bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial relaxation. II. Hemodynamic determinants of rate of left ventricular isovolumic pressure decline
Authors: Gaasch W. H. , Blaustein A. S. , Andrias C. W. , Donahue R. P. , Avitall B.
Published: December 2017

The hemodynamic determinants of the time constant of left ventricular (LV) isovolumic pressure (P) decline were studied in 32 anesthetized dogs. The time constant, tau (an index of LV relaxation), was determined from the best exponential fit of the equation P = Poe-t/r, to LVP measured at 5-ms intervals during isovolumic relaxation; Po = LVP at maximum negative dP/dt and t = time. At a constant heart rate of 120 beats/min, tau was determined during steady-state increases in preload (volume expansion), increases in afterload (methoxamine infusion), reductions in afterload (nitroprusside infusion), and in variably afterloaded beats at a constant preload (single-beat interventions). tau was directly related to LV systolic pressure and length during the alterations in LV loading conditions, but tau was not closely related to the extent of fiber shortening. During isoproterenol infusion, relaxation was more rapid (tau), and following the administration of propranolol, relaxation was prolonged (tau). While data from the variably afterloaded contractions indicate the presence of systolic load-dependent LV relaxation velocity, the steady-state studies do not exclude the possibility that altered contractility through reflex or other mechanisms contributes to the observed changes in tau.
Effect of coronary sinus occlusion on coronary pressure-flow relations
Authors: Bellamy R. F. , Lowensohn H. S. , Ehrlich W. , Baer R. W.
Published: December 2017

We studied the effect of transient occlusion of the coronary sinus on the relationship between aortic pressure and circumflex coronary blood flow in open-chest anesthetized dog preparations during artificially prolonged diastoles. The coronary pressure-flow relation was linear, and flow stopped at an arterial pressure (Pf = 0) that always exceeded coronary venous pressure (Pcv). During reactive hyperemia, Pf = 0 was 31 mmHg when Pcv was 5 mmHg and increased to 52 mmHg when the coronary sinus was occluded (Pcv, 38 mmHg). Elevation of Pcv translated the coronary pressure-flow relation to a higher Pf = 0 without altering the slope of the relation. Pf = 0 increased by about two-thirds of the increase in Pcv. We found no evidence that there existed a level of Pcv below which changes in Pcv had no effect on the coronary pressure-flow relation. These data are not compatible with the existence of a vascular waterfall mechanism in the coronary circulation unless it is assumed that Pcv is one of the determinants of Pf = 0.
Incomplete fatty acid oxidation by ischemic heart: beta-hydroxy fatty acid production
Authors: Moore K. H. , Radloff J. F. , Hull F. E. , Sweeley C. C.
Published: December 2017

A quantitative gas chromatography-mass spectrometry (GC/MS) method was developed to measure nanomolar quantities of long-chain saturated beta-hydroxy fatty acids (12, 14, 16, and 18 carbons long) produced by isolated ischemic heart. Only beta-hydroxymyristate (25-40 nmol/g dry) was found in fresh heart. Isolated rabbit heart perfused with fatty acid by the nonrecirculating Langendorff technique produced negligible beta-hydroxy fatty acids. Ischemic perfusion with 0.25-0.75 mM palmitate prompted heart beta-hydroxy fatty acid accumulation, beta-hydroxypalmitate greater than beta-hydroxystearate, up to 100 nmol x g dry-1 x 10 min-1. beta-Hydroxy fatty acid production was proportional to coronary effluent lactate-to pyruvate ratio, did not continue beyond 10 min of ischemia, was dependent on exogenous fatty acid, and was inhibited by coperfusion with 10 mM acetate. Reperfusion for 5-10 min dissipated accumulated beta-hydroxypalmitate. Hypoxic perfusion prompted beta-hydroxy fatty acid production comparable to that with severe ischemia. These data show that during oxygen deficiency heart fatty acid beta-oxidation is not only depressed but is also incomplete; beta-hydroxy fatty acyl intermediates accumulate and contribute to the increased intracellular fatty acid content characteristic of the ischemic myocardium.
Calibrated impedance plethysmograph
Authors: Yablonski M. R. , Van De Water J. M. , Mount B. E. , Laska E. D. , Indech R. B.
Published: December 2017

The accuracy of quantitative pulse-volume measurement with a calibrated electrical impedance plethysmograph was determined on a laboratory limb-segment model. Changes in electrical impedance detected via a tetraprolar electode configuration were related to pulse-volume changes by the parallel-impedance model described by Nyboer et al. (The Impedance Plethysmograph: An Electrical Volume Recorder. Natl. Res. Council, Comm. Aviation Med. 149, 1943). The instrument employed in this study calculated pulse volume assuming two standard conditions: distance between voltage electrodes, l, is 15 cm, and resistivitiy of blood, rho b, is 150 omega x cm. The effects of varying tissue and blood resistivity, pulse frequency, and electrode distance were investigated. Measurements under three ionically distinct conditions gave an overall accuracy of 96.6% with correlation coefficients of 0.99 for each condition. Measurement accuracy was maintained with a pulse-frequency variation in the range of 15-150 pulses/min and with application of correction factors for electrode distance and blood resistivity other than the standard values.
Measurement of deformation of canine epicardium in vivo during cardiac cycle
Authors: Arts T. , Reneman R. S.
Published: December 2017

