Enhanced brain natriuretic peptide response to peak exercise in heart transplant recipients

We investigatedthe atrial (ANP) and brain natriuretic peptides (BNP), catecholamines,heart rate, and blood pressure responses to graded upright maximalcycling exercise of eight matched healthy subjects andcardiac-denervated heart transplant recipients (HTR). Baseline heart rate and diastolic blood pressure, together with ANP(15.2 ± 3.7 vs. 4.4 ± 0.8 pmol/l;P < 0.01) and BNP (14.3 ± 2.6 vs. 7.4 ± 0.6 pmol/l; P < 0.01), were elevated in HTR, but catecholamine levels were similarin both groups. Peak exercise O₂uptake and heart rate were lower in HTR. Exercise-inducedmaximal ANP increase was similar in both groups (167 ± 34 vs. 216 ± 47%). Enhanced BNP increase was significant only in HTR (37 ± 8 vs. 16 ± 8%; P < 0.05).Similar norepinephrine but lower peak epinephrine levels were observedin HTR. ANP and heart rate changes from rest to 75% peak exercise werenegatively correlated (r = 0.76, P < 0.05),and BNP increase was correlated with left ventricular mass index(r = 0.83, P < 0.01) after hearttransplantation. Although ANP increase was notexaggerated, these data support the idea that the chronotropiclimitation secondary to sinus node denervation might stimulate ANPrelease during early exercise in HTR. Furthermore, the BNPresponse to maximal exercise, which is related to the left ventricularmass index of HTR, is enhanced after heart transplantation.

     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Cardiovascular and Valsalva responses during parabolic flight

We investigated the integrated cardiovascularresponses of 15 human subjects to the acute gravitational changes(micro- and hypergravity portions) of parabolic flight. Measurementswere made with subjects quietly seated and while subjects performed controlled Valsalva maneuvers. During quiet, seated, parabolic flight,mean arterial pressure increased during the transition into microgravity but decreased as microgravity was sustained. Thedecrease in mean arterial pressure was accompanied by immediate reflexive increases in heart rate but by absent (orlater-than-expected) reflexive increases in total vascular resistance.Mean arterial pressure responses in Valsalva phasesII_l, III, and IV wereaccentuated in hypergravity relative to microgravity(P < 0.01, P < 0.01, andP < 0.05, respectively), butaccentuations differed qualitatively and quantitatively from thoseinduced by a supine-to-seated postural change in 1 G. This study is thefirst systematic evaluation of temporal and Valsalva-related changes incardiovascular parameters during parabolic flight. Results suggest thatarterial baroreflex control of vascular resistance may be modified byalterations of cardiopulmonary, vestibular, and/or otherreceptor activity.

     

Neck afferents and muscle sympathetic activity in humans: implications for the vestibulosympathetic reflex

Ray, Chester A., and Keith M. Hume. Neck afferents andmuscle sympathetic activity in humans: implications for the vestibulosympathetic reflex. J. Appl.Physiol. 84(2): 450-453, 1998.We have shownpreviously that head-down neck flexion (HDNF) in humans elicitsincreases in muscle sympathetic nerve activity (MSNA). The purpose ofthis study was to determine the effect of neck muscle afferents onMSNA. We studied this question by measuring MSNA before and after headrotation that would activate neck muscle afferents but not thevestibular system (i.e., no stimulation of the otolith organs orsemicircular canals). After a 3-min baseline period with the head inthe normal erect position, subjects rotated their head to the side(~90°) and maintained this position for 3 min. Head rotation wasperformed by the subjects in both the prone(n = 5) and sitting(n = 6) positions. Head rotation did not elicit changes in MSNA. Average MSNA, expressed asburst frequency and total activity, was 13 ± 1 and 13 ± 1 bursts/min and 146 ± 34 and 132 ± 27 units/min during baselineand head rotation, respectively. There were no significant changes incalf blood flow (2.6 ± 0.3 to 2.5 ± 0.3 ml · 100 ml¹ · min¹;n = 8) and calf vascular resistance(39 ± 4 to 41 ± 4 units; n = 8). Heart rate (64 ± 3 to 66 ± 3 beats/min;P = 0.058) and mean arterial pressure(90 ± 3 to 93 ± 3; P < 0.05)increased slightly during head rotation. Additional neck flexionstudies were performed with subjects lying on their side(n = 5). MSNA, heart rate, and meanarterial pressure were unchanged during this maneuver, which also doesnot engage the vestibular system. HDNF was tested in 9 of the 13 subjects. MSNA was significantly increased by 79 ± 12% (P < 0.001) during HDNF. Thesefindings indicate that neck afferents activated by horizontal neckrotation or flexion in the absence of significant force development donot elicit changes in MSNA. These findings support the concept thatHDNF increases MSNA by the activation of the vestibular system.

