bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial oxygen consumption: the role of wall force and shortening
Authors: Weber K. T. , Janicki J. S.
Published: December 2017

The relationship between the force in the left ventricular wall during systole and myocardial O2 consumption (MVO2) was determined. In addition, the relative influence of the load imposed during shortening and fiber shortening on MVO2 was assessed. For this purpose, 14 servo-regulated, paced, isolated canine hearts were used and the steady-state response in total coronary flow and arteriovenous oxygen difference was measured. For both the isovolumetrically beating and the ejecting ventricle, statistically significant linear relations were observed between MVO2 and the integral of systolic force. These relations were not significantly different from one another, indicating that shortening was not a determinant of MVO2. Moreover, when ejecting an isolumetric beats of equivalent developed force were compared, a difference in MVO2 (deltaMVO2) was found. deltaMVO2 was a function of the force integral difference between these contractions and not fiber shortening. Thus, under the conditions of this experiment, the integral of systolic force that includes developed force and shortening load is the predominant factor regulating MVO2 for any given contractile state, whereas the influence of fiber shortening is negligible.
Dynamic compliance of arterial grafts
Authors: Baird R. N. , Kidson I. G. , L'Italien G. J. , Abbott W. M.
Published: December 2017

A cantilever transducer has been developed which allows measurements of diastolic diameter and diameter change in response to pulse pressure in dissected blood vessels during sterile procedures. Preliminary results indicate that it will detect subtle changes in wall elastic properties of arterial grafts at subtle changes in wall elastic properties of arterial grafts at and following implantation, which changes may influence graft function. Compliance, the percentage change in volume per unit pressure, was greater in normal canine femoral artery than in autogenous vein grafts (AVG). Two new graft materials were tested. Mesh-covered modified human umbilical cord vein (DBM) was similar in compliance to AVG but more compliant than double-velour Dacron. Diastolic diameter changes were also recorded. After 2 wk, all three graft materials had increased in diameter: AVG by 8%, DBM by 6%, and Dacron by 5%. After 3 mo, AVG diameter increased by 24%.
Normal and hypertrophic growth of the rat heart: changes in cell dimensions and number
Authors: Korecky B. , Rakusan K.
Published: December 2017

The length and width of enzymatically isolated individual rat cardiac myocytes were concurrently measured during normal and stimulated cardiac growth. In normal rats weighing between 75 and 750 g the length and width increased by 64 and 68% while their ratio remained constant (ca. 5.3). The cell volume, calculated on the basis of a cylindrical model, increased almost 5 times. The rates of increase in the volume of an average myocyte and in left ventricular mass were found to be similar, indicating that normal myocardial growth could be explained by hypertrophy of existing myocytes and no proliferation would be required. In cardiomegaly induced by aortic constriction in the adult rat, an increase in cell volume was observed while no significant changes in the length-to-width ratios could be detected. The cell volumes of the hypertrophic hearts corresponded to those observed in hearts of similar weight obtained from larger normal rats and the stimulated cardiac growth could also be explained solely by hypertrophy of existing cells.
Response of cultured myocardial cells to countershock-type electric field stimulation
Authors: Jones J. L. , Lepeschkin E. , Jones R. E. , Rush S.
Published: December 2017

Myocardial cells isolated from 8-day chick embryos were grown in monolayer culture under conditions that produce “standard embryonic” and “adult-type” cells. These cells were subjected to electric field stimulation that had a waveshape and intensities similar to those used in clinical electric countershock procedures. Photocell mechanograms obtained before, during, and after stimulation were correlated with simultaneously measured transmembrane potentials to determine the relationship between membrane polarization and arrhythmia production that occured after the stimulus. The results of these experiments demonstrate that a predictable sequence of mechanical responses occurs after stimuli ranging in intensity from 6 to 200 V/cm. This sequence, which closely resembles that observed in vivo after similar stimulation intensities, consists of a single response (activation), tachyarrhythmia, relaxed arrest followed by transient tachyarrhythmia, arrest with contracture, and cellular fibrillation. This diverse pattern of arrhythmias is associated with a prolonged depolarization of the cell membrane which increases with the intensity of the applied stimulus. It is probable that this depolarization is caused by a transient electromechanical deformation of the cell membrane during the shock. These findings contribute to a better understanding of the causes of the arrhythmias that appear after clinical and experimental electric countershock procedures.
Techniques for arteriography and hydraulic analysis of coronary stenoses in unsedated dogs
Authors: Gould K. L. , Lee D. , Lovgren K.
Published: December 2017

This report describes techniques for obtaining pressure flow characteristics and arteriograms of controlled coronary stenoses in unsedated, trained dogs. Coronary flow velocity was recorded by calibrated Doppler velocity transducers linear to three times maximum coronary flow velocity. Pressure losses across stenoses were measured by a differential pressure transducer through small catheters implanted in the distal and proximal left circumflex coronary artery or ascending aorta, a system that was linear within +/-5% to 30 Hz. Coronary stenoses were produced by saline-filled, perivascular cuff constrictors inflated to constant pressure by a pressure regulator. Catheters were implanted in the pulmonary artery for injection of intravenous drugs or diffusible radionuclides and in the left atrium for injection of radionuclide microspheres. Contrast medium was injected through the proximal coronary catheter, and high-resolution arteriograms were obtained by single-spot filming on ultra detail X-ray film and cassettes at end diastole by triggering X-ray exposures from the electrocardiogram. In 13 dogs studied consecutively, the surgical mortality was 15.4%. All implanted instruments functioned for an average of 8 wk per dog.
Heterogeneity of oxygen delivery in normoxic and hypoxic states: a fluorometer study
Authors: Chance B. , Barlow C. , Nakase Y. , Takeda H. , Mayevsky A. , Fischetti R. , Graham N. , Sorge J.
Published: December 2017

