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Biomedical subjects

A V Loud

Publications and source records attributed to A V Loud.

At least 19 recordsLinked to original sources
PubMed1992

Chronic elevation of norepinephrine in conscious dogs produces hypertrophy with no loss of LV reserve.

Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To determine whether the left ventricle from dogs with chronic norepinephrine infusion can sustain additional functional loads, we altered ventricular preload or afterload and determined both global and left ventricular (LV) wall function. Dogs were instrumented to measure LV wall function, LV internal base diameter, and LV pressures and were allowed to fully recover. Preload was altered by volume loading and afterload by injection of phenylephrine. Osmotic infusion pumps were implanted to continuously release norepinephrine at 0.5 micrograms.kg-1.min-1 for 28 days, and the volume loading and phenylephrine were repeated on days 14 and 28. Heart rate decreased, whereas there were no differences in mean arterial pressure, maximum first derivative of LV pressure (dP/dt), LV dP/dt/developed pressure of 40 mmHg, LV dP/dt/end-diastolic circumference, slope of the pressure-diameter relation, peak systolic wall stress, LV/end-diastolic diameter, or LV/end-systolic diameter during norepinephrine infusion. Diastolic and systolic wall thickness and chamber weights were increased (P less than 0.05). Indexes of diastolic function, including end-diastolic pressure, end-diastolic pressure-end-diastolic diameter relationship, maximum negative dP/dt, and the time constant (tau) were unchanged after chronic norepinephrine infusion, although maximum end-diastolic pressure during volume loading was increased from 17.7 +/- 2.0 to 21.7 +/- 1.0 mmHg. Chronic norepinephrine infusion did not alter tau, and tau increased equivalently with phenylephrine injection in both normal (36 +/- 1 to 62 +/- 5 ms) dogs and in those chronically infused with norepinephrine (36 +/- 1 to 56 +/- 5 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Altered function and structure of the heart in dogs with chronic elevation in plasma norepinephrine.

BACKGROUND: We have previously shown that chronic elevation of plasma norepinephrine leads to a functional independent increase in left ventricular weight. The goals of the present study were to determine quantitatively the component of the myocardium that accounted for the observed structural changes and to determine the function of the hypertrophied myocardium. METHODS AND RESULTS: Mongrel dogs were chronically instrumented for measurement of arterial and left ventricular pressures, left ventricular internal diameter, and left ventricular wall thickness. Subcutaneous osmotic pumps were implanted to release norepinephrine continuously for 28 days. Hemodynamics were measured with dogs in the quietly resting state and during infusions of isoproterenol at 0.1 and 0.5 micrograms/kg/min before and on days 14 and 28 during the infusion of norepinephrine. The hemodynamic response to 10 micrograms/kg phenylephrine, given as a bolus, was also assessed before norepinephrine and 28 days during the infusion of norepinephrine, and the end-systolic pressure-diameter or wall-stress-diameter relations were calculated. On day 28, hearts were arrested in diastole and perfusion fixed in situ. Tissue samples were prepared for electron microscopy and morphometry. Hemodynamic studies showed that isoproterenol (0.5 micrograms/kg/min) reduced mean arterial pressure (MAP) to the same point on each experimental day, and the increases in indexes of contractility were reduced during norepinephrine infusion. Left ventricular dP/dtmax increased 131 +/- 24% on control day, only 67 +/- 20% on day 14, and 55 +/- 18% on day 28. Similar changes were observed in dP/dt/DP40 and dP/dt/end-diastolic circumference. However, Emax, the slope of the end-systolic pressure-diameter or wall stress diameter relations, was unchanged, suggesting that inotropic state was not altered. Morphometric studies showed that the cross-sectional area of myocytes increased by 55%, but myocyte and capillary densities decreased by 34% and 29%, respectively (p less than 0.05) in dogs with high norepinephrine levels. There were no differences in volume fractions of myocytes, capillary lumen, or interstitium or capillary-to-myocyte ratio. CONCLUSIONS: The myocardium of dogs with high norepinephrine levels shows reduced inotropic response to beta-adrenergic stimulation despite the increases in left ventricular mass and left ventricular wall thickness, which are a result of growth of the cardiac myocytes and characteristic of concentric hypertrophy. These data suggest that chronic adrenergic stimulation of the heart reduces the beta-receptor coupling to the contractile response without importantly compromising left ventricular function.

