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Biomedical subjects

Hirotsugu Yamada

Publications and source records attributed to Hirotsugu Yamada.

At least 19 recordsLinked to original sources

Angiotensinergic stimulation of vascular endothelium in mice causes hypotension, bradycardia, and attenuated angiotensin response.

It is not clear whether endothelial cell (EC) activation by the hormone angiotensin II (Ang II) modulates contraction of vascular smooth muscle cells (VSMCs) in the vasculature and whether impairment of this regulation in vivo contributes to hypertension. Delineation of the actions of Ang II through the type 1 receptor (AT1R) on ECs in the blood vessels has been a challenging problem because of the predominance of the AT1R functions in VSMCs that lie underneath the endothelium. We have obviated this limitation by generating transgenic (TG) mice engineered to target expression of the constitutively active N111G mutant AT1R only in ECs. In these TG mice, the enhanced angiotensinergic signal in ECs without infusion of Ang II resulted in hypotension and bradycardia. The pressor response to acute infusion of Ang II was significantly reduced. Increased expression of endothelial nitric oxide synthase and production of hypotensive mediators, nitric oxide and cyclic guanosine monophosphate, cause these phenotypes. Hypotension and bradycardia observed in the TG mice could be rescued by treatment with an AT1R-selective antagonist. Our results imply that the Ang II action by means of EC-AT1R is antagonistic to vasoconstriction in general, and it may moderate the magnitude of functional response to Ang II in VSMCs. This control mechanism in vivo most likely is a determinant of altered hemodynamic regulation involved in endothelial dysfunction in hypertensive cardiovascular disease.

Angiotensins↗

Clinical features of mixed physiology of constriction and restriction: echocardiographic characteristics and clinical outcome.

AIMS: An entity of patients with mixed physiology of constriction and restriction has been reported, however, the characteristics of these patients have not been well documented. We evaluated the clinical features and the outcome of these patients. METHODS AND RESULTS: Study subjects consisted of 38 patients (57+/-14 years, 8 females, 30 males) who were diagnosed as having mixed physiology based on transthoracic and/or transesophageal echocardiography, MRI (or CT), cardiac catheterization, endomyocardial biopsy and/or surgical findings. Prior radiation therapy was the most frequent (50%) cause of mixed physiology followed by coronary artery bypass graft without prior radiation (24%) and heart transplantation (8%). The respiratory variation of peak early diastolic transmitral flow velocity by pulsed Doppler transesophageal echocardiography was 10.7% in patients with sinus rhythm and 18.1% in patients with atrial arrhythmia. Pericardial thickening was noted adjacent to the right-sided chambers in 19 patients, left-sided chambers in 10 patients, or both in 9 patients. All-cause 5-year mortality was 40% and unrelated to age, etiology, left ventricular systolic function and therapeutic course. There was a statistically significant difference (p<0.01) between the survival rates in patients with mixed physiology and in patients with pure constriction (n=125). CONCLUSIONS: Due to the high mortality in this disease, discrimination of the entity from the patients with pure constriction is mandatory. Transthoracic and transesophageal echocardiography are helpful noninvasive techniques in the diagnosis and the understanding of the physiology of patients with mixed constriction and restriction.

Adult↗

The effects of altering time delays of coupled pacing during acute atrial fibrillation.