An on-line, real-time histogram display of heterogeneity of oxygen delivery to perfused and in situ organs is afforded by a flying-spot fluorometer that provides excitation for either oxidized flavoprotein of the mitochondrial space or reduced pyridine nucleotide of mitochondrial and cytosolic spaces. Emission from the two fluorochromes is acquired at 10(4) to 10(5) data points/s and histograms of the fluorescence intensity versus the number of occurrences of that intensity are displayed at 1--10 times per second. The histograms show alterations of the intensity and of the degree of heterogeneity of the redox states of perfused heart with model coronary occlusion, of perfused and in situ rat liver, and of rat and gerbil models of stroke. The percentage change of oxygen delivery to the intracellular space can be calculated from the areas under the histogram.
Decreased renal blood flow in the baboon during mild dynamic leg exercise
Authors: Hohimer A. R. , Smith O. A.
Published: December 2017

Twelve chair-restrained baboons (Papio cynocephalus) were conditioned with operant techniques and a food reward to perform 4 min of dynamic leg exercise. During the last minute of exercise, blood flow through the left renal artery, measured by an electromagnetic flow transducer, was decreased 19 +/- 2% SEM with respect to the minute of rest preceding the exercise. This response occurred within 1.5 min, was maintained throughout the exercise, and recovered to control within 2 min. Mean arterial blood pressure rose 17 +/- 2%; renal vascular resistance, 46 +/- 6%; heart rate, 42 +/- 4%; and whole-body oxygen consumption, 233 +/- 19%. Behavioral situations simulating the arousal and feeding components of the exercise task, but not requiring muscular exertion, did not alter renal blood flow. In four animals, blood flow to the contralateral but surgically denervated kidney was measured; it increased transiently at the onset of exercise, but returned to control by the last minute of work. Thus, the baboon, like man, shows a decrease in renal blood flow during exercise. This response has a rapid onset and recovery and is primarily neurally mediated.
Hypertension in dogs during antidiuretic hormone and hypotonic saline infusion
Authors: Manning R. D. , Guyton A. C. , Coleman T. G. , McCaa R. E.
Published: December 2017

Experimental hypertension was produced in 7 dogs by continuously infusing suppressor amounts of antidiuretic hormone (ADH) and hypotonic saline after renal mass had been surgically reduced to 30% of normal. Data were collected during 9 days of control measurements, 14 days of ADH and saline infusion, and then 3 days of saline infusion to 1) determine the chronic effects of ADH on arterial pressure and 2) determine whether hypertension could be maintained during hyponatremia. During the period of ADH infusion, arterial pressure increased to hypertensive levels while plasma sodium concentration decreased almost 20 meq/1. Also, during the ADH infusion period, the dogs demonstrated decreases in heart rate, plasm potassium concentration, plasma renin activity, and plasma aldosterone concentration. Fluid volume expansion was evidenced by sustained increases in blood volume and sodium space. We conclude that when renal function is compromised, subpressor amounts of ADH can contribute to the development of hypertension, probably due to its fluid-retaining properties and in spite of the attendant hyponatremia.
Time course of infarct growth toward the endocardium after coronary occlusion
Authors: Fenoglio J. J. , Karagueuzian H. S. , Friedman P. L. , Albala A. , Wit A. L.
Published: December 2017

Transmembrane potentials and ultrastructure of subendocardial Purkinje and ventricular muscle fibers, isolated 1, 3, 5, 6, 14, and 24 h after coronary occlusion were investigated. Action potentials were recorded from progressively fewer layers of muscle cells as the age of the infarct increased. At 14 h little viable muscle remained. The decrease in the number of electrophysiologically viable muscle fibers correlated with structural evidence that the infarct moved with time toward the endocardial surface until only viable Purkinje fibers remained. Purkinje and surviving ventricular muscle fibers demonstrated a progressive decrease in resting potential, action potential amplitude, and Vmax and a progressive increase in action potential duration. Spontaneous diastolic depolarizations were found in Purkinje fibers only in 24-h infarcts and occasionally in cells deep to the endocardial surface, which may have been muscle cells. We hypothesize that during the first 24 h after coronary occlusion arrhythmias originate near the interface of infarcted and ischemic myocardium. As this interface moves toward the endocardium, this site of origin of arrhythmias moves with it until the Purkinje network is reached.
Relation of ventricular repolarization to electrocardiographic T wave-form and arrhythmia vulnerability
Authors: Burgess M. J.
Published: December 2017

