A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor.

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but regardless of the approach, an in vivo model is needed to test each treatment. The pig is one of the most used large animal models for cardiovascular disease. Its heart is very similar in anatomy and function to that of a human. The ameroid placement technique creates an ischemic area of the heart, which has many useful applications in studying myocardial infarction. This model has been used for surgical research, pharmaceutical studies, imaging techniques, and cell therapies. There are several ways of inducing an ischemic area in the heart. Each has its advantages and disadvantages, but the placement of an ameroid constrictor remains the most widely used technique. The main advantages to using the ameroid are its prevalence in existing research, its availability in various sizes to accommodate the anatomy and size of the vessel to be constricted, the surgery is a relatively simple procedure, and the post-operative monitoring is minimal, since there are no external devices to maintain. This paper provides a detailed overview of the proper technique for the placement of the ameroid constrictor.

Intraventricular pressure gradients in left ventricular aneurysms determined by color M-mode Doppler method: an animal study.

BACKGROUND: Left ventricular aneurysm (LVA) may affect diastolic intraventricular blood flow. Color M-mode (CMM) Doppler flow propagation patterns are abnormal in the presence of apical aneurysms. The aim of this study was to validate the accuracy of CMM echocardiography for assessing the existence and size of LVA and to determine the intraventricular pressure gradient in LVA. METHODS: CMM of the transmitral inflow in early diastole was obtained from the apical 4-chamber view in 19 sheep. The presence of the break point where the velocity decreased abruptly in the mitral inflow (point D) was determined and the distance between the apex and point D was measured. The intraventricular pressure difference between the base and the apex was measured by a catheter while it was calculated using CMM with the Euler equation. RESULTS: The presence of the break point D showed 84% sensitivity and 100% specificity for determining the existence of an LVA. Distance between the apex and point D correlated well with scar size. Catheter- and CMM-derived intraventricular pressure difference correlated and agreed well (y = 1.0 x -0.2, r = 0.94). CONCLUSIONS: The point of abrupt decrease in propagation velocity of the CMM recording indicated the presence and size of LVA. Intraventricular pressure gradients were determined noninvasively by CMM echocardiography with reasonable accuracy.

Acute geometric changes of the mitral annulus after coronary occlusion: a real-time 3D echocardiographic study.

We performed real-time 3D echocardiography in sixteen sheep to compare acute geometric changes in the mitral annulus after left anterior descending coronary artery (LAD, n=8) ligation and those after left circumflex coronary artery (LCX, n=8) ligation. The mitral regurgitation (MR) was quantified by regurgitant volume (RV) using the proximal isovelocity surface area method. The mitral annulus was reconstructed through the hinge points of the annulus traced on 9 rotational apical planes (angle increment=20 degrees). Mitral annular area (MAA) and the ratio of antero-posterior (AP) to commissure-commissure (CC) dimension of the annulus were calculated. Non-planar angle (NPA) representing non-planarity of the annulus was measured. After LCX occlusion, there were significant increases of the MAA during both early and late systole (p<0.01) with significant MR (RV: 30+/-14 mL), while there was neither a significant increase of MAA, nor a significant MR (RV: 4+/-5 mL) after LAD occlusion. AP/CC ratio (p<0.01) and NPA (p<0.01) also significantly increased after LCX occlusion during both early and late systole. The mitral annulus was significantly enlarged in the antero-posterior direction with significant decrease of non-planarity compared to LAD occlusion immediately after LCX occlusion.

The accuracy of left ventricular mass determined by real-time three-dimensional echocardiography in chronic animal and clinical studies: a comparison with postmortem examination and magnetic resonance imaging.

Real-time 3-dimensional echocardiography (RT3DE), 2-dimensional echocardiography (2DE), and M-mode echocardiography were performed in 28 sheep with cardiac pathologies and 27 patients with heart disease to demonstrate the superiority of RT3DE over M-mode and 2DE for the determination of left ventricular mass. Postmortem examination and magnetic resonance imaging were used as a reference standard for the animal and clinical studies, respectively. In the animal study, the highest concordance correlation (0.92) was obtained between the actual weight of left ventricular mass and that estimated by RT3DE (0.69 for 2DE and 0.77 for M-mode, P < .001). In the clinical study, RT3DE also provided the best concordance correlation with left ventricular mass determined by magnetic resonance imaging (0.91 for RT3DE, 0.83 for 2DE, and 0.38 for M-mode; P < .0001).

