Differential effects of EMD-53998 on calcium-pressure relationship in normal and ischemic guinea pig heart

1996 ◽  
Vol 271 (1) ◽  
pp. H311-H319
Author(s):  
R. Ishisu ◽  
Y. Abe ◽  
K. Onishi ◽  
K. Sekioka ◽  
T. Nakano
Keyword(s):  
Guinea Pig ◽  
Diastolic Pressure ◽  
Relative Increase ◽  
Left Ventricular ◽  
Low Flow ◽  
Lv Function ◽  
Contractile Dysfunction ◽  
Guinea Pig Heart ◽  
Emd 53998 ◽  
Contractile Failure

We investigated the effects of EMD-53998 and digoxin on Ca2+ transients and left ventricular (LV) function in indo 1-loaded Langendorff guinea pig hearts. EMD-53998 (10(-9) to 10(-5) M) and digoxin (10(-10) to 10(-6) M) increased +dP/dt and Ca2+ transients in normal hearts. The relative increase in Ca2+ transients by EMD-53998 was similar to digoxin. At 10(-5) M, EMD-53998 increased LV end-diastolic pressure. Low-flow ischemia decreased +dP/dt by 50%, while indo 1 ratio increased by 10-25%. EMD-53998 (10(-9) to 10(-6) M) effectively restored the depressed +dP/dt with little effect on indo 1 ratio, but at 10(-5) M, it markedly elevated LV end-diastolic pressure and the beneficial effect on contractile dysfunction disappeared. Digoxin (10(-10) to 10(-7) M) failed to improve LV function, but at 10(-6) M, it restored contractile dysfunction with a large increase in indo 1 ratio. The relation between indo 1 ratio and +dP/dt clearly showed that EMD-53998 restored contractile dysfunction by Ca2+ sensitization. These findings suggest that Ca2+ sensitization by EMD-53998 is an advantageous approach for ischemic contractile failure but impairs diastolic function.

Abstract 9439: Invasive Evaluation of Left Ventricular Hemodynamics with Veno-Arterial Extracorporeal Membrane Oxygenation

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Rajat Kalra ◽  
Tamas Alexy ◽  
Jason Bartos ◽  
Andrea M Elliott ◽  
Anthony Prisco ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Ecmo Support ◽  
Low Flow ◽  
Lv Function ◽  
Stroke Work ◽  
Membrane Oxygenation ◽  
End Diastolic Volume ◽  
Va Ecmo

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a frequently used hemodynamic support strategy, but considerable debate exists about its hemodynamic effects. We evaluated changes in left ventricular (LV) function, volumes, and work in patients treated with VA-ECMO using invasive LV catheterization and three-dimensional echocardiographic volumes. Methods: In this case series, patients underwent evaluation due to persistent vasoplegia or poor LV function despite treatment with VA-ECMO. Hemodynamic parameters were reported as medians with interquartile ranges. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA-ECMO support. Results: Six patients aged 53.5 (41.8, 57.8) years were included. Three patients received VA-ECMO for refractory cardiogenic shock and three patients for extracorporeal cardiopulmonary resuscitation. The baseline LV ejection fraction was 22.1% (19.0%, 24.7%). The baseline and lowest VA-ECMO flows were 4.0 (4.0, 4.0) L/min and 1.0 (1.0, 1.5) L/min, respectively. Compared to the lowest flow, full VA-ECMO support reduced LV end-diastolic volume [116 (90, 153) versus 94 (58, 119) mL, p=0.03], LV end-diastolic pressure [16 (12, 24) versus 14 (9,15) mmHg, p=0.03], LV stroke work [2640 (1800, 4275) versus 1953 (759, 2179) mL*mmHg, p=0.03], and pressure-volume area [6864 (4038, 7715) versus 4575 (3142, 5888) mL*mmHg; p=0.046], respectively. The pressure-volume curves at the highest and lowest VA-ECMO flows are represented in blue and red, respectively ( Figure ). Mean arterial pressure and heart rate were similar at the lowest and highest flows (p=0.17 and p=0.60, respectively). All patients were decannulated from VA-ECMO. Four survived the index hospitalization. Conclusion: High flow VA-ECMO support significantly reduced LV end-diastolic volume, end-diastolic pressure, stroke work, and pressure-volume area compared to low flow.

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.

