Impact of pericardial restraint on right atrial mechanics during acute right ventricular pressure load

Optimization of right atrial (RA) mechanics is important for maintaining right ventricular (RV) filling and global cardiac output. However, the impact of pericardial restraint on RA function and the compensatory role of the right atrium to changes in RV afterload remain poorly characterized. In eight open-chest sheep, RA elastance (contractility) and chamber stiffness were measured (RA pressure-volume relations) at baseline and during partial pulmonary artery (PA) occlusion. Data were collected before and after pericardiotomy. With the pericardium intact and partial PA occlusion, RA elastance increased by 28% (P < 0.04), whereas RA stiffness tended to rise (P = 0.08). However, after pericardiotomy, there was a significant fall in both RA elastance (54%, P < 0.04) and stiffness (39%, P < 0.04), and subsequent PA occlusion failed to induce a change in elastance (P > 0.19) or stiffness (P > 0.84). After pericardiotomy, RA elastance and stiffness fell dramatically, and the compensatory response of the right atrium to elevated RV afterload was lost. The ability of the right atrium to respond to changes in RV hemodynamics is highly dependent on pericardial integrity.     

Differential modulation of right ventricular strain and right atrial mechanics in mild vs. severe pressure overload

Increased right atrial (RA) and ventricular (RV) chamber volumes are a late maladaptive response to chronic pulmonary hypertension. The purpose of the current investigation was to characterize the early compensatory changes that occur in the right heart during chronic RV pressure overload before the development of chamber dilation. Magnetic resonance imaging with radiofrequency tissue tagging was performed on dogs at baseline and after 10 wk of pulmonary artery banding to yield either mild RV pressure overload (36% rise in RV pressure; n = 5) or severe overload (250% rise in RV pressure; n = 4). The RV free wall was divided into three segments within a midventricular plane, and circumferential myocardial strain was calculated for each segment, the septum, and the left ventricle. Chamber volumes were calculated from stacked MRI images, and RA mechanics were characterized by calculating the RA reservoir, conduit, and pump contribution to RV filling. With mild RV overload, there were no changes in RV strain or RA function. With severe RV overload, RV circumferential strain diminished by 62% anterior (P = 0.04), 42% inferior (P = 0.03), and 50% in the septum (P = 0.02), with no change in the left ventricle (P = 0.12). RV filling became more dependent on RA conduit function, which increased from 30 ± 9 to 43 ± 13% (P = 0.01), than on RA reservoir function, which decreased from 47 ± 6 to 33 ± 4% (P = 0.04), with no change in RA pump function (P = 0.94). RA and RV volumes and RV ejection fraction were unchanged from baseline during either mild (P > 0.10) or severe RV pressure overload (P > 0.53). In response to severe RV pressure overload, RV myocardial strain is segmentally diminished and RV filling becomes more dependent on RA conduit rather than reservoir function. These compensatory mechanisms of the right heart occur early in chronic RV pressure overload before chamber dilation develops.     

Differential impact of short periods of rapid atrial pacing on left and right atrial mechanical function

Current techniques to describe atrial function are limited by their load dependency and hence do not accurately reflect intrinsic mechanical properties. To assess the impact of atrial fibrillation on atrial function, combined pressure-volume relationships (PVR) measured by conductance catheters were used to evaluate the right (RA) and left (LA) atrium in 12 isoflurane-anesthetized pigs. Biatrial PVR were recorded over a wide range of volumes during transient caval occlusion at baseline sinus rhythm (SR), after onset of rapid atrial pacing (RAP), after 1 h of RAP, after conversion to SR, and after 1 h of recovery. Cardiac output decreased by 16% (P = 0.008) with onset of RAP. Mean LA and RA pressures increased by 21 and 40% (P < 0.001), respectively, and remained elevated during the entire recovery period. RA reservoir function increased from 51 to 58% and significantly dropped to 43% after resumption of SR (P = 0.017). Immediately after RAP, a right shift of LA end-systolic PVR-intercept for end-systolic volume required to generate an atrial end-systolic pressure of 10 mmHg (24.4 ± 4.9 to 28.1 ± 5.2 ml, P = 0.005) indicated impaired contractility compared with baseline. Active LA emptying fraction dropped from 17.6 ± 7.5 to 11.7 ± 3.7% (P < 0.001), LA stroke volume and ΔP/Δt(max)/P declined by 22% (P = 0.038 and 0.026, respectively), while there was only a trend to impaired RA systolic function. Stiffness quantified by the ratio of pressure to volume at end-diastole was increased immediately after RAP only in the RA (P = 0.020), but end-diastolic PVR shifted rightward in both atria (P = 0.011 LA, P = 0.045 RA). These data suggest that even short periods of RAP have a differential impact on RA and LA function, which was sustained for 1 h after conversion to SR.     

