Aerobic exercise training reduces cardiac function and coronary flow-induced vasodilation in mice lacking adiponectin

We tested the hypothesis that adiponectin deficiency attenuates coronary microvascular and cardiac function and prevents exercise training-induced adaptations of the coronary microvasculature and the myocardium in adult mice. Adult wild-type (WT) or adiponectin knockout (adiponectin KO) mice underwent treadmill exercise training or remained sedentary for 8-10 weeks. Systolic and diastolic function were assessed before and after exercise training or cage confinement. Vasoreactivity of coronary resistance arteries was assessed at the end of exercise training or cage confinement. Before exercise training, ejection fraction and fractional shortening were similar in adiponectin KO and WT mice, but isovolumic contraction time was significantly lengthened in adiponectin KO mice. Exercise training increased ejection fraction (12%) and fractional shortening (20%) with no change in isovolumic contraction time in WT mice. In adiponectin KO mice, both ejection fraction (-9%) and fractional shortening (-12%) were reduced after exercise training, and these decreases were coupled to a further increase in isovolumic contraction time (20%). In sedentary mice, endothelium-dependent dilation to flow was higher in arterioles from adiponectin KO mice as compared to WT mice. Exercise training enhanced dilation to flow in WT mice, but decreased flow-induced dilation in adiponectin KO mice. These data suggest that compensatory mechanisms contribute to the maintenance of microvascular and cardiac function in sedentary mice lacking adiponectin; however, in the absence of adiponectin, coronary microvascular and cardiac adaptations to exercise training are compromised.

Impact of Decreased Transmural Conduction Velocity on the Function of the Human Left Ventricle: A Simulation Study

This study investigates the impact of reduced transmural conduction velocity (TCV) on output parameters of the human heart. In a healthy heart, the TCV contributes to synchronization of the onset of contraction in individual layers of the left ventricle (LV). However, it is unclear whether the clinically observed decrease of TCV contributes significantly to a reduction of LV contractility. The applied three-dimensional finite element model of isovolumic contraction of the human LV incorporates transmural gradients in electromechanical delay and myocyte shortening velocity and evaluates the impact of TCV reduction on pressure rise (namely, dP/dtmax) and on isovolumic contraction duration (IVCD) in a healthy LV. The model outputs are further exploited in the lumped “Windkessel” model of the human cardiovascular system (based on electrohydrodynamic analogy of respective differential equations) to simulate the impact of changes of dP/dtmax and IVCD on chosen systemic parameters (ejection fraction, LV power, cardiac output, and blood pressure). The simulations have shown that a 50% decrease in TCV prolongs substantially the isovolumic contraction, decelerates slightly the LV pressure rise, increases the LV energy consumption, and reduces the LV power. These negative effects increase progressively with further reduction of TCV. In conclusion, these results suggest that the pumping efficacy of the human LV decreases with lower TCV due to a higher energy consumption and lower LV power. Although the changes induced by the clinically relevant reduction of TCV are not critical for a healthy heart, they may represent an important factor limiting the heart function under disease conditions.

P1382 Evidence for longitudinal aorta strain relationship with noninvasive left ventricular myocardial work: another component for the ventricular-aorta coupling?

