Simulation of systolic and diastolic left ventricular dysfunction in a mock circulation: the effect of arterial compliance

Arterial compliance (AC) is expected to play a major role on cardiac efficacy by acute or long-term mechanisms. The aim of this study was to investigate the purely mechanical effect of AC on left ventricular (LV) performance, for different conditions of LV dysfunction (systolic versus diastolic). A hydraulic, Windkessel model of systemic circulation was used. LV function and aortic flow were simulated using a left ventricular assist device (LVAD). Two cases of LV dysfunction were simulated: Case A, systolic and Case B, diastolic dysfunction. In Case A, AC increased from 1.14 to 2.85 ml mm Hg &#109 1 leading to an increase in LVAD stroke volume up to 6%, while no significant effect was observed in Case B. LVAD systolic work was decreased by 4% in systolic and by 11% in diastolic LVAD dysfunction. The purely mechanical effect of AC changes on LVAD function was different between systolic and diastolic dysfunction. It might be expected that even an acute reduction in arterial stiffness could enhance LV performance by different means in systolic compared to diastolic dysfunction.     

Left ventricular assist device weaning: hemodynamic response and relationship to stroke volume and rate reduction protocols

Clinical evidence of myocardial recovery in a small cohort of patients supported with a left ventricular assist device (LVAD) has been reported. Development of an optimal LVAD weaning protocol is needed for these patients to sustain recovery after device explant. In this study, we tested the hypothesis that LVAD stroke volume reduction produces a steady-state mechanical reloading of left ventricular (LV) pressures and volumes compared with LVAD rate reduction that results in transient mechanical reloading of the heart due to beat-to-beat variation in LV pressures and volumes. The relationship of LVAD flow to LVAD stroke volume and systolic interval over a range of LVAD rates (60, 80, 100, 120, and 140 bpm) was validated in a mock circulatory flow loop. In six acute experiments, calves were implanted with a pneumatic paracorporeal LVAD (PVAD, Thoratec, Pleasanton, CA). The PVAD was operated asynchronously in the auto volume mode (full decompression) for 30 minutes to establish a baseline control condition. The calf hearts were then mechanically reloaded by LVAD rate reduction (80, 60, and 40 bpm) or LVAD stroke volume reduction (100, 120, and 140 bpm) protocols consisting of 30 minutes of support at each LVAD beat rate. The order of weaning protocols was randomized with a 30-minute recovery period (LVAD volume mode to fully decompress heart allowing it to rest) between protocols to enable return to baseline control state. Aortic pressure and flow, LV pressure and volume, pulmonary artery flow, and LVAD flow waveforms were recorded for each test condition. The LVAD stroke volume reduction protocol produced steady-state mechanical reloading compared with VAD rate reduction that resulted in transient LV mechanical reloading. This distinction is due to differences in their temporal relationships between LVAD and LV filling and emptying cycles. The acute hemodynamic benefit of LVAD stroke volume reduction was greater reduction in LV end-diastolic pressure and increase in LV segmental shortening than LVAD rate reduction. The long-term effects of steady-state and transient LV mechanical reloading on myocardial structure and function toward achieving sustained myocardial recovery warrant further investigation.     

左心室辅助装置控制模式影响双心室搏动同步性的数值研究

右心室(RV)衰竭已成为左心室辅助装置(LVAD)治疗的一种致命并发症。由LVAD引起的双心室搏动的不同步是引发RV功能障碍的重要因素。本文采用数值方法研究LVAD的控制模式对左、右心室搏动同步性的影响。数值结果表明:左心室(LV)与RV的收缩持续时间在无泵模式下没有显著差异(分别为48.52%和51.77%)。连续模式下,LV收缩期明显短于RV收缩期(LV vs.RV:24.38%vs.49.16%)和无泵模式的LV收缩期。搏动模式下,LV收缩期明显短于RV收缩期(LV vs.RV:28.38%vs.50.41%)但长于连续模式的LV收缩期。反搏动模式中的LV、RV收缩期差异较小(LV vs.RV:43.13%vs.49.23%),而LV收缩期短于无泵模式,并且长于连续模式。与连续和搏动模式相比,由反搏动模式提供的收缩期转速(RS)降低显著地校正了LV收缩持续时间,连续模式下缩短的收缩持续时间在反搏动模式下被校正为LV和RV之间的重新同步。因此,本文认为LV和RV收缩的再同步有助于预防RV功能障碍。总之,使用在收缩期间降低RS的反搏动模式有望用于由LVAD引起的双心室搏动不同步的临床校正。     

