Abstract 176: Saxagliptin and Tadalafil Differentially Alter Global and Cellular Cardiac Function in a Translational Miniature Swine Model of Left Ventricle Hypertrophy

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jessica A Hiemstra ◽  
Anne K Gibson ◽  
Jan R Ivey ◽  
Melissa S Cobb ◽  
Christopher P Baines ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Pde5 Inhibitor ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Lv Function ◽  
Swine Model ◽  
Stroke Work ◽  
Wall Stiffness ◽  
Cgmp Signaling ◽  
Whole Heart

Left ventricular (LV) hypertrophy is a common characteristic of heart failure with preserved ejection fraction (HFpEF). Our lab recently characterized a mini-swine model of LV hypertrophy induced by aortic banding (AB) that displays clinical features associated with HFpEF including LV hypertrophy, diastolic dysfunction, and depressed contractile reserve. Disrupted cGMP signaling, a result of impaired production or enhanced catabolism, may play a role in development of HFpEF. We hypothesized preservation of cGMP signaling would attenuate pathological remodeling and improve cardiac function. The purpose of this study was to promote cGMP signaling via two mechanisms: 1) the DPP4 inhibitor saxagliptin; and 2) the PDE5 inhibitor tadalafil. We assessed whole heart and individual cardiomyocyte function 6 months post-AB in: control non-banded (CON; n=6), AB-control (AB; n=7), AB saxagliptin-treated (AB-SAX; n=7), and AB tadalafil-treated (AB-TAD; n=8) swine. Heart weight:body weight ratio increased to a similar extent in all AB groups. However, changes in cardiomyocyte morphology were variable. Cardiomyocyte length was increased only in the AB-TAD group, while cell width increased in both AB and AB-TAD animals. Cardiomyocyte length:width ratio decreased in the AB and AB-TAD groups, commensurate with decreased LV end diastolic (ED) and end systolic (ES) volumes. These changes were prevented in AB-SAX animals, as LV volumes and cell morphology were similar to CON. Pressure-volume analysis showed resting LV wall stiffness (ED pressure volume relationship [EDPVR] slope) was increased similarly in all AB groups. Increased resting LV contractility (ESPVR and preload recruitable stroke work) was observed in AB and AB-TAD animals. Interestingly, cardiomyocyte shortening was reduced in the AB-TAD group contrasting findings observed at the whole heart level. Saxaglitpin attenuated hypercontractile LV function at rest and preserved normal cardiomyocyte shortening. In conclusion, LV and cardiomyocyte function was distinctly altered in response to separate methods of pharmacological cGMP regulation. Our data suggest different pharmacological approaches to augment cGMP signaling promote distinct LV functional adaptations to developing HF.

Abstract 87: Alterations to Cardiac Mechanics Do Not Preserve Normal Cardiac Function in a Novel Ossabaw Swine Model of Heart Failure with Preserved Ejection Fraction

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jenna C Edwards ◽  
Madeleine Dionne ◽  
T. D Olver ◽  
Jan R Ivey ◽  
Pamela K Thorne ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Strain Rate ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Volume Index ◽  
Lv Function ◽  
Swine Model ◽  
Preserved Ejection Fraction