A new accurate method to determine the deformation of the epicardial surface during the cardiac cycle in vivo is described. Epicardial deformation is determined by a circumferential strain, a base-to-apex strain, and a shear angle. In the measuring setup, one magnetic field-generating coil (MFGC) and two sensor coils are attached to the epicardium, thus forming an approximately right-angled triangle with the MFGC at the right-angled corner and the sides containing the right angle, parallel to the circumferential and base-to-apex direction, respectively. The MFGC generates a magnetic field that rotates around the axis of the coil. The strength of that field decreases with increasing distance. Both strains and the shear angle are derived from the amplitudes of the voltages induced in the sensor coils and their phase difference. In the experimental situation the accuracy of the measurement of strain and shear angle is +/- 0.005 and +/- 1 degree, respectively. The device has a frequency response of 100 Hz (-3 dB) and practically no zero drift. In four open-chest dogs during left ventricular ejection, circumferential natural strain, base-to-apex natural strain, and shear angle at the epicardium of the left ventricular free wall ranged from -0.06 to -0.13, from -0.02 to -0.08, and from 6.8 degrees to 11.5 degrees, respectively.
Barium contracture: a model for systole
Authors: Munch D. F. , Comer H. T. , Downey J. M.
Published: December 2017

Studies of cardiac mechanics, metabolism, and coronary hemodynamics have traditionally been carried out in rhythmically beating hearts. We have developed an isolated rabbit heart preparation that is free from contractions and allows a stable graded ventricular pressure to be established. Rabbit hearts were rapidly excised and perfused at constant pressure with heated (39 degrees C) Tyrode solution bubbled with 98% O2-2% CO2. A latex balloon was inserted into the left ventricle (lv) to adjust lv volume and measure pressure. Nine hearts were depleted of calcium by reducig the calcium concentration in the Tyrode's from 5 to 0.078 mM. When barium (Ba2+) was added to the perfusate, the hearts spontaneously developed pressure that was free of an overriding beat (contracture). The intensity of the contracture increased in a sigmoid fashion as the barium concentration was increased. During contracture balloon pressure ranged between 33.8 +/- 5.0% (SE) (Ba2+ 0.5 mM) and 79.0 +/- 4.5% (Ba2+ 1.5 mM) of control systolic developed pressure Ventricular pressure-volume curves were linear (r > 0.98) and indicated increased ventricular stiffness as barium concentration increased. We believe that barium-induced contracture is a good model of systolic cardiac muscle interactions.
Disposition of biogenic amines and angiotensin I by lungs of spontaneously hypertensive rats
Authors: Roth R. A. , Wallace K. B.
Published: December 2017

Recent studies have suggested that the lung plays an important role in modifying concentrations of circulating vasoactive compounds. Isolated lungs of spontaneously hypertensive rats (SHR) were examined for their ability to modify concentrations of perfused norepinephrine, 5-hydroxytryptamine, or angiotensin I. Lungs from 4- or 14-wk-old SHR removed significantly more perfused 0.1 microM norepinephrine (NE) than lungs of normotensive controls (Wistar-Kyoto rats, WKY) of the same age. For example, lungs of 14-wk-old WKY removed 18.5 +/- 1.8% of perfused NE in a single pass through the pulmonary vasculature, whereas lungs from SHR removed 31.7 +/- 1.0%. Lungs of 14-wk-old SHR also produced more O-methylated NE metabolite than did lungs of WKY. Conversely, lungs of 14-wk-old SHR removed slightly less perfused 5-hydroxytryptamine and produced less 5-hydroxyindoleacetic acid metabolite than those of WKY. Monoamine oxidase activity, determined in 600 g supernatant fractions of lung homogenates, was the same in SHR and WKY. In addition, no difference in the ability of lungs of WKY and SHR to remove perfused angiotensin I was found either in animals 4 or 14 wk of age. These results suggest that lung may contribute to differences in concentrations of circulating biogenic amines observed in SHR and WKY.
Effects of amphiphiles on erythrocytes, coronary arteries, and perfused hearts
Authors: Bergmann S. R. , Ferguson T. B. , Sobel B. E.
Published: December 2017

Due to their unique structure, lysophosphoglycerides (such as lysophosphatidylcholine, LPC), compounds known to accumulate in ischemic myocardium, form micelles at concentrations exceeding the critical micelle concentration (CMC). In this study, we found that sub-CMC levels of LPC exerted dose-dependent morphological changes on red blood cells and elicited dysrhythmia and contracture while increasing coronary artery resistance in isolated hearts. LPC at supra-CMC concentrations lysed red blood cells, elicited virtually instantaneous contracture in perfused hearts, and constricted isolated coronary arteries. Because bile salts form micelles also, effects of LPC were compared with those induced by selected concentrations of bile salts. At sub-CMC levels, bile salts did not affect red cell morphology appreciably and exerted only negative ino- and chronotropic effects in isolated hearts. However, at supra-CMC concentrations, bile salts lysed red blood cells and caused contracture in the hearts. Thus LPC exerts specific effects at sub-CMC levels independent of nonspecific detergent effects of micelles. These specific effects may contribute to the mechanical and electrical dysfunction associated with myocardial ischemia.
In vivo cinematographic analysis of behavior of the aortic valve
Authors: Van Steenhoven A. A. , Verlaan C. W. , Veenstra P. C. , Reneman R. S.
Published: December 2017