The normal sequence of ventricular recovery proceeds from epicardium to endocardium, but on the epicardium the pattern of ventricular recovery is similar to the pattern of activation. Data concerning ventricular repolarization have been obtained from analyses of electrocardiographic recordings, suction potential recordings, a limited number of recordings of transmembrane action potentials, and from measurements of refractory periods. Normal ventricular repolarization has now been characterized in sufficient detail that it can be used with theoretic models to derive T waves with forms that correspond closely to recorded T waves. These models provide insights concerning the body surface manifestations of the electrophysiologic events of ventricular repolarization and should contribute to a more physiologic approach to interpreting T wave abnormalities in clinical electrocardiograms. A relationship between inhomogeneity of ventricular refractory period duration and arrhythmia vulnerability has also been documented. Because inhomogeneity of ventricular repolarization is a factor in both T wave-form and arrhythmia vulnerability, methods of analysis of the T wave for determining patients at risk of developing arrhythmias should be possible. One such analysis is presented. The method has been tested on experimental animals before and after interventions designed to increase arrhythmia vulnerability and in a limited number of patient studies. The results to date are encouraging and suggest that in the future electrocardiographic examination will be used as a prognostic tool in addition to its already established diagnostic function.
Regional blood flow during digestion in the conscious dog
Authors: Gallavan R. H. , Chou C. C. , Kvietys P. R. , Sit S. P.
Published: December 2017

Blood flows to the major organs of the resting conscious dog were measured prior to and 30 and 90 min after feeding using the radioactive microsphere technique. Mean systemic arterial pressure, heart rate, and arterial PO2, PCO2, and pH, as well as blood flow to the brain, heart, adrenals, skeletal muscle, hepatic artery, and gastric antrum were not significantly changed following the meal. Pancreatic and duodenal and jejunal blood flows increased at both 30 and 90 min, whereas ileal blood flow increased only at 90 min after feeding. Flow to the gastric body increased in only half of the fed animals, but it increased in all of the animals treated with histamine. In all cases where there was an increase in total wall flow the increase was confined to the mucosa-submucosal layer. Blood flow to the colon was unchanged except for a decrease in the distal colon at 30 min. Thus, the cardiovascular response to feeding appears to be limited to those organs and tissues actively involved in digestion.
Role of adenosine in exercise vasodilation in dog gracilis muscle
Authors: Honig C. R. , Frierson J. L.
Published: December 2017

Theophylline, quinidine, and dipyridamole were used to evaluate the role of adenosine in exercise vasodilation in dog gracilis muscles perfused at low, constant flow. Theophylline, 10(-3) M in blood, blocked adenosine vasodilation completely, but did not alter the magnitude or rate of vasodilation aroused by brief tetani, or by 1 min of twitch contraction. Quinidine's effects were too nonspecific to interpret in terms of the adenosine hypothesis. Dipyridamole increased and prolonged vasodilation due to injected adenosine, but did not increase the magnitude of exercise vasodilation known to be submaximal. In about half the muscles tested, dipyridamole slowed recovery of resistance after contraction stopped. Bioassay data strongly suggest it did so by enhancing the contribution of a purine metabolite. Results are interpreted to mean that adenosine does not influence the rate or magnitude of exercise vasodilation, but may prolong recovery from heavy work at constant flow. The generality of results and interpretations is discussed.
Effects of ischemia on left ventricular regional function in the conscious dog
Authors: Edwards C. H. , Rankin J. S. , McHale P. A. , Ling D. , Anderson R. W.
Published: December 2017

Three-dimensional regional geometry of the left ventricle was assessed in seven conscious trained dogs chronically implanted with pulse-transit ultrasonic-dimension transducers. Minor and major axis segment lengths and wall thickness were measured in the distribution of the left anterior descending coronary artery; transmural pressure (TMP) was measured with high-fidelity micromanometers. Data were recorded during the control state and following 30 s and 30 min of ischemia. Dimensions were normalized as a fractional extension from the length at zero TMP (Lo). Dynamic cube mass was calculated and remained constant throughout the cardiac cycle in both control and ischemic states, although the calculated mass decreased by an average of 5% during ischemia. The slope constants of the exponential diastolic pressure-dimension relationship increased following acute coronary occlusion indicating increases in regional myocardial stiffness with increasing periods of ischemia. Coronary occlusion also was associated with an increase in the Lo measurements in the major and minor axis dimensions and a decrease in the wall thickness Lo. These findings are consistent with an ischemia-induced plastic deformation of the regional myocardium defined as creep. Thus, acute ischemia results in a decline of regional systolic function, induces myocardial creep, and causes an immediate and sustained increase in regional myocardial stiffness.
Secondary driving forces affecting transcapillary osmotic flows in perfused heart
Authors: Vargas F. F. , Blackshear G. L.
Published: December 2017

We evaluated secondary hydrostatic and osmotic pressure gradients caused by an osmotic flow across the wall of rabbit heart capillaries in vitro. Tissue fluid loss after addition of 80 mM sucrose to the Ringer perfusate depressed interstitial fluid pressure (IFP) by 13.2 +/- 1.1 cmH2O, as measured with a fine intramyocardial needle. This, plus a calculated rise in capillary pressure, caused a difference of 4.3 cmH2O in transcapillary pressures which represents 1.4% of the simultaneous and opposite osmotic pressure difference. The effect of transient-induced experimental changes in interstitial effect of transient-induced experimental changes in interstitial concentration of NaCl (main resident solute) during an osmotic transient and osmotic balance experiments using opposing transcapillary flows (Jv) and a sigma sucrose = 2.9 sigma NaCl. Long-term perfusion with solutions having abnormal concentrations of NaCl did not influence Jv, whereas inclusions of sucrose as resident solute depressed Jv by 10%. Results indicate that secondary hydrostatic and osmotic forces are small relative to the main osmotic driving force. Compliance measurements and calculations suggest that cells contribute three-fourths organ water loss during an osmotic transient, thus buffering volume, pressure, and concentration changes in the interstitial spaces.
Noradrenergic mechanisms in brain and peripheral organs after aortic nerve transection
Authors: Patel K. P. , Ciriello J. , Kline R. L.
Published: December 2017