Introduction: Heart failure with preserved ejection fraction (HFpEF) is clinically characterized by an increased incidence in females and many comorbidities including type 2 diabetes (T2D) and obesity. Animal models accurately representing clinical HFpEF are lacking; thus, the purpose of this study was to examine left ventricular (LV) mechanics in a novel Ossabaw swine model of chronic pressure-overload (aortic-banding; AB) and T2D (Western diet; WD) using two dimensional speckle tracking echocardiography (2D-STE). We hypothesized that global LV strain would be decreased primarily in the longitudinal direction in WD-AB animals. Methods: Female Ossabaws were randomly divided into 2 groups: CON (n=5) and WD-AB (n=5). LV function and strain were measured at 1 year of age after 6 mo. of AB and 9 mo. of WD via pressure-volume relations and 2D-STE. Significance was set at P < 0.05 using t-test vs. CON. Results: In the WD-AB group, ejection fraction (EF%) and end diastolic volume were normal (>50%), and observed in parallel with increased LV weight, lung weight, and LV diastolic wall thickness (i.e. concentric hypertrophy). WD-AB group had increased HOMA-IR and body surface area, two common features in T2D. In WD-AB animals, although global longitudinal systolic strain rate and end systolic displacement were increased, stroke volume index was decreased. Early diastolic rotation rate was decreased, while global longitudinal late diastolic strain rate was increased in the WD-AB group. These changes, considered in parallel with an increased end diastolic pressure-volume relationship in WD-AB animals, are consistent with diastolic dysfunction. In contrast, longitudinal, radial, and circumferential early diastolic strain rates increased in the WD-AB group. Conclusion: Contrary to our hypothesis, LV longitudinal strain was increased during both systole and diastole, and observed in parallel with decreased early diastolic untwisting in WD-AB animals. Our results suggest alterations to LV mechanics do not preserve normal systolic and diastolic cardiac function, despite normal resting EF%, in this novel translational model of pressure-overload HF with potential relevance to human HFpEF including associated clinical comorbidities (sex, obesity, and T2D).

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.

Abstract 2673: Myoblast Transplantation Improves Cardiac Function Whether the Cells are Implanted Early or Late After Coronary Ligation

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Patrick Farahmand ◽  
Richard D Weisel ◽  
Philippe Menasche ◽  
Ren-Ke Li
Keyword(s):  
Cardiac Function ◽  
Left Ventricular ◽  
Border Zone ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Matrix Remodeling ◽  
Stroke Work ◽  
Artery Ligation ◽  
Skeletal Myoblasts ◽  
Myoblast Transplantation

Background: The inability of skeletal myoblasts to transdifferentiate into cardiomyocytes supports the hypothesis that their beneficial effects on cardiac function after a myocardial infarction (MI) are mediated by paracrine effects. In order to explore the role of the timing of cell therapy on the resultant angiogenesis and matrix remodeling, we compared the effects of myoblast transplantation early or late after MI. Methods: MI was generated in Lewis rats by coronary artery ligation. Skeletal myoblasts (5X10 6 ) or control media were injected into the scar and border zone either 5 days (early; n=33) or 30 days (late; n=29) after ligation. Function was assessed by echocardiography before transplantation (Tx), and 14 and 30 days thereafter. Invasive hemodynamics were measured with a Millar catheter at 30 days after Tx, following which explanted hearts were processed to assess LV volumes (computerized planimetry), fibrillar collagen (confocal microscopy), and myoblast engraftment, angiogenesis and extra-cellular matrix characteristics (immunohistochemistry). Results: Load-independent indices of left ventricular (LV) function (Emax, preload recruitable stroke work) were significantly increased in myoblast recipients compared with controls regardless of whether cells were implanted early (p=0.003, p=0.03, respectively) or late (p=0.003, p=0.0007, respectively) after MI. Changes in fractional shortening (by echocardiography) followed a similar pattern. These changes were associated with a significant reduction in LV volume (p=0.04, p=0.01 for early and late Tx groups vs. controls, respectively), and an increase in angiogenesis (p=0.02) whether the myoblasts were injected early or late after MI. The length and width of collagen fibers both in the scar and remote myocardium were also significantly increased (p<0.001) regardless of the timing of myoblast injection. Conclusions: The data suggest that myoblast transplantation improved cardiac function whether cells were injected early or late after MI. In each case, functional recovery was associated with enhanced angiogenesis, favourable effects on extracellular matrix remodeling, and improved LV geometry, supporting the paracrine hypothesis for myoblast transplantation.

