Captopril reduces left ventricular enlargement induced by chronic volume overload

1990 ◽  
Vol 259 (3) ◽  
pp. H796-H803
Author(s):  
R. G. Gay
Keyword(s):  
Pulse Pressure ◽  
Diastolic Pressure ◽  
Ex Vivo ◽  
Volume Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Aortic Occlusion ◽  
End Diastolic Volume ◽  
Volume Relation ◽  
Captopril Treatment

The effect of captopril treatment on left ventricular (LV) function, mass, and volume during chronic volume overload induced by production of aortic insufficiency (AI) was studied. AI was caused by mechanical disruption of the aortic valve in 175- to 225-g male Sprague-Dawley rats. At 24 h after surgery, AI and sham-operated rats were divided into control and captopril treatment (2 g/l drinking water) groups. After 2 mo of treatment, hemodynamics were measured in open-chest rats, and the LV pressure-volume relation was determined ex vivo. Compared with sham-operated rats, in the untreated AI rats, aortic pulse pressure was increased nearly 100%, LV end-diastolic pressure was 10 +/- 1 vs 3 +/- 1 mmHg, and LV end-diastolic volume was 1.25 +/- 0.07 vs 0.36 +/- 0.03 ml. LV weight was increased 43% and the LV pressure-volume relation was shifted rightward by AI. LV systolic and diastolic wall stress were increased in rats with AI. Peak LV pressure during aortic occlusion was decreased in AI rats, however, peak wall stress during aortic occlusion was not different compared with sham-operated rats. Captopril treatment decreased aortic pulse pressure and LV systolic pressure. Both LV weight and LV end-diastolic volume measured from the ex vivo pressure-volume relation at LV end-diastolic pressure were increased by 33% in untreated AI rats compared with captopril-treated AI rats. Captopril treatment of AI rats shifted the LV pressure-volume to the left compared with untreated rats. LV pressure and wall stress during aortic occlusion were not changed in captopril-treated AI rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Trabecular cutting: a novel surgical therapy to increase diastolic compliance

2019 ◽  
Vol 127 (2) ◽  
pp. 457-463
Author(s):  
Meagan Oglesby ◽  
Danny Escobedo ◽  
Gladys Patricia Escobar ◽  
Fatemeh Fatemifar ◽  
Edward Y. Sako ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Diastolic Pressure ◽  
Ex Vivo ◽  
Systolic Function ◽  
Wall Stress ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Before And After ◽  
Diastolic Compliance

Heart failure with preserved ejection fraction (HFpEF) is a common cause of hospital admission in patients over 65 yr old and has high mortality. HFpEF is characterized by left ventricular (LV) hypertrophy that reduces compliance. Current HFpEF therapies control symptoms, but no existing medications or therapies can sustainably increase LV compliance. LV trabeculae develop hypertrophy and fibrosis that contribute to reduced LV compliance. This study expands our previous results in ex vivo human hearts to show that severing LV trabeculae increases diastolic compliance in an ex vivo working rabbit heart model. Trabecular cutting was performed in ex vivo rabbit hearts set up in a working heart perfusion system perfused with oxygenated Krebs-Henseleit buffer. A hook was inserted in the LV to cut trabeculae. End-systolic and end-diastolic pressure-volume relationships during transient preload reduction were recorded using an admittance catheter in the following three groups: control (no cutting; n = 9), mild cutting (15 cuts; n = 5), and aggressive cutting (30 cuts; n = 5). In a second experiment, each heart served as its own control. Hemodynamic data were recorded before and after trabecular cutting ( n = 10) or sham cutting ( n = 5) within the same heart. In the first experiments, trabecular cutting did not affect systolic function ( P > 0.05) but significantly increased overall diastolic compliance ( P = 0.009). Greater compliance was seen as trabecular cutting increased ( P = 0.002, r2 = 0.435). In the second experiment, significant increases in systolic function ( P = 0.048) and diastolic compliance ( P = 0.002) were seen after trabecular cutting compared with baseline. In conclusion, trabecular cutting significantly increases diastolic compliance without reducing systolic function. NEW & NOTEWORTHY We postulate that, in mammalian hearts, free-running trabeculae carneae exist to provide tensile support to the left ventricle and minimize diastolic wall stress. Because of hypertrophy and fibrosis of trabeculae in patients with left ventricular hypertrophy, this supportive role can become pathologic, worsening diastolic compliance. We demonstrate a novel operation involving cutting trabeculae as a method to acutely increase diastolic compliance in patients presenting with heart failure and diastolic dysfunction to improve their left ventricle compliance.

