Prolonged QT Interval Is Associated with Blood Pressure Rather Than Left Ventricular Mass in Spontaneously Hypertensive Rats

QT interval is prolonged in hypertensive individuals, although the factors responsible for this increase are not completely understood. We questioned whether enhanced left ventricular mass (LVM) or increased systemic blood pressure represents the principal factor determining QT prolongation in the period of development of hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). In 12-and 20-week-old SHR (SHR12 and SHR20) and age-matched normotensive Wistar-Kyoto rats (WKY12 and WKY20), arterial systolic blood pressure (sBP) was measured using tail-cuff technique. Orthogonal Frank ECG was registered in anaesthetized animals in vivo, and bipolar ECG was measured in spontaneously beating isolated hearts in vitro. Progressive increase of sBP and LVM resulted in significant QT prolongation in SHR20 as compared to WKY12, WKY20, and also to SHR12 in vivo (WKY12: 82?±?9 ms, WKY20: 81?±?9 ms, SHR12: 88?±?15 and SHR20: 100?±?10, respectively; p?<?0.05) but not in isolated hearts (WKY20: 196?±?39 ms and SHR20: 220?±?55, respectively; NS). In whole animals, QT duration was positively related to sBP (r?=?0.6842; p?<?0.001) but not to LVM (r?=?0.1632, NS) in SHR20. The results suggest that QT prolongation in SHR developing hypertension and LVH depends on blood pressure rather than increase in LVM. In this period, myocardial hypertrophy is probably the predisposition for QT prolongation, but the significant change manifests only in the presence of elevated systemic factors.     

The initial stage of left ventricular hypertrophy in spontaneously hypertensive rats is manifested by a decrease in the QRS amplitude/left ventricular mass ratio

In this study we tested the hypothesis of the relative voltage deficit, i.e. the discrepancy between increased left ventricular mass (LVM) and QRS amplitudes, in an experimental model of spontaneously hypertensive rats (SHR) during the period of a moderate increase in blood pressure. To address this issue we recorded orthogonal electrocardiograms of male SHR at the age of 12 and 20 weeks. During this period the systolic blood pressure (sBP) increased from 165 +/- 3 mmHg to 195 +/- 1 mmHg (p < 0.001). Age and sex matched WKY rats were used as control groups. The sBP values in WKY normotensive control groups were within normal limits (122 +/- 8 mmHg and 130 +/- 4mmHg, respectively). The maximum QRS spatial vector magnitude (QRSmax) was calculated from X, Y, Z amplitudes of the orthogonal electrocardiograms. The animals were sacrificed and the left ventricular mass was weight. The specific potential of myocardium (SP) was calculated as a ratio of QRSmax to LVM. The LVM in SHR (0.86 +/- 0.05 g and 1.05 +/- 0.07 g, respectively) was significantly higher as compared to WKY (0.65 +/- 0.07 g and 0.70 +/- 0.02 g), and the increase of LVM closely correlated with the sBP increase. On the other hand, QRSmax in SHR did not follow either the increase of sBP, or LVM. The QRSmax values in SHR did not differ from those of WKY at the age of 12 weeks (0.59 +/- 0.14 mV compared to 0.46 +/- 0.05 mV), and they were even lower in SHR at the age of 20 weeks (0.74 +/- 0.08 mV compared to 0.44 +/- 0.05 mV, p < 0.001). The values of SP, quantifying the relative voltage deficit, were significantly lower in SHR as compared to the WKY control. The values decreased significantly in SHR with increasing age, sBP and LVM, i.e., with the progression of hypertrophic remodeling of the left ventricle. The results of this study support the hypothesis of the relative voltage deficit in LVH. These results are consistent with the finding of a high number of false negative ECG results in clinical ECG diagnostics of LVH, and could contribute to an understanding of the diagnostic importance of the false negative ECG results, their re-evaluation and utilization for clinical diagnosis and prognosis.     

The Initial Stage of Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats is Manifested by a Decrease in the QRS Amplitude/Left Ventricular Mass Ratio

