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Biomedical subjects

R A Walsh

Publications and source records attributed to R A Walsh.

At least 109 records · Page 6Linked to original sources
PubMed1994

Allocation of research funds in the drug and alcohol field: report of the Consensus Workshop.

Issues concerning the allocation of research funds in the drug and alcohol field have been widely debated. A consensus workshop involving senior researchers and policy makers was convened to examine the appropriateness of current drug and alcohol research activities in Australia. The workshop identified several major barriers restricting research developments including lack of monitoring of research efforts, limited community support, inappropriate allocations of research funds which contributed to a low level of intervention studies, the lack of application of research findings by practitioners and ethical constraints in studies involving Aboriginal populations and in multi-centre trials. Agreement was reached on 16 recommendations which could increase the amount of high quality research in Australia directed at reducing the harm associated with alcohol, tobacco and other drug use. Strategies which funding bodies could use to encourage intervention studies were identified. A proposal for the Australian Medical and Professional Society on Alcohol and other Drugs to establish a Researchers' Group to encourage implementation of the recommendations was also endorsed by workshop participants.

Journal Article↗
PubMed1994

Myosin heavy chain regulation and myocyte contractile depression after LV hypertrophy in aortic-banded mice.

Using an adult mouse aortic-banded model of pressure-overload hypertrophy and isolated cardiomyocyte mechanics studies, we examined the hypothesis that contractile depression is due to altered cardiac contractile proteins rather than changes in left ventricular (LV) geometry, loading, or the extracellular matrix. FVB mice were banded at the transverse aortic arch or sham operated and studied after 7 days. In nine animals the gradient across the aortic band averaged 47 +/- 4 mmHg. Compared with sham-operated controls, banded animals had increased LV weight-to-body weight ratio (2.8 +/- 0.1 and 3.5 +/- 0.1, respectively; P = 0.035). Left ventricles from additional age-matched groups of mice that underwent identical surgical procedures were examined for altered transcriptional control of myosin heavy chains (MHCs). beta-MHC protein content increased (15 +/- 2%) vs. shams (3.8 +/- 2%; P = 0.004). Dot blots of LV RNA showed a corresponding increase in beta-MHC transcripts in banded animals (15.8 +/- 2%) vs. controls (5.7 +/- 2%; P = 0.012). Contractile performance was assessed using enzymatically disaggregated isolated LV myocytes paced at 0.5 Hz. There was no difference in percentage myocyte shortening between banded (8.6 +/- 0.5%) and control (9.1 +/- 0.5%) animals. However, maximal velocity of contraction was depressed after aortic banding (129 +/- 11 vs. 233 +/- 28 microns/s; P = 0.007), as was velocity of relaxation (105 +/- 11 vs. 188 +/- 22 microns/s; P = 0.007). These results suggest that depressed myocyte contractility after induction of pressure-overload hypertrophy in aortic-banded mice may be, in part, a consequence of transcriptional upregulation of the beta-MHC.

Animals↗
PubMed1994

In vivo assessment of left atrial contractile performance in normal and pathological conditions using a time-varying elastance model.

BACKGROUND: Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo. METHODS AND RESULTS: Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2, .92 to .99). There were significant time-dependent increases in the slopes [E(t)] and small but statistically insignificant decreases in the volume axis intercepts [VO(t)] of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA volume). Emax was not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL, P < .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/- 1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals. CONCLUSIONS: We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E(t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads.

Animals↗
PubMed1994

Effects of maternal smoking on adverse pregnancy outcomes: examination of the criteria of causation.

Smoking during pregnancy has been associated with many adverse pregnancy outcomes. However, debate continues about whether smoking causes these outcomes. This review of the criteria of causation found that the relative risk of having a low-birth-weight baby is nearly doubled in women who smoke during pregnancy compared with nonsmoking women and that the relative risks of spontaneous abortion and perinatal and neonatal mortality are increased by about one-third. The magnitude of the long-term effects of maternal smoking on the physical and mental development of the offspring is small but measurable. The epidemiologic evidence associating maternal smoking with major adverse pregnancy outcomes in prospective and case-control studies displays a high degree of consistency. A dose-response gradient for smoking during pregnancy has not been clearly shown in relation to perinatal and neonatal mortality. However, there is strong support for a dose-response gradient in relation to low birth weight and spontaneous abortion and moderate support for long-term developmental effects. Although a biological causal mechanism has not been clearly delineated, considerable evidence indicates that the chemicals in tobacco smoke are capable of producing deleterious changes in the placenta and fetus.

