Effects of Proximal Pulmonary Artery Occlusion on Pulsatile Right Ventricular Afterload in Rats

Fukumitsu, Masafumi; Kawada, Toru; Shimizu, Shuji; Turner, Michael J.; Uemura, Kazunori; Sugimachi, Masaru

doi:10.1253/circj.cj-16-0349

Cited by 10 publications

(7 citation statements)

References 35 publications

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“…The extension achieved by our approach is the ability to modulate all three Windkessel parameters in order to mimic diseased arterial systems presented to isolated tissues. These “diseased loads,” such as systemic hypertension (Segers et al, ) or pulmonary hypertension (Lankhaar et al, ; Fukumitsu et al, ), can be directly parameterized by measured values, or those obtained from the literature. The “diseased models” can be applied as real‐time loads for studying disease in healthy trabeculae.…”

Section: Discussionmentioning

confidence: 99%

Mechanical loading of isolated cardiac muscle with a real‐time computed Windkessel model of the vasculature impedance

et al. 2019

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To date, the mechanical loads imposed on isolated cardiac muscle tissue in vitro have been oversimplified. Researchers typically applied loads that are time‐invariant, resulting in either isometric and auxotonic contractions, or flat‐topped (isotonic shortening) work‐loops. These contraction types do not fully capture the dynamic response of contracting tissues adapting to a variable load, such as is experienced by ventricular tissue in vivo. In this study, we have successfully developed a loading system that presents a model‐based, time‐varying, continuously updated, load to cardiac tissue preparations. We combined a Windkessel model of vascular fluid impedance together with Laplace's Law and encoded it in a real‐time hardware‐based force‐length control system. Experiments were carried out on isolated rat left ventricular trabeculae; we directly compare the work‐loops arising from this protocol with those of a typical simplified isotonic shortening work‐loop system. We found that, under body conditions, cardiac trabeculae achieved greater mechanical work output against our new loading system, than with the simplified isotonic work‐loop protocol. We further tested whether loading the tissue with a mechanical impedance defined by “diseased” Windkessel model parameters had an effect on the performance of healthy trabeculae. We found that trabecula shortening decreased when applying the set of Windkessel parameters describing the hypertensive condition, and increased in the hypotensive state. Our implementation of a real‐time model of arterial characteristics provides an improved, physiologically derived, instantly calculated load for use in studying isolated cardiac muscle, and is readily applicable to study various disease conditions.

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Section: Discussionmentioning

confidence: 99%

Mechanical loading of isolated cardiac muscle with a real‐time computed Windkessel model of the vasculature impedance

et al. 2019

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“…Detailed surgical preparation has been described previously (Fukumitsu et al. ,b). Briefly, the rat was anesthetized with an intraperitoneal injection (2 mL/kg) of α‐chloralose (40 mg/mL) and urethane (250 mg/mL).…”

Section: Methodsmentioning

confidence: 99%

“…To achieve this goal, we used an in vivo experimental technique of estimating PAZ over a wide frequency range of physiological interest (0.1–50 Hz) in rats (Fukumitsu et al. ,b).…”

Section: Introductionmentioning

confidence: 99%

The pulsatile component of left atrial pressure has little effect on pulmonary artery impedance estimation in normal rats

et al. 2018

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Pulmonary artery impedance (PAZ) that measures the pulsatile properties of the vasculature provides diagnostic and prognostic information in patients with pulmonary vascular diseases. While downstream pressure [i.e., left atrial (LA) pressure] should be considered when calculating static properties of pulmonary vasculature, PAZ is commonly estimated without taking into account the pulsatile component of LA pressure. We examined whether PAZ can be estimated with reasonable accuracy without using LA pressure. Pulmonary artery (PA) flow, PA pressure, and LA pressure were measured under irregular pacing in eight normal Sprague‐Dawley rats. PAZ was estimated by analyzing a one‐input, one‐output system (I1O1 analysis) that does not include LA pressure, and a two‐input, one‐output system (I2O1 analysis) that includes LA pressure. Using a tube and 3‐element Windkessel model, PAZ was parameterized as peripheral resistance (RP), arterial compliance (CP), characteristic impedance (ZC), and transmission time to the reflection site (TD). These parameters were not significantly different between the I1O1 and I2O1 analyses (RP: 0.286 ± 0.040 vs. 0.274 ± 0.038 mmHg·min/mL, CP: 0.352 ± 0.049 vs. 0.343 ± 0.041 mL/mmHg, ZC: 0.115 ± 0.005 vs. 0.117 ± 0.005 mmHg·min/mL, TD: 13.2 ± 1.8 vs. 12.9 ± 1.7 msec). In conclusion, the I1O1 analysis that does not use LA pressure estimates PAZ with reasonable accuracy compared with the I2O1 analysis that uses LA pressure in normal rats. Our finding that the pulsatile component of LA pressure contributes little to PAZ estimation may justify the clinical use of the I1O1 analysis.

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“…Это позволяет формировать значительные по объему исследуемые группы и таким образом частично компенсировать невысокую воспроизводимость этих моделей. В единичных работах использовались крысы [13] и кролики [14].…”

Section: моделирование тэла с помощью индукции тромбообразования In Vivounclassified

“…Однако у данной модели имеется ряд существенных недостатков: модель слабо отражает патофизиологию тромбоэмболического процесса и является необратимой. В связи с этим основной целью использования этой модели является изучение ремоделирования правого желудочка (ПЖ) после ТЭЛА [13].…”

Section: моделирование тэла с помощью индукции тромбообразования In Vivounclassified

Approaches to modeling pulmonary embolism and chronic thromboembolic pulmonary hypertension in rodents and medium-sized laboratory animals

Карпов

Smirnov

Shilenko

et al. 2021

Transl. med. (Print)

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Pulmonary embolism (PE) is the third most common cardiovascular disease. It is still associated with high hospital mortality, as well as with the development of acute and chronic complications. Treatment and prevention of PE and its complications requires high-tech approaches aimed at improving the prognosis of patients. In this regard, experimental studies aimed at studying the pathogenesis, improving diagnostic methods and searching for new pharmacological substances for the prevention and treatment of PE are in demand from the point of view of clinical practice. Considering the current trends in preclinical research, experimental work on rodents — mice, rats, hamsters, as well as on medium-sized laboratory animals (rabbits) is becoming more and more common. The use of these animal species is ethically acceptable and economically viable. The choice of a specific type of animal and a method for modeling PE is primarily determined by the objectives of the study. This article provides an overview of the main approaches to modeling PE, as well as discusses the advantages and disadvantages of each method. Special attention is paid to the modeling of chronic thromboembolic pulmonary hypertension (CTEPH) as one of the most dangerous complications of PE. The work analyzed publications from 1978 to 2020, in which PE was simulated in rodents and medium laboratory animals.

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Effects of Proximal Pulmonary Artery Occlusion on Pulsatile Right Ventricular Afterload in Rats

Cited by 10 publications

References 35 publications

Mechanical loading of isolated cardiac muscle with a real‐time computed Windkessel model of the vasculature impedance

Mechanical loading of isolated cardiac muscle with a real‐time computed Windkessel model of the vasculature impedance

The pulsatile component of left atrial pressure has little effect on pulmonary artery impedance estimation in normal rats

Approaches to modeling pulmonary embolism and chronic thromboembolic pulmonary hypertension in rodents and medium-sized laboratory animals

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