In this study we tested the hypothesis of the relative voltage deficit, i.e. the discrepancy between increased left ventricular mass (LVM) and QRS amplitudes, in an experimental model of spontaneously hypertensive rats (SHR) during the period of a moderate increase in blood pressure. To address this issue we recorded orthogonal electrocardiograms of male SHR at the age of 12 and 20 weeks. During this period the systolic blood pressure (sBP) increased from 165 ± 3 mmHg to 195 ± 1 mmHg (p < 0.001). Age and sex matched WKY rats were used as control groups. The sBP values in WKY normotensive control groups were within normal limits (122 ± 8 mmHg and 130 ± 4mmHg, respectively). The maximum QRS spatial vector magnitude (QRSmax) was calculated from X, Y, Z amplitudes of the orthogonal electrocardiograms. The animals were sacrificed and the left ventricular mass was weight. The specific potential of myocardium (SP) was calculated as a ratio of QRSmax to LVM. The LVM in SHR (0.86 ± 0.05 g and 1.05 ± 0.07 g, respectively) was significantly higher as compared to WKY (0.65 ± 0.07 g and 0.70 ± 0.02 g), and the increase of LVM closely correlated with the sBP increase. On the other hand, QRSmax in SHR did not follow either the increase of sBP, or LVM. The QRSmax values in SHR did not differ from those of WKY at the age of 12 weeks (0.59 ± 0.14 mV compared to 0.46 ± 0.05 mV), and they were even lower in SHR at the age of 20 weeks (0.74 ± 0.08 mV compared to 0.44 ± 0.05 mV, p < 0.001). The values of SP, quantifying the relative voltage deficit, were significantly lower in SHR as compared to the WKY control. The values decreased significantly in SHR with increasing age, sBP and LVM, i.e., with the progression of hypertrophic remodeling of the left ventricle. The results of this study support the hypothesis of the relative voltage deficit in LVH. These results are consistent with the finding of a high number of false negative ECG results in clinical ECG diagnostics of LVH, and could contribute to an understanding of the diagnostic importance of the false negative ECG results, their re‐evaluation and utilization for clinical diagnosis and prognosis.     

Relation between QRS amplitude and left ventricular mass in the initial stage of exercise-induced left ventricular hypertrophy in rats

The aim of the study was to analyze the relationship between QRS amplitude and left ventricular mass (LVM) in early stages of two different experimental models of left ventricular hypertrophy (LVH) in rats: in exercise-induced hypertrophy and pathological hypertrophy due to genetically conditioned pressure overload. Three groups of experimental animals were studied: healthy control Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and WKY rats exposed to training by intermittent swimming (SWIM). Orthogonal electrocardiograms were recorded in each group at the age of 12 and 20 weeks, and the maximum spatial QRS vector (QRSmax) was calculated. Then the animals were sacrificed and LVM was measured. The specific potential of myocardium (SP) was calculated as a ratio of QRSmax to LVM. The QRSmax values did not follow the changes in LVM. At the end of the follow-up period, the highest values of QRSmax were recorded in the control WKY rats (0.80 +/- 0.05 mV). The QRSmax values in both groups with experimental LVH were significantly lower as compared with control animals (SHR 0.44 +/- 0.02 mV, p < 0.001; SWIM 0.53 +/- 0.04 mV, p < 0.001). Similarly, the SP values were significantly lower in both groups with experimental LVH as compared with control animals (SHR 0.42 +/- 0.02 mV/g, p < 0.001; SWIM 0.55 +/- 0.05 mV/g, p < 0.001). A decrease in QRSmax and SP was observed in both models of experimental LVH. We attributed these findings to the changes in electrogenetic properties of myocardium in the early stage of developing LVH. In other words, it is changes of nonspatial determinants that influence the resultant QRS voltage in terms of the solid angle theory.     

Arterial hypertension, myocardial hypertrophy and disorders of cardiac rhythm induced by ligation of the left coronary artery in the rat

Cardiac hypertrophy and hypertension are major elements in sudden cardiac death in patients with coronary artery disease. To investigate in animals the hypothesis that left ventricular hypertrophy (LVH) and/or hypertension increase the incidence of severe ventricular arrhythmias, we have undertaken a 30 min period of coronary artery ligation in anaesthetized spontaneously hypertensive rats (SHR), normotensive (NT) Wistar Kyoto (WKY) and Wistar (W) rats. Mean systolic blood pressure (SBP) was 190 +/- 4 mmHg in SHR vs 123 +/- 5 mmHg in WKY and 116 +/- 4 mmHg in W (p less than 0.001). LVH index was 2.81 +/- 0.04 in SHR vs 196 +/- 0.03 in WKY and 1.65 +/- 0.05 in W (p less than 0.01). Incidence (IVF) and duration (DVF) of ventricular fibrillation were significantly more elevated in SHR than in NT rats. IVF was 100 p. 100 in SHR vs 36 p. 100 in WKY and 27 p. 100 in W (p less than 0.001); DVF was 61 +/- 17 s in SHR vs 6 +/- 6 s in WKY and W (p less than 0.001). In addition the calcium channel blocker nicardipine (N) has been administered orally to SHR either chronically during eight weeks (20 mg/kg-1 per os twice daily) or acutely as a single dose of 20 mg/kg. After long term treatment (LT) with N the LVH index and SBP were significantly reduced when compared to vehicle treated (VT) SHR; whereas a single administration of N (AT) only decreased SBP without affecting LVH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multivariate associates of QT interval parameters in diabetic patients with arterial hypertension: importance of left ventricular mass and geometric patterns

