厄贝沙坦对SHR左心室肥厚和心肌纤维化的影响

目的 探讨厄贝沙坦对自发性高血压大鼠(SHR)左心室肥厚(LVH)和心肌纤维化的影响。方法 16只16周龄雄性SHR,随机分为厄贝沙坦治疗组和SHR空白对照组;另设同源的WKY大鼠8只为正常对照组。治疗组予厄贝沙坦15 mg/（kg·d）灌胃给药,8周后处死动物,测量左心室心肌厚度并称质量,计算左心室质量/体质量比(LVM/BM);通过Van Gieson染色法观察左心室心肌胶原变化,对左心室心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)进行定性和半定量分析;HE染色光镜观察左心室心肌病理变化。结果 与WKY组相比,SHR对照组的尾动脉收缩压(SBP)、LVM/BM、左心室壁厚度、CVF、PVCA、均显著增高(P<0.01);与SHR对照组相比,厄贝沙坦治疗组能有效降低SHR的SBP,改善LVH(P<0.01),减少心肌间质及心肌小动脉周围的胶原(P<0.01)。结论 厄贝沙坦可有效降低SHR血压,减轻心肌纤维化和LVH。     

Regional myocyte size in compensated right ventricular hypertrophy in the ferret

The effect of pressure-induced right ventricular hypertrophy on regional myocyte size and shape and regional myocardial wet weight was studied by comparing 20 ferrets which underwent pulmonary artery banding at a weanling age to 19 non-operated siblings. Using isolated myocyte preparations from six myocardial regions in 10 banded and seven non-banded ferrets, a 60% increase in cell volume in the right ventricular outflow tract and the right ventricular free wall was shown to be due primarily to an increased cross-sectional area of individual myocytes. The right side of the interventricular septum exhibited an intermediate increase in cell volume, while the left side of the interventricular septum did not respond to the pulmonary artery banding procedure. These findings confirm that localized hemodynamic changes produce hypertrophy of individual myocytes in selected regions of the heart and that a pressure-induced model of hypertrophy involves an increased cross-sectional area of myocytes, with minimal change in cell length.     

Age and hypertrophy related changes in contractile post-rest behavior and action potential properties in isolated rat myocytes

“Physiological” aging as well as early and progressive cardiac hypertrophy may affect action potential (AP) pattern, contractile function, and Ca²⁺ handling. We hypothesize that contractile function is disturbed in hypertrophy from early stages and is differently affected in aged myocardium. In vivo function, cardiomyocyte contractile behavior and APs were compared in Wistar-Kyoto (WIS) rats and spontaneously hypertensive rats (SHR) at different ages and degrees of hypertrophy (3–4, 9–11, 20–24 months). Post-rest (PR) behavior was used to investigate the relative contribution of the sarcoplasmic reticulum (SR) and the Na/Ca exchanger (NCX) to cytosolic Ca²⁺ removal. APs were recorded by whole-cell current-clamp and sarcomere shortening by video microscopy. Cyclopiazonic acid was used to suppress Ca²⁺ ATPase (SERCA) function. Heart weight/body weight ratio was increased in SHR versus WIS within all age groups. Myocyte steady state (SS) shortening amplitude was reduced in young SHR versus WIS. Aging led to a significant decay of SS contractile amplitude and relengthening velocity in WIS, but the PR potentiation was maintained. In contrast, aging in SHR led to a decrease of PR potentiation, while SS contraction and relengthening velocity increased. APD_50% was always prolonged in SHR versus WIS. With aging, APD_50% increased in both WIS and SHR, but was still shorter in WIS. However, in old WIS the late AP portion (APD_90%) was prolonged. Ca²⁺ handling and AP properties are disturbed progressively with aging and with increasing hypertrophy. Decreased amplitude of shortening and velocity of relengthening in aged WIS may be attributed to reduced SERCA function. In SHR, an increase in SR leak and shift towards transmembraneous Ca handling via NCX may be responsible for the changes in contractile function. A prolonged APD_90% in aged WIS may be an adaptive mechanism to preserve basal contractility. Therefore, the effects on contractile parameters and AP are different in hypertrophy and aging.     