BACKGROUND: Coupled pacing (CP), which consists of delivering a premature electrical stimulation to the heart after the effective refractory period of ventricular activation, is a novel method for controlling ventricular rate during atrial fibrillation (AF). It also has been established that CP improves pump function by enhancing external cardiac work and myocardial efficiency. OBJECTIVE: The purpose of the present study was to determine if two time delays for CP (short and long) would result in similar improvements in ventricular function. METHODS: In a canine model, we applied CP at two time delays (CP-S and CP-L) during two stages: sinus rhythm (SR) and acute AF. The cardiac responses to CP during SR served as the nontachycardic and nondepressed control. During both rhythms, we shortened the coupling interval until we obtained maximal contractility, designated CP-S. Next, we increased the delay until we started to see a measurable secondary contraction (left ventricular pressure development of approximately 20 mmHg). These longer delays were designated CP-L. RESULTS: Our results showed that the ventricular rate of intrinsic activation (VRIA) remained decreased despite prolongation of the time delay of CP during both AF and SR. Also, both delays of CP increased left ventricular systolic pressure (LVSP) and dLVP/dt, which are indices of myocardial contractility. In contrast, CP increased external cardiac work only during AF. Prolonging this time delay did not markedly decrease the improvement in external cardiac work. Myocardial O(2) consumption (MVO(2)) did not significantly change as the result of CP during either SR or AF. Finally, myocardial efficiency improved during AF as the result of CP at both time delays. CONCLUSIONS: In conclusion, shorter time delays for CP increased contractile strength during both SR and AF. However, extending the time delay of CP had minimal effects on diminishing the improved ventricular pump function and energetics that resulted from CP during AF. Thus, the maximal enhancement of myocardial contractility via CP-S was not needed to maintain the improved ventricular function during acute AF when CP is applied.

Acute Disease↗

An experimental rabbit model for off-pump left ventricular reconstruction following left ventricular aneurysm.

BACKGROUND: Cardiac electromechanical remodeling following left ventricular reconstruction (LVR) surgery is not fully understood. Further development of an animal model will facilitate investigations in this area. In the present study, we aimed to establish a novel LVR procedure without the use of cardiopulmonary bypass in a rabbit left ventricular (LV) aneurysm model. METHODS: LV aneurysm was created in 6 rabbits by ligation of the distal left coronary artery. More than a month later, LVR aneurysm surgery was performed off-pump using a purse-string suture around the aneurysm. Cardiac dimensions and function were evaluated using echocardiographic techniques perioperatively and 4 weeks after LVR surgery. Six structurally normal hearts were used as controls. RESULTS: LVR surgery was successfully performed in all 6 rabbits. Both LV end-diastolic volume (LVEDV, 4.6 +/- 0.9 to 3.3 +/- 0.6 mL; P < .01) and LV end-systolic volume (LVESV, 2.5 +/- 0.6 to 1.5 +/- 0.2 mL, P < .01) were decreased immediately postsurgery versus presurgery, and LV ejection fraction (LVEF) was increased (44.5 +/- 5.3 to 55.6 +/- 4.8%, P < .001). For comparison, in normal rabbits (n = 6), LVEDV, LVESV and LVEF were 3.1 +/- 0.7 mL, 1.2 +/- 0.5 mL, and 64.5 +/- 8.8%, respectively. During follow-up, one rabbit died 3 weeks after surgery from an unknown cause. In the remaining 5 animals, improvements of LVEDV (3.7+/- 0.4 mL, P < .05), LVESV (1.7 +/- 0. 3 mL, P < .01), and LVEF (53.1 +/- 2.8%, P < .01) were maintained versus presurgery values for more than 4 weeks after LVR. CONCLUSIONS: Off-pump LVR of rabbit LV aneurysm is an effective and less invasive surgery that resulted in sustained improvement in cardiac function with no gross intraoperative or postoperative mortality. This may be a useful model for investigations of electromechanical remodeling following LVR.

Animals↗

Chronic atrioventricular nodal vagal stimulation: first evidence for long-term ventricular rate control in canine atrial fibrillation model.