Abortion, Spontaneous↗
PubMed1994

Myocardial uptake and kinetic properties of technetium-99m-Q3 in dogs.

UNLABELLED: We postulated that 99mTc-Q3, a cationic imaging agent, produces myocardial activity related to myocardial blood flow during myocardial ischemia and pharmacologic coronary artery vasodilation, and shows little or no myocardial redistribution over 4 hr after intravenous injection. METHODS: In six Group 1 dogs, the chest was opened, the left circumflex coronary artery was acutely ligated, and dipyridamole (0.32, 0.56 or 0.84 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q3. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized and 357 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was counted and myocardial blood flow calculated. In nine Group 2 dogs, a variable occluder was placed around the left circumflex coronary artery and an ischemic level of circumflex blood flow was maintained constant over 4 hr as measured by an ultrasonic flow meter. Dipyridamole (0.56 mg/kg) was then infused into the right atrium followed by 10 mCi of 99mTc-Q3. Gamma camera images were acquired at 5, 15, 30, 60, 120 and 240 min following 99mTc-Q3 injection. Microsphere blood flow and endocardial biopsies (n = 6 dogs) were performed at 30, 60, 120 and 240 min following 99mTc-Q3 injection. RESULTS: In the Group 1 animals, 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 6.1 ml/min/g by the relationship y = 0.83X + 0.18, r = 0.95, p = 0.0001. The scintigraphic ratio of myocardial perfusion defect zone counts-to-normal myocardial zone counts (0.54 +/- 0.05 at 30 min) remained constant over 4 hr, as did technetium counts from direct endocardial sampling. Scintigraphic count ratios allowed discrimination between perfusion defect and normal myocardial regions beginning at 5 min following 99mTc-Q3 injection. CONCLUSIONS: Over a range of myocardial blood flows from 0 to 6.1 ml/min/g, 99mTc-Q3 myocardial activity is related to myocardial flow at the time of tracer injection. Technetium-99m-Q3 shows no evidence of myocardial redistribution over a 4-hr period.

Animals↗
PubMed1994

Comparison of technetium-99m-Q3 and thallium-201 for detection of coronary artery disease in humans.

UNLABELLED: Technetium-99m-Q3 is a myocardial imaging agent that produces prompt myocardial visualization in humans. METHODS: In 19 patients with angiographic coronary artery disease, 2 patients with no angiographic coronary artery stenosis greater than 50% of the luminal diameter and 6 healthy volunteers, exercise and resting myocardial imaging were performed with 99mTc-Q3 and also with 201Tl. Technetium-99m-Q3 imaging began 15 min after injection at rest and with exercise, in a complete imaging sequence that required less than 100 min. RESULTS: Overall accuracy for coronary disease detection was 78% (21 true-positive or true-negative studies among 27 study participants) by tomographic thallium imaging versus 89% for 99mTc-Q3 tomographic imaging (p = ns). Accuracy for detection of individual coronary stenoses was 75% (61 true-positive or true-negative coronary segment classifications among 81 total coronary segments) for 201Tl imaging and 83% for 99mTc-Q3 imaging (p = ns). CONCLUSIONS: Technetium-99m-Q3 when used in a rest-exercise sequence that can be completed in 100 min appears to provide comparable diagnostic accuracy to 201Tl for overall coronary disease detection and detection of individual coronary artery stenoses.

Adult↗
PubMed1993

Correlated expression of atrial myosin heavy chain and regulatory light chain isoforms with pressure overload hypertrophy in the non-human primate.

OBJECTIVE: The aim was to determine the extent to which myosin heavy chain and light chain isoform transitions in atrial myocardium are coordinately regulated under pathological conditions in tissue from normal baboons, hypertensive baboons with myocardial hypertrophy, and baboons in which hypertrophy had regressed. METHODS: Quantitative distributions of myosin heavy chain (MHC) and regulatory myosin light chain (MLC2) isoforms in atrial myocardium from 35 adult baboons were determined by electrophoresis under denaturing conditions and laser densitometry. RESULTS: A significant association was observed between the ratios of MHC and MLC2 isoforms in atrial myocardium (r = 0.73, p < 0.001, n = 69). Expressions of alpha MHC and atrial MLC2 (ALC2) isoforms were correlated in atrial myocardium, as were those of beta MHC and ventricular MLC2 (VLC2) isoforms. In a subset of baboons with experimentally induced renal hypertension (n = 12) both beta MHC and VLC2 isoforms were found at higher levels in left atria than were present in normotensive baboons (p = 0.006, n = 15). Left atria from hypertensive baboons with regressed LVH contained intermediate levels of both beta MHC and VLC2 isoforms. CONCLUSIONS: There is tight coupling between the expression of myosin subunit isoforms under pathological conditions from a primate species closely related to humans. The data suggest that the synthesis of these subunits of myosin may be coordinated at the molecular level.