The aim of the study was to assess the determinants of increased QT interval parameters in diabetic patients with arterial hypertension and, in particular, the strength of their relationships to echocardiographically derived left ventricular mass (LVM) and geometric patterns. In a cross-sectional study with 289 hypertensive type 2 diabetic outpatients, maximal QT and QTc (heart rate-corrected) intervals, and QT, QTc, and number-of-leads-adjusted QT interval dispersions were manually measured from standard baseline 12-lead ECGs. Electrocardiographic criteria for left ventricular hypertrophy (LVH) were either Sokolow-Lyon or Cornell sex-specific voltages. LVM and geometric patterns were determined by 2D echocardiography. Statistical analyses involved bivariate tests (Mann-Whitney, chi2, Spearman's correlation coefficients, ANOVA and receiver-operating-characteristic (ROC) curve analyses) and multivariate tests (multiple linear and logistic regressions). QT dispersion measurements showed significant correlations with echocardiographic LVM (r=0.26-0.27). ROC curves demonstrated a poor isolated predictive performance of all QT parameters for detection of LVH (areas under curve: 0.58-0.59), comparable to that of electrocardiographic voltage criteria. Only patients with concentric hypertrophy had significantly increased QT dispersion (QTd) when compared to those with normal geometries (64.24+/-21.09 vs 53.20+/-15.35, P<0.05). In multivariate analyses, both electrocardiographic and echocardiographic LVH were independent predictors of increased QTd, as well as only QTd and gender were determinants of LVM. In conclusion, increased QT interval dispersion is associated with LVM and concentric hypertrophy geometric pattern in diabetic hypertensive patients, although in isolation neither QTd nor any QT parameter presents enough predictive performance to be recommended as screening procedures for detection of LVH.     

Hypertensive myocardial hypertrophy and rhythm disorders: 2 possible origins

It has been suggested that complex ventricular arrhythmias commonly occur in hypertensive patients with left ventricular hypertrophy. We have previously demonstrated that coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) resulted in a significantly increased incidence and duration of ventricular fibrillation in SHR compared with WKY. The object of the present study was to characterize the structural and electrophysiological abnormalities in hypertrophied hearts, associated with the occurrence of arrhythmias. We used a double tissue bath in which a ventricular strip was exposed simultaneously to normal and to altered conditions (low pH, hypoxia and high potassium). Electrical activity recorded using standard micro-electrode techniques showed the occurrence of arrhythmias in all preparations and the development of major alterations in conduction (a conduction block appeared at 11 +/- 1 mn in SHR vs 16 +/- 1 mn in WKY, p less than 0.05), and maximal upstroke velocity (Vmax values before and 3 mn after the beginning of ischemia were 229 +/- 12 to 46 +/- 7 v/s for the SHR and 227 +/- 10 to 106 +/- 12 v/s for the WKY; p less than 0.001). These changes were associated in hypertrophied ventricles with a marked sub-endocardial collagen fibrosis as estimated by the use of automated image analysis (subendocardial collagen density = 4.39 +/- 0.34 p. 100 in SHR vs 1.66 +/- 0.15 p. 100 in WKY; p less than 0.001). Action potential duration measured using conventional glass micro-electrodes in a single chamber tissue bath revealed a highly significant difference (p less than 0.001) in APD 90 p. 100 of papillary muscles between SHR (114.7 +/- 2.8 ms) and WKY (76.9 +/- 1.7 ms). The addition of tetra-ethylammonium to block potassium channels induced triggered activity arising from early afterdepolarizations only in muscles hypertrophied SHR hearts.(ABSTRACT TRUNCATED AT 250 WORDS)     

ECG alterations with progressive left ventricular hypertrophy in spontaneous hypertension.

Although many ECG criteria exist for diagnosis of left ventricular hypertrophy (LVH) in hypertensive man, little is known of which specific ECG changes accompany progression of LVH with duration of hypertension. The spontaneously hypertensive rat (SHR) provides the best animal model thus far developed for studying this process since these animals demonstrate a progressive increase in left ventricular/body weight ratio with age. Electrocardiograms were performed under light ether anesthesia in four age groups of SHR and two normotensive Wistar strains (NR and WKY). Analysis of variance for two factors (rat strain and age) revealed progressively increased QRS and P-wave duration and delay in intrinsicoid deflection in SHR (p less than 0.001). Bipeak P-wave notching was also noted in SHR similar to left atrial abnormality in hypertensive man. Thus, specific ECG indices can be identified in association with the known progressive increase in left ventricular mass in SHR and should provide a better means to understand evolving ECG changes in LVH.     