Volume overload hypertrophy in a closed-chest model of mitral regurgitation

1988 ◽  
Vol 254 (6) ◽  
pp. H1034-H1041 ◽  
Author(s):  
J. P. Kleaveland ◽  
W. G. Kussmaul ◽  
T. Vinciguerra ◽  
R. Diters ◽  
B. A. Carabello
Keyword(s):  
Cardiac Output ◽  
Mitral Regurgitation ◽  
Diastolic Pressure ◽  
Volume Ratio ◽  
Volume Overload ◽  
Canine Model ◽  
Left Ventricular ◽  
Closed Chest ◽  
Cardiac Decompensation ◽  
End Diastolic Volume

Chronic volume overload hypertrophy as seen in mitral regurgitation in humans eventually may cause left ventricular dysfunction. Longitudinal study of the mechanisms leading to such dysfunction is difficult in humans and more easily performed in an animal model. In this study, we describe a canine model of volume overload hypertrophy produced by mitral regurgitation. An arterially placed grasping forceps was used to disrupt mitral chordae or leaflets; thus mitral regurgitation was produced without the need for thoracotomy. Eleven of 22 dogs had severe mitral regurgitation (regurgitant fraction greater than 0.50) and survived for greater than or equal to 3 mo (average 9.2 +/- 6 mo) after the production of mitral regurgitation. At 3 mo, end-diastolic volume increased from 48 +/- 9 to 85 +/- 19 ml, P less than 0.01. Left ventricular mass increased from 71 +/- 13 to 90 +/- 10 g, P less than 0.01. Left ventricular end-diastolic pressure increased from 9 +/- 3 to 19 +/- 6 mmHg, P less than 0.01. Cardiac output decreased from 2.3 +/- 0.61 to 1.80 +/- 0.64 l/min, P less than 0.05. The mass-to-volume ratio decreased from 1.44 +/- 0.17 to 1.09 +/- 0.13, P less than 0.01. We conclude that this closed-chest model of chronic mitral regurgitation produces significant eccentric cardiac hypertrophy. Despite a doubling of end-diastolic volume, there was a fall in cardiac output and a rise in left ventricular end-diastolic pressure, suggesting cardiac decompensation.

scholarly journals Xanthine oxidase inhibition preserves left ventricular systolic but not diastolic function in cardiac volume overload

2013 ◽  
Vol 305 (10) ◽  
pp. H1440-H1450 ◽  
Author(s):  
James D. Gladden ◽  
Blake R. Zelickson ◽  
Jason L. Guichard ◽  
Mustafa I. Ahmed ◽  
Danielle M. Yancey ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Severe Heart Failure ◽  
Volume Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Lv Function ◽  
Lung Weight ◽  
Twofold Increase