Noradrenergic mechanisms were studied in the hypothalamus, midbrain, medulla, kidney, duodenum, and skeletal muscle of Wistar rats at 3 or 13 days after either bilateral transection of the aortic depressor nerve (ADN) or a sham operation. The rate of decline of tissue norepinephrine (NE) concentration after inhibition of tyrosine hydroxylase with alpha-methyltyrosine was used as an index of NE turnover. Three days after ADN transection, arterial pressure and heart rate were elevated significantly, and NE turnover was increased in all three brain areas, kidney, and skeletal muscle but not in duodenum. The largest change occurred in skeletal muscle, where the time required for tissue NE concentration to decline to 50% of control decreased from 9.0 to 2.5 h. In rats 13 days after ADN transection, arterial pressure was significantly higher than in sham-operated controls, but heart rate was similar to control values. NE turnover was slightly increased in hypothalamus but was not significantly different in muscle and kidney when compared to sham-operated controls. These results suggest that 3 days after ADN transection in the rat, arterial pressure is elevated as a result of increased activity of noradrenergic neurons in the hypothalamus and brain stem, which is translated into increased sympathetic nerve activity to peripheral organs, particularly skeletal muscle. The normal turnover of NE in peripheral organs 13 days after ADN transection suggests that mechanisms other than increased sympathetic activity are responsible for maintaining the elevated arterial pressure.
Adrenoceptor desensitization after immobilization stress or repeated injection of isoproterenol
Authors: Yamaguchi I. , Torda T. , Hirata F. , Kopin I. J.
Published: December 2017

Immobilization stress (2.5 h daily) or repeated injection of isoproterenol (1 mg/kg, 3 times daily) for 1 wk caused a subsensitivity to the chronotropic and pressor effect of epinephrine in pithed rats. Propranolol (1 mg/kg) inhibited, to a greater extent in control than in immobilized rats, the chronotropic effect of epinephrine. The residual heart rates did not differ significantly among control, immobilized, and isoproterenol-treated rats. Practolol (1 mg/kg) but not butoxamine (5 mg/kg) mimicked the effect of propranolol. The subsensitivity in the blood pressure responses was not abolished by injection of either of the beta-adrenoceptor blockers. Butoxamine or propranolol shifted the epinephrine dose-blood pressure response curves to the left. The degree of shift was similar in control and immobilized or isoproterenol-treated rats. Daily injection of quinacrine (16 mg/kg), an antimalarial agent that inhibits phospholipase A2, blocked the subsensitivity to the chronotropic effect of epinephrine, but not that to the pressor effect of epinephrine. These observations suggest that immobilization stress causes desensitization of alpha- and beta 1-receptors but not beta 2-receptors. The mechanism of desensitization of beta 1-receptors by immobilization appears to be similar to that after isoproterenol treatment, possibly due to increased turnover of phospholipids.
Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids
Authors: Ichihara K. , Neely J. R.
Published: December 2017

The relationship between tissue levels of fatty acid metabolites in ischemic and reperfused hearts and recovery of mechanical function of these hearts on reperfusion was studied. Isolated rat hearts were exposed to global ischemia for periods up to 60 min under various conditions of coronary flow, O2 supply, and fatty acid concentrations and were then reperfused for either 15 or 30 min under aerobic conditions both with and without fatty acids present. Tissue levels of ATP, creatine phosphate, long-chain acyl CoA, and long-chain acyl carnitine were determined at the end of the ischemic and reperfusion periods. In some experiments K+ arrest during ischemia was used to prevent adenine nucleotide depletion both in the absence and presence of high fatty acids. Although the ability of these hearts to recover their preischemic mechanical function varied from 8 to 90% and tissue levels of acyl CoA and acyl carnitine during ischemia varied from 3- to 10-fold depending on the condition, no correlation was found between the recovery of function during reperfusion and either the presence of fatty acid or high levels of tissue long-chain acyl CoA and carnitine esters during ischemia.
Skeletal muscle vasodilation during electrical stimulation of the preoptic recess
Authors: Proctor K. G. , Bealer S. L.
Published: December 2017