Quantitative analysis of left atrial function during left ventricular ischemia with and without left atrial ischemia: a real-time 3-dimensional echocardiographic study.

Left atrial (LA) systolic and diastolic function were analyzed in an animal model of acute left ventricular ischemia with LA ischemia by proximal left circumflex coronary artery occlusion or without LA ischemia by midleft anterior descending coronary artery occlusion (7 sheep in each group). LA pressures and LA volumes were simultaneously recorded using a catheter and real-time 3-dimensional echocardiography, respectively. LA stroke volume represented 63% of left ventricular stroke volume during left anterior descending coronary artery occlusion, but only 32% during left circumflex coronary artery occlusion. This animal study with 3-dimensional echocardiographic determination of absolute LA volumes demonstrated dramatic depression of LA function during proximal left circumflex coronary artery occlusion as compared with left anterior descending coronary artery occlusion.

Combination of pulsed-wave Doppler and real-time three-dimensional color Doppler echocardiography for quantifying the stroke volume in the left ventricular outflow tract.

Real-time three-dimensional (3-D) color Doppler echocardiography (RT3D) is capable of quantifying flow. However, low temporal resolution limits its application to stroke volume (SV) measurements. The aim of the present study was, therefore, to develop a reliable method to quantify SV. In animal experiments, cross-sectional images of the LV outflow tract were selected from the RT3D data to calculate peak flow rates (Q(p3D)). Conventional pulsed-wave (PW) Doppler was performed to measure the velocity-time integral (VTI) and the peak velocity (V(p)). By assuming that the flow is proportional to the velocity temporal waveform, SV was calculated as alpha x Q(p3D) x VTI/V(p), where alpha is a temporal correction factor. There was an excellent correlation between the reference flow meter and RT3D SV (mean difference = -1. 3 mL, y = 1. 05 x -2. 5, r = 0. 94, p < 0. 01). The new method allowed accurate SV estimations without any geometric assumptions of the spatial velocity distributions.

Myocardial strain rate is a superior method for evaluation of left ventricular subendocardial function compared with tissue Doppler imaging.

OBJECTIVES: This study was performed to evaluate subendocardial function using strain rate imaging (SRI). BACKGROUND: The subendocardium and mid-wall of the left ventricle (LV) play important roles in ventricular function. Previous methods used for evaluating this function are either invasive or cumbersome. Strain rate imaging by ultrasound is a newly developed echocardiographic modality based on tissue Doppler imaging (TDI) that allows quantitative assessment of regional myocardial wall motion. METHODS: We examined eight sheep using TDI in apical four-chamber views to evaluate the LV free wall. Peak strain rates (SRs) during isovolumic relaxation (IR), isovolumic contraction (IC), and myocardial strain were measured in the endocardial (End), mid-myocardial (Mid), and epicardial (Epi) layers. For four hemodynamic conditions (created after baseline by blood, dobutamine, and metoprolol infusion), we compared differences in SR of End, Mid, and Epi layers to peak positive and negative first derivative of LV pressure (dP/dt). RESULTS: Strain rate during IC showed a good correlation with +dP/dt (r = 0.74, p < 0.001) and during IR with -dP/dt (r = 0.67, p = 0.0003). There was a significant difference in SR between the myocardial layers during both IC and IR (End: -3.4 +/- 2.2 s(-1), Mid: -1.8 +/- 1.5 s(-1), Epi: -0.63 +/- 1.0 s(-1), p < 0.0001 during IC; End: 2.2 +/- 1.5 s(-1), Mid: 1.0 +/- 0.8 s(-1), Epi: 0.47 +/- 0.64 s(-1), p < 0.0001 during IR). Also, SRs of the End and Mid layers during IC were significantly altered by different hemodynamic conditions (End at baseline: 1.7 +/- 0.7 s(-1); blood: 2.0 +/- 1.1 s(-1); dobutamine: 3.4 +/- 2.3 s(-1); metoprolol: 1.0 +/- 0.4 s(-1); p < 0.05). Myocardial strain showed differences in each layer (End: -34.3 +/- 12.6%; Mid: -22.6 +/- 12.1%; Epi: -11.4 +/- 7.9%; p < 0.0001) and changed significantly in different hemodynamic conditions (p < 0.0001). CONCLUSIONS: Strain and SR appear useful and sensitive for evaluating myocardial function, especially for the subendocardial region.