Animals↗
PubMed1991

Carotid baroreceptor function in dogs with chronic norepinephrine infusion.

Carotid baroreceptor function, the compliance of the carotid sinus wall, and the structure of the carotid artery were examined in dogs with elevated plasma norepinephrine (2,000-4,000 pg/ml) for 28 days. The dogs with high norepinephrine were normotensive (100 +/- 4.0 versus 98 +/- 4.0 mm Hg; p greater than 0.05) with bradycardia (65 +/- 4.0 versus 87 +/- 16 beats/min; p less than 0.05) compared with normal dogs in the conscious state. However, after pentobarbital anesthesia blood pressure was significantly higher in dogs with chronic norepinephrine infusion (165 +/- 6 mm Hg) compared with normal dogs (132 +/- 6 mm Hg). To assess baroreceptor sensitivity, multiunit carotid baroreceptor activity was recorded from the right carotid sinus nerve, and the carotid sinus wall compliance (sonomicrometers) was measured during nitroglycerin and phenylephrine injections. The threshold and saturation pressures increased from 96 +/- 3.9 to 117 +/- 4.2 mm Hg and from 145 +/- 4.3 to 171 +/- 5.7 mm Hg, respectively, in the normal dogs compared with the high norepinephrine dogs. The most striking differences were the marked increases in sensitivity of carotid baroreceptors (0.47 +/- 0.05 versus 1.99 +/- 0.45 spikes.sec-1.mm Hg-1; p less than 0.01) and maximum firing frequency of the baroreceptors (24 +/- 3.1 versus 48 +/- 4.4 spikes/sec; p less than 0.01), whereas the carotid sinus wall compliance was unchanged (0.014 +/- 0.003 versus 0.012 +/- 0.002 mm/mm Hg; p greater than 0.05). Similar alterations were observed using single fiber recordings, that is, an increase in threshold and saturation pressures and slope of baroreceptor units in dogs with elevated norepinephrine. The wall thickness and area of the carotid artery were determined. Both increased significantly (0.77 +/- 0.06 versus 1.30 +/- 0.12 mm and 9.0 +/- 0.8 versus 11.9 +/- 0.9 mm2; p less than 0.05) in dogs chronically infused with norepinephrine while the dry weight-to-wet weight ratio of left carotid artery tissue also increased from 26.0 +/- 0.73% to 29.0 +/- 0.57%. These studies indicate that 1) one of the possible mechanisms responsible for bradycardia in the conscious dogs with high norepinephrine is enhanced sensitivity of carotid baroreceptors; 2) the enhanced sensitivity of carotid baroreceptors is not due to a change in compliance of the carotid sinus wall; and 3) chronic elevation of norepinephrine causes hypertrophy or hyperplasia of the wall of the common carotid artery.

Animals↗
PubMed1989

Global myocardial hypertrophy in conscious dogs with chronic elevation of plasma norepinephrine levels.

Chronically elevated plasma norepinephrine is associated with many disease states in which myocardial hypertrophy is also found, yet whether the hypertrophy results from the hemodynamic actions of catecholamines or a trophic effect is still unknown. The goal of our study was to determine the extent of hypertrophy following 28 days of norepinephrine infusion and the role of altered hemodynamics as the stimulus for the hypertrophy in conscious dogs. In a retrospective study gross cardiac weights were examined in 25 control instrumented dogs (controls) and in 41 instrumented dogs with elevated norepinephrine (NE). In the NE dogs LV (94 +/- 2.8 g), septum (33 +/- 1.5 g) and total heart weights (172 +/- 4.5 g) were greater than in controls (85 +/- 5.0, 31 +/- 1.9, and 158 +/- 9.0 g, respectively). The LV (3.95 +/- 0.10 g/kg), RV (1.91 +/- 0.06), septum (1.38 +/- 0.06) and total weight (7.23 +/- 0.15) to body weight ratios were also significantly greater (3.32 +/- 0.12, 1.73 +/- 0.08, 1.24 +/- 0.06, and 6.28 +/- 0.23 g/kg). The dry/wet weight ratios were not different in the two groups. After cutting the hearts into 1 cm rings, the planimetered area of each ring showed that the wall thickness increased at all levels, e.g. at the base by 25 +/- 3.2%. The chamber internal diameter was significantly increased only near the apex in the NE dogs making the heart more cylindrical in shape. There was no obvious sign of fibrosis in any layer of the myocardium. In physiologic studies, no index of contractility was altered including: LV dP/dt, LV dD/dt, shortening, LV dWT/dt and there was also no change in preload. Heart rate was significantly reduced throughout the 28 days of study. Cardiac output was reduced and there were no significant changes in cardiac work. Thus in these dogs NE caused a 19% and 10% increase in LV and RV to body weight ratios, respectively, without any obvious hemodynamic stimulus.