Transverse (3rd-order) arterioles (diam 12 +/- 2 micron, n = 6) in rat spinotrapezius muscle were observed with video microscopy during electrical stimulation of preoptic recess in periventricular region of hypothalamus (AV3V region) to test whether active skeletal muscle vasodilation was mediated by a beta-adrenergic mechanism. Bipolar wire electrodes were implanted in AV3V 3-7 days before an experiment. Continuous superfusion of propranolol (10(-5) M) caused steady-state reduction (3 +/- 1 microns) in arteriolar diameter and reduced steady-state vasodilation (26 +/- 2 vs. 11 +/- 2 microns) caused by a continuous superfusion of isoproterenol (10(-6) M). Six arterioles were observed with and without propranolol during four frequencies of AV3V stimulation (8-15 V, 0.2-0.5 ms pulse duration; 10, 15, 20, and 25 Hz; 1 min stimulus duration). Stimulation caused frequency-related reductions in arterial blood pressure (10-20 mmHg), which were sustained and not altered by propranolol. Transient peak diameters were observed after 30 +/- 7 s; the time was not related to stimulus frequency or affected by propranolol. Peak diameters averaged 14-17 microns during vehicle and 11-12 micron during propranolol (maximum diam 32 +/- 3). Peak vasodilations were significant but identical with vehicle or propranolol (avg 3 +/- 1 microns) and not related to stimulus frequency. Diameters stabilized at steady-state values above base line only during 15 and 20 Hz with vehicle and only during 20 Hz with propranolol. We conclude that AV3V stimulation causes transient vasodilation in spinotrapezius muscle that is probably not mediated by beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of adenosine in coronary autoregulation
Authors: Hanley F. L. , Grattan M. T. , Stevens M. B. , Hoffman J. I.
Published: December 2017

The role of cardiac interstitial adenosine as an important metabolite in coronary autoregulation has not been established. We therefore measured steady-state cardiac interstitial adenosine concentration at a high and a low coronary inflow pressure using an epicardial diffusion well in anesthetized dogs. Although coronary resistance for the high and low pressure points showed highly significant differences (P less than 0.001), adenosine averaged 302 +/- 98 and 286 +/- 91 (SD) pmol/ml for the high and low pressure points, respectively (P greater than 0.20). Cardiac interstitial adenosine concentration was then measured with and without an intracoronary infusion of adenosine deaminase catalytic subunit. Adenosine averaged 28 +/- 21 (SD) pmol/ml during the infusion compared with 281 +/- 68 during control conditions (P less than 0.001). Finally, pressure-flow relations were obtained with and without the adenosine deaminase infusion, and there was no loss of autoregulation in the pressure of adenosine deaminase. These findings indicate that intracoronary adenosine deaminase markedly reduces interstitial adenosine concentration, that cardiac interstitial adenosine concentration remains constant during autoregulation, and that the coronary bed autoregulates normally when interstitial adenosine is reduced to levels close to zero. We conclude that cardiac interstitial adenosine concentration is not an important component in coronary autoregulation.
Adrenergic vasoconstriction lessens transmural steal during coronary hypoperfusion
Authors: Nathan H. J. , Feigl E. O.
Published: December 2017

The hypothesis that alpha-receptor-mediated coronary vasoconstriction can lessen transmural steal during hypoperfusion was tested in 14 open-chest, chloralose-anesthetized dogs. Coronary flow to two regions of the left ventricle was controlled by separately cannulating and pump perfusing the anterior descending and circumflex coronary arteries. An intracoronary infusion of the alpha-receptor blocking agent phenoxybenzamine (0.25 mg/kg) was administered to one region while coronary sinus blood flow was trapped to minimize recirculation. All animals received atropine (0.5 mg/kg) and propranolol (2 mg/kg) intravenously. alpha-Receptor activation in both regions of the left ventricle was achieved with an intracoronary infusion of norepinephrine. Radioactive microspheres were used to measure the transmural distribution of myocardial blood flow as coronary flow in the paired regions was reduced from 100 to 80, 70, 60, and 50% of normal. When total coronary flow was reduced sufficiently to cause ischemia and maldistribution of flow across the myocardial wall, the subendocardial blood flow was greater in the alpha-receptor-intact region than in the alpha-blocked region. This indicates that alpha-receptor-mediated coronary vasoconstriction has an unexpected beneficial effect that lessens transmural steal during hypoperfusion.
Endothelium-dependent and independent relaxation of aortic rings from hypertensive rats
Authors: Van de Voorde J. , Leusen I.
Published: December 2017

The relaxation effects of endothelium-dependent (acetylcholine, histamine) and endothelium-independent (nitroprusside, nitrite) relaxing substances were comparatively examined on contracted thoracic aortic rings from normotensive and experimental renal and desoxycorticosterone acetate (DOCA)-salt hypertensive Wistar rats. On the aorta preparations from hypertensive animals a highly significant depression of the maximal relaxation effect of histamine and acetylcholine was observed. This was not seen with nitroprusside and nitrite. By use of a bioassay technique it was demonstrated that the depression of the endothelium-mediated response is not due to a diminished release of endothelium-derived relaxing factor. Impaired coupling between the endothelium and the smooth muscle cells is suggested to be responsible for that depression.
Lesions of nucleus tractus solitarii globally impair cerebrovascular autoregulation
Authors: Ishitsuka T. , Iadecola C. , Underwood M. D. , Reis D. J.
Published: December 2017