Relation Between QRS Amplitude and Left Ventricular Mass in the Initial Stage of Exercise-Induced Left Ventricular Hypertrophy in Rats

The aim of the study was to analyze the relationship between QRS amplitude and left ventricular mass (LVM) in early stages of two different experimental models of left ventricular hypertrophy (LVH) in rats: in exercise-induced hypertrophy and pathological hypertrophy due to genetically conditioned pressure overload. Three groups of experimental animals were studied: healthy control Wistar-Kyoto rats (WKYs), spontaneously hypertensive rats (SHRs), and WKY rats exposed to training by intermittent swimming (SWIM). Orthogonal electrocardiograms were recorded in each group at the age of 12 and 20 weeks, and the maximum spatial QRS vector (QRSmax) was calculated. Then the animals were sacrificed and LVM was measured. The specific potential of myocardium (SP) was calculated as a ratio of QRS_max to LVM. The QRSmax values did not follow the changes in LVM. At the end of the follow-up period, the highest values of QRSmax were recorded in the control WKY rats (0.80 ± 0.05 mV). The QRSmax values in both groups with experimental LVH were significantly lower as compared with control animals (SHR 0.44 ± 0.02 mV, p < 0.001; SWIM 0.53 ± 0.04 mV, p < 0.001). Similarly, the SP values were significantly lower in both groups with experimental LVH as compared with control animals (SHR 0.42 ± 0.02 mV/g, p < 0.001; SWIM 0.55 ± 0.05 mV/g, p < 0.001). A decrease in QRSmax and SP was observed in both models of experimental LVH. We attributed these findings to the changes in electrogenetic properties of myocardium in the early stage of developing LVH. In other words, it is changes of nonspatial determinants that influence the resultant QRS voltage in terms of the solid angle theory.     

QTc dispersion and complex ventricular arrhythmias in untreated newly presenting hypertensive patients.

Increased dispersion of ventricular repolarisation (increased QT dispersion) is believed to predispose to arrhythmias associated with sudden death in certain cardiac diseases. Hypertension is also associated with increased risk of sudden death, particularly in those with left ventricular hypertrophy (LVH). Therefore, the first aim of this study is to look into the possible pathogenic role of QT dispersion on the ventricular arrhythmias occurring in a group of never-treated hypertensive patients. The second aim is to look at other possible determinants of QT dispersion (ie, level of blood pressure, hypokalaemia, electrocardiographic LVH and presence or absence of strain pattern) in hypertensive patients, and their relevance to complex ventricular arrhythmias. QTc (corrected QT) was measured in 70 newly presenting (never-treated) hypertensive patients (47 male, 23 female, mean age 51.9 +/- 12.5 years) from a standard 12-lead surface electrocardiogram (ECG). Blood pressure measurements and 24-h ECG holter recordings were performed in all patients. Serum potassium level was measured in 51 of the patients. Ventricular arrhythmias were classified using a modified Lown's scoring system. Maximum QTc, minimum QTc and QTc dispersion for all patients were 442 +/- 30.3 ms, 380 +/- 26.7 ms and 61.5 +/- 21.6 ms respectively. High grade ventricular arrhythmias (Lown's score >/=3) were found in 43% of the patients. The QTc dispersion was strongly correlated with the Lown's classification of arrhythmia and the age of the patients. Patients with more severe ectopy (Lown's score >/=3) were significantly older (57.4 +/- 10.3 years) compared to those with score /=3 Lown's score compared to 39% in the group with LVH but without strain. In the presence of relative hypokalaemia, hypertensive patients with LVH showed more QTc dispersion (85.7 +/- 15.5 ms) and a greater tendency for complex ventricular arrhythmias (100% grade >/=3 Lown's score) compared to those with LVH and normal serum potassium levels (64.1 +/- 22.6 ms and 35%, QTc dispersion and Lown's score >/=3, respectively P = 0. 05). The level of blood pressure had no effect on either the QTc dispersion or the prevalence of complex ventricular arrhythmias. Prevalence of complex ventricular arrhythmias in hypertensive patients is strongly correlated with QTc dispersion and age. When hypertensive patients with LVH have low potassium levels the risk of developing complex ventricular arrhythmias is significantly increased.     

Depressed inotropic response to beta-adrenoceptor agonists in the presence of advanced cardiac hypertrophy in hearts from rats with induced aortic stenosis and from spontaneously hypertensive rats.

