Recovery of Cardiac Function by Long-Term Left Ventricular Support in Patients With End-Stage Cardiomyopathy

In human heart failure (HF), reduced cardiac function has, at least partly, been ascribed to altered calcium homeostasis in cardiomyocytes. The effects of the calcium sensitizer levosimendan on diastolic dysfunction caused by reduced removal of calcium from cytosol in early diastole are not well known. In this study, we investigated the effect of long-term levosimendan treatment in a murine model of HF where the sarco(endo)plasmatic reticulum ATPase ( Serca) gene is specifically disrupted in the cardiomyocytes, leading to reduced removal of cytosolic calcium. After induction of Serca2 gene disruption, these mice develop marked diastolic dysfunction as well as impaired contractility. SERCA2 knockout (SERCA2KO) mice were treated with levosimendan or vehicle from the time of KO induction. At the 7-wk end point, cardiac function was assessed by echocardiography and pressure measurements. Vehicle-treated SERCA2KO mice showed significantly diminished left-ventricular (LV) contractility, as shown by decreased ejection fraction, stroke volume, and cardiac output. LV pressure measurements revealed a marked increase in the time constant (τ) of isovolumetric pressure decay, showing impaired relaxation. Levosimendan treatment significantly improved all three systolic parameters. Moreover, a significant reduction in τ toward normalization indicated improved relaxation. Gene-expression analysis, however, revealed an increase in genes related to production of the ECM in animals treated with levosimendan. In conclusion, long-term levosimendan treatment improves both contractility and relaxation in a heart-failure model with marked diastolic dysfunction due to reduced calcium transients. However, altered gene expression related to fibrosis was observed.

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Oral delivery of xenon for cardiovascular protection

Scientific Reports ◽

10.1038/s41598-019-50515-3 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Xing Yin ◽

Melanie R. Moody ◽

Valeria Hebert ◽

Melvin E. Klegerman ◽

Yong-Jian Geng ◽

...

Keyword(s):

Cardiac Function ◽

Oral Delivery ◽

Noble Gas ◽

Left Ventricular ◽

Beneficial Effects ◽

Normal Left Ventricular ◽

Term Administration ◽

Apoe Knockout Mice

Abstract Cardiac hypertrophy often causes impairment of cardiac function. Xenon (Xe), a naturally occurring noble gas, is known to provide neurological and myocardial protection without side effects. The conventional method of Xe delivery by inhalation is not feasible on a chronic basis. We have developed an orally deliverable, effective Xe formulation for long-term administration. We employed 2-hydroxypropyl)-β-cyclodextrin (HPCD), which was dissolved in water to increase the Xe concentration in solution. The beneficial effects of long-term oral administration of Xe-enriched solutions on cardiovascular function were evaluated in vivo. HPCD increased Xe solubility from 0.22 mM to 0.67 mM (3.8-fold). Aged ApoE knockout mice fed high-fat diet for 6 weeks developed hypertension, and myocardial hypertrophy with impaired cardiac function. Oral Xe prevented this ischemic damage, preserving normal blood pressure, while maintaining normal left ventricular mass and wall thickness. This novel formulation allows for gastrointestinal delivery and cardiovascular stabilization.

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Abstract 15253: A Paradoxical Rise in Serum Copeptin After Non-Pulsatile LVAD: a New SIADH?

Circulation ◽

10.1161/circ.130.suppl_2.15253 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Cara M Statz ◽

Aleksandra M Ras ◽

Kevin D Ballard ◽

Jason A Gluck ◽

Detlef Wencker

Keyword(s):