     

Voluntary activation of the human diaphragm in health and disease

Intersubjectcomparison of the crural diaphragm electromyogram, as measured by anesophageal electrode, requires a reliable means for normalizing thesignal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high andreproducible diaphragm electromyogram root-mean-square (RMS) values and2) to determine the relativediaphragm activation and mechanical and ventilatory outputs duringbreathing at rest in healthy subjects(n = 5), in patients with severechronic obstructive pulmonary disease (COPD,n = 5), and in restrictive patientswith prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher duringinspiration to total lung capacity than during sniff inhalation throughthe nose (P = 0.035, ANOVA). The RMS(percentage of voluntary maximal RMS) during quiet breathing was 8% inhealthy subjects, 43% in COPD patients, and 45% in PPI patients.Despite the large difference in relative RMS(P = 0.012), there were no differencesin mean transdiaphragmatic pressure (P = 0.977) and tidal volumes (P = 0.426). We conclude that voluntary maximal RMS is reliably obtainedduring an inspiration to total lung capacity but a sniff inhalationcould be a useful complementary maneuver. Severe COPD and PPI patientsbreathing at rest are characterized by increased diaphragm activationwith no change in diaphragm pressure generation.

     

Right and left ventricular pressure-volume response to respiratory maneuvers

With respiration, right ventricular end-diastolic volume fluctuates. We examined the importance of these right ventricular volume changes on left ventricular function. In six mongrel dogs, right and left ventricular volumes and pressures and esophageal pressure were simultaneously measured during normal respiration, Valsalva maneuver, and Mueller maneuver. The right and left ventricular volumes were calculated from cineradiographic positions of endocardial radiopaque markers. Increases in right ventricular volume were associated with changes in the left ventricular (LV) pressure-volume relationship. With normal respiration, right ventricular end-diastolic volume increased 2.3 +/- 0.7 ml during inspiration, LV transmural diastolic pressure was unchanged, and LV diastolic volume decreased slightly. This effect was accentuated by the Mueller maneuver; right ventricular end-diastolic volume increased 10.4 +/- 2.3 ml (P less than 0.05), while left ventricular end-diastolic pressure increased 3.6 mmHg (P less than 0.05) without a significant change in left ventricular end-diastolic volume. Conversely, with a Valsalva maneuver, right ventricular volume decreased 6.5 +/- 1.2 ml (P less than 0.05), and left ventricular end-diastolic pressure decreased 2.2 +/- 0.5 mmHg (P less than 0.05) despite an unchanged left ventricular end-diastolic volume. These changes in the left ventricular pressure-volume relationship, secondary to changes in right ventricular volumes, are probably due to ventricular interdependence. Ventricular interdependence may also be an additional factor for the decrease in left ventricular stroke volume during inspiration.     

