bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of sympathetic tone on ventricular arrhythmias during circumflex coronary occlusion
Authors: Euler D. E. , Nattel S. , Spear J. F. , Moore E. N. , Scanlon P. J.
Published: December 2017

To determine if the sympathetic nervous system exerts an arrhythmogenic effect on the ischemic myocardium independent of heart rate, the proximal circumflex coronary artery was occluded for 1 h in 62 open-chest, anesthetized dogs. The atrial rate was maintained at 200/min, and the vagosympathetic trunks were transected in all dogs. The total incidence of ventricular fibrillation was 35% in 20 dogs with intact stellates and not significantly different from the incidence of ventricular fibrillation (15%) in another 20 dogs in which both stellate ganglia had been decentralized. Electrical stimulation of the left ansae subclavia (3 Hz, 2 ms, 6-8 V) in the remaining 22 dogs significantly increased the incidence of ventricular fibrillation to 73% (P less than 0.05). The magnitude of S-T segment elevation in the lead II electrocardiogram 90 s after occlusion was 0.69 +/- 0.08 mV in the group with left ansae stimulation and significantly elevated (P less than 0.01) compared with dogs with intact stellates (0.35 +/- 0.06 mV) and with the denervated dogs (0.19 +/- 0.05 mV). The data indicate that the sympathetic nervous system is capable of a direct arrhythmogenic influence on the ischemic myocardium independent of heart rate. The rate-independent arrhythmogenic effects of the sympathetic nervous system may be mediated by an increase in severity of the ischemic insult.
Cardiovascular and endocrine effects of potassium in spontaneously hypertensive rats
Authors: Workman M. L. , Paller M. S.
Published: December 2017

Although potassium is known to lower blood pressure in a number of forms of experimental and human hypertension, the mechanism for this effect remains unclear. We studied several possible mechanisms for this effect in the spontaneously hypertensive rat (SHR). Fourteen-week-old SHR were given 0.5% KCl in the drinking water. This potassium supplement resulted in a 16-mmHg fall in mean arterial pressure and a 22% decrease in peripheral vascular resistance. Plasma potassium increased 0.4 meq/l, while muscle potassium was unchanged. Potassium supplementation resulted in no change in plasma renin activity, plasma aldosterone, or plasma norepinephrine. Urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha was also not altered by potassium supplementation. Potassium-supplemented SHR were found to have no difference in sodium excretion compared with control SHR, and plasma volume was similar in both groups. The pressor response to angiotensin II and norepinephrine was not substantially affected by potassium supplementation. Furthermore, baroreflex control of heart rate was not altered by potassium supplementation. Finally, potassium supplementation resulted in no change in mesenteric artery angiotensin II receptor number or receptor affinity. Therefore, although potassium lowers blood pressure in the SHR by decreasing peripheral vascular resistance, the mechanism of this effect on vascular resistance remains unknown.
Differential sympathetic-parasympathetic interactions in sinus node and AV junction
Authors: Urthaler F. , Neely B. H. , Hageman G. R. , Smith L. R.
Published: December 2017

This study examined the effects and interactions evoked by various combinations of parasympathetic (P) and sympathetic (S) stimulations on sinus node automaticity and atrioventricular (AV) conduction (both anterograde and retrograde) in 11 two-mo old anesthetized puppies. The respective effects of these autonomic maneuvers were assessed by covariant analysis using a linear regression model of the form Y = alpha 0 + alpha 1 X base line + alpha 2 X sequence + alpha 3 X S + alpha 4 X S2 + alpha 5 X P + alpha 6 X P2 + alpha 7 X (P X S).... The effects of parasympathetic and sympathetic stimulation, of the quadratic term S2, and of the interaction term (P X S) were highly significant (P less than 0.0001) on both sinus node automaticity and AV conduction (anterograde and retrograde). In contrast, the effect of the quadratic term P2 was significant on sinus node automaticity only. Sequence of stimulation whether (SP) or (PS) had no significant effect on either chronotropic or dromotropic properties. Furthermore, whereas augmented antagonism with parasympathetic predominance over sympathetic activity was readily demonstrable in the control of sinus rate, the reverse, i.e., augmented antagonism with sympathetic preponderance over parasympathetic activity, was found to apply to the control of AV conduction (both anterograde and retrograde). Hence, the nature and extent of parasympathetic-sympathetic interactions vary considerably, depending on which cardiac structure and/or function is under scrutiny. It appears that AV conduction is especially sensitive to modulation of sympathoadrenergic activity, whereas sinus node automaticity is particularly responsive to cholinomimetic influences.
Effect of hypoxia and hypercapnia on neurohypophyseal blood flow
Authors: Hanley D. F. , Wilson D. A. , Traystman R. J.
Published: December 2017