The effects of asymmetric ventricular filling on left–right ventricular interaction in the normal rat heart

Heart failure is characterised by ventricular dysfunction and with the potential for changes to ventricular volumes constraining the mechanical performance of the heart. The contribution of this interaction from geometric changes rather than fibrosis or metabolic changes is unclear. Using the constant pressure Langendorff-perfused rat heart, the volume interaction between left ventricle (LV) and right ventricle (RV) was investigated. RV diastolic stiffness (P?<?0.001) and developed pressure (P?<?0.001) were significantly lower than LV. When the RV was fixed at the end-diastolic volume (EDV) or EDV?+?50?%, both LV systolic and diastolic performance were unaffected with increasing LV balloon volume. However, at fixed LV volume, RV systolic performance was significantly decreased when LV volume increased to EDV?+?50?% when RV volume was increased incrementally between 50 and 300?μl (P?<?0.001). Systolic interaction in RV was noted as declining RV peak systolic load with increasing LV systolic pressure (P?<?0.05) and diastolic interaction was noted for RV when LV volume was increased from EDV to EDV?+?50?% (P?<?0.05). RV diastolic wall stress was increased with increasing LV balloon volume (P?<?0.05), but LV wall stress was unaltered at fixed RV balloon volume. Taken together, increasing LV volume above EDV decreased systolic performance and triggered ventricular constraint in the RV but the RV itself had no effect on the performance of the LV. These results are consistent with overload of the LV impairing pulmonary perfusion by direct ventricular interaction with potential alteration to ventilation–perfusion characteristics within the lung.     

Cardiovascular ultrasound: applications for the assessment of cardiac function

Congestive heart failure(CHF) is usually associated with impaired left ventricular(LV) systolic function, and thus, the measurement of systolic function is an essential component of the evaluation of any patients with known or suspected cardiac disease. Among many parameters, most frequently used are LV percent fractional shortening and ejection fraction(EF), which can be easily measured from an M-mode echocardiogram. However, these M-mode measurements may be inaccurate in patients with asymmetrical LV due to myocardial infarction, right ventricular overload or sigmoid septum. Especially in such cases, EF should be measured using two-dimensional echocardiography. Usually, LV volumes and EF are calculated using the disc-summation method through the manual tracing of apical two-chamber and four-chamber echocardiograms. On the other hand, it has been recognized that congestive heart failure may arise in the absence of any systolic dysfunction and CHF due to systolic dysfunction never occurs in the absence of concomitant diastolic dysfunction. Although the analysis of pulsed-Doppler transmitral flow velocity has been most widely used for the noninvasive assessment of LV diastolic function, an increase in left atrial pressure during CHF can pseudonormalize an abnormal flow pattern and mask LV diastolic dysfunction. Recently, we proposed a new index for assessing LV diastolic function, flow propagation velocity, which can be measured with color M-mode Doppler echocardiography and baseline-shift technique. Recent studies have shown that the flow propagation velocity is a unique noninvasive parameter of LV diastolic function which can accurately detect the diastolic impairment in patients with different types of cardiac diseases with various loading conditions.     

