Evolving changes in lung interstitial fluid content after acute myocardial infarction: mechanisms and pathophysiological correlates

Abstract

In acute myocardial infarction (AMI), alveolar interstitium edema is generally attributed to a hydrostatic imbalance. However, inflammatory burden and/or neural/hormonal/hemodynamic stimulation might injure the microvascular endothelium, eliciting interstitial overflow and altering alveolar-capillary gas diffusion. In 118 patients with AMI (ejection fraction ≥50% and wedge pulmonary pressure <16 mmHg), admission alveolar-capillary gas diffusing membrane conductance (DM) averaged 35.1 ml·min−1·mmHg−1 and was 27% lower than in 25 controls ( P < 0.01). Infusion of saline in the pulmonary circulation (to test sodium exchange across the pulmonary capillary wall) lowered DM by 7.1% ( P < 0.01) and was neutral in controls. At 1 wk, 83 patients that showed DM improvement >5% were assigned to group 1, and 28 patients with DM worsening >5% were assigned to group 2. Saline retained efficacy in group 2 and had no DM effect in group 1 (supporting a link between changes in baseline DM and those in microvascular salt exchange). Ventricular function was unchanged in group 1, whereas group 2 had developed diastolic dysfunction. At 1 yr, 3% of cases in group 1 and 37% of cases in group 2 had alveolar edema. Thus, AMI is frequently associated with abnormal pulmonary microvascular sodium transport/water conductance that, in the case of ventricular dysfunction supervenience, may persist and worsen the outcome. In 37 AMI similar patients and 11 control subjects, nitric oxide overexpression with l-arginine improved baseline DM and in AMI patients prevented DM reduction by saline, suggesting a mechanistic role of an impaired nitric oxide pathway in the microvascular barrier dysfunction.