Left ventricular dysfunction following rewarming from experimental hypothermia

1998 ◽  
Vol 85 (6) ◽  
pp. 2135-2139 ◽  
Author(s):  
Torkjel Tveita ◽  
Kirsti Ytrehus ◽  
Eivind S. P. Myhre ◽  
Olav Hevrøy
Keyword(s):  
Systolic Function ◽  
Left Ventricular ◽  
Lv Function ◽  
Stroke Work ◽  
M 10 ◽  
Stiffness Constant ◽  
Rate Of Increase ◽  
Wall Stiffness ◽  
Significant Depression ◽  
Lv Systolic Function

This study was aimed at elucidating whether ventricular hypothermia-induced dysfunction persisting after rewarming the unsupported in situ dog heart could be characterized as a systolic, diastolic, or combined disturbance. Core temperature of 8 mongrel dogs was gradually lowered to 25°C and returned to 37°C over a period of 328 min. Systolic function was described by maximum rate of increase in left ventricular (LV) pressure (dP/d tmax), relative segment shortening (SS%), stroke volume (SV), and the load-independent contractility index, preload recruitable stroke work (PRSW). Diastolic function was described by the isovolumic relaxation constant (τ) and the LV wall stiffness constant ( Kp). Compared with prehypothermic control, a significant decrease in LV functional variables was measured at 25°C: dP/d tmax2,180 ± 158 vs. 760 ± 78 mmHg/s, SS% 20.1 ± 1.2 vs. 13.3 ± 1.0%, SV 11.7 ± 0.7 vs. 8.5 ± 0.7 ml, PRSW 90.5 ± 7.7 vs. 29.1 ± 5.9 J/m ⋅ 10−2, Kp0.78 ± 0.10 vs. 0.28 ± 0.03 mm−1, and τ 78.5 ± 3.7 vs. 25.8 ± 1.6 ms. After rewarming, the significant depression of LV systolic variables observed at 25°C persisted: dP/d tmax1,241 ± 108 mmHg/s, SS% 10.2 ± 0.8 J, SV 7.3 ± 0.4 ml, and PRSW 52.1 ± 3.6 m ⋅ 10−2, whereas the diastolic values of Kpand τ returned to control. Thus hypothermia induced a significant depression of both systolic and diastolic LV variables. After rewarming, diastolic LV function was restored, in contrast to the persistently depressed LV systolic function. These observations indicate that cooling induces more long-lasting effects on the excitation-contraction coupling and the actin-myosin interaction than on sarcoplasmic reticulum Ca2+trapping dysfunction or interstitial fluid content, making posthypothermic LV dysfunction a systolic perturbation.

Cardiovascular performance with E. coli challenges in a canine model of human sepsis

1988 ◽  
Vol 254 (3) ◽  
pp. H558-H569 ◽  
Author(s):  
C. Natanson ◽  
R. L. Danner ◽  
M. P. Fink ◽  
T. J. MacVittie ◽  
R. I. Walker ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Volume Index ◽  
Lv Function ◽  
Stroke Work ◽  
E Coli ◽  
Work Index ◽  
Stroke Work Index ◽  
Number Of Bacteria

We investigated cardiovascular dysfunction by injecting lethal and nonlethal bacterial challenges into conscious dogs. E. coli bacteria of varying numbers were placed in a peritoneal clot. Cardiovascular function was studied with simultaneous radionuclide scans and thermodilution cardiac outputs. In surviving animals, the number of bacteria in the clot increased as the corresponding systolic cardiac function decreased (P = 0.01). Cardiac function was measured by left ventricular (LV) ejection fraction (EF) and LV function curves [LV stroke work index (LVSWI) vs. end-diastolic volume index (EDVI), and peak systolic pressure vs. end-systolic volume index]. Furthermore, the diastolic volume-pressure relationship of survivors shifted progressively to the right [i.e., increasing EDVI (P less than 0.02) with minimal change (P = NS) in LV filling pressure]. This increase in LV size was associated with maintenance of measures of cardiac performance [stroke volume index (SVI) and stroke work index (SWI)] at similar levels. Death occurred only in the group with the highest bacterial dose. Compared with survivors receiving the same number of bacteria, nonsurvivors had a decrease in (P less than 0.05) LV size, a leftward shift (P less than 0.01) in LV diastolic volume-pressure relationship, and a decrease in both LVSWI and SVI (possibly related to volume and/or LV functional status). Data from survivors suggest that increasing the number of bacteria produces changes in myocardial compliance and contractility. These changes increase LV size (preload), a major determinant of cardiac performance that possibly enhances survival.

