Left ventricular spherical dilation and regional contractile dysfunction in dogs with heart failure

1997 ◽  
Vol 273 (3) ◽  
pp. H1058-H1067 ◽  
Author(s):  
M. Suzuki ◽  
C. P. Cheng ◽  
N. Ohte ◽  
W. C. Little
Keyword(s):  
Heart Failure ◽  
Structural Changes ◽  
Contractile Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
End Diastolic Volume ◽  
Work Area ◽  
Rv Pacing ◽  
Volume Relation

Left ventricular (LV) short- and long-axis contractile function and LV structural changes were serially measured in eight instrumented dogs during the development of congestive heart failure (CHF) induced by rapid right ventricular (RV) pacing. After 10 days of pacing, LV end-diastolic volume (VED) had not increased; however, the slope of LV end-systolic pressure-volume relation had decreased from 7.4 +/- 2.6 to 4.9 +/- 1.1 mmHg/ml (P < 0.05), and the slope of LV stroke work-VED relation had fallen from 78.4 +/- 9.1 to 64.2 +/- 7.2 mmHg (P < 0.05). The slopes of end-systolic pressure-dimension relation and the stroke work area-end-diastolic dimension relation in the short axes (i.e., anteroposterior and septal-lateral) had decreased by 30% (P < 0.05), whereas the slopes of the long-axis (i.e., apical-basal) relations were unchanged (not significant). After 20 days of pacing, VED had significantly increased by 14% due to selective dilation of the short axes by 7%, and LV global contractility had further declined with a 40% contractile depression in the short axes and a 25% contractile depression in the long axis. After 30 days, the long-axis dimension at end diastole was also significantly increased with a further increase in the short-axis dimensions. In contrast to the spherical dilation occurring during CHF, acute volume loading of normal animals produced symmetrical LV dilation. These observations suggest that heterogeneous contractile depression initiates the spherical end-diastolic chamber dilation in pacing-induced CHF.

scholarly journals Altered LV inotropic reserve and mechanoenergetics early in the development of heart failure

2000 ◽  
Vol 278 (3) ◽  
pp. H698-H705 ◽  
Author(s):  
Sumanth D. Prabhu ◽  
Gregory L. Freeman
Keyword(s):  
Heart Failure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Short Term ◽  
Before And After ◽  
Autonomic Blockade ◽  
Anesthetized Dogs ◽  
Rapid Ventricular Pacing ◽  
Volume Relation

To test the hypothesis that alterations in left ventricular (LV) mechanoenergetics and the LV inotropic response to afterload manifest early in the evolution of heart failure, we examined six anesthetized dogs instrumented with LV micromanometers, piezoelectric crystals, and coronary sinus catheters before and after 24 h of rapid ventricular pacing (RVP). After autonomic blockade, the end-systolic pressure-volume relation (ESPVR), myocardial O2 consumption (MV˙o 2), and LV pressure-volume area (PVA) were defined at several different afterloads produced by graded infusions of phenylephrine. Short-term RVP resulted in reduced preload with proportionate reductions in stroke work and the maximum first derivative of LV pressure but with no significant reduction in baseline LV contractile state. In response to increased afterload, the baseline ESPVR shifted to the left with maintained end-systolic elastance ( E es). In contrast, after short-term RVP, in response to comparable increases in afterload, the ESPVR displayed reduced E es ( P < 0.05) and significantly less leftward shift compared with control ( P< 0.05). Compared with the control MV˙o 2-PVA relation, short-term RVP significantly increased the MV˙o 2 intercept ( P< 0.05) with no change in slope. These results indicate that short-term RVP produces attenuation of afterload-induced enhancement of LV performance and increases energy consumption for nonmechanical processes with maintenance of contractile efficiency, suggesting that early in the development of tachycardia heart failure, there is blunting of length-dependent activation and increased O2requirements for excitation-contraction coupling, basal metabolism, or both. Rather than being adaptive mechanisms, these abnormalities may be primary defects involved in the progression of the heart failure phenotype.

scholarly journals Linearity of the left ventricular end-systolic pressure-volume relation in patients with severe heart failure

1989 ◽  
Vol 14 (1) ◽  
pp. 127-134 ◽  
Author(s):  
Constantine N. Aroney ◽  
Howard C. Herrmann ◽  
Marc J. Semigran ◽  
G. William ◽  
Charles A. Boucher ◽  
...  
Keyword(s):  
Heart Failure ◽  
Severe Heart Failure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Volume Relation

