Effects of aminophylline on respiratory muscle interaction

We studied the effects of aminophylline on respiratory muscle interaction during quiet breathing by measuring (1) changes in rib cage and abdominal cross-sectional area, (2) tidal volume, (3) abdominal and esophageal pressure, (4) diaphragm and parasternal intercostal electromyogram (EMG) and parasternal intercostal intramuscular pressure, and (5) triangularis sternl and transversus abdominis EMG, in 14 supine anesthetized dogs. Measurements were done before and 5 and 10 min after administration of progressively increasing doses of aminophylline, reaching a total dose of 5, 10, 20, 40, and 80 mg/kg. In 12 of 14 dogs after aminophylline administration, quiet inspiration became biphasic, or if inspiration was already biphasic under control conditions, the first phase was clearly enhanced after aminophylline administration. Biphasic inspiration was defined as an inspiratory pattern in which rib cage and abdominal expansion showed two distinct phases. First, the onset of inspiration was characterized by a sudden increase in rib cage cross-sectional area often associated with a decrease in abdominal dimensions. During this initial part the parasternals and the diaphragm were electrically silent, confirming that it was achieved by relaxation of expiratory muscles. Further inspiration occurred predominantly through expansion of the abdomen. In the first phase, a pressure drop in the parasternal intercostals was present, presumably due to passive shortening of these muscles caused by expiratory muscle relaxation. On the average, 42 +/- 28% of the rib cage expansion was due to expiratory muscle relaxation at a dose of 80 mg/kg versus 17 +/- 21% under control conditions (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of aminophylline on diaphragmatic fatigue during acute respiratory failure

The effects of aminophylline on diaphragmatic fatigue and recovery in the face of hypoxemia and hypercapnic acidosis were studied in anesthetized, spontaneously breathing, dogs. The phrenic nerves were stimulated supramaximally at 10, 20, 50, and 100 Hz during 2 s with electrodes placed around the fifth roots, and the resulting transdiaphragmatic pressure (Pdi) was measured with balloon catheters. The dogs were occluded before the stimulations at functional residual capacity. The latter was monitored by measuring the end-expiratory transpulmonary pressure, which remained constant throughout the experiment. Diaphragmatic fatigue was produced by resistive loaded breathing. At the end of the runs, which lasted 15 +/- 2 min, all the dogs were severely hypoxemic (30 +/- 5 mmHg), hypercapnic (65 +/- 4 mmHg), and acidotic (7.1 +/- 0.05). During the fatigue runs, phrenic stimulation resulted in a marked decrease in Pdi, which amounted at 20 Hz to 70 +/- 8% and 45 +/- 12% of the control values 5 min after the onset of the fatigue runs and at the end, respectively. After recovery (3 h), Pdi and arterial blood gas determinations returned to control values. Identical fatigue runs were repeated with aminophylline infusion (loading dose, 6 mg/kg in 10 min and maintenance dose, 1 mg/kg/h), leading to a plasmatic concentration of 16.4 +/- 2 mg/l. Aminophylline protected the diaphragm against fatigue, and despite the presence of hypoxemia and hypercapnic acidosis, the Pdi generated for a 20 Hz stimulation of the phrenic nerves at identical times of the preceding run amounting to 100 +/- 15% and 85 +/- 10% of control values, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of inhaled nitric oxide and surfactant treatment on lung function and pulmonary hemodynamics in bronchoalveolar-lavage-induced respiratory failure

Our aim was to study whether inhaled nitric oxide (iNO) moderates respiratory failure induced by bronchoalveolar lavage (BAL) without severe pulmonary hypertension. The following successive treatments, interrupted by 20-30-min rest periods, were given to piglets: iNO (20 ppm for 20 min), exogenous surfactant, iNO, Nomega-nitro-L-arginine methyl ester (L-NAME), and iNO. The controls inhaled NO first after L-NAME. Lung mechanics and hemodynamics were measured serially. The pulmonary to systemic arterial pressure ratio decreased during iNO and tended to increase after its discontinuation. In contrast, the iNO-induced decreases in severity of respiratory failure were not reversible during the rest periods. In a second experiment, iNO/placebo and surfactant containing (3)H-labeled dipalmitoyl phosphatidylcholine were given to rabbits. The surfactant aggregates and the surface activity from postmortem BAL, and extravascular lung water, were studied. Inhaled NO improved the surface activity and increased the large surfactant aggregates. There was no detectable decrease in extravascular lung water. The results suggest that a low dose of iNO has a beneficial effect on the gas exchange that is in part unrelated to its effect on the pulmonary vasculature.     

