Effects of various modes of mechanical ventilation in normal rats.

BACKGROUND: Recent studies in healthy mice and rats have reported that positive pressure ventilation delivered with physiological tidal volumes at normal end-expiratory volume worsens lung mechanics and induces cytokine release, thus suggesting that detrimental effects are due to positive pressure ventilation per se. The aim of this study in healthy animals is to assess whether these adverse outcomes depend on the mode of mechanical ventilation. METHODS: Rats were subjected to 4 h of spontaneous, positive pressure, and whole-body or thorax-only negative pressure ventilation (N = 8 per group). In all instances the ventilatory pattern was that of spontaneous breathing. Lung mechanics, cytokines concentration in serum and broncho-alveolar lavage fluid, lung wet-to-dry ratio, and histology were assessed. Values from eight animals euthanized shortly after anesthesia served as control. RESULTS: No evidence of mechanical ventilation-dependent lung injury was found in terms of lung mechanics, histology, or wet-to-dry ratio. Relative to control, cytokine levels and recruitment of polymorphonuclear leucocytes increased slightly, and to the same extent with spontaneous, positive pressure, and whole-body negative pressure ventilation. Thorax-only negative pressure ventilation caused marked chest and lung distortion, reversible increase of lung elastance, and higher polymorphonuclear leucocyte count and cytokine levels. CONCLUSION: Both positive and negative pressure ventilation performed with tidal volumes and timing of spontaneous, quiet breathing neither elicit an inflammatory response nor cause morpho-functional alterations in normal animals, thus supporting the notion of the presence of a critical volume threshold above which acute lung injury ensues. Distortion of lung parenchyma can induce an inflammatory response, even in the absence of volotrauma.

Plasma membrane disruptions with different modes of injurious mechanical ventilation in normal rat lungs*.

OBJECTIVES: Plasma membrane disruptions are caused by excessive mechanical stress and thought to be involved in inflammatory mediator upregulation. Presently, plasma membrane disruption formation has been studied only during mechanical ventilation with large tidal volumes and limitedly to subpleural alveoli. No information is available concerning the distribution of plasma membrane disruptions within the lung or the development of plasma membrane disruptions during another modality of injurious mechanical ventilation, i.e., mechanical ventilation with eupneic tidal volume (7 mL · kg) at low end-expiratory lung volume. The aim of this study is to assess whether 1) mechanical ventilation with eupneic tidal volume at low end-expiratory lung volume causes plasma membrane disruptions; and 2) the distribution of plasma membrane disruptions differs from that of mechanical ventilation with large tidal volume at normal end-expiratory lung volume. DESIGN: Experimental animal model. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: Plasma membrane disruptions have been detected as red spots in gelatin-included slices of rat lungs stained with ethidium homodimer-1 shortly after anesthesia (control) after prolonged mechanical ventilation with eupneic tidal volume at low end-expiratory lung volume followed or not by the restoration of physiological end-expiratory lung volume and after prolonged mechanical ventilation with large tidal volumes and normal end-expiratory lung volume. MEASUREMENTS AND MAIN RESULTS: Plasma membrane disruptions increased during mechanical ventilation at low end-expiratory lung volume, mainly at the bronchiolar level. Resealing of most plasma membrane disruptions occurred on restoration of normal end-expiratory lung volume. Mechanical ventilation with large tidal volume caused the appearance of plasma membrane disruptions, both bronchiolar and parenchymal, the latter to a much greater extent than with mechanical ventilation at low end-expiratory lung volume. The increase of plasma membrane disruptions correlated with the concomitant increase of airway resistance with both modes of mechanical ventilation. CONCLUSIONS: : Amount and distribution of plasma membrane disruptions between small airways and lung parenchyma depends on the type of injurious mechanical ventilation. This could be relevant to the release of inflammatory mediators.

Maintaining end-expiratory transpulmonary pressure prevents worsening of ventilator-induced lung injury caused by chest wall constriction in surfactant-depleted rats.