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.

Abstract 1876: Functional Effect of Chronic Urotensin II Receptor Antagonist on L-Type Ca 2+ Current in Mouse Model of Progressive Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Peng Zhou ◽  
Heng-Jie Cheng ◽  
Michael Cross ◽  
Michael F Callahan ◽  
Bridget Brosnihan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Receptor Antagonist ◽  
Weight Ratio ◽  
Heart Association ◽  
Cell Voltage ◽  
Fold Increase ◽  
Left Ventricular ◽  
Lv Function ◽  
List Type ◽  
Urotensin Ii

Voltage-gated Ca 2+ channels play fundamental roles in the regulation of cardiac function by various neurotransmitters. Recently, we have shown that urotensin II (UII), a potent vasoconstrictor, inhibits L-type Ca 2+ current (I Ca,L ) and produces negative inotropic action. In heart failure (HF), the UII-mediated pathway is upregulated, suggesting a therapeutic value of UII receptor antagonist (UII-ANT) for HF. However, the role and mechanism of chronic UII-ANT in HF is unclear. We tested the hypothesis that chronic UII-ANT may improve cardiac I Ca,L , preventing β-adrenergic deregulation on I Ca,L and limit HF progression. We examined plasma levels of norepinephrine (NE), left ventricular (LV) function, and myocyte I Ca,L responses to isoproterenol (ISO) in 3 age-matched groups of mice: HF (n = 7), 2 months after ISO (150 mg/kg sq for 2 days); HF/UII-ANT (n = 11), 1 month after receiving ISO, then urantide, a potent UII-ANT (10 −5 M/kg/day, sq via implanted osmotic mini pump), given for 1 month; and Controls (n = 7). I Ca,L was measured using whole-cell voltage clamp technique. Compared with controls, ISO-treated mice progressed to HF with 4.7-fold increase in plasma NE (18975 vs 4066 pg/ml) and LV dilatation associated with increased myocyte length (ML, 155 vs120 μm) and heart-to-body weight ratio (H/BW, 7.6 vs 5.5 g/kg). Stroke volume (SV, 30.3 vs 61.4 μl) and ejection fraction (EF, 39% vs 60%) were decreased. Compared with normal myocytes, in HF myocytes, I Ca,L was reduced (50%, 3.7 ± 0.2 vs 7.4 ± 0.2 pA/pF), and I Ca,L response to β-AR stimulation (ISO, 10 −8 M) was attenuated (11% vs 35%) (p < 0.01). In HF/UII-ANT mice, plasma NE (5148 pg/ml), SV (57.9 μl), and EF (57%) returned close to control levels with retained normal ML (124 μm) and H/BW (5.9 g/kg). Moreover, compared with controls, in HF/UII-ANT mice, ISO caused similar increases in the peak I Ca,L (32% vs 35%). Chronic UII-ANT treatment normalizes LV L-type Ca 2+ channel basal function and β-adrenergic regulation, leading to regression of LV and myocyte dysfunction and remodeling in mice with ISO-induced HF. This research has received full or partial funding support from the American Heart Association, AHA National Center.

