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Biomedical subjects

Bruce D Johnson

Publications and source records attributed to Bruce D Johnson.

At least 19 recordsLinked to original sources
PubMed2007

Postural differences in hemodynamics and diastolic function in healthy older men.

The shift from upright to supine posture increases stroke volume in healthy young adults, primarily through increased end-diastolic volume. Aging is associated with increased ventricular stiffness and impaired diastolic function. The purpose of this study was to determine whether the stroke volume change between the upright and supine posture was blunted in healthy older men and whether the early mitral inflow response to this postural change was reduced by aging. Pulsed Doppler echocardiography and tissue Doppler imaging were used to assess stroke volume and left ventricular function during upright and supine posture in 10 young and 12 older healthy men. Cardiac output was greater in the supine versus upright condition in both groups. In young men supine posture was associated with a large increment in stroke volume (63.1 +/- 7.2 upright to 98.6 +/- 11.7 ml supine; P < 0.05) and a decrease in heart rate. In older men, the stroke volume increment was smaller (63.9 +/- 3.6 upright to 82.0 +/- 5.7 ml supine; P < 0.05) and heart rate decreased less than young men when comparing upright to supine posture. Increased stroke volume was associated with higher peak early diastolic filling velocity (E) in young men and higher peak late diastolic filling velocity (A) in older men. These findings indicate that healthy aging attenuates the increase in early filling associated with moving from an upright to a supine posture. Furthermore, healthy older men are more dependent upon atrial diastolic filling to augment end-diastolic and stroke volume, which may be due to age-associated increases in left ventricular filling pressure and impaired compliance.

Adult↗
PubMed2007

Effects of acute changes in pulmonary wedge pressure on periodic breathing at rest in heart failure patients.

BACKGROUND: Patients with heart failure (HF) display a number of breathing abnormalities including periodic breathing (PB) at rest. Although the mechanism(s) contributing to PB remain unclear, we examined whether changes in pulmonary wedge pressure (PWP) and pulmonary vascular resistance (PVR) alter PB in patients with established HF. METHODS: We studied 12 male patients with HF (age, 50 +/- 11 years; ejection fraction, 18.3 +/- 3.8 %; New York Heart Association class, 3.2 +/- 0.4), with PB at rest, who are undergoing right heart catheterization with infusion of nitroprusside. RESULTS: At baseline, patients with HF displayed minute ventilation (V(E)) oscillations with amplitude of 5.5 +/- 2.7 L/min (57 +/- 34% of the average V(E)) and cycle length of 61 +/- 18 seconds. Cardiac index (CI), PVR, and mean PWP averaged 2.0 +/- 0.4 L min(-1) m(-2), 281.9 +/- 214.9 dyne/s per cm(-5), and 28.3 +/- 5.4 mm Hg, respectively. During nitroprusside infusion, CI increased to 3.1 +/- 0.6 L min(-1) m(-2), PVR decreased to 163.9 +/- 85.2 dyne/s per cm(-5), and PWP fell to 10.0 +/- 4.2 mm Hg. Nitroprusside reduced the amplitude (2.6 +/- 2.4 L/min, 23 +/- 21% of average V(E); P < .01) and cycle length (41.4 +/- 28.8 seconds; P < .01) of V(E) oscillations while abolishing oscillations in 3 patients. Although average V(E) and PaCO2 remained unchanged, there was a significant increase in the ratio of tidal volume to inspiratory time (V(T)/T(I); P < .01), suggesting an increase in ventilatory drive. The change in the amplitude of V(E) oscillations was positively correlated with the change in PWP (r = 0.75; P < .01), negatively correlated with the change in PVR (r = 0.63; P < .05), and not correlated with the change in CI. CONCLUSIONS: These data suggest that PWP (left atrial pressure) may play a direct role in the PB observed in HF at rest.

Adult↗
PubMed2006

Retail marijuana purchases in designer and commercial markets in New York City: sales units, weights, and prices per gram.

