bluuebunny/crossref_metadata_2025 huggingface dataset:
Autonomic neural regulation of intact Purkinje system of dogs
Authors: Wendt D. J. , Martins J. B.
Published: December 2017

To characterize autonomic influences on the Purkinje system in vivo, we measured Purkinje relative refractory period (PRRP) in response to sympathetic (SNS) and vagal nerve stimulation (VNS). Effects of SNS on PRRP were primarily mediated via beta-adrenergic mechanisms because shortening of PRRP during SNS [from 215 +/- 7 (SE) to 202 +/- 8 ms, P less than 0.01] was entirely blocked by metoprolol (1 mg/kg). Vagal influences in the ambient state did not prolong PRRP, even when effective refractory period of adjacent muscle did prolong. When VNS was augmented with physostigmine, PRRP prolonged from 205 +/- 12 to 212 +/- 13 ms, P less than 0.05. Similar provocation of parasympathetic effects on PRRP occurred when VNS was performed during SNS; PRRP prolonged from 188 +/- 9 to 193 +/- 9 ms, P less than 0.05. Also, when alpha-adrenergic stimulation was produced by phenylephrine infusion (25 micrograms.kg-1.min-1) in the presence of metoprolol (1 mg/kg), which prolonged PRRP from 242 +/- 8 to 246 +/- 9 ms, P less than 0.05, the addition of VNS further prolonged PRRP from 246 +/- 9 to 253 +/- 9 ms, P less than 0.05. Thus some refractory period responses in the Purkinje system were similar to adjacent muscle, because beta-adrenergic activation shortened refractory period and vagal stimulation antagonized the shortening. Findings unique to Purkinje tissue were refractory period prolongation by vagal stimulation when facilitated by concurrent prolongation of refractory period during alpha-adrenergic stimulation.
Centrally administered ANF promotes appearance of a circulating sodium pump inhibitor
Authors: Songu-Mize E. , Bealer S. L. , Hassid A. I.
Published: December 2017

We have previously reported that release of an endogenous Na pump inhibitor, a putative natriuretic hormone associated with many hypertensive states, may be regulated by the central nervous system (CNS). The atrial natriuretic factor (ANF), which causes diuresis, vasorelaxation, and inhibition of aldosterone and vasopressin release, has been documented in the CNS as well as the atria and peripheral blood. Our experiments investigate the possible interaction of ANF with a circulating specific inhibitor of the Na pump in normal rats. The Na pump inhibitory capacity of plasma from rats previously injected with either [Arg101-Tyr126]ANF or vehicle into the lateral cerebral ventricle was measured in cultured aortic smooth muscle cells (ASMC) using 86Rb uptake methodology. Plasma from rats injected with ANF inhibited the Na pump activity (18 +/- 4%, n = 4 experiments) in ASMC compared with plasma obtained from rats injected with the vehicle. The nonspecific 86Rb uptake was not affected by the ANF treatment. Plasma obtained from rats injected intravenously with ANF did not affect the Na pump activity in the ASMC. Furthermore, ANF did not directly affect Na pump activity in ASMC when added to the culture dishes in vitro. These findings raise the possibility that central ANF regulates the release of circulating Na pump inhibitor.
Hypoglycemia and cerebral autoregulation in anesthetized dogs
Authors: Sieber F. E. , Koehler R. C. , Derrer S. A. , Saudek C. D. , Traystman R. J.
Published: December 2017

We examined the effects of moderate hypoglycemia with near-normal cerebral glucose consumption on cerebral autoregulation during graded hemorrhagic hypotension in anesthetized dogs. Four groups of animals (n = 8 each) were studied: normoglycemia, insulin-induced hypoglycemia (1.1 mM), normoglycemia plus alpha- and beta-adrenergic blockade [propranolol (1 mg/kg loading dose + 1 mg.kg-1.h-1 infusion) plus phentolamine (2 mg/kg loading dose + 2 mg/min infusion)], and hypoglycemia plus alpha- and beta-adrenergic blockade. As cerebral perfusion pressure was reduced to 40-50 mmHg, cerebral blood flow and O2 consumption increased in the hypoglycemic group. These increases were not observed after adrenergic blockade or in the normoglycemic groups. The perfusion pressure at which cerebrovascular resistance was minimal was higher during hypoglycemia (40 mmHg) and hypoglycemia plus blockade (50 mmHg) than in either of the normoglycemic groups (30 mmHg). This study demonstrates that hypoglycemia increases the lower limit of cerebral autoregulation during hypotension. Furthermore, adrenergic mechanisms acting during combined hypoglycemia and hemorrhagic hypotension increase cerebral blood flow and O2 consumption and attenuate the hypoglycemia-induced increase in the lower limit of autoregulation.
Spatial heterogeneity in striated muscle arteriolar tone, cell flow, and capillarity
Authors: Sweeney T. E. , Sarelius I. H.
Published: December 2017

Spatial variations in microvascular function are described at two tissue sites in hamster cremaster muscle (pentobarbital sodium, 70 mg/kg ip). Arterioles observed include terminal arterioles and their feeding vessels, termed capillary network controllers (CNC). Although terminal arterioles at both sites had similar maximum diameters and cell flows, those at site I were significantly more constricted at rest (2.7 +/- 0.3 vs. 5.1 +/- 0.3 microns at site II) and showed lower resting flows (19.0 +/- 5.5 vs. 174 +/- 34 cells/s at site II). There were no spatial differences in CNC maximal parameters or CNC resting tone, yet CNC resting flow at site II (798 +/- 118 cells/s) significantly exceeded the value at site I (460 +/- 85 cells/s). At rest, median capillary cell flow at site I (3.3 cells/s) was half that at site II (6.3 cells/s). During hyperemia, perfused capillary segment length per unit volume was 84% greater at site I and estimated tissue erythrocyte content nearly double that at site II. Thus significant spatial differences in microvascular function exist in cell flow and vessel tone among terminal arterioles, in cell flow among CNC, and in capillarity and indices of capillary exchange.
Theoretical model of ventricular interdependence: pericardial effects
Authors: Santamore W. P. , Shaffer T. , Papa L.
Published: December 2017