Neurohypophyseal blood flow responses to hypoxia and hypercapnia were studied in pentobarbital anesthetized, paralyzed dogs. Arterial O2 content was lowered from control (18 +/- 2 vol%) to 8 +/- 1 vol% by either decreasing O2 tension (hypoxic hypoxia, HH) or by increasing carboxyhemoglobin saturation (carbon monoxide hypoxia, COH) at normal O2 tension. In all animals HH and COH resulted in similar increases in total cerebral blood flow (239 and 300%, respectively). Regional cerebral blood flow showed a similar increase for all brain regions except the neurohypophysis (NH). The NH increased its blood flow with HH (approximately 320% of control) but was unchanged with COH (117% of control). The responsiveness of NH blood vessels was tested under conditions of hypercapnia (10% CO2) and HH with blood pressure controlled by concurrent hemorrhage. The response of NH vessels to altered arterial O2 tension occurs independently of blood pressure. Systemic [H+] or CO2 tension produce only small changes in NH blood flow. These data suggest that hypoxic and hypercapnic regulatory mechanisms for the NH are different from those of other brain regions. The precise mechanism by which the NH hypoxic response occurs remains unclear, but our data suggest an important role for systemic arterial O2 tension and chemoreceptors.
Role of renal nerves in rats with low-sodium, one-kidney hypertension
Authors: Vari R. C. , Freeman R. H. , Davis J. O. , Sweet W. D.
Published: December 2017

This study examined the role of the renal nerves in both the maintenance and developmental phases of hypertension produced by sodium restriction in one-kidney rats. Results indicate that mild hypertension is sustained through 6 wk after unilateral nephrectomy in rats fed a sodium-deficient diet, with the greatest increase in systolic blood pressure occurring within the first 2 wk. Six weeks after nephrectomy, renal denervation was performed in the sodium-restricted, hypertensive rats, and the blood pressure returned to normotensive levels. Plasma renin activity (PRA) was elevated fourfold after 6 wk of sodium restriction and was unchanged by renal denervation. In another series of experiments that examined the development of hypertension in this experimental model, contralateral renal denervation was performed at the time of nephrectomy, and this prevented the subsequent development of hypertension. PRA was significantly attenuated in these low-sodium, renal-denervated rats that failed to become hypertensive when compared with PRA in hypertensive low-sodium, sham-denervated rats. Kidney norepinephrine content was reduced by 96% after renal denervation in both phases of the hypertension. These data demonstrate that intact renal nerves are necessary for both the development and maintenance of mild hypertension after sodium restriction in one-kidney rats. The pressor contribution of the renal nerves to the hypertension in this experimental model appears to be related, at least in part, to the activation of the renin-angiotensin pressor mechanism.
Vascular anatomy and hydrostatic pressure profile in the hamster cheek pouch
Authors: Davis M. J. , Ferrer P. N. , Gore R. W.
Published: December 2017

The purpose of this study was to describe the vascular architecture and blood supply to the hamster cheek pouch and to measure the intravascular pressure distribution in the entire pouch. Previous anatomic descriptions have focused either on the vasculature of the facial region or on the microcirculation of the cheek pouch tip. Micropressures in cheek pouch capillaries, terminal arterioles, and small venules have not previously been measured. Cheek pouches were prepared for examination under an intravital microscope using both everted and noneverted methods. Microvessel diameters were measured through a video system using a video micrometer, and intravascular hydrostatic pressures were measured with a servo null micropressure system. Blood vessels in the face and pouch were traced after injection of Microfil into the external maxillary artery. The results indicate that the pouch is supplied directly or indirectly by six small arteries in the neck and face. Fifty percent of the total pressure drop across the cheek pouch vasculature occurs in the small cheek pouch arteries, suggesting that these vessels are potentially important in controlling cheek pouch blood flow. The measurements of microvascular pressures and diameters in this study help clarify apparent discrepancies in similar measurements from previous studies.
Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle
Authors: Rouslin W. , Erickson J. L. , Solaro R. J.
Published: December 2017

The perfusion of canine cardiac muscle with 10 microM oligomycin produced a nearly 90% slowing of the net rate of tissue ATP depletion from 0.200 to 0.025 mumol X min-1 X g wet wt-1 of tissue during a subsequent myocardial autolytic interval during which tissue pH was held constant. Moreover, lowering the tissue pH during the autolytic process by 0.6 unit from approximately 6.8 to approximately 6.2 produced a nearly 60% slowing of the net rate of tissue ATP depletion from 0.200 to 0.087 mumol X min-1 X g wet wt-1. The pH dependence of the net rate of tissue ATP depletion (by an oligomycin-sensitive process) was that predicted from the mitochondrial ATPase pH-inhibition profiles reported earlier (J. Biol. Chem. 258: 9657-9661, 1983). When taken together with our observation that the mitochondrial ATPase comprises approximately 90% of the total of all of the ATP hydrolyzing activities present in cardiac muscle cells, data reported here suggest that the protonic inhibition of the mitochondrial ATPase plays a major role in regulating the rate of tissue ATP depletion during myocardial ischemia.
Dobutamine-induced cardiac adaptations: comparison with exercise-trained and sedentary rats
Authors: Davidson W. R. , Banerjee S. P. , Liang C. S.
Published: December 2017

To investigate dobutamine-induced cardiac adaptations, we compared dobutamine-treated with swim-trained and sedentary control rats. After 14 wk of treatment, heart rate was lower in the dobutamine-treated (279 +/- 6) and exercise-trained (287 +/- 4 beats/min) groups than in the control animals (305 +/- 3 beats/min; P less than 0.05). The exercised rats gained less weight (164 +/- 11 g; P less than 0.05) than the dobutamine-treated (238 +/- 16 g) and the control animals (231 +/- 12 g). Also, compared with the two other groups, the exercise group had higher relative heart weights (3.47 +/- 0.08 vs. 2.82 +/- 0.06 and 2.90 +/- 0.05 g/kg in the dobutamine and control groups, respectively; P less than 0.05) and lower epididymal fat pad weights (6.6 +/- 0.4 vs. 13.3 +/- 1.0 and 11.4 +/- 0.5 g/kg in the dobutamine and control groups, respectively; P less than 0.05). However, both the maximum heart rate produced by isoproterenol and the isoproterenol dose producing 50% of the peak heart rate response were similar among the three groups. Myocardial norepinephrine content, beta-adrenergic receptor number, and adenylate cyclase activation by isoproterenol, NaF, 5'-guanylyl imidodiphosphate, and forskolin also did not differ. Thus, although there were differences between the dobutamine-treated and the exercised rats, the two groups were similar in that they developed bradycardia that was not due to cardiac adrenergic desensitization.
Carbohydrate and fatty acid metabolism of cultured adult cardiac myocytes
Authors: Probst I. , Spahr R. , Schweickhardt C. , Hunneman D. H. , Piper H. M.
Published: December 2017