OBJECTIVE: To study the inotropic response to beta-adrenoceptor stimulation in isolated hypertrophied hearts from hypertensive rats. DESIGN AND METHODS: Cardiac hypertrophy was induced in Wistar rats by stenosing the abdominal aorta. Functional responses to isoprenaline, dobutamine, terbutaline and salbutamol were measured in paced (5 Hz), aortically stenosed hearts (18-20 and 32-34 weeks of age) and compared with those of sham-operated spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. RESULTS: Following aortic stenosis, which was accompanied by less hypertension than that sustained by SHR, the Wistar rat hearts showed more pronounced cardiac hypertrophy. An initially equal inotropic response to the beta-adrenoceptor agonists (18-20 weeks) was reduced to 45% at 32-34 weeks in SHR but not in WKY rat hearts. The response to beta-adrenoceptor stimulation in the hypertrophied Wistar rat hearts was reduced at 18-20 weeks to 30% and at 32-34 weeks to 10% of controls, respectively. The response by all hypertrophied hearts to forskolin and N,2'-O-dibutyryladenosine 3':5' monophosphate was also diminished. CONCLUSIONS: The impaired contractile response to beta-adrenoceptor agonism is more clearly related to cardiac hypertrophy than to hypertension.     

Left ventricular mass and hypertrophy assessment by means of the QRS complex voltage-independent measurements

ECG QRS-complex voltage-based criteria are relatively insensitive for detection of increased left ventricular mass (LVM). We developed and evaluate a new ECG index for LV hypertrophy (LVH) detection regardless of the QRS voltage. METHODS: Study population consisted of 106 patients (73 m, 33 f, aged 60 +/- 10 years) with established coronary artery disease (CAD). All patients had LVM assessed echocardiographically and indexed to BSA (LVMI(ECHO)). LVH was diagnosed if LVMI(ECHO) >117 g/m2 in men and >104 g/m2 in women. LV geometry was also determined. Analysed ECG variables, obtained from 12 leads recorded simultaneously, were: the QRS complex duration (QRSd, ms), the average 12-lead time to maximal deflection (TMD, ms), the average 12-lead QRS complex voltage (12QRSV, mV), the average product of 12 lead QRS voltage and duration (12QRSVd, mV ms), Sokolow-Lyon voltage and V-d product (SLV, SLVd), Cornell voltage and V-d product (CV, CVd). A newly developed index, LVM(ECG), was calculated, as LVM(ECG) = [(2 x TMD+QRSd/pi)3-(QRSd/pi)3]*0.0001 (ms3), and indexed to BSA (LVMI(ECG), ms3/m2). RESULTS: Means of the QRS voltage-related parameters were similar in patients with LVH and normal LVM. Greater differences existed between both groups when the QRS voltage-duration products were compared. LVMI(ECG) was most powerful in distinguishing between groups (130 +/- 33 LVH vs 91 +/- 21 normal LVM, p < 0.001). LVMI(ECG) correlated with LVMI(ECHO) better (r = 0.77, p < 0.001) than other indices (r coefficients between 0.24 for SLV and 0.49 for CVd). None of the examined indices allowed for distinction between eccentric and concentric LVH. The new index showed better statistical performance (area under ROC = 0.861) compared to the other indices (AUC range 0.545-0.697, p<0.001 vs LVMI(ECG)). At the specificity level of 92%, the value of LVMI(ECG) > 120 ms3/m2 had the sensitivity of 64% for detection of increased LVM. The sensitivities of the other parameters were significantly lower (sensitivity range 18-42%). Relative intra- and interobserver errors and correlation coefficients for LVMI(ECG) calculation were 0.4% and 1.6% and r = 0.94 and 0.98, respectively. CONCLUSIONS: In patients with CAD an assessment of LV mass and detection of hypertrophy using the QRS complex time-dependent index is feasible. The new index correlated well with echocardiographically-determined LVM and showed better statistical performance than indices which include QRS-voltage measurements. The results are promising and warrant further studies to evaluate the utility of the new index as a risk predictor.     

