Acquired right ventricular dysfunction.
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Biomedical subjects
Publications and source records attributed to P Steendijk.
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AIMS: Left ventricular (LV) pressure-volume relations provide relatively load-independent indexes of systolic and diastolic LV function, but few data are available on pressure-volume relations during growth and development in the normal adult heart. Furthermore, to quantify intrinsic ventricular function the indexes should be normalized for heart weight. However, in many studies the indexes are reported in absolute terms, or body weight-correction is used as a surrogate for heart weight-correction. METHODS: We determined pressure-volume relations in young (8-week-old, n = 13) and middle-aged (50-week-old, n = 19) male Wistar rats in relation to their heart and body weights. The animals were anaesthetized and a 2F pressure-conductance catheter was introduced into the LV to measure pressure-volume relations. RESULTS: Heart and body weights were significantly higher in the 50-week-old rats, whereas the heart-to-body weight ratio was significantly lower (2.74 +/- 0.32 vs. 4.41 +/- 0.37 mg g(-1), P < 0.001). Intrinsic systolic function, quantified by the slopes of the end-systolic pressure-volume relation (E(ES)), the dP/dt(MAX) vs. end-diastolic volume relation (S-dP), and the preload recruitable stroke work relation (PRSW), normalized for heart weight, was slightly decreased in the 50-week-old rats (S-dP: -6%, P < 0.004; PRSW: -3%, P < 0.06). Heart weight-corrected diastolic indexes were not significant different. The absolute indexes qualitatively showed the same results, but body-weight corrected pressure-volume indexes showed improved systolic function and significantly depressed diastolic function. CONCLUSIONS: Intrinsic systolic function slightly decreases from the juvenile to the middle-aged period in normal male Wistar rats. Furthermore, correction of pressure-volume indexes for body weight is not an adequate surrogate for heart weight-correction in these animals.
BACKGROUND: Left ventricular (LV) pacing improves hemodynamics in patients with heart failure. We hypothesized that at least part of this benefit occurs by minimization of external constraint to LV filling from ventricular interaction. METHODS AND RESULTS: We present median values (interquartile ranges) for 13 heart failure patients with LV pacing systems implanted for New York Heart Association class III/IV limitation. We used the conductance catheter method to measure LV pressure and volume simultaneously. External constraint was measured from the end-diastolic pressure-volume relation recorded during inferior vena caval occlusion, during LV pacing, and while pacing was suspended. External constraint to LV filling was reduced by 3.0 (4.6 to 0.6) mm Hg from 4.8 (0.6 to 7.5) mm Hg (P<0.01) in response to LV pacing; effective filling pressure (LV end-diastolic pressure minus external constraint) increased by 4.0 (2.2 to 5.8) mm Hg from 17.7 (13.3 to 22.6; P<0.01). LV end-diastolic volume increased by 10 (3 to 11) mL from 238 (169 to 295) mL (P=0.01), whereas LV end-systolic volume did not change significantly (-1 [-2 to 3] mL from 180 [124 to 236] mL, P=0.97), which resulted in an increase in stroke volume of 11 (5 to 13) mL from 49 (38 to 59) mL (P<0.01). LV stroke work increased by 720 (550 to 1180) mL . mm Hg from 3400 (2110 to 4480) mL . mm Hg (P=0.01), and maximum dP/dt increased by 120 (2 to 161) mm Hg/s from 635 (521 to 767) mm Hg/s (P=0.03). CONCLUSIONS: This study suggests a potentially important mechanism by which LV pacing may produce hemodynamic benefit. LV pacing minimizes external constraint to LV filling, resulting in an increase in effective filling pressure; the consequent increase in LV end-diastolic volume increases stroke volume via the Starling mechanism.
