The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.

Sheep have reactive pulmonary intravascular macrophages, which are essential for the marked pulmonary vascular response to infusions of small quantities of endotoxin. In another species with reactive pulmonary intravascular macrophages, horses, our laboratory found that an intravenous biosafe detergent, tyloxapol, inhibited some systemic and pulmonary responses to endotoxin (Longworth KE, Smith BL, Staub NC, Steffey EP, and Serikov V. Am J Vet Res 57: 1063-1066, 1996). We determined whether the same detergent would inhibit endotoxin responses in awake sheep. In 10 awake, instrumented sheep with chronic lung lymph fistulas, we did a control experiment by intravenously infusing 1 microg/kg Escherichia coli endotoxin. One week later, we gave 40 micromol/kg tyloxapol intravenously 1-4 h before infusing the same dose of endotoxin. In these paired studies, we compared pulmonary hemodynamics, lung lymph dynamics, body temperature, circulating leukocyte concentrations, and circulating tumor necrosis factor for 6 h. In all 10 sheep, tyloxapol blocked 80-90% of the pulmonary responses and 70-90% of the systemic responses. Tyloxapol is safe, inexpensive, easy to use, and effective immediately. It may be a clinically useful approach to contravening many of the effects of endotoxemia, in humans as well as animals.

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The objective of this study was to investigate the influence of volume ventilation (VE) and cardiac output (Q) on the temperature of the expired gas at the distal end of the endotracheal tube in anesthetized humans. In 63 mechanically ventilated adults, we used a step decrease in the humidity of inspired gas to cool the lungs. After change from humid to dry gas ventilation, the temperature of the expired gas decreased. We evaluated the relationship between the inverse monoexponential time constant of the temperature fall (1/tau) and either VE or Q. When VE was increased from 5.67 +/- 1.28 to 7.14 +/- 1.60 (SD) l/min (P = 0. 02), 1/tau did not change significantly [from 1.25 +/- 0.38 to 1.21 +/- 0.51 min-1, P = 0.81]. In the 11 patients in whom Q changed during the study period (from 5.07 +/- 1.81 to 7.38 +/- 2.45 l/min, P = 0.02), 1/tau increased correspondingly from 0.89 +/- 0.22 to 1. 52 +/- 0.44 min-1 (P = 0.003). We calculated the airway thermal volume (ATV) as the ratio of the measured values Q to 1/tau and related it to the body height (BH): ATV (liters) = 0.086 BH (cm) - 9. 55 (r = 0.90).

Previously, we quantified reabsorption of interstitial pulmonary edema liquid into the pulmonary circulation during recovery from hydrostatic edema. To determine whether the bronchial circulation also reabsorbs edema liquid, we induced very-low-protein interstitial edema in seven sheep lungs by perfusion of the pulmonary circulation with diluted blood and 1% albumin in Krebs-Henseleit buffer containing 125I-labeled albumin for 70 +/- 40 min. In eight control sheep we perfused the lungs with diluted blood and 5% albumin in Krebs-Henseleit buffer containing 125I-albumin without causing significant edema formation. Subsequently, we washed the intravascular tracer from the pulmonary circulation with buffered saline and then perfused the bronchial vessels via the bronchoesophageal artery with whole or diluted blood (normal protein osmotic pressure). We measured flow, hematocrit, and 125I-albumin concentration in the venous outflow into the left atrium and into the azygos vein for 2 h. We calculated the volume of liquid reabsorbed on the basis of the change in hematocrit and 12I-albumin concentration in the outflow. On the basis of hematocrit dilution, the net clearance of interstitial liquid (edema minus control) averaged 21 ml (15% of the induced edema). One the basis of 125I-albumin reabsorption, the net clearance of interstitial liquid was 12 ml. We conclude that the bronchial circulation may be a clearance route for interstitial liquid and protein during recovery from low-protein hydrostatic edema.