Spontaneously occurring hypertrophic cardiomyopathy in the rat. II. Distribution of, and correlations between, various cardiac abnormalities in the WKY/NCrj and its related strains

We performed gross-anatomic and histologic examinations quantitatively on 18 male and 30 female WKY/NCrj rats, and their 299 first generation off spring. The results were analyzed in comparison with those obtained from 3 other strains of rats. The offspring of the WKY rats showed various cardiac abnormalities quite similar to those in their parents. The cardiac abnormalities in the offspring of the WKY rats were: increased heart weight (in about 10%), left or right atrial hypertrophy (50%), disproportionate septal thickening (50%), small left ventricular cavity (40%), right ventricular hypertrophy (40%), abnormal fiber arrangement greater than 5% in either of the 3 ventricular walls (90%), myocardial fibrosis (70%), and abnormal location of arteries in the ventricular septum (30%). ECG findings of the WHY-F rats such as high QRS complexes and high T waves and axis deviation showed a high sensitivity and specificity in the diagnosis of marked cardiac hypertrophy. Another conspicuous histologic finding observed in the WKY hearts was that the continuity of the latitudinal fiber bundle of the ventricular septum with that of the left ventricular free wall, an important functioning unit for pressure generation in the left ventricle, was markedly disturbed in the area of junction between the 2 walls; the smaller the continuity, the greater the cardiac hypertrophy; the disadvantage of the discontinuity for the pressure generation may be related to the development of cardiac hypertrophy. Also examined were two strains of Wistar rats with the same origin as the WKY/NCrj. These rats also had gross-anatomic and histologic abnormalities of the heart quite similar to those in the 2 generations of WKY/NCrj rats, suggesting that a common factor related to the development of the abnormalities, probably a genetic predisposition, has been transmitted in these 3 strains.     

Myocardial function during chronic food restriction in isolated hypertrophied cardiac muscle

BACKGROUND: The effect of food restriction (FR) on myocardial performance has been studied in normal hearts. Few experiments analyzed the effects of undernutrition on hearts subjected to cardiac overload. The aim of this study was to determine whether chronic FR promotes more significant changes in hypertrophied hearts than in normal hearts. METHODS: Myocardial performance was studied in isolated left ventricular papillary muscle from young male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The animals subjected to FR were fed 50% of the amount of food consumed by control groups for 60 days. Isolated muscles were studied while contracting isometrically and isotonically. RESULTS: FR decreased the body weight and the left ventricular weight in both groups. FR increased the left ventricular weight-to-body weight ratio in the WKY rats and tended to decrease this ratio in SHR (P = 0.055). The arterial systolic pressure was greater in SHR than in WKY groups and did not change with FR. In the animals with normal diet, myocardial performance was better in SHR than in WKY. FR increased time to tension to fall from peak to 50% of peak tension and time to peak tension in the WKY rats and time to peak tension in the SHR. CONCLUSIONS: FR for 60 days has a trend to attenuate the development of cardiac hypertrophy and does not promote more mechanical functional changes in the hypertrophied myocardium than in the normal cardiac muscle.     

Echo/Doppler diagnosis of tetralogy of Fallot, ventricular septal defect, pulmonary valve dysplasia, and hypertrophic cardiomyopathy in WKY/NCrj rats.

We examined the hearts of 97 WKY/NCrj rats, a strain which spontaneously develops congenital cardiac malformations, by means of echocardiography with a pulsed Doppler ultrasound, and compared the results with those of 20 WKY/Ta rats and 30 normal Wistar rats. Dissection of these WKY/NCrj rats revealed a ventricular septal defect (VSD) in 20 and pulmonary valve dysplasia (PVD) in 41, both VSD and PVD occurring together in 18. VSD was readily diagnosed in vivo by the jet flow signal derived from the left-to-right shunt near the membranous portion, with a sensitivity of 85% and a specificity of 99%. Ultrasound imaging revealed overriding of the aorta and right ventricular (RV) hypertrophy in 18 of the 20 rats with VSD. Of the 20 rats with VSD, 10 had a systolic high-velocity jet across the RV outflow indicating an infundibular stenosis. PVD was commonly accompanied by a pulmonary regurgitation signal, with severe cases showing intensified echo and low excursion of the cusps. The regurgitation signal showed a good diagnostic value for PVD with a sensitivity of 82% and a specificity of 85%. In the remaining 54 WKY/NCrj rats without VSD or PVD, the ratio of mean left ventricular (LV) wall thickness to cavity dimension, the fractional shortening of the LV dimension, and the septal to LV free wall thickness ratio were all abnormally high, and the motion of the ventricular septum was reduced in most of the cases compared with that of the other two strains. All these features resemble the hypertrophic cardiomyopathy seen in humans, which further promises that the rats should be a useful model for the controversial disease.     