The energy metabolism of exogenous and endogenous substrates was investigated in Ca-tolerant adult ventricular myocytes in short-term culture. CO2 production from exogenous glucose (5 mM), lactate (5 mM), and palmitate (100 microM) were 8, 20, and 29 mumol X h-1 X g wet wt-1. Endogenous lipolysis shared in energy production by 78, 61, and 31%, respectively. Fatty acids represented the main respiratory fuel even when 10(-7) M insulin, 5 mM lactate, or 5 mM dichloroacetate were supplied in addition to glucose. With palmitate, triglyceride contents were doubled within 3 h of cell incubation. With 5 mM glucose as sole exogenous substrate the energy turnover in these resting cells resembled that of arrested hearts, corresponding to 2 ml O2 X min-1 X 100 g wet wt-1. It is concluded that the basic features of substrate metabolism resemble those of the intact myocardium in that fatty acids represent the major fuel, but the contribution of endogenous lipolysis is greater than in the beating heart.
Differing hemodynamic responses to atrial natriuretic factor in two models of hypertension
Authors: Volpe M. , Sosa R. E. , Muller F. B. , Camargo M. J. , Glorioso N. , Laragh J. H. , Maack T. , Atlas S. A.
Published: December 2017

Hemodynamic responses to synthetic atrial natriuretic factor (ANF), were studied in renin-dependent two-kidney, one-clip (2K,1C) and deoxycorticosterone (DOC) salt-treated hypertensive rats as well as normotensive controls. ANF infusion (800 pmol/kg prime, 120 pmol X kg-1 X min-1 for 60 min) decreased blood pressure (BP) more in conscious 2K,1C (-24 +/- 4%) than in DOC salt-treated (-12 +/- 4%, P less than 0.05) or control rats. Hemodynamic parameters were also evaluated during graded infusion of three doses, each for 30 min. At 24 and 120 pmol X kg-1 X min-1, ANF lowered BP in 2K,1C rats, both conscious (from 156 +/- 6 to 144 +/- 7, P less than 0.05 and 135 +/- 5 mmHg, P less than 0.05) and anesthetized (from 148 +/- 7 to 138 +/- 7, P less than 0.05 and 128 +/- 7, P less than 0.05). In anesthetized 2K,1C, BP changes were associated with reduction in total peripheral resistance (TPR) that became significant at 120 pmol X kg-1 X min-1 (-10 +/- 2%), whereas cardiac output (CO) and stroke volume (SV) were unchanged. In DOC-salt-treated rats these doses did not lower BP despite progressive falls in CO (-7 +/- 3% and -24 +/- 5%, P less than 0.05) and SV (-8 +/- 2% and -23 +/- 5%, P less than 0.05), which were balanced by a simultaneous rise in TPR (+12 +/- 4% and +26 +/- 10%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of diabetes on cardiac contractile proteins in rabbits and reversal with insulin
Authors: Pollack P. S. , Malhotra A. , Fein F. S. , Scheuer J.
Published: December 2017

In rats, chronic diabetes is associated with depressed cardiac myosin ATPase activity and a shift from the predominant V1 isoenzyme to V3, correlating with depressed contractility. Rabbit myocardium consists mostly of the V3 isoenzyme, and therefore a switch to even more V3 isoenzyme in diabetes might not be possible and therefore not explain the mechanical abnormalities observed. To explore this, rabbits were made diabetic with 140-150 mg/kg of alloxan, and their hearts were studied 3 days, 1 mo, 3 mo, and 6 mo later. Ca2+-myosin-ATPase activity was decreased in the diabetic rabbit at 1, 3, and 6 mo, correlating with increased percent V3. Actin-activated Mg2+-ATPase activity was not significantly decreased in diabetics, but myofibrillar ATPase activity was decreased in 6-mo diabetic animals. When 3- to 4-mo diabetic animals were administered insulin for 3-4 additional months, myosin-ATPase activity and isoenzyme distribution normalized. These results correlate well with mechanical changes in papillary muscle from these same hearts. They suggest that in rabbit, as in rat, changes in cardiac contractile function are at least partially mediated by changes in myosin isoenzyme composition and are reversible with insulin.
O2 consumption during exercise in dogs--roles of splenic contraction and alpha-adrenergic vasoconstriction
Authors: Longhurst J. C. , Musch T. I. , Ordway G. A.
Published: December 2017

