How to help patients stop smoking.
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Adolescent↗
Biomedical subjects
R A Walsh
Publications and source records attributed to R A Walsh.
Regional atrial distensibility.
We studied 12 open-chest dogs to determine whether there are regional differences in left atrial distensibility. Sonomicrometer crystal pairs were used to measure the anteroposterior diameters of the left atrial body and appendage simultaneously over a wide range of intracardiac pressures and volumes obtained by intravenous saline infusion. Left atrial pressure-natural strain data for the body and appendage were fitted to an exponential function. The mean coefficient of the left atrial monoexponential pressure-strain relationship was greater for the body than appendage (3.1 +/- 1.1 vs. 1.9 +/- 0.7 mmHg, P less than 0.01). The Y-intercepts were not significantly different (5.2 +/- 1.7 vs 4.9 +/- 1.8 mmHg). The maximum minus minimum left atrial dimension, an index of the reservoir function of the atrium, increased with volume infusion in both the body and appendage and was significantly greater in the appendage than body at each level of left atrial pressure. Similarly, atrial systolic shortening fraction increased with volume infusion, and regional shortening was greater in the appendage than the body at each level of left atrial pressure. We conclude that regional differences in atrial distensibility exist in vivo and may play an important role in modulating systolic and diastolic function of the left atrium.
Animals↗
Influence of loading conditions and contractile state on pulmonary venous flow. Validation of Doppler velocimetry.
BACKGROUND: Although recent studies suggest that pulmonary venous flow velocities may be used to evaluate left ventricular diastolic function, the influence of loading conditions and contractile state on the magnitude and pattern of pulmonary venous flow are poorly understood. METHODS AND RESULTS: Fourteen anesthetized open-chest mongrel dogs were instrumented with pulmonary venous flow probes, atrial sonomicrometer crystal paris, and high-fidelity micromanometers; transesophageal Doppler echocardiography was used to obtain simultaneous pulmonary venous flow velocities. Measurements were made over a wide range of left atrial pressure obtained by either intravascular volume infusion and inferior vena caval balloon inflation (n = 8), halothane inhalation (n = 6), or phenylephrine infusion (n = 5). There was an excellent correlation for pulmonary venous systolic (J) to diastolic (K) time integral between the Doppler and flow probe signal (r = 0.94; SEE, 0.18). When left atrial pressure was increased by volume infusion, there was a significant linear relation between mean left atrial pressure and the Doppler J/K peak (r = 0.64; SEE, 3.4 mm Hg) and flow velocity-time integral ratio (r = 0.75; SEE, 2.9 mm Hg). By contrast, when left atrial pressure was elevated by halothane-induced cardiac depression, there was no correlation. The independent determinants of the pattern of pulmonary venous flow (stepwise multiple linear regression analysis) under all conditions were atrial systolic shortening, aortic systolic pressure, heart rate, and left ventricular end-systolic dimension (cumulative r = 0.80). CONCLUSIONS: The pattern of pulmonary venous flow can be measured accurately with Doppler velocities and is differentially influenced by loading conditions and myocardial contractile state; in the absence of myocardial contractile dysfunction, the pattern of pulmonary venous flow may provide an estimate of left atrial pressure; and pulmonary venous flow is determined largely by atrial systolic function.
Animals↗
Simultaneous cardiac mechanics and phosphorus-31 NMR spectroscopy during global myocardial ischemia and reperfusion in the intact dog.
To investigate the high-energy phosphate metabolic correlates of left ventricular (LV) dysfunction during the onset and recovery from severe, global myocardial ischemia in vivo, seven preinstrumented closed-chest dogs had ECG-gated phosphorus-31 (31P) NMR-spectroscopy (NMR-S) studies performed and LV micromanometer and sonomicrometer data measured before, during, and every 5 min following severe occlusive global myocardial ischemia. Ischemic LV + dP/dtmax fell from 2396 +/- 576 mm Hg/s at baseline to 2185 +/- 478 mm Hg/s (p less than 0.05) and did not normalize until after 30 min of reperfusion. LV ejection fraction (EF) decreased significantly (0.32 +/- 0.07 EF units to 0.12 +/- 0.13 EF units; p less than 0.05) and did not recover by 30 min of reperfusion (0.27 +/- 0.09 units; P less than 0.05 vs baseline). Simultaneous 31P NMR-S studies demonstrated excellent beta-ATP signal-to-noise (10 +/- 4:1). Myocardial acidosis occurred during global ischemia (delta pH = -0.22 +/- 0.23 units; p less than 0.05), with recovery at 30 min of reperfusion. Inorganic phosphate/phosphocreatine ratio (Pi/PCr) increased significantly during ischemia (0.46 +/- 0.07 to 0.61 +/- 0.07; P less than 0.05), with delayed normalization of this ratio at 30 min of reperfusion. beta-ATP peak area did not change during ischemia. Pi/PCr and LV contractility (+dP/dtmax) were significantly correlated at baseline (r = -0.70) and during global ischemia (r = -0.78; p less than 0.01), but not during recovery (r = 0.006; p = NS). Therefore, the simultaneous evaluation of high-fidelity hemodynamic data and topical 31P NMR-S can be performed in the intact state.