Enhanced central and conduit pulmonary arterial reservoir function offsets reduced ductal systolic outflow during constriction of the fetal ductus arteriosus

Constriction of the fetal ductus arteriosus (DA) has disparate effects on mean and phasic hemodynamics, as mean DA blood flow is preserved until constriction is severe, but DA systolic and diastolic blood velocities change with only mild constriction. To determine the basis of this disparity and its physiological significance, seven anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), DA, and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and during mild, moderate, and severe DA constriction (defined as pulmonary-aortic mean pressure differences of 4, 8, and 14 mmHg, respectively), produced with an adjustable snare. With DA constriction, mean DA flow was initially maintained but decreased with severe constriction (P < 0.05) in conjunction with a reduction (P < 0.05) in PT flow (i.e., right ventricular output). By contrast, DA systolic flow fell progressively during DA constriction (P < 0.001), due to decreased transmission of both early and midsystolic proximal flow-enhancing forward-running compression waves into the DA. However, DA constriction was also accompanied by greater systolic storage of blood in the PT and main PA (P < 0.025), and increased retrograde diastolic flow from compliant major branch PA (P < 0.001). Transductal discharge of these central and conduit PA blood reservoirs in diastole offset systolic DA flow reductions. These data suggest that, during DA constriction in the fetus, enhanced central and conduit PA reservoir function constitutes an important compensatory mechanism that contributes to preservation of mean DA flow via a systolic-to-diastolic redistribution of phasic DA flow.     

Increased right ventricular output and central pulmonary reservoir function support rise in pulmonary blood flow during adenosine infusion in the ovine fetus

Although adenosine markedly increases fetal pulmonary blood flow, the specific changes in pulmonary trunk (PT), ductus arteriosus (DA), and conduit pulmonary artery (PA) flow interactions that support this increased flow are unknown. To address this issue, seven anesthetized late-gestation fetal sheep were instrumented with PT, DA, and left PA micromanometer catheters and transit-time flow probes. Blood flow profile and wave intensity analyses were performed at baseline and after adenosine infusion to increase PA flow approximately fivefold. With adenosine infusion, DA mean and phasic flows were unchanged, but increases in mean PT (500 ± 256 ml/min, P = 0.002) and the combined left and right PA flow (479 ± 181 ml/min, P < 0.001) were similar (P > 0.7) and related to a larger flow-increasing forward-running compression wave arising from right ventricular (RV) impulsive contraction. Moreover, while the increased PT flow was confined to systole, the rise in PA flow spanned systole (316 ml/min) and diastole (163 ml/min). This elevated PA diastolic flow was accompanied by a 170% greater discharge from a PT and main PA reservoir filled in systole (P < 0.001), but loss of retrograde blood discharge from a conduit PA reservoir that was evident at baseline. These data suggest that 1) an increase in fetal pulmonary blood flow produced by adenosine infusion is primarily supported by a higher PT blood flow (i.e., RV output); 2) about two-thirds of this increased RV output passes into the pulmonary circulation during systole; and 3) the remainder is transiently stored in a central PT and main PA systolic reservoir, from where it discharges into the lungs in diastole.     

Opening the pericardium during pulmonary artery constriction improves cardiac function.

During acute pulmonary hypertension, both the pericardium and the right ventricle (RV) constrain left ventricular (LV) filling; therefore, pericardiotomy should improve LV function. LV, RV, and pericardial pressures and RV and LV dimensions and LV stroke volume (SV) were measured in six anesthetized dogs. The pericardium was closed, the chest was left open, and the lungs were held away from the heart. Data were collected at baseline, during pulmonary artery constriction (PAC), and after pericardiotomy with PAC maintained. PAC decreased SV by one-half. RV diameter increased, and septum-to-LV free wall diameter and LV area (our index of LV end-diastolic volume) decreased. Compared with during PAC, pericardiotomy increased LV area and SV increased 35%. LV and RV compliance (pressure-dimension relations) and LV contractility (stroke work-LV area relations) were unchanged. Although series interaction accounts for much of the decreased cardiac output during acute pulmonary hypertension, pericardial constraint and leftward septal shift are also important. Pericardiotomy can improve LV function in the absence of other sources of external constraint to LV filling.     

