bluuebunny/crossref_metadata_2025 huggingface dataset:
Na(+)-H+ exchange in cardiac sarcolemmal vesicles isolated from diabetic rats
Authors: Pierce G. N. , Ramjiawan B. , Dhalla N. S. , Ferrari R.
Published: December 2017

Intracellular pH and [Na+] in the heart are regulated by the sarcolemmal membrane Na(+)-H+ exchange pathway. No data are currently available regarding the adaptation of this system to pathological conditions in the heart. Because ionic interactions with the heart are altered in cardiomyopathy during chronic experimental diabetes, it was hypothesized that Na(+)-H+ exchange may become abnormal. In addition, the effects of treating diabetic rats with daily injection of L-propionylcarnitine were investigated to determine whether alterations in lipid metabolism may be involved in any potential changes in ion transport. Rats were injected with streptozotocin (65 mg/kg) and killed 8–10 wk later, and sarcolemmal membrane vesicles were isolated from pooled ventricles. Significant depressions in Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity and Na(+)-Ca2+ exchange were observed in the diabetic preparations in comparison to control. L-Propionylcarnitine treatment of the diabetic rats partially normalized these activities. A striking depression in cardiac sarcolemmal Na(+)-H+ exchange was observed in the diabetic animals in comparison to control, and this was not a result of a nonspecific increase in membrane permeability. L-Propionylcarnitine treatment of the diabetic rats did not improve sarcolemmal Na(+)-H+ exchange.
Mechanisms of pulmonary edema induced by a diacylglycerol second messenger
Authors: Johnson A. , Hocking D. C. , Ferro T. J.
Published: December 2017

We investigated the effect of dioctanoylglycerol (DOG), a second messenger of protein kinase C (PKC) activation, in the absence and presence of neutrophils in isolated perfused guinea pig lung. DOG was given after a base-line isogravimetric steady-state period. Pulmonary capillary pressure (Ppc) and change in lung weight (delta W) were monitored at 15, 30, and 60 min. Capillary filtration coefficient (Kf,c, an index of vascular permeability) was measured during base-line period and at 30 min. DOG increased the Ppc and delta W at 30 and 60 min, and the Kfc at 30 min. Monooctanoylglycerol, a monoacylglycerol that does not activate PKC, had no effect on Ppc, Kf,c, and delta W. Pretreatment with two different PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine or staurosporin, prevented the pulmonary response to DOG. With neutrophils present, DOG caused greater increases in delta W and the (wet-dry)-to-dry wt ratio compared with DOG group. Response to DOG+ neutrophils was due to oxygen radical production because it was prevented by pretreatment with catalase and because DOG increased superoxide release from neutrophils. PKC activation using DOG in the isolated lung results in pulmonary edema mediated by increases in capillary pressure and vascular permeability. Lung weight-gain response to DOG is greater in the presence of neutrophils. Response to DOG+ neutrophils is mediated by oxygen radicals.
Enhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise-trained old rats
Authors: Tate C. A. , Taffet G. E. , Hudson E. K. , Blaylock S. L. , McBride R. P. , Michael L. H.
Published: December 2017

To determine whether endurance exercise training initiated during senescence improves the slower calcium transport of cardiac sarcoplasmic reticulum in senescent rats, three groups of male Fischer 344 rats were used: sedentary mature (SM), 11–12 mo of age; sedentary old (SO), 23–24 mo of age; and exercised old (EO), 23–24 mo of age. The EO rats ran on a motor-driven treadmill 5 days/wk for 8–10 wk while two other groups remained sedentary. The contraction duration of isometrically contracting papillary muscle was prolonged in the SO rats compared with the SM group, resulting from both a longer time-to-peak tension and a longer half-relaxation time. Chronic exercise improved the papillary muscle contractile function of the EO group to that observed in the younger SM rats. More importantly, the exercise regime ameliorated the slower oxalate-supported, ATP-dependent calcium transport observed in the SO group so that the EO and SM groups were the same. In contrast, the calcium-activated myosin adenosinetriphosphatase activity, which was slower in the SO group, was not altered after exercise training, so that both senescent groups were slower than the SM rats. Thus the increased calcium transport by the cardiac sarcoplasmic reticulum may be one of the potential mechanisms underlying the improvement of myocardial performance with chronic exercise initiated during senescence.
Diurnal variations in vagal and sympathetic cardiac control
Authors: Hayano J. , Sakakibara Y. , Yamada M. , Kamiya T. , Fujinami T. , Yokoyama K. , Watanabe Y. , Takata K.
Published: December 2017

To investigate the diurnal variation in autonomic cardiac control, the magnitudes of the power spectral components of supine and standing heart rate variability were measured during controlled respiration (15 breaths/min). Examination was performed hourly between 0700 and 2300 h in eight male subjects whose activities and food intake were controlled for 24 h in the laboratory. The respiratory component (0.25 Hz) was greater in the morning than in the late afternoon (P less than 0.05) and decreased 30 min after food intake (P less than 0.01) in the supine position, but it was unaffected by the time of day or food intake while in the standing position. The Mayer wave component (0.03-0.15 Hz) did not change with the time of day, but it increased 90 min after food intake in both supine and standing positions (P less than 0.01 and P less than 0.05, respectively). These data suggest that supine vagal cardiac control during the waking period increases in the morning and decreases 30 min after food intake and that sympathetic cardiac control increases 90 min after food intake.
Phase resetting in a model of sinoatrial nodal membrane: ionic and topological aspects
Authors: Guevara M. R. , Jongsma H. J.
Published: December 2017

