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[Effects of ouabain and furosemide on right ventricular function, pulmonary and renal circulation ]
Abstract:
Digitalis glycosides are often used in the treatment of cor pulmonale. However, several investigators have shown that these drugs produce an increase of pulmonary vascular resistance. Combination of other drugs which could reduce this unfavorable effects is to be explored. The purpose of this study is to observe the effects of ouabain on the systemic, pulmonary and renal hemodynamics and right ventricular function with special emphasis on modification of its effects in combination with furosemide. Normal open-chest dogs anesthetized with pentobarbital sodium were used under artificial ventilation. Isolated dog lung lobes were also examined in which perfusion was maintained with heparinized autologous blood at a constant flow rate by a pulsatile pump. In normal dogs, intravenous ouabain administration (0.03 mg/kg) resulted in rise of systemic, pulmonary and renal vascular resistance. However, furosemide (5 mg/kg), when given 3 minutes after ouabain administration, suppressed the vasoconstrictive effect of ouabain. Right ventricular tension (measured by strain gauge arch) was increased after ouabain administration, but this increase was not altered by the combination with furosemide. In the isolated lung lobe, ventilated with normal alveolar gas (14.7% O2, 5.4% CO2) and hypoxic gas (5% O2, 5.4% CO2), ouabain (0.48 mg) caused significant rise of pulmonary inflow pressure (P less than 0.05) which was suppressed significantly by furosemide administration (40 mg) given 3 minutes before and after ouabain administration (P less than 0.05). These results suggest that furosemide may be used rationally with ouabain, because of its effects to eliminate the pulmonary vasoconstriction caused by ouabain and to preserve its positive intropic action.
Insights
Furosemide counteracts ouabain-induced pulmonary vasoconstriction in dogs, potentially allowing safer use of digitalis glycosides for cor pulmonale treatment. This combination preserves ouabain's positive inotropic action without worsening right ventricular function.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Context:
- Digitalis glycosides, like ouabain, are used for cor pulmonale but increase pulmonary vascular resistance.
- Exploring drug combinations to mitigate ouabain's adverse pulmonary effects is crucial.
Purpose:
- To investigate ouabain's effects on systemic, pulmonary, and renal hemodynamics and right ventricular function.
- To evaluate furosemide's ability to modify ouabain's hemodynamic effects.
Summary:
- Ouabain administration increased systemic, pulmonary, and renal vascular resistance in dogs.
- Furosemide administration attenuated ouabain's pulmonary vasoconstrictive effects in both intact dogs and isolated lung lobes.
- Right ventricular tension increased with ouabain but was not altered by furosemide co-administration.
Impact:
- Furosemide effectively mitigates ouabain-induced pulmonary vasoconstriction.
- This suggests a rational basis for combining furosemide with ouabain in clinical settings.
- The combination may allow for the beneficial inotropic effects of ouabain while minimizing pulmonary vascular resistance.