Abstract 15989: Intracoronary Infusion of Multicellular Cardiospheres Can Be Safely Used to Prevent Adverse Remodeling in a Pig Model of Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Romain Gallet ◽  
Eleni Tseliou ◽  
James Dawkins ◽  
Ryan Middleton ◽  
Jackelyn Valle ◽  
...  
Keyword(s):  
Troponin I ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Self Assembling ◽  
Timi Flow ◽  
Intracoronary Infusion ◽  
Post Infusion ◽  
Adverse Remodeling ◽  
Hemodynamic Improvement

Background: Pre-clinical studies in rodents and pigs indicate that the self-assembling microtissues known as cardiospheres (CSp), when administered intramyocardially, may be more effective than dispersed CSp-derived cells (CDCs). However, the more desirable intracoronary (IC) route has been assumed to be unsafe for CSp delivery: CSp are large (>35 μm), raising concerns about likely microembolization. Objective: We sought to evaluate the safety and efficacy of IC delivery of allogeneic CSp in a porcine model of convalescent MI. Methods: Dosage was optimized by infusing CSp (3.25x10 5 particles [n=2], 6.5 x10 5 [n=3] and 1.3x10 6 [n=2], size=44±23, 29%>50μm) in the LAD of naïve pigs, looking for acute adverse effects (troponin I [TnI] leak, low TIMI flow, stunning). We next tested the efficacy of IC allogeneic Csp (1.3x10 6 ; n=7) or vehicle (n=8) in a minipig model of chronic MI. Animals underwent MRI before infusion and 1 month later. Left ventricular (LV) ejection fraction (EF), scar mass and viable mass were evaluated at both time points. Results: In the dosing study, we observed no impairment of TIMI flow or LVEF after CSp infusion. TnI at 24 hours was 0.7±0.5ng/mL and did not differ among groups (P=0.11). In the post-MI study, EF was identical in the two groups at baseline. One month post-infusion, LV function was preserved in the CSp group but not in controls (ΔEF=+0.5±1.6% vs. -4.5±1.8%, p<0.001). CSp reduced scar mass (P<0.001) and increased viable mass (+17±8% vs. +6±6% from baseline, P=0.04) compared to controls. IC CSp also decreased LV end diastolic pressure (-7±4mmHg vs. -1±4 mmHg in control, P<0.01)) and increased cardiac output (+0.5±0.4 mL/min vs. -0.1±0.3mL/min, P<0.01. Conclusions: IC delivery of allogeneic CSp is safe and preserves LV function after MI. In addition, global hemodynamic improvement is observed, which may have significant clinical implications. The decision to use CDCs or CSp is not forced, therefore, by an inability to infuse CSp safely via the IC route.

Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice

2001 ◽  
Vol 281 (5) ◽  
pp. H1938-H1945 ◽  
Author(s):  
Chari Y. T. Hart ◽  
John C. Burnett ◽  
Margaret M. Redfield
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Systolic Function ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Lv Function ◽  
Ketamine Anesthesia ◽  
The Difference ◽  
And Function ◽  
Derivatives Of

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (τ), and the first derivatives of LV pressure rise and fall (dP/d t max and dP/d t min, respectively). During echocardiography, HR was lower in XK than AV mice (250 ± 14 beats/min in XK vs. 453 ± 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 ± 0.08 mm in XK vs. 3.8 ± 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 ± 1.2% in XK vs. 40 ± 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 ± 24 beats/min) and XK (342 ± 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 ± 5 vs. 6.2 ± 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/d t max: 4,402 ± 798 vs. 8,250 ± 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (τ: 23 ± 2 vs. 14 ± 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.