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.     

Heterogeneous distribution of fatty acid-binding protein in the hearts of Wistar Kyoto and spontaneously hypertensive rats.

In the present study we investigated the concentrations of cardiac cytoplasmic fatty acid-binding protein (H-FABPc) in various regions of the left and right ventricles of both Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). To this end, the ventricles of six WKY and six SHR hearts were cut in three slices, which were further dissected in one right ventricular piece and ten left ventricular pieces (five inner layer and five outer layer pieces). After homogenisation. H-FABPc was assessed using an Enzyme Linked Immuno Sorbent Assay (ELISA) of the sandwich type. It was found that, when expressed per gram wet tissue, the overall concentration of H-FABPc tended to be lower in SHR than in WKY hearts (874 +/- 53 micrograms/g and 955 +/- 51 micrograms/g, respectively; 0.1 less than P less than 0.2, means +/- S.E.M. for n = 6 animals in each group). However, due to a 30-35% higher ventricular heart mass in SHR than in WKY, the total H-FABPc content per heart turned out to be about 20% higher in SHR than in WKY rats. No concentration differences could be detected between right and left ventricles in WKY and SHR but a marked difference between the outer layer and the inner layer of the left ventricular wall was monitored in both groups. In general, the concentration in the outer layer was 5-15% higher than in the corresponding inner layer. These differences reached the level of significance (P less than 0.05) in regions close to the basis of the heart.     

Increase in G(i alpha) protein accompanies progression of post-infarction remodeling in hypertensive cardiomyopathy

Hypertensive cardiac hypertrophy and myocardial infarction (MI) are clinically relevant risk factors for heart failure. There is no specific information addressing signaling alterations in the sequence of hypertrophy and post-MI remodeling. To investigate alterations in beta-adrenergic receptor G-protein signaling in ventricular remodeling with pre-existing hypertrophy, MI was induced by coronary artery ligation in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Ten weeks after the induction of MI, the progression of left ventricular dysfunction and increases in plasma atrial natriuretic peptide (ANP) and cardiac ANP mRNA were more pronounced in SHR than WKY. In addition, the impaired contractile response to beta-adrenergic stimulation was observed in the noninfarcted papillary muscle isolated from SHR. Immunochemical G(s alpha) protein and beta-adrenoceptor density were not significantly altered by MI in both strains. However, immunochemical G(i alpha) was increased (1.5-fold) in the noninfarcted left ventricle of the SHR in which infarction had been induced when compared with that in SHR that underwent sham operation. This increase was observed especially in rats with a high plasma ANP level. Furthermore, there was a positive correlation between G(i alpha) and the extent of post-MI remodeling in WKY. A similar correlation between G(i alpha) and the extent of hypertensive hypertrophy was observed in SHR. In conclusion, the vulnerability of hypertrophied hearts to ischemic damage is greater than that of normotensive hearts. An increase in G(i alpha) could be one mechanism involved in the transition from cardiac hypertrophy to cardiac failure when chronic pressure overload and loss of contractile mass from ischemic heart disease coexist.     