To examine the influence of alpha-adrenergic vasoconstriction on the aerobic capacity of dogs, we calculated O2 consumption (VO2) by the Fick method during submaximal and maximal exertion before and during alpha-adrenergic blockade with phentolamine. Regional blood flow was measured with radioactive microspheres. alpha-Adrenergic receptor blockade reduced VO2 by 12.9% during submaximal and 17.9% during maximal exercise. Arterial and venous lactic acid approximately doubled during both levels of stress in the presence of alpha-adrenergic receptor blockade. Calculated VO2 decreased because arteriovenous O2 (A-V)O2 extraction was reduced by 11.6% during submaximal exercise. During maximal exercise a 16.7% decrease in (A-V)O2 extraction and a 5.7% decrease in cardiac output contributed to the decrease in maximal VO2. During both levels of stress, (A-V)O2 extraction was reduced because arterial O2 content was decreased. Since circulating hematocrits during exercise were reduced by alpha-adrenergic receptor blockade (43-38%), we postulate that splenic contraction likely was inhibited. Additionally, distribution of blood flow to skeletal muscle and visceral organs was unaltered by alpha-blockade. To examine the importance of splenic contraction during maximal exercise, we examined hemodynamic and metabolic responses before and after splenectomy. Compared with the spleen-intact condition, splenectomized dogs demonstrated a 12.6% reduction in VO2 as a result of 7.7 and 5.5% reductions in (A-V)O2 extraction and cardiac output, respectively. (A-V)O2 extraction was reduced because arterial O2 content and circulating hematocrit during exercise were decreased. Therefore, in the exercising dog, alpha-adrenergic receptor blockade reduces O2 consumption and causes a shift to anaerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Alpha 1-adrenergic stimulation of rat myocardial cells increases protein synthesis
Authors: Meidell R. S. , Sen A. , Henderson S. A. , Slahetka M. F. , Chien K. R.
Published: December 2017

The effects of adrenergic stimulation on the rates of protein synthesis, degradation, and accumulation were examined in primary cultures of neonatal rat heart cells. Treatment of myocardial cells with norepinephrine increased total cellular protein content and the rate of incorporation of radiolabeled tyrosine into trichloroacetic acid insoluble protein. alpha 1-Adrenergic, but not alpha 2- or beta-adrenergic blockade, inhibited these norepinephrine induced increases. The rate of protein synthesis estimated from the kinetics of equilibrium labeling and from combined equilibrium and pulse labeling was increased by norepinephrine stimulation, whereas protein degradation estimated by release of previously incorporated radiolabeled tyrosine or in pulse-chase experiments was unaffected. To determine whether alpha 1-adrenergic stimulation produced similar effects on the turnover of myofibrillar proteins, rates of synthesis and degradation were estimated for a myofibrillar-enriched protein fraction and for myosin heavy chain and actin. Norepinephrine treatment produced increases in the synthesis of myofibrillar protein without significantly altering degradation rates. These experiments suggest that alpha 1-adrenergic stimulation increases myocardial cell protein content by accelerating protein synthesis.
Concealed positive force-frequency relationships in rat and mouse cardiac muscle revealed by ryanodine
Authors: Stemmer P. , Akera T.
Published: December 2017

Increases in stimulation frequency between 0.3 and 2 Hz decrease developed tension in rat, seemingly inconsistent with the explanation that an elevation of intracellular Na+-ion concentration is responsible for the positive force-frequency relationships observed in most species. Thus the force-frequency relationships were reevaluated in isolated atrial muscle of rat and mouse heart that show negative relationships, comparing them with ferret and guinea pig that show positive relationships. Ryanodine (2 nM, 45-min exposure) markedly reduced potentiated postrest contractions in all four species and caused a marked negative inotropic effect especially at low stimulation frequencies in rat and mouse, a moderate effect in ferret, but only a modest effect in guinea pig. In the presence of ryanodine, all four species showed positive force-frequency relationships. These results indicate that activator calcium in rat, mouse, and ferret cardiac muscle has a large ryanodine-sensitive component that shows a negative force-frequency relationship, masking a component for positive force-frequency relationships that exists in all species.
Studies of functional site of origin of native coronary collaterals
Authors: Harrison D. G. , Chapman M. P. , Christy J. P. , Marcus M. L.
Published: December 2017

Studies were performed to determine the pressure at the origin of the native coronary collaterals (Pstem) and thus assess the contribution of collaterals arising from proximal conduit coronary vessels vs. those arising from distal microvessels. Nine isolated blood-perfused dog hearts were studied. Aortic pressure was maintained at 80 mmHg. Collateral flow to the circumflex perfusion field was measured (radioactive microspheres) repeatedly before and after successive 25-micron nonradioactive microsphere embolization of the circumflex vasculature. After each microembolization, collateral flow decreased and peripheral coronary pressure (PCP) increased. After all embolizations collateral flow decreased from an initial value of 17 +/- 4 to 2 +/- 0.4 ml X min-1 X 100 g-1 and PCP increased from an initial value of 15 +/- 3 to 65 +/- 3 mmHg. The relationship between decreasing collateral flow and increasing PCP was linear with a pressure intercept of 74 +/- 3 mmHg. This pressure intercept predicts the PCP that would be observed if microembolization produced complete cessation of collateral flow. Accordingly, this pressure intercept allowed an accurate estimate of Pstem. This estimate of Pstem was similar to left anterior descending pressure (75 +/- 2 mmHg). These studies show that Pstem may be accurately estimated by measuring pressure in a nonoccluded large epicardial vessel. The contribution of microvascular anastomoses to total collateral flow is likely small.
Two types of transient outward currents in adult human atrial cells
Authors: Escande D. , Coulombe A. , Faivre J. F. , Deroubaix E. , Coraboeuf E.
Published: December 2017