In open-chest dogs direct-cinematographic high-speed recordings of aortic valve movement were made using a thin flexible fiberscope. Simultaneously ECG, ascending aortic flow (electromagnetically), and the pressures in the aorta, left ventricle, and left atrium were recorded. Replacement of blood by a transparent liquid (Tyrode solution) was done with two roller pumps, one connected to the left atrium and the other to the femoral artery. Free outflow occurred through a cannula in the pulmonary artery. Comparison of the film frames with the aortic flow signals revealed that 1) the valve was completely open at the moment that aortic flow had reached about 75% of its maximum value; 2) the opening time was 32 ms; 3) valve closure started before the onset of aortic flow deceleration; 4) at least 80% of the closure was completed before aortic flow becomes zero; 5) complete valve closing coincided with the moment of maximum backflow in the valve; 6) the shape of the valvular orifice at complete opening was almost circular; and 7) fluid viscosity had no significant effect on valve closure.
Mechanism of elevated left ventricular end-diastolic pressure after ischemic arrest and reperfusion
Authors: Schaff H. V. , Gott V. L. , Goldman R. A. , Frederiksen J. W. , Flaherty J. T.
Published: December 2017

The effects of ischemic arrest and reperfusion on isovolumic end-diastolic pressure, diastolic pressure-volume curves, and indices of ventricular relaxation and contractility were studied in an isolated feline heart preparation. In hearts subjected to 60 min of normothermic (37 degrees C) ischemic arrest, isovolumic developed pressure, and dP/dtmax during reperfusion returned to only approximately 60% of prearrest control levels. Isovolumic end-diastolic pressure (Ped) increased 37.0 +/- 4.3 mmHg and the time constant of ventricular relaxation was prolonged. Hearts maintained at 27 degrees C hypothermia during the 60-min ischemic period demonstrated improved contractile performance (approximately 100% of control), less elevation of Ped (21.4 +/- 4.5 mmHg), and no significant increase in the time constant of relaxation. In both groups of hearts, postarrest end-diastolic pressure-volume curves were shifted up and to the left, whereas indices of ventricular stiffness and muscle stiffness remained unchanged. These data suggest that the rise in isovolumic end-diastolic pressure observed after 1 h of ischemic arrest and reperfusion is the result of an upward and to the left shift of the entire diastolic pressure-volume relationship of the left ventricle. This shift does not appear to be related to diminished contractile performance or incomplete relaxation. Furthermore, the shift is not due to a change in muscle compliance, but to a reduction in the unstressed volume of the ventricle, which most likely results from myocardial contracture and edema.
Time course of regional function after coronary occlusions of 1- to 120-min duration
Authors: Darsee J. R. , Kloner R. A. , Braunwald E.
Published: December 2017

The purpose of this study was to characterize the degree and duration of functional impairment in previously ischemic tissue following coronary artery occlusions of varying duration. Open-chest dogs with left ventricular pressure transducers and ultrasonic segment length crystals were subjected to coronary artery occlusions of 1 (n = 22), 5 (n = 8), 10 (n = 7), 15 (n = 8), 20 (n = 7), 30 (n = 6), 60 (n = 10), or 120 (n = 8) min and segment length motion was measured during 6 h of reperfusion. Active shortening was replaced by passive lengthening during coronary occlusion and regional myocardial blood flow within the ischemic zone was always less than 0.4 ml . min-1 . g-1. Following reperfusion, the improvement of ischemic segment length function was inversely proportional to the duration of coronary occlusion. Function in previously ischemic segment lengths recovered rapidly after 1- and 5-min coronary occlusions, but after occlusions of 10-20 min, there was slow, though incomplete, return of some degree of active shortening yet no evidence of myocardial infarction. With occlusions exceeding 20 min there was persistence of systolic passive lengthening for 6 h despite the absence of infarction in the segment lengths in which function was being evaluated, although infarcted tissue was present ranging from 16.5 +/- 2.6% of the area of ischemia in dogs with 60-min coronary occlusions to 37.2 +/- 4.6% of the area of ischemia in dogs with 120-min occlusions.
Reduction in cardiac contractility during upper respiratory stimulation with cigarette smoke
Authors: Robleto D. O. , Peterson D. F.
Published: December 2017

Lightly anesthetized rabbits were instrumented to measure arterial pressure, peak left ventricular pressure (LVP) and its first derivative (LV dP/dt), electrocardiogram (ECG), heart rate (HR), and respiratory movements. Through a midtracheal incision two cannulas were inserted, one to allow spontaneous respiration of room air and the other to permit perfusion of the upper airways with unfiltered cigarette smoke. When 50 ml of smoke were passed out of the nostrils, we observed apnea (33.3 s), increases in mean arterial pressure (MAP) (31.9 mmHg) and LVP (38.3 mmHg), as well as decreases in HR (-125 beats/min) and LV dP/dtmax (-45%). After bilateral vagotomy, the responses of MAP and LVP to smoke exposure were not different from those in intact animals. The decrease in LV dP/dtmax (-27%) was, however, significantly less than in intact animals. Also, HR responses were not as pronounced after vagotomy. beta-Blockade after vagotomy abolished the LV dP/dt response to smoke, and the HR response was nearly abolished. MAP and LVP still underwent significant increases due to the smoke. After total sinoaortic denervation plus vagotomy in a second group of animals, a significant fall in LV dP/dtmax (-25%) persisted, and a small HR decrease was observed even when MAP was not allowed to change significantly. The results demonstrate that sympathetic outflow to the heart decreases while there is a net increase in sympathetic activity to the peripheral vasculature. The dramatic vagal bradycardia observed contributes part of the change in LV dP/dtmax. Reflexes originating in the circulation (vagal or sinoaortic) may also contribute to the fall in LV dP/dtmax, but a significant response persists in their absence.
An improved transducer for measurement of cardiac dimensions with sonomicrometry
Authors: Van Trigt P. , Bauer B. J. , Olsen C. O. , Rankin J. S. , Wechsler A. S.
Published: December 2017