This paper documents the bifurcation of the market for commercial marijuana from the market for designer marijuana in New York City. Commercial marijuana is usually grown outdoors, imported to NYC, and of average quality. By contrast, several varities of designer marijuana are usually grown indoors from specially bred strains and carefully handled for maximum quality. The mechanisms for marijuana sales include street/park sellers, delivery services, private sales, and storefronts. Retail sales units vary from 5 dollars to 50 dollars and more, but the actual weights and price per gram of retail marijuana purchases lacks scientific precision. Ethnographic staff recruited marijuana purchasers who used digital scales to weigh a purposive sample of 99 marijuana purchases. Results indicate clear differences in price per gram between the purchases of commercial (average 8.20 dollars/g) and designer (average 18.02 dollars/g) marijuana. Designer purchases are more likely to be made by whites, downtown (Lower East Side/Union Square area), via delivery services, and in units of 10 dollar bags, 50 dollar cubes, and eighth and quarter ounces. Commercial marijuana purchases are more likely to be made by blacks, uptown (Harlem), via street dealers, and in units of 5 dollar and 20 dollar bags. Imported commercial types Arizona and Chocolate were only found uptown, while designer brand names describing actual strains like Sour Diesel and White Widow were only found downtown. Findings indicate clear divisions between commercial and designer marijuana markets in New York City. The extent that these differences may be based upon different THC potencies is a matter for future research.

Asian People↗
PubMed2006

The effect of 18 h of simulated high altitude on left ventricular function.

High altitude produces increased pulmonary capillary pressure by hypoxia induced pulmonary vasoconstriction. It is also possible that hypoxia results in mildly elevated left ventricular (LV) filling pressures that may contribute to the elevated capillary pressures. This study investigates the impact of simulated high altitude on global and regional echocardiographic measures of LV performance and filling pressure. Seventeen healthy individuals underwent transthoracic echocardiography, including tissue Doppler of the septal mitral annulus and basal segments before and after an 18-h overnight stay in a high altitude simulation tent with a FiO(2) of 12%, simulating an altitude of approximately 4,000 m above sea level. In simulated high altitude, the ratio of early transmitral flow velocity to early myocardial relaxation velocity increased 22%, P < 0.001, and the Index of Myocardial Performance increased 30%, P < 0.01 due to an 58% increase in the isovolumic relaxation time (IVRT), P < 0.001. Simulated high altitude leads to a reduction in LV performance with an accompanying increase in markers of LV filling pressure. The significant changes in filling pattern and IVRT in the setting of normal and unchanged systolic function, indicates that hypoxia induces mild diastolic dysfunction in young healthy individuals.

Acclimatization↗
PubMed2006

The potential for accurately measuring behavioral and economic dimensions of consumption, prices, and markets for illegal drugs.

There are numerous analytic and methodological limitations to current measures of drug market activity. This paper explores the structure of markets and individual user behavior to provide an integrated understanding of behavioral and economic (and market) aspects of illegal drug use with an aim toward developing improved procedures for measurement. This involves understanding the social processes that structure illegal distribution networks and drug users' interactions with them. These networks are where and how social behaviors, prices, and markets for illegal drugs intersect. Our focus is upon getting an up close measurement of these activities. Building better measures of consumption behaviors necessitates building better rapport with subjects than typically achieved with one-time surveys in order to overcome withholding and underreporting and to get a comprehensive understanding of the processes involved. This can be achieved through repeated interviews and observations of behaviors. This paper also describes analytic advances that could be adopted to direct this inquiry including behavioral templates, and insights into the economic valuation of labor inputs and cash expenditures for various illegal drugs. Additionally, the paper makes recommendations to funding organizations for developing the mechanisms that would support behavioral scientists to weigh specimens and to collect small samples for laboratory analysis-by providing protection from the potential for arrest. The primary focus is upon U.S. markets. The implications for other countries are discussed.

Cross-Sectional Studies↗
PubMed2006

Short-term hypoxic exposure at rest and during exercise reduces lung water in healthy humans.

