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We recently developed a rat model of cardiorenal failure that is characterized by severe left ventricular systolic dysfunction (LVSD) and low nitric oxide (NO) production that persisted after temporary low-dose NO synthase inhibition. We hypothesized that LVSD was due to continued low NO availability and might be reversed by supplementing NO. Rats underwent a subtotal nephrectomy and were treated with low-dose NO synthase inhibition with [N.sup.[omega]]-nitro-L-arginine up to week 8. After 3 wk of washout, rats were treated orally with either the long-acting, tolerance-free NO donor molsidomine (Mols) or vehicle (Veh). Cardiac and renal function were measured on weeks 11, 13, and 15. On week 16, LV hemodynamics and pressure-volume relationships were measured invasively, and rats were killed to quantify histological damage. On week 15, blood pressure was mildly reduced and creatinine clearance was increased by Mols (both P < 0.05). Mols treatment improved ejection fraction (53 [+ or -] 3% vs. 37 [+ or -] 2% in Veh-treated rats, P < 0.001) and stroke volume (324 [+ or -] 33 vs. 255 [+ or -] 15 [micro]l in Veh-treated rats, P < 0.05). Rats with Mols treatment had lower end-diastolic pressures (8.5 [+ or -] 1.1 mmHg) than Veh-treated rats (16.3 [+ or -] 3.5 mmHg, P < 0.05) and reduced time constants of relaxation (21.9 [+ or -] 1.8 vs. 30.9 [+ or -] 3.3 ms, respectively, P < 0.05). The LV end-systolic pressure-volume relationship was shifted to the left in Mols compared with Veh treatment. In summary, in a model of cardiorenal failure with low NO availability, supplementing NO significantly improves cardiac systolic and diastolic function without a major effect on afterload. left ventricular systolic dysfunction; rescue therapy; hemodynamics doi: 10.1152/ajpheart.00400.2010.

The atria play an important role in cardiac performance. We evaluated their function and the atrioventricular interaction in operated patients with tetralogy of Fallot (TOF). Twenty patients who had undergone surgical repair of TOF and seven controls were investigated. Patients had residual pulmonary but no major tricuspid valve insufficiency. Atrial and ventricular strain rates were obtained by echocardiographic speckle tracking. Cine MRI-derived volumetric analysis provided atrial and ventricular time volume and time volume change curves yielding emptying and filling parameters. In addition, at the atrial level, reservoir, conduit and pump function, and cyclic volume change were calculated. At the atrioventricular valve level, tricuspid and mitral annular plane systolic excursion (TAPSE and MAPSE, respectively) were measured by two-dimensional echocardiography. In the patients compared with controls, right ventricular end-diastolic volumes were increased and biventricular ejection fraction was decreased (all P < 0.05). Biventricular measures of early diastolic ventricular filling were at control levels, but in late diastole, right ventricular filling parameters and strain rates were decreased (P < 0.001). The maximal right atrial size was slightly but not significantly diminished, but cyclic volume change was significantly reduced (P < 0.0001). Pump and reservoir function were decreased (P < 0.05), and conduit function was elevated (P < 0.001). The left atrium showed reduced reservoir function and cyclic volume change (P < 0.05). TAPSE and MAPSE were also decreased (P < 0.05). There were statistically significant interdependencies between RV ejection fraction, TAPSE, and right atrial filling and emptying parameters (all P < 0.05). In TOF patients, moderate systolic and diastolic right ventricular dysfunction is associated with clearly impaired right atrial function. The left atrium is affected to a lesser extent. congenital heart disease; atrial function; magnetic resonance imaging doi: 10.1152/ajpheart.00264.2010.