Animals↗
PubMed1989

Atrial wall function and plasma atriopeptin during volume expansion in conscious dogs.

Mean left atrial pressure is believed to be an accurate estimate of atrial stretch in vivo and is used to assess the stimulus for atriopeptin release in both animals and humans. However, for a number of years it has been known that atrial stretch receptor discharge occurs during specific phases of the atrial cycle and that B-receptor discharge correlates with the passive filling of the atrium, which occurs during the V wave. The purpose of this study was to develop the concept that phase-specific changes in atrial wall stress are responsible for atriopeptin secretion. In chronically instrumented conscious dogs, volume expansion (1,000 ml of saline in 5 min) increased left atrial pressure and dimensions and caused a 663 +/- 189% increase in plasma immunoreactive atriopeptin from 44 pg/ml. At this time, mean left atrial pressure increased only 202 +/- 36% (mean +/- SE), whereas A wave pressure increased 146 +/- 19% and V wave pressure increased 290 +/- 67%. A and V wave dimensions increased only a few percent. After developing atrial wall thickness constants for diastole (KCl fixation) and systole (BaCl2 fixation), calculated atrial A wave wall stress increased 163 +/- 25%, and V wave wall stress increased 346 +/- 85%. Minute wall stress (wall stress times heart rate) gave an even better correlation with changes in plasma atriopeptin. V wave minute wall stress increased 690 +/- 168%, whereas A wave wall stress increased 366 +/- 56%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of alveolar hypoxia on pulmonary mast cells in vivo.

This study was undertaken to explore the effects of alveolar hypoxia on perivascular and periairway mast cell populations. Pulmonary mast cells were exposed to unilateral alveolar hypoxia by ventilating one lung of a cat with nitrogen. Mast cells from the contralateral lung, which was simultaneously ventilated with air, were used as a control. The granule content of perivascular and airway mast cells was determined from electron micrographs using morphometric methods. In response to alveolar hypoxia there was a 12% (p less than 0.005) decrease in the granule content of perivascular mast cells but no statistically significant change in periairway mast cell content. Perivascular mast cells from the hypoxic lungs did not show any of the morphological changes seen in IgE-mediated mast cell degranulation, such as granule swelling, fusion, or exocytosis. In the hypoxic lung, morphometric analysis revealed a significant decrease in the proportion of heterogeneous-appearing granules in the perivascular mast cells. The different reactivity of perivascular and periairway mast cells may explain why alveolar hypoxia does not induce significant bronchospasm.

Animals↗
PubMed1987

Electron microscopic morphometry.

The fundamental concepts of morphometry, the principal correction factors for systematic errors and the basic principles of efficient sampling are outlined for quantitative morphology at the electron microscopic level of resolution. The important usefulness of correlating electron microscopic morphometry with complementary light microscopic morphometry is emphasized.

Animals↗
PubMed1985

Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy.