Cardiac Mechanical Dysfunction Induced by Ischemia‐reperfusion in Perfused Heart Isolated from Stroke‐prone Spontaneously Hypertensive Rats

We investigated the difference in mechanical function after ischemia and reperfusion between Wistar‐Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) or stroke‐prone SHR (SHRSP) using the isolated working heart model, in order to examine postischemic mechanical dysfunction in the severely hypertrophied heart. Systolic blood pressure of SHRSP was higher than that of SHR and WKY, and the left ventricular wall in SHRSP was thicker than in WKY. Mechanical dysfunction of the heart during reperfusion following ischemia (11 min) in SHRSP was severer than that in SHR and WKY, and recovery of the cardiac energy charge potential (ECP) level in SHRSP was lower than that in SHR and WKY. Twenty‐five, 12 and 11 min‐ischemia in WKY, SHR and SHRSP, respectively, caused a similar level of cardiac mechanical damage. Also, the ECP levels were almost equivalent among them at the end of 20 min reperfusion following each time of ischemia. Under each ischemic condition, a Ca^{2 +}‐channel blocker, diltiazem, and an adenosine potentiator, dilazep, produced a beneficial effect on the post‐ischemic dysfunction in SHR and WKY. However, neither cardioprotective drug led to recovery of the mechanical dysfunction of the heart during reperfusion following ischemia in SHRSP. Thus, the severely hypertrophied heart such as that in SHRSP was more susceptible to cardiac reperfusion dysfunction, than the moderately hypertrophied heart such as that in SHR. These results suggest that the cardioprotective effects of drugs may be deteriorated in severe hypertrophied hearts.     

The beta-adrenergic receptor/adenylate cyclase system in the cardiac ventricles of a hypertrophic cardiomyopathy rat model.

The WKY/NCrj rat strain is considered to be a good animal model for hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the beta-adrenergic receptor/adenylate cyclase system in the cardiac ventricles of these rats. beta-adrenergic receptor density (Bmax) in the right ventricle (RV) was higher in WKY/NCrj than in Wistar rats. In contrast, Bmax in the interventricular septum (IVS) was lower in WKY/NCrj than in Wistar rats. Isoproterenol-stimulated adenylate cyclase activity in cardiac ventricular slices showed that changes corresponded to the changes of Bmax in every type of studied cardiac ventricle. The intracellular adenylate cyclase pathway (GTP gamma S-, NaF- and forskolin-stimulated adenylate cyclase activity in cardiac ventricular particulate fraction) did not differ between WKY/NCrj and Wistar rats in any region of the cardiac ventricles. Catecholamine levels tended to be low in the RV and to increase in the IVS of WKY/NCrj rats. Our results suggest that the activity of the beta-adrenergic receptor/adenylate cyclase system varies in different cardiac ventricles of the WKY/NCrj rat model for HCM.     

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)     

Volume overload influence on hypertrophied myocardium function

The aim of this study was to demonstrate that hypertrophied cardiac muscle is more sensitive to volume-overload than normal cardiac muscle. We assessed the mechanical function of isolated left ventricular papillary muscle from male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to volume overload caused by aortocaval fistula (ACF) for 30 days. Muscles were perfused with Krebs-Henseleit solution at 28 degrees C and studied isometrically at a stimulation rate of 0.2 Hz. The ACF increased the right and left ventricular weight-to-body weight ratio in WKY rats; it also promoted right ventricular hypertrophy and further increased the basal hypertrophy in the left ventricle from SHR. The arterial systolic pressure was greater in SHR than in WKY rats, and decreased with ACF in both groups. Developed tension (DT) and maximum rate of DT (+dT/dt) were greater in the SHR-control than in the WKY-control (P < 0.05); the time from peak tension to 50% relaxation (RT 1/2) was similar in these animals. ACF did not change any parameters in the SHR group and increased the resting tension in the WKY group. However, the significant difference observed between myocardial contraction performance in WKY-controls and SHR-controls disappeared when the SHR-ACF and WKY-controls were compared. Furthermore, RT 1/2 increased significantly in the SHR-ACF in relation to the WKY-controls. In conclusion, the data lead us to infer that volume-overload for 30 days promotes more mechanical functional changes in hypertrophied muscle than in normal cardiac muscle.     