Pulmonary arterial hypertension (PAH) is a chronic lung disease that leads to right ventricular (RV) hypertrophy (RVH), remodeling, and failure. We tested treatment with bone marrow-derived mesenchymal stem cells (MSCs) obtained from donor rats with monocrotaline (MCT)-induced PAH to recipient rats with MCT-induced PAH on pulmonary artery pressure, lung pathology, and RV function. This model was chosen to mimic autologous MSC therapy. On day 1, PAH was induced by MCT (60 mg/kg) in 20 female Wistar rats. On day 14, rats were treated with [10.sup.6] MSCs intravenously (MCT + MSC) or with saline (MCT60). MSCs were obtained from donor rats with PAH at 28 days after MCT. A control group received saline on days 1 and 14. On day 28, the RV function of recipient rats was assessed, followed by isolation of the lungs and heart. RVH was quantified by the weight ratio of the RV/(left ventricle + interventricular septum). MCT induced an increase of RV peak pressure (from 27 [+ or -] 5 to 42 [+ or -] 17 mmHg) and RVH (from 0.25 [+ or -] 0.04 to 0.47 [+ or -] 0.12), depressed the RV ejection fraction (from 56 [+ or -] 11 to 43 [+ or -] 6%), and increased lung weight (from 0.96 [+ or -] 0.15 to 1.66 [+ or -] 0.32 g), including thickening of the arteriolar walls and alveolar septa. MSC treatment attenuated PAH (31 [+ or -] 4 mmHg) and RVH (0.32 [+ or -] 0.07), normalized the RV ejection fraction (52 [+ or -] 5%), reduced lung weight (1.16 [+ or -] 0.24 g), and inhibited the thickening of the arterioles and alveolar septa. We conclude that the application of MSCs from donor rats with PAH reduces RV pressure overload, RV dysfunction, and lung pathology in recipient rats with PAH. These results suggest that autologous MSC therapy may alleviate cardiac and pulmonary symptoms in PAH patients. pulmonary arterial hypertension; heart failure; hypertrophy; remodeling; monocrotaline doi: 10.1152/ajpheart.00590.2009.

The time-varying elastance concept provides a comprehensive description of the intrinsic mechanical properties of the left ventricle that are assumed to be load independent. Based on pressure-volume measurements obtained with combined pressure conductance catheterization in six open-chest anesthetized sheep, we show that the time to reach end systole (defined as maximal elastance) is progressively prolonged for increasing ventricle pressures, which challenges the original (load-independent) time-varying elastance concept. Therefore, we developed a method that takes into account load dependency by normalization of time course of the four cardiac phases (isovolumic contraction, ejection, isovolumic relaxation, filling) individually. With this normalization, isophase lines are obtained that connect points in pressurevolume loops of different beats at the same relative time in each of the four cardiac phases, instead of isochrones that share points at the same time in a cardiac cycle. The results demonstrate that pressure curves can be predicted with higher accuracy, if elastance curves are estimated using isophase lines instead of using isochrones [root-meansquare error (RMSE): 3.8 [+ or -] 1.0 vs. 14.0 [+ or -] 7.4 mmHg (P < 0.001), and variance accounted for (VAF): 94.8 + 1.3 vs. 78.6 [+ or -] 14.8% (P < 0.001)]. Similar results were found when the intercept volume was assumed to be time varying [RMSE: 1.7 [+ or -] 0.3 vs. 13.4 [+ or -] 7.4 mmHg (P < 0.001), and VAF: 97.4 + 0.5 vs. 81.8 [+ or -] 15.5% (P < 0.001)]. In conclusion, phase-dependent time normalization reduces cardiac load dependency of timing and increases accuracy in estimating time-varying elastance. ventricular loading; cardiac time course; isochrones; isophase lines

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immunecompromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 x [10.sup.5] cells in 20 [micro]l, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 [+ or -] 2% vs. 36 [+ or -] 2%: P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 [+ or -] 3% vs. 16 [+ or -] 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 [+ or -] 0.3% of injected cells) expressed von Willebrand factor (16.9 [+ or -] 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning. magnetic resonance imaging; cell therapy; animal model

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 [+ or -] 0.05 in Cont, 0.35 [+ or -] 0.05 in MCF30, and 0.49 [+ or -] 0.10 in MCT80 (P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 [+ or -] 6% in Cont, 40 [+ or -] 12% in MCT30 (P < 0.05 vs. Cont), and 26 [+ or -] 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. right ventricular hypertrophy; right ventricular failure; pressure-volume relations