Left ventricular-arterial coupling in conscious dogs

1991 ◽  
Vol 261 (1) ◽  
pp. H70-H76 ◽  
Author(s):  
W. C. Little ◽  
C. P. Cheng
Keyword(s):  
Stroke Volume ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Arterial System ◽  
Conscious Dogs ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Inotropic State ◽  
End Diastolic Volume ◽  
Wide Range

We investigated the criteria for the coupling of the left ventricle (LV) and the arterial system to maximize LV stroke work (SW) and the transformation of LV pressure-volume area (PVA) to SW. We studied eight conscious dogs that were instrumented to measure LV pressure and determine LV volume from three ultrasonically determined dimensions. The LV end-systolic pressure (PES)-volume (VES) relation was determined by caval occlusion. Its slope (EES) was compared with the arterial elastance (EA) and determined as PES per stroke volume. At rest, with intact reflexes, EES/EA was 0.96 +/- 0.20 EES/EA was varied over a wide range (0.18-2.59) by the infusion of graded doses of phenylephrine and nitroprusside before and during administration of dobutamine. Maximum LV SW, at constant inotropic state and end-diastolic volume (VED), occurred when EES/EA equaled 0.99 +/- 0.15. At constant VED and contractile state, SW was within 20% of its maximum value when EES/EA was between 0.56 and 2.29. The conversion of LV PVA to SW increased as EES/EA increased. The shape of the observed relations of the SW to EES/EA and SW/PVA to EES/EA was similar to that predicted by the theoretical consideration of LV PES-VES and arterial PES-stroke volume relations. We conclude that the LV and arterial system produce maximum SW at constant VED when EES and EA are equal; however, the relation of SW to EES/EA has a broad plateau. Only when EA greatly exceeds EES does the SW fall substantially. However, the conversion of PVA to SW increases as EES/EA increases. These observations support the utility of analyzing LV-arterial coupling in the pressure-volume plane.

Direct cardiac effects of vasopressin and their reversal by a vascular antagonist

1986 ◽  
Vol 251 (4) ◽  
pp. H734-H741 ◽  
Author(s):  
W. A. Boyle ◽  
L. D. Segel
Keyword(s):  
Coronary Flow ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Total Output ◽  
Stroke Work ◽  
Cardiac Effects ◽  
Myocardial O2 Consumption ◽  
Dose Dependent

We studied the direct cardiac effects of arginine vasopressin (AVP) by use of an isolated working rat heart model perfused with Krebs-Henseleit medium. At a concentration of 878 +/- 15 pg/ml, AVP produced significant (P less than 0.05) decreases in coronary flow (-31 +/- 2%); myocardial O2 consumption (-12 +/- 2%); left ventricular peak systolic pressure (-5 +/- 1%); dP/dtmax (-7 +/- 1%); -dP/dtmax (-6 +/- 3%); peak aortic flow rate (-5 +/- 1%); stroke work (-3 +/- 1%); peak power (-8 +/- 1%); and total output (-3 +/- 1%). Aortic output increased significantly (+7 +/- 1%) as did arteriovenous O2 difference (+108 +/- 14 mmHg); left ventricular end-diastolic pressure (+0.4 +/- 0.1 mmHg); efficiency (+1.5 +/- 0.4%); and rate of lactate release (+1.27 +/- 0.21 nmol/ml perfusate/min). Dose-response relationships were studied at 9 +/- 1, 25 +/- 1, 75 +/- 3, 303 +/- 15, and 817 +/- 42 pg AVP/ml. Significant dose-dependent depression of coronary flow occurred at the three highest AVP concentrations; cardiac function was significantly depressed at the highest dose. The AVP analogue d(CH2)5[Tyr(Me)]AVP (20 ng/ml) completely reversed the cardiac effects attributed to AVP. The data indicate that AVP is a potent direct coronary constrictor that produces myocardial ischemia and decreased contractile function at AVP concentrations that are observed in some pathophysiologic states.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of coupled pacing on cardiac performance during acute atrial tachycardia and fibrillation: an old therapy revisited for a new reason