Although pulse-transit sonomicrometry is an accurate and sensitive technique for measuring cardiac dimensions, transducer directionality has been a significant problem in certain applications. Construction of an improved ultrasonic dimension transducer is described for the measurement of global cardiac diameters. The transducer consists of a hemispheric piezoelectric crystal with a quarter-wavelength impedance matched faceplate. The in vitro acoustic characteristics of this transducer reveal a substantially improved beam pattern compared to the flat piezoceramic transducer commonly used. This improvement in transducer design greatly facilitates sonic alignment, enhances tracking throughout the cardiac cycle, and allows the measurement of more complex cardiac dimensions.
Effects of timing of atrial systole on LV filling and mitral valve closure: computer and dog studies
Authors: Meisner J. S. , McQueen D. M. , Ishida Y. , Vetter H. O. , Bortolotti U. , Strom J. A. , Frater R. W. , Peskin C. S. , Yellin E. L.
Published: December 2017

Atrioventricular (AV) delay that results in maximum ventricular filling and physiological mechanisms that govern dependence of filling on timing of atrial systole were studied by combining computer experiments with experiments in the anesthetized dog instrumented to measure phasic mitral flow. Ventricular filling volume is maximized at AV delay of 100 ms in the computer study and 80 ms in the dog study. At any time in diastole atrial contraction accelerates mitral flow, opening the mitral valve widely; atrial relaxation then decelerates mitral flow, moving the valve leaflets toward closure. The time the valve remains closed following atrial systole varies inversely with AV delay. When AV delay is optimal, the mitral valve is moving rapidly toward closure but is not yet closed at onset of ventricular systole. The decline in filling volume as AV delay decreases below its optimum value is primarily the result of premature termination of atrial ejection by ventricular systole. As AV delay increases above its optimal value, filling volume progressively decreases because of premature mitral valve closure that limits effective diastolic filling period. There is no significant retrograde mitral flow at any point in diastole for any AV delay.
Loading sequence is a major determinant of afterload-dependent relaxation in intact canine heart
Authors: Hori M. , Inoue M. , Kitakaze M. , Tsujioka K. , Ishida Y. , Fukunami M. , Nakajima S. , Kitabatake A. , Abe H.
Published: December 2017

To elucidate the role of loading sequence in afterload-dependent slowed relaxation in hearts in situ, the time constants (Texp from best exponential fitting method and TL from semilogarithmic method) of isovolumetric left ventricular (LV) pressure decay were studied in nine anesthetized open-chest dogs under the pharmacological blockade of autonomic nerve activity. An afterload change was imposed by clamping the ascending or descending aorta to make the peak LV pressure early or late in systole. During afterload interventions, in contractions with the peak LV pressure in late systole Texp and TL were significantly (P less than 0.05) larger than in those with the peak LV pressure in early systole in any comparable peak LV pressure range. Moreover, both time constants were directly correlated (P less than 0.01) with the time of peak LV pressure irrespective of peak LV pressure and clamp mode of aorta. In another protocol, marked differences both in Texp and TL were also observed between each of 25 pairs of contractions with different loading sequence but with comparable peak LV pressure and LV dimension (segment length). Thus afterload-dependent slowed relaxation in hearts in situ could not be attributed to an increased total load but to the altered loading sequence associated with an increase in afterload.
Supply-to-demand ratio for oxygen determines formation of adenosine by the heart
Authors: Bardenheuer H. , Schrader J.
Published: December 2017

To investigate the basic mechanism for formation of adenosine, cardiac work was increased using an isolated guinea pig working heart preparation. Cardiac metabolism was stimulated by intracoronary infusion of isoproterenol, norepinephrine (NE), ouabain, and the cardiotonic agent 1H-imidazo[4,5-b]pyridine, 2-[2-methoxy-4-(methylsulfinyl)-phenyl] (AR-L 115), and the release of adenosine into the effluent was determined. Besides their inotropic effects on myocardial tissue, these substances affect differently the tone of coronary arteries. Thus they influence the supply-to-demand ratio for O2 and the tissue cyclic AMP content differently. When myocardial O2 consumption was increased to the same extent, the changes in coronary flow induced followed the order of AR-L 115 greater than isoproterenol greater than NE greater than ouabain. Conversely, the rank order of potency causing adenosine and inosine release was NE greater than ouabain greater than isoproterenol greater than AR-L 115. When NE-induced vasoconstriction was abolished by prazosin, the release of adenosine and inosine was significantly diminished. Enhancement of O2 supply by overperfusion of the coronary arteries in isoproterenol-stimulated hearts was associated with a significant reduction of nucleoside release into the effluent. Our findings suggest that the major stimulus for myocardial adenosine formation is an imbalance between O2 delivery and O2 demand and not the metabolic rate as such. In the isolated heart, adenosine is formed as a feedback signal and can compete with NE- and ouabain-induced vasoconstriction.
Improvement in relaxation by nifedipine in hypoxic isometric cat papillary muscle
Authors: Carter J. E. , Palacios I. , Frist W. H. , Rosenthal S. , Newell J. B. , Powell W. J.
Published: December 2017