BACKGROUND: We have previously demonstrated that selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during atrial fibrillation (AF) in acute experiments. However, it is not known whether this approach could provide a long-term treatment in conscious animals. Thus, this study reports the first observations on the long-term efficacy and safety of this novel approach to control ventricular rate during AF in chronically instrumented dogs. METHODS AND RESULTS: In 18 dogs, custom-made bipolar patch electrodes were sutured to the epicardial AVN fat pad for delivery of selective AVN-VS by a subcutaneously implanted nerve stimulator (pulse width 100 micros or 1 ms, frequency 20 or 160 Hz, amplitude 6 to 10 V). Fast-rate right atrial pacing (600 bpm) was used to induce and maintain AF. ECG, blood pressure, and body temperature were monitored telemetrically. One week after the induction of AF, AVN-VS was delivered and maintained for at least 5 weeks. It was found that AVN-VS had a consistent effect on ventricular rate slowing (on average 45+/-13 bpm) over the entire period of observation. Echocardiography showed improvement of cardiac indices with ventricular rate slowing. AVN-VS was well tolerated by the animals, causing no signs of distress or discomfort. CONCLUSIONS: Beneficial long-term ventricular rate slowing during AF can be achieved by implantation of a nerve stimulator attached to the epicardial AVN fat pad. This novel concept is an attractive alternative to other methods of rate control and may be applicable in a selected group of patients.

Animals↗

Differences in left ventricular long-axis function from mice to humans follow allometric scaling to ventricular size.

While the heart size maintains a constant proportion to body size, heart function parameters, such as heart rate and cardiac output, show a more complex scaling pattern. How these phenomena affect the long-axis left ventricular (LV) function is unknown. We studied 10 mice, 15 rats, 6 rabbits, 8 mongrel dogs and 38 human volunteers. Doppler tissue echocardiography data were postprocessed to reconstruct mitral annulus (MA) peak systolic velocity and displacement. The relationship between MA peak velocity, MA displacement and LV ejection time, and LV end-diastolic volume (and mass) were fit to an allometric (power-law) equation Y=kMbeta. LV mass varied from 0.062 to 255 g, while end-diastolic volume varied from 0.014 to 205 ml. beta values of the relation between LV ejection time and LV end-diastolic volume and mass were 0.247+/-0.017 and 0.267+/-0.018, respectively. beta values of the relationship between MA displacement and LV end-diastolic volume and mass were 0.358+/-0.047 and 0.390+/-0.051 (P<0.023 versus beta of LV ejection time). beta values of the relationship between MA peak systolic velocity and LV end-diastolic volume and mass were 0.096+/-0.012 and 0.100+/-0.013, respectively (P<0.0001 versus 0). Finally, beta values of the relationship between the long-to-short axis displacement ratio and LV end-diastolic volume and mass were 0.077+/-0.017 and 0.086+/-0.019 (P<0.0001 versus 0). We conclude that MA velocity, displacement, and long-to-short axis displacement ratio scale allometrically to heart size. This reduces the relative long-axis contribution to heart function in small mammals.

Animals↗

Usefulness of Doppler assessment of pulmonary vein and left atrial appendage flow following pulmonary vein isolation of chronic atrial fibrillation in predicting recovery of left atrial function.

Atrial fibrillation (AF) is a widespread condition that causes significant morbidity and mortality. Recently, pulmonary venous (PV) isolation using radiofrequency ablation has been used successfully to exclude the pulmonary venous ostia, resulting in correction of AF. Further, miniaturized high-frequency ultrasound phased-array transducers currently provide Doppler and 2-dimensional imaging during the ablation procedure. We examined atrial function and its determinants using intracardiac echocardiography before and after PV isolation in 45 patients who had chronic AF (56 +/- 11 years old). PV, left atrial (LA) appendage, and mitral and tricuspid flows were recorded. Recovery of booster pump function (defined by the presence of mitral inflow A wave, LA appendage a-wave, and PV A-reversal wave velocities >10 cm/s) was observed in 39 of 45 patients (86.6%). PV flow systolic wave before and after ablation correlated with the degree of LA booster pump function after PV isolation. An early systolic PV flow peak velocity >57.47 cm/s predicted "good" LA booster pump function recovery with 96% specificity. Diastolic LA appendage emptying in AF correlated (p <0.001) and predicted good LA booster pump function with 92% specificity for velocities >46.4 cm/s. Thus, monitoring LA function during PV isolation for chronic AF is feasible. Most patients recovered LA booster pump function immediately after PV isolation, and the degree of recovery correlated with LA reservoir function. Preserved reservoir function during AF is predictive of satisfactory recovery of booster pump function after PV isolation.