Surrogate Marker ◽

Left Ventricular ◽

Serum Samples ◽

Ventricular Assist ◽

Bridge To Transplant ◽

Left Ventricular Assist ◽

End Stage ◽

A Prospective Study

Introduction: Hyponatremia (Na< 136 mmol/L) is prevalent (~28%) among hospitalized heart failure (HF) patients and a marker of advanced/end-stage HF(AHF) with increased mortality. Treatment of hyponatremia has no survival benefit in this population. In a prospective study of AHF patients, we sought to define the prevalence, pathophysiology and role of V2 vasoreceptor activity in the development of hyponatremia. Serum copeptin (S-COP), a surrogate marker for AVP activity, was assessed during AHF therapies (AHFT) which included axial-non-pulsatile left ventricular assist device (LVAD) and/or heart transplant (HTx). Methods: Serum samples were collected from AHF patients pre and post AHFT and compared with normal controls. S-COP levels were assessed using an enzyme linked immunosorbant assay and correlated to clinical variables, serum Sodium (S-Na) and glomerular filtration rate (eGFR). Results: Among 89 consecutive (mean age 56.2±15.35; M=69) patients awaiting AHFT, 54 (60%) were hyponatremic. Preop S-COP was elevated compared to controls (0.68±0.50 vs 0.53±0.13 ng/ml, P=.02) and inversely correlated to S-Na and eGFR (r=-0.23, P<.05, r=-0.23, P<.05; N=81); conversely, eGFR and S-Na were uncorrelated. AHFT (n=42) normalized S-Na (133.2±4.1 vs 136.1±3.5 mmol/l; P=.001) and improved eGFR (47.7±13.6 vs 52.7±9.7 mL/min/1.73sqm; P=.001); however, post LVAD (n=34) S-COP rose (0.67±0.21 vs 1.84±0.76 ng/ml; P<.0001) with incomplete normalization of S-NA (132.9±4.3 vs 135.9±3.8 mmol/l; P<.01). In contrast, post HTx (n=9) S-COP was unchanged to pre-AHFT (0.59±0.32 vs 0.65±0.16 ng/ml; P>.1) and was lower compared to post LVAD (0.65±0.16 vs 1.84±0.76 ng/ml; P<.0001). Elevated S-COP with LVAD as bridge to transplant (n=3) showed a marked decrease post HTx (2.7±0.50 vs 1.0±0.29 ng/ml; P<.01). Conclusions: In AHF, the prevalence of hyponatremia is double compared to acute hospitalized HF and associated with S-COP surge prior to AHFT. Unexpectedly, LVAD but not HTx was associated with rising S-COP and incomplete S-Na recovery despite clinical improvement, suggesting inappropriate antidiuretic hormone release. The association of S-COP rise with non-pulsatile LVAD and potential benefit of long-term AVP inhibition post LVAD merits further studies.

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Medical and Economic Consideration Regarding Long Term Mechanical Left Ventricular Support

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2020.01.449 ◽

2020 ◽

Vol 39 (4) ◽

pp. S366

Author(s):

H.A. Welp ◽

A.M. Dell'Aquila ◽

A. Hoffmeier ◽

S. Martens ◽

M. Scherer

Keyword(s):

Left Ventricular ◽

Economic Consideration ◽

Ventricular Support

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Effect of Ultrafiltration on Sleep Apnea and Cardiac Function in End-Stage Renal Disease

American Journal of Nephrology ◽

10.1159/000505445 ◽

2020 ◽

Vol 51 (2) ◽

pp. 139-146 ◽

Cited By ~ 2

Author(s):

Toru Inami ◽

Owen D. Lyons ◽

Elisa Perger ◽

Azadeh Yadollahi ◽

John S. Floras ◽

...

Keyword(s):