2003 ◽  
Vol 285 (6) ◽  
pp. H2630-H2638 ◽  
Author(s):  
Hirotsugu Yamada ◽  
David O. Martin ◽  
Kent A. Mowrey ◽  
Neil L. Greenberg ◽  
Don W. Wallick
Keyword(s):  
Atrial Tachycardia ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Ventricular Rate ◽  
Atrial Pacing ◽  
Stroke Work ◽  
End Diastolic Volume ◽  
Work Area ◽  
Pressure Development ◽  
Ventricular Activation

Atrial tachycardia (AT) and fibrillation (AF) result in rapid ventricular rates that are detrimental to optimal cardiac function. The purpose of this study was to determine whether the application of a coupled pacing (CP) regimen would improve ventricular function by decreasing the ventricular rate of mechanical contractions (VRMCs). We simulated AT by pacing either atrium at a rate that resulted in a rapid but regular ventricular rate in seven anesthetized dogs. AF was induced by increasing the atrial pacing rate until atrial activation did not follow the pacing. After the induction of either AT or AF, we applied CP after each intrinsic ventricular activation. We measured the VRMCs and left ventricular (LV) pressures and volumes via a pressure-conductance catheter. The marked reductions in VRMCs during CP resulted in increases in LV end-diastolic volume. The CP resulted in virtually no mechanical contractions, whereas the strength of contractions from the normal electrical activation increased. The increases in the positive LV rate of pressure development over time and LV ejection fraction during CP were the result of postextrasystolic potentiation. The average stroke work (area of the pressure-volume loops) increased as a result of CP during both AT and AF. Despite the large increases in stroke volume (≅2×) during CP, the changes in cardiac output were moderate because the VRMCs markedly decreased (≅½). We conclude that CP therapy may be a viable therapy for slowing the heart rate and improving cardiac performance in patients with AT and AF.

scholarly journals Cardiac effects of endothelin receptor antagonism in endotoxemic pigs

2007 ◽  
Vol 293 (2) ◽  
pp. H988-H996 ◽  
Author(s):  
D. Konrad ◽  
M. Haney ◽  
G. Johansson ◽  
M. Wanecek ◽  
E. Weitzberg ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Contractile Function ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Stroke Work ◽  
Receptor Antagonism ◽  
Cardiac Effects ◽  
Beneficial Effects ◽  
End Diastolic Volume ◽  
Pressure Volume Relationship

Myocardial depression in sepsis is frequently encountered clinically and contributes to morbidity and mortality. Increased plasma levels of endothelin-1 (ET-1) have been described in septic shock, and previous reports have shown beneficial effects on cardiovascular performance and survival in septic models using ET receptor antagonists. The aim of the current study was to investigate specific cardiac effects of ET receptor antagonism in endotoxicosis. Sixteen domestic pigs were anesthetized and subjected to endotoxin for 5 h. Eight of these pigs were given tezosentan (dual ET receptor antagonist) after 3 h. Cardiac effects were evaluated using the left ventricular (LV) pressure-volume relationship. Endotoxin was not associated with any effects on parameters of LV contractile function [end-systolic elastance (Ees), preload recruitable stroke work (PRSW), powermax/end-diastolic volume (PWRmax/EDV) and dP/d tmax/end-diastolic volume (dP/d tmax/EDV)] but with impairments in isovolumic relaxation (time constant for pressure decay, tau) and mechanical efficiency. Tezosentan administration decreased Ees, PWRmax/EDV, and dP/d tmax/EDV, while improving tau and LV stiffness. Thus, dual ET receptor antagonism was associated with a decline in contractile function but, in contrast, improved diastolic function. Positive hemodynamic effects from ET receptor antagonism in acute endotoxemia may be due to changes in cardiac load and enhanced diastolic function rather than improved contractile function.

