E.
Published: December 2017

The Doppler transmitral velocity curve is commonly used to assess left ventricular diastolic function. Recent investigations, however, relating Doppler mitral indexes to ventricular compliance, relaxation, and preload have been inconclusive and at times contradictory. We used a mathematical formulation to study the physical and physiological determinants of the transmitral velocity pattern for exponential chamber pressure-volume relationships with active ventricular relaxation (2,187 combinations investigated). We showed that transmitral velocity is fundamentally affected by two principal physical determinants, the transmitral pressure difference and the net atrioventricular compliance, as well as the impedance characteristics of the mitral valve. These physical determinants in turn are specified by the compliance and relaxation parameters of physiological interest. We found that the peak mitral velocity is most strongly related to initial left atrial pressure but lowered by prolonged relaxation, low atrial and ventricular compliance, and systolic dysfunction. Peak acceleration varies directly with atrial pressure and inversely with the time constant of isovolumic relaxation, with little influence of compliance, whereas the mitral deceleration rate is approximately valve area divided by atrioventricular compliance. We then used these data to suggest possible strategies for improved analysis of noninvasive data (Doppler indexes, planimetered valve area, and isovolumic relaxation time) to estimate ventricular compliance and relaxation and atrial pressure.
Acute effects of repetitive depolarization on sodium current in chick myocytes
Authors: Gold M. R. , Strichartz G. R.
Published: December 2017

Acute effects of repetitive depolarization on the inward Na+ current (INa) of cultured embryonic chick atrial cells were studied using the whole cell patch-clamp technique. Stimulation rates of 1 Hz or greater produced a progressive decrement of peak INa. With depolarizations to 0 mV of 150-ms duration, applied at 2 Hz from a holding potential of -100 mV, the steady-state decrement was approximately 20%. The magnitude of this effect increased with stimulation frequency and with test potential depolarization and decreased with membrane hyperpolarization. Analysis of INa kinetics revealed that reactivation was sufficiently slow to preclude complete recovery from inactivation with interpulse intervals less than 1,000 ms. Moreover, reactivation accelerated markedly with membrane hyperpolarization, in parallel with the response to repetitive stimulation. The multiexponential time course of recovery of peak INa from repetitive depolarization was similar to that observed after single stimuli; however, there was a shift toward a greater proportion of current recovering with the slower of two time constants. It is concluded that incomplete recovery from inactivation is responsible for the decrement in INa observed with short interpulse intervals.
Effects of atrial natriuretic factor on blood flow distribution and vascular resistance in conscious dogs
Authors: Shen Y. T. , Graham R. M. , Vatner S. F.
Published: December 2017

Systemic and regional hemodynamic responses to atrial natriuretic factor (ANF) administered by either bolus or infusion were examined in conscious dogs in the presence and absence of ganglionic blockade. In intact dogs, bolus injection of ANF (9 micrograms/kg), which increased plasma ANF by 100,913 +/- 12,330 pg/ml, initially reduced mean arterial pressure (7 +/- 1%) and total peripheral (-31 +/- 2%), coronary (-28 +/- 3%), mesenteric (-19 +/- 2%), renal (-36 +/- 2%), and iliac (-24 +/- 2%) vascular resistances. During the recovery period, resistance rose in the total peripheral (+13 +/- 3%), coronary (+19 +/- 5%), mesenteric (+7 +/- 2%), and iliac (+42 +/- 8%) beds but did not rise in the renal bed. At 15 min after infusion of ANF (0.3 micrograms.kg-1.min-1 x 30 min), which increased plasma ANF by 4,296 +/- 869 pg/ml, resistance rose in the total peripheral (+19 +/- 3%), coronary (+17 +/- 2%), mesenteric (+23 +/- 7%), and iliac (+40 +/- 11%) beds but remained slightly depressed in the renal bed (-8 +/- 5%). Ganglionic blockade with hexamethonium did not modify substantially the pattern of change of regional vascular resistances to ANF. Thus in conscious dogs, ANF under steady-state conditions was found to elicit direct vasoconstriction in most regional vascular beds and minor vasodilation in the renal vascular bed. However, after bolus administration of ANF, which results in extremely high plasma ANF levels, transient vasodilation occurs in all regional vascular beds. These data suggest that the distribution of ANF receptors, which elicit vasodilation, differs in regional vascular beds, and that in most vascular beds, except those of the kidney, these receptors require extremely high levels of ANF to be activated.