Xanthine oxidase (XO) is increased in human and rat left ventricular (LV) myocytes with volume overload (VO) of mitral regurgitation and aortocaval fistula (ACF). In the setting of increased ATP demand, XO-mediated ROS can decrease mitochondrial respiration and contractile function. Thus, we tested the hypothesis that XO inhibition improves cardiomyocyte bioenergetics and LV function in chronic ACF in the rat. Sprague-Dawley rats were randomized to either sham or ACF ± allopurinol (100 mg·kg−1·day−1, n ≥7 rats/group). Echocardiography at 8 wk demonstrated a similar 37% increase in LV end-diastolic dimension ( P < 0.001), a twofold increase in LV end-diastolic pressure/wall stress ( P < 0.05), and a twofold increase in lung weight ( P < 0.05) in treated and untreated ACF groups versus the sham group. LV ejection fraction, velocity of circumferential shortening, maximal systolic elastance, and contractile efficiency were significantly depressed in ACF and significantly improved in ACF + allopurinol rats, all of which occurred in the absence of changes in the maximum O2 consumption rate measured in isolated cardiomyocytes using the extracellular flux analyzer. However, the improvement in contractile function is not paralleled by any attenuation in LV dilatation, LV end-diastolic pressure/wall stress, and lung weight. In conclusion, allopurinol improves LV contractile function and efficiency possibly by diminishing the known XO-mediated ROS effects on myofilament Ca2+ sensitivity. However, LV remodeling and diastolic properties are not improved, which may explain the failure of XO inhibition to improve symptoms and hospitalizations in patients with severe heart failure.

scholarly journals Ventricular interaction and external constraint account for decreased stroke work during volume loading in CHF

2001 ◽  
Vol 281 (6) ◽  
pp. H2385-H2391 ◽  
Author(s):  
Thomas D. Moore ◽  
Michael P. Frenneaux ◽  
Rozsa Sas ◽  
J. J. Atherton ◽  
Jayne A. Morris-Thurgood ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Left Ventricular ◽  
Negative Slope ◽  
Segment Length ◽  
Stroke Work ◽  
Volume Loading ◽  
End Diastolic Volume ◽  
Pulmonary Capillary ◽  
Apparent Decrease ◽  
Pericardial Pressure

The slope of the stroke work (SW)-pulmonary capillary wedge pressure (PCWP) relation may be negative in congestive heart failure (CHF), implying decreased contractility based on the premise that PCWP is simply related to left ventricular (LV) end-diastolic volume. We hypothesized that the negative slope is explained by decreased transmural LV end-diastolic pressure (LVEDP), despite the increased LVEDP, and that contractility remains unchanged. Rapid pacing produced CHF in six dogs. Hemodynamic and dimension changes were then measured under anesthesia during volume manipulation. Volume loading increased pericardial pressure and LVEDP but decreased transmural LVEDP and SW. Right ventricular diameter increased and septum-to-LV free wall diameter decreased. Although the slopes of the SW-LVEDP relations were negative, the SW-transmural LVEDP relations remained positive, indicating unchanged contractility. Similarly, the SW-segment length relations suggested unchanged contractility. Pressure surrounding the LV must be subtracted from LVEDP to calculate transmural LVEDP accurately. When this was done in this model, the apparent decrease in contractility was no longer evident. Despite the increased LVEDP during volume loading, transmural LVEDP and therefore SW decreased and contractility remained unchanged.

Severe myocardial dysfunction induced by ventricular remodeling in aging rat hearts

1990 ◽  
Vol 259 (4) ◽  
pp. H1086-H1096 ◽  
Author(s):  
J. M. Capasso ◽  
T. Palackal ◽  
G. Olivetti ◽  
P. Anversa
Keyword(s):  
Ventricular Remodeling ◽  
Volume Fraction ◽  
Diastolic Pressure ◽  
Structural Characteristics ◽  
Myocardial Dysfunction ◽  
Pressure Rise ◽  
Wall Stress ◽  
Left Ventricular ◽  
Cross Sectional