Differential structural responses of small resistance vessels to antihypertensive therapy

Regression of left ventricular hypertrophy after control of blood pressure has been documented with some antihypertensive agents but not with others. To determine whether similar differences in regression of wall thickening also occur in resistance vessels during treatment, matched groups of spontaneously hypertensive rats (SHR) were treated for 12 weeks with either hydralazine (H) or captopril and hydrochlorothiazide (C-D) and they were compared with untreated SHR and Wistar-Kyoto rats (WKY). Perfusion pressure was then determined in the hindlimbs of pithed rats under conditions of constant blood flow (4.0 ml/min) and maximal vasodilation (hemodilution to 22% hematocrit combined with continuous nitroprusside and papaverine infusion). This perfusion pressure, which has been validated as an index of thickening (hypertrophy) of resistance vessels walls, averaged 26.8 +/- 0.4(SE) mm Hg in untreated WKY (n = 12) and 37.6 +/- 0.4 mm Hg in untreated SHR (n = 11) (p less than .01). Treatment with H or C-D controlled blood pressure equally in SHR, but the two drugs had significantly different effects on both left ventricular hypertrophy and resistance vessels. Perfusion pressure was reduced from 37.6 +/- 0.4 mm Hg to 34.0 +/- 0.5 mm Hg (p less than .01) with C-D but only to 36.5 +/- 0.5 mm Hg with H (NS). Left ventricular weight was significantly reduced by C-D (2.02 +/- 0.02 vs 2.63 +/- 0.05 mg/g, p less than .01) but only to 2.44 +/- 0.05 mg/g by H.(ABSTRACT TRUNCATED AT 250 WORDS)     

QT dispersion intervals in hypertensives with left ventricular hypertrophy

Left ventricular hypertrophy is an important risk factor of cardiovascular complications during the course of hypertension. Increased QT dispersion is associated with sudden cardiac death in congestive heart failure and in other cardiovascular diseases. Our aim was to compare QT dispersion from routine ECG in hypertensive patients with and without left ventricular hypertrophy defined by echocardiography. Authors examined 71 hypertensives treated in our medical department. Left ventricular hypertrophy was defined by echocardiography (Penn convention) as left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women. QT dispersion was defined from routine ECG (QTmax - QTmin). Presence of LVH was found in 26 patients (mean age 59.3 years), absence of LVH in 45 patients (mean age 57.8 years). Hypertensives with secondary hypertension, hypertrophic cardiomyopathy, sings of ischemia in ECG, arrhythmias, myocardial infarction, heart failure, diabetes mellitus and patients treated by antiarrhythmic drugs of the Ic and III groups were excluded. Both groups of hypertensives were matched by demographic parameters, and by the presence of hypertension, obesity, hyperlipidemia and smoking habites. There were statistically significant longer QT dispersion and QTc dispersion (59.0 +/- 20.1 ms, 64.0 +/- 23.7 ms) in LVH-positive patients than in LVH-negative once (43.2 +/- 9.5 ms, 48.4 +/- 11.1 ms). Left ventricular hypertrophy in patients with hypertension brings usually a complicated course of the disease. Authors recommend to look after left ventricular hypertrophy presence in hypertensives as it carries much more complicated course of the disease. Measurment of QT dispersion adds farther stratificational information to these patients.     

Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats

The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial and coronary vascular function and structure. Twelve-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with and without 12 weeks of vasodilator antihypertensive treatment (hydralazine) were studied using an isolated perfused rat heart model. Hydralazine treatment normalized blood pressure in SHR but did not cause regression of cardiac hypertrophy (heart weight to body weight ratio of SHR + hydralazine 4.33 +/- 0.098 vs. SHR 4.66 +/- 0.091; WKY 3.21 +/- 0.092 and WKY + hydralazine 3.38 +/- 0.152; mean +/- SEM). Coronary flow reserve, elicited by adenosine vasodilation in the perfused heart, was decreased in SHR (29%) compared with WKY (105%) and WKY + hydralazine (100%) and was significantly improved in SHR + hydralazine (75%). Morphometric evaluation of perfusion-fixed coronary arteries and arterioles (30-400 microns diameter) demonstrated a significant increase in the slope of the regression line comparing the square root of medial area versus outer diameter in SHR (0.444) compared with WKY (0.335) and WKY + hydralazine (0.336, p less than 0.05). Blood vessels from SHR + hydralazine were not different from control (0.338). Cardiac oxygen consumption was decreased in SHR (10.9 +/- 0.74 mumols oxygen/min/g/60 mm Hg left ventricular pressure) compared with WKY (22.4 +/- 1.47) and WKY + hydralazine (23.4 +/- 1.90; p less than 0.01), while SHR + hydralazine was intermediate (16.0 +/- 1.60). These studies suggest that significant alterations in myocardial and coronary vascular structure and function occur in hypertension-induced cardiac hypertrophy. The coronary vasculature is responsive to blood pressure, independent of cardiac hypertrophy, although moderate coronary deficits do remain after chronic antihypertensive therapy.     