Aged↗

Aggregation behavior of latex particles in shear flow confined between two parallel plates.

In this study, the aggregation and breakup behaviors of latex particles in shear flow confined between two parallel plates were investigated using an in situ observation apparatus with a laser scanning confocal microscope. To investigate the effects of shear rate and the gap width between two parallel plates on the size and structure of the aggregates in the steady state, the distributions of the projected cross-sectional area and perimeter-based fractal dimension of the aggregates were measured. As a result, the average size of the aggregates decreases as shear rate increases and the gap width decreases due to the hydrodynamic effect acting on the aggregates. The size distributions of the aggregates become narrow as the gap width decreases. In addition, the fractal dimension, that is, the structure of the aggregates, was almost independent of shear rate and the gap width and approximately 1.2, which suggests that the aggregates are relatively compact.

Journal Article↗

Assessment of left ventricular torsional deformation by Doppler tissue imaging: validation study with tagged magnetic resonance imaging.

BACKGROUND: Left ventricular (LV) torsional deformation is a sensitive index for LV performance but difficult to measure. The present study tested the accuracy of a novel method that uses Doppler tissue imaging (DTI) for quantifying LV torsion in humans with tagged magnetic resonance imaging (MRI) as a reference. METHODS AND RESULTS: Twenty patients underwent DTI and tagged MRI studies. Images of the LV were acquired at apical and basal short-axis levels to assess LV torsion. We calculated LV rotation by integrating the rotational velocity, determined from DTI velocities of the septal and lateral regions, and correcting for the LV radius over time. LV torsion was defined as the difference in LV rotation between the 2 levels. DTI rotational and torsional profiles throughout systole and diastole were compared with those by tagged MRI at isochronal points. Rotation and torsion by DTI were closely correlated with tagged MRI results during systole and early diastole (apical and basal rotation, r=0.87 and 0.90, respectively; for torsion, 0.84; P<0.0001, by repeated-measures regression models). Maximal torsion showed even better correlation (r=0.95, P<0.0001). CONCLUSIONS: The present study has shown that DTI can quantify LV torsional deformation over time. This novel method may facilitate noninvasive quantification of LV torsion in clinical and research settings.

Aortic Valve Insufficiency↗

Automated mitral annular tracking: a novel method for evaluating mitral annular motion using two-dimensional echocardiography.

We developed an automated mitral annular tracking method based on a digital processing of high frame rate cineloop images of 2-dimensional echocardiography. In this study, its feasibility and accuracy was validated in 11 healthy volunteers and 16 patients with left ventricular (LV) dysfunction. The mitral annular excursion measured by automated mitral annular tracking agreed well with that measured by 3-dimensional echocardiography and correlated with LV ejection fraction. The longitudinal mitral annular excursion was reduced whereas the radial one was preserved for patients with LV dysfunction compared with control subjects. The novel automated mitral annular tracking method is clinically feasible and has potential capability to quantify the comprehensive mitral annular motion for evaluating LV function in a clinical setting.

Adult↗

Left ventricular geometry and myocardial contractility in patients with essential hypertension evaluated by myocardial velocity profile.