Hypoxia and hypoxic exercise increase pulmonary arterial pressure, cause pulmonary capillary recruitment, and may influence the ability of the lungs to regulate fluid. To examine the influence of hypoxia, alone and combined with exercise, on lung fluid balance, we studied 25 healthy subjects after 17-h exposure to 12.5% inspired oxygen (barometric pressure = 732 mmHg) and sequentially after exercise to exhaustion on a cycle ergometer with 12.5% inspired oxygen. We also studied subjects after a rapid saline infusion (30 ml/kg over 15 min) to demonstrate the sensitivity of our techniques to detect changes in lung water. Pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (D(M)) were determined by measuring the diffusing capacity of the lungs for carbon monoxide and nitric oxide. Lung tissue volume and density were assessed using computed tomography. Lung water was estimated by subtracting measures of Vc from computed tomography lung tissue volume. Pulmonary function [forced vital capacity (FVC), forced expiratory volume after 1 s (FEV(1)), and forced expiratory flow at 50% of vital capacity (FEF(50))] was also assessed. Saline infusion caused an increase in Vc (42%), tissue volume (9%), and lung water (11%), and a decrease in D(M) (11%) and pulmonary function (FVC = -12 +/- 9%, FEV(1) = -17 +/- 10%, FEF(50) = -20 +/- 13%). Hypoxia and hypoxic exercise resulted in increases in Vc (43 +/- 19 and 51 +/- 16%), D(M) (7 +/- 4 and 19 +/- 6%), and pulmonary function (FVC = 9 +/- 6 and 4 +/- 3%, FEV(1) = 5 +/- 2 and 4 +/- 3%, FEF(50) = 4 +/- 2 and 12 +/- 5%) and decreases in lung density and lung water (-84 +/- 24 and -103 +/- 20 ml vs. baseline). These data suggest that 17 h of hypoxic exposure at rest or with exercise resulted in a decrease in lung water in healthy humans.

Adult↗
PubMed2006

Smoking marijuana in public: the spatial and policy shift in New York City arrests, 1992-2003.

BACKGROUND: During the 1990s, the New York Police Department (NYPD) greatly expanded arrests for smoking marijuana in public view (MPV). By 2000, MPV accounted for 15% of all arrests. The NYPD's supporters report this arrest activity is just part of quality-of-life (QOL) policing, which seeks to promote order in public locations by aggressively patrolling for behaviors that offend the general population. The NYPD's critics contend the NYPD has disproportionately targeted poor, black and Hispanic communities. METHODS: This paper analyzes the geographic distribution of MPV arrests from 1992 to 2003 to evaluate these alternative perspectives. A sequence of maps identify that the focus of MPV arrests shifted over time. RESULTS: In the early 1990s, most MPV arrests were recorded in the lower half of Manhattan (NYC's business and cultural center) and by the transit police. However, in the later 1990s and into the 2000s, most MPV arrests were recorded in high poverty, minority communities outside the lower Manhattan area and by the NYPD's policing of low-income housing projects. CONCLUSION: These findings suggest that current levels of MPV arrests in NYC may not be justifiable, at least based solely on the purpose of QOL policing. Accordingly, we suggest the NYPD seriously consider less stringent measures for public marijuana smokers, especially for use outside of highly public locations in recessed locations hidden from open view (like the stairwell of a housing project). Alternatives could include Desk Appearance Tickets, fines, or simply requiring smokers to desist, discard their product, and move along.

Journal Article↗
PubMed2006

Relationship between cardiac output and oxygen consumption during upright cycle exercise in healthy humans.

The relationship between cardiac output (CardOut) and oxygen consumption (VO2) during exercise has generally been assumed to be linear. To test this assumption, we studied 72 healthy subjects using a graded, 2-min cycle-ergometry exercise test to maximum while measuring gas exchange continuously and CardOut at the end of each stage, the latter using an open-circuit gas technique. Data for VO2 and CardOut at each stage were fit to a quadratic expression y = a + (b.VO2) + (c.VO2(2)), and statistical significance of the quadratic c term was determined in each subject. Subjects were then divided into two groups: those with statistically significant negative quadratic term ("negative curvature group," n = 25) and those with either nonsignificant quadratic term or c significantly > 0 ("non-negative curvature group," n = 47, 2 with c significantly > 0). We found the negative curvature group had significantly higher maximal VO2/kg (median 37.9 vs. 32.4 ml x min(-1) x kg(-1); P = 0.03) higher resting stroke volume (SV; median 77 vs. 60 ml; P = 0.04), lower resting heart rate (HR; median 72 vs. 82 beats/min, P = 0.04), and higher tissue oxygen extraction at maximal exercise (17.1 +/- 2.2 vs 15.5 +/- 2.1 ml/100 ml; P < 0.01), with tendencies for higher maximal CardOut and SV. We also found the HR vs. VO2 relationship to be negatively curved, with negative curvature in HR associated with the negative curvature in CardOut (P < 0.05), suggesting the curvature in the CardOut vs. VO2 relationship was secondary to curvature in HR vs. VO2. We conclude that the CardOut vs. VO2 relationship is not always linear, and negative curvature in the relationship is associated with higher fitness levels in normal, non-elite-athletic subjects.