Effects of intravenous nesiritide on pulmonary vascular hemodynamics in pulmonary hypertension

BACKGROUND: Nesiritide is effective in the treatment of decompensated heart failure (HF). We evaluated the acute hemodynamic effects of nesiritide, a recombinant B-type natriuretic peptide, in patients with HF and pulmonary hypertension (PH). METHODS AND RESULTS: Twenty patients with HF and PH (mean pulmonary arterial [PA] pressure >25 mm Hg) were enrolled: 10 with postpulmonary capillary wedge (PCW) >15 mm Hg and 10 with precapillary PH (PCW) < or =15. The pulmonary and systemic hemodynamics were determined by right heart catheterization at baseline and at 15 and 30 minutes after an intravenous nesiritide infusion (2 mcg/kg bolus and 0.01 mcg.kg.min). For the patients with postcapillary PH, the mean left ventricular ejection fraction was 28 +/- 15%. After the 30-minute nesiritide infusion, right atrial (RA) pressure decreased 48% (P < .0001), mean PA pressure decreased 29% (P < .0001), PCW pressure decreased 40% (P < .0001), cardiac index (CI) increased 35% (P = .009), pulmonary vascular resistance index (PVRI) decreased 35% (P = .01), and arteriovenous oxygen difference (AVDO(2)) decreased 27% (P = .0003). For precapillary PH patients, there was no change in RA, PA, or PCW pressure, nor any change in CI, PVRI, or AVDO(2). CONCLUSIONS: Nesiritide acutely and significantly reduced PA pressure, PVRI, and biventricular filling pressures in patients with postcapillary PH. However, for patients with precapillary PH, nesiritide had no significant acute hemodynamic effect on the pulmonary hemodynamics. The lack of acute beneficial effects of nesiritide in patients with advanced precapillary PH may be related to their relatively fixed remodeling of the pulmonary vasculature.     

Effects of positive intrathoracic pressure on pulmonary and systemic hemodynamics

The Frank-Starling Law accounts for many changes in cardiac performance previously attributed to changes in contractility in that changes in contractility might have been incorrectly inferred from changing ventricular function curves (i.e. systolic performance plotted against filling pressure) if diastolic compliance also changed. To apply the Frank-Starling Law in the presence of changing diastolic compliance, it is necessary to measure end-diastolic volume directly or to calculate end-diastolic transmural pressure, which requires that pericardial pressure be known. Under most normal circumstances, increased intrathoracic pressure (and other interventions, such as vasodilators or lower-body negative pressure, that decrease central blood volume) decreases the transmural end-diastolic pressures of both ventricles, their end-diastolic volumes and stroke work. However, when ventricular interaction is significant, the effects of these interventions might be quite different; this may be important in patients with heart-failure. Although these interventions decrease RV transmural pressure, they may increase LV transmural pressure, end-diastolic volume, and thus stroke work by the Frank-Starling mechanism.     

Effects of alcohol on systemic and pulmonary hemodynamics in normal humans

Even at low doses, alcohol has been reported to impair left ventricular pump function. To characterize further the effects of alcohol on the normal cardiovascular system, using the Swan-Ganz thermodilution catheter, we studied 6 healthy physicians, aged 27-36 years, while they were lightly intoxicated. Within a period of 30 min the subjects ingested 0.5 g/kg of ethanol diluted to 15% (w/v) in fruit juice. Hemodynamic measurements were obtained before the first ingestion and every half-hour thereafter for 2 hours. A peak blood ethanol concentration (mean +/- SE) of 13.3 +/- 1.6 mmol/l (0.61 mg/dl) was recorded at 60 min. Unexpectedly, pulmonary artery pressure rose during the early part of the increasing blood ethanol phase, probably due to pulmonary vascular constriction. At 30 min, the systolic pulmonary artery pressure had increased by 10% (p less than 0.05) and the diastolic pressure by 14% (p less than 0.001); both returned to baseline levels by the end of the experiment. Calculated pulmonary vascular resistance rose from a baseline value of 0.50 +/- 0.30 to 0.85 +/- 0.34 units (p less than 0.01) at 30 min. Left ventricular preload decreased significantly during the declining blood ethanol phase: mean pulmonary capillary wedge pressure decreased from 12 +/- 3 to 10 +/- 2 mmHg (p less than 0.01), and mean right atrial pressure decreased significantly. This study suggests that alcohol causes changes in cardiac function by altering its loading conditions. The combined diuretic and systemic venodilatory actions of alcohol provide the most probable explanation for the decrease in preload.     

Effects of hyperoxia and dimethylthiourea on neonatal pulmonary hemodynamics in piglets

Exposure of piglets to 68-72 h of hyperoxia has previously been shown to blunt hypoxic pulmonary vasoconstriction (HPV). We tested the hypothesis that the administration of a scavenger of toxic oxygen radicals during exposure to hyperoxia would preserve HPV in piglets. Newborn piglets were kept in FIO2 greater than 0.90 for 68-72 h and compared to control animals kept in room air. Randomly selected animals from both groups were given the O2 metabolite scavenger, dimethylthiourea (DMTU) (500 mg/kg followed by 250 mg/kg/d), resulting in plasma levels of 2-6 mM. Following the oxygen or room air (RA) exposure period, piglets had pulmonary vascular resistance (PVR) measured following a 20 min exposure to alveolar hypoxia (FIO2 = 0.12). Both groups of RA-exposed animals (DMTU and saline treatment) as well as the hyperoxia-exposed saline group had almost 2-fold increases in PVR during exposure to hypoxia (P less than 0.05). Contrary to expectations, the PVR in the hyperoxia-exposed DMTU group did not rise significantly during hypoxia and the use of DMTU did not restore HPV by increasing PVR to levels greater than the hyperoxia/saline group (P = 0.70). Therefore DMTU does not appear to prevent hyperoxia-induced blunting of HPV in piglets.     