Hypoxia has been demonstrated to cause impairment of myocardial relaxation. This impairment of relaxation is particularly pronounced during early reoxygenation. This study was undertaken in 24 isometric cat papillary muscles at 38 degrees C to determine if nifedipine can influence the impairment of relaxation produced during reoxygenation following hypoxia. A dose of nifedipine was chosen that produced only a minimal depression of peak systolic tension and no change in the half time to relaxation (RT 1/2) under well-oxygenated conditions. Thirty minutes of hypoxia were produced in 12 muscles, and systolic tension decreased by the same amount in muscles treated or not treated with nifedipine. During early hypoxia in the absence of nifedipine, RT1/2 was significantly prolonged (P less than 0.01) from 104 +/- 7 to 126 +/- 9 ms. After pretreatment with nifedipine, the change in RT1/2 with hypoxia was not significant. More striking was the near abolition of the marked impairment of relaxation seen during early reoxygenation (238 +/- 33 ms without nifedipine and 128 +/- 8 ms with nifedipine, P less than 0.01). These data establish that, although nifedipine only minimally attenuates the relaxation impairment early during hypoxia, this agent can substantially reduce the impairment of relaxation produced by early reoxygenation.
Gradients in fiber shortening and metabolism across ischemic left ventricular wall
Authors: Prinzen F. W. , Arts T. , van der Vusse G. J. , Coumans W. A. , Reneman R. S.
Published: December 2017

Blood flow, metabolism, and fiber shortening in various layers of left ventricular wall were studied during the initial 5 min of ischemia. In open-chest dogs (n = 51) ischemia was induced by coronary arterial stenosis (median value of mean perfusion pressure distal to stenosis 3.3 kPa). Epicardial deformation measurements with an inductive technique allowed estimation of fiber shortening in inner (eendo,est) and outer layers (eepi) of left ventricular free wall during the ejection phase. The decrease of eendo,est occurred within a few seconds after onset of stenosis, whereas eepi started to decrease 30 s later. After 1 min, eendo,est diminished to zero concomitantly with a reduction of blood flow and creatine phosphate content in the inner layers by 68 and 46%, respectively. In contrast a 60% reduction of eepi was associated with a decrease in blood flow of only 32% and no significant decrease in creatine phosphate in the outer layers. H+ and inorganic phosphate were released simultaneously into the local venous blood starting within 1 min of ischemia. During the initial 5 min of ischemia the content of ATP and glycogen remained unchanged across the ischemic wall. Present results indicate that the decrease of fiber shortening in the inner layers is associated with severe metabolic dearrangements, as reflected by the depletion of creatine phosphate. They also indicate that, during coronary arterial stenosis, impaired fiber shortening in the outer layers may result from the impairment of mechanical function in the inner layers, rather than from metabolic disturbances in the outer layers themselves.
Assessment of slope of end-systolic pressure-volume line of in situ dog heart
Authors: Igarashi Y. , Suga H.
Published: December 2017

The purpose of this study was to establish a new method of assessment of the slope (Emax) of the end-systolic pressure-volume line (ESPVL) of the in situ heart. In anesthetized open-chest dogs, an isovolumic contraction was produced by an aortic occlusion after steady-state ejecting contractions in the left ventricle. We plotted ventricular pressure measured with a catheter-tip manometer against time integral of aortic flow measured with an electromagnetic flowmeter of the last ejecting and the first isovolumic contraction, assuming the same end-diastolic volume. ESPVL was drawn from the peak isovolumic pressure-volume point tangential to the left upper corner of the +/- 3.0 (SE) mmHg/ml (n = 9 dogs) in control run and was increased by 59 +/- 19% under isoproterenol and decreased by 47 +/- 9% after propranolol. Emax was little changed by atrial pacing. We conclude that Emax by this aortic occlusion method is useful for assessment of left ventricular contractility of the in situ dog heart.
Vasoactive intestinal peptide: vasodilatation and cyclic AMP generation
Authors: Ganz P. , Sandrock A. W. , Landis S. C. , Leopold J. , Gimbrone M. A. , Alexander R. W.
Published: December 2017

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter that causes vasodilation when injected intravenously. To learn more about the vasodilator actions of VIP, studies were performed on the rat mesenteric arterial bed and on cultured smooth muscle cells derived from both the rat mesenteric artery and aorta. In isolated perfused rat mesenteric artery beds, VIP caused relaxation at the threshold concentration of less than 1 nM and a maximal fall in perfusion pressure similar to that obtained with isoproterenol. VIP stimulated adenylate cyclase in cultured vascular smooth muscle cells in a concentration range of 10(-10)-10(-6) M; maximum activity was increased 2.7 +/- 0.6- and 3.4 +/- 0.4-fold above basal in mesenteric and aortic smooth muscle cells, respectively. The threshold and the half-maximal concentrations of VIP for adenylate cyclase stimulation were more than 50-fold lower than those for both prostaglandin E1 and isoproterenol in cultured mesenteric and aortic cells. Similar effects on cyclic AMP generation in response to VIP were observed in isolated rat mesenteric artery rings. Immunocytochemical examination of the rat mesenteric artery bed in situ demonstrated dense innervation of small- and medium-size vessels with nerve fibers containing VIP-like immunoreactivity. Thus VIP is present in the rat mesenteric artery, a peripheral arterial bed, and is a potent vasodilator that can activate vascular smooth muscle adenylate cyclase and thus potentially contribute to the regulation of vascular tone.
Effect of endorphins on heart rate and blood pressure in adult dogs
Authors: Haddad G. G. , Jeng H. J. , Lai T. L.
Published: December 2017