Effects of hypoproteinemia-induced myocardial edema on left ventricular function

1998 ◽  
Vol 274 (3) ◽  
pp. H937-H944 ◽  
Author(s):  
M. Miyamoto ◽  
D. E. McClure ◽  
E. R. Schertel ◽  
P. J. Andrews ◽  
G. A. Jones ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Protein Concentration ◽  
Systolic Dysfunction ◽  
Myocardial Edema ◽  
Left Ventricular ◽  
Control Group ◽  
Lv Function ◽  
Stroke Work ◽  
Plasma Protein Concentration ◽  
Total Plasma Protein

In previous studies, we observed left ventricular (LV) systolic and diastolic dysfunction in association with interstitial myocardial edema (IME) induced by either coronary venous hypertension (CVH) or lymphatic obstruction. In the present study, we examined the effects of myocardial edema induced by acute hypoproteinemia (HP) on LV systolic and diastolic function. We also combined the methods of HP and CVH (HP-CVH) to determine their combined effects on LV function and myocardial water content (MWC). We used a cell-saving device to lower plasma protein concentration in HP and HP-CVH groups. CVH was induced by inflating the balloon in the coronary sinus. Six control dogs were treated to sham HP. Conductance and micromanometer catheters were used to assess LV function. Contractility, as measured by preload recruitable stroke work, did not change in control or HP groups but declined significantly (14.5%) in the HP-CVH group. The time constant of isovolumic LV pressure decline (τ) increased significantly from baseline by 3 h in the HP (24.8%) and HP-CVH (27.1%) groups. The end-diastolic pressure-volume relationship (stiffness) also increased significantly from baseline by 3 h in the HP (78.6%) and HP-CVH (42.6%) groups. Total plasma protein concentration decreased from 5.2 ± 0.2 g/dl at baseline to 2.5 ± 0.0 g/dl by 3 h in the HP and HP-CVH groups. MWC of the HP (79.8 ± 0.25%) and HP-CVH groups (79.8 ±0.2%) were significantly greater than that of the control group (77.8 ± 0.3%) but not different from one another. In conclusion, hypoproteinemia-induced myocardial edema was associated with diastolic LV dysfunction but not systolic dysfunction. The edema caused by hypoproteinemia was more than twice that produced by our previous models, yet it was not associated with systolic dysfunction. CVH had a negative inotropic effect and no significant influence on MWC. IME may not have the inverse causal relationship with LV contractility that has been previously postulated but appears to have a direct causal association with diastolic stiffness as has been previously demonstrated.

Abstract 3292: Cardiac Dysfunction Induced By Chronic Restrain Stress Is Mediated By Opioid Receptors

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jinping Gao ◽  
Chu C Chua ◽  
Deling Yin ◽  
Hong Wang ◽  
Ronald C Hamdy ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Chronic Stress ◽  
Opioid Receptors ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Opioid Antagonist ◽  
Stroke Work ◽  
Ventricular Performance ◽  
Major Health Problem ◽  
Stressed Group