BACKGROUND: Left ventricular (LV) systolic function in the hypertensive heart has been evaluated considering geometric differences. The maximal systolic myocardial velocity gradient (Gmax) obtained from myocardial velocity profile can evaluate regional myocardial contractility. The purpose of this study was to assess LV myocardial contractility in the hypertensive heart using Gmax regarding geometric differences. METHODS: The study included 93 patients with essential hypertension. Gmax was correlated with relative wall thickness and LV mass index. LV myocardial contractility was assessed by classifying patients into normal geometry, concentric remodeling (CR), eccentric hypertrophy, and concentric hypertrophy (CH). RESULTS: Gmax has shown significant negative relationship with LV end-diastolic dimension. LV end-diastolic dimension in CH and eccentric hypertrophy groups was significantly greater than that in normal geometry and CR groups (CH vs CR, 4.9 vs 4.2 cm, P < .001). LV mass index was significantly greater in CH and eccentric hypertrophy groups than in the other groups (CH vs CR, 196 vs 122 g/m2, P < .001). Although there was no difference in relative wall thickness between CH and CR groups, Gmax was significantly smaller in CH than in CR group (1.8 vs 2.8 s(-1), P < .05). CONCLUSIONS: In patients with essential hypertension, LV myocardial contractility worsened corresponding to increase in LV dimension with similar wall thickness. Gmax obtained from myocardial velocity profile detected depressed myocardial contractility in patients with increased LV dimension.

Female↗

The left atrial appendage, a small, blind-ended structure: a review of its echocardiographic evaluation and its clinical role.

The increasing prevalence of stroke and atrial fibrillation is a stimulus for new therapeutic strategies and also warrants a review of imaging modalities of the most important source of cardiac systemic embolic events: the left atrial appendage (LAA). This blind-ended, complex structure is embryologically distinct from the body of the left atrium and is sometimes regarded as just a minor extension of the atrium. However, it should routinely be analyzed as part of a transesophageal echocardiographic (TEE) examination. A pulsed Doppler TEE analysis of LAA emptying flow should supplement a two-dimensional (2-D) analysis; these examinations have proven to be highly reproducible and to help assess thromboembolic risk. In 2-D imaging, potential thrombus and spontaneous echo contrast should be sought. In addition, LAA plays a hemodynamic role that participates in atrial function and is influenced by various hemodynamic conditions. In view of the embolic risks from a dysfunctional appendage, the LAA is often ligated during cardiac valve surgery. New devices are under evaluation for percutaneous closure of the LAA, and further studies should improve the definition, understanding, and treatment of LAA dysfunction.

Age Factors↗

Usefulness of intracardiac Doppler assessment of left atrial function immediately post-pulmonary vein antrum isolation to predict short-term recurrence of atrial fibrillation.

Doppler assessments of pulmonary venous (PV) and left atrial appendage flows are useful surrogates of left atrial (LA) function, but it is unknown if these can predict atrial fibrillation (AF) recurrence after pulmonary vein antrum isolation. We compared Doppler surrogates of LA function immediately after pulmonary vein antrum isolation in patients with AF recurrence versus matched patients without recurrence. Patients with a 6-month recurrence had significantly lower LA appendage peak emptying velocity (19 +/- 10 vs 29 +/- 11 cm/s) and lower peak PV systolic wave velocity (36 +/- 17 vs 46 +/- 22 cm/s) compared with those without, suggesting that intracardiac Doppler assessment of LA function after AF ablation predicts AF recurrence.

Aged↗

Coupled pacing improves cardiac efficiency during acute atrial fibrillation with or without cardiac dysfunction.

Coupled pacing (CP), a method for controlling ventricular rate during atrial fibrillation (AF), consists of a single electrical stimulation applied to the ventricles after each spontaneous activation. CP results in a mechanical contraction rate approximately one-half the rate during AF. Paired stimulation in which two electrical stimuli are delivered to the ventricles has also been proposed as a therapy for heart failure. Although paired stimulation enhances contractility, it greatly increases energy consumption. The primary hypothesis of the present study is that CP improves cardiac function during acute AF without a similar increase in energy consumption because of the reduced rate of ventricular contractions. In a canine model, CP was applied during four stages: sinus rhythm (SR), acute AF, cardiac dysfunction (CD), and AF in the presence of cardiac dysfunction. The rate of ventricular contraction decreased in all four stages as the result of CP. In addition, we determined the changes in external cardiac work, myocardial oxygen consumption, and myocardial efficiency in the each of four stages. CP partially reversed the effects of AF and CD on external cardiac work, whereas myocardial oxygen consumption increased only moderately. In all stages but SR, CP increased myocardial efficiency because of the marked increases in cardiac work compared with the moderate increases in total energy consumed. Thus this pacing therapy may be a viable therapy for patients with concurrent atrial fibrillation and heart failure.