We studied the effects of acute bilateral electrolytic lesions of the nucleus tractus solitarii (NTS) on regional cerebral blood flow (rCBF) and its autoregulation in rats anesthetized (alpha-chloralose, 40 mg/kg), paralyzed (tubocurarine), and artificially ventilated. rCBF or regional cerebral glucose utilization (rCGU) was measured 30 min after NTS lesions, by the 14C-iodoantipyrine technique or 2-deoxyglucose method, respectively. Cerebrovascular autoregulation was assessed in groups of 4-5 rats at three levels of arterial pressure (AP): 90, 125, and 140 mmHg. AP was lowered by hemorrhage or elevated by intravenous infusion of phenylephrine. NTS lesions did not alter rCBF at 125 mmHg (P greater than 0.05) but resulted in loss of autoregulation (P less than 0.05, analysis of variance). In contrast, lesions of the cuneate nucleus or transection of the baroreceptor afferents did not alter autoregulation. NTS lesions did not affect the reactivity of the cerebrovascular bed to hypercarbia (PaCO2 57.4 +/- 1; n = 5) or hypocarbia (PaCO2 24.4 +/- 1; n = 5) nor the rCGU in any brain regions (P greater than 0.05; n = 5). We conclude that lesions of the NTS impair cerebrovascular autoregulation. The effect is not due to changes in metabolism, nonspecific effects of the lesions, vasoparalysis, or interruption of the baroreceptor reflex arch. Neural pathways originating in or passing through the NTS can regulate the cerebrovascular autoregulation of the entire brain.
Cardiac sympathetic nerve activity and heart rate during coronary occlusion in awake cats
Authors: Ninomiya I. , Matsukawa K. , Honda T. , Nishiura N. , Shirai M.
Published: December 2017

Responses in efferent cardiac sympathetic nerve activity (CSNA) and heart rate (HR) to a 100-s anterior descending coronary artery occlusion were measured in cats under awake, atropinized, anesthetized, or anesthetized and atropinized states. In the conscious state, at 20 and 90 s of occlusion, CSNA increased by 23% and then decreased by 7%, respectively, whereas HR decreased by 5 and 17%, respectively. With atropinization and/or anesthesia, the initial increase in CSNA was inhibited and the later decrease in CSNA was enhanced, whereas the bradycardia was diminished. HR changed in proportion to CSNA responses with high correlations, i.e., r = +0.89, +0.90, +0.96, and +0.91 for the four states, respectively. In the conscious state, the CSNA-HR relation line shifted toward bradycardia, but this shift was blocked by atropinization and anesthesia. This finding suggested that, in the conscious state, cardiac vagal nerve activity (CVNA) increased immediately and did not decrease during occlusion. At the early stage of occlusion, HR response (bradycardia or tachycardia) was determined by the relative contribution of enhanced CSNA and CVNA. At the later stage of occlusion, bradycardia was induced by a combination of decreased CSNA and enhanced CVNA. In anesthesia and/or atropinization it was induced mainly by the decreased CSNA.
Use of the Frank-Starling mechanism during submaximal versus maximal upright exercise
Authors: Plotnick G. D. , Becker L. C. , Fisher M. L. , Gerstenblith G. , Renlund D. G. , Fleg J. L. , Weisfeldt M. L. , Lakatta E. G.
Published: December 2017

To evaluate the extent to which the Frank-Starling mechanism is utilized during successive stages of vigorous upright exercise, absolute left ventricular end-diastolic volume and ejection fraction were determined by gated blood pool scintigraphy at rest and during multilevel maximal upright bicycle exercise in 30 normal males aged 26-50 yr, who were able to exercise to 125 W or greater. Left ventricular end-systolic volume, stroke volume, and cardiac output were calculated at rest and during each successive 3-min stage of exercise [25, 50, 75, 100, and 125–225 W (peak)]. During early exercise (25 W), end-diastolic and stroke volumes increased (+17 +/- 1 and +31 +/- 4%, respectively), with no change in end-systolic volume. With further exercise (50–75 W) end-diastolic volume remained unchanged as end-systolic volume decreased (-12 +/- 4 and -24 + 5%, respectively). At peak exercise end-diastolic volume decreased to resting level, stroke volume remained at a plateau, and end-systolic volume further decreased (-48 +/- 7%). Thus the Frank-Starling mechanism is used early in exercise, perhaps because of a delay in sympathetic mobilization, and does not appear to play a role in the later stages of vigorous exercise.
Transmembrane mechanochemical coupling in cardiac myocytes: novel activation of Gi by hyposmotic swelling
Authors: Hilal-Dandan R. , Brunton L. L.
Published: December 2017

We have studied the effect of hyposmotic swelling on adenosin 3',5'-cyclic monophosphate (cAMP) metabolism in isolated cardiac myocytes. Decreasing extracellular osmolarity by 12.5-50% results in graded inhibition (10-40%) of isoproterenol-stimulated and forskolin-stimulated cAMP accumulation but does not affect basal and hormone-stimulated phosphoinositide hydrolysis or cellular ATP content. Treatment with pertussis toxin does not alter the swelling response but abolishes the inhibitory effect of swelling on cAMP accumulation. The response to swelling seems not to involve the release of effectors known to couple to inhibitory G protein (Gi) in myocytes: BQ-123, atropine, and adenosine deaminase do not alter the inhibitory effect of swelling on isoproterenol-stimulated cAMP accumulation; conditioned medium from swollen cells, with restored osmolarity, has no effect on cAMP accumulation when added to control myocytes. In distinction to these effects on myocytes, swelling enhances hormone-stimulated cAMP accumulation in cultured S49 lymphoma cells. We conclude that swelling of cardiac myocytes inhibits cAMP accumulation through a mechanism that involves activation of a pertussis toxin-sensitive Gi protein. Activation of Gi by this means may contribute to adrenergic hyporesponsiveness in hypoxic and ischemic myocardium.
NMDA receptors in NTS are involved in bradycardic but not in pressor response of chemoreflex
Authors: Haibara A. S. , Colombari E. , Chianca D. A. , Bonagamba L. G. , Machado B. H.
Published: December 2017