The force required to produce longitudinal strain of the aorta represents an often overlooked mechanical load imposed on the left ventricle (LV). 2D speckle tracking strain analysis (2D-SpTa) may be applied on aorta wall in order to evaluate regional longitudinal strain (AoSTR). A noninvasive method for measuring LV myocardial work (MW) has been recently proposed, based on 2D-SpTa combined with estimated pressure curve. Aim of the study was to assess the relationship of both LV conventional functional indices and the new MW ones with the aorta function estimated by AoSRT in normals and to interrogate the potential effect of aging. Methods Fifty four normals, 24 males (M) and 30 females(F), age: 52 ± 13 (25-75 years), were selectively studied, provided that they had an efficient image quality to apply both AFI analysis for MW estimation and ascending aorta interrogation for AoLSTR (EchoPac GE) . LAoLSTR was measured in the posterior aorta wall (apical long axis view). Aortic wall borders were traced longitudinally adjusting width using 4 points of interest. The first point was put at the sinotubular junction and approximately 3-4 cm of the ascending aorta were analyzed. 2D-SpTa divided the regions of interest into proximal, middle and distal segments and the respective peak LAoSTR were considered. The following indexes of MW were estimated: GWI (global work index = total work from mitral valve closure to mitral valve opening), GCW (global constructive work = total work contributing to pump function, namely due to shortening during isovolumic contraction and ejection and lengthening during isovolumic relaxation), GWW (global wasted work = elongation during isovolumic contraction/ejection and shortening during isovolumic relaxation), GWE (global work efficiency = fraction of GCW/[GCW + GWW]). AFI derived LV strain (LVGS), biplane LV ejection fraction and stroke volume (SV) were also calculated. Results LAoSTR in any wall position was not affected by age. LAoLSTR of the proximal segment was related to both EF and LVGS (r = 0.31, p = 0.03 and r=-0.28 p = 0.05, respectively). Middle and distal LAoSTR were not related to either EF or LVGS. SV was not related to any of LAoSTR. LAoSTR of the proximal segment was related to both GWI and GCW ( r = 0.34 p = 0.016 and r = 0,31 p = 0.03 respectively). LAoSTR of the middle and distal segments were not related with any LV MW parameters. Conclusion Longitudinal aorta strain evaluation by 2D-SpTa is feasible and it is related with functional performance of the LV estimated by either conventional or MW indices based on 2D-SpTa. Moreover , the longitudinal performance of the proximal segment of the aorta above the sinotubular junction is linked to the constructive component of the LV myocardial work thus providing an alternative evidence for the LV ventricular–aorta coupling which was independent from aging.

P3467Tricuspid annular isovolumic acceleration is more useful for the assessment of right ventricular systolic function in patients after repair of tetralogy of Fallot with pulmonary regurgitation

Introduction The detrimental impact of pulmonary regurgitation (PR) on right ventricular (RV) function of patients after repair of tetralogy of Fallot (TOF) is recognized. Although tricuspid annular isovolumic acceleration (IVA) is useful for the evaluation of RV function, it requires complicated measurement. Tricuspid annular plane systolic excursion (TAPSE) is measured easily and has also been validated as a marker of RV systolic function. Hypothesis We assessed the hypothesis that IVA has advantage to the stratification of the detrimental impact of PR on RV systolic function after TOF repair compared with TAPSE. Methods We prospectively examined patients after TOF repair. Patients <1 year after the repair, those with the history of sustained arrhythmia and those who required concomitant tricuspid and/or pulmonary valve surgery were excluded from the study. IVA was measured by dividing the myocardial velocity during isovolumic contraction by the time interval from the onset of the myocardial velocity during the isovolumic contraction to the time at the peak velocity of this wave. TAPSE was measured using M-mode echocardiography with the M-line passing through the lateral annulus of tricuspid valve in the apical 4-chamber plane. PR jets were evaluated in the parasternal short-axis plane. PR degree was assessed by the number of correspondence to the following conditions; 1) diastolic flow reversal in the main pulmonary artery, 2) diastolic flow reversal in the branch pulmonary arteries, 3) pressure half-time of PR signal <100 msec and 4) the ratio of the duration of the PR signal to the total duration of diastole <0.77. PR degree was graded from 0 to 4. Results Twenty-two patients were enrolled to the study. Age, female, period after the TOF repair and body height of the patients were 11±6 years, 55%, 9±5 years and 137±28 cm, respectively. In all the patients, IVA and TAPSE were 160±27 cm/sec2 and 12±2 mm, respectively. PR degrees were graded as 2, 3 and 4 in 4, 14 and 4 patients, respectively. By the Kruskal-Wallis test, only IVA showed a significant difference among the 3 PR degrees. Conclusion In conclusion, IVA can be a useful index for the stratification of RV function in patients after TOF repair with various degrees of PR.