Effects of chronic hypertension and left ventricular hypertrophy on the extent of infarct expansion in rats

Left ventricular hypertrophy is an adaptive response to long standing hypertension. However, the influence of left ventricular hypertrophy with hypertension on extent of infarct expansion has not been studied. We compared the effects of left ventricular hypertrophy with hypertension on infarct expansion in spontaneously hypertensive rats (SHR, n = 76), Wistar-Kyoto rats (WKY; n = 46) and spontaneously hypertensive rats treated with delapril, an angiotensin converting enzyme (ACE) inhibitor (SHRD; n = 39). The survival rates at 7 days after myocardial infarction were 41%, 24%, and 46% for WKY, SHR, and SHRD. The survival rate of SHR was significantly lower than those of both SHRD and WKY (P < .05). In the surviving rats (18 SHR, 19 WKY, 18 SHRD), both left ventricular cavity area (LCVA) and the infarct segment length per the noninfarct segment length (FW/IVS), measured as indices of left ventricular dilation, were significantly less in SHR and SHRD than in WKY, and the thickness of the left ventricular free wall (Wth), used as an index of left ventricular thinning, was significantly higher in both SHR and SHRD than in WKY (P < .01). However, there was no significant difference in FW/IVS, LCVA, and Wth between SHR and SHRD. Hemodynamic findings 1 week after coronary occlusion demonstrated that all rats were in heart failure, and there were no significant differences in hemodynamics among the three groups. In conclusion, our findings showed that hypertrophy with hypertension reduced infarct expansion, but that reduction of blood pressure by ACE inhibitor did not reduce infarct expansion more than hypertrophy did. However, this finding suggests that an ACE inhibitor may improve the rate of survival of patients with left ventricular hypertrophy with hypertension.     

Cardiac mechanical dysfunction induced by ischemia-reperfusion in perfused heart isolated from stroke-prone spontaneously hypertensive rats

We investigated the difference in mechanical function after ischemia and reperfusion between Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) or stroke-prone SHR (SHRSP) using the isolated working heart model, in order to examine postischemic mechanical dysfunction in the severely hypertrophied heart. Systolic blood pressure of SHRSP was higher than that of SHR and WKY, and the left ventricular wall in SHRSP was thicker than in WKY. Mechanical dysfunction of the heart during reperfusion following ischemia (11 min) in SHRSP was severer than that in SHR and WKY, and recovery of the cardiac energy charge potential (ECP) level in SHRSP was lower than that in SHR and WKY. Twenty-five, 12 and 11 min-ischemia in WKY, SHR and SHRSP, respectively, caused a similar level of cardiac mechanical damage. Also, the ECP levels were almost equivalent among them at the end of 20 min reperfusion following each time of ischemia. Under each ischemic condition, a Ca2+-channel blocker, diltiazem, and an adenosine potentiator, dilazep, produced a beneficial effect on the post-ischemic dysfunction in SHR and WKY. However, neither cardioprotective drug led to recovery of the mechanical dysfunction of the heart during reperfusion following ischemia in SHRSP. Thus, the severely hypertrophied heart such as that in SHRSP was more susceptible to cardiac reperfusion dysfunction, than the moderately hypertrophied heart such as that in SHR. These results suggest that the cardioprotective effects of drugs may be deteriorated in severe hypertrophied hearts.     

Reduced left ventricular hypertrophy following long-term water deprivation in the young spontaneously hypertensive rat

Biochemical and physical parameters of cardiac hypertrophy accompanying hypertension were studied in water deprived versus non-deprived immature spontaneously hypertensive rats (SHR) and their normotensive progenitor strain, Wistar Kyoto (WKY). A 23.5 hour/day water deprivation schedule was maintained from 5 to 13 weeks of age in 23 SHR and 8 WKY rats to compare the non-deprived animals (16 SHR and 8 WKY controls). Water deprived SHR had lower left ventricular weight, lower total protein and hydroxyproline and the same total DNA as the non-deprived SHR. DNA concentration was higher in the deprived SHR than in the non-deprived SHR. No differences were found among the four groups in right ventricular weight or DNA concentration. Left to right ventricular weight ratio was significantly lower and left to right ventricular DNA concentration ratio significantly higher in the deprived SHR relative to non-deprived SHR. These data indicate that the water deprived SHR, which was less hypertensive than the non-deprived SHR, had less hypertrophy of their left ventricles. While water deprivation lowered mean arterial pressure in the WKY, also, there was no effect on left ventricular weight or biochemical indices of left ventricular cell size and cell number.     