OBJECTIVE: To see whether in acute lung injury 1) compression of the lungs caused by thoracoabdominal constriction degrades lung function and worsens ventilator-induced lung injury; and 2) maintaining end-expiratory transpulmonary pressure by increasing positive end-expiratory pressure reduces the deleterious effects of chest wall constriction. DESIGN: Experimental study in rats. SETTING: Physiology laboratory. INTERVENTIONS: Acute lung injury was induced in three groups of nine rats by saline lavage. Nine animals immediately killed served as a control group. Group L had lavage only, group LC had the chest wall constricted with an elastic binder, and group LCP had the same chest constriction but with positive end-expiratory pressure raised to maintain end-expiratory transpulmonary pressure. After lavage, all groups were ventilated with the same pattern for 1½ hrs. MEASUREMENTS AND MAIN RESULTS: Transpulmonary pressure, measured with an esophageal balloon catheter, lung volume changes, arterial blood gasses, and pH were assessed during mechanical ventilation. Lung wet-to-dry ratio, albumin, tumor necrosis factor-α, interleukin-1ß, interleukin-6, interleukin-10, and macrophage inflammatory protein-2 in serum and bronchoalveolar lavage fluid and serum E-selectin and von Willebrand Factor were measured at the end of mechanical ventilation. Lavage caused hypoxemia and acidemia, increased lung resistance and elastance, and decreased end-expiratory lung volume. With prolonged mechanical ventilation, lung mechanics, hypoxemia, and wet-to-dry ratio were significantly worse in group LC. Proinflammatory cytokines except E-selectin were elevated in serum and bronchoalveolar lavage fluid in all groups with significantly greater levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in group LC, which also exhibited significantly worse bronchiolar injury and greater heterogeneity of airspace expansion at a fixed transpulmonary pressure than other groups. CONCLUSIONS: Chest wall constriction in acute lung injury reduces lung volume, worsens hypoxemia, and increases pulmonary edema, mechanical abnormalities, proinflammatory mediator release, and histologic signs of ventilator-induced lung injury. Maintaining end-expiratory transpulmonary pressure at preconstriction levels by adding positive end-expiratory pressure prevents these deleterious effects.

Na+-glucose cotransporter is also expressed in mesothelium of species with thick visceral pleura.

Molecular evidence for Na+-glucose cotransporter (SGLT1) in rabbit pleural mesothelium has been recently provided, confirming earlier functional findings on solute-coupled liquid absorption from rabbit pleural space. In this research we checked whether SGLT1 is also expressed in pleural mesothelium of species with thick visceral pleura, which receives blood from systemic circulation, but drains it into pulmonary veins. To this end immunoblot assays were performed on total protein extract of scraped visceral and parietal mesothelium of lambs and adult sheep, and of a human mesothelial cell line. All of them showed SGLT1 specific bands. Moreover, confocal immunofluorescence images of lamb pleural mesothelium showed that SGLT1 is located in apical membrane. Therefore, a solute-coupled liquid absorption should also occur from pleural space of species with thick visceral pleura. Because of this protein-free liquid entering interstitium between visceral mesothelium and capillaries, inherent Starling forces should be different than hitherto considered, and visceral pleura capillaries could absorb liquid even in these species.

The effect of maternal hypothermic cardiopulmonary bypass on fetal lamb temperature, hemodynamics, oxygenation, and acid-base balance.

OBJECTIVE: To evaluate fetal-maternal temperature relationship and fetal cardiovascular and metabolic response during maternal hypothermic cardiopulmonary bypass in pregnant ewes. METHODS: Cardiopulmonary bypass was instituted in 9 pregnant ewes, reaching 2 different levels of maternal hypothermia: 24 degrees C to 20 degrees C (deep hypothermia) in group A (5 cases) and less than 20 degrees C (very deep hypothermia) in group B (4 cases). Hypothermic levels were maintained for 20 minutes, then the rewarming phase was started. Fetal and maternal temperature, blood pressure, heart rate, electrocardiogram, blood gases, and acid-base balance were evaluated at different levels of hypothermia and during recovery. RESULTS: Fetal survival was related to maternal hypothermia: all group A fetuses survived, while 2 of 4 fetuses of group B in which maternal temperature was lowered below 18 degrees C died in a very deep acidotic and hypoxic status. Maternal temperature was always lower than fetal temperature during cooling; during rewarming the gradient was inverted. The start of cardiopulmonary bypass and cooling was associated with transient fetal tachycardia and hypertension; then, both fetal heart rate and blood pressure progressively decreased. The reduction of fetal heart rate was of 7 beats per minute for each degree of fetal cooling. Deep maternal hypothermia was associated with fetal alkalosis and reduction of Po(2). Very deep hypothermia, in particular below 18 degrees C, caused irreversible fetal acidosis and hypoxia. CONCLUSIONS: Deep maternal hypothermic cardiopulmonary bypass was associated with reversible modifications in fetal cardiovascular parameters, blood gases, and acid-base balance and therefore with fetal survival. On the contrary, fetuses did not survive to a very deep hypothermia below 18 degrees C.

