Two-Dimensional Echocardiography with a 15-MHz Transducer Is a Promising Alternative for In Vivo Measurement of Left Ventricular Mass in Mice

Murine models of left ventricular (LV) hypertrophy recently have been developed. We tested the accuracy of 2-dimensional (2D) echocardiographic measurement of LV mass with high-frequency imaging in mice. Ten anesthetized mice (weight 20 to 31 g, aged 1 to 5 months) were examined with a 15-MHz transthoracic linear-array transducer. End-diastolic myocardial area (A)(epicardial – endocardial) from the parasternal short-axis view at the midpapillary level and LV length (L) from the parasternal long-axis view were measured to calculate LV mass with the area-length method (1.05 [5/6 × A × L]) and data were compared with LV-mass with the 2D guided M-mode method. Within 3 days of echocardiography, the hearts were removed and weighed after potassium-induced cardiac arrest. Two-dimensional echocardiographic measurement with a 15-MHz transducer was performed in all mice. LV chamber dimensions included end-diastolic septal (0.80 ± 0.12 mm) and posterior wall thickness (0.76 ± 0.13 mm), end-diastolic dimension (3.64 ± 0.28 mm), and end-systolic dimension (2.34 ± 0.32 mm). Echocardiographic LV mass with the area-length method, 2D guided M-mode method, and autopsy LV weight were 80.8 ± 16.1 mg, 97.6 ± 17.8 mg, and 78.8 ± 13.2 mg, respectively. A strong correlation existed between LV weight (x ) and echocardiographic LV mass (y ) with the area–length method: y = 0.745x + 18.9, r =0.908, standard error of estimate (SEE) = 5.9 mg, P < .0005. This correlation was stronger than that of LV weight (x ) and echocardiographic LV mass (y ) with the 2D guided M-mode method: y = 0.577x + 22.6, r =0.779, SEE = 8.8 mg, P = .008. These data suggest that serial in vivo measurements of LV mass with the 2D area-length method may be more accurate than M-mode methods in experimental murine models of LV pathology. (J Am Soc Echocardiogr 1999;12:70-5.)     

Doppler estimation of reduced coronary flow reserve in mice with pressure overload cardiac hypertrophy

Aortic banding produces pressure overload cardiac hypertrophy in mice, leading to decompensated heart failure in four to eight weeks, but the effects on coronary blood flow velocity and reserve are unknown. To determine whether coronary flow reserve (CFR) was reduced, we used noninvasive 20-MHz Doppler ultrasound to measure left main coronary flow velocity at baseline (B) and at hyperemia (H) induced by low (1%) and high (2.5%) concentrations of isoflurane gas anesthesia. Ten mice were studied before (Pre) and at 1 d, 7 d, 14 d and 21 d after constricting the aortic arch to 0.4 mm diameter distal to the innominate artery. We also measured cardiac inflow and outflow velocities at the mitral and aortic valves and velocity at the jet distal to the aortic constriction. The pressure drop as estimated by 4V2 at the jet was 51 +/- 5.1 (mean +/- SE) mm Hg at 1 d, increasing progressively to 74 +/- 5.2 mm Hg at 21 d. Aortic and mitral blood velocities were not significantly different after banding (p = NS), but CFR, as estimated by H/B, dropped progressively from 3.2 +/- 0.3 before banding to 2.2 +/- 0.4, 1.7 +/- 0.3, 1.4 +/- 0.2 and 1.1 +/- 0.1 at 1 d, 7 d, 14 d and 21 d, respectively (all p < 0.01 vs. Pre). There was also a significant and progressive increase the systolic/diastolic velocity ratio (0.17 Pre to 0.92 at 21 d, all p < 0.01 vs. Pre) suggesting a redistribution of perfusion from subendocardium to subepicardium. We show for the first time that CFR, as estimated by the hyperemic response to isoflurane and measured by Doppler ultrasound, can be measured serially in mice and conclude that CFR is virtually eliminated in banded mice after 21 d of remodeling and hypertrophy. These results demonstrate that CFR is reduced in mice as in humans with cardiac disease but before the onset of decompensated heart failure.     