Real-time three-dimensional color doppler evaluation of the flow convergence zone for quantification of mitral regurgitation: Validation experimental animal study and initial clinical experience.

BACKGROUND: Pitfalls of the flow convergence (FC) method, including 2-dimensional imaging of the 3-dimensional (3D) geometry of the FC surface, can lead to erroneous quantification of mitral regurgitation (MR). This limitation may be mitigated by the use of real-time 3D color Doppler echocardiography (CE). Our objective was to validate a real-time 3D navigation method for MR quantification. METHODS: In 12 sheep with surgically induced chronic MR, 37 different hemodynamic conditions were studied with real-time 3DCE. Using real-time 3D navigation, the radius of the largest hemispherical FC zone was located and measured. MR volume was quantified according to the FC method after observing the shape of FC in 3D space. Aortic and mitral electromagnetic flow probes and meters were balanced against each other to determine reference MR volume. As an initial clinical application study, 22 patients with chronic MR were also studied with this real-time 3DCE-FC method. Left ventricular (LV) outflow tract automated cardiac flow measurement (Toshiba Corp, Tokyo, Japan) and real-time 3D LV stroke volume were used to quantify the reference MR volume (MR volume = 3DLV stroke volume - automated cardiac flow measurement). RESULTS: In the sheep model, a good correlation and agreement was seen between MR volume by real-time 3DCE and electromagnetic (y = 0.77x + 1.48, r = 0.87, P <.001, delta = -0.91 +/- 2.65 mL). In patients, real-time 3DCE-derived MR volume also showed a good correlation and agreement with the reference method (y = 0.89x - 0.38, r = 0.93, P <.001, delta = -4.8 +/- 7.6 mL). CONCLUSIONS: real-time 3DCE can capture the entire FC image, permitting geometrical recognition of the FC zone geometry and reliable MR quantification.

Pulmonary venous flow determinants of left atrial pressure under different loading conditions in a chronic animal model with mitral regurgitation.

BACKGROUND: The aim of our study was to quantitatively compare the changes and correlations between pulmonary venous flow variables and mean left atrial pressure (mLAP) under different loading conditions in animals with chronic mitral regurgitation (MR) and without MR. METHODS: A total of 85 hemodynamic conditions were studied in 22 sheep, 12 without MR as control (NO-MR group) and 10 with MR (MR group). We obtained pulmonary venous flow systolic velocity (Sv) and diastolic velocity (Dv), Sv and Dv time integrals, their ratios (Sv/Dv and Sv/Dv time integral), mLAP, left ventricular end-diastolic pressure, and MR stroke volume. We also measured left atrial a, x, v, and y pressures and calculated the difference between v and y pressures. RESULTS: Average MR stroke volume was 10.6 +/- 4.3 mL/beat. There were good correlations between Sv (r = -0.64 and r = -0.59, P <.01), Sv/Dv (r = -0.62 and r = -0.74, P <.01), and mLAP in the MR and NO-MR groups, respectively. Correlations were also observed between Dv time integral (r = 0.61 and r = 0.57, P <.01) and left ventricular end-diastolic pressure in the MR and NO-MR groups. In velocity variables, Sv (r = -0.79, P <.001) was the best predictor of mLAP in both groups. The sensitivity and specificity of Sv = 0 in predicting mLAP 15 mm Hg or greater were 86% and 85%, respectively. CONCLUSION: Pulmonary venous flow variables correlated well with mLAP under altered loading conditions in the MR and NO-MR groups. They may be applied clinically as substitutes for invasively acquired indexes of mLAP to assess left atrial and left ventricular functional status.

A validation study of aortic stroke volume using dynamic 4-dimensional color Doppler: an in vivo study.

