scholarly journals Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study

2021 ◽  
Author(s):  
Takuya Nishikawa ◽  
Kazunori Uemura ◽  
Yohsuke Hayama ◽  
Toru Kawada ◽  
Keita Saku ◽  
...  
Keyword(s):  
Heart Failure ◽  
Oxygen Consumption ◽  
Myocardial Oxygen Consumption ◽  
Atrial Pressure ◽  
Right Atrial ◽  
Canine Heart ◽  
Circulatory Collapse ◽  
Inotropic Effects ◽  
Administration System ◽  
Β Blocker

AbstractBeta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and PLA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean PLA were controlled within the acceptable ranges (AP within 5 mmHg below target; PLA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2–3.8)] and PLA [3.6% (2.2–5.7)]. The system decreased MVO2 and PLA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and PLA to avoid circulatory collapse, and reduced MVO2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted.

scholarly journals Development of an Automated Drug Delivery System for an Ultra-Short-acting β-Blocker, Landiolol, to Stably Reduce Myocardial Oxygen Consumption without Inducing Circulatory Collapse in a Canine Heart Failure Model

2020 ◽  
Author(s):  
Takuya Nishikawa ◽  
Kazunori Uemura ◽  
Yohsuke Hayama ◽  
Toru Kawada ◽  
Keita Saku ◽  
...  
Keyword(s):  
Heart Failure ◽  
Drug Delivery ◽  
Oxygen Consumption ◽  
Drug Delivery System ◽  
Acute Phase ◽  
Delivery System ◽  
Myocardial Oxygen Consumption ◽  
Circulatory Collapse ◽  
Β Blocker ◽  
Β Blockers

Abstract Background: Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. Although the use of β-blockers in the acute phase of HF can be expected to be beneficial, the negative chronotropic and inotropic effects limit their use due to the risk of circulatory collapse (cardiogenic shock, and/or pulmonary congestion). A safe method to administer β-blockers in the acute phase of HF is in great need. In this study, we developed an automated drug delivery system that controls the infusion of landiolol, an ultra-short-acting β-blocker, while preventing circulatory collapse. Method: We designed a system that simultaneously regulates cardiac function and volume status to control haemodynamics. The system monitors arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of haemodynamics, the system controls mean AP and mean PLA by administering landiolol, dextran, and furosemide. We applied the system for 60 min to 5 mongrel dogs with rapid pacing-induced HF, and assessed haemodynamics, MVO2 and lactate.Results: In all dogs, the system successfully adjusted delivery of the drugs resulting in accurate control of mean AP and mean PLA. From 15 to 60 min after the system was activated, median of absolute performance error (index of precision of control) was small for mean AP (median [interquartile range], 2.5 [2.1 – 3.7] %) and mean PLA (4.1 [1.8 – 6.2] %). Although the system decreased mean AP compared to baseline, mean and systolic AP were maintained not lower than 70 and 100 mmHg, respectively, and lactate did not increase. Furthermore, the system significantly decreased PLA and MVO2 (3.6 [3.3 – 4.0] to 2.7 [2.5 – 3.3] ml·min-1·100 g left ventricular weight-1) compared to baseline. Consequently, the automated drug delivery system successfully reduced MVO2 without inducing circulatory collapse.Conclusion: We developed an automated landiolol delivery system that achieved safe administration of landiolol in a canine model of acute HF. The system controlled AP and PLA accurately and stably, and reduced MVO2. With further development for clinical application, the automated drug delivery system may be the key tool to improve management of patients with HF.

Mechanoenergetics of the Negative Inotropism of Isoflurane in the Canine Left Ventricle 

1997 ◽  
Vol 87 (1) ◽  
pp. 82-93 ◽  
Author(s):  
Yasunori Nakayama ◽  
Miyako Takaki ◽  
Kunihisa Kohno ◽  
Junichi Araki ◽  
Hiroyuki Suga
Keyword(s):  
Oxygen Consumption ◽  
Myocardial Oxygen Consumption ◽  
Mechanical Energy ◽  
Contractile Proteins ◽  
Left Ventricular ◽  
Free Calcium ◽  
Canine Heart ◽  
Inotropic Effects ◽  
Total Mechanical Energy ◽  
Lv Volume

Background The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross-circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure-volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2). Methods Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane. Results Emax, PVA, and VO2 dose-dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05). Conclusions These mechanoenergetic findings suggest that the primary method by which isoflurane decreases contractility is not by decreasing Ca2+ sensitivity of contractile proteins but mainly by decreasing Ca2+ handling in the excitation-contraction coupling without myocardial oxygen wasting effect.