To determine whether left ventricular failure after acute myocardial infarction is associated with a growth response of the myocytes that tends to compensate for the loss of muscle mass and function, the left coronary artery in rats was ligated near its origin, and the animals were killed 3 days later. Elevated left ventricular end-diastolic pressure and decreased first derivative of left ventricular pressure and systolic arterial pressure indicated significant impairment of ventricular function. Absolute infarct size, determined morphometrically by measurement of the fraction of myocyte nuclei lost, averaged 57%. Hypertrophy of surviving left ventricular myocytes was 28%, involving a 14% increase in cell length and a 6% increase in diameter. Right ventricular myocyte volume per nucleus increased 21% by a 10% enlargement of cellular diameter with no change in length. These results show on a cellular basis that myocardial hypertrophy in the left ventricle is accomplished by cellular shape changes characteristic of a combination of pressure and volume overload hypertrophy, whereas cellular growth in the right ventricle is consistent with pressure overload hypertrophy.

Animals↗
PubMed1985

Left ventricular failure induced by myocardial infarction. II. Tissue morphometry.

Three days after myocardial infarction involving 57% of the left ventricle in rats, the viable tissue of the left ventricle expanded 29%, whereas myocardial hypertrophy in the right ventricle was 19%. To determine whether tissue oxygenation in the hypertrophied ventricles was supported by a proportional growth of the capillary network, morphometric analysis was used to measure capillary luminal volume and surface densities and the diffusion distance for O2. The volume fraction of capillary lumen and the luminal surface of capillaries, related to O2 availability and diffusion, were altered by -21 and -19%, respectively, in the left ventricle and by -23 and -20%, respectively, in the right ventricle. The path length for O2 transport was found to be increased by 12 and 15% in the left and right ventricle, respectively. In contrast, myocyte mass expanded in proportion to tissue growth in the left ventricle and exceeded tissue growth by 5% in the right ventricle. Myocyte mitochondria and myofibrils both grew in proportion to the cells, so that their volume ratio was not changed in either ventricle. The relatively inadequate adaptation of the capillary vasculature suggests that hypertrophy after severe myocardial infarction may initially leave the heart more vulnerable to additional ischemic episodes.

Adenosine Triphosphate↗
PubMed1978

Absolute morphometric study of myocardial hypertrophy in experimental hypertension. I. Determination of myocyte size.

A method for determining the mean absolute volume of a specific population of cells within a tissue is described and applied to the measurement of endocardial and epicardial myocytes in the left ventricle of normal and hypertensive rats. The technique, based on nuclear counts per unit area in tissue slices of different known thicknesses, measures the mean cell volume per nucleus independent of previously unknown nuclear dimensions and systematic counting errors. Duplicate determinations, demonstrating reproducibility, were made in mutually perpendicular longitudinal and transverse sections of the myocardium. Combining these light microscopic measurements with electron microscopic data enabled the evaluation of the mean diameter and length of the cylindrical myocyte nuclei showing those in the epicardial cells to be significantly longer than the nuclei in endocardial cells. It was estimated that 2 to 4 per cent of ventricular myocytes are binucleate. After 1 to 4 weeks of hypertension, induced by constriction of the left renal artery, endocardial myocytes were enlarged 21 per cent, from 10,370 +/- 410 to 12,520 +/- 490 cu. micrometer., while epicardial myocytes showed a 37 per cent hypertrophy, from 12,600 +/- 1,600 to 17,300 +/- 1,100 cu. micrometer. The availability of a reliable determination of cell volume will make possible the interpretation of much biochemical, functional, and morphometric data at the whole cell level.

Animals↗
PubMed1978

Absolute morphometric study of myocardial hypertrophy in experimental hypertension. II. Ultrastructure of myocytes and interstitium.