Acute Disease↗

Diagnosis of cardiac amyloidosis based on the myocardial velocity profile in the hypertrophied left ventricular wall.

The myocardial velocity profile (MVP), derived from color-coded tissue Doppler imaging (TDI), can identify transmural heterogeneity based on the physiology and pathology of the myocardium. This study sought to clarify whether the MVP can differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy. We recorded the MVP and determined its myocardial velocity gradient (MVG) in the ventricular septum and left ventricular posterior wall using color-coded TDI in 10 patients with cardiac amyloidosis, in 25 patients with hypertensive hypertrophied left ventricular wall, in 25 patients with asymmetric septal hypertrophy of hypertrophic cardiomyopathy, and in 20 clinically normal controls. End-diastolic ventricular septal thickness was similar among the cardiac amyloidosis, hypertension, and hypertrophic cardiomyopathy groups. Percent systolic thickening of the ventricular septum and left ventricular posterior wall calculated from M-mode left ventricular echocardiograms was lower in the cardiac amyloidosis group than in the hypertension, hypertrophic cardiomyopathy, or control group. Peak MVGs during systole and early diastole were lowest in the cardiac amyloidosis group, followed, in order, by the control, hypertension, and hypertrophic cardiomyopathy groups. The systolic and early diastolic MVPs in the ventricular septum and left ventricular posterior wall showed a characteristic serrated pattern in all patients with cardiac amyloidosis, but not in any other patient groups. In conclusion, MVPs in the ventricular septum and left ventricular posterior wall show a distinctive serrated pattern that may be related to amyloid deposition in the myocardium. Myocardial tissue characterization using color-coded TDI provides diagnostic information in patients with cardiac amyloidosis.

Adult↗

Losartan improves regional left ventricular systolic and diastolic function in patients with hypertension: accurate evaluation using a newly developed color-coded tissue doppler imaging technique.

BACKGROUND: Angiotensin II receptor antagonists have recently been accepted as antihypertensive therapy. Tissue Doppler imaging (TDI) has been developed as a noninvasive tool to assess quantitatively regional myocardial motion abnormalities. This study was designed to determine whether our newly developed technique of color-coded TDI may be a useful means of quantifying the improvement in regional left ventricular (LV) myocardial contractility and relaxation after treatment with losartan in patients with hypertension. METHODS AND RESULTS: Losartan (50 to 100 mg) was administered for 6 months to 37 previously untreated patients with essential hypertension. Averaged myocardial velocity profiles (MVPs) for color-coded TDI were recorded in the ventricular septum and LV posterior wall before and after treatment. Peak myocardial velocities and peak myocardial velocity gradients (MVGs) in the LV walls were determined during systole and early diastole. The plasma concentration of transforming growth factor (TGF)-beta1 also was measured in all patients. Blood pressure and plasma TGF-beta1 level decreased after initiation of losartan therapy. The LV mass index and LV meridional end-systolic wall stress also decreased after treatment with losartan. LV geometry changed from a pattern consistent with concentric hypertrophy to normal geometry in 10 patients and to a pattern consistent with concentric remodeling in 5 patients, and from concentric remodeling to normal geometry in 5 patients after treatment with losartan. The ratio of early to late diastolic filling for the transmitral flow velocity increased after losartan treatment. The peak systolic and early diastolic myocardial velocities and MVGs in the ventricular septum and LV posterior wall increased after treatment with losartan, although the values 6 months after treatment with losartan were still lower than those in normal individuals. There were good correlations between changes in plasma TGF-beta1 level and changes in systolic and early diastolic MVGs 6 months after losartan. However, there were no significant correlations between changes in the systolic blood pressure and LV end-systolic wall stress and changes in the TDI parameters. CONCLUSION: Losartan improves regional LV function in patients with hypertension. Our newly developed averaged MVP and MVG measurements may be useful for accurately evaluating regional LV myocardial contractility and relaxation in these patients.