To determine if aging engenders alterations in the functional properties of the myocardium and ventricular remodeling, the hemodynamic performance and structural characteristics of the left ventricle of male Fischer 344 rats at 4, 12, 20, and 29 mo of age were studied by quantitative physiology and morphology. In vivo assessment of cardiac pump function showed no change up to 20 mo, whereas left ventricular end-diastolic pressure was increased at 29 mo. Moreover, peak rates of pressure rise and decay, stroke volume, ejection fraction, and cardiac output were depressed at the later age interval, demonstrating the presence of ventricular failure at this time. The measurements of chamber size and wall thickness showed that ventricular end-diastolic and end-systolic volumes progressively increased with age with the greatest change occurring at 20-29 mo. Aging was also accompanied by a marked augmentation in the volume fraction of fibrotic areas in the ventricular myocardium that was due to an increase in their number and cross-sectional area with time. These architectural rearrangements, in combination with the abnormalities in ventricular function, resulted in an elevation in the volume of wall stress throughout the cardiac cycle. Wall stress increased by 64, 44, and 50% from 4 to 12, 12 to 20, and 20 to 29 mo of age. In conclusion, aging leads to a continuous rise in wall stress that is not normalized by ventricular remodeling. These two independent processes appear to be responsible for the onset of heart failure in the senescent rat.

Left ventricular diastolic function of remodeled myocardium in dogs with pacing-induced heart failure

1998 ◽  
Vol 274 (3) ◽  
pp. H945-H954 ◽  
Author(s):  
Steven B. Solomon ◽  
Srdjan D. Nikolic ◽  
Stanton A. Glantz ◽  
Edward L. Yellin
Keyword(s):  
Heart Failure ◽  
Elastic Properties ◽  
Diastolic Pressure ◽  
Left Ventricular Diastolic Function ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Elastic Recoil ◽  
Systolic Volume ◽  
Left Ventricular Chamber ◽  
Volume Relation

In patients with heart failure, decreased contractility resulting in high end-diastolic pressures and a restrictive pattern of left ventricular filling produces a decrease in early diastolic filling, suggesting a stiff ventricle. This study investigated the elastic properties of the myocardium and left ventricular chamber and the ability of the heart to utilize elastic recoil to facilitate filling during pacing-induced heart failure in the anesthetized dog. Elastic properties of the myocardium were determined by analyzing the myocardial stress-strain relation. Left ventricular chamber properties were determined by analyzing the pressure-volume relation using a logarithmic approach. Elastic recoil was characterized using a computer-controlled mitral valve occluder to prevent transmitral flow during diastole. We conclude that, during heart failure, the high end-diastolic pressures suggestive of a stiff ventricle are due not to stiffer myocardium but to a ventricle whose chamber compliance characteristics are changed due to geometric remodeling of the myocardium. The restrictive filling pattern is a result of the ventricle being forced to operate on the stiff portion of the diastolic pressure-volume relation to maintain cardiac output. Slowed relaxation and decreased contractility result in an inability of the heart to contract to an end-systolic volume below its diastolic equilibrium volume. Thus the left ventricle cannot utilize elastic recoil to facilitate filling during heart failure.

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.

Aortic pressure reduction redistributes transmural blood flow in dog left ventricle

1988 ◽  
Vol 254 (2) ◽  
pp. H361-H368 ◽  
Author(s):  
J. J. Smolich ◽  
P. L. Weissberg ◽  
A. Broughton ◽  
P. I. Korner
Keyword(s):  
Blood Flow ◽  
Diastolic Pressure ◽  
Blood Pressure Reduction ◽  
Wall Stress ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Pressure Reduction ◽  
Flow Ratio ◽  
Flow Reserve ◽  
Aortic Blood Pressure

We studied the effect of graded aortic blood pressure reduction on left ventricular (LV) blood flow in anesthetized, autonomically blocked, open-chest dogs at constant heart rate and mean left atrial pressure. Aortic diastolic pressure (ADP) was lowered from rest (average 116 mmHg) to 90, 75, and 60 mmHg with an arteriovenous fistula. Global and regional LV blood flow was measured with radioactive microspheres. Mean LV blood flow fell stepwise from 145 ml.min-1.100 g-1 at rest to 116 ml.min-1.100 g-1 at ADP of 60 mmHg, whereas the endocardial-to-epicardial flow ratio decreased from 1.20 to 0.84. The transmural redistribution of LV blood flow was not accompanied by increases in LV oxygen extraction, depression of LV contractility, LV dilatation or LV electrical dysfunction and also occurred in the presence of considerable coronary vasodilator flow reserve. Electrical evidence of subendocardial ischemia appeared at ADP of 32 mmHg and an endocardial-to-epicardial flow ratio of 0.41 in a subgroup of animals. We conclude that the redistribution of LV flow during moderate aortic pressure reduction was an appropriate physiological adjustment to uneven transmural alterations in regional LV wall stress and that it preceded a more pronounced redistribution evident with myocardial ischemia.