In many patients with congenital heart disease, the right ventricle (RV) is subjected to abnormal loading conditions. To better understand the state of compensated RV hypertrophy, which could eventually progress to decompensation, we studied the effects of RV pressure overload in rats. In the present study, we report the biventricular adaptation to 6 wk of pulmonary artery banding (PAB). PAB resulted in an RV pressure overload to ~60% of systemic level and a twofold increase in RV mass (P < 0.01). Systemic hemodynamic parameters were not altered, and overt signs of heart failure were absent. Load-independent measures of ventricular function (end-systolic pressure-volume relation, preload recruitable stroke work relation, maximum first time derivative of pressure divided by end-diastolic volume), assessed by means of pressure-volume (PV) loops, demonstrated a two- to threefold increase in RV contractility under baseline conditions in PAB rats. RV contractility increased in response to dobutamine stimulation (2.5 [micro]g x [kg.sup.-1] x [min.sup.-1]) both in PAB and sham-operated rats in a similar fashion, indicating preserved RV contractile reserve in PAB rats. Left ventricular (LV) contractility at baseline was unaffected in PAB rats, although LV volume in PAB rats was slightly decreased. LV contractility increased in response to dobutamine (2.5 [micro]g x [kg.sup.-1] x [min.sup.-1]), both in PAB and sham rats, whereas the response to a higher dose of dobutamine (5 [micro]g x [kg.sup.-1] x [min.sup.-1]) was blunted in PAB rats. RV pressure overload (6 wk) in rats resulted in a state of compensated RV hypertrophy with preserved RV contractile reserve, whereas LV contractile state at baseline was not affected. Furthermore, this study demonstrates the feasibility of performing biventricular PV-loop measurements in rats. right ventricle; hypertrophy; congenital heart disease; pressure-volume loops

The purpose of this study was to investigate the relationship between right atrial (RA) reservoir and conduit function and to determine how hemodynamic changes influence this relationship and its impact on cardiac output. In 11 open-chest sheep, RA reservoir and conduit function were quantified as RA inflow with the tricuspid valve closed versus open, respectively. Conduit function was separated into early (before A wave) and late (after A wave) components. The effects of inotropic stimulation, partial pulmonary artery occlusion, and pericardiotomy were tested. At baseline with the pericardium intact, reservoir function accounted for 0.56 (SD 0.13) of RA inflow, early conduit for 0.29 (SD 0.07), and late conduit (during RA contraction) for 0.16 (SD 0.11). Inotropic stimulation decreased conduit function and increased reservoir function, but these effects did not reach statistical significance. With partial pulmonary artery occlusion, early conduit function fell to 0.20 (SD 0.11) (P < 0.04), and the conduit-to-reservoir ratio decreased by 41% (P < 0.03). Similarly, after pericardiotomy, early conduit function fell to 0.14 (SD 0.09) (P < 0.004), reservoir function increased to 0.72 (SD 0.08) (P < 0.04), and, consequently, the early conduit-to-reservoir ratio decreased by 63% (P < 0.006). Cardiac output was inversely related to the conduit-to-reservoir ratio (r = 0.39, P < 0.001). This study demonstrated that the right atrium adjusts its ability to act more as a reservoir than a conduit in a dynamic manner. The RA conduit-to-reservoir ratio was directly related to the right ventricular pressure-RA pressure gradient at the time of maximum RA volume, with increased ventricular pressures favoring conduit function, but it was reversely related to cardiac output, with an increase in the reservoir contribution favoring improved cardiac output. right atrial function; conductance catheter, right ventricular afterload; inotropic stimulation; pulmonary artery occlusion