Adenosine Triphosphate↗
Opioid drug accidental deaths in the Newcastle area of New South Wales, 1970-1987.
Opioid drug accidental deaths were reviewed in coronial post-mortem files of the Newcastle City Morgue, New South Wales, between 1970 and 1987. There were 23 accidental deaths directly caused by opioids, with 19 deaths (83%) involving the use of heroin/morphine. Deaths on weekends/public holidays were over-represented compared with weekdays. In 14 cases (61%), the police notes suggested that help-seeking had been inappropriately delayed by people in the presence of the subject. In almost half the cases where blood alcohol analyses were performed, the results were positive with a mean of 0.14 g alcohol per 100 ml. For a shorter time period 1985-1987, opioid-related suicides were also examined. Data on the five subjects involved in the suicides suggested they were a different target group for prevention. Opioids appear to be a very much smaller cause of death than alcohol and tobacco in the Newcastle Area.
Journal Article↗
Diastolic dysfunction as a precursor of myocardial damage by reoxygenation.
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Animals↗
Rorschach assessment of purging and nonpurging bulimics.
Research in bulimia has flourished in recent years, and yet minimal attention has been devoted to explorations of the bulimic's basic personality organization. We utilized the Rorschach to differentiate between purging and nonpurging bulimics and controls. There were 15 subjects in each group. The Comprehensive System (Exner, 1986) was used for the scoring of the protocols. Statistically significant differences were not found between the two bulimia groups, but interesting trends were detected in the areas of depression, anger, and self-preoccupation. Results appear to be constrained by the low rate of purging behavior. Comparisons between the combined bulimia groups and the controls resulted in solidly characterizing the bulimics as displaying perceptual inaccuracies, disordered thinking, a vulnerability to interpersonal problems, a damaged self-image, and a pessimistic outlook. The strengths of the study were its use of the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987) nonpatients bulimic subtypes and a control group that was comparable in terms of demographics. Future Rorschach studies with bulimics displaying higher frequencies of binging and purging behaviors are suggested.
Adaptation, Psychological↗
Selenium as a protector of diastolic function during oxidant stress.
Interventional studies yielded conflicting results on reperfusion injury. They are unable to discriminate between lesions due to ischemia or to additional damage during reoxygenation. Since reactive oxygen metabolites have been implicated as a major cause of reperfusion injury, 375 nmol/min of hydrogen peroxide was infused in a Langendorff rat heart preparation as a model of oxidant stress without previous ischemic contractile dysfunction. Impaired endogenous defense was remodeled, using selenium-deficient hearts with reduced glutathione peroxidase activity. Measurements of hemodynamic parameters demonstrate increased myocardial susceptibility to oxidant stress in hearts with decreased antioxidant defense. Defined concentrations of hydrogen peroxide produce isolated impairment of active and passive diastolic properties of the ventricle in this model.
Animals↗
Comparative effects of pacing-induced and flow-limited ischemia on left ventricular function.