Effect of vasopressin on left ventricular performance

1993 ◽  
Vol 264 (1) ◽  
pp. H53-H60
Author(s):  
C. P. Cheng ◽  
Y. Igarashi ◽  
H. S. Klopfenstein ◽  
R. J. Applegate ◽  
Z. Shihabi ◽  
...  
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular ◽  
Systemic Resistance ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Ventricular Performance ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
End Systolic Volume ◽  
The Right

We assessed the effect of arginine vasopressin (AVP) on left ventricular (LV) performance in eight conscious dogs. Five minutes after AVP infusion (6 microns.kg-1 x min-1 for 2 min) the plasma AVP was elevated from 3.9 +/- 0.9 to 14.7 +/- 4.6 pg/ml (P < 0.05). With all reflexes intact, AVP caused significant increases in LV end-systolic pressure (P) (112 +/- 8 vs. 122 +/- 7 mmHg, P < 0.05) end-systolic volume (V) (30 +/- 5.8 vs. 38 +/- 7.7 ml, P < 0.05), total systemic resistance (6.2 +/- 1.8 vs. 10.6 +/- 4.0 mmHg.dl-1 x min, P < 0.01) and arterial elastance (Ea) (6.8 +/- 3.0 vs. 8.6 +/- 3.9 mmHg/ml, P < 0.05), while the heart rate (110 +/- 6 vs. 82 +/- 10 beats/min, P < 0.05) and stroke volume (16.5 +/- 4.3 vs. 14.2 +/- 3.9 ml, P < 0.05) were decreased. There was no significant change in the coronary sinus blood flow (82 +/- 19 vs. 78 +/- 22 ml/min, P = not significant). AVP decreased the slopes of LV end-systolic P-V relation (10.7 +/- 1.1 vs. 8.1 +/- 1.9 mmHg/ml, P < 0.05), the maximal first derivative of LV pressure (dP/dtmax)-end-diastolic volume (VED) relation (135.2 +/- 18.7 vs. 63.1 +/- 7.7 mmHg.s-1 x ml-1, P < 0.05), and the stroke work-VED relation (81.1 +/- 4.1 vs. 66.7 +/- 2.8 mmHg, P < 0.05) and shifted the relations to the right, indicating a depression of LV performance. A similar increase in Ea produced by methoxamine did not depress LV performance.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Endotoxin impairs cardiac hemodynamics by affecting loading conditions but not by reducing cardiac inotropism

2010 ◽  
Vol 299 (2) ◽  
pp. H492-H501 ◽  
Author(s):  
Li Jianhui ◽  
Nathalie Rosenblatt-Velin ◽  
Noureddine Loukili ◽  
Pal Pacher ◽  
François Feihl ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Laboratory Animals ◽  
Lv Function ◽  
Stroke Work ◽  
Loading Conditions ◽  
Arterial Elastance ◽  
End Diastolic Volume

Acute myocardial dysfunction is a typical manifestation of septic shock. Experimentally, the administration of endotoxin [lipopolysacharride (LPS)] to laboratory animals is frequently used to study such dysfunction. However, a majority of studies used load-dependent indexes of cardiac function [including ejection fraction (EF) and maximal systolic pressure increment (dP/d tmax)], which do not directly explore cardiac inotropism. Therefore, we evaluated the direct effects of LPS on myocardial contractility, using left ventricular (LV) pressure-volume catheters in mice. Male BALB/c mice received an intraperitoneal injection of E. coli LPS (1, 5, 10, or 20 mg/kg). After 2, 6, or 20 h, cardiac function was analyzed in anesthetized, mechanically ventilated mice. All doses of LPS induced a significant drop in LV stroke volume and a trend toward reduced cardiac output after 6 h. Concomitantly, there was a significant decrease of LV preload (LV end-diastolic volume), with no apparent change in LV afterload (evaluated by effective arterial elastance and systemic vascular resistance). Load-dependent indexes of LV function were markedly reduced at 6 h, including EF, stroke work, and dP/d tmax. In contrast, there was no reduction of load-independent indexes of LV contractility, including end-systolic elastance (ejection phase measure of contractility) and the ratio dP/d tmax/end-diastolic volume (isovolumic phase measure of contractility), the latter showing instead a significant increase after 6 h. All changes were transient, returning to baseline values after 20 h. Therefore, the alterations of cardiac function induced by LPS are entirely due to altered loading conditions, but not to reduced contractility, which may instead be slightly increased.

scholarly journals Levosimendan restores the positive force-frequency relation in heart failure

2011 ◽  
Vol 301 (2) ◽  
pp. H488-H496 ◽  
Author(s):  
Satoshi Masutani ◽  
Heng-Jie Cheng ◽  
Hideo Tachibana ◽  
William C. Little ◽  
Che-Ping Cheng
Keyword(s):  
Heart Failure ◽  
Contractile Function ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Force Frequency ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Major Mechanism ◽  
Frequency Relation ◽  
Positive Force