Animals↗
PubMed1993

Comparative assessment of regional left atrial perfusion by laser Doppler and radionuclide microsphere techniques.

OBJECTIVE: The aim was to study the relation between left atrial microcirculatory flux, using laser Doppler flowmetry (LDF), and blood flow, using radiolabelled microspheres (MS). METHODS: Studies were done in five anaesthetised dogs. LDF probes were sewn to the appendage and body of the left atrium. Radionuclide spheres (15 microns) were used to quantitate blood flow at baseline, and during atrial pacing at 3.5 Hz, atrial fibrillation, and intravenous adenosine infusion (1 mg.kg-1 x min-1). RESULTS: In the left atrial body, both MS and LDF perfusion increased significantly during pacing and adenosine infusion; only LDF registered significant increases during atrial fibrillation. In the left atrial appendage, MS flow failed to increase significantly with any intervention and LDF perfusion increased significantly only during atrial fibrillation. There was a significant but weak correlation (r = 0.36, p < 0.05) between LDF and MS when data from all sample sites (n = 40) were compared, but good correlation when only baseline and pacing data were compared (r = 0.72, p = 0.0004, n = 20). In four additional dogs with heart failure [mean left atrial pressure 25.3(SD 7.4) mm Hg] produced by three weeks of rapid right ventricular pacing, flux values at baseline were increased significantly compared to control dogs and the responses registered by LDF to pacing, atrial fibrillation, and adenosine infusion were attenuated markedly. CONCLUSIONS: (1) Microcirculatory flux detected by LDF can identify the direction, and to a lesser extent, the magnitude of changes in regional atrial perfusion; and (2) LDF may be useful in identifying abnormalities of vasodilator reserve that accompany chronic left atrial myocardial dysfunction.

Animals↗
PubMed1993

Determination of left atrial volume using sonomicrometry: a cast validation study.

We developed a technique for left atrial (LA) volume estimation using two pairs of sonomicrometers sewn to the anteroposterior (LAX) and mediolateral (SAX) LA diameters and validated the method against water displacement of LA casts in 15 dogs. LA pressure was adjusted to a preselected level (5, 10, or 15 mmHg) by dextran infusion and was matched by postmortem infusion of casting resin (Conthane DPEN-18402). LA volume was modeled empirically as an ellipsoid of revolution without regression constants [(SAX)2(LAX)]. There was a strong correlation between the calculated LA volume and water displacement of the LA body [r = 0.87, standard error of estimate (SEE) = 3.3 ml, P = 0.0001] but a weaker correlation against water displacement of the entire LA (body+appendage, r = 0.81, SEE = 3.9 ml, P = 0.0003). The appendage volume fraction (appendage volume/total LA volume), as determined by water displacement of the casts, increased with increasing LA size (r = 0.78, P = 0.001). These data indicate that, in the normal canine heart, LA volume can be estimated accurately with high temporal and spatial resolution sonomicrometry using two atrial dimensions, and the contribution of appendage to total LA volume may become significant as the atrium enlarges.

Animals↗
PubMed1993

Influence of pericardium on left atrial compliance and pulmonary venous flow.