Adult↗
PubMed2006

Dietary sodium restriction and beta2-adrenergic receptor polymorphism modulate cardiovascular function in humans.

Dietary Na+ intake influences beta2-adrenergic receptor (beta2AR) responsiveness. While receiving a normal Na+ diet (150 mmol day(-1)), subjects homozygous for glycine at amino acid 16 (Gly16) have greater forearm beta2AR-mediated vasodilatation than subjects homozygous for arginine (Arg16), an effect that is mediated by endothelial NO. We tested the hypothesis that dietary Na+ restriction eliminates genotype differences in forearm and systemic beta2AR-mediated dilatation in these groups. We measured heart rate, mean arterial pressure and cardiac output (CO, acetylene breathing) responses to administration of intravenous terbutaline (TRB) before and after 5 days of low dietary Na+ intake (10 mmol day(-1)) in healthy Gly16 (n = 17; age, 31 +/- 7 year) and Arg16 homozygotes (n = 15; age, 29 +/- 8 year). After the low-Na+ diet, a catheter was placed in the brachial artery to measure forearm blood flow (FBF, plethysmography) responses to administration of isoprenaline (isoproterenol) before and after NO inhibition with NG-mono-methyl-L-arginine (L-NMMA). In the Gly16 group, the low-Na+ diet decreased baseline CO from 6.4 +/- 1.4 to 5.5 +/- 1.2 l min(-1) (P = 0.003, paired t test), tended to decrease stroke volume from 97.0 +/- 20.6 to 86.9 +/- 21.7 ml (P = 0.06) and increased peripheral resistance from 1106 +/- 246 to 1246 +/- 222 dynes s cm(-5) (P = 0.02); significant effects of the low-Na+ diet were not observed in Arg16 subjects. In a repeated measures ANOVA, the responses of all cardiovascular measures to systemic administration of TRB were not influenced by genotype or diet. Additionally, the FBF response to incremental doses of isoprenaline did not differ between genotype groups before or after administration of L-NMMA. We conclude that dietary Na+ restriction blunted the increased forearm NO-mediated beta2AR responsiveness in Gly16 homozygotes observed in a previous study after normal dietary Na+ intake, while baseline CO decreased and peripheral resistance increased in this group. This study provides evidence that dietary Na+ modulates effects of the Arg16Gly polymorphism on cardiovascular function.

Adult↗
PubMed2006

Cardiopulmonary exercise testing determination of functional capacity in mitral regurgitation: physiologic and outcome implications.

OBJECTIVES: This study was designed to evaluate prevalence, determinants, and clinical outcome implications of reduced functional capacity (FC) in patients with organic mitral regurgitation (MR). BACKGROUND: Evaluation of FC by exercise testing is rarely performed in MR because little is known about the clinical determinants and outcome implications of FC. METHODS: Cardiopulmonary exercise testing (CPET) was prospectively performed in 134 asymptomatic patients with organic MR to assess FC (peak oxygen consumption [VO2]) simultaneously to Doppler-echocardiographic quantitation of MR (effective regurgitant orifice [ERO]) and left ventricular (LV) systolic and diastolic function. RESULTS: Peak VO2 was 26 +/- 6 ml/kg/min (96 +/- 16% of age-predicted), but varied widely (57% to 145% of predicted) and was markedly reduced (< or =84% of predicted) in 19% of patients. Although ERO of MR was univariately associated with reduced FC (26 vs. 9% with ERO > or =40 vs. <40 mm2), independent determinants of reduced FC were LV diastolic function (higher E/E' ratio, p = 0.006), atrial fibrillation (p = 0.01), and lower forward stroke volume (p = 0.03). Clinical events (death, heart failure, new atrial fibrillation) and clinical events or surgery were more frequent with than without reduced FC (3 years, 36 +/- 14% vs. 13 +/- 4%, p = 0.02; and 66 +/- 11% vs. 29 +/- 5%, p = 0.001, respectively), even adjusting (risk ratios 1.80 and 1.54 respectively, both p < or = 0.03) for age and ERO. CONCLUSIONS: In asymptomatic organic MR, FC quantitatively assessed by CPET is unexpectedly markedly reduced in one out of every four to five patients. Reduced FC is independently determined by consequences rather than severity of MR and predicts increased subsequent clinical events. Therefore, CPET frequently reveals functional limitations not detected clinically and is an important tool in managing patients with organic MR.