Arterial compliance is a main variable determining the effectiveness of intra-aortic balloon counterpulsation: quantitative data from an in vitro study

Quantitative data concerning the effect of arterial compliance (AC) on the effectiveness of intra-aortic balloon counterpulsation (IABC) are lacking. The main objective of this study was to investigate the relationship between AC and IABC performance. For this purpose we constructed a Windkessel, lumped-element, hydraulic model of the systemic circulation. The model consisted of a left ventricular assist device (LVAD), a compliance chamber, a peripheral resistor and two open reservoirs. Two Datascope Driving systems were used to operate the LVAD and intra-aortic balloon. We studied the effect of arterial compliance on the effectiveness of IABC at different levels of mean pressure (55, 75 and 95 mmHg) and heart rates (80, 100, 120 bpm). Three indices were used to evaluate IABC performance: the reduction of systolic and end-diastolic "arterial" pressure and the augmentation of diastolic pressure, induced by the IABC. A 22% decrease in AC (1.8-1.4 ml/mmHg) lead to a 30-40% increase in the indices of IABC performance, independently from pressure. In conclusion, arterial compliance significantly affects IABC efficacy and it could be considered as a further clinical criterion to decide IABC application.     

Assessment of synchronized direct mechanical ventricular actuation in a canine model of left ventricular dysfunction

Direct mechanical ventricular actuation (DMVA) is an experimental procedure that provides biventricular cardiac assistance by intracorporeal pneumatic compression of the heart. The advantages this technique has over other assist devices are biventricular assistance, no direct blood contact, pulsatile blood flow, and rapid, less complicated application. Prior studies of nonsynchronized DMVA support have demonstrated that a subject can be maintained for up to 7 days. The purpose of this study was to determine the acute hemodynamic effects of cardiac synchronized, partial DMVA support in a canine model (RVP) of left ventricular (LV) dysfunction. The study consisted of rapidly pacing seven dogs for 4 weeks to create LV dysfunction. At the conclusion of the pacing period, the DMVA device was positioned around the heart by means of a median sternotomy. The animals were then imaged in a 1.5 T whole body high speed clinical MR system, with simultaneous LV pressure recording. Left ventricular pressure-volume (PV) loops of the nonassisted and DMVA assisted heart were generated and demonstrated that DMVA assist shifted the loops leftward. In addition, assist significantly improved pressure dependent LV systolic parameters (left ventricular peak pressure and dp/dt max, p < 0.05), with no diastolic impairment. This study demonstrates that DMVA can provide synchronized partial assist, resulting in a decrease in the workload of the native heart, thus having a potential application for heart failure patients.     

Alteration of LV end-diastolic volume by controlling the power of the continuous-flow LVAD, so it is synchronized with cardiac beat: development of a native heart load control system (NHLCS)

There are many reports comparing pulsatile and continuous-flow left ventricular assist devices (LVAD). But continuous-flow LVAD with the pulsatile driving technique had not been tried or discussed before our group's report. We have previously developed and introduced a power-control unit for a centrifugal LVAD (EVAHEART?; Sun Medical), which can change the speed of rotation so it is synchronized with the heart beat. By use of this unit we analyzed the end-diastolic volume (EDV) to determine whether it is possible to change the native heart load. We studied 5 goats with normal hearts and 5 goats with acute LV dysfunction because of micro-embolization of the coronary artery. We used 4 modes, "circuit-clamp", "continuous", "counter-pulse", and "co-pulse", with the bypass rate (BR) 100%. We raised the speed of rotation of the LVAD in the diastolic phase with the counter-pulse mode, and raised it in the systolic phase with the co-pulse mode. As a result, the EDV decreased in the counter-pulse mode and increased in the co-pulse mode, compared with the continuous mode (p?相似文献   

Successful bridge to recovery with VAD implantation for anthracycline-induced cardiomyopathy

