Effects of mechanical ventilation with expiratory negative airway pressure on porcine pulmonary and systemic circulation: mechano-physiology and potential application

Hiroko Izumi-Nakaseko,Keith G Lurie,Akio Matsumoto,Ryuichi Kambayashi,Takeshi Wada,Ai Goto,Mihoko Hagiwara-Nagasawa,Atsushi Sugiyama,Yoshinori Takei,Yoshio Nunoi,Koki Chiba

doi:10.1186/s12576-021-00801-5

Abstract

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 cmH2O. 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.

Highlights

A severe low cardiac-output state requires assist devices including intra-aortic balloon pump, ventricular assist device and extracorporeal circulation to avoid life-threatening end-organ hypoperfusion [1]
Since the benefits of expiratory” negative airway pressure (ENAP) are not completely understood, we primarily focused on mechano-physiology of this new treatment; namely, how ENAP may affect pulmonary as well as systemic circulation, whether the effects of ENAP may depend on adrenergic activity, and whether ENAP can be effective against the drug-induced cardiovascular collapse as a non-invasive treatment
Effects of ENAP on pulmonary and systemic circulation in animals without pharmacological adrenergic denervation Typical tracings of intra-tracheal pressure, electrocardiogram, aortic pressure and pulmonary arterial pressure without and with ENAP are depicted in Fig. 3 left and right panels, respectively

Summary

Introduction

A severe low cardiac-output state requires assist devices including intra-aortic balloon pump, ventricular assist device and extracorporeal circulation to avoid life-threatening end-organ hypoperfusion [1]. These devices can be effective for ameliorating the cardiovascular collapse, their application may be time-consuming, highly invasive and expensive with less versatility. “inspiratory” negative airway pressure with impedance threshold device has been shown to increase the cardiac output during cardiac arrest resuscitation with cardiac massage [10,11,12,13] Another technology with an intrathoracic pressure regulator was developed, which actively creates a continuous low level of negative intrathoracic pressure during cardiac massage following each inspiratory positive pressure breath [14,15,16]. Since the benefits of ENAP are not completely understood, we primarily focused on mechano-physiology of this new treatment; namely, how ENAP may affect pulmonary as well as systemic circulation, whether the effects of ENAP may depend on adrenergic activity, and whether ENAP can be effective against the drug-induced cardiovascular collapse as a non-invasive treatment

Methods

Results

Discussion

Conclusion