One ventricle can influence the filling characteristics of the opposite ventricle directly through the myocardium and indirectly through the pericardium. Based on definitions of compliances and volumes, we developed a theoretical analysis that indicated that the magnitude of interdependence was related to the relative compliances of the left and right ventricular free walls, septum, and pericardium. This analysis was verified in postmortem canine hearts. Balloons were inserted into each ventricle, and left ventricle pressure (delta Pl) and volume (delta Vl) changes caused by increasing right ventricular pressure (delta Pr) and volume (delta Vr) or pericardial pressure (delta Pp) were recorded. For delta Pl/delta Pr, delta Pl/delta Pp, delta Pl/delta Vr, delta Vl/delta Pr, delta Vl/delta Pp, and delta Vl/delta Vr measurements, the standard error of estimates was small and the predicted and measured values were significantly related (P less than 0.05); the values were 0.88 +/- 0.16, 0.87 +/- 0.17, 0.93 +/- 0.05, 0.95 +/- 0.09, 0.96 +/- 0.05, and 0.96 +/- 0.04, respectively. These coupling coefficients (delta Pl/delta Pr, delta Pl/delta Pp, etc.) a direct measurement of interdependence, indicated that pericardial-to-ventricular coupling is greater than ventricular-ventricular coupling (delta Pl/delta Pp greater than delta Pl/delta Pr, 0.91 +/- 0.09 vs. 0.23 +/- 0.09, P less than 0.01; delta Vl/delta Pp greater than delta Vl/delta Pr, -1.04 +/- 0.35 vs. -0.19 +/- 0.05, P less than 0.05). This study, by developing a theoretical analysis and by direct measurements, provides a better understanding of ventricular interdependence and may help to predict effects of cardiac tamponade and constrictive pericarditis on ventricular interdependence.
Association between cardiovascular reactivity to stress and hypertension or behavior
Authors: Knardahl S. , Hendley E. D.
Published: December 2017

The spontaneously hypertensive rat (SHR) exhibits increased cardiovascular reactivity (CVR) to environmental stress and behavioral hyperactivity relative to the Wistar-Kyoto rat (WKY). This study sought to determine whether enhanced CVR to stress in the SHR is related to hypertension or to behavioral hyperactivity. By breeding SHR with WKY, followed by inbreeding, E. D. Hendley has developed two strains in which the hypertensive trait seems to be separated from the hyperactivity trait: the Wistar-Kyoto hypertensive (WK-HT) and the Wistar-Kyoto hyperactive (WK-HA) strains. Male SHR, WKY, WK-HT, and WK-HA rats were implanted with intravascular catheters and Doppler flow-velocity probes to record arterial pressure, heart rate (HR), and changes in regional vascular resistances. Five days after surgery, the rats were subjected to air-jet stress and pharmacological interventions. The hyperactive strains (SHR and WK-HA) exhibited enhanced pressor, renal, and mesenteric responses to stress, and higher HRs under all conditions, even after autonomic blockade. Both hypertension and hyperactivity were associated with reduced baroreceptor sensitivity. These data indicate that CVR to stress is related to behavioral traits.
Adrenergic denervation in rabbits with diabetes mellitus
Authors: Cohen R. A. , Tesfamariam B. , Weisbrod R. M. , Zitnay K. M.
Published: December 2017

The influence of alloxan-induced diabetes mellitus on the sympathetic neuroeffector junction of the rabbit carotid artery denuded of endothelium was studied. Six weeks of diabetes resulted in a neuropathy characterized by a 38% reduction in the arterial content of norepinephrine. Norepinephrine release from the nerves measured from electrically stimulated superfused arterial segments was decreased. The cocaine-sensitive accumulation of [3H]-norepinephrine (NE) was also reduced, reflecting decreased neuronal uptake. The consequences of these prejunctional changes were studied by measuring isometric contractions of arterial rings caused by electrical nerve stimulation or by exogenous norepinephrine. Despite the reduced release of norepinephrine, neurogenic contractions were normal, suggesting an increased sensitivity of the smooth muscle. After neuronal uptake was blocked, the neurogenic contractions of diabetic arteries were less than normal, reflecting the reduction in transmitter release. The sensitivity of diabetic arteries to exogenous norepinephrine was increased under control conditions; maximal contractions were unchanged. Blockade of norepinephrine uptake increased norepinephrine sensitivity more in normal than in diabetic arteries, and there was no longer a significant difference in sensitivity. Thus, under control conditions, neurogenic contractions of the partially denervated diabetic rabbit carotid artery are paradoxically normalized by increased alpha-adrenergic sensitivity of the smooth muscle. The increased sensitivity caused by reduced neuronal uptake can thus preserve neurogenic vasoconstriction and cause supersensitivity to exogenous catecholamines in the sympathetic neuropathy caused by diabetes mellitus.
Contrasting effects of hypoxia on tension in rat pulmonary and mesenteric arteries
Authors: Yuan X. J. , Tod M. L. , Rubin L. J. , Blaustein M. P.
Published: December 2017