To investigate the role of opioids in regulating cardiovascular function, we administered delta-opioid receptor agonists D-Ala-D-Leu enkephalin (DADLE) and D-Ala-Met enkephalinamide (DAME), and mu-opioid receptor agonist, a morphiceptin analogue (MA), intracisternally in 13 unanesthetized, chronically instrumented adult dogs in 2 doses (25 and 125 micrograms/kg). After an initial transient drop, the R-R interval increased (peak approximately 25–60 min) postadministration of opioids. The time course and the magnitude of the change in R-R interval depended on the agonist: delta-agonists induced a more prolonged and marked change in R-R interval than mu-agonists at both doses. Mean arterial blood pressure (MAP) increased initially but dropped toward or even below base line 30 min after opioids administration. Atropine, given intravenously or intra-arterially at peak action of agonist in relatively low doses (0.02 mg/kg), induced an AV block followed by a marked decrease in R-R interval. There was also an increase in MAP after atropine. Naloxone, given intracisternally, reversed both delta- and mu-opioid effects but did not induce changes in the R-R interval without prior administration of opioids. We conclude that in unanesthetized adult dogs 1) both mu- and delta-receptor opioid agonists prolong the R-R interval, and this depends on the type of receptor stimulated; 2) opioids induce slowing in heart rate, possibly by increasing parasympathetic activity to the heart; 3) enkephalin and morphiceptin analogues induce a biphasic response in MAP; and 4) endorphins do not modulate cardiovascular function tonically; we speculate that they can alter the R-R interval and MAP in the presence of stimuli.
Reduced chronotropic responsiveness of the heart in experimental uremia
Authors: Mann J. F. , Jakobs K. H. , Riedel J. , Ritz E.
Published: December 2017

Cardiac beta-adrenoceptor responsiveness was evaluated in experimental uremia by in vivo and in vitro techniques. Uremia was induced in rats by bilateral nephrectomy for 48 h. In rats with chronic intra-arterial and intravenous catheters, cardiovascular reflexes and the renin-angiotensin system were blocked with atropine, pentolinium, and a converting-enzyme inhibitor, respectively. Blood pressure (BP) and heart rate (HR) were continuously recorded. Cumulative doses of isoproterenol were injected intravenously. In uremic rats, the dose-response curve for the HR response showed a lower maximal response (P less than 0.01) and no significant difference in 50% effective dose values compared with controls, whereas the BP decrease caused by isoproterenol was similar in control and uremic rats. When forskolin was injected intravenously to stimulate adenylate cyclase in a receptor-independent manner, the maximal HR increase was lower in uremic rats (P less than 0.01). beta-Adrenoceptor density and affinity, measured by 125I-cyanopindolol binding to sarcolemmal membranes, was not different between control and uremic rats. Also binding affinities for the agonist isoproterenol were not different between groups. Basal adenylate cyclase activity, as well as activity after maximal stimulation by isoproterenol and by forskolin were lower in uremic than in control rats (P less than 0.01). The results show that the chronotropic response of the heart is reduced in uremia. Such hyporesponsiveness may be due, at least in part, to a reduced activity of cardiac adenylate cyclase.
Protection of the blood-brain barrier by hypercapnia during acute hypertension
Authors: Baumbach G. L. , Mayhan W. G. , Heistad D. D.
Published: December 2017

The purpose of this study was to examine effects of hypercapnia on susceptibility of the blood-brain barrier to disruption during acute hypertension. Two methods were used to test the hypothesis that cerebral vasodilatation during hypercapnia increases disruption of the blood-brain barrier. First, permeability of the blood-brain barrier was measured in anesthetized cats with 125I-labeled serum albumin. Severe hypertension markedly increased permeability of the blood-brain barrier during normocapnia, but not during hypercapnia. The protective effect of hypercapnia was not dependent on sympathetic nerves. Second, in anesthetized rats, permeability of the barrier was quantitated by clearance of fluorescent dextran. Disruption of the blood-brain barrier during hypertension was decreased by hypercapnia. Because disruption of the blood-brain barrier occurred primarily in pial venules, we also measured pial venular diameter and pressure (with a servo-null method). Acute hypertension increased pial venular pressure and diameter in normocapnic rats. Hypercapnia alone increased pial venular pressure and pial venular diameter, and acute hypertension during hypercapnia further increased venular pressure. The magnitude of increase in pial venular pressure during acute hypertension was significantly less in hypercapnic than in normocapnic rats. We conclude that hypercapnia protects the blood-brain barrier. Possible mechanisms of this effect include attenuation of the incremental increase in pial venular pressure by hypercapnia or a direct effect on the blood-brain barrier not related to venous pressure.
Coronary constrictor effect of stroma-free hemoglobin solutions
Authors: Vogel W. M. , Dennis R. C. , Cassidy G. , Apstein C. S. , Valeri C. R.
Published: December 2017

A coronary vasoconstrictor effect of human stroma-free hemoglobin (SFH) was identified in isolated rabbit hearts perfused with Krebs-Henseleit buffer or whole rabbit blood at a constant coronary flow rate. In buffer-perfused hearts, SFH in concentrations of 5 to 200 mg/dl produced dose-related increases of coronary perfusion pressure. At a concentration of 150 mg/dl, SFH, equilibrated with CO to form carboxyhemoglobin, caused an increase in perfusion pressure (55 +/- 7 mmHg), similar to that observed with oxyhemoglobin (57 +/- 6 mmHg); addition of potassium ferricyanide to form methemoglobin reduced the increase of perfusion pressure to 34 +/- 5 mmHg (P less than 0.05). The vasoconstrictor activity could not be eliminated by dialyzing against the perfusion buffer. Human SFH prepared by different methods had similar vasoconstrictor activity. Rabbit SFH and human SFH were equi-effective in the rabbit heart. Less constrictor activity of SFH was evident in rat and guinea pig heart. Polymerized, pyridoxalated SFH had greatly reduced constrictor effect compared with unmodified or pyridoxalated tetramer SFH. In blood-perfused hearts, increasing plasma hemoglobin to 1.6 +/- 0.1 g/dl, without changing total hemoglobin or arterial O2 content, increased coronary perfusion pressure by 36 +/- 13 mmHg (P less than 0.05). We conclude that stroma-free hemoglobin solutions exert a coronary vasoconstrictor effect that is unrelated to O2 delivery.
Lack of sympathetic vasoconstriction in hypoxemic humans at rest
Authors: Rowell L. B. , Blackmon J. R.
Published: December 2017