ID: 137: GRK2 INHIBITION REDUCES POST-MYOCARDIAL INFARCTION CARDIAC FIBROBLAST MEDIATED ADVERSE REMODELING

2016 ◽  
Vol 64 (4) ◽  
pp. 912.1-912
Author(s):  
M Razzaque ◽  
JL Philip ◽  
X Xu ◽  
M Han ◽  
J Li ◽  
...  
Keyword(s):  
Collagen Synthesis ◽  
Left Ventricular ◽  
Male Rats ◽  
Lv Function ◽  
Intracellular Camp ◽  
Adrenergic Signaling ◽  
Adenoviral Delivery ◽  
Collagen Iii ◽  
Adverse Remodeling ◽  
Fractional Shortening

ObjectivesRemote (non-infarct) territory fibrosis is a significant cause of post-infarction heart failure (HF). We have previously shown that increased G protein-coupled receptor kinase-2 (GRK2) activity in adult human cardiac fibroblasts (CF) isolated from failing hearts is an important mechanism of cardiac fibrosis through uncoupling β-adrenergic receptor (β-AR) signaling. This study investigates the potential therapeutic role of GRK2 inhibition on CF biology in vivo.MethodsAdult male rats underwent LAD ligation to induce post-MI HF. Left ventricular (LV) function was assessed by echocardiography. Myocardial fibrosis was quantitated by histologic staining. LV CF were isolated and cultured. GRK2 was inhibited by intra-coronary adenoviral-mediated delivery of a GRK2 inhibitor (Ad-GRK2ct) immediately following LAD ligation (n=11). Control rats received a null adenovirus (n=10). Animals were studied prior to and 12 weeks post-MI and adenoviral delivery.ResultsThere was a significant decline in LV function at 12 weeks post-MI which [Fractional shortening: 0.35±0.01 vs. 0.52±0.01, p<0.01]. There was significant increase in remote territory (non-infarct area) fibrosis at 12 weeks post-MI compared to control [12±1% vs. 2±1% fibrosis, p<0.05], consistent with adverse remodeling. Additionally, collagen synthesis was significantly upregulated in isolated CF 12 weeks post-MI compared to control CF [3559±760 vs. 1029±45 cmp/mg protein, p<0.02]. At 12 weeks post-MI, GRK2 activity was increased 1.4-fold [p<0.01]. There was a 42% decrease in intracellular cAMP [p<0.05] and loss of b-agonist (isoproterenol)-stimulated inhibition of collagen synthesis characteristic of normal CF, indicating uncoupling of β-AR signaling post-MI. Adenoviral mediated overexpression of GRK2ct, GRK2 inhibitor, in vitro in the cultured CF post-MI led to a 50% decrease in aSMA expression (p<0.01) as well as a significant decreased collagen expression and synthesis compared to null adenovirus (Ad-Null) control [1928±126 vs. 2611±213 cmp/mg protein, p<0.05], restoring the control CF phenotype. Intra-coronary delivery of Ad-GRK2ct following MI significantly reduced post-MI LV dysfunction vs. Ad-Null as measured by improved fractional shortening [0.42±0.01 vs. 0.30±0.02, p<0.01] and ejection fraction [72±1% vs. 57±2%, p<0.03]. Ad-GRK2ct also decreased peri-infarct and remote territory fibrosis by 60% [p<0.03]. Consistent with these findings, Ad-GRK2ct resulted in an over 25% decreased in α-SMA, collagen I, and collagen III expression in CF isolated 12 weeks post-MI vs. Ad-Null [p<0.04] providing evidence of decreased post-MI CF activation and myofibroblast transformation with Ad-GRK2ct.ConclusionsUncoupling of β-adrenergic signaling in CF via increased GRK2 appears to be a key mechanism of post-MI fibrosis. Targeted inhibition of GRK2 and restoration of b-adrenergic signaling/cAMP production in CF may represent a novel therapeutic approach to prevent pathological fibrosis and maladaptive remodeling.

scholarly journals Contractile protein phosphorylation predicts human heart disease phenotypes

2013 ◽  
Vol 304 (12) ◽  
pp. H1644-H1650 ◽  
Author(s):  
Lori A. Walker ◽  
David A. Fullerton ◽  
Peter M. Buttrick
Keyword(s):  
Heart Failure ◽  
Heart Disease ◽  
Protein Phosphorylation ◽  
Protein Phosphatase ◽  
Human Heart ◽  
Troponin I ◽  
Systolic Function ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function