The effects of hypoxia on resting and K-stimulated tension were tested on small rings of rat pulmonary and mesenteric resistance arteries (SPA and SMA, respectively) and on the large branches of the main pulmonary artery (LPA). Reduction of PO2 from approximately 135 Torr to less than 40 Torr slowly increased SPA and LPA resting tension but did not affect SMA tension. The increases in SPA and LPA tension during hypoxia were reversible and were dependent on external Ca2+. Verapamil, 10(-6) M, inhibited the hypoxic pulmonary vasoconstriction by 53-78%. The hypoxia-contracted SPA and LPA were relaxed by 2-4 microM cromakalim; these relaxations were reversed by 2 microM glibenclamide. Hypoxia attenuated the K-stimulated tension (delta TK) in both SPA and SMA at all external K+ concentrations ([K+]o = 10-100 mM) without affecting the shapes of the respective [K+]o-tension curves. However, the SPA curve was located much farther to the left on the [K+]o axis than the SMA curve. [K+]o congruent to 13 mM evoked a half-maximal increase in SPA tension; maximal delta TK was observed at [K+]o greater than or equal to 30 mM. In contrast, [K+]o less than 20 mM induced a negligible increase in SMA tension, whereas 35-40 mM K+ activated about one-half of the increase in tension elicited by 100 mM K+. The LPA [K+]o-tension curve in normoxia was intermediate between the SMA and SPA curves, but hypoxia shifted the LPA curve to the left: delta TK was augmented at [K+]o less than 20 mM and attenuated at high [K+]o.(ABSTRACT TRUNCATED AT 250 WORDS)
A mathematical model of a bullfrog cardiac pacemaker cell
Authors: Rasmusson R. L. , Clark J. W. , Giles W. R. , Shibata E. F. , Campbell D. L.
Published: December 2017

Previous models of cardiac cellular electrophysiology have been based largely on voltage-clamp measurements obtained from multicellular preparations and often combined data from different regions of the heart and a variety of species. We have developed a model of cardiac pacemaking based on a comprehensive set of voltage-clamp measurements obtained from single cells isolated from one specific tissue type, the bullfrog sinus venosus (SV). Consequently, sarcolemmal current densities and kinetics are not influenced by secondary phenomena associated with multicellular preparations, allowing us to realistically simulate processes thought to be important in pacemaking, including the Na(+)-K+ pump and Na(+)-Ca2+ exchanger. The membrane is surrounded extracellularly by a diffusion-limited space and intracellularly by a limited myoplasmic volume containing Ca2(+)-binding proteins (calmodulin, troponin). The model makes several predictions regarding mechanisms involved in pacing. 1) Primary pacemaking cannot be attributed to any single current but arises from both the lack of a background K+ current and a complex interaction between Ca2+, delayed-rectifier K+, and background leak currents. 2) Ca2+ current displays complex behavior and is important during repolarization. 3) Because of Ca2+ buffering by myoplasmic proteins, the Na(+)-Ca2+ exchanger current is small and has little influence on action potential repolarization but may modulate the maximum diastolic potential. 4) The Na(+)-K+ pump current does not play an active role in repolarization but is of sufficient size to modulate the rate of diastolic depolarization. 5) K+ accumulation and Ca2+ depletion may occur in the extracellular spaces but play no role in either the diastolic depolarization or repolarization of a single action potential. This model illustrates the importance of basing simulations on quantitative measurements of ionic currents in myocytes and of including both electrogenic transporter mechanisms and Ca2+ buffering by myoplasmic Ca2(+)-binding proteins.
Angiotensin II and alpha-agonist. I. Responses of ovine fetoplacental vasculature
Authors: Yoshimura T. , Magness R. R. , Rosenfeld C. R.
Published: December 2017

During ovine pregnancy the uteroplacental vasculature is less responsive to angiotensin II (ANG II)-induced vasoconstriction than the systemic vasculature, whereas responses to alpha-agonists are just the opposite. Comparisons of fetal systemic and placental vascular responses to these agents are not well described, nor have they been compared with maternal responses. We determined steady-state responses to fetal infusions (5-7 min) of ANG II (0.023-5.73 micrograms/min) and phenylephrine (PHEN, 0.031-7.64 micrograms/min), continuously monitoring mean arterial pressure (MAP), heart rate (HR), and umbilical blood flow (UmBF). Although both vasoconstrictors caused dose-dependent increases in MAP and umbilical vascular resistance (UmVR), responsiveness (delta MAP and delta UmVR) to ANG II (mol/min) was 35- to 60-fold greater than to PHEN. ANG II caused dose-dependent decreases in UmBF (2-48%); PHEN had minimal effects except at the highest dose, UmBF decreasing only 18%. Although patterns of fetal responses of MAP, UmBF, and UmVR to ANG II resembled maternal responses of MAP and uterine blood flow and uterine vascular resistance, the former were greatly attenuated. Similar observations were made with PHEN for UmBF and UmVR but not MAP. ANG II is a more potent fetal systemic and placental vasoconstrictor than PHEN; however, compared with those of the mother the responses are attenuated. Moreover, the fetoplacental vascular bed appears unresponsive to alpha-adrenergic stimulation, possibly reflecting a mechanism for maintaining UmBF when plasma catecholamines are elevated.
AV junctional rhythm induced by sympathetic-parasympathetic imbalance in dog hearts
Authors: Furukawa Y. , Martin P. , Levy M. N.
Published: December 2017

We studied the atrioventricular (AV) junctional rhythm induced by stimulation of discrete autonomic nerves to the AV nodal area in spontaneously beating hearts of anesthetized dogs where all central autonomic connections to the heart had been cut. Simultaneous stimulation of intracardiac sympathetic and parasympathetic nerves to the AV nodal area (AVSP stimulation, at the junction of the inferior vena cava and left atrium) initially increased and then decreased the AV interval. During such stimuli no AV junctional rhythm was observed; however, after cessation of stimulation, an AV junctional rhythm then appeared in 6 of 12 dogs. Because norepinephrine (NE) persists much longer than acetylcholine in cardiac tissues, we postulated that the junctional rhythm was ascribable to the residual NE that had been released during stimulation. After the animals had been given atropine, an AV junctional rhythm was induced in all animals during AVSP stimulation. These junctional rhythms were suppressed by propranolol or by pacing the atria at a rate faster than the rate of the junctional rhythm. These results suggest that a regional sympathetic-parasympathetic imbalance may unmask subsidiary pacemaking activity, such as an AV junctional rhythm.
Pacing during reperfusion elevates regional myocardial oxygen consumption
Authors: Kedem J. , Acad B. A. , Weiss H. R.
Published: December 2017