scholarly journals NO modulates myocardial O2consumption in the nonhuman primate: an additional mechanism of action of amlodipine

1999 ◽  
Vol 276 (6) ◽  
pp. H2069-H2075 ◽  
Author(s):  
Paul R. Forfia ◽  
Xiaoping Zhang ◽  
Delvin R. Knight ◽  
Andrew H. Smith ◽  
Christopher P. A. Doe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Nonhuman Primate ◽  
Myocardial Oxygen Consumption ◽  
Channel Blocker ◽  
Tissue Response ◽  
Canine Heart ◽  
Additional Mechanism

Recent evidence from our laboratory and others suggests that nitric oxide (NO) is a modulator of in vivo and in vitro oxygen consumption in the murine and canine heart. Therefore, the goal of our study was twofold: to determine whether NO modulates myocardial oxygen consumption in the nonhuman primate heart in vitro and to evaluate whether the seemingly cardioprotective actions of amlodipine may involve an NO-mediated mechanism. Using a Clark-type O2 electrode, we measured oxygen consumption in cynomologous monkey heart at baseline and after increasing doses of S-nitroso- N-acetylpenicillamine (SNAP; 10−7–10−4M), bradykinin (10−7–10−4M), ramiprilat (10−7–10−4M), and amlodipine (10−7–10−5M). SNAP (−38 ± 5.8%), bradykinin (−19 ± 3.9%), ramiprilat (−28 ± 2.3%), and amlodipine (−23 ± 4.5%) each caused significant ( P < 0.05) reductions in myocardial oxygen consumption at their highest dose. Preincubation of tissue with nitro-l-arginine methyl ester (10−4 M) blunted the effects of bradykinin (−5.4 ± 3.2%), ramiprilat (−4.8 ± 5.0%), and amlodipine (−5.3 ± 5.0%) but had no effect on the tissue response to SNAP (−38 ± 5.8%). Our results indicate that NO can reduce oxygen consumption in the primate myocardium in vitro, and they support a role for the calcium-channel blocker amlodipine as a modulator of myocardial oxygen consumption via a kinin-NO mediated mechanism.

The time interval between the onset of tricuspid E wave and annular Ea wave (TE-Ea) can predict right atrial pressure in patients with heart failure

2014 ◽  
Vol 14 (7) ◽  
pp. 585-590 ◽  
Author(s):  
Nasim Naderi ◽  
Ahmad Amin ◽  
Zahra Ojaghi Haghighi ◽  
Maryam Esmaeilzadeh ◽  
Hooman Bakhshandeh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Pressure ◽  
Right Atrial ◽  
Right Atrial Pressure ◽  
Time Interval ◽  
Patients With Heart Failure

scholarly journals Echocardiographic RV-E/e’ for predicting right atrial pressure: a review

2020 ◽  
Author(s):  
Andrew John Fletcher ◽  
Shaun Robinson ◽  
Bushra Rana
Keyword(s):  
Heart Failure ◽  
Clinical Decision Making ◽  
Prognostic Significance ◽  
Atrial Pressure ◽  
Right Atrial ◽  
Right Atrial Pressure ◽  
Future Research ◽  
Accurate Estimation ◽  
Diagnostic Ability ◽  
Wide Range

Right atrial pressure (RAP) is a key cardiac parameter of diagnostic and prognostic significance, yet current two-dimensional echocardiographic methods are inadequate for the accurate estimation of this haemodynamic marker. Right-heart trans-tricuspid Doppler and tissue Doppler echocardiographic techniques can be combined to calculate the right ventricular (RV) E/e’ ratio – a reflection of RV filling pressure which is a surrogate of RAP. A systematic search was undertaken which found seventeen articles that compared invasively measured RAP with RV-E/e’ estimated RAP. Results commonly concerned pulmonary hypertension or advanced heart failure/transplantation populations. Reported receiver operator characteristic analyses showed reasonable diagnostic ability of RV-E/e’ for estimating RAP in patients with coronary artery disease and RV systolic dysfunction. The diagnostic ability of RV-E/e’ was generally poor in studies of paediatrics, heart failure and mitral stenosis, whilst results were equivocal in other diseases. Bland-Altman analyses showed good accuracy but poor precision of RV-E/e’ for estimating RAP, but were limited by only being reported in seven out of seventeen articles. This suggests that RV-E/e’ may be useful at a population level but not at an individual level for clinical decision making. Very little evidence was found about how atrial fibrillation may affect the estimation of RAP from RV-E/e’, nor about the independent prognostic ability of RV-E/e’ . Recommended areas for future research concerning RV-E/e’ include; non-sinus rhythm, valvular heart disease, short and long term prognostic ability, and validation over a wide range of RAP.

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