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Implantable cardioverter defibrillator (ICD)-therapy prevents sudden death in patients at high risk, but incidence of death due to heart failure remains unaltered. Recent data suggest that biventricular (BV) pacing is useful in patients with heart failure. It is unclear, how many patients with an ICD indication may have an indication for BV pacing. Therefore all patients who received an ICD were analyzed for eligibility of BV pacing using the following criteria: NYHA class III or IV, QRS duration >120 ms, depressed LVEF. Three hundred and ninety consecutive patients received an ICD from June 1996 to March 2001. Underlying disease was ischemic heart disease in 66%. In the 390 patients the mean LVEF was 36+/-17%, 20% were in NYHA class III-IV and 16% were in NYHA class II with an LVEF <30%. Of these 140 patients, 79 had a QRS duration >120 ms. Thus, 79 (20%) patients were eligible for BV pacing in addition to ICD-therapy. Patients who received a BV pacemaker in addition to ICD-therapy had a superior survival, improved in NYHA class and showed a significantly lower hospitalization rate as compared to patients who received an ICD only. Screening for eligibility of BV pacing may be considered in patients with CHF scheduled for ICD implantation.
We developed a mathematical model describing the interaction between the heart and the arterial system. The model was constructed and tested on basis of invasive hemodynamic data in six sheep. Data from a first group of three animals (49 cardiac cycles) were used to assess a template time-varying elastance curve for the left ventricle, while the baseline steady-state data of a second group of three animals were used to assess reference cardiac and arterial parameters in sheep. The model is fully characterized by nine parameters, which were converted into 6 dimensionless numbers using the Buckingham pi theorem. The model was then used to generate LV pressure and volume and aortic pressure and flow for 86 conditions obtained by varying parameters 50 to 200% of their reference value. Systolic (SBP) and diastolic (DBP) blood pressure and stroke volume (SV) were determined from these model-generated curves and multiple linear regression analysis yielded the following expressions: SBP = Pisovolumic [0.638 - 0.0773 Emax C + 0.0507 RC/T] (r2 = 0.89); DBP = Pisovolumic [0.438-0.0712 Emax C + 0.0655RC/T] (r2 = 0.88) and SV = LVEDV [1.265-1.040 LVEDV/(LVEDV - Vd) + 0.125 Emax C-0.0777RC/T] (r2 = 0.93) with Pisovolumic = Emax (LVEDV - Vd), Emax and Vd being the slope and intercept of the end-systolic pressure-volume relation, R and C the total peripheral resistance and compliance, LVEDV the left ventricular end-diastolic volume, and T the cardiac cycle length. These expressions were validated using data from the second group of three animals obtained during vena cava occlusion at baseline and during administration of dobutamine (61 cycles). The correlation between measured and predicted values was 0.98, 0.97 and 0.92 for SBP, DBP and SV, respectively. Compared to the measured values, SBP and DBP were, on average, underestimated by 5 and 6mmHg, respectively, and SV overestimated by 1.4 ml. We conclude that the derived expressions for blood pressure and stroke volume remain valid in the intact sheep for various hemodynamic conditions, and, taking into account their dimensionless form, may hold in other species and in humans.
Birth asphyxia impairs the autoregulatory ability of the cerebral blood flow. Inappropriate synthesis of vasodilatory nitric oxide may be important in this respect. We investigated if nitric oxide synthesis inhibition by N(omega)-nitro-L-arginine (NLA) could restore cerebral autoregulation after severe hypoxia-ischemia (HI). HI was induced in 15 newborn lambs. Cerebral blood flow (carotid artery blood flow [ml/min]: Qcar) and mean aortic blood pressure [mmHg]: MABP) were measured over a 30 min period before HI (pre-HI), 0-30 min after completion of HI (0-30 post-HI) and from 60 to 120 min post-HI (60-120 post-HI). Immediately after completion of HI, 5 lambs received a placebo (PLAC), 5 low dose NLA (10 mg/kg/iv: NLA-10) and 5 high dose NLA (40 mg/kg/iv: NLA-40). Pre-HI, all groups showed cerebral autoregulation with an upper limit of regulatory ability between 75 and 90 mm Hg. At 0-30 post-HI, all groups lacked autoregulatory ability of the cerebral vascular bed and showed an aortic blood pressure-passive Q(car). At 60-120 post-HI autoregulation was restored in NLA-10 and NLA-40-treated lambs (upper limit of autoregulation was shifted to higher MABP in NLA40-treated lambs), but not in placebo-treated lambs. At 60-120 post-HI MABP was higher in both NLA-groups than in PLAC group (83+/-15 [NLA-10] and 78+/-14 [NLA-40] vs. 65+/-9 mmHg [PLAC], P<0.05). We conclude that severe HI in newborn lambs induces impairment of the autoregulatory ability of the cerebral vascular bed. Even low-dose nitric oxide-synthesis inhibition started upon reperfusion restored autoregulation, suggesting a role for nitric oxide-induced vasodilation in the impairment of autoregulation of the cerebral blood flow after birth asphyxia.