OBJECTIVE: To explore the feasibility of directly quantifying transaortic stroke volume with a newly developed dynamic 3-dimensional (3D) color Doppler flow measurement technique, an in vivo experimental study was performed. BACKGROUND: Traditional methods for flow quantification require geometric assumptions about flow area and flow profiles. Accurate quantification of flow across the aortic valve is clinically important as a means of estimating cardiac output. METHODS: Eight open-chest sheep were scanned with apical epicardial placement of a 7 to 4 MHz multiplane transesophageal probe scanning parallel to aortic flow and running on an ATL HDI 5000 system. An electromagnetic flow meter implanted on the ascending aorta was used as reference. Thirty different hemodynamic conditions were studied after steady states were obtained in the animals by administration of blood, angiotensin, and sodium nitroprusside. Electrocardiogram-gated digital color 3D velocity data were acquired for each of the 30 steady states. The aortic stroke volumes were computed by temporal and spatial integration of flow areas and actual velocities across a projected surface perpendicular to the direction of flow, at a level just below the aortic valve. RESULTS: There was close correlation between the 3D color Doppler calculated aortic stroke volumes and the electromagnetic data (r = 0.91, y = 0.96x + 1.01, standard error of the estimate = 2.6 mL/beat). CONCLUSION: Our results showed that dynamic 3D color Doppler measurements obtained in an open-chest animals provide the basis for accurate, geometry-independent quantitative evaluation of the aortic flow. Therefore, 3D digital color Doppler flow computation could potentially represent an important method for noninvasively determining cardiac output in patients.

Left ventricular outflow tract mean systolic acceleration as a surrogate for the slope of the left ventricular end-systolic pressure-volume relationship.

OBJECTIVE: The goal of this study was to analyze left ventricular outflow tract systolic acceleration (LVOT(Acc)) during alterations in left ventricular (LV) contractility and LV filling. BACKGROUND: Most indexes described to quantify LV systolic function, such as LV ejection fraction and cardiac output, are dependent on loading conditions. METHODS: In 18 sheep (4 normal, 6 with aortic regurgitation, and 8 with old myocardial infarction), blood flow velocities through the LVOT were recorded using conventional pulsed Doppler. The LVOT(Acc) was calculated as the aortic peak velocity divided by the time to peak flow; LVOT(Acc) was compared with LV maximal elastance (E(m)) acquired by conductance catheter under different loading conditions, including volume and pressure overload during an acute coronary occlusion (n = 10). In addition, a clinically validated lumped-parameter numerical model of the cardiovascular system was used to support our findings. RESULTS: Left ventricular E(m) and LVOT(Acc) decreased during ischemia (1.67 +/- 0.67 mm Hg.ml(-1) before vs. 0.93 +/- 0.41 mm Hg.ml(-1) during acute coronary occlusion [p < 0.05] and 7.9 +/- 3.1 m.s(-2) before vs. 4.4 +/- 1.0 m.s(-2) during coronary occlusion [p < 0.05], respectively). Left ventricular outflow tract systolic acceleration showed a strong linear correlation with LV E(m) (y = 3.84x + 1.87, r = 0.85, p < 0.001). Similar findings were obtained with the numerical modeling, which demonstrated a strong correlation between predicted and actual LV E(m) (predicted = 0.98 [actual] -0.01, r = 0.86). By analysis of variance, there was no statistically significant difference in LVOT(Acc) under different loading conditions. CONCLUSIONS: For a variety of hemodynamic conditions, LVOT(Acc) was linearly related to the LV contractility index LV E(m) and was independent of loading conditions. These findings were consistent with numerical modeling. Thus, this Doppler index may serve as a good noninvasive index of LV contractility.

A new dynamic three-dimensional digital color doppler method for quantification of pulmonary regurgitation: validation study in an animal model.

OBJECTIVES: The purpose of the present study was to validate a newly developed three-dimensional (3D) digital color Doppler method for quantifying pulmonary regurgitation (PR), using an animal model of chronic PR. BACKGROUND: Spectral Doppler methods cannot reliably be used to assess pulmonary regurgitation. METHODS: In eight sheep with surgically created PR, 27 different hemodynamic states were studied. Pulmonary and aortic electromagnetic (EM) probes and meters were used to provide reference right ventricular (RV) forward and pulmonary regurgitant stroke volumes. A multiplane transesophageal probe was placed directly on the RV and aimed at the RV outflow tract. Electrocardiogram-gated and rotational 3D scans were performed for acquiring dynamic 3D digital velocity data. After 3D digital Doppler data were transferred to a computer workstation, the RV forward and pulmonary regurgitant flow volumes were obtained by a program that computes the velocity vectors over a spherical surface perpendicular to the direction of scanning. RESULTS: Pulmonary regurgitant volumes and RV forward stroke volumes computed by the 3D method correlated well with those by the EM method (r = 0.95, mean difference = 0.51 +/- 1.89 ml/beat for the pulmonary regurgitant volume; and r = 0.91, mean difference = -0.22 +/- 3.44 ml/beat for the RV stroke volume). As a result of these measurements, the regurgitant fractions derived by the 3D method agreed well with the reference data (r = 0.94, mean difference = 2.06 +/- 6.11%). CONCLUSIONS: The 3D digital color Doppler technique is a promising method for determining pulmonary regurgitant volumes and regurgitant fractions. It should have an important application in clinical settings.

