Publications

To determine whether beta-adrenergic agonist therapy increases alveolar liquid clearance during the resolution phase of hydrostatic pulmonary edema, we studied alveolar and lung liquid clearance in two animal models of hydrostatic pulmonary edema. Hydrostatic pulmonary edema was induced in sheep by acutely elevating left atrial pressure to 25 cmH(2)O and instilling 6 ml/kg body wt isotonic 5% albumin (prepared from bovine albumin) in normal saline into the distal air spaces of each lung. After 1 h, sheep were treated with a nebulized beta-agonist (salmeterol) or nebulized saline (controls), and left atrial pressure was then returned to normal. beta-Agonist therapy resulted in a 60% increase in alveolar liquid clearance over 3 h (P < 0.001). Because the rate of alveolar fluid clearance in rats is closer to human rates, we studied beta-agonist therapy in rats, with hydrostatic pulmonary edema induced by volume overload (40% body wt infusion of Ringer lactate). beta-Agonist therapy resulted in a significant decrease in excess lung water (P < 0.01) and significant improvement in arterial blood gases by 2 h (P < 0.03). These preclinical experimental studies support the need for controlled clinical trials to determine whether beta-adrenergic agonist therapy would be of value in accelerating the resolution of hydrostatic pulmonary edema in patients.

Many physiologic roles of PTHrP are emerging. The protein functions locally in diverse tissues, often regulating the entry of cells into a differentiation pathway or acting as an epithelial signal in epithelial-mesenchymal interactions. To carry out these functions, PTHrP uses the receptor it shares with PTH or one of several PTHrP receptors that have evolved to recognize selectively the PTH-like region of PTHrP or other domains. Thus, PTHrP is a polyhormone. An exquisite selectivity barrier allows PTHrP to carry out its local tissue functions at the same time PTH uses their shared receptor to regulate systemic calcium homeostasis. This barrier is breached under pathologic circumstances, such as when malignant tumors secrete enough PTHrP into blood to cause PTH-like effects, including hypercalcemia. Powerful genetic models that have been developed in the past 7 years promise to give continuing insights into the physiology and pathophysiology of PTHrP.