OBJECTIVE: Elevated plasma concentrations of endothelin-1 (ET-1) have been reported with pulmonary hypertension during respiratory distress syndrome (RDS). However, the exact role of ET-1 in the development of pulmonary hypertension during RDS is unclear. The relative time-course of changes in ET-1 concentrations and pulmonary artery pressure (P(ap)) during RDS may give insight in the role of ET-1. METHODS: ET-1 and P(ap) changes were studied in an experimental model of RDS, induced by lung lavages in seven newborn lambs. Five other lambs served as controls. RESULTS: Lung lavages induced a twofold increase of mean P(ap) (from 15 to 34 mm Hg) that remained present throughout the 4-h study period. Along with the increased P(ap), ET-1 plasma concentration showed a significant increase 15 min after induction of RDS at all three sample locations (pulmonary artery 198%, aorta 181% and right atrium 195% compared to baseline). This increased concentration remained high at 1 and 4 h of RDS. In control animals, no significant changes in ET-1 concentrations were observed. Plotting ET-1 concentration values against mean P(ap), in RDS and control animals at all time points, a correlation was found between the severity of the pulmonary hypertension and ET-1 concentration. CONCLUSION: This experimental model of RDS shows that ET-1 concentration increases concomitant with the development of pulmonary hypertension, from an early time point onward. More severe pulmonary hypertension is associated with higher ET-1 concentrations, but whether ET-1 is a marker or a mediator of pulmonary hypertension remains as yet unsettled.
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The first stage of the two-stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post-operative course. It is unclear if this is because of the acute increase in afterload of the thin-walled, low-pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin-walled ventricles, we studied the right ventricular pressure-volume relations of seven sheep before and 30 min after PAB using combined pressure-conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 +/- 0.05 to 0.64 +/- 0.10, P < 0.05 (mean +/- SD). There were no significant changes in heart rate and end-systolic volume after banding although there was an incremental trend in the end-diastolic volume and stroke volume. Right ventricular output (530 +/- 163-713 +/- 295 mL min (-1), P < 0.05), slope of the end-systolic pressure-volume relation (ESPVR) (3.7 +/- 2.8-10.0 +/- 4.8 mmHg mL (-1), P < 0.05) and slope of the pre-load recruitable stroke work (PRSW) relation (9.6 +/- 1.8-15.0 +/- 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end-diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank-Starling mechanism without associated change in right ventricular diastolic performance.
OBJECTIVES: Chronic pressure overload cardiac hypertrophy produces ventricular dysfunction. There is evidence that clenbuterol, a beta(2)-adrenoceptor agonist, produces cardiac hypertrophy with preserved function in rodents. We sought to determine the cardiac hypertrophic effects of clenbuterol on the thin-walled ventricles of large animals undergoing chronic pressure overload by means of pulmonary artery banding. METHODS: Right ventricular pressure-volume loops were obtained in open-chest sheep before and after 6-1/2 weeks of pulmonary artery banding by using micromanometer conductance catheters. Animals were randomly assigned to treatment with either saline solution (n = 7) or clenbuterol (n = 8). Treatment was started immediately after pulmonary artery banding. RESULTS: Acute pulmonary artery banding increased the right ventricular systolic pressure equally in both groups (saline group, 23.9 +/- 3.3 to 48.1 +/- 9.7 mm Hg; clenbuterol group, 24.3 +/- 2.8 to 48.6 +/- 10.7 mm Hg [mean +/- standard deviation]). Six weeks of treatment produced no significant differences in the body weight, heart weight, heart/body weight ratio, right ventricular wall thickness, heart rate, and stroke volume between the groups. However, the slope of the end-systolic pressure-volume relation and the slope of the first derivative of the right ventricular developed pressure/end-diastolic volume relation were significantly increased when compared with baseline values in clenbuterol-treated animals but not in saline-treated animals. CONCLUSION: Clenbuterol treatment during pulmonary artery banding improves systolic function of the chronically pressure-overloaded right ventricle. This has important implications for the use of pharmacologic agents in modulating cardiac adaptation.