Reperfusion after 2 h of coronary artery occlusion has been shown to result in depressed coronary blood flow to the reperfused region and elevated regional myocardial extraction. This suggests that reperfused myocardium, even after 4 h of reperfusion, possesses limited flow and O2 consumption reserves. We studied the capacity of reperfused myocardium to elevate regional blood flow and regional O2 consumption in response to sustained increased O2 demand, produced by atrial pacing. Two groups of anesthetized open-chest dogs were subjected to 2 h of left anterior descending coronary artery occlusion followed by 4 h of reperfusion. One group was subjected to atrial pacing (40% increase in heart rate) during the entire 4-h reperfusion period. Regional O2 saturation was measured by microspectrophotometry in samples of reperfused and nonoccluded subepicardium and subendocardium, which were taken at the end of the reperfusion period. In the paced group, regional blood flow (radiolabeled microspheres) to reperfused myocardium was significantly higher than to corresponding regions of unpaced hearts (110 +/- 22 vs. 40 +/- 9 ml.min-1 x 100 g-1 in the subendocardium). In the control group, O2 extraction of reperfused subendocardium was significantly higher than that measured in the corresponding nonoccluded region (11.0 +/- 0.9 vs. 8.0 +/- 0.6 ml O2/100 ml). Pacing did not elevate O2 extraction of reperfused myocardium (8.7 +/- 0.6 vs. 8.3 +/- 0.7 ml O2/100 ml). Myocardial O2 consumption was significantly elevated in all regions of the paced heart. It is concluded that reperfused myocardium possesses significant unutilized O2 supply and consumption reserves.
Potassium dilates rat cerebral arteries by two independent mechanisms
Authors: McCarron J. G. , Halpern W.
Published: December 2017

Cerebral blood flow is regulated by brain metabolism, and there is evidence to suggest that changes in extracellular potassium concentration are important in linking brain metabolic activity with blood supply. In this study, the effect of low concentrations of potassium on the spontaneous tone of resistance-sized isolated posterior cerebral arteries from Wistar-Kyoto rats was examined. At a transmural pressure of approximately 58 mmHg, the vessels developed spontaneous tone that was 69 +/- 2% of their fully relaxed diameter of 184 +/- 2 microns (n = 50). Introduction of potassium (less than 5 mM) after a 5-min period in potassium-free physiological saline solution resulted in transient dilations, which were not attenuated by barium or cesium but abolished by ouabain. However, potassium concentrations between 7 and 15 mM produced dilations that lacked a transient component and were sensitive to barium, cesium, and ouabain. Maintained dilations to 10 mM K+ persisted in tetrodotoxin, tetraethylammonium, and glibenclamide and after endothelium removal. These results suggest that potassium dilation of cerebral arteries has two independent components, the first of which may be caused by stimulation of the electrogenic sodium pump (0-5 mM K+), whereas the second (greater than 7 mM K+) results from activation of a ouabain-, barium-, and cesium-sensitive process. The latter process describes a means by which potassium may effect prolonged changes in cerebral blood flow.
Propagation and collision characteristics of calcium waves in rat myocytes
Authors: Ishide N. , Urayama T. , Inoue K. , Komaru T. , Takishima T.
Published: December 2017

In myocytes, local contractions occur spontaneously and propagate as traveling waves. We observed the waves in myocytes as local changes in fura-2 fluorescence and determined some characteristics of the wave. Myocytes were enzymatically isolated from rat left ventricles and incubated with 2 microM fura-2/AM for 60 min. Microscopic fluorescence images of myocytes were recorded with a high-sensitivity video camera. The images were digitally analyzed, frame by frame, and temporal changes in local fluorescence were displayed. With the excitation wavelength at 380 nm, the darker band propagates as the traveling wave. With the excitation wavelength at 340 nm, the wave appears brighter. With the isosbestic wavelength at 360 nm, the wave is not discernible. The waves are thus considered to be traveling waves of change in local cytoplasmic calcium ion concentration (calcium wave). Velocity, amplitude, and width of the calcium waves appeared to be fairly constant during their propagation. When two waves propagating in opposite directions collided, summation of the waves did not occur. After the collision both waves disappeared. These observations support the idea that the waves propagate by inducing calcium release from adjacent sarcoplasmic reticulum. Phenomena observed during the collision indicate that there is a refractory period after the calcium transient; spatially, a refractory zone exists in the wake of the wave.
Diaphragm does not produce ammonia or lactate during high-intensity short-term exercise
Authors: Manohar M. , Hassan A. S.
Published: December 2017