We describe the phase-resetting effect of injecting an isolated current pulse in an ionic model of a single cell of the sinoatrial node. Delivery of a depolarizing pulse early (late) in the cycle results in a prolongation (abbreviation) of the cycle length. With a hyperpolarizing pulse, the effect is reversed. We determine the topological type or degree of phase resetting in two ways: 1) by analyzing interbeat intervals extracted from the voltage waveform, and 2) by analyzing the waveform, not only of the voltage, but of all the activation and inactivation variables. The two methods give similar results. At low (high) pulse amplitudes, there is type 1 (0) phase resetting. When type 1 phase resetting occurs, the new phase is a monotonically increasing function of the old phase at sufficiently low stimulus amplitudes, whereas at higher stimulus amplitudes it is not. Leading roles in generating phase resetting are attributed to the slow inward current and to the leakage current. Comparison is made with experimental phase-resetting findings in the sinoatrial node and other cardiac oscillators. Implications for unidirectional and bidirectional synchronization are also sketched out.
Dynamic changes in cardiac vagal tone as measured by time-series analysis
Authors: Billman G. E. , Dujardin J. P.
Published: December 2017

A time-series analysis of heart rate variability was evaluated as a marker of cardiac vagal tone using well-characterized autonomic interventions. Heart period (R-R interval) was recorded in 14 mongrel dogs from which the amplitude of the respiratory sinus arrhythmia (0.24-1.04 Hz) was determined. Exercise elicited significant (P less than 0.01) reductions in the index of vagal tone (control 6.3 +/- 0.3 ln ms2 vs. exercise 2.4 +/- 0.4 ln ms2) that were accompanied by significant (P less than 0.01) increases in heart rate (control 123.1 +/- 5 vs. exercise 201.0 +/- 7.7 beats/min). The vagal tone index remained greater than 0 throughout exercise. After propranolol HCl pretreatment, the vagal tone index rapidly decreased toward zero (control 6.2 +/- 0.5; exercise 0.7 +/- 0.3 ln ms2), despite significantly lower increases in heart rate (control 109.3 +/- 4.2; exercise 178.0 +/- 7.6 beats/min). Atropine given during exercise evoked significantly greater increases in heart rate in the control (+48.7 +/- 7.9 beats/min) vs. propranolol (+14.2 +/- 6.7 beats/min) conditions. These data suggest that 1) high levels of cardiac vagal tone remain during exercise; 2) vagal withdrawal is largely responsible for the heart rate increase after beta-adrenergic receptor blockade; and 3) time-series analysis of the R-R interval can provide a dynamic and noninvasive index of cardiac vagal tone.
Short-term systemic autoregulation
Authors: Borgdorff P. , Gross D. R. , Burattini R. , Duijst P. , Westerhof N.
Published: December 2017

We studied total systemic autoregulation in closed-chest, chloralose-anesthetized dogs. Cardiac out-put (previously implanted electromagnetic flow probe on ascending aorta) and aortic pressure were varied by reducing venous return using a balloon catheter in the vena cava. Compensatory action of the baroreflex was prevented by bilateral vagotomy and isolation of both carotid sinuses. To avoid high vessel tone carotid sinus pressure was set at the original baseline value using a pressurized blood reservoir. With each balloon inflation aortic flow and aortic pressure decreased and stabilized in about 1 min. Pressure and flow were allowed to return to base-line values after each balloon inflation in an attempt to minimize the activation of slower regulatory mechanisms. The steady-state pressure-flow relations could be fitted with a sigmoidal curve. The mean quality (0 less than Q less than 1) of autoregulation in eight dogs was 0.41 +/- 0.08 (SD). Autoregulation was found in the pressure range from 42 to 140 mmHg. The early appearance of total systemic autoregulation suggests that, in the intact animal, it may counteract baroreflex control.
Effect of pulmonary venous pressure elevation on vascular resistance and compliance
Authors: Barman S. A. , Taylor A. E.
Published: December 2017

The effect of pulmonary venous pressure elevation on the longitudinal distribution of resistance and compliance in the canine pulmonary circulation was determined at control vascular tone and after vascular tone was increased with histamine. The arterial, venous, and double-occlusion techniques were used in isolated dog lungs blood perfused at constant flow. The large and small blood vessel resistances and compliances were studied under both vascular tone conditions when pulmonary venous pressure was elevated above isogravimetric venous pressure conditions in successive 5 cmH2O increments up to 30 cmH2O. The results of this study indicate that pulmonary venous pressure elevations to 20 cmH2O above isogravimetric venous pressure significantly decrease total vascular resistance by reducing both the small and large vein resistances, an effect which is more pronounced in the histamine-treated lungs. Also, under control vascular tone, both the middle compartment compliance and total compliance were greatly decreased over this pressure range. Histamine treatment significantly reduced both the large vessel and middle compartment compliances before and during low venous pressure elevation. When venous pressure was then raised to at least 25 cmH2O above control outflow pressure with histamine present, the middle compartment compliance was again significantly decreased.
Analysis of short-term oscillations of R-R and arterial pressure in conscious dogs
Authors: Rimoldi O. , Pierini S. , Ferrari A. , Cerutti S. , Pagani M. , Malliani A.
Published: December 2017