Regulation of ventricular atrial natriuretic peptide release in hypertrophied rat myocardium. Effects of exercise

Left ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). This study was designed to test the hypothesis that the increased ventricular ANP levels participate in the release of ANP into the circulation. Swimming was used as a physiologic model to induce ANP release from the heart, and atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP messenger RNA (mRNA) were measured simultaneously in the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at rest and after swimming. IR-ANP concentration in the left ventricle of 1-year-old SHR with severe left ventricular hypertrophy was increased in association with the augmentation of ANP mRNA levels, whereas right ventricular levels of ANP were reduced in SHR compared with normotensive controls. A 30-minute exercise in hypertensive and in normotensive rats resulted in marked increases in mean arterial pressure, heart rate, plasma catecholamine levels, blood lactate levels, and plasma IR-ANP concentration. The increased ANP secretion was associated with a decrease in left (34-39%) and right (24%) ventricular concentration of IR-ANP; transmurally, this depletion of ventricular IR-ANP was greatest (28%) in the endocardial layer of the left ventricle of SHR. No significant differences were noted in total atrial and left or right auricular IR-ANP concentration between SHR and WKY rats or between the resting and swimming rats. When studied in vitro with an isolated, perfused heart preparation, the hypertrophic ventricular tissue after atrialectomy secreted more ANP into the perfusate than did control hearts; in SHR, ventricles contributed 28% of the total ANP release to perfusate, and in normotensive control rats, ventricles contributed 8%. These studies show that stimulated release of ANP is associated with depletion of endocardial left ventricular stores. The amount of ANP released in vitro and in vivo correlated with the degree of hypertrophy of the ventricle. Finally, the phorbol ester, known to increase ANP secretion from intact perfused hearts, had only a limited effect on ANP release after atrialectomy, suggesting that the secretion of ANP from ventricular cells may be mainly of the constitutive type.     

Increased injury of hypertrophied myocardium with ischemic arrest: Preservation with hypothermia and cardioplegia

Many patients undergoing cardiac surgery have some degree of myocardial hypertrophy. To assess the response of hypertrophied myocardium to simulated cardiac surgery, left ventricular hypertrophy was induced in rats by aortic banding, and ventricular function was measured by means of the isolated, isovolumic heart perfusion technique. The hypertrophied hearts had a greater susceptibility to ischemic injury than nonhypertrophied control hearts, as manifested by a greater degree of diastolic contracture during the recovery period after 30 minutes of ischemic arrest at 37 degrees C. Hypothermia without cardioplegia during a 2-hour arrest did not completely preserve diastolic function in the hypertrophied hearts, but cardioplegia combined with hypothermia completely protected the hypertrophied hearts against 2 hours of ischemia. The results suggest a need for both hypothermic and cardioplegic preservation techniques in patients with myocardial hypertrophy who have cardiac surgical procedures requiring a significant period of myocardial ischemia.     

Pathological features of hypertrophic cardiomyopathy without asymmetrical septal hypertrophy.

In a heart with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the number of transmural myocytes, the mean size of myocytes, and the percentage area of interstitial space were similar in the ventricular septum and left ventricular posterior wall, whereas in a reported series of 14 hearts with hypertrophic cardiomyopathy with asymmetrical septal hypertrophy the number of transmural myocytes was greater in the ventricular septum than in the left ventricular posterior wall. In hearts with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the mean size of myocytes was significantly greater than that of normal hearts, but the number of transmural myocytes was not increased. The extent and distribution pattern of myocardial fibre disarray and fibrosis in the left ventricle were similar in hearts with hypertrophic myopathy whether or not asymmetrical septal hypertrophy was present.     

Sympathetic nerves modify mitochondrial and capillary growth in normotensive and hypertensive rats