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 +/- 0.6 ml at baseline and 6.1 +/- 1.4 ml at 4 h of RDS), while RV end-diastolic volume showed only a slight increase (from 6.5 +/- 2.3 ml at baseline to 7.7 +/- 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.
Conversion of conductance catheter data to absolute ventricular volumes requires assessment of parallel conductance (G(P)). We determined the accuracy of GP obtained by the hypertonic saline method (G(P)saline) compared with angiographically derived GP (G(P)Angio) and quantified the variabilities of GP 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. G(P)saline and G(P)Angio showed an excellent linear correlation (G(P)saline = 1.002 x G(P)Angio + 0.001 Omega(-1), R2 = 0.92), and Bland-Altman analysis yielded a nonsignificant bias and narrow limits of agreement (bias +/- 2SD = 0.002 +/- 0.112 Omega(-1)). Within-animal variability of GP 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 G(P)saline and 25.7% for G(P)Angio) 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 GP for the dual-field conductance catheter over a wide range of hemodynamic conditions.
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.
OBJECTIVE: The conductance catheter provides a continuous measure of left ventricular volume. Conversion of raw data to calibrated absolute volume requires assessment of parallel conductance. Conventionally, parallel conductance is determined by injecting a small bolus hypertonic saline into the pulmonary artery and analyzing the signal obtained during passage of the bolus through the left ventricle. However, in some cases, a pulmonary artery catheter is not practicable. Therefore, we investigated whether intravenous hypertonic saline injections yield reliable parallel conductance estimates. METHODS: In 13 anesthetized sheep (33+/-5 kg) parallel conductance was obtained by pulmonary artery and by intravenous injections. Measurements (triplicate) were done at baseline, during dobutamine and pacing, and repeated after embolization of the right coronary artery in order to assess the effects of enlarged right ventricular volumes. We used a multiple linear regression model to determine the relation between parallel conductance obtained by the two methods and to quantify the effects of dobutamine, pacing, and embolization. RESULTS: The two methods show an excellent correlation with a systematic overestimation for intravenous injection. The mean parallel conductance obtained by pulmonary artery injection was 0.690+/-0.009 ohm(-1) whereas intravenous injection yielded 0.739+/-0.015 ohm(-1). Interanimal variability was 0.138 ohm(-1). The difference between the two methods was relatively small, but highly significant (+0.049+/-0.012 ohm(-1), P<0.001). Embolization resulted in significantly higher values (+0.141+/-0.017 ohm(-1), P<0.001), but dobutamine and pacing did not significantly affect parallel conductance (+0.021+/-0.016 ohm(-1), NS). There was no interaction between these interventions and the injection method, indicating that the relation between parallel conductances obtained by the two methods was maintained in all conditions. CONCLUSION: Parallel conductance obtained by intravenous injection was significantly higher (+7%) than by pulmonary artery injection. However, the relation between the two methods is highly linear with an excellent correlation and is not affected by large hemodynamic changes. The systematic difference between the two methods is likely due to increased conductivity of blood in the right ventricle which is present with intravenous injection but not with pulmonary artery injection. Determination of parallel conductance by intravenous injection is a good alternative for conventional pulmonary artery injection and may be applied in studies where pulmonary artery injection is problematic. This may include studies in very small animals or studies in patients prone to arrhythmias or with cardiac anomalies such as pulmonary artery stenosis. In addition, intravenous injection could be used in biventricular studies to obtain right and left ventricular parallel conductances from a single saline injection.