We studied the neural determinants of the second (i.e., high frequency, HF)- and third-order (i.e., low frequency, LF) spontaneous oscillations of heart period (R-R interval) and arterial pressure (AP) in conscious dogs, with the hypothesis that they might furnish quantitative markers of autonomic controlling activities. Spectral analysis of simultaneous R-R and AP variabilities quantified these oscillations that were also evaluated in units normalized by total power to focus on the balance of these two major components. At rest we observed a prevalent HF component (approximately 0.25 Hz) in R-R and AP variabilities that was synchronous with respiration. This HF component of R-R variability disappeared after atropine infusion and can be considered a marker mostly of vagal activity. When baroreceptor unloading, obtained by moderate hypotension, increased sympathetic activity the LF component increased in R-R, systolic, and diastolic AP variabilities. This increase in LF was not present after ganglionic blockade or after chronic arterial baroreceptor denervation. After chronic bilateral stellectomy, hypotension was not accompanied by an increase in LF component of R-R variability, while LF component remained in AP variability. An increase in LF component of R-R and AP variabilities was observed during transient coronary artery occlusion.
Time-domain formulation of asymmetric T-tube model of arterial system
Authors: Campbell K. B. , Burattini R. , Bell D. L. , Kirkpatrick R. D. , Knowlen G. G.
Published: December 2017

An asymmetric T-tube model of the arterial system with complex terminal loads was formulated in the time domain. The model was formulated to allow it to be fitted to the aortic pressure waveform, the aortic flow waveform, or simultaneously to both the aortic and descending aortic flow waveforms. Pressure and flow measurements were taken in anesthetized open-chest dogs under basal, vasoconstricted, and vasodilated states. It was found that the T-tube model fitted the data well in all formulations and in all vasoactive states. However, all parameters were estimated accurately in all vasoactive states only with the formulation that fitted to both aortic and descending aortic flow simultaneously. The T-tube model was compared with the three-element windkessel model with regard to the respective models' ability to recreate specific aspects of the pressure waveform and with regard to the estimates of global arterial parameters. The T-tube model recremated those features of the pressure waveform, such as diastolic waves, that the windkessel model could not. Also, the T-tube model systematically estimated lower global arterial compliance and higher characteristic impedance than the windkessel. It was argued that the T-tube model accurately represented important wave transmission features of the arterial loading system. The model is recommended for use in characterizing the arterial load and for merging with representations of the left ventricle in studies of left ventricle-systemic arterial interaction.
Vasomotion of basilar arteries in vivo
Authors: Fujii K. , Heistad D. D. , Faraci F. M.
Published: December 2017

Vasomotion is a rhythmic change in vascular caliber that has been described in vivo mainly in peripheral arterioles. In this study, we have characterized vasomotion in a large artery of the brain in vivo. In anesthetized rats, spontaneous vasomotion was observed in 38 of 47 basilar arteries visualized through a cranial window. Base-line arterial diameter was 259 +/- 9 (means +/- SE) microns. Under control conditions, the frequency of vasomotion was 4.8 +/- 0.2 cycles/min, and the amplitude was 19 +/- 2% of the mean diameter. Vasomotion usually occurred simultaneously along the entire length of the vessel, but in some arteries it propagated in either direction. Moderate hypertension (phenylephrine) or vasoconstriction induced by topical application of serotonin, vasopressin, or the thromboxane analogue U 46619 increased the frequency of vasomotion. Moderate hypotension or vasodilation induced by nitroglycerin, adenosine, or acetylcholine decreased the frequency. Marked hypertension, hypotension, or vasodilatation abolished vasomotion. Thus vasomotion of the basilar artery in vivo 1) is common and of relatively large amplitude, 2) does not seem to be driven by a single pacemaker, and 3) is dependent on vessel diameter or vasomotor tone.
Two pathways for Ca2+ channel gating differentially modulated by physiological stimuli
Authors: Richard S. , Tiaho F. , Charnet P. , Nargeot J. , Nerbonne J. M.
Published: December 2017

In cardiac muscle, Ca2+ entry through voltage-gated Ca2+ channels plays an important role in the generation of action potentials and in the development of tension. Although it had been assumed that there was a single type of cardiac Ca2+ channel, recent studies reveal that multiple Ca2+ channel types coexist in some myocardial cells. Here, we report that macroscopic Ca2+ current (ICa) waveforms in isolated adult rat ventricular myocytes comprise two kinetically distinct components; these are referred to here as ICa (fc) and ICa (sc) to denote the fast and slow components, respectively, of ICa decay. In contrast to findings in other cells, the properties of ICa (fc) and ICa (sc) suggest the presence of two pathways for gating of a single type of high-threshold Ca2+ channel rather than two distinct Ca2+ channel types. In addition, gating via ICa (fc) and ICa (sc) is regulated by changes in membrane potential and stimulation frequency. Hyperpolarized potentials and low stimulation frequencies reveal preferential activation via ICa (fc); depolarized potentials and high stimulation frequencies, in contrast, favor activation via ICa (sc). After exposure to beta-adrenergic agonists or the Ca2+ agonist BAY K 8644, peak ICa amplitudes increase owing to the preferential augmentation of ICa (fc); beta-agonists and BAY K 8644 also increase ICa (sc), albeit to a smaller extent than ICa (fc). Thus, in addition to voltage- and frequency-dependent regulation, the two pathways for Ca2+ channel gating are modulated differentially by beta-adrenergic and Ca2+ channel agonists.
Effect of pinacidil on ion permeability in resting and contracted resistance vessels
Authors: Videbaek L. M. , Aalkjaer C. , Hughes A. D. , Mulvany M. J.
Published: December 2017