Sleep Apnea ◽

Renal Disease ◽

Cardiac Function ◽

End Stage Renal Disease ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Systolic And Diastolic Function ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Rationale: End-stage renal disease (ESRD) patients have high annual mortality mainly due to cardiovascular causes. The acute effects of obstructive and central sleep apnea on cardiac function in ESRD patients have not been determined. We therefore tested, in patients with ESRD, the hypotheses that (1) sleep apnea induces deterioration in cardiac function overnight and (2) attenuation of sleep apnea severity by ultrafiltration (UF) attenuates this deterioration. Methods: At baseline, ESRD patients, on conventional hemodialysis, with left ventricular ejection fraction (LVEF) >45% had polysomnography (PSG) performed on a non-dialysis day to determine the apnea-hypopnea index (AHI). Echocardiography was performed at the bedside, before and after sleep. Isovolumetric contraction time divided by left ventricular ejection time (IVCT/ET) and isovolumetric relaxation time divided by ET (IVRT/ET) were measured by tissue doppler imaging. The myocardial performance index (MPI), a composite of systolic and diastolic function was also calculated. One week later, subjects with sleep apnea (AHI ≥15) had fluid removed by UF, followed by repeat PSG and echocardiography. Results: Fifteen subjects had baseline measurements, of which 7 had an AHI <15 (no–sleep-apnea group) and 8 had an AHI ≥15 (sleep-apnea group). At baseline, there was no overnight change in the LVEF in either the no-sleep-apnea group or the sleep-apnea group. In the no-sleep-apnea group, there was also no overnight change in MPI, IVCT/ET and IVRT/ET. However, in the sleep-apnea group there were overnight increases in MPI, IVCT/ET and IVRT/ET (p = 0.008, 0.007 and 0.031, respectively), indicating deterioration in systolic and diastolic function. Following fluid removal by UF in the sleep-apnea group, the AHI decreased by 48.7% (p = 0.012) and overnight increases in MPI, IVCT/ET and IVRT/ET observed at baseline were abolished. Conclusions: In ESRD, cardiac function deteriorates overnight in those with sleep apnea, but not in those without sleep apnea. This overnight deterioration in the sleep-apnea group may be at least partially due to sleep apnea, since attenuation of sleep apnea by UF was accompanied by elimination of this deleterious overnight effect.

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Cardiac function in fetal sheep during two weeks of hypoxemia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.6.r1778 ◽

1994 ◽

Vol 266 (6) ◽

pp. R1778-R1785 ◽

Cited By ~ 6

Author(s):

M. Kamitomo ◽

L. D. Longo ◽

R. D. Gilbert

Keyword(s):

Arterial Pressure ◽

Cardiac Function ◽

Ventricular Function ◽

Left Ventricular ◽

Pressure Sensitivity ◽

Sensitivity Curve ◽

Fetal Sheep ◽

Cardiac Responses ◽

Ovine Fetal

Although several studies have examined fetal cardiac responses to acute hypoxemia, relatively little is known of the response to prolonged hypoxemia. To determine the effects of long-term hypoxemia on ovine fetal cardiac function, we measured right (QRV) and left ventricular outputs (QLV) and determined the effects of increasing preload (ventricular function curve) and afterload (arterial pressure sensitivity curve) on the left ventricle. Six days after fetal surgical instrumentation with catheters and electromagnetic flow probes (approximately 123 days gestation), we administered N2 into the maternal trachea for 14 days to reduce maternal PO2 to approximately 55 Torr (hypoxemic group, Hyp, n = 6). Normoxic animals were used as controls (Cont, n = 6). With the onset of hypoxemia, fetal arterial PO2 was reduced from approximately 27 to approximately 18 Torr. Fetal heart rate in Hyp fetuses decreased approximately 22% on day 14 compared with Cont (P < 0.05). Mean arterial pressure in the Hyp group was higher than that of Cont but not significantly so. Right and left atrial pressures were not affected by hypoxemia. QRV in Hyp fetuses was maintained on day 1 but decreased significantly by day 3 (approximately 19%) and further decreased on days 7 (approximately 28%) and 14 (approximately 34%). QLV was not depressed until day 7 (approximately 20%), with a further decrease on day 14 (approximately 38%). In association with the decreased QLV the plateau of the ventricular function curve in Hyp fetuses was depressed significantly on days 7 and 14. In contrast, the slope of the arterial pressure sensitivity curve in the Hyp group did not differ from Cont.(ABSTRACT TRUNCATED AT 250 WORDS)

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