Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts

2004 ◽  
Vol 287 (1) ◽  
pp. H277-H285 ◽  
Author(s):  
Yutaka Kitagawa ◽  
Daisuke Yamashita ◽  
Haruo Ito ◽  
Miyako Takaki
Keyword(s):  
Cardiac Hypertrophy ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Osmotic Minipump ◽  
Good Index ◽  
Rat Hearts ◽  
Lv Volume ◽  
Work Capability

The aim of the present study was to evaluate specifically left ventricular (LV) function in rat hearts as they transition from the normal to hypertrophic state and back to normal. Either isoproterenol (1.2 and 2.4 mg·kg−1·day−1 for 3 days; Iso group) or vehicle (saline 24 μl·day−1 for 3 days; Sa group) was infused by subcutaneous implantation of an osmotic minipump. After verifying the development of cardiac hypertrophy, we recorded continuous LV pressure-volume (P-V) loops of in situ ejecting hypertrophied rat hearts. The curved LV end-systolic P-V relation (ESPVR) and systolic P-V area (PVA) were obtained from a series of LV P-V loops in the Sa and Iso groups 1 h or 2 days after the removal of the osmotic minipump. PVA at midrange LV volume (PVAmLVV) was taken as a good index for LV work capability ( 13 , 15 , 20 , 21 ). However, in rat hearts during remodeling, whether PVAmLVV is a good index for LV work capability has not been determined yet. In the present study, in contrast to unchanged end-systolic pressure at midrange LV volume, PVAmLVV was significantly decreased by isoproterenol treatment relative to saline; however, these measurements were the same 2 days after pump removal. Simultaneous treatment with a β1-blocker, metoprolol (24 mg·kg−1·day−1), blocked the formation of cardiac hypertrophy and thus PVAmLVV did not decrease. The reversible changes in PVAmLVV reflect precisely the changes in LV work capability in isoproterenol-induced hypertrophied rat hearts mediated by β1-receptors. These results indicate that the present approach may be an appropriate strategy for evaluating the effects of antihypertrophic and antifibrotic modalities.

A Brief Regional Ischemic-reperfusion Enhances Propofol-induced Depression in Left Ventricular Function of in situ  Rat Hearts

2004 ◽  
Vol 101 (4) ◽  
pp. 879-887 ◽  
Author(s):  
Naoya Kuzumoto ◽  
Yutaka Kitagawa ◽  
Koichi Uemura ◽  
Takashi Ueyama ◽  
Ken-ichi Yoshida ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Inhibitory Effects ◽  
Ischemic Reperfusion ◽  
Kinase C ◽  
Rat Hearts

Background Propofol is short-acting intravenous general anesthetics that reduces cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial contractility, however, remain debatable. The aim of the current study was to test the hypothesis that inhibitory effects of propofol on left ventricular (LV) contractility and mechanical work capability of in situ ejecting rat hearts are attenuated after a brief regional ischemia and reperfusion. Methods The authors obtained steady-state LV pressure-volume loops and intermittently obtained LV end-systolic pressure-volume relation and evaluated effects of propofol on LV function by end-systolic pressure (ESPmLVV), systolic pressure-volume area (PVAmLVV) at midrange LV volume (mLVV). Results Propofol (5.2 +/- 0.3 approximately 11.1 +/- 3.7 microg.ml) significantly decreased ESP0.08 to 78 +/- 12% approximately 64 +/- 13% of prepropofol and PVA0.08 to 76 +/- 13%approximately 63 +/- 16% of prepropofol in normal hearts, whereas propofol at a lower concentration (4.1 +/- 1.0 microg/ml) did not. Although brief ischemic-reperfusion per se did not affect LV function, propofol after that, even at a lower concentration (4.1 +/- 1.0 microg/ml), significantly decreased ESP0.08 to 70 +/- 27% of prepropofol and PVA0.08 to 68 +/- 33% of prepropofol. Pretreatment with a protein kinase C (PKC) inhibitor, bisindolylmaleimide reduced the propofol (4.1 +/- 1.0 microg/ml)-induced greater decreases in ESP0.08 and PVA0.08 after brief ischemic-reperfusion to 94 +/- 33% and 92 +/- 39% of prepropofol. In the propofol-infused hearts after brief ischemic-reperfusion, protein kinase C-epsilon translocation to the nucleus-myofibril fraction was found. Conclusion In contrast to the study hypothesis, brief ischemic-reperfusion enhanced the inhibitory effects of propofol on LV systolic function; this enhancement is attributable to activation of protein kinase C.