Exercise Test↗
PubMed2006

The Arg16Gly polymorphism of the beta2-adrenergic receptor and the natriuretic response to rapid saline infusion in humans.

The beta2-adrenergic receptors (beta2ARs) play a role in renal Na+ regulation. Subjects homozygous for glycine at amino acid 16 (Gly16) of the beta2AR have been shown to have enhanced beta2-mediated vascular relaxation when compared to subjects homozygous for arginine (Arg16). However, Gly16 subjects have been shown to have higher blood pressure than Arg16 subjects. Given the dominant role of the kidneys in long-term blood pressure regulation, we sought to determine whether there were differences in renal Na+ handling between Gly16 (n = 17) and Arg16 (n = 14) subjects (Gly16: age, 30 +/- 2 years; body mass index (BMI), 25 +/- 11 kg m(-2); Arg16: age, 30 +/- 2 years; BMI, 25 +/- 1 kg m(-2)). We measured urinary Na+ content before and for 3 h following rapid intravenous saline infusion (30 ml kg(-1) in approximately 16 min). Prior to the infusion, there were no differences in 24-h Na+ excretion between Gly16 and Arg16 subjects (Gly16, 183 +/- 21 mmol; Arg16, 184 +/- 20 mmol); however, systolic blood pressure (SBP) was significantly higher in Gly16 than Arg16 subjects with no differences observed in diastolic blood pressure (DBP) or mean arterial pressure (MAP) (SBP: Gly16, 117 +/- 3 mmHg; Arg16, 109 +/- 2 mmHg; DBP: Gly16, 78 +/- 2 mmHg; Arg16, 77 +/- 2 mmHg; MAP: Gly16, 90 +/- 2 mmHg; Arg16, 89 +/- 2 mmHg). With rapid saline infusion, MAP increased in both genotype groups (Gly16, 6.7%; Arg16, 3.4%; P > 0.05). In the 3 h following Na+ infusion, Na+ excretion was less in Gly16 when compared to Arg16 subjects, with a trend towards significance when expressed as total Na+ excreted (Gly16, 66 +/- 7 mmol; Arg16, 85 +/- 9 mmol; P = 0.07), and a significant difference when expressed as a fraction of the administered load (Gly16, 0.18 +/- 0.02; Arg16, 0.28 +/- 0.03; P < 0.01). These results suggest that the Arg16Gly polymorphism of the beta2AR is associated with differences in natriuretic response to rapid saline infusion, which may influence long-term regulation of blood pressure.

Adult↗
PubMed2006

Beta-2 adrenergic receptor polymorphisms and the forearm blood flow response to mental stress.

Circulating epinephrine plays an important role in skeletal muscle vasodilation during mental stress. Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2-adrenergic receptor polymorphism have a greater forearm beta2-receptor mediated vasodilation and a higher cardiac output response to isometric handgrip than arginine (Arg) homozygotes. To test the hypothesis that the Arg16/Gly beta2-adrenergic receptor polymorphism affects the forearm blood flow (FBF) and hemodynamic response to mental stress, and whether venous catecholamine concentrations predicted these responses, we measured venous epinephrine, norepinephrine, heart rate (HR), arterial pressure (Finapres), and FBF during mental stress in healthy subjects homozygous for Gly16 (n = 30; mean age +/- SE: 30 +/- 1.2, 13 women) and Arg16 (n = 17, age 30 +/- 1.6, 11 women). Resting HR, blood pressure, and FBF responses to mental stress were similar between genotype groups. There were positive correlations between epinephrine and peak FBF (r = 0.694, P < 0.001), peak forearm vascular conductance (r = 0.677, P < 0.001) and the change in epinephrine to the change in HR (r = 0.456, P = 0.002) in all subjects. These correlations were not significantly different in the Gly16 and Arg16 groups. We conclude that venous epinephrine predicts the FBF response to mental stress, and the increase in epinephrine is also correlated with the increase in HR. Furthermore, the Arg16/Gly beta2-receptor polymorphism has no significant influence on the FBF or cardiovascular responses to mental stress.