Pinacidil is thought to cause vasodilatation by opening K+ channels and consequent hyperpolarization. This proposed mechanism of action is based mainly on membrane potential measurements and 42K or 86Rb efflux experiments under resting conditions. We have measured the simultaneous effect of pinacidil on force and membrane potential in resting and norepinephrine-contracted rat mesenteric resistance vessels. Also the effect of pinacidil on 42K and 36Cl efflux and 22Na uptake in the absence and presence of norepinephrine was examined. From the membrane potential and ion flux measurements the ion permeabilities were calculated. In both resting and norepinephrine-contracted vessels, pinacidil caused a large hyperpolarization, the latter situation being associated with an almost complete relaxation. In both resting and norepinephrine-stimulated vessels, pinacidil caused a large increase in K+ permeability and a decrease in Cl-permeability, whereas no significant change of Na+ permeability was found. Our results suggest that pinacidil causes vasodilation due to hyperpolarization. The major cause for the hyperpolarization is an increase in K+ permeability.
Transport of inert gases in mammalian myocardium: comparison with a convection-diffusion model
Authors: Wolpers H. G. , Hoeft A. , Korb H. , Lichtlen P. R. , Hellige G.
Published: December 2017

Because tracer techniques are gaining an increasing importance for imaging flow (and metabolism) in the heart, experimental evidence is needed on the role of convection and diffusion in the transcoronary transport of solutes. In the present work, the transport of four different inert gases through the coronary system is studied in five closed-chest dog experiments and is compared with a digital multicapillary convection-diffusion model. Transport may be defined as flow dependent, as judged by the gross similarity of shape of the time-normalized dilution curves. However, the results show that the transcoronary transport of helium and xenon is more dispersed than that of argon and krypton, probably because of differences in diffusibility and solubility. A comparison of the animal and model experiments emphasizes the importance of diffusive transport of the gases. It is suggested that there is a diffusion shunt that is mainly located within the capillary network itself rather than between conduit vessels. Only for helium (which has the highest diffusivity) was a small arteriovenous shunt fraction seen that is thought to bypass the capillary exchange region. The conclusion is that although there is evidence of diffusional shunting at a capillary level, the inert gas kinetics in the heart are compatible with a basically flow-limited transport.
Chronic supraventricular tachycardia causes ventricular dysfunction and subendocardial injury in swine
Authors: Spinale F. G. , Hendrick D. A. , Crawford F. A. , Smith A. C. , Hamada Y. , Carabello B. A.
Published: December 2017

Chronic supraventricular tachycardia has been associated with ventricular dysfunction in humans and animals. However, this ventricular failure is poorly characterized, and the ultrastructural consequences of supraventricular tachycardia are unknown. We serially examined right and left ventricular function, endomyocardial ultrastructure, and creatine kinase activity in eight pigs at base line and again at 1, 2, and 3 wk following rapid atrial pacing. Left and right ventricular ejection fractions fell significantly from base line after 1 wk of chronic tachycardia. Three weeks of chronic pacing resulted in further deterioration in ejection fractions. Significant biventricular chamber dilatation developed and was associated with a reduction in end-diastolic wall thickness after 2 wk of tachycardia. Mitochondrial injury and diminished mitochondrial cytochrome oxidase staining of subendocardial myocytes were observed after 2 wk of tachycardia. Endomyocardial creatine kinase activity fell from control levels following 2 wk of pacing. Postmortem examination revealed a reduction in left ventricular wall thickness compared with 14 control animals. Fibrosis occurred along the subendocardial layer in paced animals, and glycogen content was also reduced. In summary, chronic supraventricular tachycardia resulted in severe biventricular pump dysfunction and chamber dilatation that were associated with ultrastructural alterations and reduced enzyme activity of the subendocardial myocytes. These ultrastructural and metabolic changes may be potential mechanisms responsible for the ventricular dysfunction and dilatation observed in this model.
Redistribution of myocardial fiber strain and blood flow by asynchronous activation
Authors: Prinzen F. W. , Augustijn C. H. , Arts T. , Allessie M. A. , Reneman R. S.
Published: December 2017

Hearts of 11 anesthetized open-chest dogs were paced from the right atrium (RA), right ventricular outflow tract (RVOT), and left ventricular apex (LVA). Maps of the sequence of electrical activation (192 electrodes), fiber strain (video technique), and blood flow (microsphere technique) in the epicardial layers were obtained from a 15- to 20-cm2 area of the anterior left ventricular wall. Electrical asynchrony in this area was 10 +/- 5 (RA), 52 +/- 12 (RVOT), and 30 +/- 16 ms (LVA, mean +/- SD, P less than 0.05 for RVOT and LVA compared with RA). Epicardial fiber strain during the ejection phase was uniformly distributed during RA pacing. However, during ventricular pacing it ranged from 13 +/- 33% (RVOT) and 23 +/- 29% (LVA) of the value during RA pacing in early-activated regions to 268 +/- 127% (RVOT) and 250 +/- 130% (LVA) of this value in late-activated regions. Epicardial blood flow ranged from 81 +/- 22% (RVOT) and 79 +/- 23% (LVA) in early-activated regions to 142 +/- 42% (RVOT) and 126 +/- 22% (LVA) in late activated regions. In all above values P less than 0.05 compared with RA. During RVOT pacing, gradients of epicardial electrical activation time, fiber strain, and blood flow pointed in the same direction. Compared with RVOT pacing, during LVA pacing all gradients were opposite in direction, and the gradients of electrical activation time and blood flow appeared to be smaller. These results indicate that timing of electrical activation is an important determinant for the distribution of fiber strain and blood flow in the left ventricular wall.
Removal rate of [3H]hyaluronan injected subcutaneously in rabbits
Authors: Reed R. K. , Laurent U. B. , Fraser J. R. , Laurent T. C.
Published: December 2017

Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable ("free") hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of [3H]hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of 3H in plasma. During the first 24 h after injection, 10-87% of the tracer entered blood, less in injectates with high concentrations of hyaluronan. The removal was monoexponential with a half-life of 0.5-1 day when concentration of hyaluronan was 5 mg/ml or less. When hyaluronan concentration was 10 mg/ml or higher, the removal was slow for about 24 h and then became similar to that in experiments with low hyaluronan concentration. Free hyaluronan at physiological concentrations is thus turned over with the same rate as serum albumin, supporting the concept that hyaluronan is removed essentially by lymph flow to be degraded in lymph nodes and liver.
Rat venular pressure-diameter relationships are regulated by sympathetic activity
Authors: Shoukas A. A. , Bohlen H. G.
Published: December 2017

The hypothesis that the pressure-diameter relationship of intestinal venules in rats is primarily determined by sympathetic nervous system activity was tested. The pressure-diameter relationship of the smallest to largest diameter (20-100 microns) intestinal venules of the rat was measured at rest, during hemorrhage to increase sympathetic neural activity, and during saline volume expansion to decrease sympathetic activity. During hemorrhage, the diameter of all venules decreased approximately 10% at 10 mmHg venous pressure, and the slope of the pressure-diameter relationship increased approximately 50% above control. Blood volume expansion led to an approximately 10% increase in venule diameter at 10 mmHg and a 25% decrease in slope. Denervation of the vessels causes concomitant vasodilation, which was greater than the vasodilation caused by blood volume expansion. Hemorrhage after denervation caused no significant changes in the relationship when compared with denervated control. Nitroprusside caused an even greater vasodilation when compared with the pressure-diameter relationship after denervation. The results suggest that the slope and 10-mmHg intercept of the pressure-diameter relationship for the largest through smallest intestinal venules and, therefore, their vascular compliance and capacitance characteristics are primarily determined by sympathetic activity.
Direct evidence of changes in myofilament responsiveness to Ca2+ during hypoxia and reoxygenation in myocardium
Authors: Hajjar R. J. , Gwathmey J. K.
Published: December 2017

In the presence of 1 microM ryanodine, muscles loaded with the calcium indicator aequorin were stimulated at 15-20 Hz to produce steady levels of force and intracellular Ca2+ concentrations [( Ca2+]i) at various extracellular Ca2+ concentration ([Ca2+]o). After 5, 10, and 15 min of hypoxia and 3 min of reoxygenation, tetani were initiated. Force vs. [Ca2+]i relation was shifted to the right 0.11, 0.18, and 0.24 pCa units, and maximal force was down 66, 48, and 37% after start of hypoxia. During reoxygenation, the relationship was shifted up by 26%. In skinned fiber preparations, an increase in inorganic phosphate ion concentration from 0 to 10 mM and 15 mM decreased maximal force development by 32 and 53%, respectively, and shifted the pCa-force curve to the right by 0.08 and 0.14 pCa. A decrease in pH from 7.1 to 6.8 shifted the pCa-force curve to the right by 0.20 pCa units without affecting maximal force. These changes indicate that during hypoxia, a decrease in the sensitivity of the myofilaments to Ca2+ and a depression of maximal Ca2(+)-activated force occur, whereas during reoxygenation, there is an increase in maximal Ca2(+)-activated force.
Compliance of left atrium with and without left atrium appendage
Authors: Davis C. A. , Rembert J. C. , Greenfield J. C.
Published: December 2017

Compliance of the left atrial chamber was estimated with and without the appendage intact in six isolated canine left atria. Pressure-volume determinations were measured over a range of 5-30 mmHg for the whole left atrium and were repeated with the appendage excluded. The slope of the pressure vs. normalized volume data for the left atrium without the appendage (10.45 +/- 0.87) was significantly greater (P less than 0.01) than with the appendage intact (4.10 +/- 0.72). These data suggest that the left atrial appendage is more compliant than the remaining left atrium. Assuming that this relationship remains in vivo, the left atrial appendage may play an augmented role in maintaining hemodynamic function when filling pressures are elevated.
Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts
Authors: McVeigh J. J. , Lopaschuk G. D.
Published: December 2017