A three-part experiment was designed to show whether hypoxemia alters splanchnic vasomotor responses to other stresses by vasodilating splanchnic organs, preventing norepinephrine (NE)-induced vasoconstriction, or altering total sympathetic nervous activity (SNA) assessed by plasma levels of NE and epinephrine (Epi). Splanchnic blood flow (SBF) was measured by plasma clearance and hepatic extraction of indocyanine green (constant infusion). Part I: two degrees of hypoxemia [fractional concn of inspired O2 (FIO2) = 10.4 and 7.6%, arterial PO2 (PaO2) = 34.8 and 27 Torr] caused a small splanchnic vasodilation; resistance fell 16 and 26%, respectively, in five men; and SBF rose from 1.78 to 2.04 (10.4% O2) and to 2.02 1 X min-1 (7.6% O2). Plasma NE was unaffected by hypoxemia and by a fall in mean arterial pressure from 82 to 63 Torr at FIO2 = 7.6%. Part II: NE infused intravenously to raise pressure by 20 Torr in five subjects breathing air and 10.3% O2 caused splanchnic vasoconstriction irrespective of PaO2. Part III: in six subjects, two levels of hypoxemia (FIO2 = 10.4 and 7.7%) did not increase NE levels in five men, and Epi increased in two men only at FIO2 = 7.7%. We conclude that hypoxemia caused only a small splanchnic vasodilation not mediated by Epi, did not prevent transient NE-induced vasoconstriction, and either did not significantly increase SNA or prejunctionally inhibited NE release. Severe hypoxemia abolished the rise in NE and heart rate in response to falling pressure.
Effect of atriopeptin III on hematocrit and volemia of nephrectomized rats
Authors: Fluckiger J. P. , Waeber B. , Matsueda G. , Delaloye B. , Nussberger J. , Brunner H. R.
Published: December 2017

The effect of a synthetic atrial natriuretic peptide (atriopeptin III) on blood pressure, heart rate, and hematocrit was investigated in conscious, nephrectomized (n = 6), and sham-operated (n = 6) rats. Atriopeptin III infusion (1 microgram/min iv for 30 min) decreased mean blood pressure to a similar extent in nephrectomized [from 122 +/- 5 to 108 +/- 3 (SE) mmHg; P less than 0.01] and in sham-operated rats (from 124 +/- 4 to 103 +/- 2 mmHg; P less than 0.01), whereas it had no significant effect on heart rate. Hematocrit rose similarly in nephrectomized (from 45 +/- 1 to 49 +/- 1%; P less than 0.01) and in sham-operated rats (from 46 +/- 1 to 50 +/- 1%; P less than 0.001). Infusion of the vehicle of atriopeptin III to nephrectomized rats (n = 7) did not change any of these parameters. Plasma volume and red cell mass of nephrectomized rats infused with atriopeptin III was measured by use of radiolabeled albumin and erythrocytes, respectively. A plasma volume contraction of approximately 10% (P less than 0.01) was observed, whereas red cell mass did not change. In an additional group of nephrectomized rats (n = 6), Na nitroprusside was infused intravenously at a rate of 2 micrograms/min for 30 min. Na nitroprusside reduced mean blood pressure from 127 +/- 4 to 106 +/- 3 mmHg (P less than 0.001), but hematocrit remained unchanged (46 +/- 1% before vs. 45 +/- 1% after infusion). In four anesthetized rats with both kidneys and the spleen removed atriopeptin III still raised the hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin responses and receptors in the mesenteric vasculature of estrogen-treated rats
Authors: St-Louis J. , Parent A. , Lariviere R. , Schiffrin E. L.
Published: December 2017

The effect of treatment with estrogens on the biological activity of arginine8 vasopressin (AVP) in the in vitro perfused mesenteric vascular bed and on the binding characteristics of [3H]AVP on membranes prepared from the same vascular bed was studied. Female rats treated with estradiol (400 micrograms/24 h sc), compared with ovariectomized rats, had an increase in the maximum response to AVP (from 128 +/- 3 to 153 +/- 3 mmHg) in the perfused preparation and an increase in the density of AVP binding sites (from 402 to 732 fmol/mg protein) in the membrane preparation. In male rats, the injection of estradiol increased the maximum response to AVP (from 109 +/- 4 to 137 +/- 3 mmHg) and the density of AVP binding sites (from 289 to 519 fmol/mg protein). The effective concentration producing 50% of maximum response of AVP in the perfused preparation was higher in male than in female rats, while the Kd in the binding experiments was similar in the four experimental groups. Our results show that estrogens upregulate the number of AVP binding sites, leading to an increase in the pressor response to AVP in the rat mesenteric vascular bed.
Lack of liver vascular response to carotid occlusion in mildly acidotic dogs
Authors: Goresky C. A. , Cousineau D. , Rose C. P. , Lee S.
Published: December 2017