Finger photoplethysmography during the Valsalva maneuver reflects left ventricular filling pressure

It is often challenging to assess cardiac filling pressure clinically. An improved system for detecting or ruling out elevated cardiac filling pressure may help reduce hospitalizations for heart failure. The blood pressure response to the Valsalva maneuver reflects left heart filling pressure, but its underuse clinically may be due in part to lack of continuous blood pressure recording along with lack of standardization of expiratory effort. In this study, we tested whether Valsalva-induced changes in the pulse amplitude of finger photoplethysmography (PPG), a technology already widely available in medical settings, correlate with invasively measured left ventricular end-diastolic pressure (LVEDP). We tested 33 subjects before clinically scheduled cardiac catheterizations. A finger photoplethysmography waveform was recorded during a Valsalva effort of 20 mmHg expiratory pressure sustained for 10 s, an effort most patients can achieve. Pulse amplitude ratio (PAR) was calculated as the PPG waveform amplitude just before release of expiratory effort divided by the waveform amplitude at baseline. PAR was well correlated with LVEDP (r = 0.68; P < 0.0001). For identifying LVEDP > 15 mmHG, PAR > 0.4 was 85% sensitive [95% confidence interval (95CI): 54-97%] and 80% specific (95CI: 56-93%). In conclusion, finger PPG, a technology already ubiquitous in medical centers, may be useful for assessing clinically meaningful categories of left heart filling pressure, using simple analysis of the waveform after a Valsalva maneuver effort that most patients can achieve.     

Effects of stem cells on non-ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials

Background aimsTo assess the impacts of stem cell therapy on clinical outcomes in patients with non-ischemic cardiomyopathy (NICM). The effect of stem cell therapy on prognosis is unclear and controversial.MethodsThe authors performed a systematic review and meta-analysis of the effects of autologous stem cell transplantation in patients with NICM on a composite outcome of all-cause mortality and heart transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, 6-minute walk test (6-MWT) distance and serum brain natriuretic peptide (BNP) level, considering studies published before March 19, 2020.ResultsTwelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93–6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62–157.35, P = 0.0004) and reduced BNP level (–294.94 pg/mL, 95% CI, –383.97 to –205.90, P < 0.00001) and NYHA classification (–0.70, 95% CI, –0.98 to –0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, –0.09 cm, 95% CI, –0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52–1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23–0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27–0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive.ConclusionsThis meta-analysis demonstrates that stem cell therapy may improve survival, exercise capacity and cardiac ejection fraction in NICM, which suggests that stem cells are a promising option for NICM treatment.     

Premature ventricular contractions of the right ventricular outflow tract: is there an incipient underlying disease? New insights from a speckle tracking echocardiography study

ContextPremature ventricular contractions (PVCs) originating in the right ventricular outflow tract (RVOT) are traditionally considered idiopathic and benign. Echocardiographic conventional measurements are typically normal.AimsTo assess whether right ventricle longitudinal strain, determined by two-dimensional speckle tracking echocardiography, differ between RVOT PVCs patients (treated with catheter ablation) and healthy controls.MethodsWe retrospectively selected patients with PVCs from the RVOT who underwent electrophysiological study and catheter ablation between 2016 and 2019. Patients with documented structural heart disease were excluded. Transthoracic echocardiography was performed and right ventricle global longitudinal strain (RV-GLS), free wall longitudinal strain (RVFW-LS) and left ventricle global longitudinal strain (LV-GLS) were determined as well as conventional ultrasound measurements of RV and LV function.ResultsWe studied 21 patients with RVOT PVCs and 13 controls. Patients with PVCs from the RVOT had lower values of RV-GLS and RVFW-LS compared with the control group (?19.4% versus ?22.5%, P = 0.015 and ?22.1% versus ?25.5, P = 0.041, respectively). They also had lower values of LV-GLS, although still within the normal range (?19.1% versus ?20.9%, P = 0.047). Regarding RVOT PVCs patients only, RV-GLS and RVFW-LS had no correlation with the PVCs burden prior to catheter ablation and they did not differ between the patients in whom the catheter ablation was successful and those in whom it was not. RV-GLS also had a positive correlation with RVOT proximal diameter (r = 0.487, P = 0.025).ConclusionsIn this group of RVOT PVCs patients, we found worse RV longitudinal strain values (and therefore sub-clinical myocardial dysfunction) when compared to healthy controls.     

Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans

Nóbrega, Antonio C. L., Jon W. Williamson, Jorge A. Garcia, and Jere H. Mitchell. Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans. J. Appl. Physiol. 83(3): 712-717, 1997.Ten patients with preserved inotropic function having adual-chamber (right atrium and right ventricle) pacemaker placed forcomplete heart block were studied. They performed static one-leggedknee extension at 20% of their maximal voluntary contraction for 5 minduring three conditions: 1)atrioventricular sensing and pacing mode [normal increase in heart rate (HR; DDD)], 2) HRfixed at the resting value (DOO-Rest; 73 ± 3 beats/min), and3) HR fixed at peak exercise rate(DOO-Ex; 107 ± 4 beats/min). During control exercise (DDD mode),mean arterial pressure (MAP) increased by 25 mmHg with no change instroke volume (SV) or systemic vascular resistance. During DOO-Rest andDOO-Ex, MAP increased (+25 and +29 mmHg, respectively) because of aSV-dependent increase in cardiac output (+1.3 and +1.8 l/min,respectively). The increase in SV during DOO-Rest utilized acombination of increased contractility and the Frank-Starling mechanism(end-diastolic volume 118-136 ml). However, during DOO-Ex, agreater left ventricular contractility (end-systolic volume 55-38ml) mediated the increase in SV.

     

Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure

To elucidate thetime course of sympathovagal balance and its relationship to leftventricular function in heart failure, we serially evaluated leftventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined adynamic map of sympathetic and parasympathetic modulation by powerspectral analysis of heart rate variability. The left ventricular peak+dP/dt substantially fell from 3,364 ± 338 to 1,959 ± 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 ± 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the timeconstant of left ventricular pressure decay and end-diastolic pressureincreased gradually from 25 ± 4 to 47 ± 5 ms(P < 0.05) and from 10 ± 2 to21 ± 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component(0.15-1.0 Hz), a marker of parasympathetic modulation, decreasedfrom 1,928 ± 1,914 to 62 ± 68 × 10³ms²(P < 0.05) on the third day andfurther to 9 ± 12 × 10³ms²(P < 0.05) at 2 wk. Similar to thetime course of left ventricular diastolic dysfunction, plasmanorepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- tohigh-frequency component increased progressively from 135 ± 50 to 532 ± 186 pg/ml (P < 0.05) and from 0.06 ± 0.06 to 1.12 ± 1.01 (P < 0.05), respectively, at 2 wk ofpacing. These cardiac and autonomic dysfunctions recovered graduallytoward the normal values at 2 wk after cessation of pacing. Thus aparallel decline in left ventricular contractility with parasympatheticinfluence and a parallel progression in left ventricular diastolicdysfunction with sympathoexcitation suggest a close relationshipbetween cardiac dysfunction and autonomic dysregulation duringdevelopment of heart failure.

     

