Key result
Tezosentan treatment in a piglet model of acute pulmonary thromboembolism showed that endothelin-mediated vasoconstriction accounted for about 25% of the increase in pulmonary vascular resistance.
Why the study?
Does Tezosentan reduce pulmonary vascular resistance index in a piglet model of acute pulmonary thromboembolism?
Does Tezosentan reduce pulmonary vascular resistance index in a piglet model of acute pulmonary thromboembolism?
In a piglet model of acute pulmonary embolism, increased pulmonary vascular resistance is primarily due to mechanical obstruction, but endothelin-mediated vasoconstriction contributes approximately 25% to the increase.
Answers are grounded in this paper and cite their sources.
Endothelin antagonism may offset vasoconstriction in acute PTE; animal data leaves open human therapeutic potential.
We aimed to investigate the role of endothelin-mediated vasoconstriction following acute pulmonary thromboembolism (APTE). Thirteen anesthetized piglets (~25 kg) were ventilated with 0 PEEP. Cardiac output (Qt) and wedge pressure (Pw) were measured by a Swan Ganz catheter, along with arterial and venous blood gases. APTE was induced by autologous blood clots (~0.8 g/kg, 12-16 pieces) via a jugular venous catheter at time = 0 minutes until the mean pulmonary arterial pressure (Ppa) was about 2.5 times the baseline at 30 minutes. Eight control animals (Group 1) received only normal saline afterward, while the remaining five (Group 2) received at time = 40-minute saline plus Tezosentan, a nonspecific endothelin antagonist. The drug was initially given as an intravenous bolus (10 mg/kg), followed by an infusion (2 mg/min) until the end of the experiment at 2 hours. Hemodynamic data were measured before APTE and then at 30-minute intervals. Pulmonary vascular resistance index (PVRI) was calculated as (Ppa-Pw)/CI, where CI was cardiac index or Qt/W (body weight). Fluorescent microspheres (FMS) were used to mark regional blood flows and ventilation for cluster analysis. PVRI acutely increased within minutes and remained high despite some recovery over time. With Tezosentan treatment, the results showed that endothelin-mediated vasoconstriction persisted significantly up to 2 hours and accounted for about 25% of the increase in PVRI while clot obstruction accounted for the remaining 75%. CI remained relatively constant throughout. Tezosentan also affected PVRI indirectly by mitigating the shift of regional blood flow back to the embolized areas over time, possibly by attenuating vasoconstriction in the nonembolized areas. We conclude that following APTE, although the increased PVRI is mostly due to mechanical embolic obstruction, secondary factors such as vasoconstriction and pattern of regional blood flow over time also play important roles.
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Tsang et al. (2012) studied Acute pulmonary thromboembolism (n=13). Tezosentan vs. Normal saline was evaluated on Pulmonary vascular resistance index (PVRI). Tezosentan treatment in a piglet model of acute pulmonary thromboembolism showed that endothelin-mediated vasoconstriction accounted for about 25% of the increase in pulmonary vascular resistance.
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