The effect of mild acidosis on the reduction in liver vascular volume provoked by reflex sympathetic activation was ascertained in dogs by use of the multiple indicator-dilution technique. Portal vein-hepatic vein dilution patterns were obtained following injection of a mixture containing 51Cr-labeled red blood cells (a vascular reference), 14C-labeled sucrose (an interstitial reference), and 3H-labeled water (a cellular reference). Liver vascular, interstitial, and cellular water spaces were measured in normal and mildly acidotic dogs under basal conditions and during bilateral carotid artery occlusion. Carotid occlusion resulted in a large increase in arterial blood pressure in normal and a lesser increase in acidotic dogs, but the increase in portal and hepatic vein norepinephrine and decrease in liver vascular and interstitial volumes observed in normal dogs did not occur in the acidotic animals; no change in labeled water accessible liver cellular spaces was perceptible. The data indicate that mild acidosis abolishes the ordinarily expected reduction in liver vascular volumes on sympathetic activation in the intact dog but not the arterial pressor response.
Effects of acute lung injury and anesthesia on left ventricular mechanics
Authors: Hansen D. E. , Borow K. M. , Neumann A. , Lang R. M. , Fujii A. M. , Schumacker P. T. , Wood L. D.
Published: December 2017

Traditional left ventricular (LV) function curves are frequently depressed in patients with acute lung injury. Similar findings in pentobarbital sodium-anesthetized dogs with oleic acid lung injury (OALI) have been observed. To test the hypothesis that acute OALI produces a significant injury to the heart, the LV mechanics of pentobarbital-anesthetized dogs with (n = 6) and without (n = 6) OALI were evaluated. End-systolic force-length and force-velocity relations determined echocardiographically during afterload manipulation with sodium nitroprusside demonstrated a marked deterioration in LV shortening characteristics over 90 min in both groups of pentobarbital-anesthetized dogs. In contrast, LV mechanics studied using the same protocol in fentanyl-anesthetized dogs were unchanged in both the injured (n = 6) and noninjured (n = 6) lung groups. Comparisons with data acquired over a wide range of LV afterload from six conscious, instrumented dogs showed that LV contractile state was normal to slightly increased with fentanyl and markedly depressed with pentobarbital. Diastolic properties, as assessed by end-diastolic pressure-dimension relations, were essentially unchanged in all anesthetized animals. We conclude that OALI has no effect on LV systolic or diastolic mechanics; the LV dysfunction attributed to OALI in previous studies is due to an acute, severe cardiomyopathy induced by pentobarbital; and unlike pentobarbital, anesthesia with fentanyl has no discernible time-dependent effect on LV mechanics. These findings have important implications for future studies of canine cardiovascular physiology employing anesthetized animal preparations.
O2 free radical-mediated myocardial and vascular dysfunction
Authors: Jackson C. V. , Mickelson J. K. , Pope T. K. , Rao P. S. , Lucchesi B. R.
Published: December 2017

In the present investigation electrolysis of a physiological buffer solution for 2 min with a constant current (20 mA, DC stainless steel anode) was observed to generate free radicals, determined by a luminol assay. Rabbit isolated hearts perfused with physiological buffer subjected to electrolysis were observed to undergo an increase in coronary artery perfusion pressure (PP) and in left ventricular end-diastolic pressure (LVEDP), 80 +/- 4 and 52 +/- 7 mmHg, respectively. Immediately after electrolysis of the physiological buffer, the hearts were observed to accumulate and retain (8-fold) more 125I-labeled albumin than hearts perfused with normal buffer without electrolysis, indicating an increased vascular permeability. The free radical scavengers, dimethyl sulfoxide (DMSO) and catalase (CAT), provided significant protection of the hearts against the changes in PP, LVEDP, and vascular permeability. This study demonstrates that toxic oxygen species generated independently of circulating blood elements or enzymatic reactions can have a direct effect on the vasculature of an isolated heart leading to alterations in cardiac function. The protection afforded by the addition of DMSO or CAT to the perfusion system would suggest that the OH. radical and H2O2 were the reactive oxygen species involved in producing the observed vascular and cardiac effects.
Mitogen-activated protein kinase and proliferation of human vascular smooth muscle cells
Authors: Mii S. , Khalil R. A. , Morgan K. G. , Ware J. A. , Kent K. C.
Published: December 2017

The intracellular messenger mitogen-activated protein kinase (MAPK) is activated in vascular smooth muscle cells (SMC) by various growth factors as well as by agonists that have no proliferative effect. We explored the hypotheses that SMC proliferation is associated with a specific pattern of MAPK activation by evaluating the kinetics of MAPK activation and tyrosine phosphorylation and the intracellular location of MAPK in SMC following addition of agonists of varying mitogenic potential. A peak in MAPK activation and tyrosine phosphorylation occurred 3-10 min after the addition of agonists to SMC derived from human saphenous vein (early phase), followed by a plateau of activity, which was variable in duration (late phase). A correlation was not found between mitogenicity and the degree to which MAPK became activated or tyrosine phosphorylated in the early phase. However, the duration of MAPK activation and tyrosine phosphorylation correlated strongly with the ability of agonists to stimulate SMC proliferation. Nuclear translocation of MAPK was associated with SMC proliferation, although the degree to which each agonist induced nuclear translocation did not parallel its mitogenic potential. The relative dependency of all three events on protein kinase C differed for each agonist and was greater in the late versus the early phase. Thus, in human SMC, nuclear translocation of MAPK and prolonged activation and tyrosine phosphorylation of MAPK are associated with growth factor-induced mitogenesis.