Effect of long-term heart rate reduction by If current inhibition on pressure overload-induced heart failure in rats

We investigated the effects of long-term heart rate reduction (HRR) on pressure overload-induced heart failure. Pressure overload of the left ventricle was induced in 21-day-old rats by banding the ascending aorta. HRR was induced for 3 months with ivabradine (n = 44), a selective I(f) current inhibitor, at 10 mg/kg/day, starting 14 days after banding. Thirty-six control banded rats and 16 sham-operated rats received standard chow. Banding resulted in severe left ventricular (LV) hypertrophy (+55% versus shams; p < 0.001) and fibrosis, together with a 34% decrease (p < 0.01) in the LV shortening fraction. Heart rate decreased by 19% in ivabradine-treated rats (p < 0.005 versus controls). Stroke volume increased (by 17%; p < 0.01), whereas cardiac output did not change with HRR. In contrast, HRR resulted in 1) a marked increase in LV filling pressure (p < 0.01) and in atrial, lung, and right ventricular weights (38, 30, and 54%, respectively; p < 0.001); 2) a 50% increase in the incidence of pleural/abdominal effusion (p < 0.001); 3) 7 and 26% increases in LV hypertrophy and fibrosis, respectively (p < 0.05); and 4) a 53% increase in the atrial natriuretic peptide mRNA level compared with controls (p < 0.001). After 3 months of treatment, ivabradine withdrawal normalized the heart rate and reduced LV size and LV filling pressure (p < 0.05). In conclusion, pure longstanding HRR showed no beneficial effect on LV dysfunction in a rat model of pressure overload-induced LV hypertrophy, and it seemed to favor adverse LV remodeling and its congestive consequences.     

Doppler evaluation of peripheral vascular adaptations to transverse aortic banding in mice

Transverse aortic banding in mice is commonly used to produce pressure overload, but the resulting cardiac hypertrophy is variable and the actual load produced is unknown. The purposes of the study were to characterize peripheral blood flow in banded mice using noninvasive Doppler methods, investigate whether changes in flow could predict the amount of cardiac hypertrophy induced and validate the simplified Bernoulli equation for estimating the pressure drop across the stenosis in very small vessels. Wild-type mice underwent aortic banding (n=15) or sham operation (n=6). Doppler velocity was measured in the right and left carotid arteries (RCA and LCA) 1 day later, and the heart weight/body weight ratio was measured at 7 days. The RCA/LCA peak velocity ratio at 1 day was significantly correlated with the heart weight/body weight ratio at 7 days after banding (r=0.62, p<0.005). In another 12 banded mice, serial Doppler velocity signals were obtained from the aortic banding site, the abdominal aorta (ABD) and the RCA and LCA before, 1 day after and 7 days after banding. Peak RCA velocity increased significantly after banding and both peak LCA velocity and peak ABD velocity decreased significantly. Mean velocities of RCA, LCA and ABD were unchanged before and after banding, suggesting that mice utilize peripheral arterial adaptations to maintain normal cerebral and peripheral perfusion. There was a significant positive correlation (r=0.83, p<0.001) between the RCA/LCA peak velocity ratio and peak jet velocity across the aortic banding site. Our data indicate that changes in carotid velocity after aortic banding can be used to estimate the pressure drop across the aortic band and to predict loading and resulting cardiac hypertrophy in mice. Additionally, we validated that the simplified Bernoulli equation (DeltaP=4V2) can be used to estimate the pressure drop across the aortic band in mice noninvasively.     

Effects of pressure overload, left ventricular hypertrophy on beta-adrenergic receptors, and responsiveness to catecholamines.