NHE-1 participates in isoproterenol-induced downregulation of SERCA2a and development of cardiac remodeling in rat hearts

2011 ◽  
Vol 301 (5) ◽  
pp. H2154-H2160 ◽  
Author(s):  
Munetaka Shibata ◽  
Daisuke Takeshita ◽  
Koji Obata ◽  
Shinichi Mitsuyama ◽  
Haruo Ito ◽  
...  
Keyword(s):  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Cardiac Remodeling ◽  
Mechanical Energy ◽  
Systolic Pressure ◽  
Beneficial Effects ◽  
Rat Hearts ◽  
Total Mechanical Energy ◽  
Male Wistar Rats ◽  
Lv Volume

Impaired Ca2+ handling is one of the main characteristics in heart failure patients. Recently, we reported abnormal expressions of Ca2+-handling proteins in isoproterenol (ISO)-induced hypertrophied rat hearts. On the other hand, Na+/H+ exchanger (NHE)-1 inhibitor has been demonstrated to exert beneficial effects in ischemic-reperfusion injury and in the development of cardiac remodeling. The aims of the present study are to investigate the role of NHE-1 on Ca2+ handling and development of cardiac hypertrophy in ISO-infused rats. Male Wistar rats were randomly divided into vehicle [control (CTL)] and ISO groups without or with pretreatment with a selective NHE-1 inhibitor, BIIB-723. ISO infusion for 1 wk significantly increased the ratios of heart to body weight and left ventricle (LV) to body weight and collagen accumulation. All of these increases were antagonized by coadministration with BIIB-723. The ISO-induced significant increase in LV wall thickness was suppressed significantly ( P < 0.05) by BIIB-723. ISO-induced decreases in cardiac stroke volume and a total mechanical energy per beat index, systolic pressure-volume area at midrange LV volume, were normalized by BIIB-723. The markedly higher expression of NHE-1 protein in the ISO group than that in CTL group was suppressed ( P < 0.05) by BIIB-723. Surprisingly, ISO induced downregulation of the important Ca2+-handling protein sarcoplasmic reticulum Ca2+-ATPase 2a, the expression of which was also normalized by BIIB-723 without changes in phosphorylated phospholamban (PLB)/PLB expression. We conclude that NHE-1 contributes to ISO-induced abnormal Ca2+ handling associated with cardiac hypertrophy. Inhibition of NHE-1 ameliorates cardiac Ca2+-handling impairment and prevents the development of cardiac dysfunction in ISO-infused rats.

New mechanoenergetic evaluation of left ventricular contractility in in situ rat hearts

1997 ◽  
Vol 272 (6) ◽  
pp. H2671-H2678 ◽  
Author(s):  
H. Tachibana ◽  
M. Takaki ◽  
S. Lee ◽  
H. Ito ◽  
H. Yamaguchi ◽  
...  
Keyword(s):  
Mechanical Energy ◽  
Left Ventricular ◽  
Aortic Occlusion ◽  
Ventricular Contractility ◽  
Left Ventricular Contractility ◽  
Rat Hearts ◽  
Total Mechanical Energy ◽  
Work Capability

We recorded a series of ejecting left ventricular (LV) pressure (P)-volume (V) loops of in situ rat hearts during a gradual ascending aortic occlusion. The end-systolic (ES) P-V relationship (ESPVR) was upward convex curvilinear regardless of LV contractility. The ESPVR was shifted upward in an enhanced contractility by dobutamine and downward in a depressed contractility by propranolol; ESP at a midrange V of 0.1 ml/g LV on each ESPVR increased from 131 +/- 11 to 192 +/- 17 mmHg and decreased from 136 +/- 10 to 110 +/- 7 mmHg, respectively. Furthermore, we obtained an upward concave curvilinear pressure-volume area (PVA; a measure of total mechanical energy)-V (preload) relationship to assess LV work capability in each contractility. This relationship also shifted upward in enhanced contractility and downward in depressed contractility; the PVA at midrange V increased from 7.9 +/- 1.2 to 12.3 +/- 1.5 mmHg. ml.beat-1.g-1 and decreased from 8.2 +/- 0.9 to 6.4 +/- 0.8 mmHg.ml.beat-1.g-1. We conclude that the heights of the ESPVR and PVA-V relationship curves can evaluate LV contractility mechanoenergetically.

scholarly journals Effects of Myosin Isozyme Shift on Curvilinearity of the Left Ventricular End-Systolic Pressure-Volume Relation of In Situ Rat Hearts.

