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We studied the impact of mechanically regulated, expiratory negative airway pressure (ENAP) ventilation on pulmonary and systemic circulation including its mechanisms and potential applications. Microminipigs weighing about 10 kg were anesthetized (n = 5). First, hemodynamic variables were evaluated without and with ENAP to approximately -16 cmH.sub.2O. ENAP significantly increased heart rate and cardiac output, but decreased right atrial, pulmonary arterial and pulmonary capillary wedge pressures. Second, the evaluation was repeated following pharmacological adrenergic blockade, modestly blunting ENAP effects. Third, fluvoxamine (10 mg/kg) was intravenously administered to intentionally induce cardiovascular collapse in the presence of adrenergic blockade. ENAP was started when systolic pressure was < 40 mmHg in the animals assigned to ENAP treatment-group. Fluvoxamine induced cardiovascular collapse within 4 out of 5 animals. ENAP increased systolic pressure to > 50 mmHg (n = 2): both animals fully recovered without neurological deficit, whereas without ENAP both animals died of cardiac arrest (n = 2). ENAP may become an innovative treatment for drug-induced cardiovascular collapse. Keywords: Cardiovascular collapse, Expiratory negative airway pressure, Hemodynamics, Mechano-physiology, Resuscitation, Author(s): Mihoko Hagiwara-Nagasawa[sup.1], Ryuichi Kambayashi[sup.1], Ai Goto[sup.1], Koki Chiba[sup.1], Takeshi Wada[sup.1,2], Yoshio Nunoi[sup.1], Hiroko Izumi-Nakaseko[sup.1], Yoshinori Takei[sup.3], Akio Matsumoto[sup.4], Keith G. Lurie[sup.5] and Atsushi Sugiyama[sup.1,3,4] Background A severe low cardiac-output [...]