Pressure overload left ventricular (LV) hypertrophy was produced by banding the ascending aorta of puppies and allowing them to grow to adulthood. LV free wall weight per body weight increased by 87% from a normal value of 3.23 +/- 0.19 g/kg. Hemodynamic studies of conscious dogs with LV hypertrophy and of normal, conscious dogs without LV hypertrophy showed similar base-line values for mean arterial pressure, heart rate, and LV end-diastolic pressure and diameter. LV systolic pressure was significantly greater, P less than 0.01, and LV stroke shortening was significantly lss, P less than 0.01, in the LV hypertrophy group. In both normal and LV hypertrophy groups, increasing bolus doses of norepinephrine or isoproterenol produced equivalent changes in LV dP/dt. beta-adrenergic receptor binding studies with [3H]-dihydroalprenolol ( [3H]DHA) indicated that the density of binding sites was significantly elevated, P less than 0.01, in the hypertrophied LV plasma membranes (111 +/- 8.8, n = 8), as compared with normal LV (61 +/- 5.6 fmol/mg protein, n = 11). The receptor affinity decreased, i.e., disassociation constant (KD) increased, selectively in the LV of the hypertrophy group; the KD in the normal LV was 6.8 +/- 0.7 nM compared with 10.7 +/- 1.8 nM in the hypertrophied LV. These effects were observed only in the LV of the LV hypertrophy group and not in the right ventricles from the same dogs. The plasma membrane marker, 5' -nucleotidase activity, was slightly lower per milligram protein in the LV hypertrophy group, indicating that the differences in beta-adrenergic receptor binding and affinity were not due to an increase in plasma membrane protein in the LV hypertrophy group. The EC50 for isoproterenol-stimulated adenylate cyclase activity was similar in both the right and left ventricles and in the two groups. However, maximal-stimulated adenylate cyclase was lower in the hypertrophied left ventricle. Plasma catecholamines were similar in the normal and hypertrophied groups, but myocardial norepinephrine was depressed in the dogs with LV hypertrophy (163 +/- 48 pg/mg) compared with normal dogs (835 +/- 166 pg/mg). Thus, severe, but compensated LV hypertrophy, induced by aortic banding in puppies, is characterized by essentially normal hemodynamics in adult dogs studied at rest and in response to catecholamines in the conscious state. At the cellular level, reduced affinity and increased beta-adrenergic receptor number characterized the LV hypertrophy group, while the EC50 for isoproterenol-stimulated adenylate cyclase activity was normal. By these mechanisms, adequate responsiveness to catecholamines is retained in conscious dogs with severe LV hypertrophy.     

Echocardiographic evaluation of ventricular remodeling in a mouse model of myocardial infarction.

Gene-targeting in mice is a powerful tool to define molecular mechanisms of ischemic heart disease that determine infarct size, postinfarct left ventricular (LV) remodeling, and arrhythmogenesis. Coronary ligation in mice is becoming a widely used model of myocardial infarction (MI), but the pathophysiologic consequences of MI in mice and its relevance to human MI have not been fully elucidated. To characterize structural and functional changes during evolving MI, we analyzed 2-dimensional-based reconstruction of the left ventricle by noninvasive echocardiography obtained 1 day and 1 week after surgical ligation of the left anterior descending coronary artery in mice. Sequential 2-dimensional short-axis cineloops of the left ventricle were used to measure LV mass, and LV volumes at end-diastole and end-systole. Echocardiographic infarct size was estimated by measuring the volume of akinetic LV segments. Histologic infarct size was measured by planimetry of 9 transverse sections of each heart. There was close correlation between the 2 methods (31% +/- 20% of LV mass and 34% +/- 17% of LV area, respectively; y =.83x + 7.9, r = 0.96, P <.01). LV volumes at end diastole increased significantly between 1 day and 1 week (51 +/- 17 microL vs 78 +/- 46 microL, respectively, P <.05). The relative change in LV volumes at end diastole varied as a function of infarct size (r = 0.93, P <.01). LV mass and the extent of hypertrophy of noninfarcted segments also varied with infarct size (r = 0.92, P <.01; r = 0.90, P <.01, respectively). Thus, echocardiography is an accurate noninvasive tool for determination of infarct size and quantitative characterization of postinfarct remodeling in the mouse model of MI. Alterations in cardiac structure and function after coronary ligation in mice closely resemble pathophysiologic changes in human ischemic heart disease.     

Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure overload in the rat.

Using an experimental model of ascending aortic banding in the rat, we examined whether coronary circulation abnormalities in hypertrophied hearts are reversible after debanding. 4-wk banding produced significant increases in in vivo left ventricular (LV) pressure (194 +/- 13 vs. 114 +/- 9 mmHg in shamoperated controls) and LV dry wt/body wt (48 +/- 5% above controls). In isolated hearts perfused with Krebs-Henseleit buffer, coronary flow rate (CFR) was estimated under nonworking conditions. During maximal vasodilation after 1 min-ischemia, CFR at a coronary perfusion pressure (CPP) of 100 mmHg and CFR/myocardidial mass at CPPs of 100 and 150 mmHg decreased significantly (72 +/- 5%; 53 +/- 4 and 61 +/- 4% of controls). 1 or 4 wk after debanding, LV systolic pressures were similar to control values, and the degree of myocardial hypertrophy decreased to levels 23 +/- 6 (P less than 0.01) and 11 +/- 6% (P less than 0.01) above their control values, respectively. At 1 wk there was no significant increase in CFR/myocardial mass, compared to values in the banded group (67 +/- 8 vs. 53 +/- 4% of controls at 100 mmHg and 67 +/- 9 vs. 61 +/- 4% at 150 mmHg of CPP). At 4 wk, CFR and the ratio had increased toward normal. Thus, decreased coronary perfusion in hypertrophied hearts is completely reversible.     

HMG CoA reductase inhibition and left ventricular mass in hypertrophic cardiomyopathy: a randomized placebo-controlled pilot study

BACKGROUND: Statins reduce cardiomyocyte hypertrophy in animal models of hypertrophic cardiomyopathy, aortic banding and heart failure after myocardial infarction. We investigated the effect of the hydroxymethylglutaryl coenzyme A reductase inhibitor atorvastatin on left ventricular (LV) mass in patients with hypertrophic cardiomyopathy in a randomized placebo-controlled double-blind pilot study. MATERIALS AND METHODS: Patients with hypertrophic cardiomyopathy were randomized to be treated once daily by atorvastatin 80 mg or placebo for nine months. LV mass was assessed by serial cardiac magnetic resonance imaging. LV systolic and diastolic function was determined by echocardiography. Markers of collagen metabolism and inflammation were also assessed. RESULTS: Out of 78 screened patients with hypertrophic cardiomyopathy 28 (2 x 14) patients were eligible for randomization. Eleven patients in each group completed the study with cardiac magnetic resonance imaging assessments meeting the evaluation standards at baseline and at follow-up. Low-density lipoprotein cholesterol levels in the atorvastatin group decreased from 3.24 +/- 1.14 mmol L(-1) (125 +/- 44 mg dL(-1)) at baseline to 1.37 +/- 0.49 mmol L(-1) (53 +/- 19 mg dL(-1)) at follow-up (P < 0.001), but were unchanged in the placebo group. Baseline LV mass was 228 +/- 51 g in the placebo and 232 +/- 67 g in the atorvastatin group. The primary endpoint of change in LV mass from baseline to follow-up was 2 +/- 10% in the atorvastatin group versus 0 +/- 13% in the placebo group (P = NS). Parameters of LV volumes and diameters, systolic and diastolic function, and markers of collagen metabolism were also unchanged in both groups. CONCLUSION: In patients with hypertrophic cardiomyopathy, this randomized placebo-controlled double-blind pilot study did not demonstrate an effect of 9-month treatment with atorvastatin 80 mg on LV mass reduction.     