It has been suggested in a previous article [Escande et al., Am. J. Physiol. 249 (Heart Circ. Physiol. 18): H843-H850, 1985] that transient outward currents may participate in the initial repolarization of human atrial fibers. The present study substantiates the existence of such currents in human myocardium. Membrane currents were recorded in enzymatically dissociated cells using the whole cell patch-clamp technique. Two kinds of transient outward currents were observed: 1) a long-lasting outward current, (ilo), which was suppressed by 4-aminopyridine. The time to peak of ilo was 18.0 +/- 0.7 ms, and its inactivation time constant was 35.7 +/- 2.1 ms at room temperature (test pulses, +20 mV; holding potential, -40 mV); 2) a brief outward current (ibo), which persisted with 3 mM 4-aminopyridine and exhibited a shorter time to peak (5.5 +/- 0.2 ms) and a faster decay (time constant, 9.1 +/- 1.8 ms). ilo was inhibited by Ba but was insensitive to the calcium blocker Co. Co blocked both the slow inward current (isi) and ibo. It is concluded that two different transient outward currents control the repolarization in human atrial cells.
End-systolic pressure-volume relationship and intracellular control of contraction
Authors: Landesberg A.
Published: December 2017

The left ventricular (LV) pressure-volume relationship and the effect of ejection on pressure generation are predicted theoretically based on the intracellular control mechanisms. The control of contraction is described based on coupling calcium kinetics and cross-bridge cycling. The analysis of published skinned and intact cardiac muscle data suggests two feedback control loops: 1) a positive cooperative mechanism that determines the force-length relationship, the length dependence calcium sensitivity of the contractile filaments, and the related Frank Starling law; and 2) a negative mechanical feedback that determines the force-velocity relationship and the generated power. The interplay between these two feedback mechanisms explains the wide spectrum of phenomena associated with the end-systolic pressure-volume relationship (ESPVR); it provides an explanation for the "shortening deactivation" and for the recent observations of the positive effect of ejection on the ESPVR, i.e., the increase of the end-systolic pressure of the ejecting beat over the pressure of the isovolumic beat at the same end-systolic volume. Furthermore, the analysis suggests that the LV contractility depends on the balance between the two intracellular mechanisms and that the effect of loading conditions is determined through these intracellular mechanisms.
Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium
Authors: Morbidelli L. , Chang C. H. , Douglas J. G. , Granger H. J. , Ledda F. , Ziche M.
Published: December 2017

Vascular endothelial growth factor (VEGF) is a secreted protein that is a specific growth factor for endothelial cells. We have recently demonstrated that nitric oxide (NO) donors and vasoactive peptides promoting NO-mediated vasorelaxation induce angiogenesis in vivo as well as endothelial cell growth and motility in vitro; in contrast, inhibitors of NO synthase suppress angiogenesis. In this study we investigated the role of NO in mediating the mitogenic effect of VEGF on cultured microvascular endothelium isolated from coronary postcapillary venules. VEGF induced a dose-dependent increase in cell proliferation and DNA synthesis. The role of NO was determined by monitoring proliferation or guanosine 3',5'-cyclic monophosphate (cGMP) levels in the presence and absence of NO synthase blockers. The proliferative effect evoked by VEGF was reduced by pretreatment of the cells with NO synthase inhibitors. Exposure of the cells to VEGF induced a significant increment in cGMP levels. This effect was potentiated by superoxide dismutase addition and was abolished by NO synthase inhibitors. VEGF stimulates proliferation of postcapillary endothelial cells through the production of NO and cGMP accumulation.
Effects of a monoclonal antibody directed against P-selectin after myocardial ischemia and reperfusion
Authors: Lefer D. J. , Flynn D. M. , Buda A. J.
Published: December 2017

Neutrophils (polymorphonuclear leukocytes, PMNs) play a role in tissue injury after ischemia and reperfusion. We investigated the effects of a monoclonal antibody (MAb), PB1.3, directed against P-selectin in an acute model of myocardial ischemia-reperfusion injury. Dogs were subjected to 120 min of coronary arterial occlusion and 240 min of reperfusion. MAb PB1.3 (1 mg/kg), the nonblocking P-selectin antibody, MAb PNB1.6 (1 mg/kg), or saline was administered 5 min before reperfusion. Dogs treated with saline (n = 7), MAb PB1.3 (n = 7), and MAb PNB1.6 (n = 5) all experienced similar myocardial blood flows during ischemia, and treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow. Measurement of myocardial contractility failed to demonstrate any beneficial effects of MAb PB1.3 on postischemic myocardial contractility. However, myocardial necrosis (% of area at risk) was significantly reduced (P < 0.01) in dogs receiving MAb PB1.3 (20.8 +/- 4.8%) compared with dogs receiving either normal saline (41.7 +/- 4.5%) or MAb PNB1.6 (46.7 +/- 7.6%). Myocardial myeloperoxidase activity in the ischemic zone was 4.8 +/- 0.6 in the vehicle group and 3.7 +/- 0.5 in the MAb PNB1.6 group compared with 2.0 +/- 0.5 in MAb PB1.3-treated dogs (P < 0.01 vs. saline; P < 0.05 vs. PNB1.6). In summary, treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow or myocardial contractility. In contrast, P-selectin immunoneutralization reduced PMN accumulation and myocardial tissue injury in a canine model of coronary occlusion and reperfusion.
Phasic and tonic components of gustatory response in the frog
Authors: Kashiwagura T , Kamo N , Kurihara K , Kobatake Y
Published: December 2017