To ascertain whether costal diaphragm engages in ammonia and lactate production (like limb muscles) during high-intensity short-term exercise, experiments were carried out on six healthy trained ponies in which phrenic venous catheters had been implanted 5-9 days earlier. Simultaneous anaerobically obtained blood samples from abdominal aorta and the phrenic vein at rest and during 4 min of exertion at 32 km/h and at a 7% grade were analyzed for blood-gas variables as well as lactate and ammonia concentrations using standard procedures. At rest, heart rate was 47 +/- 4 beats/min and the diaphragmatic O2 extraction was 26.5%. With exercise, heart rate rose to 218 +/- 6 beats/min, marked acidosis and hyperventilation occurred, and the diaphragmatic O2 extraction increased threefold (80.9%). Such exercise is known to dramatically increase the work of breathing as respiratory frequency and change in pleural pressure approach 138 +/- 4 breaths/min and 30 +/- 3 cmH2O, respectively. Despite the fact that phrenic-venous O2 tension of exercised ponies decreased to 15.5 +/- 0.6 Torr, the phrenic-venous lactate and ammonia concentrations did not exceed corresponding arterial values. These data thus revealed that the diaphragm is uniquely unlike limb muscles, which at high workloads readily engage in net ammonia and lactate production, and that the diaphragmatic energy needs during high-intensity short-term exercise are primarily met by aerobic metabolism.
Role of nitric oxide in regulation of basilar artery tone in vivo
Authors: Faraci F. M.
Published: December 2017

Previous studies have suggested that nitric oxide (NO) may be a major endothelium-derived relaxing factor in peripheral blood vessels. This study tested the hypotheses that 1) formation of NO from L-arginine contributes to basal tone of cerebral arteries in vivo and 2) dilator responses of cerebral arteries to acetylcholine are dependent on formation of NO. Diameter of the basilar artery was measured through a cranial window in anesthetized rats. Under control conditions, topical application of 10 microM NG-monomethyl-L-arginine (L-NMMA, an arginine analogue that inhibits enzymatic formation of NO), constricted the basilar artery by 11 +/- 1% (means +/- SE). L-Arginine (100 microM), which had no effect on baseline diameter, abolished vasoconstriction in response to L-NMMA. L-Arginine did not alter vasodilation during acetylcholine (1 microM) (11 +/- 2 vs. 12 +/- 2%) or vasoconstriction during serotonin (1 nM) (-15 +/- 3 vs. -16 +/- 2%). L-NMMA (5-10 microM) abolished the dilator response of the basilar artery to acetylcholine but did not alter responses to nitroglycerin (0.01 microM) (24 +/- 4 vs. 20 +/- 3%). The inhibitory effect of L-NMMA on the vasodilator response to acetylcholine was prevented by L-arginine. These studies suggest that synthesis of NO from L-arginine influences resting tone of the basilar artery in vivo. Dilatation of the basilar artery to acetylcholine in vivo appears to be dependent on formation of NO from L-arginine.
Non-NMDA receptors mediate sensory afferent synaptic transmission in medial nucleus tractus solitarius
Authors: Andresen M. C. , Yang M. Y.
Published: December 2017

Indirect evidence suggests that excitatory amino acids (EAA) are involved in synaptic transmission of visceral afferents at their synapses within the nucleus tractus solitarius (NTS). Little is known about the identity of the postsynaptic receptors or response mechanisms. Here we report results from a longitudinal brain slice of the rat medulla. Intracellular recordings were made from neurons in delimited portions of the dorsal medial NTS (mNTS) known to receive baroreceptor inputs. Stimulation of the solitary tract 1-3 mm from the mNTS recording site evoked short (2 ms) latency excitatory postsynaptic potentials (EPSPs), which had durations of 40-50 ms. Addition of the non-N-methyl-D-aspartate (non-NMDA) selective antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) to the slice surface near the recording electrode resulted in a rapid (within 30-45 s) suppression of the EPSP. Complete EPSP blockade was only slowly reversed by drug-free saline. Concentration-response relations (n = 14) showed 50% depression of EPSPs by surface concentrations of 1-10 microM CNQX. EPSP amplitude was resistant to the selective NMDA antagonist 2-amino-5-phosphonovalerate (AP 5) and, on average, was reduced less than 20% at 100 microM AP 5, an effect that was not statistically significant (n = 10; P greater than 0.05). In conclusion, this study offers the first direct evidence that EAAs mediate the primary events of afferent synaptic transmission in NTS. The experiments suggest that excitatory sensory afferent synaptic transmission to mNTS neurons is mediated by an EAA transmitter acting at non-NMDA receptors, but NMDA receptors may have a modulatory role.
Myocyte structure, function, and calcium kinetics in the cardiomyopathic hamster heart
Authors: Sen L. Y. , O'Neill M. , Marsh J. D. , Smith T. W.
Published: December 2017

The hereditary cardiomyopathic strain of the Syrian hamster has been studied extensively as a model of cardiomyopathy and heart failure. However, the primary defect underlying the cascade of events leading to heart failure has not been identified. In the present study, isolated cardiac cells were obtained for study from 8-mo-old cardiomyopathic (Bio 14.6) and age-matched normal hamsters (F1B). We examined the relationships among structure, contractile function, and calcium kinetics in these isolated cardiomyocytes. The cardiomyopathic myocytes were wider and longer than controls, and myopathic cells were less calcium tolerant. The sarcoplasmic reticulum and T-tubule systems from myopathic hearts were more abundant as determined by electron microscopy. The amplitude and velocity of contraction was decreased in cardiomyopathic cells, whereas diastolic relaxation velocity was not different between the two groups. The size of the rapidly exchangeable calcium pool determined by 45Ca2+ uptake was significantly increased in cardiomyopathic myocytes. Time-averaged cytosolic Ca2+ in these cells (472 +/- 60 nM) was significantly higher than control (260 +/- 15 nM) as measured by the fura-2 fluorescence ratio. When extracellular Ca2+ ([Ca2+]o) was increased to greater than 1.2 mM, the resulting increase in intracellular calcium concentration was less than that in normal control cells. The corresponding [Ca2+]o-induced increase in amplitude of cell motion was significantly attenuated in the cardiomyopathic cells compared with normal control myocytes. We conclude that distinct abnormalities of contractile function and calcium homeostasis can be identified in single cells isolated from cardiomyopathic hamster hearts.
Age-related cerebrovascular response to global ischemia in pigs
Authors: Kirsch J. R. , Helfaer M. A. , Blizzard K. , Toung T. J. , Traystman R. J.
Published: December 2017