We have previously shown that high concentrations of fatty acids depress reperfusion recovery of ischemic rat hearts as a result of a fatty acid inhibition of glucose oxidation. In this study, we determined whether dichloroacetate, an activator of pyruvate dehydrogenase, could overcome fatty acid inhibition of glucose oxidation and thereby improve mechanical recovery of hearts reperfused after a period of transient global ischemia. Isolated working rat hearts, perfused with 11 mM glucose, 1.2 mM palmitate, and 500 microU/ml insulin, were subjected to a 30-min period of no flow ischemia, followed by a 30-min period of reperfusion. Under these conditions, control hearts recovered 37% of preischemic function. The addition of 1 mM dichloroacetate to the perfusate at reperfusion resulted in a significant improvement in recovery of mechanical function (to 73% of preischemic function). When dichloroacetate was added before the onset of ischemia, however, this protective effect was lost, and a significant increase in myocardial lactate accumulation during ischemia was observed. The effects of dichloroacetate on glucose oxidation rates in both nonischemic and reperfused ischemic hearts was determined by perfusing hearts with 11 mM [U-14C]glucose and 1.2 mM palmitate and quantitatively collecting 14CO2 produced by the heart. In nonischemic hearts, 1 mM dichloroacetate increased steady-state glucose oxidation rates from 298 +/- 69 to 1,223 +/- 135 nmol.g dry wt-1.min-1. The addition of dichloroacetate to hearts reperfused after a 25-min period of ischemia also increased glucose oxidation rates from (112 +/- 25 to 561 +/- 83 nmol.g dry wt-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Severe myocardial dysfunction induced by ventricular remodeling in aging rat hearts
Authors: Capasso J. M. , Palackal T. , Olivetti G. , Anversa P.
Published: December 2017

To determine if aging engenders alterations in the functional properties of the myocardium and ventricular remodeling, the hemodynamic performance and structural characteristics of the left ventricle of male Fischer 344 rats at 4, 12, 20, and 29 mo of age were studied by quantitative physiology and morphology. In vivo assessment of cardiac pump function showed no change up to 20 mo, whereas left ventricular end-diastolic pressure was increased at 29 mo. Moreover, peak rates of pressure rise and decay, stroke volume, ejection fraction, and cardiac output were depressed at the later age interval, demonstrating the presence of ventricular failure at this time. The measurements of chamber size and wall thickness showed that ventricular end-diastolic and end-systolic volumes progressively increased with age with the greatest change occurring at 20-29 mo. Aging was also accompanied by a marked augmentation in the volume fraction of fibrotic areas in the ventricular myocardium that was due to an increase in their number and cross-sectional area with time. These architectural rearrangements, in combination with the abnormalities in ventricular function, resulted in an elevation in the volume of wall stress throughout the cardiac cycle. Wall stress increased by 64, 44, and 50% from 4 to 12, 12 to 20, and 20 to 29 mo of age. In conclusion, aging leads to a continuous rise in wall stress that is not normalized by ventricular remodeling. These two independent processes appear to be responsible for the onset of heart failure in the senescent rat.
Role of endocardial endothelium in positive inotropic action of vasopressin
Authors: Schoemaker I. E. , Meulemans A. L. , Andries L. J. , Brutsaert D. L.
Published: December 2017

We have studied the effects of vasopressin on isolated cat papillary muscle both before and after damaging the endocardium. The experiments were performed in physiological conditions of temperature (35 degrees C) and calcium concentration (1.25 mM Ca2+). Isometric and isotonic twitches as well as maximal unloaded velocity of shortening (Vmax) were measured. In muscles with an intact endocardium (n = 13), vasopressin (10(-12) to 10(-6) M) induced early twitch relaxation with a significant reduction of time to half isometric tension decline and with concomitant significant decrease in peak twitch performance. In a second group of muscles (n = 13) the endocardial endothelial surface was damaged by briefly (1 s) exposing the muscles to a 0.5% Triton X-100 followed by abundant wash with Krebs-Ringer solution, thereby irreversibly decreasing time to half twitch relaxation and peak twitch tension without significantly affecting Vmax. After this intervention, vasopressin had a positive inotropic effect with a significant increase in peak twitch tension and Vmax with no significant changes in twitch duration. Accordingly, in the presence of a functional endocardium, the direct myocardial positive inotropic effect of vasopressin was reversed, with early twitch relaxation and diminished peak twitch performance. At the highest concentrations of vasopressin, vasopressin-induced functional and morphological damage of the endocardium was observed.
Leukocyte and platelet-derived factors augment canine coronary constriction to serotonin
Authors: Cappelli-Bigazzi M. , Lamping K. G. , Nuno D. W. , Harrison D. G.
Published: December 2017

In open-chest anesthetized dogs acute hypertension causes neutrophil and platelet adhesion to vascular endothelium and selectively potentiates constriction to serotonin in proximal coronary arteries. To examine underlying mechanisms, canine left anterior descending coronary arteries subjected to 15 min hypertension (LAD-HYP) and control left circumflex coronary arteries (CX) perfused at normal pressure were studied in organ chambers. In endothelium-intact LAD-HYP rings, constriction to serotonin was potentiated fourfold compared with control CX rings but was similar in denuded LAD-HYP and CX vessels. Endothelium-dependent relaxation to acetylcholine was not affected by acute hypertension. In LAD-HYP rings 10 microM LY 83583 (which depletes guanosine 3',5'-cyclic monophosphate and inhibits effects of endothelium-derived relaxing factor) augmented constriction to serotonin twofold. LY 83583 did not affect the serotonin response in hypertensive rings whose endothelium was mechanically removed. Blockade of either leukotriene D4 (LTD4) receptors (either with LY 171883 or SKF 102992) or thromboxane A2 (TxA2) receptors (with SQ 29548) partially blunted constriction to serotonin. Combined LTD4- and TxA2-receptor blockade completely normalized serotonin-induced constriction in LAD-HYP rings. In preconstricted LAD-HYP rings, relaxations to serotonin were markedly impaired but were restored by addition of ketanserin. Normalization of relaxation to serotonin in hypertensive vessels by ketanserin is likely due to inhibition of 5-hydroxytryptamine2 (5-HT2) receptors on platelet membranes. In conclusion, augmented constriction to serotonin in canine epicardial vessels exposed to acute hypertension is not due to an impairment of endothelium-dependent relaxation to the amine but to concomitant release of leukotrienes and TxA2 from leukocytes and platelets adhering to damaged endothelium. Activation of 5-HT2 serotonergic receptors on platelet membranes could be a possible trigger mechanism.
Dilation of cerebral arterioles by cytochrome P-450 metabolites of arachidonic acid
Authors: Ellis E. F. , Police R. J. , Yancey L. , McKinney J. S. , Amruthesh S. C.
Published: December 2017