Frequency potentiation of contractile function is a major mechanism of the increase in myocardial performance during exercise. In heart failure (HF), this positive force-frequency relation is impaired, and the abnormal left ventricular (LV)-arterial coupling is exacerbated by tachycardia. A myofilament Ca2+ sensitizer, levosimendan, has been shown to improve exercise tolerance in HF. This may be due to its beneficial actions on the force-frequency relation and LV-arterial coupling (end-systolic elastance/arterial elastance, EES/ EA). We assessed the effects of therapeutic doses of levosimendan on the force-frequency relation and EES/ EA in nine conscious dogs after pacing-induced HF using pressure-volume analysis. Before HF, pacing tachycardia increased EES, shortened τ, and did not impair EES/ EA and mechanical efficiency (stroke work/pressure-volume area, SW/PVA). In contrast, after HF, pacing at 140, 160, 180, and 200 beat/min (bpm) produced smaller a increase of EES or less shortening of τ, whereas EES/ EA (from 0.56 at baseline to 0.42 at 200 bpm) and SW/PVA (from 0.52 at baseline to 0.43 at 200 bpm) progressively decreased. With levosimendan, basal EES increased 27% (6.2 mmHg/ml), τ decreased 11% (40.8 ms), EES/ EA increased 34% (0.75), and SW/PVA improved by 15% (0.60). During tachycardia, EES further increased by 23%, 37%, 68%, and 89%; τ decreased by 9%, 12%, 15%, and 17%; and EES/ EA was augmented by 11%, 16%, 31%, and 33%, incrementally, with pacing rate. SW/PVA was improved (0.61 to 0.64). In conclusion, in HF, treatment with levosimendan restores the normal positive LV systolic and diastolic force-frequency relation and prevents tachycardia-induced adverse effect on LV-arterial coupling and mechanical efficiency.

Abstract 14613: Preclinical Animal Model of Doxorubicin-induced Left Ventricular Dysfunction: Echocardiography and Pressure-volume Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Petr Kala ◽  
Zuzana Honetschlagerova ◽  
Zuzana Huskova ◽  
Zdenka Vanourkova ◽  
Petra Škaroupková ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Model ◽  
Left Ventricle ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Cardiac Efficiency ◽  
Volume Analysis

Introduction: There is a need to implement a preclinical model in addition to the well established ischemic or volume-overload models that would mimic the clinical course of patients with chemotherapy-induced heart failure. Doxorubicin is an anthracycline chemotherapeutic that is widely used in oncology, although its cardiotoxicity. Hypothesis: Doxorubicin-induced left ventricular dysfunction in rats fulfills echocardiography and hemodynamic characteristics of chemotherapy-induced heart failure. Methods: We randomly assigned Ren-2 transgenic hypertensive (TGR, n = 17) and normotensive rats (HanSD, n = 22), at the age of 8 weeks to doxorubicin (2.5 mg/kg in 0.5 ml of normal saline) or placebo in 6 intraperitoneal doses within two weeks (cumulative doxorubicin dose 15 mg/kg). Two weeks later, we performed echocardiography study, pressure-volume analysis (PV), and we weighed the organs. Results: In doxorubicin groups, there was a decrease in the left ventricle weight (1,22 vs. 0,85 g in TGR), while an increase in wall stress (22036 vs. 29754 μL*mmHg/g in TGR). Echocardiography suggested heart remodeling with a decrease in relative wall thickness - RWT (1.02 vs. 0.65 mm in TGR), and together with PV analysis showed a decrease in systolic parameters - left ventricle ejection fraction - LVEF (71.41 vs. 59.96 % in TGR), end-systolic pressure-volume ratio - ESPVR (0.82 vs. 0.45 mmHg/uL in TGR) and preload recruitable stroke work - PRSW (75.71 vs. 60.98 mmHg in TGR). Ventricular-arterial coupling (VAC = Ea/Ees, a measure of cardiac efficiency) was worsened in the doxorubicin groups (1.69 vs. 2.52 in TGR). For all the above p < 0.05, in HanSD, the results were similar (all p < 0.05). Conclusions: Our results suggest that systolic dysfunction and decrease of cardiac efficiency in this model could be caused by heart atrophy, and such an animal model could potentially be an easily reproducible model of chemotherapy-induced heart failure in preclinical cardio-oncology studies.

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