Psychological and physical stressors are a major health problem in our society. The effect of chronic stress on myocardial function has not been assessed. Our hypothesis is that chronic stress induces cardiac dysfunction and that its effect is mediated by activation of opioid receptors (OPR). Six week-old male ICR mice were restrained for 12 h with no food and water. This was followed by 12 h of rest with food and water provided ad labium. Unstressed (control) mice were kept in the original cage and were not given food and water during the stress period of the experimental group. Left ventricular performance was analyzed in mice anesthetized with 2% isoflurane using an ARIA pressure-volume conductance system (Millar Instruments). Our studies demonstrated for the first time that cardiac function was significantly depressed in restrained mice, as evidenced by a significant decrease in body weight (9%), heart rate (21%), stroke volume (38%), cardiac output (52%), ejection fraction (27%) and preload recruitable stroke work (43%). Systolic function (control vs. stressed group) (P<0.05), was 88 ± 2.2 vs. 68 ± 2.8 mmHg for end-systolic pressure, 6.1 ± 0.15 vs. 7.6 ± 0.15 μl for end-systolic volume, and 11,471 ± 913 vs. 5,860 ± 761 mmHg/s for +dP/dt. Diastolic function (control vs. stressed group) (P<0.05), was 2.9 ± 0.3 vs. 5.0 ± 0.5 mmHg for end-diastolic pressure, 17.1 ± 0.4 vs. 14.4 ± 0.5 μl for end-diastolic volume, 7,678 ± 419 vs. 4,195 ± 358 mmHg/s for -dP/dt, and 7.1 ± 0.5 vs. 10.8 ± 1.1 ms for tau (time constant of isovolumic relaxation). Peripheral vascular resistance (Ea) increased from 7.7 ± 0.2 in the control group to 9.8 ± 0.7 mmHg/μ l in the stressed group (P<0.05). Administration of an opioid antagonist naltrexone (8 mg/kg, i.p.) during each cycle of stress completely restored the cardiac function of stressed mice. Naltrexone alone had no effect on cardiac function in unstressed mice. These intriguing data suggest that opioid receptors are involved in the chronic stress-induced cardiac dysfunction and that treatment with an opioid antagonist can prevent this cardiac dysfunction.

scholarly journals Dietary Calanus oil recovers metabolic flexibility and rescues postischemic cardiac function in obese female mice

2019 ◽  
Vol 317 (2) ◽  
pp. H290-H299 ◽  
Author(s):  
Kirsten M. Jansen ◽  
Sonia Moreno ◽  
Pablo M. Garcia-Roves ◽  
Terje S. Larsen
Keyword(s):  
Fatty Acid ◽  
Cardiac Function ◽  
Glucose Oxidation ◽  
Myocardial Metabolism ◽  
Dietary Supplementation ◽  
Left Ventricular ◽  
Lv Function ◽  
Marine Oil ◽  
Normal Chow ◽  
Postischemic Recovery

The aim of this study was to find out whether dietary supplementation with Calanus oil (a novel marine oil) or infusion of exenatide (an incretin mimetic) could counteract obesity-induced alterations in myocardial metabolism and improve postischemic recovery of left ventricular (LV) function. Female C57bl/6J mice received high-fat diet (HFD, 45% energy from fat) for 12 wk followed by 8-wk feeding with nonsupplemented HFD, HFD supplemented with 2% Calanus oil, or HFD plus exenatide infusion (10 µg·kg−1·day−1). A lean control group was included, receiving normal chow throughout the whole period. Fatty acid and glucose oxidation was measured in ex vivo perfused hearts during baseline conditions, while LV function was assessed with an intraventricular fluid-filled balloon before and after 20 min of global ischemia. HFD-fed mice receiving Calanus oil or exenatide showed less intra-abdominal fat deposition than mice receiving nonsupplemented HFD. Both treatments prevented the HFD-induced decline in myocardial glucose oxidation. Somewhat surprising, recovery of LV function was apparently better in hearts from mice fed nonsupplemented HFD relative to hearts from mice fed normal chow. More importantly however, postischemic recovery of hearts from mice receiving HFD with Calanus oil was superior to that of mice receiving nonsupplemented HFD and mice receiving HFD with exenatide, as expressed by better pressure development, contractility, and relaxation properties. In summary, dietary Calanus oil and administration of exenatide counteracted obesity-induced derangements of myocardial metabolism. Calanus oil also protected the heart from ischemia, which could have implications for the prevention of obesity-related cardiac disease. NEW & NOTEWORTHY This article describes for the first time that dietary supplementation with a low amount (2%) of a novel marine oil (Calanus oil) in mice is able to prevent the overreliance of fatty acid oxidation for energy production during obesity. The same effect was observed with infusion of the incretin mimetic, exanatide. The improvement in myocardial metabolism in Calanus oil-treated mice was accompanied by a significantly better recovery of cardiac performance following ischemia-reperfusion. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/dietary-calanus-oil-energy-metabolism-and-cardiac-function/ .

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