We tested the hypothesis that 1- to 2-wk-old pigs (piglet) have improved recovery of cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and somatosensory-evoked potentials (SEP) compared with 6- to 8-mo-old pigs (pig) after transient global cerebral ischemia. All animals were anesthetized with pentobarbital sodium. After tracheostomy ventilation was adjusted to maintain normoxia (arterial oxygen pressure, 100-150 mmHg) and normocarbia (arterial carbon dioxide pressure, 35-40 mmHg). Arterial blood gases, blood pressure, and hemoglobin concentration remained within physiological limits throughout the experiment. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta. During ischemia the electroencephalogram and SEP became isoelectric within 40 and 120 s, respectively. At 10 min of reperfusion hyperemia occurred in most brain regions (e.g., whole brain: piglet, 270 +/- 45%; pig, 316 +/- 48%). In pigs delayed hypoperfusion occurred in all regions except white matter. In contrast, piglets only had delayed hyperperfusion to the brain stem and caudate nucleus. Throughout reperfusion CMRO2 was decreased in pigs (3.3 +/- 0.4 to 1.9 +/- 0.2 ml.min-1.100 g-1) but was not different from control (2.7 +/- 0.3 ml.min-1.100 g-1) in piglets. By the end of reperfusion SEP amplitude was closer to control in piglets than pigs (55 +/- 9 vs. 32 +/- 4% of control). We conclude that 1- to 2-wk-old piglets have quicker return of CBF, CMRO2, and SEP to control values after global ischemia, which mechanistically may explain previous reports of improved neurological recovery in young animals after transient ischemia.
Ontogeny of adenosine response in guinea pig heart and aorta
Authors: Matherne G. P. , Headrick J. P. , Berne R. M.
Published: December 2017

Effects of maturation on the responses of isolated perfused hearts and aortic rings to adenosine were examined. Dose-response relationships for adenosine were obtained in aortic rings and hearts isolated from immature (5 days) and mature (1-2 mo) guinea pigs. Immature and mature hearts were perfused at constant flows of 9.9 +/- 0.3 and 9.5 +/- 0.4 ml.min-1.g-1, respectively, and displayed basal resistances of 4.8 +/- 0.1 and 6.7 +/- 0.2 mmHg.ml-1.min.g. Immature hearts were more sensitive to exogenous adenosine, displaying a significantly lower 50% effective concentration (EC50, 2.5 x 10(-8) M) than mature hearts (1.1 x 10(-7) M, P less than 0.05). Adenosine induced dilation at a lower threshold dose in immature hearts (3 x 10(-9) M, 6.0 +/- 0.3% relaxation) than in mature hearts (10(-8) M, 3.1 +/- 1.3% relaxation). The time required to elicit 50% of the observed dilation was similar in immature and mature hearts, yet the time required for basal tone to recover by 50% was approximately 100% greater in immature hearts (P less than 0.05). Immature aortic rings, stretched to their optimal resting tensions and contracted with EC85 doses of prostaglandin F2 alpha, displayed a significantly lower EC50 (7.7 x 10(-5) M) than mature rings (1.1 x 10(-4) M, P less than 0.05). The maximum percent response to adenosine was greater in immature vessels (64 +/- 1 vs. 54 +/- 0.4%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of ANP-(95-126) in dogs before and after induction of heart failure
Authors: Riegger G. A. , Elsner D. , Forssmann W. G. , Kromer E. P.
Published: December 2017

In conscious dogs with and without congestive heart failure, we investigated hemodynamic, hormonal, and renal effects of a new natriuretic peptide [ANP-(95-126)]. Unlike ANP-(99-126), which is secreted in the heart and rapidly inactivated in the kidney, ANP-(95-126) most likely originates from the kidney and is not destroyed by proteolysis in membrane preparations of kidney cortex. In healthy animals intravenous ANP-(95-126) significantly decreased mean arterial pressure, cardiac output, stroke volume, and right atrial pressure and increased heart rate without changing mean pulmonary arterial pressure and total peripheral vascular resistance. In dogs with congestive heart failure, ANP-(95-126) showed no effects on mean arterial pressure, cardiac output, stroke volume, and peripheral vascular resistance but reduced right atrial pressure and pulmonary arterial pressure. Both, in dogs before and after the induction of heart failure, the new peptide led to a significant increase of urine flow and sodium and chloride excretion. In healthy dogs there were indirect indications for a small inhibitory effect on renin and aldosterone secretion. Thus, in contrast to the considerable attenuation of renal effects of ANP-(99-126) in heart failure, the efficacy of ANP-(95-126) on renal excretory function is well preserved, which may be because of the lack of proteolytic degradation in the kidney. These results suggest that ANP-(95-126) may have clinical implications for the treatment of patients with congestive heart failure.
No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia
Authors: Mink R. B. , Dutka A. J. , Kumaroo K. K. , Hallenbeck J. M.
Published: December 2017

Xanthine oxidase (XO) has been implicated as a source of free radicals mediating ischemia-reperfusion injury. Conversion of the non-free radical generating xanthine dehydrogenase (XD) to the free radical producing XO during ischemia has been demonstrated in several tissues. We examined the irreversible conversion of XD to XO in the dog brain after ischemia and after ischemia and reperfusion. Under pentobarbital sodium anesthesia and by use of a cerebrospinal fluid compression model of global cerebral ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure of 60 mmHg was maintained during reperfusion. Eight control dogs were not subjected to ischemia. After the dogs were killed their brains were rapidly removed and frozen in liquid nitrogen. XO and XD + XO activities were measured with a radioassay utilizing 8-[14C]hypoxanthine and separating substrate and products by thin-layer chromatography. Total XD + XO activity was significantly (P less than 0.05) decreased after ischemia and reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4). XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to XO conversion is not an important mechanism leading to early tissue injury in global cerebral ischemia.
Hemodynamic and sympathetic effects of spinal administration of neuropeptide Y in rats
Authors: Chen X. L. , Knuepfer M. M. , Westfall T. C.
Published: December 2017