Age and gender dependency of baroreflex sensitivity in healthy subjects

Laitinen, Tomi, Juha Hartikainen, Esko Vanninen, LeoNiskanen, Ghislaine Geelen, and Esko Länsimies. Age andgender dependency of baroreflex sensitivity in healthy subjects.J. Appl. Physiol. 84(2): 576-583, 1998.We evaluated the correlates of baroreflex sensitivity (BRS) inhealthy subjects. The study consisted of 117 healthy, normal-weight,nonsmoking male and female subjects aged 23-77 yr. Baroreflexcontrol of heart rate was measured by using the phenylephrinebolus-injection technique. Frequency- and time-domain analysis of heartrate variability and an exercise test were performed. Plasmanorepinephrine, epinephrine, insulin, and arginine vasopressinconcentrations and plasma renin activity were measured. In theunivariate analysis, BRS correlated with age(r = 0.65,P < 0.001), diastolic blood pressure(r = 0.47, P < 0.001), exercise capacity(r = 0.60, P < 0.001), and the high-frequency component of heart rate variability (r = 0.64, P < 0.001). There was also asignificant correlation between BRS and plasma norepinephrine concentration (r = 0.22,P < 0.05) and plasma renin activity (r = 0.32, P < 0.001). According to themultivariate analysis, age and gender were the most importantphysiological correlates of BRS. They accounted for 52% ofinterindividual BRS variation. In addition, diastolic blood pressureand high-frequency component of heart rate variability were significantindependent correlates of BRS. BRS was significantly higher in men thanin women (15.0 ± 1.2 vs. 10.2 ± 1.1 ms/mmHg, respectively;P < 0.01). Twenty-four percent ofwomen >40 yr old and 18% of men >60 yr old had markedly depressedBRS (<3 ms/mmHg). We conclude that physiological factors, particularly age and gender, have significant impact on BRS in healthysubjects. In addition, we demonstrate that BRS values that have beenproposed to be useful in identifying postinfarction patients at highrisk of sudden death are frequently found in healthy subjects.

     

Ventricular activation during sympathetic imbalance and its computational reconstruction

We characterized the epicardialactivation sequence during a norepinephrine (NE)-induced ventriculararrhythmia in anesthetized pigs and studied factors that modulatedit. Subepicardial NE infusion caused the QRS complex to invertwithin a single beat (n = 35 animals, 101 observations), and the earliest epicardial activation consistentlyshifted to the randomly located infusion site (n = 14).This preceded right atrial activation, whereas the total ventricularepicardial activation time increased from 20 ± 4 to 50 ± 9 ms (P < 0.01). These events were accompanied by aventricular tachycardia and a drop in left ventricular pressure, whichwere fully reversed after the infusion was stopped. Epicardial pacing at the infusion site mimicked all electrical and hemodynamic changes induced by NE. The arrhythmia was prevented by propranolol and abolished by cardiac sympathetic or vagal nerve stimulation. Focal automaticity was computationally reconstructed using a two-dimensional sheet of 256 × 256 resistively coupled ventricular cells, where calcium handling was abnormally high in the central region. We concludethat adrenergic stimulation to a small region of the ventricle elicitstriggered automaticity and that computational reconstruction implicatescalcium overload. Interventions that reduce spatial inhomogeneities ofintracellular calcium may prevent this type of arrhythmia.

     

Systemic and myocardial hemodynamics during periodic obstructive apneas in sedated pigs

The effects of periodic obstructive apneas onsystemic and myocardial hemodynamics were studied in ninepreinstrumented sedated pigs under four conditions: breathing room air(RA), breathing 100% O₂,breathing RA after critical coronary stenosis (CS) of the left anteriordescending coronary artery, and breathing RA after autonomic blockadewith hexamethonium (Hex). Apneas with RA increased mean arterialpressure (MAP; from baseline 103.0 ± 3.5 to late apnea 123.6 ± 7.0 Torr, P < 0.001) and coronary blood flow (CBF; late apnea 193.9 ± 22.9% of baseline,P < 0.001) but decreased cardiacoutput (CO; from baseline 2.97 ± 0.15 to late apnea 2.39 ± 0.19 l/min, P < 0.001). Apneas withO₂ increased MAP (from baseline105.1 ± 4.6 to late apnea 110.7 ± 4.8 Torr, P < 0.001). Apneas with CS producedsimilar increases in MAP as apneas with RA but greater decreases in CO(from baseline 3.03 ± 0.19 to late apnea 2.1 ± 0.15 l/min,P < 0.001). In LAD-perfused myocardium, there was decreased segmental shortening (baseline 11.0 ± 1.5 to late apnea 7.6 ± 2.0%,P < 0.01) and regionalintramyocardial pH (baseline 7.05 ± 0.03 to late apnea 6.72 ± 0.11, P < 0.001) during apneas withCS but under no other conditions. Apneas with Hex increased to the sameextent as apneas with RA. Myocardial O₂ demand remained unchangedduring apnea relative to baseline. We conclude that obstructiveapnea-induced changes in left ventricular afterload and CO aresecondary to autonomic-mediated responses to hypoxemia. Increased CBFduring apneas is related to regional metabolic effects of hypoxia andnot to autonomic factors. In the presence of limited coronary flowreserve, decreased O₂ supply during apneas can lead to myocardial ischemia, which in turnadversely affects left ventricular function.