Effects of abdominal distension on breathing pattern and respiratory mechanics in rabbits.

The effects of acute abdominal distension (AD) on the electromechanical efficiency (Eff) of the inspiratory muscles were investigated in anesthetized rabbits by recording the electrical activity (A), pressure (P) exerted by the diaphragm (di) and parasternal intercostal muscles (ic), and lung volume changes when an abdominal balloon was inflated to various degrees. Eff,ic increased with increasing AD both in supine and upright postures. In upright rabbits Eff,di increased for intermediate but decreased at higher levels of AD, whilst it decreased at all levels of AD in supine rabbits. Tidal volume (VT) response followed that of Eff,di. Tonic Aic and Adi and inspiratory prolongation were elicited by AD. The effects of these neural mechanisms, acting to limit end-expiratory lung volume and VT changes, were however small since vagotomy prevented tonic Adi and inspiratory prolongation and reduced tonic Aic, but changed lung volume responses to AD only little. Hence, reduced respiratory system compliance and changes in inspiratory muscle electromechanical efficiency dominate lung volume responses to acute AD.

Motor control of the diaphragm in anesthetized rabbits.

Diaphragmatic regions are recruited in a specialized manner either as part of a central motor program during non-respiratory maneuvers, e.g. vomiting, or because of reflex responses, e.g. esophageal distension. Some studies in cats and dogs suggest that crural and costal diaphragm may be differentially activated also in response to respiratory stimuli from chemoreceptors or lung and chest wall mechanoreceptors. To verify whether this could occur also in other species, the EMG activity from the sternal, costoventral, costodorsal, and crural diaphragm was recorded in 42 anesthetized rabbits in response to various respiratory maneuvers, such as chemical stimulation, mechanical loading, lung volume and postural changes before and after vagotomy, or a non-respiratory maneuver such as esophageal distension. Regional activity was evaluated from timing of the raw EMG signal, and amplitude and shape of the moving average EMG. In all animals esophageal distension caused greater inhibition of the crural than sternal and costal diaphragm, whereas under all the other conditions differential diaphragmatic activation never occurred. These results indicate that in response to respiratory stimuli the rabbit diaphragm behaves as a single unit under the command of the central respiratory control system.

Spinal cord retrograde perfusion: review of the literature and experimental observations.

BACKGROUND: Spinal cord damage represents a devastating complication of thoracic and thoracoabdominal aortic surgery. Retrograde perfusion as an alternative route to protect the spinal cord has recently been investigated with controversial results. We reviewed the literature and analyzed additional experimental observations. METHODS: Ten juvenile pigs were divided into control and study groups (A and B, respectively). Through a lateral thoracotomy the distal aortic arch was cannulated and connected to a cardiotomy reservoir. All animals underwent 40-minute single cross-clamping of the proximal descending aorta while keeping proximal systolic arterial pressure above 100 mmHg. In group B, normothermic arterial blood was delivered retrogradely through the azygos vein, maintaining perfusion pressure within 25-30 mmHg. Animals were allowed to recover to perform a primary neurologic evaluation. RESULTS: Flaccid paraplegia was uniformly observed in group A. In group B, all animals showed mild-to-moderate voluntary hind limb movements on awakening (p = 0.007). Controls also showed urine incontinence short after cross-clamping, and this was not observed in group B (p = 0.008). A different veno-arterial oxygen step-down was observed in blood collected from the excluded aorta in the two groups (p < 0.001). CONCLUSIONS: Preliminary results indicate that controlled retrograde normothermic perfusion alone through the azygos system provides some degree of protection from spinal cord ischemia. Bladder dysfunction may represent a simple test to detect massive cord damage intraoperatively. Retrograde spinal cord perfusion warrants further investigation.