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.     

NO supports right ventricular flow dominance and whole body O(2) utilization in midgestation fetal lambs

It is unknown if nitric oxide (NO) modulates the relative levels of left (LV) and right (RV) ventricular output, fetal O2 consumption, or blood flow distribution between the body and placenta at midgestation. To address these questions, six fetal lambs were instrumented at 89-96 days gestation (term 147 days), and blood flows were measured with radioactive microspheres 3-4 days later at baseline and after inhibition of NO synthesis with 10 mg/kg (L-NNA10) and 25 mg/kg (L-NNA25) N(omega)-nitro-L-arginine. LV output fell by 74 +/- 15 ml. min(-1). kg(-1) at L-NNA10 (P < 0.005), whereas RV output decreased by 90 +/- 18 ml. min(-1). kg(-1) at L-NNA10 (P < 0.02) and by a further 80 +/- 22 ml. min(-1). kg(-1) at L-NNA25 (P < 0.05). As a result, RV output exceeded LV output at baseline (P = 0.03) and L-NNA10 (P < 0.02) but not at L-NNA25. Fetal body blood flow fell by 95 +/- 25 ml. min(-1). kg(-1) at L-NNA10 (P < 0.01), but because placental blood flow decreased by 70 +/- 22 ml. min(-1). kg(-1) at L-NNA10 (P < 0.01) and a further 71 +/- 21 ml. min(-1). kg(-1) at L-NNA25 (P < 0.01), the fetal body-to-placental blood flow ratio was near unity at baseline and L-NNA10 but rose to 1.5 +/- 0.3 at L-NNA25 (P < 0.05). In association with these flow changes, fetal O2 consumption declined by 1.4 +/- 0.3 ml. min(-1). kg(-1) at L-NNA10 (P < 0.05) and by a further 1.5 +/- 0.6 ml. min(-1). kg(-1) at L-NNA25 (P < 0.02). These findings suggest that, in midgestation fetal lambs, NO supports an RV flow dominance, whole body O2 utilization, and the maintenance of a near-equal fetoplacental blood flow distribution.     

Effect of right ventricular hypertrophy on cardiac performance and the relation between right ventricular systolic peak pressure and end-systolic volume

To investigate the role of hypertrophy of the right ventricle upon right heart performance and the significance of the peak systolic pressure/end-systolic volume (P/V) ratio in terms of right ventricular systolic performance, simultaneous measurements of radionuclide ventriculograms and central hemodynamics were done in 32 patients with chronic obstructive pulmonary disease. In 26 of the patients (80%) technically adequate two-dimensional echocardiograms could be performed. In the subset of patients with increased (greater than or equal to 6 mm) right ventricular end-diastolic wall thickness no relationship between pulmonary artery pressure and right ventricular ejection fraction (RVEF) existed in comparison with the remaining patients. P/V indices and cardiac output were not decreased. Considering the patients, whose P/V ratio did not increase from rest to exercise, RVEF decreased highly significantly more than in the remaining patients. The ratio of wall thickness and end-diastolic radius as determinant of peak systolic stress was significantly decreased in these patients compared with the remaining patients. In the patients with right ventricular hypertrophy despite significantly higher values of pulmonary artery pressures and resistances, the afterload in terms of systolic wall stress is markedly reduced. We conclude that in the hypertrophic state, right ventricular performance is not impaired despite decreased RVEF values. In the patients whose P/V ratio does not increase from rest to exercise, an inappropriate high peak systolic wall stress may exist both due to inadequate wall thickness and increased diameter of the right ventricle. The role of P/V in terms of prognosis and development of decompensated right heart failure remains undetermined.     

Stroke volume and cardiac output decrease at termination of obstructive apneas.

Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations of systemic arterial pressure that occur in association with changes in respiration and changes in sleep state. To investigate cardiac function during the cycle of obstruction (apnea) and resumption of ventilation (recovery), we continuously measured left ventricular stroke volume (LVSV) and mean arterial blood pressure (MAP) during non-rapid-eye-movement sleep in six males with severe OSA (apnea/hypopnea index > or = 30 events/h associated with oxygen saturation < 82%). LVSV was assessed continuously using an ambulatory ventricular function monitor (VEST; Capintec). The apnea-recovery cycle was divided into three phases: 1) early apnea (EA), 2) late apnea (LA), and 3) recovery (Rec). In all subjects recovery was associated with an abrupt decrease in LVSV [54.0 +/- 14.5 (SD) ml] compared with either EA (91.4 +/- 14.7 ml; P < 0.001) or LA (77.1 +/- 15.2 ml; P < 0.005). Although heart rate increased with recovery, the increase was not sufficient to compensate for the decrease in LVSV so that cardiac output (CO) fell (EA: 6,247 +/- 739 ml/min; LA: 5,741 +/- 1,094 ml/min; Rec: 4,601 +/- 1,249 ml/min; EA vs. Rec, P < 0.01; LA vs. Rec, P < 0.025). Recovery was also associated with a significant increase in MAP. We speculate that such abrupt decreases in LVSV and CO at apnea termination, occurring coincident with the nadir of oxygen saturation, may further compromise tissue oxygen delivery.     

Retinoid signaling and cardiac anteroposterior segmentation

Summary: Establishment of anterior–posterior polarity is one of the earliest decisions in cardiogenesis. Specification of anterior (outflow) and posterior (inflow) structures ensures proper connections between venous system and inflow tract and between arterial tree and outflow tract. The last few years have witnessed remarkable progress in our understanding of cardiac anteroposterior patterning. Molecular cloning and subsequent studies on RALDH2, the key embryonic retinaldehyde dehydrogenase in retinoic acid (RA) synthesis, provided the missing link between teratogenic studies on RA deficiency and excess and normal chamber morphogenesis. We discuss work establishing the foundations of our current understanding of the mechanisms of cardiac anteroposterior segmentation, the reasons why early evidence pointing to the role of RA in anteroposterior segmentation was overlooked, and the key experiments unraveling the role of RA in cardiac anteroposterior segmentation. We have also integrated recent experiments in a model of cardiac anteroposterior patterning in which RALDH2 expression determines anteroposterior boundaries in the heart field. genesis 31:97–104, 2001. © 2001 Wiley‐Liss, Inc.     

Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat

We characterized hemodynamics and systolic and diastolic right ventricular (RV) function in relation to structural changes in the rat model of monocrotaline (MCT)-induced pulmonary hypertension. Rats were treated with MCT at 30 mg/kg body wt (MCT30, n = 15) and 80 mg/kg body wt (MCT80, n = 16) to induce compensated RV hypertrophy and RV failure, respectively. Saline-treated rats served as control (Cont, n = 13). After 4 wk, a pressure-conductance catheter was introduced into the RV to assess pressure-volume relations. Subsequently, rats were killed, hearts and lungs were rapidly dissected, and RV, left ventricle (LV), and interventricular septum (IVS) were weighed and analyzed histochemically. RV-to-(LV + IVS) weight ratio was 0.29 +/- 0.05 in Cont, 0.35 +/- 0.05 in MCT30, and 0.49 +/- 0.10 in MCT80 (P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 +/- 6% in Cont, 40 +/- 12% in MCT30 (P < 0.05 vs. Cont), and 26 +/- 6% in MCT80 (P < 0.05 vs. Cont and MCT30) rats. In MCT30 rats, cardiac output was maintained, but RV volumes and filling pressures were significantly increased compared with Cont (all P < 0.05), indicating RV remodeling. In MCT80 rats, RV systolic pressure, volumes, and peak wall stress were further increased, and cardiac output was significantly decreased (all P < 0.05). However, RV end-systolic and end-diastolic stiffness were unchanged, consistent with the absence of interstitial fibrosis. MCT-induced pressure overload was associated with a dose-dependent development of RV hypertrophy. The most pronounced response to MCT was an overload-dependent increase of RV end-systolic and end-diastolic volumes, even under nonfailing conditions.     