     

Effects of Obesity and Weight Loss on Cardiac Function and Valvular Performance

KARASON, KRISTJAN, INGEMAR WALLENTIN, BO LARSSON, LARS SJOSTROM. Effects of obesity and weight loss on cardiac function and valvular performance. Obes Res. 1998;6:422–429. Objective : To study the consequences of long-standing obesity on myocardial function and valvular performance and to determine the effects of weight loss on these cardiovascular features. Research Methods and Procedures : We included 41 patients with obesity referred for weight-reducing gastroplasty, 31 patients with obesity who received dietary recommendations, and 43 lean subjects. Body weight and blood pressure were measured, and cardiac function and valvular performance were estimated echocardiographically. Left ventricular ejection fraction was used to assess systolic heart function, and the ratio of transmitral early to atrial (E/A) peak flow velocity was used as an estimate of diastolic filling. All three study groups were investigated at baseline, and the two groups with obesity were re-examined at 1-year follow-up. Results : Patients with obesity had higher blood pressure, greater cardiac output, lower ejection fraction, and reduced E/A ratio, compared with lean subjects (p<0.01). Surgical treatment of obesity led to significant decreases in body weight, whereas body weight remained unchanged in the group treated with dietary recommendations (p<0.001). In the weight loss group, blood pressure and cardiac output decreased and the E/A ratio increased (p<0.001). Left ventricular ejection fraction tended to increase in the weight loss group and decrease in the obese control group p<0.01). No significant valvular disease was observed in any of the subjects with obesity at baseline or after weight loss. Discussion : We conclude that weight reduction in subjects with obesity is associated with improvements in left ventricular diastolic filling and has favorable effects on left ventricular ejection fraction. Neither obesity nor weight loss seem to promote valvular heart disease.     

Beta-Blockers,Left and Right Ventricular Function,and In-Vivo Calcium Influx in Muscular Dystrophy Cardiomyopathy

Beta-blockers are used to treat acquired heart failure in adults, though their role in early muscular dystrophy cardiomyopathy is unclear. We treated 2 different dystrophic mouse models which have an associated cardiomyopathy (mdx: model for Duchenne Muscular Dystrophy, and Sgcd-/-: model for limb girdle muscular dystrophy type 2F) and wild type controls (C57 Bl10) with the beta blocker metoprolol or placebo for 8 weeks at an early stage in the development of the cardiomyopathy. Left and right ventricular function was assessed with cardiac magnetic resonance imaging (MRI) and in-vivo myocardial calcium influx with manganese enhanced MRI. In the mdx mice at baseline there was reduced stroke volume, cardiac index, and end-diastolic volume with preserved left ventricular ejection fraction. These abnormalities were no longer evident after treatment with beta-blockers. Right ventricular ejection fraction was reduced and right ventricular end-systolic volume increased in the mdx mice. With metoprolol there was an increase in right ventricular end-diastolic and end-systolic volumes. Left and right ventricular function was normal in the Sgcd-/- mice. Metroprolol had no significant effects on left and right ventricular function in these mice, though heart/body weight ratios increased after treatment. In-vivo myocardial calcium influx with MEMRI was significantly elevated in both models, though metoprolol had no significant effects on either. In conclusion, metoprolol treatment at an early stage in the development of cardiomyopathy has deleterious effects on right ventricular function in mdx mice and in both models no effect on increased in-vivo calcium influx. This suggests that clinical trials need to carefully monitor not just left ventricular function but also right ventricular function and other aspects of myocardial metabolism.     

Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit

Campbell, Hillary, Krishnan Ravi, Emigdio Bravo, and C. Tissa Kappagoda. Effect of Diazinon PLUS on rapidly adapting receptors in the rabbit. J. Appl.Physiol. 81(6): 2604-2610, 1996.The effects ofDiazinon PLUS aerosol on the activities of rapidly adapting receptors(RARs) and slowly adapting receptors (SAR) of the airways wereinvestigated in anesthetized rabbits. The effects on boththe baseline activity and the responses to stimulation by increasingmean left atrial pressure were examined. Action potentialswere recorded from the left cervical vagus nerve. Aerosols (particlesize 3 µm) were generated by a Mini-HEART nebulizer. We observed thatan aerosol of Diazinon PLUS (1:10 vol/vol dilution in normal saline)decreased the baseline RAR activity (n = 10) significantly (P < 0.05) from209 ± 77 to 120 ± 40 impulses/min. In the post-Diazinon PLUScontrol period, the RAR activity recovered partially to 185 ± 75 impulses/min and decreased significantly to 131 ± 52 impulses/min(P < 0.05) after a second exposureof Diazinon PLUS (undiluted) aerosol. Aerosols of normal saline in thecontrol state did not produce a significant change in the RAR activity.A group of SAR (n = 8) were examinedunder similar conditions, and it was found that only the exposure toDiazinon PLUS (undiluted) aerosol decreased the activity significantly (P < 0.05) from 1,536 ± 206 to1,367 ± 182 impulses/min. The effect of Diazinon PLUS on theresponse to increasing mean left atrial pressure was examined in sevenRARs. In the control state, RAR activity increased significantly(P < 0.05) during elevation of meanleft atrial pressure. This response was abolished after exposure toDiazinon PLUS. These findings suggest that diazinon may interfere withairway defense mechanisms by reducing the activity of RARs.

     

三维斑点追踪技术对慢性肾功能不全患者左心室收缩功能和右心室功能的评估价值研究

摘要 目的：探讨慢性肾功能不全患者应用三维斑点追踪技术对其左心室收缩功能和右心室功能的评估价值。方法：选择我院收治的慢性肾功能不全患者82例,根据患者肾功能将其分为轻度慢性肾功能不全组[慢性肾脏病（CKD） 2期,47例],中-重度慢性肾功能不全组（CKD 3~5期,35例）,另选取同期医院体检的健康志愿者30例作为对照组,应用二维超声及三维斑点追踪技术检测各组心脏指标,比较三组二维超声指标、三维斑点追踪技术指标,应用受试者工作特征（ROC）曲线分析三维斑点追踪技术对患者左心室收缩功能和右心室功能的评估价值。结果：中-重度慢性肾功能不全组室间隔舒张末期厚度（IVSTd）、肺动脉收缩压（PASP）显著高于轻度慢性肾功能不全组、对照组,右心室面积变化分数（RVFAC）、组织运动三尖瓣环位移（TAPSE）、左心室射血分数（LVEF）显著低于轻度慢性肾功能不全组、对照组（P<0.05）。中-重度慢性肾功能不全组左室整体圆周收缩期峰值应变（LGCS）、左室整体纵向收缩期峰值应变（LGLS）、右室整体圆周收缩期峰值应变（RGCS）右室整体纵向收缩期峰值应变（RGLS）、显著高于轻度慢性肾功能不全组、对照组,左室整体径向收缩期峰值应变（LGRS）、三维左室射血分数（3D-LVEF）、右室整体径向收缩期峰值应变（RGRS）、三维右室射血分数（3D-RVEF）显著低于轻度慢性肾功能不全组、对照组（P<0.05）。ROC曲线分析显示,三维斑点追踪技术对慢性肾功能不全患者左心室收缩功能和右心室功能的评估价值较高。结论：三维斑点追踪技术可以准确检测心脏的纵向运动、圆周运动、径向运动,为临床早期发现慢性肾功能不全患者的心脏功能异常提供依据。     