Transmural distribution of myocardial blood flow and of coronary reserve in canine left ventricular hypertrophy

Summary Left ventricular hypertrophy was induced by banding of the ascending aorta in puppies at the age of 6 weeks. At the age of one year left ventricular weight per body weight was increased by 87% compared to control litter mates. While myocardial perfusion and myocardial oxygen consumption per 100 g were identical in the hypertrophy and control group, there was a significantly diminished ratio of subendocardial/subepicardial flow in the hypertrophy group during moderate exercise. With maximal coronary dilation subendocardial diastolic resistance (mm Hg/ml·min^–1 per 100 g) was 0.16±0.03 in the control group and 0.26±0.03 in the hypertrophy group. This diminished coronary reserve indicates an insufficient growth of the vascular bed in these hypertrophied hearts.

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Transmurale Verteilung der Myokarddurchblutung und der Koronarreserve in Hunden mit Hypertrophie des linken Ventrikels

Zusammenfassung Jungen Hunden im Alter von 6 Wochen wurde ein Ring um die Aorta ascendens gelegt. Dadurch wurde eine Hypertrophie des linken Ventrikels induziert, so daß im Alter von einem Jahr das Gewichtsverhältnis des linken Ventrikels pro Körpergewicht um 87% höher war als in normalen Wurfgeschwistern. Während die Myokardperfusion und der myokardiale Sauerstoffverbrauch pro 100 g in der normalen Gruppe und in der Gruppe mit Hypertrophie identisch waren, ergab sich bei Arbeit ein signifikant erniedrigtes Verhältnis der subendokardialen Druchblutung zur subepikardialen Durchblutung in den Hunden mit hypertrophierten Herzen. Bei maximaler Koronardilatation betrug der subendokardialen Durchblutung zur subepikardialen Durchblutung in den Hunden in normalen Hunden und 0,26±0,03 in Hunden mit Herzhypertrophie. Diese verminderte Koronarreserve spricht für ein nicht ausreichendes Wachstum des Koronargefäßbettes in diesen hypertrophierten Herzen.

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Paper, presented at the Erwin Riesch Symposium, Tübingen, September 26–29, 1976

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With 2 figures and 3 tables     

Association between left ventricular hypertrophy and changes in arterial stiffness during hypertensive treatment

Cardio-ankle vascular index (CAVI) has been demonstrated as a parameter of arterial stiffness, which antihypertensive therapy may improve. However, little information is available about the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. We performed a study to examine the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. Eighty treated hypertensive patients (71?±?10 years) were divided into two groups: 50 patients showing a decrease in CAVI (Group 1) and 30 patients showing an increase (Group 2) during observation (24?±?11 months) of antihypertensive therapy. The groups did not differ in the rates of use of angiotensin II receptor blockers or calcium channel blockers. Age (Group 1: 67?±?11 versus Group 2: 74?±?8 years), left ventricular mass index (LVMI) (Group 1: 103?±?19 versus Group 2: 120?±?24?g/m²) and systolic blood pressure (Group 1: 133?±?17 versus Group 2: 144?±?23?mm?Hg) at the start of observation were significantly higher in Group 2 than in Group 1 (p?=?0.003, p?=?0.001 and p?=?0.027, respectively). The changes in CAVI during observation were correlated only with LVMI (r?=?0.289, p?=?0.009) at the start of observation for all 80 patients. It may be difficult to improve arterial stiffness assessed by CAVI during antihypertensive therapy in hypertensive patients with left ventricular hypertrophy.     

Simultaneous changes of left ventricular and left atrial size and function in normal subjects during exercise

We performed dual M-mode exercise echocardiography, which records left ventricular (LV) and left atrial (LA) echocardiograms simultaneously, in 10 normal subjects to investigate mechanisms of cardiac adaptation to dynamic exercise. The LV end-diastolic dimension (EDD) increased significantly as exercise increased from mild to moderate (3-5%, p less than 0.05 and 0.001). At peak exercise the EDD was slightly increased, but it returned to the baseline during recovery. The LV end-systolic dimension (ESD) showed a progressive decrease with the severity of exercise (5-13%, p less than 0.05 and 0.001). It decreased further immediately after exercise (17-20%) and then returned to the resting value. The LV stroke dimension and fractional shortening increased as exercise changed from mild to moderate and reached a plateau at peak exercise. During recovery, they showed a transient increase and then decreased. By contrast, the LA dimensions, both maximum and minimum, increased significantly as exercise changed from mild to moderate (15-16% and 16-19%, p less than 0.01 and 0.001, respectively), but they were lower at peak exercise (12 and 14%). They returned rapidly to the resting values immediately after exercise. Thus, during exercise, LV function is augmented by the Frank-Starling mechanism in combination with increased contractility, while the LA is enlarged to receive the increased venous return accompanying dynamic exercise. These exercise-induced changes in LV performance return gradually to the resting state, but LA size recovers rapidly after the cessation of exercise.     