Analysis of right ventricular function in healthy mice and a murine model of heart failure by in vivo MRI

Because of its complex geometry, assessment of right ventricular (RV) function is more difficult than it is for the left ventricle (LV). Because gene-targeted mouse models of cardiomyopathy may involve remodeling of the right heart, the purpose of this study was to develop high-resolution functional magnetic resonance imaging (MRI) for in vivo quantification of RV volumes and global function in mice. Thirty-three mice of various age were studied under isoflurane anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close correlations between RV and LV stroke volume and cardiac output (r = 0.97, P < 0.0001 each). Consistent with human physiology, murine RV end-diastolic and end-systolic volumes were significantly higher compared with LV volumes (P < 0.05 each). MRI in mice with LV heart failure due to myocardial infarction revealed significant structural and functional changes of the RV, indicating RV dysfunction. Hence, MRI allows for the quantification of RV volumes and global systolic function with high accuracy and bears the potential to evaluate mechanisms of RV remodeling in mouse models of heart failure.     

Evaluating the effectiveness of rosuvastatin in preventing the progression of diastolic dysfunction in aortic stenosis: A substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study

Background

The aim of this study was to verify the benefits and limitations of repeated bedside echocardiographic examinations in children during mechanical ventilation. For the purposes of this study, we selected the data of over a time period from 2006 to 2010.

Methods

A total of 235 children, average age 3.21 (SD 1.32) years were included into the study and divided into etiopathogenic groups. High-risk groups comprised: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS), return of spontaneous circulation after cardiopulmonary resuscitation (ROSC), bronchopulmonary dysplasia (BPD), cardiomyopathy (CMP) and cardiopulmonary disease (CPD). Transthoracic echocardiography was carried out during mechanical ventilation. The following data were collated for statistical evaluation: right and left ventricle myocardial performance indices (RV MPI; LV MPI), left ventricle shortening fraction (SF), cardiac output (CO), and the mitral valve ratio of peak velocity of early wave (E) to the peak velocity of active wave (A) as E/A ratio. The data was processed after a period of recovery, i.e. one hour after the introduction of invasive lines (time-1) and after 72 hours of comprehensive treatment (time-2). The overall development of parameters over time was compared within groups and between groups using the distribution-free Wilcoxons and two-way ANOVA tests.

Results

A total of 870 echocardiographic examinations were performed. At time-1 higher average values of RV MPI (0.34, SD 0.01 vs. 0.21, SD 0.01; p < 0.001) were found in all groups compared with reference values. Left ventricular load in the high-risk groups was expressed by a higher LV MPI (0.39, SD 0.13 vs. 0.29, SD 0.02; p < 0.01) and lower E/A ratio (0.95, SD 0.36 vs. 1.36, SD 0.64; p < 0.001), SF (0.37, SD 0.11 vs. 0.47, SD 0.02; p < 0.01) and CO (1.95, SD 0.37 vs. 2.94, SD 1.03; p < 0.01). At time-2 RV MPI were lower (0.25, SD 0.02 vs. 0.34, SD 0.01; p < 0.001), but remained higher compared with reference values (0.25, SD 0.02 vs. 0.21, SD 0.01; p < 0.05). Other parameters in high-risk groups were improved, but remained insignificantly different compared with reference values.

Conclusion

Echocardiography complements standard monitoring of valuable information regarding cardiac load in real time. Chest excursion during mechanical ventilation does not reduce the quality of the acquired data.     

Left Atrial Systolic and Diastolic Dysfunction in Patients with Chronic Constrictive Pericarditis: A Study Using Speckle Tracking and Conventional Echocardiography

Background

Left atrial (LA) function plays an important role in the maintenance of cardiac output, however, in patients with constrictive pericarditis (CP), whether pericardial restriction and adhesion can lead to LA dysfunction, and the characteristics of LA function remain unclear. The aim of the study is to compare the left atrial (LA) function of patients with CP to that of healthy study participants using speckle tracking echocardiography (STE) and conventional echocardiography.