In vivo assessment of changes in air and tissue volumes after pneumonectomy

Takeda, S., E. Y. Wu, R. H. Epstein, A. S. Estrera, and C. C. W. Hsia. In vivo assessment of changes in air and tissue volumes after pneumonectomy. J. Appl.Physiol. 82(4): 1340-1348, 1997.We examined theprogression and topographical distribution of postpneumonectomy volumechanges in immature foxhounds undergoing right pneumonectomy (R-Pnx,n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequentlyraised to maturity. Volumes of lung air (Vair) and tissue(Vti) were estimated by computerized tomography (CT) scan at 7, 22, and52 wk after surgery at a transpulmonary pressure of 20 cmH₂O. Estimates of Vti by CT scanincluded both septal tissue as well as nonseptal tissue (small- andmedium-sized airways and blood vessels); these were compared withestimates of septal Vti by an acetylene rebreathing (Rb) method. Wefound significant correlations between these techniques(Vair_CT = 0.83 Vair_Rb + 275, R = 0.97;Vti_CT = 1.62 Vti_Rb  30, R = 0.81). Extravascular septal Vtireturned to normal 7 wk after R-Pnx and remained normal up to maturity.Nonseptal Vti remained significantly below normal. The greatestincrease in Vti occurred in the midlung region just cephalad and caudalto the heart. After an early period of accelerated tissue growth afterR-Pnx, the rate of septal tissue growth matched that of somatic growth,whereas nonseptal tissue growth lagged behind. Compensatory growth ofthe remaining left lung was not associated with selectivealterations in thoracic development.

     

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

Brändle, Marian, Kaushik P. Patel, Wei Wang, andIrving H. Zucker. Hemodynamic and norepinephrine responses topacing-induced heart failure in conscious sinoaortic-denervated dogs.J. Appl. Physiol. 81(4):1855-1862, 1996.The present study was undertaken to determinethe effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations thatoccur in the pacing-induced model of congestive heart failure. Twogroups of dogs were examined: intact(n = 9) and SAD(n = 9). Both groups of dogs werestudied in the control (prepace) state and each week after theinitiation of ventricular pacing at 250 beats/min. After the pacemakerwas turned off, hemodynamic and plasma norepinephrine levels returnedtoward control levels in the prepaced state and after 1 and 2 wk ofpacing. However, by 3 wk all hemodynamic and norepinephrine levelsremained relatively constant over the 10-min observation period withthe pacemaker off. With the pacemaker off, left ventricularend-diastolic pressure went from 2.7 ± 1.4 (SE) mmHg during theprepace state to 23.2 ± 2.9 mmHg in the heart failure state inintact dogs (P < 0.01). Leftventricular end-diastolic pressure increased to 27.1 ± 2.2 mmHgfrom a control level of 4.2 ± 1.9 mmHg in SAD dogs(P < 0.0003). Mean arterial pressuresignificantly decreased in intact and SAD dogs. Resting heart rate wassignificantly higher in SAD dogs and increased to 135.8 ± 8.9 beats/min in intact dogs and 136.1 ± 6.5 beats/min in SAD dogs.There were no significant differences in the hemodynamic parametersbetween intact and SAD dogs after pacing. Plasma norepinephrine wassignificantly lower in intact than in SAD dogs before pacing (197.7 ± 21.6 vs. 320.6 ± 26.6 pg/ml;P < 0.005). In the heart failurestate, plasma norepinephrine increased significantly in both intact(598.3 ± 44.2 pg/ml) and SAD (644.0 ± 64.6 pg/ml) groups. Therewere no differences in the severity or the magnitude of the developedheart failure state in SAD vs. intact dogs. We conclude from these datathat the arterial baroreflex is not the sole mechanism for the increasein sympathetic drive in heart failure.