Activation of carotid chemoreceptors with intravenous potassium cyanide (KCN) produces increases in arterial pressure, bradycardia, and tachypnea. In the present study, we activated carotid chemoreceptors with KCN and the neurotransmission of the chemoreceptor reflex into the commissural nucleus tractus solitarii (NTS) was blocked with phosphonovaleric acid (AP-5), an N-methyl-D-aspartate (NMDA)-selective antagonist. The aim of this study was to evaluate the involvement of NMDA receptors in the cardiovascular and respiratory responses produced by chemoreceptor activation in unanesthetized rats. The pressor response to KCN was not changed after microinjection of three different doses of AP-5 into the NTS, whereas the bradycardic response was reduced in a dose-dependent manner. The increase in respiratory frequency in response to carotid chemoreceptor activation was also not affected by AP-5 microinjected into the NTS. The data indicate that the activation of the cardiovagal component of the chemoreflex in the commissural NTS is mediated by NMDA receptors, whereas pressor and ventilatory responses are not.
Influence of respiration on metabolic, hemodynamic, psychometric, and R-R interval power spectral parameters
Authors: De Meersman R. E. , Reisman S. S. , Daum M. , Zorowitz R. , Leifer M. , Findley T.
Published: December 2017

Because respiration modulates autonomic activity, we determined the magnitude of perturbation of changing breathing frequency and tidal volume on metabolic, hemodynamic, psychometric, and R-R interval power spectral parameters. Seated subjects breathed at three different rates and five different volumes with each of the different rates. Breathing rates and volumes were percentages of the subject's resting breathing pattern and, therefore, identical across all subjects. Increases in rate and volume resulted in significant perturbations in end-tidal CO2 production, CO2 production, ventilatory equivalent for O2, comfort levels, and R-R interval power spectra (P < 0.05). The magnitude of the perturbations in the above parameters indicated a substantial upset in all subjects' metabolic, hemodynamic, and comfort homeostasis, precipitating a significant loss of vagal tone. The implications of our findings are that imposed breathing patterns used to modulate autonomic outflow should be tailored to the individual's resting breathing pattern. These data further support the urgent need for concomitant metabolic and respiratory measurements when analyzing and interpreting heart rate variability data.
Basic fibroblast growth factor increases nitric oxide synthase production in bovine endothelial cells
Authors: Kostyk S. K. , Kourembanas S. , Wheeler E. L. , Medeiros D. , McQuillan L. P. , D'Amore P. A. , Braunhut S. J.
Published: December 2017

Basic fibroblast growth factor (bFGF) and nitric oxide (NO) are expressed by endothelial cells (EC) and are involved in regulation of endothelial functions. In vivo, bFGF has a hypotensive effect which is mediated, in part, through activation of nitric oxide synthase (NOS) and the subsequent generation of NO. Thus we hypothesized that regulation of NOS in EC might be modulated by bFGF. bFGF treatment of EC in vitro resulted in increased NADPH diaphorase staining, a histochemical marker associated with the presence of NOS. Using cGMP generation in a reporter cell as a bioassay for NO release, we demonstrated that bFGF treatment of EC leads to increased production of biologically active NO. Furthermore, bFGF treatment of EC resulted in an increase in cellular content of the endothelial form of NOS as shown by Western blot analysis. Finally, Northern blot analysis was used to demonstrate that message levels of the constitutive, calcium-dependent, endothelial form of NOS is increased in EC by treatment with bFGF in vitro. These results suggest that bFGF has potential to regulate vascular tone through the modulation of levels of endothelial NOS.
Structure and hemodynamics of microvascular networks: heterogeneity and correlations
Authors: Pries A. R. , Secomb T. W. , Gaehtgens P.
Published: December 2017

The objective of this study was to quantify the heterogeneity of topological, morphological, and hemodynamic parameters in microvascular networks and to identify functionally relevant correlations among these parameters. Seven networks in the rat mesentery (383-913 vessel segments per network) were examined, and measurements were made of segment generation, diameter, length, and hematocrit in all segments (n = 3,129) and of flow velocity (only in 3 networks, 1,321 segments). In addition, hematocrit, flow rate, and pressure were derived for all segments from a mathematical simulation. All parameters obtained exhibit heterogeneous distributions with coefficients of variation ranging from 0.28 (capillary diameter) to > 1.5 (volume flow and pressure gradient). Several strong correlations exist between parameters, e.g., discharge hematocrit increases with vessel diameter, and shear rate increases with intravascular pressure. Because of such correlations, the extrapolation from average values for "typical vessels" to network properties can lead to substantial errors. For example, the mean network transit time estimated based on averaged quantities is 6.5 s, which is about 60% higher than the true value (4.08 s). Simplified models of the vascular bed may therefore be inadequate to describe functional properties of the microcirculation.
DNA synthesis and multinucleation in embryonic stem cell-derived cardiomyocytes
Authors: Klug M. G. , Soonpaa M. H. , Field L. J.
Published: December 2017

