Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin
In patients at risk for sudden ethanol (ETOH) intravascular absorption, prompt treatment of pulmonary hypertension (PHTN) will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2008-01-01
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| Series: | Annals of Cardiac Anaesthesia |
| Subjects: | |
| Online Access: | http://www.annals.in/article.asp?issn=0971-9784;year=2008;volume=11;issue=2;spage=96;epage=103;aulast=Sidi |
| _version_ | 1818030509424377856 |
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| author | Sidi Avner Naik Bhiken Urdaneta Felipe Muehlschlegel Jochen Kirby David Lobato Emilio |
| author_facet | Sidi Avner Naik Bhiken Urdaneta Felipe Muehlschlegel Jochen Kirby David Lobato Emilio |
| author_sort | Sidi Avner |
| collection | DOAJ |
| description | In patients at risk for sudden ethanol (ETOH) intravascular absorption, prompt treatment of pulmonary hypertension (PHTN) will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664) and nitroglycerin (NTG) during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT), as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP), and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg (<i> n</i> = 7) normal saline, a 500-<i>μ</i>g/kg bolus of UK343-664 (<i> n</i> = 8), or NTG 1 <i>μ</i>g/kg (<i> n</i> = 8); each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP), and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR). Within 2 minutes after treatment with either drug, CVP, heart rate (HR), and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR) ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241±579 and 1224±494 dyne · cm/sec<sup> 5</sup> , which were threefold-to-fourfold increased baseline values, to 672±308 and 538±203 dyne · cm/sec<sup> 5</sup> respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from baseline values of PVR, and the partial recovery of systemic pressure and RV contractility compared to the maximal change during target PHTN, were significant only in the sildenafil analogue group. |
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| institution | Directory Open Access Journal |
| issn | 0971-9784 |
| language | English |
| last_indexed | 2024-12-10T05:36:43Z |
| publishDate | 2008-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
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| series | Annals of Cardiac Anaesthesia |
| spelling | doaj.art-0e9e4dba4f3f4f418f9fbc6143b0cd8e2022-12-22T02:00:24ZengWolters Kluwer Medknow PublicationsAnnals of Cardiac Anaesthesia0971-97842008-01-0111296103Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerinSidi AvnerNaik BhikenUrdaneta FelipeMuehlschlegel JochenKirby DavidLobato EmilioIn patients at risk for sudden ethanol (ETOH) intravascular absorption, prompt treatment of pulmonary hypertension (PHTN) will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664) and nitroglycerin (NTG) during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT), as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP), and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg (<i> n</i> = 7) normal saline, a 500-<i>μ</i>g/kg bolus of UK343-664 (<i> n</i> = 8), or NTG 1 <i>μ</i>g/kg (<i> n</i> = 8); each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP), and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR). Within 2 minutes after treatment with either drug, CVP, heart rate (HR), and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR) ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241±579 and 1224±494 dyne · cm/sec<sup> 5</sup> , which were threefold-to-fourfold increased baseline values, to 672±308 and 538±203 dyne · cm/sec<sup> 5</sup> respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from baseline values of PVR, and the partial recovery of systemic pressure and RV contractility compared to the maximal change during target PHTN, were significant only in the sildenafil analogue group.http://www.annals.in/article.asp?issn=0971-9784;year=2008;volume=11;issue=2;spage=96;epage=103;aulast=SidiEthanolnitroglycerinpulmonary hypertensionright ventricular dysfunctionsildenafil |
| spellingShingle | Sidi Avner Naik Bhiken Urdaneta Felipe Muehlschlegel Jochen Kirby David Lobato Emilio Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin Annals of Cardiac Anaesthesia Ethanol nitroglycerin pulmonary hypertension right ventricular dysfunction sildenafil |
| title | Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin |
| title_full | Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin |
| title_fullStr | Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin |
| title_full_unstemmed | Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin |
| title_short | Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin |
| title_sort | treatment of ethanol induced acute pulmonary hypertension and right ventricular dysfunction in pigs by sildenafil analogue uk343 664 or nitroglycerin |
| topic | Ethanol nitroglycerin pulmonary hypertension right ventricular dysfunction sildenafil |
| url | http://www.annals.in/article.asp?issn=0971-9784;year=2008;volume=11;issue=2;spage=96;epage=103;aulast=Sidi |
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