We compared left ventricular (LV) myocardial blood flow and function accompanying severe demand ischemia (rapid atrial pacing in the presence of critical bilateral coronary stenoses) and supply ischemia (complete bilateral coronary occlusion) of the same ischemic regions in 14 pentobarbital-anesthetized dogs. Pacing-induced ischemia resulted in pronounced reductions in average regional epicardial blood flow (0.8 +/- 0.4 vs. control 1.2 +/- 0.4 [+/- SD] ml/g/min, p less than 0.05) and endocardial blood flow (0.4 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05). More severe reductions in average regional epicardial and endocardial blood flow were seen after bilateral coronary occlusion (BCO) (0.3 +/- 0.3 and 0.1 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05, respectively). Hemodynamics of postpacing ischemia (PPi) were consistently characterized by systolic impairment including depressed systolic contractile performance [(+)dP/dtmax 1,281 +/- 442 vs. control 2,173 +/- 775 mm Hg/sec, p less than 0.05], ventricular dilation (left ventricular [LV] end-diastolic dimension [EDD] 47.6 +/- 7.8 vs. control 44.7 +/- 8.6 mm, p less than 0.05), and an increase in LV end-diastolic pressure (EDP) (14.4 +/- 2.8 vs. control 4.2 +/- 2.8 mm Hg, p less than 0.05). Abnormalities in early and late diastolic function with PPi included increased time constant of isovolumic relaxation (78.0 +/- 40.4 vs. control 46.4 +/- 20.5 msec, p less than 0.05) and increased chamber stiffness (1.9 +/- 0.77 vs. control 0.81 +/- 0.55 mm Hg/mm, p less than 0.05), respectively. The LV diastolic pressure-dimension relation, however, shifted upward and to the right in eight of nine animals, whereas an upward shift was observed in only one animal. Thus, in this model of postpacing ischemia, we observed contractile failure and passive changes in diastolic function. Alterations in ventricular function occurred consistently earlier and to a greater extent during BCO than PPi, including higher LVEDP (25.3 +/- 8.1 vs. 14.9 +/- 6.6 mm Hg, p less than 0.05), greater ventricular dilation (delta LVEDD 4.9 +/- 2.5 vs. 3.5 +/- 2.8 mm, p less than 0.05), and reduced minor-axis dimension shortening (3.3 +/- 3.1% vs. 6.5 +/- 3.6%, p less than 0.05). To detect potential qualitative differences in ventricular function between the two types of ischemia, we evaluated hemodynamics at comparable loading conditions (30 seconds to 1 minute of BCO).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Sympathetic control of diastolic function in congestive heart failure.
Sympathetic cardiac stimulation is a major extrinsic compensatory mechanism that maintains or augments systolic and diastolic ventricular function during physiological stress or pathological conditions. In particular, catecholamines may selectively improve diastolic function by reducing myofilament calcium sensitivity, accelerating sequestration of calcium into the sarcoplasmic reticulum, and increasing the rate of actin-myosin cross-bridge turnover. These subcellular mechanisms, unique to inotropic agents that increase myocyte cyclic adenosine monophosphate, result in an increased rate and extent of ventricular relaxation and diastolic filling and a decrease in cardiac filling pressures. Despite these potentially favorable biochemical and mechanical actions, a number of limitations and theoretical concerns remain to be addressed before catecholamine therapy is widely administered to patients with congestive heart failure and diastolic dysfunction.
Animals↗
Effect of intravenous metoprolol on left ventricular performance in Q-wave acute myocardial infarction.
To determine the effects of intravenous metoprolol on left ventricular (LV) function in acute myocardial infarction (AMI), 16 patients were studied within 48 hours of Q-wave AMI (mean ejection fraction 47 +/- 6%, mean pulmonary artery wedge pressure 22 +/- 6 mm Hg) with high fidelity pressure and biplane cineventriculography before and after intravenous metoprolol (dose 12 +/- 4 mg). Heart rate decreased from 90 +/- 13 to 74 +/- 11 beats/min (p less than 0.001), pulmonary arterial wedge pressure and LV end-diastolic pressure were unchanged (22 +/- 6 to 21 +/- 6 and 27 +/- 8 to 26 +/- 8 mm Hg, respectively), despite impaired LV relaxation (P = Poe-t/T) after intravenous metoprolol (T from 59 +/- 13 to 72 +/- 12 ms, p less than 0.001). Peak systolic circumferential LV wall stress decreased after beta-adrenergic blockade (330 +/- 93 to 268 +/- 89 g/cm2, p less than 0.05) and LV contractility decreased (dP/dtmax from 1,480 +/- 450 to 1,061 +/- 340 mm Hg/s, p less than 0.001). The ejection fraction decreased (48 +/- 7 to 43 +/- 7%, p less than 0.05) due to an increase in LV end-systolic volume (85 +/- 19 to 93 +/- 19 ml, p less than 0.05) since LV end-diastolic volume was unchanged (161 +/- 30 to 163 +/- 30 ml, difference not significant). In patients with Q-wave AMI, intravenous metoprolol reduces the major determinants of myocardial oxygen demand including heart rate, contractility and peak systolic wall stress. Further, despite decreased heart rate, (+)dP/dtmax, ejection fraction, isovolumic relaxation, LV end-diastolic pressure and end-diastolic volume remain unchanged.