Methods and Results

Thirty patients with CP and 30 healthy volunteers (controls) were enrolled in the study. The underlying cause of CP was viral pericarditis in 24 (80%) patients and unknown in 6 (20%) patients. The LA maximum volume (Vmax), LA minimal volume (Vmin), and LA volume before atrial contraction (Vpre-a) were measured using biplane modified Simpson’s method. The LA expansion index (LA reservoir function) was determined as follows: ([LAVmax - LAVmin]/LAVmin) ×100. The passive emptying index (LA conduit function) was calculated as follows: ([LAVmax - LAVpre-a]/LAVmax) ×100, and the active emptying index (booster pump function) was calculated as follows: ([LAVpre-a - LAVmin]/LAVpre-a) ×100. All the patients underwent two-dimensional STE. The LA global systolic strain (S), systolic strain rate (SrS), early diastolic strain rate (SrE) and late diastolic strain rate (SrA) were measured. The LA expansion index, passive emptying index, the active emptying index and the LA global S, SrS, SrE, SrA were found to be significantly lower in patients with CP than in the control participants (P <0.001). LA function was correlated with the early diastolic velocity of the lateral mitral annulus (P <0.05).

Conclusions

Although left ventricular systolic function was preserved in patients with CP, the LA reservoir, conduit, and booster functions were impaired. Pericardial restriction and impairment of the LA myocardium may play an important role in the reduction of LA function in patients with CP.     

Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude

In pulmonary hypertension right ventricular pressure overload leads to abnormal left ventricular (LV) diastolic function. Acute high-altitude exposure is associated with hypoxia-induced elevation of pulmonary artery pressure particularly in the setting of high-altitude pulmonary edema. Tissue Doppler imaging (TDI) allows assessment of LV diastolic function by direct measurements of myocardial velocities independently of cardiac preload. We hypothesized that in healthy mountaineers, hypoxia-induced pulmonary artery hypertension at high altitude is quantitatively related to LV diastolic function as assessed by conventional and TDI Doppler methods. Forty-one healthy subjects (30 men and 11 women; mean age 41 +/- 12 yr) underwent transthoracic echocardiography at low altitude (550 m) and after a rapid ascent to high altitude (4,559 m). Measurements included the right ventricular to right atrial pressure gradient (DeltaP(RV-RA)), transmitral early (E) and late (A) diastolic flow velocities and mitral annular early (E(m)) and late (A(m)) diastolic velocities obtained by TDI at four locations: septal, inferior, lateral, and anterior. At a high altitude, DeltaP(RV-RA) increased from 16 +/- 7 to 44 +/- 15 mmHg (P < 0.0001), whereas the transmitral E-to-A ratio (E/A ratio) was significantly lower (1.11 +/- 0.27 vs. 1.41 +/- 0.35; P < 0.0001) due to a significant increase of A from 52 +/- 15 to 65 +/- 16 cm/s (P = 0.0001). DeltaP(RV-RA) and transmitral E/A ratio were inversely correlated (r(2) = 0.16; P = 0.0002) for the whole spectrum of measured values (low and high altitude). Diastolic mitral annular motion interrogation showed similar findings for spatially averaged (four locations) as well as for the inferior and septal locations: A(m) increased from low to high altitude (all P < 0.01); consequently, E(m)/A(m) ratio was lower at high versus low altitude (all P < 0.01). These intraindividual changes were reflected interindividually by an inverse correlation between DeltaP(RV-RA) and E(m)/A(m) (all P < 0.006) and a positive association between DeltaP(RV-RA) and A(m) (all P < 0.0009). In conclusion, high-altitude exposure led to a two- to threefold increase in pulmonary artery pressure in healthy mountaineers. This acute increase in pulmonary artery pressure led to a change in LV diastolic function that was directly correlated with the severity of pulmonary hypertension. However, in contrast to patients suffering from some form of cardiopulmonary disease and pulmonary hypertension, in these healthy subjects, overt LV diastolic dysfunction was not observed because it was prevented by augmented atrial contraction. We propose the new concept of compensated diastolic (dys)function.     

Mechanism of transient nocturnal hypoxemia in hypoxic chronic bronchitis and emphysema