Anthracyclines are effective antineoplastic drugs, but they are known to be cardiotoxic. Recovery of cardiac function is rare. A few studies on implantation of a ventricular assist device (VAD) have been performed for anthracycline-induced cardiomyopathy. Recovery of left ventricular (LV) function with an LVAD is also rare. Recently, several adjunctive therapies were attempted to restore ventricular function. We report a successful bridge to recovery of ventricular function using VAD implantation for anthracycline-induced cardiomyopathy. The patient was a 57-year-old man who had been diagnosed with diffuse large B-cell lymphoma (DLBCL) at age 52. Combination chemotherapy including hydroxydaunorubicin was started. Complete remission was achieved after chemotherapy. Heart failure symptoms such as fatigue, dyspnea on exertion, and weight gain appeared 5 months later. A cardiac resynchronization device was implanted. His heart function deteriorated. He underwent implantation of a Toyobo LVAD and mitral annuloplasty. After implantation, he was prescribed carvedilol with spironolactone. He was weaned from the LVAD on postoperative day (POD) 239 and discharged on POD 37 after weaning. He remained in New York Heart Association classes within the first- to second-degree range, the LV dimention diastolic/systolic ratio was 56/46 mm, ejection fraction 38%, and mitral regurgitation mild at 3 years after weaning from the LVAD. Our patient could be weaned from LVAD probably due to the combination management strategy employing mitral valvuloplasty, use of cardiac resynchronization therapy, and taking carvedilol with spironolactone. Further studies will be needed to clarify the efficacy of these adjunctive therapies.     

Myocardial size and fibrosis changes during left ventricular assist device support

Previous studies have demonstrated that left ventricular assist device (LVAD) implantation significantly decreases myocyte size and reduces fibrosis of the left ventricle (LV). The objectives of the present study were to evaluate LV functional recovery after LVAD implantation and to assess its predictive factors, including histological findings of LV. Six patients with idiopathic cardiomyopathy underwent LVAD support with an EVAHEART implantable centrifugal pump (Sun Medical Technology Research, Nagano, Japan) for an average support duration of 2.91 years. Histologic samples were obtained from their LV apexes at the time of implantation. At 1 month and at 24 months after implantation, brain natriuretic peptide (BNP) and echocardiographic parameters were evaluated. Brain natriuretic peptide values, LV end-diastolic dimension, LV end-systolic dimension, functional shortening, and right ventricular systolic pressure (RVSP) were improved after LVAD implantation. Patients with developing fibrosis had longer durations of heart-failure history and higher pulmonary artery pressures. Patients with hypertrophic myocytes had smaller FS preoperatively. There was a correlation between the amount of fibrosis and the rate of BNP value change after LVAD implantation. In patients with less fibrosis and smaller myocytes preoperatively, improvement in LV function was observed during LVAD support.     

Shifting the pulsatility by increasing the change in rotational speed for a rotary LVAD using a native heart load control system

We have previously developed a native heart load control system for a continuous-flow left ventricular assist device (LVAD) ((EVAHEART^®; Sun Medical) and demonstrated that the rotational speed (RS) in synchronization with the cardiac cycle can alter pulsatility and left ventricular (LV) load under general anesthesia. In this study, we assessed the effects of different levels of increase in RS on pulsatility and LV load in the chronic awake phase. We implanted the EVAHEART via left thoracotomy in 7 normal goats (59.3 ± 4.6 kg). Two weeks after implantation, we examined the effects of co-pulse mode (increased RS in the systolic phase) and counter-pulse mode (increased RS in the diastolic phase), as well as shifting the change in RS from 250 to 500 rpm, and 750 rpm in both modes on pulsatility and LV load. Pulsatility was assessed using pulse pressure and mean dP/dt max of aortic pressure. LV load was assessed using stroke work and left ventricle end-diastolic volume determined from LV pressure–volume loops. In the co-pulse mode, pulsatility values increased as the change in RS increased. By contrast, in the counter-pulse mode, these values decreased as the change in RS increased. LV load increased significantly in the co-pulse mode compared with the counter-pulse mode, but there were no significant differences among the three levels of RS increase in either mode. Increasing RS to varying degrees with our newly developed system could contribute to pulsatility. However, it appeared to have little effect on LV load in normal hearts.     