Adult↗
Diltiazem attenuates the inotropic and peripheral vascular effects of cardiac glycosides.
The influence of diltiazem on the hemodynamic effects of ouabain in 10 preinstrumented awake dogs was studied. Mean aortic pressure increased from 102 to 119 mm Hg with ouabain (p less than 0.05), an effect that was attenuated by pretreatment with diltiazem. The increase in systemic vascular resistance of 30% with ouabain was ablated by prior diltiazem. Heart rate did not significantly change with ouabain or with diltiazem plus ouabain, but intravenous diltiazem alone produced a reflex increase in heart rate of 26%. Left ventricular (LV) end-diastolic dimension was significantly greater with ouabain alone, but not with ouabain after pretreatment with diltiazem. LV dP/dt max increased by 40% with ouabain alone, but by only 23% (p less than 0.001) after pretreatment with diltiazem plus ouabain. When observed at matched preload and heart rate, diltiazem markedly attenuates the positive inotropic and peripheral arterial constrictive effects of acute ouabain administration in the conscious animal with normal LV function.
Animals↗
Diastolic dysfunction of perfused rat hearts induced by hydrogen peroxide. Protective effect of selenium.
Oxidant substances such as hydrogen peroxide are postulated to cause cardiac dysfunction and injury in a number of pathological conditions. Selenium is an essential nutrient which serves as an oxidant defense through the selenoenzyme glutathione peroxidase. This enzyme metabolizes hydrogen peroxide; its activity in rat heart is reduced to 5% of control by selenium deficiency. Left ventricular function of selenium-deficient and control rat hearts was studied in a Langendorff preparation under isovolumic conditions. A stabilization period of 20 min was followed by a 70 min infusion of hydrogen peroxide at 375 or 1500 nmol/min. When no hydrogen peroxide was infused, perfusion for 90 min had no effect on systolic or diastolic function and no effect of selenium deficiency was detected. Hydrogen peroxide infusion into selenium-deficient hearts at 375 nmol/min led to impaired isovolumic relaxation and a substantial increase in end-diastolic pressure after 45 min which worsened progressively until the experiment was terminated. By contrast no effect was observed on systolic contractile function as assessed by peak pressure or developed pressure. Infusion of this dose of hydrogen peroxide into control hearts had no significant effect on diastolic or systolic function. However, infusion of 1500 nmol hydrogen peroxide/min into control hearts caused diastolic dysfunction after 30 min without affecting systolic function. These results indicate that hydrogen peroxide injury to the perfused rat heart is manifested by diastolic dysfunction before systolic dysfunction occurs. Selenium deficiency lowers the dose of hydrogen peroxide needed to cause diastolic dysfunction. This suggests that the selenoenzyme glutathione peroxidase protects the heart against hydrogen peroxide injury.
Animals↗
Alpha-myosin heavy chain cDNA structure and gene expression in adult, fetal, and premature baboon myocardium.
To examine cardiac myosin gene structure and expression in a non-human primate model for human heart development and disease, we have constructed a cDNA library from baboon atrium and used baboon beta-myosin heavy chain (beta-MHC)* cDNA probes to isolate atrial MHC clones. The nucleotide sequence of one such clone, lambda BMHC alpha 3, contains sequences that encode part of the light meromyosin region (LMM) and the 3' untranslated region of the baboon alpha-MHC. To study cardiac MHC gene transcription, we constructed probes from the baboon alpha-MHC cDNA for S1 nuclease analyses of RNA from atria and ventricles. To examine translational regulation of cardiac MHC gene expression, we used monoclonal antibodies (MAb) against specific alpha- and beta-MHC epitopes for Western blot analyses. In atria and ventricles from adult baboons, we detected predominantly alpha- and beta-MHC gene transcripts, respectively. In ventricles from fetal baboons at two stages of development (140 and 160 days gestation), we also detected predominantly beta-MHC gene transcripts and isoforms. To investigate changes induced by parturition, we obtained ventricles from baboons that were prematurely delivered at 140 days gestation and supported for 10 days in an extrauterine environment. In contrast to adult and fetal patterns, we observed an increase in alpha-MHC transcripts and isoforms in ventricles of premature baboons. Because alpha-MHC gene expression is increased in premature baboons (total age of 150 days) compared to their older 160 day fetal counterparts, the induction of ventricular alpha-MHC synthesis must have resulted from factor(s) associated with parturition or prolonged mechanical ventilation rather than at predetermined stages of gestational development.