Alterations in sarcoplasmic reticulum and angiotensin II receptor type 1 gene expression in spontaneously hypertensive rat hearts

Left ventricular hypertrophy (LVH) is an adaptive change in response to hypertensive pressure overload. Some evidence indicates that the decrease in sarcoplasmic reticulum (SR) Ca2+-ATPase mRNA expression, which may contribute to a diastolic dysfunction of the heart, occurs in the experimental pressure overload model. Also, recent studies have demonstrated that angiotensin II (Ang II) and angiotensin II receptor type 1 (AT1) play important roles in LVH. The purpose of this study was to investigate the function of the SR and the role of AT1 in genetic hypertension in spontaneously hypertensive rats (SHR) at ages 10 and 18 weeks. In SHR, cardiac hypertrophy has already developed at 10 weeks of age. SR Ca2+-ATPase activity and mRNA expression were significantly lower in SHR than in Wistar-Kyoto rats (WKY). Plasma renin activity in SHR was unchanged compared with WKY, whereas the Ang II concentration in SHR was significantly higher than that in WKY. AT1 mRNA expression in SHR was similar to that in WKY. These results suggest that in the early stage of hypertension in SHR Ang II may stimulate hypertrophy in the cardiomyocytes through the AT1, which is not downregulated by a high concentration of Ang II.     

Arterial hypertension,left ventricular geometry and QT dispersion in a middle-aged Estonian female population

The aim of the present study was to determine the prevalence of Left ventricular hypertrophy (LVH) and different left ventricular (LV) geometric patterns in the middle-aged women population of Tallinn, to assess the relationship between LV geometry, age, blood pressure and LV repolarization duration and inhomogeneity. A random sample of the population, 482 women aged 35-59, was examined in the framework of a cardiovascular risk factors survey for the WHO/CINDI programme years 1999-2000. Patients with valvular pathology, primary cardiomyopathy, atrial fibrillation, bundle branch blocks and flat T wave on electrocardiography (ECG) were excluded; 398 (82.2%) of the participants underwent echocardiography (Echo) and standard 12-lead ECG at rest and were included in the study. LVH was defined if left ventricular mass (LVM), LVM/height and LVM/BSA were >198 g, >121 g/m and > 120 g/m2, respectively. Arterial hypertension was determined in 23.1% of the women. The prevalence of arterial hypertension was three times higher in those aged 50-59 than in those aged 40-49 (37.4% vs 13.2%; p < 0.05). Different geometric patterns were found as follows: concentric hypertrophy in 9.1%; eccentric hypertrophy 33.9%; concentric remodelling 9.5% and normal geometry 47.5% of the participants. Concentric hypertrophy was found exclusively in hypertensive women and increased with age. No age-related eccentric hypertrophy and concentric remodelling differences were found, either in the normotensive or in the hypertensive group. Prolonged QT dispersion--a marker of increased myocardial electrical instability, was associated with LVH and arterial hypertension and was related mostly to concentric hypertrophy in hypertensives.     

Reflex cardiovascular responses to somatic stimulation in spontaneously hypertensive rats

OBJECTIVES: This study aimed to test whether the cardiovascular responses to somatic stimulation in spontaneously hypertensive rats (SHR) were enhanced compared with those in normotensive Wistar-Kyoto (WKY) rats, and to examine any role of the impaired baroreflex function in the hypertensive rats. METHODS: Experiments were done in anaesthetized SHR (n = 34) and WKY (n = 31). Baroreceptor reflexes were assessed by continuous infusion of incremental doses (5-30 microg/kg per min) of phenylephrine over a 3 min infusion period. Cardiovascular responses to sciatic nerve stimulation (5 s trains, 1 ms pulse duration, 400 microA intensity) were studied before and after baroreceptor deactivation. The latter was achieved either by carotid occlusion and cutting the vagi and aortic nerves (SHR, n = 28 and WKY rats, n = 27), or by complete baroreceptor denervation (SHR, n = 6 and WKY rats, n = 4). RESULTS: We confirmed that baroreceptor sensitivity was significantly lower in SHR (0.40 +/- 0.05 ms/mmHg) than in WKY rats (0.90 +/- 0.04 ms/mmHg). Sciatic nerve stimulation elicited significantly greater increases in mean arterial pressure (MAP) and in heart rate in SHR than in WKY rats (+32.5 +/- 1.9 mmHg versus +20.2 +/- 1.1 mmHg and +13.5 +/- 1.5 bpm versus +8.0 +/- 1.1 bpm, respectively). Following baroreceptor deactivation, the responses to the same sciatic nerve stimulation of MAP and heart rate in SHR (+38.5 +/- 2.4 mmHg and +15.5 +/- 1.5 bpm) were still significantly greater than those in WKY rats (+29.5 +/- 1.3 mmHg and +11.6 +/- 1.2 bpm). CONCLUSIONS: These results show that cardiovascular responses to sciatic nerve stimulation are increased in SHR compared to WKY rats, and that this increased reactivity to somatic stimuli in hypertensive rats does not depend upon the impairment in baroreflex function demonstrated in this strain.     

