Johnson, Bruce D.

The gold standard for noninvasive blood pressure (BP) measurement, the Doppler technique, does not provide systolic blood pressure (SBP) and diastolic blood pressure (DBP) and may limit therapy outcomes. To improve patient care, we tested specifically designed experimental BP (ExpBP) monitor and the Doppler technique by comparing noninvasive measures to the intraarterial (I-A) BP in 31 patients with end-stage heart failure (4 females) 2.6 ± 3.4 days post-LVAD implantation (20 HeartMate II and 11 HeartWare). Bland–Altman plots revealed that the ExpBP monitor overestimated mean arterial pressure (MAP) by 1.2 (4.8) mm Hg (mean difference [standard deviation]), whereas the Doppler by 6.7 (5.8) mm Hg. The ExpBP SBP was overestimated by 0.8 (6.1) mm Hg and DBP by 1.9 (5.3) mm Hg compared with the respective I-A pressures. Both techniques achieved similar measurement reliability. In the measurement “success rate” expressed as a frequency (percent) of readable BP values per measurement attempts, Doppler accomplished 100% vs. 97%, 97%, and 94% of successful detections of MAP, SBP, and DBP provided by the ExpBP monitor. The ExpBP monitor demonstrated higher accuracy in the MAP assessment than the Doppler in addition to providing SBP and DBP in majority of subjects. Improved BP control may help to mitigate related neurologic adverse event rates.

Abstract Aims The effect of extravascular lung water (EVLW) and relationship to functional status as a result of acute decompensated heart failure (ADHF) are not well understood. We sought to quantify changes in clinical variables, EVLW, airway anatomy, spirometry, and diffusing capacity for carbon monoxide before and after treatment for ADHF. Methods and results Fifteen patients were recruited within 24 h of hospital admission. Spirometry, diffusing capacity for carbon monoxide, and surrogates of EVLW by computed tomography were measured and were then repeated within 24 h of discharge. From the computed tomography (CT) scan, surrogates of EVLW were calculated from the distribution of CT attenuation of the lung tissue. Airways were segmented using the Vida Apollo software. Patients were hospitalized for 4.6 ± 2.1 days, had 10 ± 4.8 L of fluid removed (7.0 ± 4.2 L between study visits), and lost 7.1 ± 4.9 kg. Patients had significant clearance of fluid from the lungs (per cent change: mean, 4.2 ± 6.1%; skew, 17.5 ± 27.0%; kurtosis, 37.6 ± 56.7%; full-width half-maximum, 10.2 ± 13.5%). Static lung volumes and maximal flows improved significantly (per cent change: forced vital capacity, 14.5 ± 13.6%; forced expiratory volume in 1 s, 15.9 ± 14.0%; forced expiratory flow at 25–75% of forced vital capacity, 27.2 ± 42.9%). The ratio of membrane conductance to capillary blood volume improved significantly (per cent change: alveolar–capillary membrane conductance/capillary blood volume, 23.4 ± 22.8%). Weight loss during hospitalization was significantly correlated with improved spirometry and diffusing capacity. Conclusions Extravascular lung water contributes to the pulmonary congestive syndrome in ADHF patients, and its clearance is an important component of the improvement in pulmonary function as a result of inpatient treatment.

Sieck, Gary C., Louise E. Wilson, Bruce D. Johnson, and Wen-Zhi Zhan. Hypothyroidism alters diaphragm muscle development. J. Appl. Physiol. 81(5): 1965–1972, 1996.—The impact of hypothyroidism (Hyp) on myosin heavy chain (MHC) isoform expression, maximum specific force (Po), fatigability, and maximum unloaded shortening velocity ( Vo) was determined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with 6- n-propyl-2-thiouracil (0.05% in drinking water) beginning at gestational day 10 and was confirmed by reduced plasma levels of 3,5,3′-triiodothyronine and thyroxine. MHC isoforms were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. Isometric Poand fatigue resistance of the Dia were measured in vitro at 26°C, and Vowas determined at 15°C with the slack test. Compared with control muscles, expression of MHC-slow was higher and expression of adult fast MHC isoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day 28. At each age, Poand fatigability were reduced and Vowas slower in the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.