Byline: Eva M. Staal (1), Jan Baan (1), J. Wouter Jukema (1), Ernst E. Wall (1), Paul Steendijk (1) Keywords: Ventricular volume; Monitoring; Angiocardiography; Ventricular remodeling Abstract: Objective To test the feasibility of the transcardiac conductance (TCC) method for continuous, on-line measurement of absolute left ventricular (LV) volume and to validate the method by comparison with biplane angiography. Design and setting Prospective clinical feasibility and validation study in a cardiac catheterization laboratory in a university hospital. Patients and interventions Ten patients scheduled for electrophysiological studies (n=5), percutaneous transluminal coronary angioplasty (n=3), and left- and right-sided cardiac catheterization (n=2) were enrolled in the feasibility study. Twenty patients scheduled for diagnostic left- and right-sided cardiac catheterization were included in the validation study. The latter were studied at baseline and during right atrial pacing 30 beats/min above baseline. Measurements and results In the feasibility study satisfactory ventricular volume signals were obtained by TCC in eight of ten patients. In the validation study calibration factors ([alpha] and V.sup.p) for TCC were obtained by thermodilution and hypertonic saline dilution, to yield absolute LV volume. Results indicate a good linear correlation with angiographic volume (R .sup.2=0.78) with an intercept of 10+-15 ml, not significantly different from 0 and slope of 1.17+-0.16. Mean calibration factors [alpha] and V.sup.p were 0.017+-0.002 (interpatient variability 0.018) and 75.1+-0.4 ml (interpatient variability 35.4 ml), respectively. Conclusions The TCC method provides on-line and continuous LV volume signals in patients in a relatively noninvasive way. Calibration yields absolute LV volumes with a good linear correlation in comparison to biplane LV angiography. TCC appears to be a promising methodology for monitoring absolute LV volume in the ICU. Author Affiliation: (1) Department of Cardiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands Article History: Registration Date: 25/03/2004 Received Date: 13/06/2003 Accepted Date: 25/03/2004 Online Date: 04/05/2004 Article note: This research was supported by a grant from The Netherlands Heart Foundation (NHS 98-151) J.W.J. is an established clinical investigator of The Netherlands Heart Foundation (2001-D032)

Mechanical dyssynchrony is an important codeterminant of cardiac dysfunction in heart failure. Treatment, either medical, surgical, or by pacing, may improve cardiac function partly by improving mechanical synchrony. Consequently, the quantification of ventricular mechanical (dys)synchrony may have important diagnostic and prognostic value and may help to determine optimal therapy. Therefore, we introduced new indexes to quantify temporal and spatial aspects of mechanical dyssynchrony derived from online segmental conductance catheter signals obtained during diagnostic cardiac catheterization. To test the feasibility and usefulness of our approach, we determined cardiac function and left ventricular mechanical dyssynchrony by the conductance catheter in heart failure patients with intraventricular conduction delay (n = 12) and in patients with coronary artery disease (n = 6) and relatively preserved left ventricular function. The heart failure patients showed depressed systolic and diastolic function. However, the most marked hemodynamic differences between the groups were found for mechanical dyssynchrony, indicating a high sensitivity and specificity of the new indexes. Comparison of conductance catheter-derived indexes with septal-to-lateral dyssynchrony derived by tissue-Doppler velocity imaging showed highly significant correlations. The proposed indexes provide additional, new, and quantitative information on temporal and spatial aspects of mechanical dyssynchrony. They may refine diagnosis of cardiac dysfunction and evaluation of interventions, and ultimately help to select optimal therapy. ventricular function

The trans-cardiac conductance (TCC) method provides on-line left ventricular (LV) volume signals by determining the electrical conductance of blood in the LV by means of central venous and epithoracic electrodes. Conductive structures outside the LV blood pool cause a 'parallel conductance' offset term ([V.sup.p]) that can be determined by bolus injections of hypertonic saline in the pulmonary artery ([[V.sup.p.sub.saline]), which cause a transient increase in blood conductivity. This study in anesthetized sheep evaluates the accuracy of the saline calibration method and the variabilities of [V.sup.p] between animals, between hemodynamic conditions and during the cardiac cycle. The conventional intra-cardiac conductance catheter method was used to obtain independent estimates of [V.sup.p] by the zero-volume method ([[V.sup.p.sub.zero volume]). Mean baseline ([[V.sup.p.sub.saline]) and ([[V.sup.p.sub.zero volume]) were 104 [+ or -] 106 ml [+ or -] 6 ml respectively. Bland-Altman analysis showed a small nonsignificant bias (-2.5 ml) and narrow limits of agreement (4.6 ml). [V.sup.p] was not significantly different between hemodynamic conditions (baseline, dobutamine, volume load, propranolol), but had a substantial interanimal variability (IAV) (38%). Average variations during the cardiac cycle were < 10% of mean [V.sup.p]. We conclude that the saline method can be applied to determine [V.sup.p] for TCC. IAV is substantial, so that [V.sup.p] must be determined in each animal, but within-animal variability is relatively small. Index Terms--Calibration procedure, continuous on-line monitoring of absolute volume, hypertonic saline, left ventricular volume, sheep.