Characteristics of phasic and tonic responses of the frog glossopharyngeal nerve to various salts were examined under a variety of conditions. The results obtained are summarized as follows: 1) The salt concentration of adapting solutions affected greatly the phasic component of the responses to NaCl, KCl, MgCl2, and CaCl2, whereas the tonic component was independent of the adapting condition. 2) Either the phasic or tonic component was preferentially suppressed under appropriate conditions. 3) An abrupt rise of temperature of stimulating solution produced a phasic response. Magnitude of the phasic response induced by a rise of temperature was a function of both species and concentration of salts in the stimulating solution. 4) Binding of Hg2+ to the receptor and elimination of the bound Hg2+ by mercaptoethanol gave similar large phasic response. A slow elimination of the bound Hg2+ led to no response. It was concluded that a phasic response appears only when environments such as salt concentration or temperature are changing and that its magnitude is related to the rate of changes, whereas a tonic response represents information of the receptor membrane in an equilibrium state. Discussion on the obtained results was made under an assumption that the phasic response is attributed to a dynamic conformational change of the receptor membrane.
Impaired urinary concentrating ability and cyclic AMP in K+-depleted rat kidney
Authors: Beck N , Webster SK
Published: December 2017

The possibility that an alteration of the vasopressin-dependent cyclic AMP system plays a pathogenic role in the urinary concentrating defect in K+ depletion was investigated in the rat. The antidiuretic response to vasopressin was significantly less in K+-depleted rats. In these K+-depleted rats, the increase in urinary cyclic AMP excretion in response to vasopressin was also significantly less. However, repletion of K+ for 1 wk by feeding high-K+ diets restored the ability to increase urinary cyclic AMP excretion in response to vasopressin. In the in vitro incubation of renal medullary slices, the increase in cyclic AMP concentration in response to vasopressin was also significantly less in the slices obtained from K+-depleted rats than in those obtained from control rats. These findings suggest that, in K+ depletion, there is a reversible impairment of the vasopressin-dependent cyclic AMP system in the renal medulla; this impairment may play a pathogenic role in the urinary concentrating defect in K+ depletion.
Lower esophageal sphincter pressures and serum gastrin levels after cholinergic stimulation
Authors: Higgs RH , Humphries TJ , Castell DO , McGuigan JE
Published: December 2017

To define the role of gastrin, if any, in the response of the lower esophageal sphincter (LES) to bethanechol, serum gastrin determinations and LES pressure measurements were made in controls, patients with vagotomy and antrectomy (V&A), and patients with vagotomy and pyloroplasty (V&P). Despite significant differences in mean basal serum gastrin levels no differences were found in mean resting LES pressures among these groups. In controls significant increases in LES pressure occurred after subcutaneous bethanechol, but serum gastrin levels did not change from basal values. Subcutaneous injections of bethanechol produced significantly greater increases in LES pressures in V&P patients than in V&A patients. Serum gastrin levels did not change in either group; however, background serum gastrin concentrations were significantly greater for V&P patients than V&A patients throughout the study. Intravenous infusion of human gastrin I heptadecapeptide in controls significantly increased sphincter responses to bethanechol. Thus, these studies provide evidence to suggest that the LES response to bethanechol is affected by background serum gastrin levels.
Regional shortening patterns in canine right ventricle
Authors: Raines RA , LeWinter MM , Covell JW
Published: December 2017

The right ventricular outflow tract (OT) is a functionally distinct area of the right ventricle. However, there is little information on the contrdingly, inflow tract (IT) and OT chords and right ventricular free wall segmental changes were measured with implanted ultrasound crystals. The timing and extent of shortening of IT and OT chords and free wall segments were determined both at rest and after stellate ganglion stimulation. At rest, IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening was 38% while OT shortening was 34%. In contrast, OT segments did not show systolic expansion. IT segment shortening was 13% while OT shortening was 21%. With stellate stimulation, IT-OT gradients of 15-25 mmHg developed. The lag between IT and OT shortening decreased to 30 ms and segmental shortening increased. We conclude that the OT is a physiologically distinct region which contracts later and remains contracted longer than the IT. Both septal and free wall movements contribute to these changes.
Control of baboon limb blood flow and heart rate-role of skin vs. core temperature
Authors: Proppe DW , Brengelmann GL , Rowell LB
Published: December 2017

To discover the relative importance of body core temperature versus bodyskin temperature in raising limb blood flow and heart rate, we exposed seven unanesthetized, chaired baboons (Papio anubis) to a variety of heating protocols. First, the baboons were exposed to a 40-45 degrees C environment for 0.75-1.5 h. Arterial or right atrial blood temperature (Tbl), skin temperature (Tsk), mean right iliac blood flow (MRIF), and heart rate (HR) all increased gradually during heating. On the average, HR increased from 106 to 160 beats/min and MRIF rose to 286% of control level. To separate influences of Tbl and Tsk on cardiovascular changes, we manipulated Tbl and Tsk independently via a heat exchanger incorporated into a chronic femoral arteriovenous shunt. In most baboons, the MRIF and HR response to a hot environment could be essentially duplicated by elevation of bTbl with Tsk held neutral, while elevation of Tsk with Tbl held neutral had little effect. One baboon exhibited significant response to Tsk elevation with Tbl held neutral, although subsequent manipulation of Tbl overrode this response. We conclude that the normal response to heating in baboons is mainly attributable to drives from internal temperature-sensitive mechanisms. Elevated Tsk shows large effects only in exceptional cases.
Regulation of plasma calcium in rats: age-related roles of PTH and calcitonin
Authors: Kalu DN , Foster GV
Published: December 2017