Compensatory hypertrophy and failure in gradual pressure-overloaded guinea pig heart

1989 ◽  
Vol 257 (3) ◽  
pp. H1016-H1024 ◽  
Author(s):  
F. M. Siri ◽  
C. Nordin ◽  
S. M. Factor ◽  
E. Sonnenblick ◽  
R. Aronson
Keyword(s):  
Heart Failure ◽  
Left Ventricular Hypertrophy ◽  
Guinea Pig ◽  
Ventricular Hypertrophy ◽  
Significant Proportion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Compensatory Hypertrophy ◽  
Guinea Pig Heart ◽  
Ventricular Afterload

Left ventricular hypertrophy has been produced in the guinea pig by a procedure that gradually increases left ventricular afterload. A mildly constricting band was placed around the ascending aortas of very young guinea pigs (225–275 g). With growth to 500–1,000 g, left ventricular systolic pressure increased and left ventricular hypertrophy developed. In approximately 50% of these animals, the hypertrophy was associated with normal left ventricular function and with no unusual symptoms or evidence of heart failure. The other animals developed dyspnea, which appeared an average of 41 days after banding. Dyspneic animals had normal body weight, markedly increased right ventricular and lung weights, decreased left ventricular norepinephrine content, diminished maximum left ventricular pressure generating capacity, and a significantly higher incidence of left ventricular interstitial and perivascular fibrosis. These findings demonstrate that even when left ventricular overload is imposed gradually by banding the aortas of young animals, myocardial decompensation ultimately ensues in a significant proportion of such animals. The slow imposition of loading, the slow rate of decompensation, and the ability to identify animals in heart failure by clinical dyspnea make this model uniquely valuable for studies on the mechanisms of heart failure.

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 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.

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.

Hypoxia-induced activation of KATP channels limits energy depletion in the guinea pig heart

1995 ◽  
Vol 269 (2) ◽  
pp. H734-H742 ◽  
Author(s):  
U. K. Decking ◽  
T. Reffelmann ◽  
J. Schrader ◽  
H. Kammermeier
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Monophasic Action Potential ◽  
Resonance Spectroscopy ◽  
Energy Status ◽  
Guinea Pig Heart

The functional role of ATP-dependent potassium (KATP) in hypoxic cardiac failure was investigated in isolated guinea pig hearts with glibenclamide and rimalkalim as inhibitor and activator, respectively. Monophasic action potential duration at 90% of repolarization (MAP50), left ventricular function, and cardiac energy status (31P nuclear magnetic resonance spectroscopy) were measured during normotoxic (95% O2) and hypoxic (20% O2) perfusion. In normoxic hearts, 1 microM glibenclamide did not affect MAP50, left ventricular function, and coronary flow (n = 4). In contrast, rimalkalim rapidly shortened MAP50 and left ventricular pressure (LVP) in a dose-dependent fashion (e.g., by 60.2 +/- 3.5 and 80.8 +/- 8.2%, respectively, with 0.6 microM rimalkalim). This latter effect was reversed by 1 microM (glibenclamide (n = 4). With hypoxic perfusion, a reduction in LVP was observed, along with a shortening of the action potential (MAP90; 202 +/- 13 vs. 164 +/- 9 ms) and an increase in coronary flow. Glibenclamide (1 microM) reversed the MAP90 shortening and the increase in coronary flow. In addition, glibenclamide increased LVP transiently (n = 4). When coronary flow of hypoxic hearts was kept constant, however, glibenclamide elicited a sustained positive inotropic effect (n = 7). After glibenclamide, an increase in LVP from 54 +/- 4 to 64 +/- 3 mmHg was observed, along with a reduction in the free energy change of ATP hydrolysis from -54.5 +/- 1.9 to -52.9 +/- 0.2 nJ/mol and a further increase in the coronary venous adenosine from 269 +/- 48 to 1,680 +/- 670 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals ATP is involved in myocardial and vascular effects of exogenous bradykinin in ejecting guinea pig heart

1999 ◽  
Vol 277 (2) ◽  
pp. H818-H825 ◽  
Author(s):  
Peter B. Anning ◽  
Bernard D. Prendergast ◽  
Philip A. MacCarthy ◽  
Ajay M. Shah ◽  
Derek C. Buss ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Coronary Flow ◽  
Pyridoxal Phosphate ◽  
Left Ventricular ◽  
Luciferase Assay ◽  
Disulfonic Acid ◽  
Vascular Effects ◽  
Guinea Pig Heart ◽  
Nitric Oxide Release

It has recently been reported that bradykinin induces selective left ventricular (LV) relaxation in isolated guinea pig hearts via the release of nitric oxide. Exogenous bradykinin also induces vasodilation, which is only partly due to nitric oxide release. In the present study we investigated the role of adenyl purines on these bradykinin-induced effects. Isolated ejecting guinea pig hearts were studied. LV pressure was monitored by a 2-Fr micromanometer-tipped catheter. ATP concentrations were measured using a luciferin-luciferase assay. Bradykinin (1 and 100 nM) caused a progressive acceleration of LV relaxation together with a transient increase in coronary flow. These effects were inhibited by the nonselective P2 purinoceptor antagonist suramin (1 μM, n = 6) but were unaffected by the selective P2x purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2′,4′-disulfonic acid (1 μM, n = 6). These myocardial and vascular effects of bradykinin were associated with increased ATP levels in coronary effluent. These data suggest that the selective enhancement of LV relaxation and rise in coronary flow induced by exogenous bradykinin involve endogenous ATP and the subsequent stimulation of P2 purinoceptors.

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.

Sign in / Sign up

Export Citation Format

Share Document