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. atrial function; conductance catheter; pulmonary artery occlusion

Diastolic function is a major determinant of ventricular performance, especially when loading conditions are altered. We evaluated biventricular diastolic function in lambs and studied possible load dependence of diastolic parameters [minimum first derivative of pressure vs. time (dP/[dt.sub.min]) and time constant of isovolumic relaxation ([tau])] in normal (n = 5) and chronic right ventricular (RV) pressure-overloaded (n = 5) hearts by using an adjustable band on the pulmonary artery (PAB). Pressure-volume relations were measured during preload reduction to obtain the end-diastolic pressure-volume relationship (EDPVR). In normal lambs, absolute dP/[dt.sub.min] and [tau] were lower in the RV than in the left ventricle whereas the chamber stiffness constant (b) was roughly the same. After PAB, RV [tau] and dP/[dt.sub.min] were significantly higher compared with control. The RV EDPVR indicated impaired diastolic function. During acute pressure reduction, both dP/[dt.sub.min], and [tau] showed a relationship with end-systolic pressure. These relationships could explain the increased dP/[dt.sub.min] but not the increased [tau]-value after banding. Therefore, the increased [tau] after banding reflects intrinsic myocardial changes. We conclude that after chronic RV pressure overload, RV early relaxation is prolonged and diastolic stiffness is increased, both indicative of impaired diastolic function. hemodynamics; hypertrophy; pressure-volume relation; ventricular function, diastole

Leeuwenburgh, Boudewijn P. J., Willem A. Helbing, Paul Steendijk, Paul H. Schoof, and Jan Baan. Biventricular systolic function in young lambs subject to chronic systemic right ventricular pressure overload. Am J Physiol Heart Circ Physiol 281: H2697-H2704, 2001.--In various clinical situations of congenital heart disease, the right ventricle (RV) is subject to a chronic systemic pressure overload which affects biventricular function and may progress to the development of RV failure. Young lambs (2-3 wk old) underwent adjustable pulmonary artery banding (PAB) at systemic (aortic) level for 8 wk. Biventricular function was determined by using load-independent indexes of global ventricular contractile performance by the end-systolic pressure-volume relationship (ESPVR) using the conductance catheter at baseline and during dobutamine infusion. PAB resulted in a significant fivefold increase in RV end-systolic pressure (12-64 mmHg) and a doubling of the RV-to-left ventricular (LV) wall thickness ratio (P < 0.01). RV global contractile performance increased significantly, as indicated by an increased slope of the ESPVR. Compared with age-matched control lambs, cardiac output decreased from 2.6 to 1.6 l/min (P < 0.05) whereas heart rates were equal. In contrast with RV volume, LV volume decreased significantly after PAB (P < 0.01), whereas the LV-ESPVR slope was unchanged. In the PAB group, the RV, but not the LV, showed a reduced response to dobutamine. We concluded that chronic RV pressure overload for 8 wk results in diminished pump function despite compensatory increased RV global contractile performance. contractile performance; hypertrophy; pressure-volume loops; ventricular function Received 7 February 2001; accepted in final form 24 August 2001

Several aspects of the four-electrode resistivity technique were studied with special emphasis on the theoretical determination of penetration depth and sample volume in anisotropic media such as (cardiac) muscle. Moreover, the presence of a thin disturbing layer on top of the medium under study was analyzed. A four-electrode sensor was developed for the measurement of local myocardial resistivity in two orthogonal directions. The sensor was applied to the epicardium of anesthetized open chest dogs and, as an example, results are given on the frequency dependence (5-60 kHz) and the changes during the cardiac cycle of longitudinal and transverse myocardial resistivity.

The comparative study of conductance-derived stroke volulme (SV), derived as a result of single and dual-excitation of the conductance catheter with SV by electromagnetic (EM) flow probes surrounding the ascending aorta, is conducted in six anesthetized open-chest dogs. The dual-excitation technique is a modified form of the conductance method, and makes use of two extra electrodes on the conductance catheter, which are aimed at generating a more uniform intracavitary electric field. The slope of the linear relation between SV, determined by flow probes and by multielectrode catheter, is augmented by the use of the dual- excitation technique.

