Mechanical Effects Of Positive Intrathoracic Pressure On Left Ventricular Function In Healthy Subjects And Its Mechanism

Intrathoracic pressure changes with respiration, which exerts mechanicaleffects on cardiovascular hemodynamics. However, the mechanism of thisphenomenon still remains obscure. For over one hundred and thirty years, themechanism study for this phenomenon has challenged investigators and manyproposed hypotheses were proved to be irrational. Some have suggested thatinspiration increases venous capacitance of the pulmonary vessels, therebyreducing venous return to the left heart. But the results of the study by Scharf SMverified that without expansion of the pulmonary vessels, left heart output willstill decrease. Some have proposed that LV filling during inspiration decreasesbecause of compression of the LV from the enlarging right ventricle, however,this is just the description of the phenomenon but not the mechanism. It is alsoproposed that LV ejection is impeded by the fall of the intrathoracic pressurearound the heart comparable to an increase in arterial pressure, however, whichseems the consequence of decreased intrathoracic pressure and can notreasonably explain it.We find that the above hypotheses failing to explain this phenomenon is that previous studies only involved the changes of LV hemodynamics and theresulting changes in LV function while neglected the directly mechanical effectsof intrathoracic pressure on LV ejection and filling. Accordingly, using theValsalva maneuver (VM) to simulate and amplify the situation of expiratoryphase, we designed these studies with echocardiography to evaluate the changesof LV ejection and filling induced directly by increased positive intrathoracicpressure.Part1. Changes of left ventricular filling during the strain phase of Valsalvamaneuver in healthy subjects and its mechanismObjectiveThe aim of this study was to explore changes of left ventricular filling duringthe strain phase of Valsalva maneuver (VM) and its mechanism.Methods30healthy volunteers were recruited to perform VM with a load of40mmHg.Left ventricular filling parameters (E, A, E/A ratio, e and E/e ratio) weredetermined by echocardiography at baseline, at the first beat and at the secondbeat during the strain phase of VM, respectively.ResultsCompared to those at baseline, E, E/A ratio and E/e ratio increased (P＜0.05）while A and e did not change (P＞0.05）at the first beat during the strain phase;Compared to those at the first beat during the strain phase, E, E/A ratio and E/eratio decreased (P＜0.05）while A and e did not change (P＞0.05）at the secondbeat during the strain phase.ConclusionsLeft ventricular filling decreased at the second beat during the strain phase of VM, which is different from the present knowledge that left ventricular fillingwould begin to decrease4-5beats later during the strain phase of VM. Positiveintrathoracic pressure decreases left-side heart and pulmonary vessel’ transmuralpressure while increases the blood resistance, which might be the reason that E,E/A ratio and E/e ratio decreased at the second beat during the strain phase ofVM. Part2. Evaluation of the motion of septum during the strain phase ofValsalva maneuver in normal person by radius of curvatureObjectiveThe aim of this study was to evaluate the displacement of septum during thestrain phase of Valsalva maneuver (VM) in normal person by radius of curvature(RC).Methods23healthy volunteers were recruited to perform VM with a load of40mmHglasted for10seconds. The two-dimensional short-axis images of left ventricularduring quiet breath and during the VM were recorded and were analyzed withself-designed software to gain RC of septum and to calculate the changes.ResultsRC of septum during inspiration＞10th second during the VM＞duringexpiration＞5th second during the VM, any two of which, there is a significantchange (P＜0.01）.ConclusionsDuring the strain phase of VM, septum will displace towards right ventricular at the5th second while there is no significant displacement at10th second. Part3. Mechanical Effects of Positive Intrathoracic Pressure on LeftVentricular Filling in Healthy Subjects and Its MechanismObjectiveOur aim was to explore the mechanical effects of positive intrathoracicpressure on left ventricular (LV) filling in healthy subjects and its mechanism.Methods1、 SubjectsWe recruited thirty healthy volunteers,21men and9women, with a meanage of39±17years（range,23to66years), height of171±8cm, and weight of68±9kg in this study. None of these subjects had clinical symptoms, signs orhistory of any disease as determined by detailed inquiry, physical examination,electrocardiogram (ECG), chest X-ray and echocardiography. Alcohol, tobacco,strong tea and coffee were not allowed on the day of the test.2、 Quantification of the load of VMA self-made device was used to quantify and standardize the load of VM,which was modified from a watch style sphygmomanometer and has beendescribed in our previous study. Differently, a facial mask that could cut offventilation from both mouth and nose was used in