We have recently shown that brain tissue can synthesize cytochrome P-450 monooxygenase metabolites of arachidonic acid (AA), including 5,6-epoxyeicosatrienoic acid (5,6-EET), and 14,15-EET. The purpose of this investigation was to determine the vasoactivity of EETs and AA on the cerebral microcirculation. Pial arteriolar diameter was measured in rabbits and cats using in vivo microscopy and the closed cranial window technique. Prostaglandin (PG) E2 and 6-keto-PGF1 alpha formed by the brain cortex during application of these fatty acids was measured in cerebrospinal fluid by use of radioimmunoassay. A transient dose-dependent dilation was produced by 5,6-EET (1-15 micrograms/ml), with the maximum being 23% of control in both species. Other EETs had little or no activity, and AA-induced dilation was greater in rabbits than in cats. Indomethacin or superoxide dismutase plus catalase prevented dilation by 5,6-EET and AA, indicating that both produce dilation via cyclooxygenase-dependent oxygen radicals. PGE2 and 6-keto-PGF1 alpha levels were increased by AA but not by EETs, implying that EETs do not directly activate AA metabolism. Since 5,6-EET, but not other EETs, is known to be a substrate for cyclooxygenase, our data are consistent with brain cyclooxygenase metabolism of 5,6-EET with concomitant generation of dilator oxygen radicals. An implication of these results is that many previous studies of the cerebral circulation which based conclusions on results with cyclooxygenase inhibitors may need to be additionally interpreted.
Adenosine and active hyperemia in soleus and gracilis muscle of cats
Authors: Schwartz L. M. , McKenzie J. E.
Published: December 2017

Exercise-induced increases in tissue adenosine level vary in muscles having different oxidative capacities. These studies were designed to further evaluate the role of this potent vasodilator as a modulator of active hyperemia in muscles having different intrinsic metabolic profiles. Soleus (slow-twitch oxidative) and gracilis (fast-twitch glycolytic) muscles of anesthetized cats were stimulated to contract isometrically in the presence of adenosine deaminase (ADA) or ADA that had been deactivated by boiling (BADA). Stimulation parameters were chosen to provide similar high and low blood flow responses in the two muscle types. ADA did not affect resting blood flow or vascular resistance. In the soleus muscle, ADA attenuated both the increase in blood flow and oxygen consumption and the decrease in vascular resistance at the high level of muscle stimulation. In addition, muscle performance decreased to 60% of its initial level in the presence of ADA, although the same initial performance level was maintained over the stimulation period during BADA infusion. Temporal studies in the soleus muscle demonstrated an ADA-induced decrease in oxygen consumption, which was the product of an attenuated blood flow, followed by reductions in muscle performance. ADA had no effect on active hyperemia in either muscle at the low stimulation level. Additionally, ADA did not attenuate active hyperemia in the gracilis when stimulated at a level that normally produced muscle fatigue. Therefore these data support a role for adenosine in mediating vasodilation in skeletal muscle composed of high-oxidative fibers at high levels of muscle performance but do not support a role for adenosine in skeletal muscle having low-oxidative fibers, even at levels of exercise which produce fatigue.
Effects of sympathectomy on blood pressure and its variability in conscious rats
Authors: Julien C. , Kandza P. , Barres C. , Lo M. , Cerutti C. , Sassard J.
Published: December 2017

To further assess the role of the sympathetic nervous system (SNS) in the control of blood pressure (BP), continuous recordings of BP were performed in conscious freely moving rats that had received daily injections of guanethidine or saline from 7 to 90 days of age. Guanethidine extensively destroyed the peripheral sympathetic fibers as indicated by marked decreases in the norepinephrine content of the heart and kidneys and the absence of pressor response to tyramine injection. Such a chronic sympathectomy did not alter the BP and heart rate (HR) levels but markedly enhanced the BP variability while the HR variability and the sensitivity of the cardiac baroreceptor reflex were not altered. Angiotensin-converting enzyme inhibition with perindopril induced a rapid fall in BP and normalized the BP variability in sympathectomized animals. It is concluded that in rats, the SNS is not necessary for the full development of the BP level but is essential to buffer the spontaneous variability of BP. After sympathectomy, BP is maintained at nearly normal levels mainly through activation of the renin angiotensin system.
Reflex responses of renal nerve activity during isometric muscle contraction in cats
Authors: Matsukawa K. , Wall P. T. , Wilson L. B. , Mitchell J. H.
Published: December 2017