Longitudinal trends in left ventricular cardiac output in healthy infants in the first year of life

We studied left ventricular (LV) cardiac output as estimated by ascending aorta blood flow (QAo) longitudinally in 31 healthy infants from birth through the first year of life using noninvasive pulsed Doppler ultrasound technique. The temporal mean ascending aortic blood flow velocity (VAo) was measured with a 5-MHz pulsed Doppler velocimeter and on line integration system. Ascending aortic cross-sectional area (AAo) was determined using M-mode echography. Ascending aortic blood flow was calculated as QAo = VAo X AAo and was corrected to body weight (BW) in kilograms or body surface area (BSA) in meters squared. Mean ascending aortic flow velocity (VAo) remained relatively constant over the first year, averaging 20.5 +/- 3.4 cm/sec (+/- SD). Changes in AAo over time correlated strongly with changes in BW or BSA (r = 0.99). Therefore, changes in QAo correlated strongly with changes in AAo, BW, and BSA (r = 0.99). LV cardiac output corrected for body weight or BSA remained relatively constant throughout the first year, mean values ranging from 180-226 ml/min/kg or 3.06-3.76 L/min/m2 and averaging 204 +/- 45 ml/min/kg or 3.48 +/- 0.74 L/min/m2. A similar strong correlation was seen between serial changes in LV stroke volume and changes in BW or BSA (r = 0.99).     

应用高频超声评价小鼠缺血性心肌病左室重塑的实验研究

目的应用15MHz线阵超声探头评价小鼠缺血性心肌病左室重塑的发生规律，探讨缺血性心肌病左室形态功能障碍的发生机制。 方法60只昆明小鼠随机分为两组，其中一组45只小鼠行开胸左冠状动脉高位结扎术为手术组，另一组15只仅开胸不结扎左冠状动脉为假手术组。两组应用15MHz高频线阵探头分别于术前、术后1、2、4、6周行经胸心脏超声检查。并于术后6周时行微导管血流动力学及病理学检查。 结果超声观察到缺血性心肌病左室重塑开始于模型制作成功后第1周，并于第6周最为显著，表现为：早期梗死区的过度伸展，左室舒、缩末内径，左室舒张末外径，左室质量显著增加（P均〈0．05），左室前壁厚度、左心室短轴缩短率和血流动力学指标的显著降低（P均〈0．05）。 结论高频超声是一种可靠无创的连续评价手段，小鼠心肌缺血后梗死区的早期伸展是左室发生心肌病样重塑的主要原因。     

Functional assessment of isolated right heart failure by high resolution in-vivo cardiovascular magnetic resonance in mice.

Precise and noninvasive characterization of the development of the cardiac phenotype in murine models of heart failure has been widely demanded in modern cardiovascular research. High-resolution cardiovascular magnetic resonance (CMR) has been proven to be a powerful tool for the accurate and reproducible assessment of LV and RV parameters in healthy mice. Whereas changes in LV parameters in models of heart failure have been thoroughly evaluated, RV dysfunction has not. Purpose of this study was to characterize a model of isolated RV failure induced by pulmonal banding by in vivo CMR at 7T. RV parameters differed significantly from those of normal mice in terms of RV end-diastolic volume (EDV: 85 +/- 14 microL vs. control 36 +/- 3 microL, p < 0.0001), RV end-systolic volume (ESV: 121 +/- 10 microL vs. control 84 +/- 4 microL, p < 0.005) and RV ejection fraction (EF: 31 +/- 6 % vs. control 57 +/- 2 %, p < 0.001). With regard to EDV, ESV, SV and EF LV parameters, there were no significant differences between pulmonary banded and control mice indicating overt isolated RV failure.     