Effective ventricular unloading by left ventricular assist device varies with stage of heart failure: cardiac simulator study

Although the use of left ventricular assist devices (LVADs) as a bridge-to-recovery (BTR) has shown promise, clinical success has been limited due to the lack of understanding the timing of implantation, acute/chronic device setting, and explantation. This study investigated the effective ventricular unloading at different heart conditions by using a mock circulatory system (MCS) to provide a tool for pump parameter adjustments. We tested the hypothesis that effective unloading by LVAD at a given speed varies with the stage of heart failure. By using a MCS, systematic depression of cardiac performance was obtained. Five different stages of heart failure from control were achieved by adjusting the pneumatic systolic/diastolic pressure, filling pressure, and systemic resistance. The Heart Mate II? (Thoratec Corp., Pleasanton, CA) was used for volumetric and pressure unloading at different heart conditions over a given LVAD speed. The effective unloading at a given LVAD speed was greater in more depressed heart condition. The rate of unloading over LVAD speed was also greater in more depressed heart condition. In conclusion, to get continuous and optimal cardiac recovery, timely increase in LVAD speed over a period of support is needed while avoiding the akinesis of aortic valve.     

Atrial, ventricular, or both cannulation sites to optimize left ventricular assistance?

The efficiency of left ventricular assist devices (LVADs) depends on the capacity of the inflow cannula to drain blood into the pump. Left atrial (LA) and left ventricular (LV) sites were compared in an animal model mimicking different hemodynamic conditions. Three calves (56.3+/-5.0 kg) were equipped with a Thoratec LVAD. A regular cardiopulmonary bypass (CPB) circuit was used as a right ventricular assist device (RVAD) (jugular vein/pulmonary artery), and preload conditions were adjusted by storage (or perfusion) of blood into (or from) the venous reservoir. LA and LV drainage, tested separately or simultaneously, was measured by its effect on the LVAD's performance. The LVAD was used alone on a beating heart or together with the RVAD (biVAD) on a beating and on a fibrillating heart. Increasing the central venous pressure (CVP) highlighted the differences between the LA and LV cannulation sites when the LVAD was tested either alone or together with the RVAD (biVAD) on a beating heart. Drainage through the LA or the LV was similar when CVP was set at 8 mm Hg, and increasing CVP to 14 mm Hg allowed for better drainage through the LV cannula. In contrast, after induction of fibrillation to mimic extreme heart failure, the drainage was better through the LA cannula. Using both LA and LV cannulae simultaneously did not improve the LVAD output in any of the conditions tested. LV cannulation provides better blood drainage when used on a normal beating heart and, therefore, allows for increased LVAD performance. However, in severe heart failure, blood drainage through the LV cannula decreases and the LA cannulation site is superior.     

Left ventricular outflow tract obstruction associated with chronic ventricular assist device support

Favorable long-term patient outcome after insertion of a left ventricular assist device (LVAD) as a bridge to recovery or destination therapy for the treatment of end-stage cardiomyopathy is adversely affected by pathophysiologic changes affecting the heart. Alterations in the native aortic valve apparatus, specifically aortic valve cusp fusion, is an example of such a phenomenon and may especially affect patients in cases of bridge to recovery, a rare but reported event. A retrospective review of the last 33 LVAD placements at our institution was conducted, including reviews of operative reports and pathologic examinations of the native hearts. Seven hearts were found to have varying degrees of aortic valve cusp fusion after chronic LVAD support (63-1, 339 days). Five of these patients had native aortic valves, and two had bioprosthetic valves. The left ventricular outflow tracts in two patients were surgically occluded at the time of LVAD insertion. Aortic valve cusp fusion occurs in roughly 25% of patients on chronic LVAD support. This phenomenon may prove to be clinically significant by creating a potential source of emboli and infection. In addition, in the case of myocardial recovery, left ventricular outflow tract obstruction could limit parallel flow and produce suprasystemic ventricular pressures that in turn would elevate left ventricular end diastolic pressures. The latter may contribute to further myocardial injury, ultimately limiting the ability of an otherwise recovered heart to be weaned from LVAD support.     

