Modeling of Acute Pulmonary Arterial Hypertension in Pigs Using a Stable Thromboxane A2 Analogue (U46619): Dose Adjustment and Assessment of Hemodynamic Reactions

Гончарова, Н. С.; Andreeva, E. M.; Вахрушев, А. Д.; Leandro, Heber Ivan Condori; Мурашова, Лада; Voronin, S. E.; Korobchenko, L; Mitrofanova, Lubov; Skorik, Y. A.; Галагудза, М. М.; Моисеева, О. М.; Mikhaylov, Evgeny N.

doi:10.1007/s10517-021-05142-2

Cited by 5 publications

(9 citation statements)

References 12 publications

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“…The slightly higher correlation between mPAP and PWTT during hypoxia can be explained by the more stable heart rate under short hypoxia and lack of the TXA-related chronotropic effects [32]. Nevertheless, using the TXA analogue U46619 is highly recommended for reversible PH induction in porcine models [32]. During hypoxic pulmonary vasoconstriction, we obtained a smaller range of pulmonary hypertension, knowing that higher variance of PWTT occurs especially under very high pressures (Figure 5).…”

Section: Discussionmentioning

confidence: 86%

“…The subset of experiments during hypoxia was conducted for two reasons: (1) knowing that hypoxia increases PAP due to hypoxic pulmonary vasoconstriction; (2) to exclude possible variations in PWTT by TXA itself. The slightly higher correlation between mPAP and PWTT during hypoxia can be explained by the more stable heart rate under short hypoxia and lack of the TXA-related chronotropic effects [32]. Nevertheless, using the TXA analogue U46619 is highly recommended for reversible PH induction in porcine models [32].…”

Section: Discussionmentioning

confidence: 99%

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Correlation of Pulse Wave Transit Time with Pulmonary Artery Pressure in a Porcine Model of Pulmonary Hypertension

et al. 2021

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For the non-invasive assessment of pulmonary artery pressure (PAP), surrogates like pulse wave transit time (PWTT) have been proposed. The aim of this study was to invasively validate for which kind of PAP (systolic, mean, or diastolic) PWTT is the best surrogate parameter. To assess both PWTT and PAP in six healthy pigs, two pulmonary artery Mikro-Tip™ catheters were inserted into the pulmonary vasculature at a fixed distance: one in the pulmonary artery trunk, and a second one in a distal segment of the pulmonary artery. PAP was raised using the thromboxane A2 analogue U46619 (TXA) and by hypoxic vasoconstriction. There was a negative linear correlation between PWTT and systolic PAP (r = 0.742), mean PAP (r = 0.712) and diastolic PAP (r = 0.609) under TXA. During hypoxic vasoconstriction, the correlation coefficients for systolic, mean, and diastolic PAP were consistently higher than for TXA-induced pulmonary hypertension (r = 0.809, 0.778 and 0.734, respectively). Estimation of sPAP, mPAP, and dPAP using PWTT is feasible, nevertheless slightly better correlation coefficients were detected for sPAP compared to dPAP. In this study we establish the physiological basis for future methods to obtain PAP by non-invasively measured PWTT.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Correlation of Pulse Wave Transit Time with Pulmonary Artery Pressure in a Porcine Model of Pulmonary Hypertension

et al. 2021

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“…In one animal, a lethal massive pulmonary embolism possibly associated with TXA2 infusion was detected. The thrombogenic effect of TXA2 despite adequate anticoagulation might be responsible for this complication, as shown in a previous report [ 13 ].…”

Section: Discussionmentioning

confidence: 69%

“…During induction, the mean PA pressure was targeted at 40 mmHg. Continuous administration of TXA2 was gradually increased every 5 min according to a previously established protocol [ 13 ]. Electrocardiography (ECG) and both systemic pressure and PAP were continuously recorded.…”

Section: Methodsmentioning

confidence: 99%

“…Among several PAH models, intravenous thromboxane A2 (TXA2) infusion has been tested for the evaluation of acute hemodynamic changes after PADN [ 12 ]. Previous reports have described an escalating dosage protocol for reproducible PAH modeling [ 13 ]. Therefore, because of the rapid inducibility, stable PAP elevation, and complete reversibility after TXA2 withdrawal, we have chosen this model for the current experiment.…”

Section: Introductionmentioning

confidence: 99%

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Pulmonary and Systemic Hemodynamics following Multielectrode Radiofrequency Catheter Renal Denervation in Acutely Induced Pulmonary Arterial Hypertension in Swine