To determine the influence of aging on the relative roles of parathyroid hormone (PTH) and calcitonin in the control of calcium homeostasis during fasting, we assessed changes in plasma calcium in fasted rats following simultaneous removal of the glands that secrete both hormones. Animals ranging in age from 3 to 34.7 wk were thyroparathyroidectomized or sham operated and bled by orbital puncture prior to and 1.5, 3, and 6 h after surgery. After thyroparathyroidectomy (TPTX), plasma calcium fell immediately and progressively in very young rats (3-6 wk old); in young animals (6.5-9.4 wk old), there was a delay of about 1.5 h pceded by a rise, which persisted for at least 3 h. Since the rise and fall in plasma calcium after TPTX are most likely due to calcitonin and PTH deficiencies, respectively, our observations are consistent with the following hypothesis; in the fasting state, the relative importance of calcitonin and PTH in the regulation of plasma calcium varies with age; PTH appears to play the dominant role in young rats; however, during maturation the importance of calcitonin appears to increase progressively.
Changes in renal hemodynamics and renin release caused by increased plasma oncotic pressure
Authors: Hall JE , Guyton AC
Published: December 2017

The effect of increased plasma oncotic pressure on renal blood flow (RBF), glomerular filtration rate (GFR), electrolyte excretion, and renin secretion rate (RSR) was studied in dogs anesthetized with sodium pentobarbital. Renal artery infusions of hyperoncotic dextran or human serum albumin raised renal venous colloid osmotic pressure an average of 7.3 and 10.1 mmHg, respectively, and caused small but consistent increases in RBF, large increases in RSR, marked decreases in urine flow rate and electrolyte excretion, with either no change or small decreases in GFR, and no change in renal artery pressure. Renal vasodilation was confined primarily to afferent arterioles and was not measureable until approximately 45 s after the start of infusions. The renal responses to increased plasma oncotic pressure appeared to be an autoregulatory phenomenon, consistent with a tubular mechanism dependent on an altered distal tubular fluid flow and/or composition. The increased renin release during increased plasma oncotic pressure is not compatible with a renal baroreceptor mechanism that responds to decreases in afferent arteriolar pressure because calculated glomerular pressure increased during albumin and dextran infusions.
PO2-modulated performance of cardiac muscle
Authors: Frezza WA , Bing OH
Published: December 2017

An inverse linear relationship between normalized tension development (T/mm2) and muscle cross-sectional area (range 0.32-1.68 mm2) is seen in fully oxygenated rat papillary and columnar carnease muscles studied while contracting isometrically at the apex of the length-tension curve. The data demonstrate progressively poorer performance with thicker preparations, presumatic blockade) is added to fully oxygenated muscle preparations, no significant change in performance is seen even with the thickest preparations, suggesting that no portion of mechanical activity is supported by anaerobic glycolysis. With progressive lowering of the muscle bath PO2, the relative contributions of aerobic and glycolytic activity to mechanical performance are demonstrated. Viewed from the Hill model of oxygen and lactic acid distribution in a cylindrical section of muscle, the data that suggest the presence of a hypoxic core appear contrary to the evidence that indicates the absence of tension supported by glycolytic activity. A possible solution to this apparent contradiction is presented. The findings of these experiments emphasize limitations of isolated muscle studies and help define the relationship between oxygenation and mechanical activity of cardiac muscle.
Effect of pH on ammonia production by renal mitochondria
Authors: Tannen RL , Kunin AS
Published: December 2017

NH3 production by renal cortical mitochondria was studied under conditions of metabolic acidosis induced in vivo and with pH manipulations of the media bathing mitochondria from normal rats. A HCO3- medium equilibrated with O2 and CO2 was utilized with glutamine concentrations of either 10 or 0.5 mM. With chronic acidosis NH3 production increased significantly at either substrate concentration. Similar results were obtained with rotenone in the media, both with chronic acidosis and with acidosis of 3 h duration, indicating that increased glutamine entry and/or phosphate-dependent glutaminase (PDG) activity accounts for the increased ammoniagenesis. In contrast to acidosis induced in vivo, mitochondria from normal rats subjected to a diminution in medium pH, either by manipulation of HCO3 concentration or PCO2, significantly decrease NH3 production. Mitochondrial studies with rotenone, as well as studies of solubilized PDG, suggest that a low pH diminishes NH3 production by directly altering PDG activity. Furthermore, regardless of the specifics of the mechanism, these studies indicate that adaptation to metabolic acidosis is not the immediate, direct result of a change in pH.
Glycogen levels and peripheral mechanisms of glucose-induced spppression of feeding
Authors: VanderWeele DA , Skoog DR , Novin D
Published: December 2017