the present study. Its functioncan compare with the previously used. All subjects were trained on how to usethe device to quantify and standardize a VM3、 Examining protocolAt first, the subjects were asked to breathe quietly and naturally. After the subjects’ heart rate remaining at a stable level, echocardiography images wererecorded. Then the subjects were instructed to perform VM, at a load of40mmHg lasted for10seconds, with the self-made device quantified and standardized.Echocardiography images were recorded during the strain phase of VM.Measurements were performed at rest and at10th second during the strain phase.During measurements, investigators were blinded to the subjects’ data. HR wasobtained from the simultaneously recorded ECG. LV inflow velocities weredetermined using pulse-wave Doppler. Early diastolic flow velocity (E) and latediastolic flow velocity（A) were analyzed and E/A ratio was calculated. Earlydiastolic velocity (e) of the septal portion of the mitral annulus was determinedusing pulse-wave tissue Doppler imaging and E/e ratio was calculated.4、 Statistics analysisSPSS13.0statistic software was used. Data were expressed as mean±standard deviation. Continuous data were compared with paired Student’s t-testwhen appropriate. Probability ratio P＜0.05was considered statisticallysignificant.ResultsCompared to the rest, at10th second, early diastolic velocity (E)significantly decreased (P＜0.05), late diastolic velocity (A) insignificantlydecreased (P＞0.05) and E/A ratio significantly decreased (P＜0.05); earlydiastolic velocity (e) of the mitral annulus did not changed (P＞0.05) and E/eratio significantly decreased (P＜0.05), heart rate (HR) dramatically increased (P＜0.001).ConclusionsMechanical effect of positive intrathoracic pressure on LV free wall impedesLV diastolic motion, which could cause the decrease of E and E/A ratio. Positive intrathoracic pressure increases the flow resistance of LV and pulmonaryvasculature, which may contribute to the decrease of E and E/e ratio. Part4. Mechanical Effects of Positive Intrathoracic Pressure on LeftVentricular systolic function in Healthy Subjects and Its MechanismObjectiveOur aim was to explore the mechanical effects of positive intrathoracicpressure on left ventricular (LV) systolic function in healthy subjects and itsmechanism.Methods1、SubjectsWe recruited twenty healthy volunteers,15men and5women, with a meanage of38.3years（range,24to62years). None of these subjects had the signs,symptoms, or history of disease as determined by history-taking, physicalexamination, electrocardiography (ECG), chest radiography, andechocardiography. Consumption of alcohol, tobacco, strong tea or coffee was notallowed on the test day.2、Quantification of VMA self-made device which was refitted from a watch-stylesphygmomanometer, as described in our previous study. A face-mask that couldcut off ventilation from the mouth and nose (and whose function could becompared with the face-mask used in our previous study) was employed. Allsubjects were trained on how to use the device to quantify and standardize a VM 2、Examining protocolAll experiments were undertaken in the evening≥2h after a light supper.GE Vivid7(GE Healthcare, Piscataway, NJ, USA) echocardiographic systemswere used with probe frequencies of2.5–4.0MHz.Subjects were initially asked to breathe quietly and naturally. After a stableHR was achieved, echocardiographic images were recorded. Subjects were theninstructed to carry out the VM at a load of40mmHg for10s. This action wascarefully monitored using a self-made device. Echocardiographic images werealso recorded at10s during the strain phase. Measurements were recorded at restand at10s during the strain phase. During measurements, investigators wereblinded to the subjects’ data. Off-line analyses included left-ventricularend-diastolic volume (LVEDV), left-ventricular end-systolic volume (LVESV),stroke volume (SV), ejection fraction (EF), cardiac output (CO), peak aorticvelocity(PV) and mean local acceleration(MAC). HR was obtained from thesimultaneously recorded ECG.4、 Statistics analysisSPSS13.0statistical software (SPSS, Chicago, IL, USA) was used. Data aremean±standard deviation. Continuous data were compared using the pairedStudent’s t-test if appropriate. P＜0.05was considered significant.ResultsCompared to the rest, at10th second, LVEDV, LVESV and LV strokevolume (SV) dramatically decreased (P＜0.001) while heart rate (HR)dramatically increased (P＜0.001), and ejection fraction (EF) insignificantlyincreased (P＞0.05), CO and PV significantly decreased (P＜0.05), MAC hadnot changed (P＞0.05).Conclusions Mechanical effects of positive intrathoracic pressure acts on LV free wall, itsdirection is nearly identical to that for the direction of the LV contraction force.Hence, cardiac systolic was enhanced and EF increased at10s during the strainphase of the VM. Mechanical effects of positive intrathoracic pressure increasesthe flow resistance of LV and pulmonary vasculature, which may contribute tothe decrease of blood volume, then the decrease of CO and PV.