The left ventricular myocardium of normal and hypertensive rats has been characterized morphometrically in the endocardial and epicardial zones. Compared to the epicardial regions, the normal endocardial regions contain 30 per cent more myocytes, 27 per cent less interstitial space, 48 per cent less capillary volume, 17 per cent less capillary surface, and the same capillary length per unit tissue volume. In terms of both the relative and absolute volumes and surface areas of their organelles, the cytoplasmic composition of normal endocardial and epicardial myocytes is nearly identical. After 14 weeks of hypertension, induced by constriction of the left renal artery, left ventricular weight is increased by 30 per cent, wall thickness by 42 per cent. The number of myocytes and the total length of capillaries remain constant. The epicardial region enlarged 37 per cent with proportional increases of myocyte and interstitial volumes. In contrast, the endocardial enlargement was only 26 per cent, comprised of 21 per cent hypertrophy of myocytes and a 55 per cent increase in interstitial components. Expansion of capillary lumina accounted for much of the interstitial enlargement throughout the myocardium. Hypertrophy of myocytes is 76 per cent greater in the epicardial region and is accompanied by a reduced mitochondria to myofibril ratio and disproportionately large increases (2- to 3-fold) in both smooth endoplasmic reticulum and T-system volume and surface area. On a cellular basis the absolute morphometric characteristics of myocytes from hypertensive rats are significantly different from normal, and significant differences occur between the inner and outer layers of the myocardium for practically every cytoplasmic component.

Animals↗
PubMed1977

Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy. A light microscope study.

Renal corpuscles from the juxtamedullary and subcapsular regions of the renal cortex were morphometrically analyzed in young rats and in adult rats that had been unilaterally nephrectomized or sham-operated at an early age. Mean corpuscular volumes increased 4.5-fold during normal development, and 7.7-fold as a result of compensatory hypertrophy in both cortical regions. Relative and absolute volumes were determined for Bowman's space, the glomerular tuft, and five glomerular components: epithelial, endothelial, and mesangial cells, capillaries, and the filtration membrane. Normal and hypertrophic enlargement of Bowman's space was slightly greater than glomerular growth, and the growth response of subcapsular glomeruli was greater than that of juxtamedullary glomeruli. The ratio of mean glomerular volumes between outer and inner glomeruli was 1:2 in both adult groups. Both adult groups also developed nearly identical proportions of all glomerular component structures, representing a relative decrease of epithelial cells and increase of capillaries compared to the young animals. Normal and hypertrophic maturation involved absolute increases in all glomerular cell populations, the length of capillary loops and the surface area of the filtration membrane, all nearly in proportion to the respective four- and seven-fold increases in glomerular volume. Changes in the filtration surface area are consistent with published data for glomerular filtration rates in normal and hypertrophied kidneys. The mean cell size in epithelial and mesangial populations doubled during growth, but was not greater than normal in mononephrectomized rats. Hyperplasia among all populations of glomerular cells is indicated in normal growth, and to a greater extent in compensatory renal hypertrophy.

Aging↗
PubMed1977

Morphometric analysis of hypertension-induced hypertrophy of rat thoracic aorta.

The response of the intima-media of the thoracic aorta to 1 to 4 weeks of two-kidney renal hypertension in the rat has been analyzed by morphometric techniques at light and electron microscopic levels. The increased thickness of the aorta that ensues is the result of an increase in the size but not the number of smooth muscle cell layers. The volume fractions of intima occupied by endothelium (26%), internal elastic lamina (37%), and subendothelial space (37%) in normotensive animals are not significantly altered by the hypertension. The percent increases in muscle cross-sectional area is greatest (58 to 60%) in the two innermost layers (M1 and M2). M1 is composed of nearly equal compartments of smooth muscle cells and interstitial space that expand 69% and 50%, respectively, with hypertension. Analysis of the subcellular constituents of the M1 smooth muscle cells indicates that significant changes in absolute volume include increases of caveolae (45%), myofibrils (59%), mitochondria (81%), glycogen (163%), and rough endoplasmic reticulum (221%). Factors contributing to these alterations are discussed.

Animals↗
PubMed1976

Substrate-induced acceleration of lactase synthesis in fetal rat intestine.

Twenty milligrams of lactose were injected into the amniotic sacs of fetuses in one uterine horn and 20 mg glucose were injected into the amniotic sacs of fetuses in the opposite uterine horn of six rats on days 17-19 of pregnancy. Two or 3 days later the pregnant animals were killed and segments of jejunum obtained from their fetuses were homogenized in water. Assays for lactase and protein determinations were performed on these homogenates. Lactase values were significantly higher in the lactose-injected group than in fetuses receiving glucose (Table 2), P less than 0.0005. Thus, fetal intestinal lactase activity can be increased by exposure to the substrate lactose during late fetal life.

Amnion↗