Differences in left ventricular hypertrophy and dysfunction between patients with cerebral hemorrhage and those with cerebral infarction

Left ventricular (LV) hypertrophy and dysfunction due to hypertension have been established as risk markers for stroke in hypertensive patients. The purpose of this study was to examine the differences in LV hypertrophy and dysfunction between patients with cerebral hemorrhage and those with cerebral infarction. The study enrolled 23 hypertensive patients with cerebral infarction, 25 hypertensive patients with cerebral hemorrhage, and 24 normotensive controls (controls). Standard echocardiography was performed; LV mass index was measured to evaluate LV hypertrophy, and conventional diastolic transmitral flow velocities were measured to assess LV diastolic function, which was also evaluated by measuring mitral annular velocities using tissue Doppler echocardiography. The Tei index, which reflects both the diastolic and systolic function of LV, was also calculated. The LV mass index and Tei index were significantly higher in cerebral hemorrhage (116 +/- 38 g/m(2) and 0.57 +/- 0.13) than those in controls (92 +/- 20 g/m(2) and 0.46 +/- 0.10) (p < 0.05). In contrast, the LV mass index and Tei index in cerebral infarction (100 +/- 27 g/m(2) and 0.46 +/- 0.12) were not different from those in controls. Thus, the Tei index was significantly worse in the patients with cerebral hemorrhage than in those with cerebral infarction (p < 0.05). On the other hand, the parameters, which reflect diastolic function, showed no significant differences between cerebral hemorrhage and cerebral infarction. These results indicate that LV hypertrophy and dysfunction due to hypertension are more apparent in patients with cerebral hemorrhage than in those with cerebral infarction.     

Left ventricular stiffness and chamber geometry in the pressure-overloaded hypertrophied heart.

Pressure-overloaded hypertrophy of the left ventricle (LV) was produced by coarctation of the ascending aorta in 7 dogs. The overall mean weight of the left ventricle (LVW) was 7.86 +/- 1.49 (S.D.) g/kg body weight; (normal, 5.99 +/- 0.70 g/kg: p less than 0.05). After potassium arrest, pressure-volume (P-V) relationships were examined with the left ventricles isolated from the normals and from the dogs of left ventricular hypertrophy (LVH-dogs). In both groups, the P-V relationships could be expressed by an equation deltaV=a-be-cP throughout the range of filling pressure of 2.5 to 35 cmH2O, where deltav was the actual volume change of LV, P intraventricular pressure, and a, b and c constants. A sensitive index of LV stiffness, the half-inflation pressure (h), was defined as 1n (2b/a)/c. In hypertrophied hearts, h was 10.5 +/- 0.7 cmH2O; (normal 8.0 +/- 0.4 cmH2O; P less than 0.001). The ratio of LVW to LVVp=h (the left ventricular volume at h) in hypertrophy, which was related to the LV chamber geometry, was 3.1 +/- 0.6 in contrast with the normal value of 2.0 +/- 0.3. The development of concentric hypertrophy was thus demonstrated. Moreover, h was closely correlated with LVW/LVVp=h in both the normals and the LVH-dogs (r=0.83; p less than 0.01). On the other hand, an index of LV wall stiffness h/LVW/LVVP=h was relatively constant. Therefore, the increase of LV stiffness in the LVH-dogs was attributed to the change in chamber geometry.     

Three-dimensional echocardiography with tissue harmonic imaging shows excellent reproducibility in assessment of left ventricular volumes.

We studied the reproducibility of repeated measurements of left ventricular (LV) volumes by 2-dimensional (biplane method of disks) and 3-dimensional echocardiography (coaxial scanning) with tissue harmonic imaging. Ten healthy subjects underwent estimation of LV volumes by transthoracic echocardiography twice within 1 week by 2 different operators to investigate interexamination and operator variance. In addition, the analysis of LV volume was done manually by 2 observers to assess both interobserver and intraobserver variances. With 3D echocardiography, observer variation had the greatest impact on variance. Operator variability showed important contributions to total variance with the use of 2D echocardiography. The reproducibility of 3D echocardiography and tissue harmonic imaging is excellent and comparable to magnetic resonance imaging techniques; 3D echocardiography therefore should provide a powerful tool for noninvasive LV volume estimation.     

Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-myosin heavy chain in rat hearts.

We asked whether thyroid hormone (T4) would improve heart function in left ventricular hypertrophy (LVH) induced by pressure overload (aortic banding). After banding for 10-22 wk, rats were treated with T4 or saline for 10-14 d. Isovolumic LV pressure and cytosolic [Ca2+] (indo-1) were assessed in perfused hearts. Sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, and alpha- and beta-myosin heavy chain (MHC) proteins were assayed in homogenates of myocytes isolated from the same hearts. Of 14 banded hearts treated with saline, 8 had compensated LVH with normal function (LVHcomp), whereas 6 had abnormal contraction, relaxation, and calcium handling (LVHdecomp). In contrast, banded animals treated with T4 had no myocardial dysfunction; these hearts had increased contractility, and faster relaxation and cytosolic [Ca2+] decline compared with LVHcomp and LVHdecomp. Myocytes from banded hearts treated with T4 were hypertrophied but had increased concentrations of alpha-MHC and SERCA proteins, similar to physiological hypertrophy induced by exercise. Thus thyroid hormone improves LV function and calcium handling in pressure overload hypertrophy, and these beneficial effects are related to changes in myocyte gene expression. Induction of physiological hypertrophy by thyroid hormone-like signaling might be a therapeutic strategy for treating cardiac dysfunction in pathological hypertrophy and heart failure.     

Cardiac magnetic resonance imaging in small animal models of human heart failure

The aim of this study was to test the feasibility of cine magnetic resonance imaging (MRI) for assessment of the infarcted rat and mouse heart and to compare the results with established methods. These models have been proven to predict genesis and prevention of heart failure in patients. The value of cine MRI was tested in studies investigating interventions to change the course of the remodeling process. MRI was performed for determination of left ventricular (LV) volumes and mass, myocardial infarct (MI) size and cardiac output. LV wet weight was determined after MRI. Rats underwent conventional hemodynamic measurements for determination of cardiac output and LV volumes by electromagnetic flowmeter and pressure-volume curves. Infarct size was determined by histology. MRI-acquired MI-size (18.5+/-2%) was smaller than that found by histology (22.8+/-2.5%, p<0.05) with close correlation (r=0.97). There was agreement in LV mass between MRI and wet weight (r=0.97, p<0.05) and in the MRI- and flowmeter measurements of cardiac output (r=0.80, p<0.05). Volume by MRI differed from pressure-volume curves with good correlation (r=0.96, p<0.05). In a serial study of mice after coronary ligation, LV hypertrophy at 8 weeks was detected (Sham 105.1+/-7.9 mg, MI 144.4+/-11.7 mg, p<0.05). Left ventricles were enlarged in infarcted mice (end-diastolic volume, week 8: Sham 63.5+/-4 microl, MI 94.2 microl, p<0.05). In conclusion, cine MRI is a valuable diagnostic tool applicable to the rat and mouse model of MI. Being non-invasive and exact it offers new insights into the remodeling process after MI because serial measurements are possible. The technique was applied to study several interventions and proved its usefulness.     

Effect of potassium-channel opener therapy on reperfused infarction in hypertrophied hearts: demonstration of preconditioning by using functional and contrast-enhanced magnetic resonance imaging