Diastolic function in healthy humans: non-invasive assessment and the impact of acute and chronic exercise

Left ventricular (LV) diastolic function is important because the enhanced systolic function that underpins high levels of cardio-respiratory fitness has to be matched by changes in LV filling, and LV diastolic dysfunction plays a key early role in the development and progression of a myriad of cardiovascular diseases. This review serves to detail knowledge in relation to: (1) the definition of diastole and the mechanical processes that occur during the diastolic period, (2) the quantitative assessment of diastolic function, predominantly focusing on non-invasive echocardiographic imaging modes such as tissue Doppler imaging and deformation analysis, (3) the impact of acute aerobic exercise on diastolic function, from the augmentation of function necessary to meet the demand for an increased cardiac output at exercise onset, to current concerns related to the impact of prolonged or ultra-endurance activity on diastolic function during recovery, (4) the adaptation in diastolic function observed with chronic aerobic exercise training in athletes and sedentary individuals who undergo training programmes, and (5) directions for future research.     

Mechanical function,glycolysis, and ultrastructure of perfused working mouse hearts following thoracic aortic constriction

BackgroundGlycolytic flux in the mouse heart during the progression of left ventricular hypertrophy (LVH) and mechanical dysfunction has not been described.MethodsThe main objectives of this study were to characterize the effects of thoracic aortic banding, of 3- and 6-week duration, on: (1) left ventricular (LV) systolic and diastolic function of perfused working hearts quantified by analysis of pressure–volume loops; (2) glycolytic flux in working hearts expressed as the rate of conversion of ³H-glucose to ³H₂O, and (3) ultrastructure of LV biopsies assessed by quantitative and qualitative analysis of light and electron micrographs.ResultsResults revealed that (1) indexes of systolic function, including LV end-systolic pressure, cardiac output, and rate of LV pressure development and decline, were depressed to similar degrees at 3 and 6 weeks post-banding; (2) diastolic dysfunction, represented by elevated LV end-diastolic pressure and volume, was more severe at 6 than at 3 weeks, consistent with a transition to failure; (3) a progressive decline in glycolytic flux that was roughly half the control rate by 6 weeks post-banding; and (4) structural derangements, manifested by increases in interstitial collagen content and myocyte Z-band disruption, that were more marked at 3 weeks than at 6 weeks.ConclusionThe results are consistent with the view that myocyte damage, fibrosis, and suppressed glycolytic flux represent maladaptive structural and metabolic remodeling that contribute to the development of failure in high pressure load-induced LVH in the mouse.     

Emergency implantation of a left ventricular assist device in adolescents with biventricular failure

Adolescents with congestive cardiomyopathy who present with intractable arrhythmia or progressive ventricular failure have a very poor prognosis and often die awaiting cardiac transplantation (CTx). We present our recent experience with a pneumatically powered left ventricular assist device (LVAD) implanted emergently to salvage adolescents with severe biventricular failure. Four patients, aged 15-17 years, body surface areas of 1.5-1.7 m2, with dilated cardiomyopathy (LV diastolic dimension, 7.1-8.3 cm); two presented with cardiovascular collapse, one with refractory ventricular tachycardia, and one with cardiac arrest. Hemodynamic and biochemical data before and 1 week after LVAD placement are expressed as mean and range values. None of the patients required right ventricular assist, and all patients achieved functional recovery while on LVAD support (8-71 days). Currently, all four patients are alive (11-22 months) after successful CTx. We conclude that emergency implantation of an LVAD in adolescents with biventricular heart failure can be life saving. As has been shown in the adult population, such a ventricular assist system restores normal circulatory hemodynamics, reverses multi-organ dysfunction, and provides a "safe" bridge to transplantation.     

