BRIEF REVIEW Mechanisms of Neurogenic Pulmonary Edema

The pulmonary edema that develops quickly after a variety of cerebral insults, such as head injury, epileptic seizures, intracranial hypertension, and subarachnoid hemorrhage, is often accompanied by rapid flooding of airways with a protein-rich edema fluid (Weisman, 1939; MacKay, 1950; Richards, 1963; Simmons et al., 1968; Ciongoli and Posner, 1972; Theodore and Robin, 1976; Fisher and AboulNasr, 1979; Bayne and Simon, 1981; Fein and Rackow, 1982; Lee and Kobrine, 1983). To lay the framework for an understanding of the genesis of neurogenic pulmonary edema, a schematic representation of the pulmonary capillary-tissue-lymphatic system is indicated in Figure 1. Transcapillary fluid filtration is governed by the four Starling forces represented in the equation (Fig. 1): capillary hydrostatic pressure (Pc), plasma colloid osmotic pressure (irp), interstitial hydrostatic pressure (Pi), and interstitial tissue colloid osmotic pressure (vi). The plasma protein concentration is greater than the tissue fluid and lymph protein concentrations (Fig. 1). The lymph flow represents an overflow system. The tight alveolar interepithelial junctions in the normal lung (Taylor, 1981) restrict solute and water movement into the airspaces (Fig. 1). The protein concentration of airway edema fluid in neurogenic pulmonary edema approached that of plasma (Theodore and Robin, 1976; Fein and Rackow, 1982), suggesting that increases in permeability of pulmonary capillaries and alveolar epithelium to proteins are prominently involved in the development of pulmonary edema. Morphological studies in experimental animal models have supported these clinical observations (Hucker et al., 1976; Minnear and Connell, 1981). Since pulmonary arterial hypertension has been observed with the pulmonary edema in experimental animals and patients after central nervous system (CNS) injury (Sarnoff and Sarnoff, 1952; Wray and Nicotra, 1978), a rise in Pc may also be an important factor in edema formation. A purpose of this review is to discuss the relative roles of increases in permeability vs. capillary hydrostatic pressure in the development of neurogenic pulmonary edema. The rise in intracranial pressure, which is often observed in conjunction with neurogenic pulmonary edema (Ducker and Simmons, 1968; Simmons et al., 1968), may be a requirement for the development of pulmonary edema. Intracranial hypertension elicits the cardiopulmonary responses such as systemic arterial hypertension, left atrial hypertension, and pulmonary vasoconstriction that may be involved in pulmonary edemagenesis. Therefore, in this review, these responses to intracranial hypertension, the mechanisms mediating these responses, and their role in the development of pulmonary edema will be discussed. Lesions of specific anatomical sites in the brainstem and hypothalamus have been shown to lead to pulmonary edema. The following section reviews the role of CNS structures in the genesis of neurogenic pulmonary edema.