Epicardial coronary artery size in hypertensive and physiologic left ventricular hypertrophy

BACKGROUND: In the hypertensive heart, epicardial arteries are not enlarged, despite increased total coronary flow related to augmented cardiac workload, wall stress, and left ventricular (LV) mass. The aims of this study were to assess the impact of different hemodynamic factors and LV mass on baseline left main coronary artery (LMA) size in hypertensive LV hypertrophy (LVH) and physiologic LVH, used as a pressure-independent model of hypertrophy. METHODS: In 104 subjects without coronary disease (26 normotensive subjects without LVH, 15 athletes with physiologic LVH, and 63 untreated hypertensive subjects [28 without and 35 with LVH]), LMA size and coronary flow reserve (CFR) were measured by transesophageal echocardiography, and LV mass, volumes, stroke work, and wall stress were measured by transthoracic echocardiography. RESULTS: The LMA area in normotensive control subjects, athletes, and hypertensive subjects without and with LVH was 13.2 +/- 4.2, 17.5 +/- 2.9, 10.1 +/- 3.2 and 13.1 +/- 3.9 mm(2). In normotensive control subjects, LMA size increased with body surface area, rate-pressure product, stroke work, and LV mass or wall thickness (r = 0.39, 0.39, 0.47 and 0.67 or 0.62, P < .05-0.01). In athletes with physiologic LVH, LMA area increased with CFR (0.65, P < .01). In the whole hypertensive population, LMA lumen increased with LV mass (r = 0.40, P < .01), and decreased with office systolic blood pressure (r = -0.48, P < .01). CONCLUSIONS: In the hypertensive LVH, baseline LMA area is not increased and is inversely related to office systolic blood pressure. In the physiologic LVH, increase in baseline LMA size seems to reflect effect of high-flow stimuli.     

Paradoxical cellular Ca2+ signaling in severe but compensated canine left ventricular hypertrophy

In conscious dogs with severe left ventricular (LV) hypertrophy (H) (doubling of LV/body weight), which developed gradually over 1 to 2 years after aortic banding, baseline LV function was well compensated. The LV was able to generate twice the LV systolic pressure without an increase in LV end-diastolic pressure, or decrease in LV dP/dt or LV wall thickening. However, LV myocytes isolated from LVH dogs exhibited impaired contraction at baseline and in response to Ca2+. There was no change in L-type Ca2+ channel current (ICa) density but the ability of ICa to trigger Ca2+ release from the sarcoplasmic reticulum (SR) was reduced. Immunoblot analysis revealed a 68% decrease in SERCA2a, and a 35% decrease in the number of ryanodine receptors (RyR2), with no changes in protein level of calsequestrin, Na+/Ca2+ exchanger or phospholamban (PLB), but with both RyR2 and PLB hyperphosphorylated. Spontaneous Ca2+ sparks in LVH cells were found to have prolonged duration but similar intensities despite the reduced SR Ca2+ load. A higher Ca2+ spark rate was observed in LVH cells, but this is inconsistent with the reduced SR Ca2+ content. However, Ca2+ waves were found to be less frequent, slower and were more likely to be aborted in Ca2+-challenged LVH cells. These paradoxical observations could be accounted for by a nonuniform SR Ca2+ distribution, RyR2 hyperphosphorylation in the presence of decreased global SR Ca2+ load. We conclude that severe LVH with compensation masks cellular and subcellular Ca2+ defects that remain likely contributors to the limited contractile reserve of LVH.     