Intrathecal administration of 4 nmol/kg neuropeptide Y in Dial-urethane-anesthetized rats elicited decreases in arterial pressure, renal sympathetic nerve activity, and a slight decrease in heart rate. The depressor response was associated with a sustained hindquarters and mesenteric vasodilation resulting in a decrease in total peripheral resistance. Intrathecal NPY also resulted in a decrease in renal sympathetic nerve activity. There was a positive correlation between the percent changes in arterial pressure and renal sympathetic nerve activity. With the use of renal nerve activity and heart rate as indexes, NPY resulted in a decrease in baroreflex sensitivity. The depressor effect of intrathecal NPY did not appear to be due to spinal vasoconstriction and ischemia, since spinal microvascular resistance was decreased slightly. We conclude that the intrathecal administration of NPY produces an inhibition of sympathetic nerve activity, resulting in a decrease in total peripheral resistance and arterial pressure.
Neutrophils accumulate and contribute to skeletal muscle dysfunction after ischemia-reperfusion
Authors: Walden D. L. , McCutchan H. J. , Enquist E. G. , Schwappach J. R. , Shanley P. F. , Reiss O. K. , Terada L. S. , Leff J. A. , Repine J. E.
Published: December 2017

Skeletal muscles subjected to ischemia and then reperfusion develop contractile dysfunction for reasons that are unclear. We found that rats pretreated with vinblastine 4 days before study had decreased numbers of blood neutrophils and increased gastrocnemius muscle function after ischemia (3h) and reperfusion (4 h) compared with untreated rats or rats treated 4 days before study with saline. By comparison, rats pretreated with vinblastine or saline 1 day before study had increased blood neutrophils and decreased gastrocnemius muscle contractile function after ischemia-reperfusion compared with untreated rats. In addition, numbers of neutrophils in gastrocnemius muscles paralleled numbers of blood neutrophils and correlated with gastrocnemius muscle edema and contractile function after ischemia and reperfusion. The results indicate that neutrophils accumulate and may play an important role in the genesis of skeletal muscle contractile dysfunction after ischemia-reperfusion.
Inhibition of protein synthesis does not block myocardial protection afforded by preconditioning
Authors: Thornton J. , Striplin S. , Liu G. S. , Swafford A. , Stanley A. W. , Van Winkle D. M. , Downey J. M.
Published: December 2017

It is currently unknown how preconditioning the heart with brief periods of ischemia makes it resistant to infarction from a subsequent ischemic insult. The protein synthesis inhibitors, cycloheximide and actinomycin D, were used to determine whether preconditioning involves synthesis of a protective protein. Ischemia was produced by occlusion of a branch of the left coronary artery in open-chest anesthetized rabbits. All groups were subjected to 30 min of ischemia followed by 3 h of reperfusion. The first two groups served as noninhibited controls. Group 1 was subjected to ischemia with no preconditioning. Group 2 was preconditioned with two 5-min ischemic periods each followed by 10 min of reperfusion, before the 30-min ischemic period. Groups 3 and 4 were the same as groups 1 and 2, respectively, except that cycloheximide was administered before coronary occlusion. Groups 5 and 6 were also the same as groups 1 and 2 except that actinomycin D was administered before coronary occlusion. After 3 h of reperfusion all hearts were removed and the size of the ischemic zone and infarct were determined. The percent of the ischemic zone infarcted was small and similar in all preconditioned groups (3.3 +/- 1.1% for group 2, 7.4 +/- 3.3% for group 4, and 0.5 +/- 0.7% for group 6). All nonpreconditioned groups had large infarcts with no differences between groups (39.0 +/- 8.5% for group 1, 31.6 +/- 6.3% for group 3, 30.8 +/- 5.9% for group 5). Because neither cycloheximide nor actinomycin D could block protection afforded by preconditioning, it seems unlikely that synthesis of a protective protein is the mechanism of protection.
Effects of extracellular Mg2+ on T- and L-type Ca2+ currents in single atrial myocytes
Authors: Wu J. Y. , Lipsius S. L.
Published: December 2017

Whole cell voltage-clamp techniques were used to study the effects of extracellular Mg2+ on T- and L-type Ca2+ currents recorded from single atrial myocytes from cat heart. T and L currents were distinguished primarily by their voltage dependence. With 5.4 mM Ca2+ as charge carrier, maximal T- and L-current densities were 1.0 +/- 0.06 and 9.7 +/- 0.4 pA/pF, respectively. Nickel (Ni2+, 50 microM) inhibited maximal T current (-65.6 +/- 5.9%) more than L current (-15.7 +/- 2.4%), and 10 microM cadmium (Cd2+) inhibited L current (-65.5 +/- 5.9%) without significant effect on T current (-8.7 +/- 8.1%). Mg2+ elicited a dose-dependent inhibition of both T and L currents. Mg2+ less than 8.4 mM inhibited T current more than L current. At Mg2+ greater than or equal to 8.4 mM, T-current inhibition reach a plateau at approximately 52%, whereas L current was further inhibited (-65%) at 16.8 mM Mg2+. Mg2+ elicited a dose-dependent positive shift in half-maximal voltages of activation and inactivation for both T and L currents. Mg2(+)-induced inhibition of both T and L currents was greater in lower (2.7 mM) external Ca2+. Finally, 4.2 mM Mg2+ and 50 microM Ni2+ elicited a similar decrease in the late diastolic slope of subsidiary pacemaker action potentials, whereas 10 microM Cd2+ markedly inhibited action potential amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)
Determination of microvascular oxyhemoglobin saturations using cryospectrophotometry
Authors: Fenton B. M. , Gayeski T. E.
Published: December 2017