Genetic, neurohumoral, and hemodynamic influences on spontaneously hypertensive rat heart development in oculo

To distinguish among genetic, neurohumoral, and hemodynamic explanations for structural and functional differences in the hearts of young spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) control rats, embryonic SHR and WKY rat heart tissue was cultured in the anterior eye chamber of adult SHR and WKY rats. In study 1, atria from E-12 WKY rat embryos grafted into anterior eye chambers of either SHR or WKY host rats achieved a larger size than did SHR grafts by 8 weeks in oculo (2.98 +/- 0.75 and 2.55 +/- 0.32 mm2 vs. 1.80 +/- 0.20 and 2.04 +/- 0.44 mm2). Beating rates did not differ between SHR and WKY rat atria implanted into SHR or WKY host rats. In study 2, ventricles from E-13 embryonic SHR and WKY rat hearts grew to similar size and weight when implanted into SHR or WKY host rats (e.g., SHR hearts, 1.81 +/- 0.32 vs. 1.74 +/- 0.33 mm2; WKY rat hearts, 1.75 +/- 0.29 vs. 2.29 +/- 0.32 mm2). Ventricle grafts from SHR embryos into SHR host rats beat more rapidly (165 +/- 19 beats/min) during weekly measurements than either WKY rat ventricles (92 +/- 9 beats/min in SHR hosts and 99 +/- 9 beats/min in WKY host rats) or SHR ventricles grafted into WKY host rats (109 +/- 7 beats/min, p less than 0.001). In study 3, atria from E-13 SHR and WKY rat embryos were grafted into sympathectomized and intact eye chambers of SHR or WKY host rats. Sympathectomy of the eye chamber compromised growth of grafts into WKY host rats (1.54 +/- 0.24 vs. 0.90 +/- 0.14 mm2) but not SHR hosts (1.54 +/- 0.25 vs. 1.73 +/- 0.24 mm2). Grafts into sympathectomized eye chambers of WKY host rats beat more slowly than grafts into eye chambers with sympathetic innervation intact (282 +/- 14 vs. 202 +/- 14 beats/min); sympathectomy did not alter beating rate of grafts in SHR hosts (266 +/- 14 vs. 255 +/- 18 beats/min). These results suggest that the growth and beating rate of SHR atrial grafts may be less sensitive to sympathetic innervation than WKY rat atrial grafts. In these studies, SHR grafts did not grow larger than WKY heart grafts and did not show an increased intrinsic beating rate, suggesting that the cardiac hypertrophy and increased intrinsic beating rate observed in intact SHR are unlikely to result from direct genetic programming.     

Relation of QT interval and QT dispersion to echocardiographic left ventricular hypertrophy and geometric pattern in hypertensive patients. The LIFE study. The Losartan Intervention For Endpoint Reduction

OBJECTIVE: In hypertensive patients, left ventricular hypertrophy (LVH) predicts increased mortality, in part due to an increased incidence of sudden death. Repolarization-related arrhythmogenesis may be an important mechanism of sudden death in hypertensive patients with LVH. Increased QT interval and QT dispersion are electrocardiographic (ECG) measures of ventricular repolarization, and also risk markers for ventricular tachyarrhythmias. We assessed the relation of QT intervals and QT dispersion to echocardiographically determined left ventricular (LV) mass and geometry in a large population of hypertensive patients with ECG evidence of LVH. METHODS: QT intervals and QT dispersion were determined from baseline 12-lead ECGs in 577 (57% male; mean age 65 +/- 7 years) participants in the LIFE study. LV mass index (LVMI) and geometric pattern were determined by echocardiography and QT interval duration and QT dispersion were assessed in relation to gender-specific LVMI quartiles. RESULTS: In both genders, increasing LVMI was associated with longer rate-adjusted QT intervals. QT dispersion measures showed a weaker association with LVMI quartiles. Both concentric and eccentric LVH were associated with increased QT interval duration and QT dispersion. These relations remained significant after controlling for relevant clinical variables. CONCLUSIONS: In hypertensive patients with ECG evidence of LVH, increased LVMI and LVH are associated with a prolonged QT interval and increased QT dispersion. These findings suggest that an increased vulnerability to repolarization-related ventricular arrhythmias might in part explain the increased risk of sudden death in hypertensive patients with increased LV mass.