Electrocardiographic diagnosis of left ventricular hypertrophy: depolarization changes

Electrocardiographic signs of left ventricular hypertrophy (LVH) are on one hand accepted as independent cardiovascular risk factors and indicators of target organ damage in hypertensive patients, but, on the other hand they are strongly criticized for their low sensitivity. In this paper, a historic perspective on the ECG dignosis of LVH is presented, showing the development of current views on the role of ECG in LVH detection. Based on the fact that ECG provides information on the electrical properties of myocardium and on new knowledge about electrical remodeling in LVH, a shift of paradigm in our consideration of the diagnosis of left ventricular hypertrophy is proposed, based on changes in the electrical properties of hypertrophied myocardium. This new paradigm could explain the broad spectrum of QRS patterns seen in LVH, including increased QRS voltage, prolonged duration of QRS complex, left axis deviation, prolonged intrinsicoid deflection, LBBB and LAFB patterns, as well as pseudo-normal ECG findings.     

Regression of left ventricular hypertrophy during antihypertensive treatment

Left ventricular hypertrophy is a risk factor for cardiovascular events and stroke. It has been demonstrated that the regression of left ventricular hypertrophy (evaluated by 12-lead electrocardiography and by echocardiography) during antihypertensive treatment is associated with a lower risk of cardiovascular mortality and may thus improve the prognosis. Black people run a disproportionately high risk of developing essential arterial hypertension which frequently results in end organ damage, including left ventricular hypertrophy, haemorrhagic stroke and renal failure. We report a case of significant regression of left ventricular hypertrophy in a sub-Saharan African patient, during antihypertensive treatment.     

Early changes in left ventricular size and function after correction of left ventricular volume overload

The ability to predict early postoperative left ventricular size and function in patients with isolated aortic or mitral regurgitation was determined utilizing multigated blood pool imaging before and 2 to 4 weeks after valve replacement (aortic valve, 20 patients; mitral valve, 20 patients). Early postoperatively, ejection fraction decreased significantly (p <0.001) in both patient groups (from 0.55 ± 12 to 0.40 ± 0.14 [mean ± 1 standard deviation] in patients with aortic regurgitation and from 0.66 ± 0.09 to 0.48 ± 0.11 in patients with mitral regurgitation). The decrease in ejection fraction was associated with a large decrease in stroke volume with minimal or no change in end-systolic volume; it was unrelated to the preoperative ejection fraction. Early postoperative ejection fraction correlated best with preoperative end-systolic volume and was normal in 14 (67 percent) of 21 patients with a preoperative ejection fraction above 0.60; 4 (27 percent) of 15 patients with a preoperative ejection fraction of 0.50 to 0.60; and in 0 of 4 patients with a preoperative ejection fraction below 0.50 (p <0.05). In addition, a repeated scan in 16 patients late (1 to 2 years) after operation showed a further reduction in endsystolic volume in patients with aortic regurgitation with an increase in ejection fraction toward preoperative values. There was no significant change in patients with mitral regurgitation.End-diastolic volume decreased significantly (p <0.001) early postoperatively (from 162 ± 60 to 102 ± 41 ml/m² in patients with aortic regurgitation and from 131 ± 40 to 78 ± 30 ml/m² in patients with mitral regurgitation). This decrease was closely related to a decrease in stroke volume and was unrelated to preoperative ejection fraction. Early postoperative end-diastolic volume correlated best with the preoperative end-systolic volume. The major part of the reduction in end-diastolic volume occurred within 2 weeks of valve replacement.Removal of chronic left ventricular volume overload due to aortic or mitral regurgitation produces a decrease in ejection fraction and end-diastolic volume. The early reduction is in part a result of altered loading conditions and may not necessarily imply alterations in myocardial contractile function. The reduction in ejection fraction appears to persist in patients with mitral regurgitation.     

Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension

The effects of circadian blood pressure (BP) changes on the echocardiographic parameters of left ventricular (LV) hypertrophy were investigated in 235 consecutive subjects (137 unselected untreated patients with essential hypertension and 98 healthy normotensive subjects) who underwent 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) and cross-sectional and M-mode echocardiography. In the hypertensive group, LV mass index correlated with nighttime (8:00 PM to 6:00 AM) systolic (r = 0.51) and diastolic (r = 0.35) blood pressure more closely than with daytime (6:00 AM to 8:00 PM) systolic (r = 0.38) and diastolic (r = 0.20) BP, or with casual systolic (r = 0.33) and diastolic (r = 0.27) BP. Hypertensive patients were divided into two groups by presence (group 1) and absence (group 2) of a reduction of both systolic and diastolic BP during the night by an average of more than 10% of the daytime pressure. Casual BP, ambulatory daytime systolic and diastolic BP, sex, body surface area, duration of hypertension, prevalence of diabetes, quantity of sleep during monitoring, funduscopic changes, and serum creatinine did not differ between the two groups. LV mass index, after adjustment for the age, the sex, the height, and the daytime BP differences between the two groups (analysis of covariance) was 82.4 g/m2 in the normotensive patient group, 83.5 g/m2 in hypertensive patients of group 1 and 98.3 g/m2 in hypertensive patients of group 2 (normotensive patients vs. group 1, p = NS; group 1 vs. group 2, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of left ventricular contractile behaviour during atrial fibrillation

SummaryObjectives The purpose of this study was to explore the physiology underlying the beat-to-beat variations of ventricular function during atrial fibrillation (AF).Methods Left ventricular pressure, and its first derivative (LVdP/dt_max, an index of contractility, and aortic blood velocity (and its integral AVI, an ejection index), were recorded using cathetermounted transducers in 15 patients with AF during cardiac catheterisation. Transfer function modelling was used to examine the influence of preceding intervals on LVdP/dt_max, and of LVdP/dt_max on AVI. The technique also allowed simulation of the behaviour of LVdP/dt_max in response to specific manipulations of interval.Results The variations in LVdP/dt_max recorded from the AF patients were shown to be dependent on up to six preceding intervals; a maximum of 91 % of the variation was explicable in this way. The influences of mechanical restitution (MR, the relationship between preceding interval and contractility), postextrasystolic potentiation (PESP, the inverse relationship between pre-preceding interval and contractility) and the decay of that potentiation were all demonstrated. These influences collectively appeared to be powerful determinants of AVI. Simulations of LVdP/dt_max, following single interval perturbations, were entirely consistent with these interval force effects.Conclusions The cardiac interval force relationship in man is an important determinant of the beat-to-beat variations of contractile and ejection function during AF: the beat-to-beat variations in contractile (or inotropic) function are independent of changes in ventricular filling or fibre-length.     

辛伐他汀对自发性高血压大鼠左心室肥厚作用及心肌转化生长因子-β1表达影响

目的观察辛伐他汀对自发性高血压大鼠左心室肥厚作用及心肌转化生长因子-β1(TGF-β1)表达的的影响。方法实验用WKY大鼠做阴性对照组,SHR大鼠分为对照组和辛伐他汀治疗组。测量大鼠尾动脉收缩压(SBP)及左心室重量指数(LVMI)。应用HE、VG染色、免疫组织化学的方法,结合计算机图像分析技术,检测心肌细胞的直径(TDM)和面积(CA)、心肌组织胶原体积比例(CVF)、血管周围胶原面积和管腔面积比例(PVCA)以及左心室心肌TGF-β1表达。结果辛伐他汀组未能有效降低血压,但可以降低左心室肥厚;SHR辛伐他汀组与SHR对照组相比TDM、CA、CVF、PVCA明显降低,TGF-β1表达下调明显(均P<0.05)。结论应用辛伐他汀治疗可逆转高血压大鼠左心室肥厚形成,TGF-β1可能与辛伐他汀逆转左心室肥厚的机制有关。     

Transmural coronary vasodilator reserve, and flow distribution during tachycardia in conscious young swine with right ventricular hypertrophy

Regional distribution of myocardial blood flow (MBF) was examined in eight normal and nine pulmonary artery banded (PAB) pigs before and during pacing induced tachycardia (heart rates: 175, 225 and 275 beats X min-1) as well as during iv adenosine infusion (1.5 mg X kg-1 X min-1; maximal coronary vasodilatation) using radionuclide labelled 15 micron diameter microspheres that were injected into the left atrium. It was observed that MBF per unit myocardial mass in the hypertrophied right ventricle (RV) of PAB pigs was similar to that in the RV of normal pigs. Also, minimal coronary vascular resistance per unit myocardial mass was similar between the two groups of pigs for RV as well as left ventricle (LV). This suggests that the increase in RV myocardial mass of young PAB swine was attended by appropriate adjustments in functional cross-sectional area of the RV coronary vascular bed. Despite similarity of maximal coronary vasodilator capacity in the two groups of swine, during pacing induced tachycardia MBF in the hypertrophied RV subendocardium as well as the right and middle layers of the interventricular septum in PAB pigs increased to a significantly lower level than in normal pigs and the RV endo:epi perfusion ratio, unlike in normal pigs, decreased to near unity. Increments in transmural LV MBF of PAB pigs were also attenuated during pacing at 225 and 275 beats X min-1 but the LV endo:epi perfusion ratio for the two groups of pigs remained similar. These findings suggest a possible overall depression of myocardial function in PAB swine.     