Вахрушев

Leonardo

Гончарова

et al. 2021

BioMed Research International

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Objective. We aimed to assess the effects of renal denervation (RDN) on systemic and pulmonary hemodynamics in a swine model of thromboxane A2- (TXA2-) induced pulmonary arterial hypertension (PAH). Methods. The study protocol comprised two PAH inductions with a target mean pulmonary artery pressure (PAP) of 40 mmHg at baseline and following either the RDN or sham procedure. Ten Landrace pigs underwent the first PAH induction; then, nine animals were randomly allocated in 1 : 1 ratio to RDN or sham procedure; the second PAH induction was performed in eight animals (one animal died of pulmonary embolism during the first PAH induction, and one animal died after RDN). In the RDN group, ablation was performed in all available renal arteries, and balloon inflation within artery branches was performed in controls. An autopsy study of the renal arteries was performed. Results. At baseline, the target mean PAP was achieved in all animals with 25.0 [20.1; 25.2] mcg of TXA2. The second PAH induction required the same mean TXA2 dose and infusion time. There was no statistically significant difference in the mean PAP at second PAH induction between the groups ( 39.0 ± 5.3 vs. 39.75 ± 0.5 mmHg, P > 0.05 ). In the RDN group, the second PAH induction resulted in a numerical but insignificant trend toward a decrease in the mean systemic blood pressure and systemic vascular resistance, when compared with the baseline induction ( 74 ± 18.7 vs. 90.25 ± 28.1 mmHg and 1995.3 ± 494.3 vs. 2433.7 ± 1176.7 d y n ∗ sec ∗ c m − 5 , P > 0.05 , respectively). No difference in hemodynamic parameters was noted in the sham group between the first and second PAH induction. Autopsy demonstrated artery damage in both groups, but RDN resulted in more severe lesions. Conclusions. According to our results, RDN does not result in significant acute pulmonary or systemic hemodynamic changes in the TXA2-induced PAH model. The potential chronic effects of RDN on PAH require further research.

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Respiratory gating improves correlation between pulse wave transit time and pulmonary artery pressure in experimental pulmonary hypertension

Mueller-Graf,

Frenkel,

Merz

et al. 2024

Physiol. Meas.

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Since pulse wave transit time (PWTT) shortens as pulmonary artery pressure (PAP) increases it was suggested as a potential non-invasive surrogate for PAP. The state of tidal lung filling is also known to affect PWTT independently of PAP. The aim of this retrospective analysis was to test whether respiratory gating improved the correlation coefficient between PWTT and PAP. In each one of five anesthetized and mechanically ventilated pigs two high-fidelity pressure catheters were placed, one directly behind the pulmonary valve, and the second one in a distal branch of the pulmonary artery. PAP was raised using the thromboxane A2 analogue U46619 and animals were ventilated in a pressure controlled mode (I:E ratio 1:2, respiratory rate 12/min, tidal volume of 6 ml/kg). All signals were recorded using the multi-channel platform PowerLab®. The arrival of the pulse wave at each catheter tip was determined using a MATLAB-based modified hyperbolic tangent algorithm and PWTT calculated as the time interval between these arrivals. Correlation coefficient for PWTT and mean PAP was r = 0.932 for thromboxane. This correlation coefficient increased considerably when heart beats either at end-inspiration (r = 0.978) or at end-expiration (r = 0.985) were selected (= respiratory gating). Therefore the estimation of mean PAP from PWTT improved significantly when taking the respiratory cycle into account. Respiratory gating is suggested to improve for the estimation of PAP by PWTT.

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Modeling of Acute Pulmonary Arterial Hypertension in Pigs Using a Stable Thromboxane A2 Analogue (U46619): Dose Adjustment and Assessment of Hemodynamic Reactions

Cited by 5 publications

References 12 publications

Correlation of Pulse Wave Transit Time with Pulmonary Artery Pressure in a Porcine Model of Pulmonary Hypertension

Correlation of Pulse Wave Transit Time with Pulmonary Artery Pressure in a Porcine Model of Pulmonary Hypertension

Pulmonary and Systemic Hemodynamics following Multielectrode Radiofrequency Catheter Renal Denervation in Acutely Induced Pulmonary Arterial Hypertension in Swine

Respiratory gating improves correlation between pulse wave transit time and pulmonary artery pressure in experimental pulmonary hypertension

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