We studied seven open-chest anesthetized dogs to test the hypothesis that left atrial (LA) compliance is increased after pericardiectomy and to determine the effect of pericardiectomy on left atrial reservoir and conduit function. Two orthogonal sonomicrometer crystal pairs were used to estimate LA volume, and LA filling was assessed with a pulmonary vein (PV) flow probe. The left ventricular (LV) systolic (JFTI) and diastolic (KFTI) PV flow integrals were used as indexes of LA reservoir and conduit function, respectively. Diastolic LV transmitral flow was assessed with transesophageal Doppler echocardiography. Data were acquired over a wide range of intracardiac pressures and volumes obtained by intravenous hetastarch infusion both before and after pericardiectomy. The mean dynamic stiffness constant of the LA diastolic pressure-volume relation was significantly greater before pericardiectomy than afterwards (0.15 +/- 0.04 vs. 0.08 +/- 0.03 ml-1, P < 0.05). Data were analyzed before and after pericardiectomy at three matched levels of left atrial pressure (LAP; 7, 13, and 20 mmHg). The J-to-KFTI ratio increased significantly with volume infusion and was significantly less after pericardiectomy than before (1.2 +/- 0.7 vs. 1.2 +/- 0.6, 1.8 +/- 0.6 vs. 2.2 +/- 0.9, and 2.0 +/- 0.8 vs. 2.6 +/- 0.9 at low, mid, and high levels of LAP, respectively; P < 0.05 at mid and high levels of LAP). Peak early transmitral velocity increased with both volume infusion and pericardiectomy. We conclude that pericardiectomy increases LA compliance and early LV filling rate and is accompanied by a relatively greater augmentation in conduit than reservoir function of the left atrium.

Animals↗
PubMed1993

Altered left atrial compliance after atrial appendectomy. Influence on left atrial and ventricular filling.

Previous studies have shown regional differences in atrial distensibility. We studied 12 open-chest dogs to test the hypothesis that left atrial compliance is decreased after removal of the left atrial appendage and to determine the effect of altered atrial compliance on atrial reservoir and conduit function. Sonomicrometer crystal pairs were used to measure the long- and short-axis diameters of the left atrium over a wide range of intracardiac pressures and volumes obtained by intravenous hetastarch infusion both before and after suture ligation of the left atrial appendage (appendectomy). Pulmonary venous flow was measured with an ultrasonic flowmeter, and transmitral flow velocities were measured with transesophageal Doppler echocardiography. After appendectomy, the diastolic pressure-volume relation was shifted upward and to the left in six of seven dogs. The mean dynamic stiffness constant of the left atrial diastolic pressure-volume relation was significantly greater after appendectomy than before (0.20 +/- 0.11 [mean +/- SD] versus 0.14 +/- 0.08 ml-1, p < 0.01); the mean y intercept was slightly, but significantly, less after appendectomy (0.6 +/- 0.3 versus 1.3 +/- 0.6 mm Hg, p < 0.05). The left atrial reservoir volume (maximum minus minimum left atrial volume) was significantly less after appendectomy at matched left atrial pressures. The systolic to diastolic flow integral ratio of pulmonary venous flow (JFTI/KFTI), an index of the relative reservoir to conduit functions of the left atrium, increased significantly with volume infusion only before appendectomy; at matched left atrial pressure, JFTI/KFTI was significantly less afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Load independence of early diastolic filling parameters in the anesthetized canine model.

To evaluate radionuclide diastolic filling indices during acute pharmacologic changes in ventricular loading, 11 atrially paced dogs underwent simultaneous micromanometer left atrial and left ventricular pressure measurements. During phenylephrine infusion, systolic blood pressure increased from 110 +/- 16 (s.d.) to 147 +/- 19 mmHg (p < 0.01), causing the atrioventricular gradient to increase from 5 +/- 2 to 8 +/- 5 mmHg (p < 0.03) with no change in the time constant of isovolumic relaxation (Tau). Absolute peak filling rate increased from 40 +/- 21 to 59 +/- 44 kcts/sec (p < 0.05), but there was no change in first-half filling fraction. During dobutamine infusion, Tau shortened from 43 +/- 13 msec to 33 +/- 5 msec (p < 0.01) and first-half filling fraction increased from 39% +/- 19% to 56% +/- 18% (p < 0.05), with no change in atrioventricular gradient or absolute peak filling rate. Absolute changes from baseline for the first-half filling fraction were inversely proportional to absolute changes in Tau (r = -0.76, p < 0.05). We conclude that the left ventricular absolute peak filling rate is a load dependent index of diastolic function. In contrast, the radionuclide first-half filling fraction is independent of loading conditions, but is sensitive to substantial alterations in the rate of left ventricular isovolumic myocardial relaxation.

Animals↗
PubMed1993

Family caregivers of institutionalized and noninstitutionalized elderly individuals.

This article provides an overview of the literature that has examined the issues of institutionalization and community care of elderly persons. Specifically, those studies are discussed that report on the family's decision to institutionalize the elderly person and those that report on the effect of institutionalization of the family. Studies about community caregiving that report on caregiver characteristics, the stress of caregiving, and interventions to manage care issues and caregiver stress also are detailed. Implications for nursing research and practice can be derived from the article.

Adaptation, Psychological↗