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Differential cardiac remodeling in preload versus afterload.

ABSTRACT: Hemodynamic load regulates myocardial function and gene expression. We tested the hypothesis that afterload and preload, despite similar average load, result in different phenotypes.Afterload and preload were compared in mice with transverse aortic constriction (TAC) and aortocaval shunt (shunt). Compared with sham mice, 6 hours after surgery, systolic wall stress (afterload) was increased in TAC mice (+40%; P<0.05), diastolic wall stress (preload) was increased in shunt (+277%; P<0.05) and TAC mice (+74%; P<0.05), and mean total wall stress was similarly increased in TAC (69%) and shunt mice (67%) (P=NS, TAC versus shunt; each P<0.05 versus sham). At 1 week, left ventricular weight/tibia length was significantly increased by 22% in TAC and 29% in shunt mice (P=NS, TAC versus shunt). After 24 hours and 1 week, calcium/calmodulin-dependent protein kinase II signaling was increased in TAC. This resulted in altered calcium cycling, including increased L-type calcium current, calcium transients, fractional sarcoplasmic reticulum calcium release, and calcium spark frequency. In shunt mice, Akt phosphorylation was increased. TAC was associated with inflammation, fibrosis, and cardiomyocyte apoptosis. The latter was significantly reduced in calcium/calmodulin-dependent protein kinase IIdelta-knockout TAC mice. A total of 157 mRNAs and 13 microRNAs were differentially regulated in TAC versus shunt mice. After 8 weeks, fractional shortening was lower and mortality was higher in TAC versus shunt mice.Afterload results in maladaptive fibrotic hypertrophy with calcium/calmodulin-dependent protein kinase II-dependent altered calcium cycling and apoptosis. Preload is associated with Akt activation without fibrosis, little apoptosis, better function, and lower mortality. This indicates that different loads result in distinct phenotype differences that may require specific pharmacological interventions.

SUBMITTER: Toischer K

PROVIDER: S-EPMC2955196 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Differential cardiac remodeling in preload versus afterload.

Toischer Karl K Rokita Adam G AG Unsöld Bernhard B Zhu Wuqiang W Kararigas Georgios G Sossalla Samuel S Reuter Sean P SP Becker Alexander A Teucher Nils N Seidler Tim T Grebe Cornelia C Preuss Lena L Gupta Shamindra N SN Schmidt Kathie K Lehnart Stephan E SE Krüger Martina M Linke Wolfgang A WA Backs Johannes J Regitz-Zagrosek Vera V Schäfer Katrin K Field Loren J LJ Maier Lars S LS Hasenfuss Gerd G

Circulation 20100823 10

<h4>Background</h4>Hemodynamic load regulates myocardial function and gene expression. We tested the hypothesis that afterload and preload, despite similar average load, result in different phenotypes.<h4>Methods and results</h4>Afterload and preload were compared in mice with transverse aortic constriction (TAC) and aortocaval shunt (shunt). Compared with sham mice, 6 hours after surgery, systolic wall stress (afterload) was increased in TAC mice (+40%; P<0.05), diastolic wall stress (preload) ...[more]

PMID: 20733099

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Project description:BackgroundLeft ventricular (LV) diastolic function (DF) may play an important role in predicting fluid responsiveness. However, few studies assessed the role of diastolic function in predicting fluid responsiveness. The aim of this pilot study was to assess whether parameters of right and left diastolic function assessed with transesophageal echocardiography, including the mitral E/e' ratio, is associated with fluid responsiveness among patients undergoing elective bypass graft surgery. We also sought to compare other methods of fluid responsiveness assessment, including echocardiographic and hemodynamic parameters, pulse pressure variation, and stroke volume variation (SVV) (arterial pulse contour analysis, Flotrac/Vigileo system).ResultsWe prospectively studied seventy patients undergoing coronary artery bypass grafting (CABG) monitored with a radial arterial catheter, transesophageal echocardiography (TEE), and a pulmonary artery catheter (for cardiac output measurements), before and after the administration of 500 mL of crystalloid over 10 min after the anesthetic induction. Thirteen patients were excluded (total of 57 patients). Fluid responsiveness was defined as an increase in cardiac index of ≥ 15%. There were 21 responders (36.8%) and 36 non-responders (63.2%). No difference in baseline pulsed wave Doppler echocardiographic measurements of any components of the mitral, tricuspid, and pulmonary and hepatic venous flows were found between responders and non-responders. There was no difference in MV tissue Doppler measurements between responders and non-responders, including E/e' ratio (8.7 ± 4.1 vs. 8.5 ± 2.8 in responders vs. non-responders, P = 0.85). SVV was the only independent variable to predict an increase in cardiac index by multivariate analysis (P = 0.0208, OR = 1.196, 95% CI (1.028-1.393)).ConclusionsIn this pilot study, we found that no parameters of right and left ventricular diastolic function were associated with fluid responsiveness in patients undergoing CABG. SVV was the most useful parameter to predict fluid responsiveness.Trial registrationClinicalTrials.gov , NCT02714244 . Registered 21 March 2016-retrospectively registered.

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Differential cardiac remodeling in preload versus afterload.

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Differential cardiac remodeling in preload versus afterload.

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