Radionuclide left ventricular contractile indices and their relationship to heart size in dogs

To identify possible mechanisms to explain differences between the maximum time-varying elastance (Emax) and end-systolic pressure-volume (Ees) slope values calculated with radionuclide angiography and to establish whether they have a relationship to heart size, we studied 16 dogs that were instrumented with micromanometer left ventricular catheters and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics and radionuclide angiograms were obtained under control conditions and during six additional steady-state loading conditions. Isochronal Emax averaged 7.14 +/- 2.54 mm Hg/ml, while Ees averaged 5.68 +/- 1.88 mm Hg/ml (p less than 0.01), but they were highly correlated (r = 0.95, p less than 0.001). This observation was related to the assumption of linearity when curvilinearity was present and to the important influence of timing on these relationships. The Emax and Ees slope values were compared to dog weight; left ventricular weight, which ranged from 85 to 142 gm (mean 113 +/- 18 gm); and left ventricular end-diastolic volume, which ranged from 15 to 56 ml (mean 29 +/- 10 ml) using multiple regression analyses. The Emax and Ees slope values demonstrated a comparable inverse linear relationship with only left ventricular end-diastolic volume (r = 0.76 and -0.69, p less than 0.001 and p less than 0.01). We conclude that the differences between Emax and Ees slope values calculated with radionuclide angiography are related to the assumption of linearity when curvilinearity is present and to the importance of the timing of systolic events and that both Emax and Ees are comparably related to left ventricular end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gender differences in electrical remodeling and susceptibility to ventricular arrhythmias in rabbits with left ventricular hypertrophy

BACKGROUND: Left ventricular hypertrophy (LVH) is associated with an increased risk of death, vulnerability to ventricular arrhythmia, and multiple electrophysiological abnormalities. OBJECTIVES: The purpose of the present study was to determine the gender-dependent differences in electrical remodeling and the susceptibility to ventricular arrhythmias in a rabbit model of renovascular hypertension. METHODS: Rabbits of both sexes underwent unilateral renal artery banding and contralateral nephrectomy or were placed in the control group. Data are expressed as mean +/- standard error of the mean. RESULTS: The duration of action potentials was prolonged in the LVH group compared with the control group in both male (123 +/- 2.4 ms and 151 +/- 2.3 ms vs. 180 +/- 5.1 ms and 196 +/- 3.1 ms for action potential duration [APD](90 Epi) and APD(90 Endo) of control [n = 5] and LVH rabbits [n = 8], respectively; P<.05) and female rabbits (131 +/- 1.9 ms and 166 +/- 2.0 ms vs. 156 +/- 4.2 ms and 175 +/- 2.2 ms for APD(90 Epi) and APD(90 Endo) of control [n = 5] and LVH rabbits [n = 7], respectively; P<.05). Moreover, the gender-dependent differences in repolarization were opposite to those seen under control conditions. In LVH rabbits, APD(90) was greater in males than in females. The changes induced in APD lead to a greater transmural dispersion of repolarization (38 +/- 6.6 ms vs. 19 +/- 6.5 ms for males and females, respectively; P<.05). In addition, while control rabbits did not show induction of arrhythmias, an enhanced susceptibility to ventricular arrhythmia was seen in LVH male rabbits (6/8 male vs. 1/7 female LVH rabbits; P<.05). CONCLUSION: We conclude that the electrical remodeling associated with LVH inverted the gender-dependent differences, with male rabbits now exhibiting action potentials with longer durations both in the endocardial and epicardial surface of the left ventricle, increased dispersion of repolarization, and increased vulnerability to ventricular arrhythmia induction.