Human heart failure has been associated with a low level of thin-filament protein phosphorylation and an increase in calcium sensitivity of contraction relative to both “control” human heart tissue and tissue from small animal models. However, diverse strategies of human tissue procurement and the reliance on tissue obtained from subjects with end-stage heart failure suggest this may be an incomplete characterization. Therefore, we evaluated cardiac left ventricular (LV) biopsy samples from patients with aortic stenosis undergoing valve replacement who presented either with LV hypertrophy and preserved systolic function (Hyp) or with LV dilation and reduced ejection fraction (Dil). In Hyp, total troponin I (TnI) phosphorylation was markedly increased and myosin light chain 2 (MLC2) phosphorylation was unchanged relative to a control group of patients with normal LV function. Conversely, in Dil, total TnI phosphorylation was significantly reduced compared with control subjects and MLC2 phosphorylation was increased. Site-specific analysis of TnI phosphorylation revealed phenotype-specific differences such that Hyp samples demonstrated significant increases in phosphorylation at serine 22/23 and Dil samples had significant decreases at serine 43. The ratio of phosphorylation at the two sites was biased toward serine 22/23 in Hyp and toward serine 43/45 in Dil. Western blot analysis showed that protein phosphatase-1 was reduced in Hyp and protein phosphatase-2 was reduced in Dil. These data suggest that posttranslational modifications of sarcomeric proteins, both singly and in combination, are stage specific. Defining these changes in progressive heart disease may provide important diagnostic and treatment information.

scholarly journals Sodium nitrate supplementation alters mitochondrial H2O2 emission but does not improve mitochondrial oxidative metabolism in the heart of healthy rats

2018 ◽  
Vol 315 (2) ◽  
pp. R191-R204 ◽  
Author(s):  
Cynthia M. F. Monaco ◽  
Paula M. Miotto ◽  
Jason S. Huber ◽  
Luc J. C. van Loon ◽  
Jeremy A. Simpson ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Muscle Fibers ◽  
Coupling Efficiency ◽  
Left Ventricular ◽  
Lv Function ◽  
Mitochondrial Bioenergetics ◽  
Isolated Mitochondria ◽  
Nitrate Supplementation ◽  
Permeabilized Muscle ◽  
Invasive Hemodynamics

Supplementation with dietary inorganic nitrate ([Formula: see text]) is increasingly recognized to confer cardioprotective effects in both healthy and clinical populations. While the mechanism(s) remains ambiguous, in skeletal muscle oral consumption of NaNO3 has been shown to improve mitochondrial efficiency. Whether NaNO3 has similar effects on mitochondria within the heart is unknown. Therefore, we comprehensively investigated the effect of NaNO3 supplementation on in vivo left ventricular (LV) function and mitochondrial bioenergetics. Healthy male Sprague-Dawley rats were supplemented with NaNO3 (1 g/l) in their drinking water for 7 days. Echocardiography and invasive hemodynamics were used to assess LV morphology and function. Blood pressure (BP) was measured by tail-cuff and invasive hemodynamics. Mitochondrial bioenergetics were measured in LV isolated mitochondria and permeabilized muscle fibers by high-resolution respirometry and fluorometry. Nitrate decreased ( P < 0.05) BP, LV end-diastolic pressure, and maximal LV pressure. Rates of LV relaxation (when normalized to mean arterial pressure) tended ( P = 0.13) to be higher with nitrate supplementation. However, nitrate did not alter LV mitochondrial respiration, coupling efficiency, or oxygen affinity in isolated mitochondria or permeabilized muscle fibers. In contrast, nitrate increased ( P < 0.05) the propensity for mitochondrial H2O2 emission in the absence of changes in cellular redox state and decreased the sensitivity of mitochondria to ADP (apparent Km). These results add to the therapeutic potential of nitrate supplementation in cardiovascular diseases and suggest that nitrate may confer these beneficial effects via mitochondrial redox signaling.