Although a four-wavelength method for cryospectrophotometric measurement of intravascular oxyhemoglobin (HbO2) saturations has previously been described, the relationship between experimental measurements and theory has not been clearly detailed. The current work utilizes an empirical relationship between HbO2 saturation measurements and reflected light oximetry, which is consistent with the two-flux theory of Kubelka and Munk (Z. Tech. Phys. 11a: 593-603, 1931). To obtain linear, concentration-independent calibration curves, the theoretical results require that 1) the complex function relating optical density, scattering, and absorption can be linearly approximated over the range of scattering and absorption coefficients used; and 2) the scattering coefficient is independent of wavelength. Incident light cannot easily be measured using reflection spectroscopy, which precludes the determination of isosbestic points. Therefore, equibestic wave-length pairs were used at which optical density differences were invariant with saturation. This allows numerous wavelength sets over the range 540-600 nm to be selected, rather than the limited choices of isosbestic wavelengths. Finally, the effects of freeze rate, freeze depth, Hb concentration, and vessel diameter are each discussed in terms of their influence on experimental measurements.
Carotid baroreceptor control of liver and spleen volume in cats
Authors: Maass-Moreno R. , Rothe C. F.
Published: December 2017

Pages H254–H259: R. Maass-Moreno and C. F. Rothe. “Carotid baroreceptor control of liver and spleen volume in cats.” Page H254: The sentence beginning on line 11 of the abstract should read: In vagotomized cats, increasing Pcs by 100 mmHg caused a significant reduction in Psa (–67.8%), cardiac output (–26.6%), total peripheral resistance (–49.5%), and heart rate (–15%) and significantly increased spleen volume (9.7%, corresponding to a 0.21 ± 0.05 mm increase in thickness). The sentence beginning on line 16 of the abstract should read: The liver volume decreased, but only by 1.6% (0.06 ± 0.02 mm decrease in thickness), a change opposite that observed in the spleen. Page H256: The sentence beginning on line 20 of the first paragraph should read: The liver thickness significantly decreased 0.06 ± 0.02 mm when increasing Pcs by 100 mmHg, whereas the spleen increased 0.21 ± 0.05 mm.
Metabolic correlates of adenosine formation in stimulated guinea pig heart
Authors: Headrick J. P. , Matherne G. P. , Berr S. S. , Han D. C. , Berne R. M.
Published: December 2017

Adenosine release into epicardial fluid and coronary effluent of isolated isovolumic guinea pig hearts was examined at baseline and after stimulation with norepinephrine (30 nM) during 31P-nuclear magnetic resonance spectroscopy to monitor myocardial metabolism. At baseline flow (9.6 +/- 0.3 ml.min-1.g-1), epicardial and venous adenosine concentrations were 154 +/- 40 and 17 +/- 5 nM, respectively. The phosphorylation potential (log[ATP]/[ADP][Pi]) and the phosphocreatine-inorganic phosphate ratio ([PCr]/[Pi]) were 5.26 +/- 0.04 and 8.5 +/- 0.7, respectively. Norepinephrine increased left ventricular pressure, heart rate, and myocardial O2 consumption rate by approximately 21, 70, and 45%, respectively, and increased epicardial and venous adenosine to 496 +/- 74 and 461 +/- 94 nM, respectively. Log-[ATP]/[ADP][Pi] and [PCr]/[Pi] declined to 4.57 +/- 0.06 and 1.9 +/- 0.3, respectively. Epicardial [AMP] increased from 54 +/- 13 to 123 +/- 24 nM. AMP was not detectable in the venous effluent. Coronary resistance correlated with epicardial and venous [adenosine] (r = 0.86 and 0.90). Epicardial and venous [adenosine] correlated with log[ATP]/[ADP][Pi], [PCr]/[Pi], and cytosolic [AMP]. Hence, interstitial adenosine is linked to cytosolic metabolism and may regulate coronary vascular resistance. Venous adenosine underestimates epicardial adenosine at baseline but more closely approximates epicardial adenosine during norepinephrine infusion.
Sustained fetal pulmonary vasodilation with prolonged atrial natriuretic factor and GMP infusions
Authors: Abman S. H. , Accurso F. J.
Published: December 2017

To study mechanisms of vasodilation and factors that maintain high pulmonary vascular resistance in utero, we measured changes in blood flow and the pressure-flow relationship of the pulmonary circulation during prolonged exposures to direct-acting guanosine 3',5'-cyclic monophosphate (cGMP) vasodilators, atrial natriuretic factor (ANF), and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) and compared hemodynamic responses with other vasodilator stimuli in chronically prepared fetal lambs. The fetus was treated with 2 h of intrapulmonary infusions of ANF (0.15 micrograms/min), 8-BrcGMP (50 micrograms/min), prostaglandin D2 (PGD2, 0.4 micrograms/min), or acetylcholine (ACh, 1.5 micrograms/min) or increases in fetal Po2. Despite continued exposure to increased Po2, PGD2, and ACh, elevations of pulmonary blood flow and slopes of the pressure-flow relationship were not sustained, with both significantly decreased at 2 h from peak values. In contrast, pulmonary blood flow and pressure-flow slopes remained increased throughout 2 h of exposures to ANF and 8-BrcGMP. Adenosine 3',5'-cyclic monophosphate caused less change in blood flow than 8-BrcGMP within the dose range studied. We conclude that unlike other stimuli, direct-acting cGMP vasodilators are able to sustain vascular relaxation of the fetal pulmonary circulation.