Rabbits deprived of food for 0, 2, 4, 6, 8, 16, and 24 h were assessed for glucose-induced feeding suppression, refeeding after deprivation, and liver glycogen. In previous research, we hypothesized a relationship between liver glycogen and the transition from duodenal to hepatic glucose suppression. In duodenally cannulated rabbits, the infusion of 10 ml of isotonic glucose in awake, free-feeding animals significantly suppressed food intake but did not do so in those food deprived for 2, 4, 6, 8, or 24 h. In hepatic-cannulated rabbits, similar amounts of glucose significantly suppressed food intake in 4-, 6-, 16-, and 24-h-deprived animals. Also, refeeding after deprivation increased as a function of continued deprivation until 6 or 8 h, when refeeding reached asymptote, or decreased through 24-h deprivations. In agreement with these observations, liver glycogen showed a sharp decline between 4, 6, and 8 h of deprivation (depending on circadian cycle). It is proposed that liver glycogen depletion, or some correlate, alters liver glucostatic regulation and determines refeeding after deprivation.
Nephron function of the isolated perfused rat kidney
Authors: De Mello G , Maack T
Published: December 2017

Nephron functions of an improved isolated perfused rat kidney preparation were studied by micropuncture techniques. Single-nephron glomerular filtration rate (SNGFR), intratubular pydrostatic pressures (IP), transit time (TT), and the reabsorption (R) of H2O, Na, Cl, and K were measured in superficial proximal (PT) and distal tubules (DT) of the preparation. Mean SNGFR was 27.2 nl/min and 25.2 nl/min when measured in PT and DT, respectively. The PT transport functions were well maintained throughout the perfusion (mean values were: IP, 14.3 mmHg; TT, 17.7 s; fractional (F) RH2O, 64%; absolute RH2O, 15.4 nl/min; FRNA, 66.5%; FRK, 71%, and tubular fluid-to-perfusate tf/p) ratio of Cl, 1.37). The short loops of Henle reabsorbed less than 10% of the load of H2O and Na delivered to them and the TF/P ratio of electrolytes in the earliest DT segments were high (TF/P)Na = 0.88, (TF/P)Cl = 1.27, and (TF/P)K = 1.11). This deficiency in function of Henle's loop explains, at least in part, the degree of natriuresis of the preparation (overall FRNa = 97.5%). Transit time to end DT was prolonged (82.3 S) and IP in DT elevated (14.9 mmHg). The DT was able to compensate, in part, for the overload from Henle's loop by reabsorbing 36% of the fluid load and 54% of the Na load delivery to it. We concluded that the improved isolated perfused rat kidney is a suitable preparation with which to study several aspects of renal function, particularly proximal tubules transport functions.
Characterization of leucine transport by toadfish liver in vivo
Authors: Persell R , Haschemeyer AE
Published: December 2017

Kinetic analysis of L-leucine uptake by toadfish liver at 20 degrees C in vivo has been carried out after pulse injection of L-[14C]leucine into the hepatic portal vein. D-[3H]mannitol, which is taken up slowly by toadfish liver, is used as a marker for extracellular space and space accessible by simple diffusion. At normal plasma leucine concentration (0.1 mM), leucine uptake occurs rapidly (t1/2 = 0.25 min), representing a flux of 0.6 mumol/min for the liver as a whole. Analysis of the distribution of radioactive leucine among intracellular and extracellular free pools and protein-bound form at times of 30 s to 5 min after injection is consistent with operation of a concentrative or uphill transport system accounting for 40% of uptake at normal plasma concentration. Saturation of uptake occurs at increasing leucine loads; calculation of intracellular pool dilution from protein synthesis data indicates that 20-30% of liver intracellular space is occupied by incoming leucine during the first 2 min after portal injection. Maximal flux (V max) is 4.1 mumol/min per 7-g liver as a whole with Km = 0.6 mM. Competitive inhibition of leucine uptake is afforded by isoleucine and phenylalanine with lesser effects by aspartic acid, cysteine, methionine, threonine, tyrosine, and valine. No effect is observed with alanine, glycine, histidine, lysine, and proline.
Relationship of cerebral oxygen uptake to EEG frequency in isolated canine brain
Authors: Fitzpatrick JH , Gilboe DD , Drewes LR , Betz AL
Published: December 2017

Cerebral oxygen uptake was correlated with electroencephalographic (EEG) frequency and amplitude in 87 isolated canine brains. Group I (71 brains) was perfused with diluted blood and Group II (16 brains) was perfused with whole blood equilibrated with oxygen at various partial pressures. The EEG's were classified as follows: A, highest frequency greater than or equal to 17 Hz, alpha (8-13 Hz) amplitude less than 50 muv, delta (less than or equal to 3.5 Hz), amplitude less than 100 muv; B, highest frequency greater than or equal to 17 Hz, alpha amplitude greater to or equal to 50 muv, and/or delta amplitude greater than or equal to 100 muv. C, highest frequency 8-16 Hz, alpha amplitude greater than or equal to 25 muv, and delta amplitude greater than 100 muv, D, highest frequency 0.5-16 Hz, alpha, if present, amplitude less than 25 muv, and/or delta amplitude less than 100 muv, and E, highest frequency 0-16 Hz, alpha, if present, amplitude less than 10 muv, and/or delta amplitude less than 15 muv. The Group I oxygen uptakes in ml/100 g of brain per min+/-SE for the five EEG classifications were A, 4.39+/-0.06, B, 4.13+/-0.08, C, 3.76+/-0.09, D, 3.40+/-0.12, and E, 2.55+/-0.06, whereas the corresponding Group II values were A, 4.64+/-0.22, B, 4.28+/-0.15, C, 3.82+/-0.24, D, 3.39+/-0.40, and E, 1.38+/-0.42. As the EEG deteriorates, cerebral oxygen uptake tends to decrease in a significant and parallel manner in both the diluted and whole blood groups.