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

2002 ◽  
Vol 282 (4) ◽  
pp. H1197-H1205 ◽  
Author(s):  
Michael J. Cox ◽  
Harpreet S. Sood ◽  
Matthew J. Hunt ◽  
Derrick Chandler ◽  
Jeffrey R. Henegar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blot Analysis ◽  
Diastolic Pressure ◽  
Volume Overload ◽  
Left Ventricular ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Lung Weight ◽  
Cardiac Relaxation

The hypothesis is that chronic increases in left ventricular (LV) load induce oxidative stress and latent matrix metalloproteinase (MMP) is activated, allowing the heart to dilate in the absence of endothelial nitric oxide (NO) and thereby reduce filling pressure. To create volume overload, an arteriovenous (A-V) fistula was placed in male Sprague-Dawley rats. To decrease oxidative stress and apoptosis, 0.08 mg/ml nicotinamide (Nic) was administered in drinking water 2 days before surgery. The rats were divided into the following groups: 1) A-V fistula, 2) A-V fistula + Nic, 3) sham operated, 4) sham + Nic, and 5) control (unoperated); n = 6 rats/group. After 4 wk, hemodynamic parameters were measured in anesthetized rats. The heart was removed and weighed, and LV tissue homogeneates were prepared. A-V fistula caused an increase in heart weight, lung weight, and end-diastolic pressure compared with the sham group. The levels of malondialdehyde (MDA; a marker of oxidative stress) was 6.60 ± 0.23 ng/mg protein and NO was 6.87 ± 1.21 nmol/l in the LV of A-V fistula rats by spectrophometry. Nic treatment increased NO to 13.88 ± 2.5 nmol/l and decreased MDA to 3.54 ± 0.34 ng/mg protein ( P= 0.005). Zymographic levels of MMP-2 were increased, as were protein levels of nitrotyrosine and collagen fragments by Western blot analysis. The inhibition of oxidative stress by Nic decreased nitrotyrosine content and MMP activity. The levels of tissue inhibitor of metalloproteinase-4 mRNA were decreased in A-V fistula rats and increased in A-V fistula rats treated with Nic by Northern blot analysis. TdT-mediated dUTP nick-end labeling-positive cells were increased in A-V fistula rats and decreased in fistula rats treated with Nic. Acetylcholine and nitroprusside responses in cardiac rings prepared from the above groups of rats suggest impaired endothelial-dependent cardiac relaxation. Treatment with Nic improves cardiac relaxation. The results suggest that an increase in the oxidative stress and generation of nitrotyrosine are, in part, responsible for the activation of metalloproteinase and decreased endocardial endothelial function in chronic LV volume overload.

scholarly journals Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload

2000 ◽  
Vol 279 (6) ◽  
pp. H2939-H2946 ◽  
Author(s):  
Hiroshi Yamakawa ◽  
Takuroh Imamura ◽  
Takeshi Matsuo ◽  
Hisamitsu Onitsuka ◽  
Yoko Tsumori ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Channel Blocker ◽  
Volume Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Expression Level ◽  
Ang Ii ◽  
Similar Extent

We investigated the effects of diastolic wall stress (WS) and angiotensin II (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial natriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologically manipulated with (candesartan) or without (calcium channel blocker manidipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats over 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manidipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene expression increased as LVH developed but were completely suppressed by candesartan over 6 wk. ANP expression level was also attenuated by manidipine over 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload and that diastolic WS could be relatively involved in the early LVH and in the gene expression of ANP rather than of AM.

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