Adult↗
PubMed2006

Reduced rate of alveolar-capillary recruitment and fall of pulmonary diffusing capacity during exercise in patients with heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have reduced pulmonary diffusing capacity for carbon monoxide (DLCO). Acute pulmonary congestion also causes reduction of DLCO, which is reversible. We hypothesized for patients with CHF that the rate of rise of exercise DLCO is reduced compared to healthy controls and falls near end-exercise consistent with progressive interstitial edema. METHODS AND RESULTS: DLCO and pulmonary blood flow (QC)) were measured by a rebreathe technique in CHF subjects (n = 11) and controls (n = 8) at rest, during constant workload exercise, and after exercise. DLCO of CHF subjects was less than controls at rest (16.5 +/- 1 vs. 21.9 +/- 2 mL/min/mm Hg, P < .01). CHF subjects exercised 11 +/- 2 minutes to 90% peak VO2, whereas controls exercised 17 +/- 2 minutes, reaching 88% peak VO2. In CHF subjects, DLCO increased to 19 +/- 2 mL/min/mm Hg and for controls to 38 +/- 3 mL/min/mm Hg. During the final 3 minutes of exercise, DLCO increased 5% in controls while decreasing 5% in CHF subjects (DLCO/Q(C)) was lower in CHF subjects at rest and progressively lower throughout exercise (P < .01). CONCLUSION: In patients with CHF, DLCO has reduced rate of rise with exercise and falls near end-exercise consistent with limitation of alveolar-capillary recruitment and progressive interstitial edema.

Aged↗
PubMed2006

Impact of preload and afterload on global and regional right ventricular function and pressure: a quantitative echocardiography study.

BACKGROUND: Several quantitative echocardiographic measures of global and regional right ventricular (RV) function have been proposed, but knowledge of the impact of increases in preload and afterload is limited. METHODS: Seventeen healthy participants were exposed to increased preload by rapid infusion of 30 mL/kg of saline over 15 minutes, and to increased afterload simulated in an 16- to 18-hour stay in a controlled hypoxic environment (fractional concentration of oxygen in inspired gas = 12.3%). Two-dimensional, Doppler, and Doppler tissue echocardiography evaluations were performed to evaluate global and regional RV function, with changes evaluated by paired analysis. RESULTS: Peak tricuspid regurgitation velocity increased in both conditions, whereas the RV end-diastolic diameter and acceleration time of the pulmonary forward flow only increased with increased preload and afterload, respectively. Estimates of RV function and contractility remained stable: no changes in the RV isovolumic acceleration (1.6 +/- 0.6 vs 1.6 +/- 0.4 and 1.3 +/- 0.4 cm/s2) or tricuspid annular plane systolic excursion (2.5 +/- 0.4 vs 2.5 +/- 0.3 and 2.6 +/- 0.3 cm) were seen (baseline compared with increased afterload and preload, respectively). The RV index of myocardial performance was increased with increased afterload (0.26 +/- 0.08 vs 0.34 +/- 0.13, P < .05), whereas no changes with increased preload were seen. Changes in loading conditions did not affect the regional strain. CONCLUSION: Moderate volume and pressure loading of the RV induces detectable changes in the RV pressure and morphology. Modern echocardiographic measures of systolic RV function seem stable with moderate increases in preload and afterload.

Adult↗
PubMed2006

Exercise-disordered breathing in chronic heart failure.

Patients with heart failure develop various ventilatory abnormalities, including reduced ventilatory reserves, increased ventilatory demands, and high work and cost of breathing. They tend to breathe with a rapid-shallow pattern, have low end-expiratory lung volumes, and may develop rhythmic oscillations in ventilation and tidal volume. These abnormalities likely contribute to exercise limitations and are associated with a worsening prognosis.

