Chronic opiate-receptor inhibition in experimental congestive heart failure in dogs

1997 ◽  
Vol 272 (1) ◽  
pp. H478-H484
Author(s):  
A. Yatani ◽  
N. Imai ◽  
Y. Himura ◽  
M. Suematsu ◽  
C. S. Liang
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Output ◽  
Opiate Receptor ◽  
Left Ventricular ◽  
Right Atrial ◽  
Acute Administration ◽  
Ventricular Performance ◽  
Inotropic Effects ◽  
Receptor Inhibition

Acute administration of opiate-receptor antagonists has previously been shown to improve cardiac output aortic blood pressure, systolic ventricular performance, and the baroreflex function in conscious dogs with right-sided congestive heart failure (RHF). However, whether similar changes occur after chronic opiate-receptor inhibition in congestive heart failure is not known. To determine the chronic effects of opiate-receptor antagonism on RHF, we administered naltrexone (200 mg/day), a long-acting, orally active opiate-receptor blocking agent, to RHF and sham-operated animals for 6 wk. Naltrexone had no effects on resting heart rate, right atrial pressure, aortic pressure, or cardiac output in RHF dogs but increased the first derivative of right and left ventricular pressure with respect to time (dP/dt) at rest and improved the dP/dt response to isoproterenol. The inotropic responses to isoproterenol and forskolin in isolated right ventricular trabeculate muscle also were improved by chronic naltrexone in RHF. Myocardial beta-receptor density was reduced in the failing right ventricle compared with the control (58 +/- 3 vs. 108 +/- 6 fmol/mg protein, P < 0.01) but was unaffected by addition of naltrexone. Finally, naltrexone prevented the decline in baroreflex sensitivity that occurred in RHF (-0.2 +/- 0.5 vs. -6.0 +/- 0.5 ms/mmHg, P < 0.01). These effects of naltrexone did not occur in the shamoperated animals. Chronic opiate-receptor blockade with naltrexone attenuates the development of reduced adrenergic inotropic responsiveness and baroreflex subsensitivity that occur in RHF. Because there was a similar improvement in the forskolin response in the absence of significant alterations in myocardial beta-adrenoceptor density after naltrexone treatment, the improvement in adrenergically mediated inotropic effects probably is mediated via a postreceptor mechanism.

1406Inhaled iloprost, exercise hemodynamics, and ventricular performance in heart failure with preserved ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J.-F Cheng ◽  
C.-K Wu ◽  
C.-Y Huang ◽  
Z.-W Chen ◽  
S.-Y Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Ejection Fraction ◽  
Study Drug ◽  
Left Ventricular ◽  
Stroke Work ◽  
Preserved Ejection Fraction ◽  
Ventricular Performance ◽  
Inhaled Iloprost ◽  
Exercise Hemodynamics

Abstract Background A dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). The prostacyclin pathway is involved in pulmonary hypertension and iloprost is a prostacyclin analogue. The acute onset vasodilator effect of inhaled iloprost makes it a good candidate to decrease exercise-induced PCWP. This study determined whether iloprost inhalation could improve exercise hemodynamics and cardiac reserve in HFpEF. Methods Thirty-four HFpEF subjects were enrolled in this double-blind, randomized, placebo-controlled, parallel-group trial. Subjects received invasive cardiac catheterization and underwent expired gas analysis at rest and during exercise, before and 15 minutes after treatment with either inhaled iloprost or placebo. Results At baseline, enrolled subjects showed an increase in PCWP during exercise (PCWP = 16 (14–23) mmHg to 27 (21–36) mmHg; p<0.0001). After drug inhalation treatment, the primary endpoint was achieved whereby exercise PCWP was significantly reduced by iloprost compared to placebo (adjusted mean: 20 (16–29) mmHg vs. 23 (17–32) mmHg; p=0.002). Iloprost showed a trend for better cardiac output reserve with exercise (0.2 (−1.3 to 1.2) L/min vs. −0.7 (−1.9 to 0.1) L/min; p=0.099) and normalized the increase in cardiac output relative to oxygen consumption. Iloprost improved the pulmonary artery pressure flow relationships in HFpEF and showed a trend for increased left ventricular stroke work with exercise compared to placebo, indicating an improvement in ventricular performance with stress. Table shows exercise baseline-corrected values (exercise values after receiving study drug minus exercise values prior to study drug) Placebo (n=17) Iloprost (n=17) p Value PA systolic, mmHg 0 (−4 to 6) −11 (−23 to −5) <0.0001 PCWP, mmHg −2 (−3 to 2) −7 (−12 to −5) <0.0001 PVR, mmHg/l/min 0 (−0.5 to 0.3) −0.1 (−0.5 to 0.4) 0.9 SVR, DSC 102 (16 to 188) 5 (−162 to 108) 0.057 LVSW, g/beat −3 (−30 to 6) 7 (−13 to 20) 0.079 CO, l/min −0.7 (−1.9 to 0.1) 0.2 (−1.3 to 1.2) 0.099 Stroke volume, ml −8 (−24 to 1) 0 (−19 to 10) 0.3 Values are median (interquartile range). Conclusions Iloprost inhalation improved hemodynamic deficit during exercise in patients with HFpEF. Prospective trials testing long-term iloprost therapy in this population are warranted.

scholarly journals Relationship between Cognitive Function, Depression/Anxiety and Functional Parameters in Patients Admitted for Congestive Heart Failure

2013 ◽  
Vol 7 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Mauro Feola ◽  
Sonia Garnero ◽  
Paola Vallauri ◽  
Luigi Salvatico ◽  
Antonello Vado ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Output ◽  
Cognitive Impairment ◽  
Plasma Level ◽  
Nyha Class ◽  
Depression Scale ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Anxiety And Depression

Cognitive impairment, anxiety and depression have been described in patients with congestive heart failure (CHF). We analyzed in-hospital CHF patients before discharge with neuropsychological tests attempting to correlate with prognostic parameters. Methods: All subjects underwent a mini mental state examination (MMSE), geriatric depression scale (GDS), anxiety and depression scale test (HADS). We evaluated NYHA class, brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF) and non-invasive cardiac output (CO). Results: Three-hundred and three CHF patients (age 71.6 ys) were analysed. The mean NYHA class was 2.9±0.8, LVEF was 43.4±15.8%; BNP plasma level and CO were calculated as 579.8±688.4 pg/ml and 3.9±1.1 l/min, respectively. In 9.6% a pathological MMSE score emerged; a depression of mood in 18.2% and anxiety in 23.4% of patients were observed. A significant correlation between MMSE and age (r=0.11 p=0.001), BNP (r=0.64 p=0.03) but not between MMSE and NYHA class and LVEF was observed. GDS and HADS were inversely correlated with NYHA class (r=0.38 p=0.04) and six-minute walking test (r=0.18 p=0.01) without an association with objective parameters in CHF (BNP, LVEF and cardiac output). At multivariate analysis only MMSE and BNP are inversely correlated significantly (p=0.019 OR=-0.64, CI=-042-0.86). Conclusions: in-hospital CHF patients may manifest a reduction of MMSE and important anxiety/depression disorders. The results of the study suggest that the presence of cognitive impairment in older CHF patients with higher BNP plasma level should be considered. In admitted CHF patients anxiety and depression of mood are commonly reported and influenced the perception of the severity of illness.

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