Effects of therapy with the potassium-channel opener and vasodilator nicorandil were studied in reperfused infarction of hypertrophied hearts by using magnetic resonance imaging (MRI), hemodynamic measurements, and histochemical staining. Aortic banding was performed on 22 Sprague-Dawley rats to induce left ventricular (LV) hypertrophy; 11 were the controls. Eight weeks later, the left coronary artery was occluded for 25 minutes in all 33 animals, followed by 3 hours of reperfusion. During occlusion, 11 rats with LV hypertrophy received nicorandil (0.1 mg/kg bolus and 1.5 mg/kg/h for 3 hours). The new necrosis-specific contrast agent Gadophrin-3 was administered to all animals to delineate infarction on multislice T1-weighted spin-echo MRI. Nicorandil increased ischemic tolerance of LV hypertrophy as shown by the reduction of infarction size from 19.3% +/- 1.3% to 10.0% +/- 2.5% LV (P = .005). Infarction size in treated animals was identical to control (9.3% +/- 1.6%). Close correlation was found between MRI and postmortem findings. Functional MRI revealed an improvement in ejection fraction in nicorandil-treated hearts (48.5% +/- 3.4% vs 38.1% +/- 3.2%, P = .04). LV end-diastolic volume and pressure, aortic pressure, and peripheral vascular resistance were highest in untreated hypertrophied hearts. Brief ischemia caused severe injury in hypertrophied hearts. Infusing nicorandil increased the tolerance of hypertrophied hearts to ischemia. MRI is a suitable technique for the evaluation of new therapies in LV hypertrophy.     

Three-dimensional echocardiographic measurement of left ventricular wall thickness: In vitro and in vivo validation.

INTRODUCTION: Three-dimensional (3D) echocardiography has been shown to accurately measure left ventricular (LV) volume and mass. This study evaluated the accuracy of 3D echocardiography and the CenterSurface method for measuring LV wall thickness in vitro and in vivo. METHOD: Three-dimensional echocardiography scans, obtained from 7 LV phantoms and subjects having healthy (n = 5) or diseased (n = 8) hearts, were digitized. Endocardial and epicardial borders were outlined and used in 3D LV reconstruction. In vitro wall thickness was compared with true micrometer measurements. Three-dimensional in vivo wall thickness was compared with 2-dimensional (2D) thickness measured by the centerline method. RESULTS: The in vitro 3D echocardiography measurements agreed closely with true wall thickness (P <.0001), as did in vivo measurements (P <.0001). CONCLUSION: Three-dimensional echocardiography reconstruction has previously been shown to provide accurate representation of LV shape in addition to volume and mass. This study demonstrates that the CenterSurface method provides accurate quantification of wall thickness.     

Left ventricular hypertrophy induced by aortic banding impairs relaxation of isolated coronary arteries

LVH (left ventricular hypertrophy) is associated with impaired coronary vascular reserve. In the present study, we examined the effect of pressure-overload hypertrophy on vasorelaxant responses of guinea-pig isolated coronary small arteries and compared them with mesenteric small arteries. Pressure-overload was induced by banding the ascending aorta of guinea-pigs. Haemodynamics, and ventricular, atrial and lung weights were measured 168 days after banding. Isolated coronary and mesenteric small arteries were contracted with a thromboxane mimetic (U46619) and relaxation to ACH (acetylcholine), ISO (isoprenaline), FSK (forskolin) and SNP (sodium nitroprusside) was examined. Arterial wall morphology was examined by light microscopy. Aortic banding reduced cardiac output and increased systemic vascular resistance; atrial, ventricular and lung weights were increased. Coronary artery adventitial and medial thickness were increased, but mesenteric arterial wall morphology was unaffected. Coronary artery relaxation to ACH, ISO, FSK and SNP were reduced in banded animals. In contrast, relaxation of mesenteric arteries to ACH, FSK and SNP were unaffected by banding, although ISO-induced relaxation was reduced. A COX (cyclo-oxygenase) inhibitor, indomethacin, had no effect on coronary artery responses to ACH in banded or sham animals, but the differences in relaxation of coronary arteries between banded and sham animals were no longer significant following pre-incubation with the NO inhibitors L-NMMA (N(G)-monomethyl-L-arginine) and oxyhaemoglobin. In conclusion, pressure-overload-induced LVH causes impaired relaxation of small coronary arteries to endothelium-dependent and -independent relaxants. These findings are indicative of alterations in vascular smooth muscle responsiveness to vasodilators. Impairment of coronary arterial vasodilation may contribute to the reduced coronary vascular reserve seen in LVH.