Abstract Aims Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇E/V̇CO2) slope. The physiological correlates of the V̇E/V̇CO2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (VD/VT) and arterial CO2 tension (PaCO2) differentially contribute to the V̇E/V̇CO2 slope in HFrEF vs. HFpEF. Methods and results Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m2 and 33 ± 6 kg/m2, respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO2 was measured via radial arterial catheterization. We calculated the V̇E/V̇CO2 slope via linear regression, and VD/VT = 1 − [(863 × V̇CO2)/(V̇E × PaCO2)]. Resting VD/VT (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise VD/VT (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇E/V̇CO2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇E/V̇CO2 slope in HFrEF and HFpEF was explained by peak exercise VD/VT (R2 = 0.30 and R2 = 0.50, respectively) and PaCO2 (R2 = 0.64 and R2 = 0.28, respectively), but the relative contributions of each differed (all P < 0.01). Conclusions Relationships between the V̇E/V̇CO2 slope and both VD/VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing V̇E/V̇CO2 slope appears to be strongly explained by mechanisms influential in regulating PaCO2 in HFrEF, which contrasts with the strong role of increased VD/VT in HFpEF.

Background Pulmonary arterial pressure (PAP) varies considerably in heart failure (HF) despite similar degrees of left ventricular (LV) dysfunction. Bradykinin alters vascular tone and common variations in the kinin B2 receptor (BDKRB2) gene exists. We hypothesized that genetic variation in this receptor would influence PAP in HF. Methods 131 HF patients (>1yr history systolic HF), without COPD, not currently smoking, BMI < 40, without atrial fibrillation completed the study which included a blood draw for genotyping and neurohormones (ACE, A-II, Bradykinin, ANP, BNP, and catecholamines), an echocardiogram for cardiac function and systolic PAP (PAPsys). Results Mean LVEF was 29% ∓ 12%, NYHA class 2 ∓ 1, age 56 ∓ 12 yr, BMI 28 ∓ 5 kg/m 2 . Forty-six patients (35%) were homozygous for the +9 allele, 58 (44%) were heterozygous (+9/-9) and 27 (21%) were homozygous for the -9 allele of the BDKRB2. PAPsys averaged 42 ∓ 13, 38 ∓ 12, and 35 ∓ 11 mmHg for +9/+9, +9/-9 and -9/-9, respectively (p = 0.03). There was a trend towards gene effect for plasma ACE with the highest values in +9/+9 and lowest in -9/-9 patients (9.5 ∓ 10.7, 7.1 ∓ 8.7, and 5.4 ∓ 6.4 U/L, respectively, p = 0.06). There were no differences in plasma bradykinin or A-II, LVEF, or NYHA across genotypes. Conclusion These data suggest the +9/+9 polymorphism of the BDKRB2 receptor influences pulmonary vascular tone in stable HF.

Introduction Submaximal exercise gas exchange may be a useful tool to track responses to therapy in pulmonary arterial hypertension (PAH) patients. Methods Three patients diagnosed with idiopathic PAH, on differing therapies, were included. Standard clinical tests (echocardiography; 6 minute walk) were performed pre and 3-5 months after treatment. Gas exchange was measured during 3 minutes of step exercise at both time points. Results Gas exchange variables, end tidal CO 2 (P ET CO 2 ) and the ratio of ventilation to CO 2 production (V E /VCO 2 ), during submaximal exercise were able to track patient responses to therapy over a 3-5 month period. Two patients demonstrated positive improvements, with an increased P ET CO 2 and decreased V E /VCO 2 during light exercise, in response to an altered therapeutic regime. The third patient had a worsening of gas exchange (decreased P ET CO 2 and increased V E /VCO 2 ) following no changes in the medical regime from the baseline visit. Conclusion Gas exchange variables measured during light submaximal exercise, such as P ET CO 2 and V E /VCO 2 , may be able to better detect small changes in functional status following treatment and could, therefore, be a useful tool to track disease severity in PAH patients. Further study is required to determine the clinical usefulness of these gas exchange variables.

We developed a simplified automated algorithm to interpret noninvasive gas exchange in healthy subjects and patients with heart failure (HF, n = 12), pulmonary arterial hypertension (PAH, n = 11), chronic obstructive lung disease (OLD, n = 16), and restrictive lung disease (RLD, n = 12). They underwent spirometry and thereafter an incremental 3-minute step test where heart rate and SpO 2 respiratory gas exchange were obtained. A custom-developed algorithm for each disease pathology was used to interpret outcomes. Each algorithm for HF, PAH, OLD, and RLD was capable of differentiating disease groups ( P < .05) as well as healthy cohorts (n = 19, P < .05). In addition, this algorithm identified referral pathology and coexisting disease. Our primary finding was that the ranking algorithm worked well to identify the primary referral pathology; however, coexisting disease in many of these pathologies in some cases equally contributed to the cardiorespiratory abnormalities. Automated algorithms will help guide decision making and simplify a traditionally complex and often time-consuming process.