Abstract 16121: Recombinant Human Placental Growth Factor 2 is a Safe and Effective Therapy for Ischemic Cardiomyopathy in Atherosclerotic Mice

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ming Wu ◽  
Melissa Swinnen ◽  
Ellen Caluwe ◽  
Hilde Gillijns ◽  
Nina Vanden Driessche ◽  
...  
Keyword(s):  
Growth Factor ◽  
Atherosclerotic Plaque ◽  
Ischemic Cardiomyopathy ◽  
Contractile Function ◽  
Left Ventricular ◽  
Placental Growth Factor ◽  
Plaque Burden ◽  
Lv Function ◽  
Plaque Vulnerability ◽  
Adverse Remodeling

Aim: Angiogenic growth factor therapy carries a risk of stimulating atherosclerotic plaque growth. We evaluated whether systemic infusion of recombinant human placental growth factor (rhPlGF) 2 improves myocardial neovascularization, left ventricular (LV) function and adverse remodeling in a murine model of advanced atherosclerosis and chronic myocardial infarction (MI) without increasing atherosclerotic plaque size and plaque vulnerability. Methods: ApoE -/- mice were fed a high cholesterol diet and MI was induced 4 weeks (w) later using 60 min LAD occlusion followed by reperfusion. After 8 w, we assessed LV function using echocardiography and randomized mice to receive rhPlGF2 (450μg/kg/day, n=20) or PBS (n=20) via osmotic minipumps for 28 days. Echocardiography and histological analyses were performed at 12 and 20 w. Results: Infusion of rhPlGF2 increased PlGF plasma levels for 3 w up to ~1600-fold without adverse side effects, or changes in total cholesterol and high sensitive CRP levels. In rhPlGF2-treated mice, capillary and arteriolar density was significantly higher in ischemic myocardium (2813±212 capillaries/mm 2 at 12 w vs 2144±478 in PBS, P <0.05; 125±18 arterioles/mm 2 at 20 w vs 77±13 in PBS, P =0.001). RhPlGF2 significantly improved ejection fraction (EF), reduced LV end-systolic and end-diastolic volume indices at 12 w and prevented further LV dilation and EF deterioration at 20 w (Figure). RhPlGF2 did not increase plaque area in the aortic arch, or the degree of fibrosis, calcification, capillary or arteriolar density and MAC3-positive cell areas in plaques at 12 and 20 w. Conclusion: Systemic rhPlGF2 infusion significantly improves neovascularization and contractile function, and prevents LV adverse remodeling in chronic ischemic cardiomyopathy without increasing atherosclerotic plaque burden or plaque vulnerability. RhPlGF2 may represent a promising and safe therapeutic strategy in chronic ischemic cardiomyopathy.

Abstract 15172: Murf1 Inhibitor Embl205 is a New Approach for Treatment of Heart Failure With Preserved Ejection Fraction in an Animal Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anett Jannasch ◽  
Antje Schauer ◽  
Virginia Kirchhoff ◽  
Runa Draskowsi ◽  
Claudia Dittfeld ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Skeletal Muscle Atrophy ◽  
Lv Function ◽  
Preserved Ejection Fraction ◽  
The Impact ◽  
Peak Gradient

Background: The novel MuRF1 inhibitor EMBL205 attenuates effectively developing skeletal muscle atrophy and dysfunction in animals with heart failure with preserved ejection fraction (HFpEF, ZSF1 rat model). The impact of EMBL205 on myocardial function in the HFpEF setting is currently unknown and was evaluated in ZSF1 rats. Methods: 20 wks-old female obese ZSF1 rats received EMBL205 (12 wks, conc. of 0.1% in chow; HFpEF-EMBL205). Age-matched untreated lean (con) and obese (HFpEF) ZSF1 rats served as controls. At 32 wks of age left ventricular (LV)-, aortic valve (AV) function and LV end diastolic pressure (LVEDP) was determined by echocardiography and invasive hemodynamic measurements. LV expression of collagen 1A (Col1A) and 3A (Col3A) was assessed by qRT-PCR, MMP2 expression was obtained by zymography and perivascular fibrosis was quantified in histological sections. Results: Development of HFpEF in ZSF1 obese animals is associated with cardiac enlargement and hypertrophy, as evident by increased myocardial weight, an increase in end diastolic volume (EDV) and LV anterior and posterior wall diameters. Diastolic LV-function is disturbed with elevation of E/é, an increased LVEDP and a preserved LV ejection fraction. AV peak velocity and peak gradient are significantly increased and AV opening area (AVA) significantly decreased. Col1A and Col3A expression are increased in HFpEF animals. EMBL205 treatment results in a significant reduction of myocardial weight and a trend towards lower EDV compared to HFpEF group. EMBL205 attenuates the increase in E/é, LVEDP, AV peak gradient and the decrease of AVA. EMBL205 significantly reduces Col3A expression and a trend for Col1A expression is seen. Increased perivascular fibrosis and MMP2 expression in HFpEF is extenuated by EMBL205 treatment (table 1). Conclusions: Application of EMBL205 attenuated the development of pathological myocardial alterations associated with HFpEF in ZSF1rats due to antifibrotic effects.