1998 ◽  
Vol 48 (6) ◽  
pp. 445-455 ◽  
Author(s):  
Shinyu LEE ◽  
Yoshimi OHGA ◽  
Hideo TACHIBANA ◽  
Yi SYUU ◽  
Haruo ITO ◽  
...  
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular ◽  
Rat Hearts ◽  
Volume Relation ◽  
Myosin Isozyme

Calpain inhibitor-1 protects the rat heart from ischemia-reperfusion injury: analysis by mechanical work and energetics

2005 ◽  
Vol 288 (4) ◽  
pp. H1690-H1698 ◽  
Author(s):  
Yoshiro Yoshikawa ◽  
Hiroji Hagihara ◽  
Yoshimi Ohga ◽  
Chikako Nakajima-Takenaka ◽  
Ken-ya Murata ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mechanical Energy ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Mechanical Work ◽  
Lv Function ◽  
Calpain Inhibitor ◽  
Lv Volume

We hypothesized that calpain inhibitor-1 protected left ventricular (LV) function from ischemia-reperfusion injury by inhibiting the proteolysis of α-fodrin. To test this hypothesis, we investigated the effect of calpain inhibitor-1 on LV mechanical work and energetics in the cross-circulated rat hearts that underwent 15-min global ischemia and 60-min reperfusion ( n = 9). After ischemia-reperfusion with calpain inhibitor-1, mean end-systolic pressure at midrange LV volume and systolic pressure-volume area (PVA) at midrange LV volume (total mechanical energy per beat) were hardly changed, although they were significantly ( P < 0.01) decreased after ischemia-reperfusion without calpain inhibitor-1. Mean myocardial oxygen consumption per beat (Vo2) intercepts (PVA-independent Vo2; Vo2 for the total Ca2+ handling in excitation-contraction coupling and basal metabolism) of Vo2-PVA linear relations were also unchanged after ischemia-reperfusion with calpain inhibitor-1, although they were significantly ( P < 0.01) decreased after ischemia-reperfusion without calpain inhibitor-1. There were no significant differences in O2 costs of LV PVA and contractility among the hearts in control (or normal) postischemia-reperfusion and postischemia-reperfusion with calpain inhibitor-1. Western blot analysis of α-fodrin and the immunostaining of 150-kDa products of α-fodrin confirmed that calpain inhibitor-1 almost completely protected the proteolysis of α-fodrin. Our results indicate that calpain inhibitor-1 prevents the heart from ischemia-reperfusion injury associated with the impairment of total Ca2+ handling by directly inhibiting the proteolysis of α-fodrin.

Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes

2008 ◽  
Vol 294 (3) ◽  
pp. H1274-H1281 ◽  
Author(s):  
Xinhua Yan ◽  
Adam J. T. Schuldt ◽  
Robert L. Price ◽  
Ivo Amende ◽  
Fen-Fen Liu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Ventricular Myocytes ◽  
Diastolic Pressure ◽  
Tyrosine Phosphatase ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Lv Function ◽  
Aortic Banding

The role of the angiotensin II type 2 (AT2) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT2 receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT2TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice.

Protamine-induced Cardiotoxicity Is Prevented by Anti-TNF-α Antibodies and Heparin

2001 ◽  
Vol 95 (6) ◽  
pp. 1389-1395 ◽  
Author(s):  
Dmitry Pevni ◽  
Inna Frolkis ◽  
Adrian Iaina ◽  
Yoram Wollman ◽  
Tamara Chernichovski ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Tnf Alpha ◽  
Control Group ◽  
Lv Function ◽  
Heparin Group ◽  
Necrosis Factor Alpha ◽  
Rat Hearts ◽  
Factor Alpha

Background We investigated the role of tumor necrosis factor alpha (TNF-alpha) in protamine-induced cardiotoxicity and the possibility of preventing or decreasing this effect by anti TNF-alpha antibodies and heparin. Methods Isolated rat hearts were perfused for 60 min with Krebs-Henseleit solution (KH). The control group was perfused with KH alone, the KH &gt; protamine &gt; KH group was treated from the 20th to the 40th minute with protamine, and the KH + anti-TNF &gt; protamine + anti-TNF &gt; KH + anti-TNF group was treated the same as the KH &gt; protamine &gt; KH group but with anti-TNF-alpha antibodies added throughout perfusion. The KH + heparin &gt; protamine + heparin &gt; KH + heparin group was treated the same as the KH &gt; protamine &gt; KH group but with heparin added to KH throughout perfusion. The KH &gt; protamine &gt; KH + heparin was perfused the same as the KH&gt; protamine &gt; KH group but with heparin added to KH for the last 20 min. Left ventricular (LV) function and coronary flow were measured every 10 min. TNF-alpha was measured in the coronary sinus effluent. Left ventricular TNF messenger RNA was determined in the control and KH &gt; protamine &gt; KH groups at baseline and after the 40-min perfusion. Results Protamine caused a significant decrease of peak systolic pressure and dP/dt (to 25% of baseline). Significant amounts of TNF-alpha in the effluent in the KH &gt; protamine &gt; KH group (102.3 +/- 15.5 pg/min) and TNF messenger RNA expression in left ventricular samples were detected. TNF-alpha was below detectable concentrations in the control, KH + anti-TNF &gt; protamine + anti-TNF &gt; KH + anti-TNF, and KH + heparin &gt; protamine + heparin &gt; KH + heparin groups. TNF-alpha concentrations correlated with depression of LV peak systolic pressure (r = 0.984; P = 0.01) and first derivate of the increase of LV pressure (r = 0.976; P = 0.001). Heparin improved LV recovery and decreased protamine-induced TNF-alpha release (KH &gt; protamine &gt; KH + heparin group). Conclusions Anti-TNF-alpha antibodies and heparin prevent protamine-induced TNF-alpha release and depression of LV function. Heparin improves protamine-induced depression of cardiac function.