Amino Acid Sequence↗
Load dependence of the single beat maximal pressure (stress)/volume ratios in humans.
To determine whether the slopes of the single beat maximal pressure (stress)/volume ratios are sensitive to changes in loading conditions in humans, 16 patients without cardiac disease were studied with simultaneous micromanometer-determined left ventricular pressures and biplane contrast cineangiograms under control conditions and during methoxamine and nitroprusside infusions. Left ventricular volumes were calculated with use of a Simpson's rule algorithm, wall thickness was obtained iteratively, and both midwall circumferential and meridional stresses were computed frame by frame. The maximal pressure/volume and both circumferential and meridional maximal stress/volume ratios were calculated using a single beat from each loading condition assuming a zero volume-axis intercept. Mean left ventricular systolic pressure increased 47% during the methoxamine infusion and decreased 22% during the nitroprusside infusion compared with control (p less than 0.001 for both). Despite these changes in left ventricular systolic pressure, heart rate was eliminated as a confounding variable by right atrial pacing; and mean maximal rate of change of left ventricular pressure [(+)dP/dtmax] and rate of change at developed pressure 40 mm Hg [(+)(dP/dt) per DP40] values did not differ significantly. Mean single beat maximal pressure/volume ratios also did not differ significantly among the three loading conditions. In contrast, mean single beat circumferential and meridional maximal stress/volume ratios were 3.15 +/- 1.83 and 1.40 +/- 0.82 g/cm2 per ml at control; they increased to 4.47 +/- 2.44 and 2.21 +/- 1.25 g/cm2 per ml during the methoxamine infusion (p less than 0.001 for both), and they decreased during the nitroprusside infusion to 2.58 +/- 1.47 and 1.14 +/- 0.57 g/cm2 per ml (p less than 0.05 and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cardiac beta myosin heavy chain diversity in normal and chronically hypertensive baboons.
We have identified two distinct beta-myosin heavy chains (MHCs) present in baboon myocardium by electrophoresis in gradient pore gels and by Western blots with anti-MHC MAb. The two beta-MHCs have molecular masses of 210 and 200 kD and share several antigenic determinants including an epitope recognized by a beta-MHC-specific MAb. A fivefold increase in the level of the 200-kD beta-MHC was observed in the hypertrophied left ventricles of baboons with chronic (5.3 +/- 0.7 yr) renal hypertension. A 60% increase (P less than 0.01) in BP and a 100% increase (P less than 0.001) in left ventricular mass to body weight ratio occurred in hypertensive baboons compared with normotensive animals. The Ca2+-activated myosin ATPase activity in hypertrophied left ventricles was decreased by 35% (P less than 0.05) compared with controls. Normal levels of the 200-kD MHC were detected in the right ventricles and intraventricular septa of the hypertensive animals. These data suggest that cardiac MHCs of primates may exist in alternative molecular forms that are indistinguishable by nondenaturing gel electrophoresis and that increased concentration of a second beta-MHC is associated with ventricular hypertrophy (r = 0.55). The functional significance and mechanisms that control the concentration of beta-MHC subspecies remain to be determined.
Adenosine Triphosphatases↗
The effects of calcium entry blockade on normal and ischemic ventricular diastolic function.
There is increasing evidence that the clinically available calcium entry blockers (i.e., diltiazem, nifedipine, and verapamil) improve noninvasively determined indexes of diastolic filling in patients with chronic coronary artery disease, hypertensive heart disease, and hypertrophic cardiomyopathy. These favorable alterations in diastolic function are often associated with clinical improvement. Current information suggests that salutary indirect actions of these agents on ventricular loading, sympathetic reflexes, and myocardial supply-demand relations, rather than direct effects on transsarcolemmal myocyte calcium influx, underlie these beneficial effects.
Animals↗
Acute total aortic occlusion during cardiac catheterization associated with polycythemia vera.
We present a case of acute total aortic occlusion at the time of cardiac catheterization in a 62-yr-old female with an acute myocardial infarction and newly diagnosed polycythemia vera. Despite normalization of serum viscosity and red cell mass by phlebotomy, her predisposition to thrombosis persisted. Caution is advised when considering cardiac catheterization in patients with this disease.
Acute Disease↗