Aged↗

The pseudorestrictive pattern of transmitral Doppler flow pattern after conversion of atrial fibrillation to sinus rhythm: is atrial or ventricular dysfunction to blame?

Patients with paroxysmal atrial fibrillation (AF) who have recently converted from AF to sinus rhythm often exhibit a restrictive Doppler pattern in the transmitral flow (TMF) velocity. However, the mechanism of this phenomenon has not been well defined. We evaluated the temporal change of TMF pattern and hemodynamics after conversion of AF to in sinus rhythm in an animal model. Eight open-chest dogs underwent 3 hours of pacing-induced AF. TMF velocities and pressure data were acquired at baseline (sinus rhythm), immediately after conversion of AF, and every 10 minutes thereafter. Early diastolic TMF velocity was increased immediately after conversion and recovered to the baseline value in 20 minutes. Atrial systolic TMF velocity was reduced after AF and recovered to baseline value in 20 to 30 minutes. Early diastolic/atrial systolic TMF velocity was increased after conversion, and recovered to baseline value in 20 to 30 minutes. The mean left atrial (LA) pressure increased immediately, 10 and 20 minutes after the conversion of AF to sinus rhythm. The left ventricular end-diastolic pressure was increased and positive left ventricular dP/dt and tau were decreased immediately after AF, whereas they recovered within 10 minutes. In conclusion, a pseudorestrictive pattern of TMF after AF occurred as a result of transient LA mechanical functional impairment and increased LA pressure caused by LA stunning. Transient left ventricular diastolic dysfunction also effected the TMF velocity immediately after the conversion from AF to sinus rhythm, although it recovered faster than LA mechanical dysfunction.

Animals↗

Frank-Starling mechanism contributes modestly to ventricular performance during atrial fibrillation.

OBJECTIVES: The aim of this study was to assess whether Frank-Starling mechanism has an independent effect on left ventricular (LV) performance in atrial fibrillation (AF). BACKGROUND: Ventricular performance in AF depends on variable contractility through the interval-force mechanism based on the ratio of preceding and pre-preceding RR intervals (RR(p)/RR(pp)). The impact of end-diastolic volume (EDV) variability, through the Frank-Starling mechanism, is not well understood. METHODS: We induced AF in 16 open chest dogs. RR intervals, LV pressure, LV volume, and aortic flow were collected for >400 beats during rapid AF (ventricular cycle length 292 +/- 66 ms). In six of the dogs, additional data were collected while average ventricular cycle length was prolonged from 258 +/- 34 ms to 445 +/- 80 ms by selective vagal nerve stimulation of the AV node. RESULTS: The relations of maximal LV power (LVPower) and peak LV pressure derivative (dP/dt) versus RR(p)/RR(pp) were fitted to the equation y = A * (1 - EXP (RR(p)/RR(pp)min - RR(p)/RR(pp))/C) and the residuals (RES) of these relations were analyzed. LVPower and dP/dt strongly correlated with RR(p)/RR(pp) (r(2) = 0.67 +/- 0.12 and 0.66 +/- 0.12, P < .0001 for all correlations). Importantly, RES-LVPower and RES-dP/dt showed linear correlation with EDV (r(2) = 0.20 +/- 0.14 and r(2) = 0.24 +/- 0.17, P < .01 for all correlations). In the six dogs with slowed average ventricular rate, the slope of both residual relationships (RES-LVPower vs EDV and RES- dP/dt vs EDV) decreased (P < .03 for both). CONCLUSIONS: The Frank-Starling mechanism contributes to ventricular performance in AF independently of the interval-force effects of the beat-to-beat variability in cardiac contractility. The Frank-Starling mechanism is sensitive to the average ventricular rate.

Action Potentials↗