Hemodynamic and pressure-volume responses to continuous and pulsatile ventricular assist in an adult mock circulation

This study investigated the hemodynamic and left ventricular (LV) pressure-volume loop responses to continuous versus pulsatile assist techniques at 50% and 100% bypass flow rates during simulated ventricular pathophysiologic states (normal, failing, recovery) with Starling response behavior in an adult mock circulation. The rationale for this approach was the desire to conduct a preliminary investigation in a well controlled environment that cannot be as easily produced in an animal model or clinical setting. Continuous and pulsatile flow ventricular assist devices (VADs) were connected to ventricular apical and aortic root return cannulae. The mock circulation was instrumented with a pressure-volume conductance catheter for simultaneous measurement of aortic root pressure and LV pressure and volume; a left atrial pressure catheter; a distal aortic pressure catheter; and aortic root, aortic distal, VAD output, and coronary flow probes. Filling pressures (mean left atrial and LV end diastolic) were reduced with each assist technique; continuous assist reduced filling pressures by 50% more than pulsatile. This reduction, however, was at the expense of a higher mean distal aortic pressure and lower diastolic to systolic coronary artery flow ratio. At full bypass flow (100%) for both assist devices, there was a pronounced effect on hemodynamic parameters, whereas the lesser bypass flow (50%) had only a slight influence. Hemodynamic responses to continuous and pulsatile assist during simulated heart failure differed from normal and recovery states. These findings suggest the potential for differences in endocardial perfusion between assist techniques that may warrant further investigation in an in vivo model, the need for controlling the amount of bypass flow, and the importance in considering the choice of in vivo model.     

Initial report of bridge to recovery in a patient with DuraHeart LVAD

Continuous-flow left ventricular assist devices (LVADs) provide acceptable clinical results, but the long waiting period for heart transplantation leads to diverse complications. LVAD support can cause reverse left ventricular (LV) remodeling that results in the improvement of LV function and allows LVAD removal. We present a case of successful removal of a DuraHeart LVAD because of sufficient recovery of LV function. Before LVAD removal, we conducted an “LVAD weaning test” by decreasing pump speed and performing an additional normal saline infusion test. We consider that the LVAD weaning test can be used in place of the “pulsatile LVAD off test.”     

Experimental acute hypoxia in healthy subjects: evaluation of systolic and diastolic function of the left ventricle at rest and during exercise using echocardiography

To clarify whether or not systolic and diastolic function of the human left ventricle (LV) were decreased during acute hypoxia, at rest and with exercise, 14 healthy male volunteers [age 25.9 (SD 3.0) years, height 182.9 (SD 7.1) cm, body mass 75.9 (SD 6.9)kg] were examined using M-mode and 2D-mode echocardiography to determine the systolic LV function as well as Doppler-echocardiography for the assessment of diastolic LV function on 2 separate test days. In random order, the subjects breathed either air on 1 day (N) or a gas mixture with reduced oxygen content on the other (H; oxygen fraction in inspired gas 0.14). Measurements on either day were made at rest, several times during incremental cycle exercise in a supine position (6-min increments of 50 W, maximal load 150 W) and in 6th min of recovery. Corresponding measurements during N and H were compared statistically. Arterial O₂ tension (P _aO₂) was normal on N-day. All subjects showed a marked acute hypoxia at rest [P _aO₂, 54.5 (SD 4.6) mmHg], during exercise and recovery on H-day. The latter was associated with tachycardia compared to N-day. All echocardiographic measurements at rest were within the limits of normal values on both test days. Ejection time, end-systolic and end-diastolic left ventricular dimensions as well as the thickness of left posterior wall and of interventricular septum showed no statistically significant influence of H either at rest or during exercise. Stroke volume and cardiac output were always higher on H-day, which could be attributed to a slight reduction in end-systolic volume with unaffected end-diastolic volume as well as to increased heart rates. Among the indices of systolic LV function the fractions of thickening in the left ventricular posterior wall and interventricular septum showed no differences between H and N at rest or during exercise. However, fibre shortening, ejection fraction and mean circumferential fibre shortening were increased on H-day on all occasions. The mitral-valve-Doppler ratio, the index of diastolic LV function, was decreased with H at rest, showed a more pronounced reduction during exercise and was still lower in 6th min of recovery compared to N-day. It was concluded that with acute hypoxia of the severity applied in this study left ventricular systolic function in our healthy subjects showed a pronounced improvement and left ventricular diastolic function was reduced, both at rest and with exercise.