Exercise Tolerance↗
PubMed2006

Genotype related differences in beta2 adrenergic receptor density and cardiac function.

INTRODUCTION: Several common polymorphisms of the beta2 adrenergic (ADRB2) have been described including a Glycine (Gly) for arginine (Arg) substitution at amino acid 16. In vivo studies have attributed phenotypic differences in the Arg16Gly polymorphism of the ADRB2 to differences in agonist-mediated desensitization. Some studies, however, have shown differences between genotype groups under non-agonist-mediated conditions suggesting baseline differences in receptor function or in receptor density. We sought to determine whether genetic variation of the ADRB2 influenced ADRB2 density and, consequently, resting cardiovascular function. METHODS: We measured ADRB2 density on isolated lymphocytes in 30 healthy subjects (15 homozygous for Arg, Arg16, and 15 homozygous for Gly, Gly16) matched for age, cardiovascular fitness, BMI, and gender. In addition, we measured cardiac output (Q), heart rate (HR), and stroke volume (SV) after 5 min of quiet rest in these same subjects. RESULTS: Arg16 subjects had lower receptor density (1220 +/- 78 vs 1574 +/- 110, mean +/- SE, P < 0.01) as well as lower resting cardiac output due to a reduced stroke volume, but a higher HR when compared with the Gly16 subjects (Q = 4.3 +/- 0.2 vs 5.0 +/- 0.3 L.min(-1), SV = 65 +/- 6 vs 86 +/- 7 mL.beat(-1), HR = 70 +/- 4 vs 60 +/- 3 beats.min(-1), for the Arg16 and Gly16 groups, respectively, P < 0.01). In addition, ADRB2 density for all subjects was positively associated with cardiac output (r = 0.428, P = 0.009) and stroke volume (r = 0.407, P = 0.001). CONCLUSIONS: These data suggest that the Arg16Gly polymorphism of the ADRB2 influences receptor density, which, in turn, contributes to resting differences in cardiac output and stroke volume.

Adult↗
PubMed2006

Pathophysiological characteristics of heart rate recovery in heart failure.

PURPOSE: Heart failure (HF) is associated with blunted HR recovery after exercise. The determinants of altered HR recovery in HF are unknown. The aim of this study was to investigate clinical correlates of HR recovery in HF patients. METHODS: Echocardiography, pulmonary function tests, exercise testing, and neurohormonal measurements were performed in 98 HF patients. HR recovery was calculated as the difference between heart rate at peak exercise and at 1 min into a recovery period. Study subjects were divided into three groups based on HR recovery tertiles: group 1 (HR recovery < or = 6 bpm), group 2 (7 < or = HR recovery < or = 12), and group 3 (HR recovery > or = 13). RESULTS: There were significant differences between the groups in multiple parameters. Compared with group 3, patients in group 1 had greater E/A ratios (1.81 +/- 0.26 vs 0.98 +/- 0.12, P = 0.011), shorter deceleration time (170 +/- 11 vs 223 +/- 11 ms, P = 0.016), and higher plasma atrial natriuretic peptide levels (207 +/- 32 vs 101 +/- 12 pg.mL, P = 0.008), indicating higher left ventricular filling pressures and elevated left atrial pressures. Pulmonary function tests were suggestive of greater restrictive changes in the lungs. Finally, subjects in group 1 had impaired exercise capacity, as evidenced by shorter exercise duration (5.2 +/- 0.2 vs 8.3 +/- 0.4 min, P < 0.001), lower peak VO2 (14.6 +/- 0.6 vs 22.2 +/- 1.0 mL.kg(-1).min(-1), P < 0.001), higher VE/VCO2 ratios (36.4 +/- 1.1 vs 31.1 +/- 0.9, P = 0.001), and reduced chronotropic responses to exercise (39 +/- 3 vs 69 +/- 4 bpm, P < 0.001). CONCLUSION: HR recovery may be a clinically useful index identifying HF patients with distinct echocardiographic, neurohormonal, and hemodynamic characteristics. This may have implications for our understanding of the pathophysiology of impaired HR recovery in HF as well as for the clinical evaluation of such patients.

Analysis of Variance↗