大鼠脑桥呼吸调整中枢神经元对低氧呼吸反应的调节作用

目的探讨大鼠脑桥呼吸调整中枢神经元N-甲基-D-天氡氨酸(NMDA)受体及γ-氨基丁酸(GABA)受体对低氧呼吸反应的调节作用。方法通过显微注射技术向大鼠脑桥呼吸调整中枢内微量注射NMDA受体阻断剂D-2-氨基-5-磷酸基戊酸(D-AP5)和GABA受体阻断剂荷包牡丹碱(BIC),观察其对低氧呼吸反应膈神经放电的影响。结果脑桥微量注射D-AP5后,急性低氧反应膈神经放电无显著性改变,但低氧后呼气时间延长的幅度及呼吸频率下降的幅度均减小(P均<0.05),低氧后呼吸频率下降(PHFD)被削弱;脑桥微量注射BIC后,急性低氧反应膈神经放电频率升高的幅度及呼吸时间缩短的幅度均增大(P均<0.05),PHFD无显著性改变。结论大鼠脑桥呼吸调整中枢神经元NMDA受体介导的突触传递主要影响PHFD,GABA受体介导的突触传递主要影响急性低氧反应。     

Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.

Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.     

Effects of left ventricular assist device on pulmonary functions and pulmonary hemodynamics: A meta-analysis

BACKGROUNDGiven current evidence, the effect of left ventricular assist device (LVAD) implantation on pulmonary function tests remains controversial.AIMTo better understand the factors contributing to the changes seen on pulmonary function testing and the correlation with pulmonary hemodynamics after LVAD implantation.METHODSElectronic databases were queried to identify relevant articles. The summary effect size was estimated as a difference of overall means and standard deviation on a random-effects model.RESULTSA total of four studies comprising 219 patients were included. The overall mean forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion lung capacity of carbon monoxide (DLCO) after LVAD implantation were significantly lower by 0.23 L (95%CI: 0.11-0.34, P = 00002), 0.18 L (95%CI: 0.03-0.34, P = 0.02), and 3.16 mmol/min (95%CI: 2.17-4.14, P < 0.00001), respectively. The net post-LVAD mean value of the cardiac index was significantly higher by 0.49 L/min/m² (95%CI: 0.31-0.66, P < 0.00001) compared to pre-LVAD value. The pulmonary capillary wedge pressure and pulmonary vascular resistance were significantly reduced after LVAD implantation by 8.56 mmHg (95%CI: 3.78-13.35, P = 0.0004), and 0.83 Woods U (95%CI: 0.11-1.55, P = 0.02), respectively. There was no significant difference observed in the right atrial pressure after LVAD implantation (0.61 mmHg, 95%CI: -2.00 to 3.32, P = 0.65). Overall findings appear to be driven by studies using HeartMateII devices.CONCLUSIONLVAD implantation might be associated with a significant reduction of the spirometric measures, including FEV1, FVC, and DLCO, and an overall improvement of pulmonary hemodynamics.     

Effects of free fatty acids on insulin sensitivity and hemodynamics during mental stress

Mental stress is known to decrease systemic vascular resistance and increase muscle blood flow and to acutely enhance insulin-mediated glucose disposal in healthy humans. These effects are abolished in obese patients. We therefore proposed the hypothesis that elevated free fatty acid levels may be responsible for the abnormal responses to mental stress in obesity by inhibiting endothelial cell function. To test this hypothesis, we studied a group of eight lean females during a hyperinsulinemic clamp study with and without lipid infusion. A 30-min mental stress was applied during 30 min after 150 min of hyperinsulinemia. In the study without lipid infusion, mental stress increased heart rate by 26.5%, blood pressure by 7.9%, and cardiac index (measured with thoracic bioimpedance) by 35.9%; it decreased systemic vascular resistance by 21.9% and increased insulin-mediated glucose disposal by 18.9%. During lipid infusion, the increase in heart rate was not affected, but the increase in cardiac index, the decrease in systemic vascular resistance, and the increase in insulin-mediated glucose disposal were all inhibited. In contrast, the rise in blood pressure was increased about 2-fold (control plus 6 mm Hg vs. lipid plus 13 mm Hg, P: < 0.01). These results indicate that lipid inhibits the stimulation of glucose uptake and enhances the pressor effect of mental stress, presumably by altering endothelial cell function.