We tested the hypothesis that sympathetic nerves influence cardiocyte organelle volumes and capillarity in spontaneously hypertensive rats (SHR) with long-standing hypertension and left ventricular hypertrophy. SHR and their normotensive, Wistar Kyoto (WKY), controls were treated with 6-hydroxydopamine from birth to prevent the establishment of the sympathetic nervous system. To determine whether beta adrenergic receptors were the major pathway of sympathetic influence, another group of SHR and WKY were chronically treated from weaning with the beta 1 adrenergic antagonist, metoprolol. In SHR sympathectomy failed to alter, while metoprolol attenuated, hypertension. Stereological analyses of perfuse-fixed hearts showed that in both SHR and WKY mitochondria/myofibrils volume ratio was increased by long-term sympathectomy, mainly by limiting mitochondrial volume density, even though this intervention failed to alter left ventricular mass. In contrast, long-term beta 1 blockade attenuated hypertrophy in SHR but had no effect on mitochondria/myofibrils volume ratio. Capillary numerical density was increased significantly in sympathectomized SHR and WKY. However, despite this increase, capillary volume density was similar in control and sympathectomized rats, since capillary diameter was less in the latter. Metoprolol-treated SHR showed a trend toward higher capillary numerical densities consistent with their attenuation of hypertrophy. These findings indicate that sympathetic nerves, either directly or indirectly, inhibit cardiocyte mitochondrial growth and capillary proliferation during both normal and pressure-overload induced cardiac enlargement.     

Recognition of regional hypertrophy in hypertrophic cardiomyopathy using thallium-201 emission-computed tomography: Comparison with two-dimensional echocardiography

The configuration of the hypertrophied myocardium was evaluated by thallium-201 emission-computed tomography and 2-dimensional (2-D) sector scan in 10 patients with obstructive hypertrophic cardiomyopathy (HC), 10 with nonobstructive HC with giant negative T waves and 10 with concentric left ventricular (LV) hypertrophy. Thallium-201 myocardial imaging was reconstructed into multiple 12-mm-thick slices in 3 planes. The thickness ratio of the ventricular septum and the LV posterior wall in the short-axis plane and the ratio of the ventricular septum and the apical wall in the long-axis plane were analyzed. In the patients with obstructive HC the ventricular septal wall thickness index was increased, and the ratio of septal to posterior wall thickness index (1.45 ± 0.23) was greater than that in the patients with nonobstructive HC with giant negative T waves or in those with concentric LV hypertrophy (1.03 ± 0.20 and 0.98 ± 0.11, respectively; p <0.01 for each). In the patients with nonobstructive HC with giant negative T waves, increased apical wall thickness with apical cavity obliteration was characteristic, and the ratio of ventricular septal to apical wall thickness index (0.66 ± 0.14) was less than that in the patients with obstructive HC or in those with concentric LV hypertrophy (1.46 ± 0.38 and 1.04 ± 0.09, respectively; p <0.001 for each). In contrast, technically satisfactory 2-D sector scanning (83%) demonstrated various configurations of the hypertrophied ventricularseptum, but could not detect apical hypertrophy in 4 of the 10 patients with nonobstructive HC with giant negative T waves whose LV cineangiograms demonstrated apical hypertrophy. Thus, thallium-201 emission-computed tomography is useful in evaluating the characteristics of LV hypertrophy and assists 2-D sector scan, especially in patients with apical hypertrophy in HC.     

Impaired vasodilator and chronotropic responses to 5-hydroxytryptamine in two models of hypertension-associated cardiac hypertrophy.

OBJECTIVE: In connection with hypertension, research concerning 5-hydroxytryptamine (5-HT) receptors and subtypes in the cardiovascular system has so far been predominantly focused on various vascular tissues. In this study, the effects of 5-HT were investigated in isolated hearts with experimental cardiac hypertrophy. DESIGN AND METHODS: Cardiac hypertrophy was induced by stenosing the abdominal aorta (ASR) of 5-week-old Wistar rats. The functional response to serotonin was measured in unpaced, ASR hearts (18-20 weeks) and compared with those of "sham" operated SHR and WKY rats. RESULTS: The ASR, less hypertensive than SHR, showed more pronounced cardiac hypertrophy. The positive chronotropic and coronary vasodilator response to 5-HT was reduced in hypertrophied hearts from SHR and ASR when compared to "sham" operated and normotensive controls. The positive chronotropic effect of 5-HT could be antagonised with ketanserin, without affecting the coronary vasodilation. 5-HT did not induce any change in contractile force. CONCLUSIONS: Cardiac hypertrophy is associated with impaired coronary vasodilator and chronotropic responsiveness to serotonin. The chronotropic response to 5-HT is mediated by the 5-HT2-receptor subtype.