Renal sympathetic nerve activity (RSNA), arterial blood pressure (AP), and heart rate (HR) were measured during isometric muscle contraction of a hindlimb in chloralose-anesthetized cats. In 14 cats RSNA, AP, and HR increased during a 1-min contraction by 45%, 39 mmHg, and 11 beats/min, respectively; however, in three cats there was a brief initial decrease in RSNA followed by an increase. In 11 cats isometric contraction was maintained for 5 min by alternate stimulation of the L7 and S1 ventral roots. In the first 1 min of sustained contraction, there was a positive correlation (gamma = 0.58, P less than 0.005) between RSNA and tension development. Thereafter RSNA remained elevated despite a tension decrease, and there was no significant correlation between these changes. The RSNA response to contraction of both hindlimbs was greater than that to contraction of either hindlimb alone. Passive stretch of the hindlimb muscle significantly increased RSNA. Thus the initial increase in RSNA during sustained contraction is likely due to activation of muscle mechanoreceptors, whereas the later increase is probably caused by activation of the muscle metaboreceptors.
Excitatory amino acid receptors of guinea pig medial nucleus tractus solitarius neurons
Authors: Drewe J. A. , Miles R. , Kunze D. L.
Published: December 2017

Neurons isolated from the medial subnuclei of nucleus tractus solitarius in adult guinea pigs were studied for responses to the excitatory amino acid glutamate and its analogues using the whole cell tight-seal voltage clamp technique. In 80% of the cells studied (n = 60) 100 microM glutamate produced inward currents at negative voltages. To further characterize the glutamate response, the agonists for three glutamate receptor subtypes, N-methyl-D-aspartate (NMDA), kainate, and quisqualate, were examined for their effects on membrane conductance. NMDA (25-250 microM) activated currents in 85% of the neurons tested (n = 30). NMDA currents were generally very small in amplitude. Of the neurons tested, 84% responded to kainate (10-30 microM, n = 19) and only 50% to quisqualate (25-50 microM, n = 26). The conductance activated by NMDA was outwardly rectifying. The conductance activated by kainate was voltage independent, while that activated by quisqualate showed varying degrees of outward rectification. Responses to NMDA were specifically antagonized by DL-2-amino-5-phosphonovaleric acid (AP-5, 50-100 microM). Kainate responses were blocked by kynurenate at concentrations (0.5-1.5 mM) ineffective on quisqualate-induced current. Glutamic acid diethyl ester (GDEE, 2-15 mM) was effective in reducing quisqualate responses at concentrations that had no effect on kainate responses. This characterization of the glutamate receptor subtypes and effective antagonists provides a basis for future determination of the specific receptor of glutamate responsible for mediation of the excitatory postsynaptic potentials produced by activation of the baroreceptor input.
Three-dimensional mapping of acute ischemic regions using MRI: wall thickening versus motion analysis
Authors: Azhari H. , Sideman S. , Weiss J. L. , Shapiro E. P. , Weisfeldt M. L. , Graves W. L. , Rogers W. J. , Beyar R.
Published: December 2017

Three-dimensional (3D) endocardial wall motion and thickening were compared as quantitative methods for distinguishing ischemic from non-ischemic myocardium and for their potential to map regional left ventricular (LV) function. Data were obtained by gated magnetic resonance (MR) images in seven open-chest dogs with acute ischemia. The LVs were reconstructed in 3D at end diastole (ED) and end systole (ES) with a helical coordinate system that wraps the endocardium and epicardium. Thickness and percent wall thickening were calculated by a 3D volume element method. Wall motion was calculated by the 3D displacement of the endocardium perpendicular to the wall using both fixed and floating centroids. Monastral blue nonstaining identified the ischemic regions from five anatomical slices of the LV, which corresponded to the in vivo image planes. Thickening and motion were compared at the centers of the ischemic and the remote normal zones, in addition to comparing the functional maps of the entire LV to the postmortem anatomical maps. All methods distinguished between the center of the ischemic zone and the remote normal zone; however, thickening discriminated most strongly between zones. Comparison of the 3D in vivo maps with the 3D postmortem maps showed that the sensitivity, specificity, and overall accuracy of the thickening algorithm exceeded those obtained by the wall motion algorithms with fixed or floating centroids. Thus wall thickening utilizing the 3D volume element approach is superior to 3D wall motion algorithms in distinguishing ischemic from nonischemic zones and in mapping regional function in the entire LV.
Mechanism underlying the response to vasodilator nerve stimulation in isolated dog and monkey cerebral arteries
Authors: Toda N. , Okamura T.
Published: December 2017

Relaxant responses to transmural electrical stimulation and nicotine of cerebral artery strips obtained from dogs and Japanese monkeys were abolished by tetrodotoxin and hexamethonium, respectively, and suppressed by treatment with NG-monomethyl-L-arginine (L-NMMA), a nitric oxide (NO) synthesis inhibitor. The inhibitory effect was prevented and reversed by L-arginine but not by D-arginine. The relaxations suppressed by L-NMMA were not increased by exogenously applied NO. Endothelium denudation did not alter the response to transmural stimulation and nicotine or the inhibitory effect of L-NMMA. D-NMMA did not inhibit the response to vasodilator nerve stimulation. Dog coronary artery relaxations caused by transmural stimulation were not inhibited by L-NMMA but reversed to contractions by propranolol. Relaxations caused by substance P of dog cerebral arteries treated with indomethacin were dependent on endothelium and inhibited by L-NMMA, whereas those by NO and nitroglycerin, endothelium-independent relaxations, were unaffected. It is concluded that chemical and electrical stimulation of vasodilator nerves relaxes dog and monkey cerebral arteries, possibly by a mediation of NO rather than a stimulating action of NO on the release of vasodilator transmitter. Endothelium-dependent relaxations by substance P of dog cerebral arteries appear to be mediated by NO.