In five patients with hypoxic chronic bronchitis and emphysema we measured ear O2 saturation (SaO2), chest movement, oronasal airflow, arterial and mixed venous gas tensions, and cardiac output during nine hypoxemic episodes (HE; SaO2 falls greater than 10%) in rapid-eye-movement (REM) sleep and during preceding periods of stable oxygenation in non-REM sleep. All nine HE occurred with recurrent short episodes of reduced chest movement, none with sleep apnea. The arterial PO2 (PaO2) fell by 6.0 +/- 1.9 (SD) Torr during the HE (P less than 0.01), but mean arterial PCO2 (PaCO2) rose by only 1.4 +/- 2.4 Torr (P greater than 0.4). The arteriovenous O2 content difference fell by 0.64 +/- 0.43 ml/100 ml of blood during the HE (P less than 0.05), but there was no significant change in cardiac output. Changes observed in PaO2 and PaCO2 during HE were similar to those in four normal subjects during 90 s of voluntary hypoventilation, when PaO2 fell by 12.3 +/- 5.6 Torr (P less than 0.05), but mean PaCO2 rose by only 2.8 +/- 2.1 Torr (P greater than 0.4). We suggest that the transient hypoxemia which occurs during REM sleep in patients with chronic bronchitis and emphysema could be explained by hypoventilation during REM sleep but that the importance of changes in distribution of ventilation-perfusion ratios cannot be assessed by presently available techniques.     

Heterogeneity in conduit artery function in humans: impact of arterial size

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men (n = 20; 31 +/- 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response (r = -0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial (r = -0.66, P = 0.001), brachial (r = -0.55, P = 0.01), and popliteal artery (r = -0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size (r = -0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size (r = -0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.     

Differential effects of left ventricular pacing sites in an acute canine model of contraction dyssynchrony

The goal of the present study was to assess the effects of left ventricular (LV) pacing sites (apex vs. free wall) on radial synchrony and global LV performance in a canine model of contraction dyssynchrony. Ultrasound tissue Doppler imaging and hemodynamic (LV pressure-volume) data were collected in seven anesthetized, opened-chest dogs. Right atrial (RA) pacing served as the control, and contraction dyssynchrony was created by simultaneous RA and right ventricular (RV) pacing to induce a left bundle-branch block-like contraction pattern. Cardiac resynchronization therapy (CRT) was implemented by adding simultaneous LV pacing to the RV pacing mode at either the LV apex (CRTa) or free wall (CRTf). A new index of synchrony was developed via pair-wise cross-correlation analysis of tissue Doppler radial strain from six midmyocardial cross-sectional regions, with a value of 15 indicating perfect synchrony. Compared with RA pacing, RV pacing significantly decreased radial synchrony (11.1 +/- 0.8 vs. 4.8 +/- 1.2, P < 0.01) and global LV performance (cardiac output: 2.0 +/- 0.3 vs. 1.4 +/- 0.1 l/min and stroke work: 137 +/- 22 vs. 60 +/- 14 mJ, P < 0.05). Although both CRTa and CRTf significantly improved radial synchrony, only CRTa markedly improved global function (cardiac output: 2.1 +/- 0.2 l/min and stroke work: 113 +/- 13 mJ, P < 0.01 vs. RV pacing). Furthermore, CRTa decreased LV end-systolic volume compared with RV pacing without any change in LV end-systolic pressure, indicating an augmented global LV contractile state. Thus, LV apical pacing appears to be a superior pacing site in the context of CRT. The dissociation between changes in synchrony and global LV performance with CRTf suggests that regional analysis from a single plane may not be sufficient to adequately characterize contraction synchrony.     

Longitudinal strain quantitates regional right ventricular contractile function

The assessment of contractile function of the right ventricle (RV) is an important clinical issue, but this remains difficult because of its complex anatomy and structure. We thought to investigate whether new Doppler-derived myocardial deformation indexes may quantify regional contractile RV function during varying loading conditions. In nine pigs, ultrasonic crystals were inserted longitudinally in the RV inflow and outflow tracts to assess regional contractile function. The same RV segments and the interventricular septum were imaged using apical echocardiographic views. Regional function was assessed using two parameters: 1) systolic strain (SS), representing the relative magnitude of segmental systolic shortening; and 2) its temporal derivative, peak systolic strain rate (SR), i.e., the maximal velocity of segmental shortening. Data were acquired at baseline and during partial pulmonary artery constriction (PAC) and inferior vena cava occlusion (IVCO). SS decreased significantly after PAC and IVCO in both the inflow and outflow tracts but only during IVCO in the septum. SR was less sensitive to loading variations in all segments. A significant correlation was found between SS values derived from sonomicrometry and myocardial Doppler in RV segments (r = 0.84, P < 0.001). Thus regional strain and SR provide complementary information on the heterogeneous RV contractile function and can be accurately and noninvasively quantified using Doppler myocardial imaging.