The purpose of this study was to directly assess (patho)physiology of intraventricular hemodynamic interplay between fourdimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI)... Show moreThe purpose of this study was to directly assess (patho)physiology of intraventricular hemodynamic interplay between fourdimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI)-derived vorticity with kinetic energy (KE) and viscous energy loss (EL) over the cardiac cycle and their association to ejection fraction (EF) and stroke volume (SV). Fifteen healthy subjects and thirty Fontan patients underwent whole heart 4D Flow MRI. Ventricular vorticity, KE, and EL were computed over systole (vorticity_volavg systole, KEavg systole, and ELavg systole) and diastole (vorticity_volavg diastole, KEavg diastole, and ELavg diastole). The association between vorticity_vol and KE and EL was tested by Spearman correlation. Fontan patients were grouped to normal and impaired EF groups. A significant correlation was found between SV and vorticity in healthy subjects (systolic: r = 0.84, P < 0.001; diastolic: r = 0.81, P < 0.001) and in Fontan patients (systolic: r = 0.61, P < 0.001; diastolic: r = 0.54, P = 0.002). Healthy subjects showed positive correlation between vorticity_vol versus KE (systole: r = 0.96, P < 0.001; diastole: r = 0.90, P < 0.001) and EL (systole: r = 0.85, P < 0.001; diastole: r = 0.84, P < 0.001). Fontan patients showed significantly elevated vorticity_vol compared with healthy subjects (vorticity_volavg systole: 3.1 [2.3-3.9] vs. 1.7 [1.3-2.4] L/s, P < 0.001; vorticity_volavg diastole: 3.1 [2.03.7] vs. 2.1 [1.6-2.8] L/s, P = 0.002). This elevated vorticity in Fontan patients showed strong association with KE (systole: r = 0.91, P < 0.001; diastole: r = 0.85, P < 0.001) and EL (systole: r = 0.82, P < 0.001; diastole: r = 0.89, P < 0.001). Fontan patients with normal EF showed significantly higher vorticity_volavg systole and ELavg systole, but significantly decreased KE avg diastole, in the presence of normal SV, compared with healthy subjects. Healthy subjects show strong physiological hemodynamic interplay between vorticity with KE and EL. Fontan patients demonstrate a pathophysiological hemodynamic interplay characterized by correlation of elevated vorticity with KE and EL in the presence of maintained normal stroke volume. Altered vorticity and energetic hemodynamics are found in the presence of normal EF in Fontan patients.NEW & NOTEWORTHY Physiologic intraventricular hemodynamic interplay/coupling is present in the healthy left ventricle between vorticity versus viscous energy loss and kinetic energy from four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI). Conversely, Fontan patients present compensatory pathophysiologic hemodynamic coupling by an increase in intraventricular vorticity that positively correlates to viscous energy loss and kinetic energy levels in the presence of maintained normal stroke volume. Altered vorticity and energetics are found in the presence of normal ejection fraction in Fontan patients. Show less
Alogna, A.; Schwarzl, M.; Manninger, M.; Hamdani, N.; Zirngast, B.; Kloth, B.; ... ; Post, H. 2018
Bongartz LG, Braam B, Verhaar MC, Cramer MJ, Goldschmeding R, Gaillard CA, Steendijk P, Doevendans PA, Joles JA. The nitric oxide donor molsidomine rescues cardiac function in rats with chronic... Show moreBongartz LG, Braam B, Verhaar MC, Cramer MJ, Goldschmeding R, Gaillard CA, Steendijk P, Doevendans PA, Joles JA. The nitric oxide donor molsidomine rescues cardiac function in rats with chronic kidney disease and cardiac dysfunction. Am J Physiol Heart Circ Physiol 299: H2037-H2045, 2010. First published September 17, 2010; doi: 10.1152/ajpheart.00400.2010.-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-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 +/- 3% vs. 37 +/- 2% in Veh-treated rats, P < 0.001) and stroke volume (324 +/- 33 vs. 255 +/- 15 mu 1 in Veh-treated rats, P < 0.05). Rats with Mols treatment had lower end-diastolic pressures (8.5 +/- 1.1 mmHg) than Veh-treated rats (16.3 +/- 3.5 mmHg, P < 0.05) and reduced time constants of relaxation (21.9 +/- 1.8 vs. 30.9 +/- 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. Show less
Riesenkampff, E.; Mengelkamp, L.; Mueller, M.; Kropf, S.; Abdul-Khaliq, H.; Sarikouch, S.; ... ; Kuehne, T. 2010
Riesenkampff E, Mengelkamp L, Mueller M, Kropf S, Abdul-Khaliq H, Sarikouch S, Beerbaum P, Hetzer R, Steendijk P, Berger F, Kuehne T. Integrated analysis of atrioventricular interactions in... Show moreRiesenkampff E, Mengelkamp L, Mueller M, Kropf S, Abdul-Khaliq H, Sarikouch S, Beerbaum P, Hetzer R, Steendijk P, Berger F, Kuehne T. Integrated analysis of atrioventricular interactions in tetralogy of Fallot. Am J Physiol Heart Circ Physiol 299: H364-H371, 2010. First published May 21, 2010; doi:10.1152/ajpheart.00264.2010.-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. Show less
Taherzadeh, Z.; VanBavel, E.; Vos, J. de; Matlung, H.L.; Montfrans, G. van; Brewster, L.M.; ... ; Bakker, E.N.T.P. 2010
Taherzadeh Z, VanBavel E, de Vos J, Matlung HL, van Montfrans G, Brewster LM, Seghers L, Quax PH, Bakker EN. Strain-dependent susceptibility for hypertension in mice resides in the natural killer... Show moreTaherzadeh Z, VanBavel E, de Vos J, Matlung HL, van Montfrans G, Brewster LM, Seghers L, Quax PH, Bakker EN. Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex. Am J Physiol Heart Circ Physiol 298: H1273-H1282, 2010. First published February 12, 2010; doi: 10.1152/ajpheart. 00508.2009.-Hypertension is associated with chronic vascular inflammation. We tested the hypothesis that the sensitivity to develop hypertension and vascular remodeling depends on the immunological background. Blood pressure, vascular remodeling, endothelial function, vascular architecture ( number of collateral arteries), and expression of inflammatory cytokines were determined in mice that received N-G-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthesis. We studied C57BL/6, BALB/c, and BALB. B6-Cmv1r mice, a congenic strain where the natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c background. During a 4-wk treatment with L-NAME, blood pressure initially increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice showed a significant increase in mean arterial blood pressure (+53 mmHg; P < 0.001) and small artery inward remodeling. Endothelial function and vascular design were significantly different between C57BL/6 mice and BALB/C mice. The inflammatory response was similar in C57BL/6 and BALB/C mice, except for the leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the recruitment of NK cells in C57BL/6 mice. Congenic BALB. B6-Cmv1r mice showed the same endothelial response and vascular architecture as BALB/c mice. However, BALB. B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex as an important determinant in the genetically determined sensitivity to develop L-NAME-induced hypertension in mice. Show less
