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CLINICAL STUDY: HEART FAILURE

Modulation of alveolar-capillary sodium handling as a mechanism of protection of gas transfer by enalapril, and not by losartan, in chronic heart failure

^a Istituto di Cardiologia dell’Università degli Studi, Centro di Studio per le Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche, Centro Cardiologico, I.R.C.C.S., Milano, Italy

Manuscript received May 18, 2000; revised manuscript received August 18, 2000, accepted October 2, 2000.

Reprint requests and correspondence: Dr. Marco Guazzi, Istituto di Cardiologia, dell’Università degli Studi, Via C. Parea 4, 20138 Milan, Italy
marco.guazzi{at}cardiologicomonzino.it

OBJECTIVES

We sought to compare the protective efficacy of enalapril and losartan on lung diffusion in chronic heart failure (CHF).

BACKGROUND

In CHF, hydrostatic overload causes disruption of the alveolar-capillary membrane and depression of carbon monoxide diffusion (DCO); enalapril improves DCO through mechanisms still undefined; and saline infusion in the pulmonary circulation worsens DCO, putatively because of an upregulated sodium transport to the alveolar interstitium. We investigated whether enalapril modulates sodium handling and whether losartan shares the same properties.

METHODS

In 29 patients with CHF, DCO, its membrane diffusion subcomponent (DM) and right atrial and pulmonary wedge pressures were monitored during saline infusion, in the control condition, during enalapril therapy (20 mg/day) for two weeks and after crossover to losartan (50 mg/day) for two weeks (first 20 patients), or after the combination of enalapril with aspirin (325 mg/day) for one week (last 9 patients).

RESULTS

Saline, 150 ml, lowered DCO (–7.9%; p < 0.01) and DM (–9.9%; p < 0.01) without hydrostatic variations. Responses to 750 ml of saline were qualitatively similar. After treatment with enalapril, baseline DCO (p < 0.01) and DM (p < 0.01) were augmented; after sodium loading, the percent reductions of DCO (p < 0.01) and DM (p < 0.01) were comparable to those before it, resulting in higher absolute values. This suggests that the greater the gas conductance improvement with enalapril, the lower the impedance with saline. Losartan was ineffective on gas transfer at rest and under salt challenge. Aspirin counteracted the benefits of enalapril.

CONCLUSIONS

In CHF, enalapril protects lung diffusion, possibly through a prostaglandin-mediated modulation of sodium overfiltration to the alveolar interstitium; losartan does not share this ability.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AT1 = angiotensin type 1 receptor   CHF = chronic heart failure   DCO = diffusing capacity for carbon monoxide   DM = alveolar-capillary membrane diffusing capacity   HCT = hematocrit   LVEF = left ventricular ejection fraction   NE = norepinephrine   PRA = plasma renin activity   VA = alveolar volume   Vc' = pulmonary capillary blood volume

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