Ventricular performance and myocardial water content during hemodilution in dogs

1978 ◽  
Vol 235 (6) ◽  
pp. H767-H775 ◽  
Author(s):  
G. A. Geffin ◽  
M. A. Vasu ◽  
D. D. O'Keefe ◽  
D. G. Pennington ◽  
A. J. Erdmann ◽  
...  
Keyword(s):  
Water Content ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Stroke Work ◽  
Ventricular Performance ◽  
End Diastolic Volume ◽  
Lv Mass ◽  
Right Heart Bypass ◽  
Water Gain

In dogs anesthetized with chloralose-urethan on right heart bypass, left ventricular (LV) performance was assessed at constant LV stroke work before and for up to 2.5 h after crystalloid hemodilution was established. Lowering the hematocrit from 43.3 +/- 1.3% to 13.6 +/- 1.7% (SE) did not significantly change LV end-diastolic pressure (LVEDP) initially. After 80 min LVEDP increased slightly by 1.7 +/- 0.6 cmH2O (P less than 0.05) at a stroke work of 17.3 +/- 2.3 g.m. The value of dP/dt did not change significantly throughout. When LV function curves were generated by increasing cardiac output, the stroke work attained at an LVEDP of 10 cmH2O decreased with hemodilution from 23.9 +/- 3.5 to 20.8 +/- 3.9 g.m (NS). LV wall water content increased with hemodilution, from which it could be calculated that there was an 18.6% increase in LV mass. Thus, despite an increase in LV external girth demonstrated by LV circumferential gauges, it is possible that increased wall thickness due to the water gain resulted in little change or an actual decrease in LV end-diastolic volume. Thus, profound hemodilution can be attained with only slight depression of LV performance.

Colchicine attenuates left ventricular hypertrophy but preserves cardiac function of aortic-constricted rats

2003 ◽  
Vol 94 (4) ◽  
pp. 1627-1633 ◽  
Author(s):  
Beatriz S. Scopacasa ◽  
Vicente P. A. Teixeira ◽  
Kleber G. Franchini
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Colchicine Treatment ◽  
Average Diameter ◽  
Left Ventricular ◽  
Lv Function ◽  
Right Ventricular Mass ◽  
Lv Mass ◽  
Phenylephrine Infusion

To investigate the effects of colchicine on left ventricular (LV) function and hypertrophy (LVH) of rats subjected to constriction of transverse aorta (TAoC), we evaluated SO (sham operated, vehicle; n = 25), SO-T (sham operated, colchicine 0.4 mg/kg body wt ip daily; n = 38), TAoC (vehicle; n = 37), and TAoC-T (TAoC, colchicine; n = 34) on the 2nd, 6th, and 15th day after surgery. Colchicine attenuated LVH of TAoC-T compared with TAoC rats, as evaluated by ratio between LV mass (LVM) and right ventricular mass, LV wall thickness, and average diameter of cardiac myocytes. Systolic gradient across TAoC (∼45 mmHg), LV systolic pressure, LV end-diastolic pressure, and rate of LV pressure increase (+dP/d t) were comparable in TAoC-T and TAoC rats. However, the baseline and increases of LV systolic pressure-to-LVM and +dP/d t-to-LVMratios induced by phenylephrine infusion were greater in TAoC-T and SO-T compared with SO rats. Baseline and increases of +dP/d t-to-LVM ratio were reduced in TAoC compared with SO rats. TAoC rats increased polymerized fraction of tubulin compared with SO, SO-T, and TAoC-T rats. Our results indicate that colchicine treatment reduced LVH to pressure overload but preserved LV function.

