Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations

Chen, Hsing I

ALI or pulmonary embolism (PE) has been reported in humans and animals with intracranial disorders such as head trauma, brain tumor, intracranial hypertension or cerebral compression. Early studies in our laboratory demonstrated that acute PE of hemorrhagic and fulminant type occurred accompanying severe hypertension and bradycardia (Cushing responses) in rats following cerebral compression (CC) or intracranial hypertension (ICH). The lung pathology was characterized by intravascular congestion and disruption of pulmonary large and small vessels leading to severe alveolar hemorrhage (alveolar flooding). These changes was prevented by spinal transection, sympathectomy and sympathoadrenergic blocking agents, but was not affected by decerebration, adrenalectomy, vagotomy and atropine. These results suggest that sympathetic nervous system is pivotal in the neurogenic PE. Brain areas above the medulla oblongata and parasympathetic nervous system play little role. [2] A series of studies was carried out to elucidate the hemodynamic events involved in the neurogenic PE. In anesthetized rats, we measured the aortic and pulmonary blood flow and used techniques of right and left heart bypass. The imbalance in the right and left ventricular output was characterized by a rapid and dramatic decline in aortic flow accompanying a gradual decrease in pulmonary arterial flow. In rats with a right heart bypass, ICH produced severe pulmonary hypertension and PE. In the left heart-bypassed rats, ICH induced systemic hypertension, http://www.jgc301.com; [e-mail] | Journal of Geriatric Cardiology whereas no significant changes occurred in the lungs. [4] In anesthetized dogs with a total heart bypass preparation, ICH produced constriction of the systemic and pulmonary resistance and capacitance vessels. [21] [22] [23] [24] The implications of these findings are: (1) Central sympathetic activation elicits increase in the systemic and pulmonary vascular resistance associated with decreases in vascular capacity in both circulations; (2) The major cause of volume and pressure loading in the pulmonary circulation is acute left ventricular failure resulting in a marked decrease in aortic flow; and (3) Systemic venous constriction causes a shift of blood from the systemic to the pulmonary circulation ( Figure 1) . A schematic representation summarizes the neural and hemodynamic consequence caused by cerebral compression (Figure 2 ). Spectral analysis of the aortic flow and pressure wave was employed to evaluate the hemodynamics of steady and pulsatile components. In anesthetized dogs, ICH caused significant increases in characteristic impedance, pulse wave reflection and total peripheral resistance with decrease in arterial compliance and cardiac output. The ventricular work was elevated. [25] Clinical study in patients with head injury of various severities, analysis of the heart rate variability with frequency analysis revealed increased low frequency percentage, and low to high frequency ratio with decrease in high frequency. The findings indicate augmented sympathetic and attenuated parasympathetic drive. These autonomic functional changes were related to the severity of brain-stem damage. [26] These two studies further support the contention that central sympathetic activation is involved in the Cushing pressor response and consequent hemodynamic and autonomic alterations.