The proliferative capacity of embryonic stem (ES) cell-derived cardiomyocytes was assessed. Enriched preparations of cardiomyocytes were isolated by microdissection of the cardiogenic regions of cultured embryoid bodies. The identity of the isolated cells was established by immunocytology, and mitotic activity was monitored by [3H]thymidine incorporation and pulse-chase experiments. ES-derived cardiomyocytes were mitotically active and predominantly mononucleated at 11 days after cardiogenic induction. By 21 days postinduction, cardiomyocyte DNA synthesis was markedly decreased, with a concomitant increase in the percentage of multinucleated cells. Interestingly, the duration of active cardiomyocyte reduplication in the ES system appeared to be roughly similar to that observed during normal murine cardiogenesis. Given these observations, as well as the genetic tractability of ES cells, ES-derived cardiogenesis might provide a useful in vitro system with which to assess the molecular regulation of the cardiomyocyte cell cycle.
Transport in lymphatic capillaries. I. Macroscopic measurements using residence time distribution theory
Authors: Swartz M. A. , Berk D. A. , Jain R. K.
Published: December 2017

We present a novel integrative method for characterizing transport in the lymphatic capillaries in the tail of the anesthetized mouse, which is both sensitive and reproducible for quantifying uptake and flow. Interstitially injected, fluorescently labeled macromolecules were used to visualize and quantify these processes. Residence time distribution (RTD) theory was employed to measure net flow velocity in the lymphatic network as well as to provide a relative measure of lymphatic uptake of macromolecules from the interstitium. The effects of particle size and injection pressure were determined. The uptake rate was found to be independent of particle size in the range of a 6- to 18-nm radius; beyond this size, the interstitial matrix seemed to pose a greater barrier. A comparison of 10 vs. 40 cmH2O injection pressure showed a significant influence on the relative uptake rate but not on the net velocity within the network (3.3 +/- 0.8 vs. 3.8 +/- 1.0 micron/s). This suggested the presence of a systemic driving force for baseline lymph propulsion that is independent of the local pressure gradients driving the uptake. This model can be used to examine various aspects of transport physiology of the initial lymphatics.
Flow velocity of single lymphatic capillaries in human skin
Authors: Fischer M. , Franzeck U. K. , Herrig I. , Costanzo U. , Wen S. , Schiesser M. , Hoffmann U. , Bollinger A.
Published: December 2017

The purpose of this study was to investigate the previously unknown flow velocity in single lymphatic capillaries of humans in the supine position. Fifteen healthy subjects (10 women and 5 men; mean age 35.8 +/- 13.1 yr) were studied. Ten microliters of fluorescein isothiocyanate-dextran (150,000 mol wt) were injected into the subepidermal layer of the foot dorsum. The filling of the microlymphatics from the resulting depot was visualized by fluorescence video microscopy and stored on videotape. Flow velocity in the microlymphatics was determined on the video screen by direct measurement of the advancement of dyed lymph during a given time. The following median velocities were obtained: 0.51 mm/s (0.27 and 0.61 mm/s for lower and upper quartiles, respectively) for velocity during initial network filling and 9.7 microns/s (6.9 and 14.2 microns/s for lower and upper quartiles, respectively) for resting velocity at the end of the filling period. Mean lymphatic capillary diameter was 54.8 +/- 8.2 microns, and mean network extension was 8.3 +/- 3.2 mm. The high filling velocities are probably due to increased interstitial pressure and volume caused by dye microinjection, whereas the values measured during the end of network filling seem to approach resting flow velocities.
Acetylcholine- and flow-induced production and release of nitric oxide in arterial and venous endothelial cells
Authors: Fukaya Y. , Ohhashi T.
Published: December 2017

To study flow-mediated responses in a conduit vein, we investigated the physiological characteristics of endothelium-dependent acetylcholine (ACh)- and flow-induced relaxations using a conventional bioassay cascade. Cylindrical segments isolated from canine common carotid arteries and external jugular veins were perfused at a constant mean flow rate ranging from 1 to 8 ml/min. Endothelium-derived nitric oxide (NO) activity in perfusion effluent through the arterial and venous segments was measured by relaxation of endothelium-denuded arterial rings and arterial and/or venous rings precontracted by prostaglandin F2 alpha, respectively. Stimulation by a flow rate of 8 ml/min on the arterial and venous endothelial cells produced approximately 60 and 20% of the maximum relaxation in the arterial and venous rings, respectively. ACh (10(-6) and 10(-5) M) perfused through the arterial and venous segments with endothelium caused dose-related relaxations of both bioassay rings. The ACh- and flow-induced relaxations were completely reduced by mechanical removal of the endothelial cells. Pretreatment with 5 x 10(-5) M NG-nitro-L-arginine methyl ester (L-NAME) produced a significant reduction of the ACh- and flow-induced vasodilation. Additional treatment with 10(-4) M L-arginine significantly reversed the L-NAME-induced inhibition of ACh-induced relaxation but had no effect on flow-induced relaxation. When the flow rate was increased from 2 to 4 ml/min, the same concentrations of ACh produced larger dose-related relaxations than those obtained at a flow rate of 2 ml/min. Pretreatment with 25 U/ml superoxide dismutase caused no significant effect on the flow-mediated potentiation of ACh-induced relaxation. These findings suggest that venous endothelial cells of canine large vein are able to produce and release NO by stimulation of increased flow or ACh to a significantly lesser extent compared with the artery and that ACh-induced vasodilation is potentiated by an increase in shear stress up to approximately 4 dyn/cm2 loaded on the endothelial cells.