Quantitative analysis of aortic regurgitation: real-time 3-dimensional and 2-dimensional color Doppler echocardiographic method--a clinical and a chronic animal study.

BACKGROUND: For evaluating patients with aortic regurgitation (AR), regurgitant volumes, left ventricular (LV) stroke volumes (SV), and absolute LV volumes are valuable indices. AIM: The aim of this study was to validate the combination of real-time 3-dimensional echocardiography (3DE) and semiautomated digital color Doppler cardiac flow measurement (ACM) for quantifying absolute LV volumes, LVSV, and AR volumes using an animal model of chronic AR and to investigate its clinical applicability. METHODS: In 8 sheep, a total of 26 hemodynamic states were obtained pharmacologically 20 weeks after the aortic valve noncoronary (n = 4) or right coronary (n = 4) leaflet was incised to produce AR. Reference standard LVSV and AR volume were determined using the electromagnetic flow method (EM). Simultaneous epicardial real-time 3DE studies were performed to obtain LV end-diastolic volumes (LVEDV), end-systolic volumes (LVESV), and LVSV by subtracting LVESV from LVEDV. Simultaneous ACM was performed to obtain LVSV and transmitral flows; AR volume was calculated by subtracting transmitral flow volume from LVSV. In a total of 19 patients with AR, real-time 3DE and ACM were used to obtain LVSVs and these were compared with each other. RESULTS: A strong relationship was found between LVSV derived from EM and those from the real-time 3DE (r = 0.93, P <.001, mean difference (3D - EM) = -1.0 +/- 9.8 mL). A good relationship between LVSV and AR volumes derived from EM and those by ACM was found (r = 0.88, P <.001). A good relationship between LVSV derived from real-time 3DE and that from ACM was observed (r = 0.73, P <.01, mean difference = 2.5 +/- 7.9 mL). In patients, a good relationship between LVSV obtained by real-time 3DE and ACM was found (r = 0.90, P <.001, mean difference = 0.6 +/- 9.8 mL). CONCLUSION: The combination of ACM and real-time 3DE for quantifying LV volumes, LVSV, and AR volumes was validated by the chronic animal study and was shown to be clinically applicable.

Direct quantification of transmitral flow volume with dynamic 3-dimensional digital color Doppler: a validation study in an animal model.

Accurately quantifying transmitral flow volume is clinically important not only as a measure of cardiac output, but also as a value from which to subtract aortic flow, for determining the severity of mitral regurgitation. However, controversy exists over the accuracy of pulsed Doppler for mitral flow quantification because of the complexity of mitral flow geometry and dynamic changes in flow profile and flow area. To explore the feasibility of directly quantifying transmitral flow volume with a newly developed dynamic 3-dimensional digital color Doppler technique, this in vivo experimental study was conducted to validate the method. Eight open chest sheep were imaged with a multiplane transesophageal (TEE) probe placed on the heart for digital 3-dimensional gated acquisition of mitral inflow over a 180-degree acquisition. The digital velocity data were contour detected for flow area after computing the velocity vectors and flow profile perpendicular to a spherical 3-dimensional surface across the mitral annulus. Flow areas and actual velocities were then integrated in time and space and the resulting flow volumes were compared with those obtained by a reference electromagnetic flowmeter on the aorta for 26 steady hemodynamic states. The flow volumes correlated closely to the electromagnetic references (y = 0.87x + 2.49, r = 0.92, SEE = 1.9 Ml per beat). Our study shows that transmitral flow volume can be accurately determined in vivo by this dynamic 3-dimensional digital color Doppler flow quantification method.