Conversion of conductance catheter data to absolute ventricular volumes requires assessment of parallel conductance ([G.sup.P]). We determined the accuracy of [G.sup.P] obtained by the hypertonic saline method [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] compared with angiographically derived [G.sup.P] [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] and quantified the variabilities of [G.sup.P] for the dual-field conductance catheter method in nine anesthetized sheep studied at baseline, treated with dobutamine, and subjected to volume loading and [Beta]-blockade. [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] and [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] showed an excellent linear correlation [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] = 1.002 [multiplied by] [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] + 0.001 [[Omega].sup.-1], [R.sup.2] = 0.92), and Bland-Altman analysis yielded a nonsignificant bias and narrow limits of agreement (bias [+ or -] 2SD = 0.002 [+ or -] 0.112 [[Omega].sup.-1]). Within-animal variability of [G.sup.P] was very similar with both methods and was due to changes in blood conductivity rather than geometrical changes. Variability between animals was significant (26.3% of mean for [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] and 25.7% for [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] and thus warrants individual assessment. Variations during the cardiac cycle were not significantly different from zero. With biplane angiography used as gold standard, the hypertonic saline method accurately determines [G.sup.P] for the dual-field conductance catheter over a wide range of hemodynamic conditions. angiography; left ventricular volume; sheep; ventricular function

Enhanced systolic function of the right ventricle during respiratory distress syndrome in newborn lambs. Am J Physiol Heart Circ Physiol 280: H392-H400, 2001.--Respiratory distress syndrome (RDS) causes pulmonary hypertension. It is often suggested that this increased afterload for the right ventricle (RV) might lead to cardiac dysfunction. To examine this, we studied biventricular function in an experimental model. RDS was induced by lung lavages in seven newborn lambs. Five additional lambs served as controls. Cardiac function was quantified by indexes derived from end-systolic pressure-volume relations obtained by pressure-conductance catheters. After lung lavages, a twofold increase of mean pulmonary arterial pressure (from 15 to 34 mmHg) was obtained and lasted for the full 4-h study period. Stroke volume was maintained (5.2 [+ or -] 0.6 ml at baseline and 6.1 [+ or -] 1.4 ml at 4 h of RDS), while, RV end-diastolic volume showed only a slight increase (from 6.5 [+ or -] 2.3 ml at baseline to 7.7 [+ or -] 1.3 ml at 4 h RDS). RV systolic function improved significantly, as indicated by a leftward shift and increased slope of the end-systolic pressure-volume relation. Left ventricular systolic function showed no changes. In control animals, pulmonary arterial pressure did not increase and right and left ventricular systolic function remained unaffected. In the face of increased RV afterload, the newborn heart is able to maintain cardiac output, primarily by improving systolic RV function through homeometric autoregulation. biventricular function; end-systolic pressure-volume relation; homeometric autoregulation; pulmonary hypertension

De Vroomen, Maartje, Robbert H. Lopes Cardozo, Paul Steendijk, Frank Van Bel, and Jan Baan. Improved contractile performance of right ventricle in response to increased RV afterload in newborn lamb. Am. J. Physiol. Heart Circ. Physiol. 278: H100-H105, 2000.--Pulmonary hypertension results in an increased afterload for the right ventricle (RV). To determine the effects of this increased afterload on RV contractile performance, we examined RV performance before and during 4 h of partial balloon occlusion of the pulmonary artery and again after releasing the occlusion in nine newborn lambs. RV contractile performance was quantified by indexes derived from systolic RV pressure-volume relations obtained by a combined pressure-conductance catheter during inflow reduction. An almost twofold increase of end-systolic RV pressure (from 22 to 38 mmHg) was maintained during 4 h. Cardiac output (CO) (0.74 [+ or -] 0.08 1/min) and stroke volume (4.3 [+ or -] 0.4 ml) were maintained, whereas end-diastolic volume (7.9 [+ or -] 1.3 ml) did not change significantly during this period. RV systolic function improved substantially; the end-systolic pressure-volume relation shifted leftward indicated by a significantly decreased volume intercept (up to 70%), together with a slightly increased slope. In this newborn lamb model, maintenance of CO during increased RV afterload is not obtained by an increased end-diastolic volume (Frank-Starling mechanism). Instead, the RV maintains its output by improving contractile performance through homeometric autoregulation. conductance catheter; end-systolic pressure-volume relation; homeometric autoregulation; pulmonary hypertension; right ventricular function.