scholarly journals Benefits of long-term β-blockade in experimental chronic aortic regurgitation

2008 ◽  
Vol 294 (4) ◽  
pp. H1888-H1895 ◽  
Author(s):  
Eric Plante ◽  
Dominic Lachance ◽  
Serge Champetier ◽  
Marie-Claude Drolet ◽  
Élise Roussel ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Prolonged Treatment ◽  
Adrenergic System ◽  
Lv Function ◽  
Adrenergic Blockade ◽  
Long Term Effects ◽  
Lv Remodeling

The objective of this study was to assess the long-term effects of β-blockade on survival and left ventricular (LV) remodeling in rats with aortic valve regurgitation (AR). The pharmacological management of chronic AR remains controversial. No drug has been definitively proven to delay the need for valve replacement or to affect morbidity and/or mortality. Our group has reported that the adrenergic system is activated in an animal model of AR and that adrenergic blockade may help maintain normal LV function. The effects of prolonged treatment with a β-blocker are unknown. Forty Wistar rats with severe AR were divided into 2 groups of 20 animals each and treated with metoprolol (Met, 25 mg·kg−1·day−1) or left untreated for 1 yr. LV remodeling was evaluated by echocardiography. Survival was assessed by Kaplan-Meir curves. Hearts were harvested for tissue analysis. All Met-treated animals were alive after 6 mo vs. 70% of untreated animals. After 1 yr, 60% of Met-treated animals were alive vs. 35% of untreated animals ( P = 0.028). All deaths, except one, were sudden. There were no differences in LV ejection fraction (all >50%) or LV dimensions. LV mass tended to be lower in the Met-treated group. There was less subendocardial fibrosis in this group, as well as lower LV filling pressures (LV end-diastolic pressure). β-Adrenergic receptor ratio (β1/β2) was improved. One year of treatment with Met was well tolerated. Met improved 1-yr survival, minimized LV hypertrophy, improved LV filling pressures, decreased LV subendocardial fibrosis, and helped restore the β-adrenergic receptor ratio.

Effects of L-thyroxine in rats with chronic heart failure after myocardial infarction

1987 ◽  
Vol 253 (2) ◽  
pp. H341-H346 ◽  
Author(s):  
R. Gay ◽  
T. A. Gustafson ◽  
S. Goldman ◽  
E. Morkin
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Pressure ◽  
Treated Group ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Myosin Isoenzyme ◽  
Pressure Development ◽  
Isoenzyme Composition

The effects of thyroid hormone on left ventricular (LV) function and myosin isoenzyme distribution were evaluated in rats 3 wk after myocardial infarction. When compared with normal rats, animals selected for study had moderately severe LV dysfunction as judged by decreased aortic and LV systolic pressures and a 34% decrease in LV maximum rate of pressure development (dP/dt). Average LV end-diastolic pressure was increased to 26 +/- 1 mmHg from 5 +/- 1 mmHg. The infarcted rats were divided into saline-treated control (n = 10) and treatment (n = 13) groups. The latter group received thyroxine (T4, 1.5 micrograms/100 g body wt) immediately after the first determination of pressures and at 24 and 48 h. At 72 h, aortic and LV pressures and myosin isoenzyme composition were measured. In the thyroxine-treated group LV end-diastolic pressure decreased from 27 +/- 2 to 18 +/- 2 mmHg, and LV dP/dt increased from 5,627 +/- 249 to 6,064 +/- 355 mmHg/s. Heart rate and aortic pressure did not change. After saline injections, LV end-diastolic pressure remained elevated, and the other hemodynamic parameters were unchanged. Determination of ventricular myosin isoenzyme composition in the saline-treated group revealed an increase in the V3 myosin isoform and a decrease in the V1 isoform as compared with the normal values. This pattern was not altered by T4 treatment. A separate group (n = 7) of rats was treated with a 10 times larger dose of thyroxine (15 micrograms/100 g body wt) for the same period of time. In this group, there was neither hemodynamic improvement nor changes in myosin isoenzyme distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

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