Length-dependent Regulation of Left Ventricular Function in Coronary Surgery Patients 

1999 ◽  
Vol 91 (2) ◽  
pp. 379-387 ◽  
Author(s):  
Stefan G. De Hert ◽  
Thierry C. Gillebert ◽  
Pieter W. Ten Broecke ◽  
Adriaan C. Moulijn
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Stroke Work ◽  
Coronary Surgery ◽  
Volume Data ◽  
Load Dependence ◽  
End Diastolic Volume ◽  
Lv Volume ◽  
Underlying Mechanisms

Background Load-dependent impairment of left ventricular (LV) function was observed after leg elevation in a subgroup of coronary surgery patients. The present study investigated underlying mechanisms by comparing hemodynamic effects of an increase in LV systolic pressures with leg elevation to effects of a similar increase in systolic pressures with phenylephrine. Methods The study was performed in patients undergoing elective coronary surgery prior to cardiopulmonary bypass. High-fidelity LV pressure tracings (n = 25) and conductance LV volume data (n = 10) were obtained consecutively during leg elevation and after phenylephrine administration (5 microg/kg). Results Leg elevation resulted in a homogeneous increase in end-diastolic volume. The change in stroke volume (SV), stroke work (SW) and dP/dtmax was variable, with an increase in some patients but no change or a decrease in other patients. For a matched increase in systolic pressures, phenylephrine increased SW and dP/dtmax in all patients with no change in SV. Load dependence of relaxation (slope R of the tau-end-systolic pressure relation) was inversely related for changes in SV, SW, and dP/dtmax with leg elevation but not with phenylephrine. Conclusions The different effects of leg elevation and phenylephrine suggest that the observed decrease in SV, SW, and dP/dtmax with leg elevation in some patients could not be attributed to an impaired contractile response to increased systolic LV pressures. Instead, load-dependent impairment of LV function after leg elevation appeared related to a deficient length-dependent regulation of myocardial function.

scholarly journals Left ventricular volumetric conductance catheter for rats

1996 ◽  
Vol 270 (4) ◽  
pp. H1509-H1514 ◽  
Author(s):  
H. Ito ◽  
M. Takaki ◽  
H. Yamaguchi ◽  
H. Tachibana ◽  
H. Suga
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular ◽  
Conductance Catheter ◽  
Inferior Vena Caval ◽  
Essential Parameter ◽  
Cardiac Pump Function ◽  
Catheter Tip ◽  
Electromagnetic Flow Probe ◽  
Lv Volume

Left ventricular (LV) volume (V) is an essential parameter for assessment of the cardiac pump function. Measurement of LVV in situ by a conductance catheter method has been widely used in dogs and humans but not yet in small experimental animals such as rats. We instituted a miniaturized six-electrode conductance catheter (3-F) for rat LVV measurement and its signal processing apparatus. We compared stroke volumes (SVs) simultaneously measured with this conductance catheter introduced into the LV through the apex and an electromagnetic flow probe placed on the ascending aorta during gradual decreases in LVV by an inferior vena caval occlusion. A high and linear correlation (r = 0.982) was obtained between these differently measured by SVs pooled from six rats. In another group of three rats, LV pressure was simultaneously measured with a 3-F catheter-tip micromanometer introduced into the LV through the apex. We obtained the slope of the end-systolic pressure-volume (P-V) relationship (Emax) by a gradual ascending aortic occlusion. After administration of propranolol, Emax obviously decreased with no change in volume intercept of the P-V relationship. The conductance volumetry proved to be useful in rats.

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