OBJECTIVES: The aim of this study was to evaluate the short-term effects of partial left ventriculectomy (PLV) on left ventricular (LV) pressure-volume (P-V) loops, wall stress, and the synchrony of LV segmental volume motions in patients with dilated cardiomyopathy. BACKGROUND: Surgical LV volume reduction is under investigation as an alternative for, or bridge to, heart transplantation for patients with end-stage dilated cardiomyopathy. METHODS: We measured P-V loops in eight patients with dilated cardiomyopathy before, during and two to five days after PLV. The conductance catheter technique was used to measure LV volume instantaneously. RESULTS: The PLV reduced end-diastolic volume (EDV) acutely from 141+/-27 to 68+/-16 ml/m2 (p < 0.001) and to 65+/-6 ml/m2 (p < 0.001) at two to five days postoperation (post-op). Cardiac index (CI) increased from 1.5+/-0.5 to 2.6+/-0.6 l/min/m2 (p < 0.002) and was 1.8+/-0.3 l/min/m2 (NS) at two to five days post-op. The LV ejection fraction (EF) increased from 15+/-8% to 35+/-6% (p < 0.001) and to 26+/-3% (p < 0.003) at two to five days post-op. Tau decreased from 54+/-8 to 38+/-6 ms (p < 0.05) and was 38+/-5 ms (NS) at two to five days post-op. Peak wall stress decreased from 254+/-85 to 157+/-49 mm Hg (p < 0.001) and to 184+/-40 mm Hg (p < 0.003) two to five days post-op. The synchrony of LV segmental volume changes increased from 68+/-6% before PLV to 80+/-7% after surgery (p < 0.01) and was 73+/-4% (NS) at two to five days post-op. The LV synchrony index and CI showed a significant (p < 0.0001) correlation. CONCLUSIONS: The acute decrease in LV volume in heart-failure patients following PLV resulted at short-term in unchanged SV, increases in LVEF, and decreases in peak wall stress. The increase in LV synchrony with PLV suggests that the transition to a more uniform LV contraction and relaxation pattern might be a rationale of the working mechanism of PLV.
OBJECTIVE: To evaluate a new, less invasive, conductance method to measure continuous on-line left ventricular volume. End-systolic and end-diastolic volumes obtained with this transcardiac conductance method were compared with simultaneous measurements using the conventional intracardiac conductance catheter. DESIGN: Controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Six sheep. INTERVENTIONS: Anesthetized sheep were instrumented and inotropic condition was varied by beta-receptor stimulation (5 microg/kg/min of dobutamine) and beta-receptor blockade (1 mg/kg of propranolol). In each condition (control, dobutamine, repeat control, propranolol), ventricular volume was varied over a wide range by gradual preload reduction using a vena caval balloon catheter. MEASUREMENTS AND MAIN RESULTS: We compared the two methods by performing linear regression analysis on simultaneous end-systolic and end-diastolic volumes obtained during gradual caval occlusions. We statistically analyzed the intercepts, slopes, and correlation coefficients of the regression equations relating the transcardiac and conductance catheter measurements to determine the effects of interanimal variability, inotropic condition, and cardiac phase on the relationship between the two methods. The results show an excellent linear correlation between the two methods (mean intercept, -1.82+/-1.24 mL; mean slope, 0.787+/-0.024 and r2 = .94). Both slope and intercept of the relationship between the two methods show a significant interanimal and cardiac phase related variability but no significant dependence on inotropic condition. CONCLUSIONS: The significant interanimal variability indicates that the new method requires individual calibration in each subject. However, the small variability of the regression coefficients with changes in condition indicates that after initial calibration, end-systolic and end-diastolic volume can be followed accurately even in the presence of large changes in volume and inotropic state. This new method may facilitate quantitative continuous assessment of cardiac function in clinical practice, for example, in the intensive care unit.