Search PubMed⌕ Search

Biomedical subjects

S Zakynthinos

Publications and source records attributed to S Zakynthinos.

34 records · Page 2Linked to original sources
PubMed1999

Strenuous resistive breathing induces proinflammatory cytokines and stimulates the HPA axis in humans.

Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), powerful stimulants of the hypothalamic-pituitary-adrenal (HPA) axis, increase in response to whole body exercise. Strenuous inspiratory resistive breathing (IRB), a form of clinically relevant "exercise" for the respiratory muscles, produces beta-endorphin through a largely unknown mechanism. We investigated (in 11 healthy humans) whether strenuous IRB produces proinflammatory cytokines and beta-endorphin in parallel with stimulation of the HPA axis, assessed by concurrent measurement of ACTH. Subjects underwent either severe [at 75% of maximal inspiratory pressure (P(m) (max))] or moderate (at 35% of P(m) (max)) IRB. Plasma cytokines, beta-endorphin, and ACTH were measured at rest (point R), at the point at which the resistive load could not be sustained (point F), and at exhaustion [15 min later (point E)]. During severe IRB, IL-1beta increased from 0.83 +/- 0.12 pg/ml at point R to 1.88 +/- 0. 53 and 4.06 +/- 1.27 pg/ml at points F and E, respectively (P < 0. 01). IL-6 increased from 5.30 +/- 1.02 to 10.33 +/- 2.14 and 11.66 +/- 2.29 pg/ml at points F and E, respectively (P = 0.02). ACTH and beta-endorphin fluctuated from 20.87 +/- 5.49 and 25.03 +/- 3.97 pg/ml at point R to 22.97 +/- 4.41 and 26.32 +/- 3.93 pg/ml, respectively, at point F and increased to 46.96 +/- 8.55 and 40.32 +/- 5.94 pg/ml, respectively, at point E (P < 0.01, point E vs. point F). There was a positive correlation between the IL-6 at point F and the ACTH and beta-endorphin at point E (r = 0.88 and 0.94, respectively; P < 0.01) as well as between the increase in IL-6 (between points R and F) and the increases in ACTH and beta-endorphin (between points F and E, r = 0.91 and 0.92, respectively; P < 0.01). Moderate IRB did not produce any change. We conclude that severe IRB produces proinflammatory cytokines and stimulates the HPA axis in humans secondary to the production of cytokines (especially IL-6).

Adrenocorticotropic Hormone↗
PubMed1999

Effects of different expiratory maneuvers on inspiratory muscle force output.

We assessed the effects of two different expiratory maneuvers (fast [F] or slow [S]) on the ability of normal subjects (n = 12, age 35 +/- 6 yr) to generate maximal inspiratory pressures and maximal inspiratory flows near residual volume (RV). With the F maneuver, the subject exhaled rapidly to RV and immediately performed a maximal inspiratory effort, whereas with the S maneuver the subject exhaled slowly to RV, paused for 4 to 6 s at RV, and then inspired forcefully. Maximal static inspiratory pressure against an occluded airway (PImax), and maximal dynamic inspiratory pressure (PIdyn) and maximal inspiratory flow (V Imax) with no added resistance, as well as the electromyographic activity of the parasternal muscles, were measured during each maneuver. Both maneuvers were initiated from TLC and were performed randomly. In comparison with the S maneuver, the F maneuver yielded values of higher (mean +/- SE) PImax (148 +/- 5 cm H2O versus 135 +/- 7 cm H2O, p < 0.05), PIdyn (33 +/- 2 cm H2O versus 28 +/- 2 cm H2O, p < 0.05), and V Imax (12.3 +/- 0.4 L/s versus 11.4 +/- 0.6 L/s, p < 0.05). In addition, the rate of rise of PImax, the rate of rise of PIdyn, and the integrated peak electromyographic activity of the parasternal muscles were significantly greater with the F than with the S maneuver, suggesting greater inspiratory muscle (IM) activation. The enhanced IM activation may be related to a specific inspiratory-expiratory muscle interaction similar to the agonist-antagonist interactions described for a pair of skeletal muscles.

Adult↗
PubMed1999

Respiratory muscles in heart failure.

This paper reviews respiratory muscle performance in patients suffering from congestive heart failure. Respiratory muscle dysfunction is well documented in these patients, and is thoroughly discussed. The mechanisms underlying its development and the potential consequences are also presented.

Dyspnea↗
PubMed1998

The tension-time index and the frequency/tidal volume ratio are the major pathophysiologic determinants of weaning failure and success.

We have previously shown (Am. J. Respir. Crit. Care Med. 1995;152:1248-1255) that in patients needing mechanical ventilation, the load imposed on the inspiratory muscles is excessive relative to their neuromuscular capacity. We have therefore hypothesized that weaning failure may occur because at the time of the trial of spontaneous breathing there is insufficient reduction of the inspiratory load. We therefore prospectively studied patients who initially had failed to wean from mechanical ventilation (F) but had successful weaning (S) on a later occasion. Compared with S, during F patients had greater intrinsic positive end-expiratory pressure (6. 10 +/- 2.45 versus 3.83 +/- 2.69 cm H2O), dynamic hyperinflation (327 +/- 180 versus 213 +/- 175 ml), total resistance (Rmax, 14.14 +/- 4.95 versus 11.19 +/- 4.01 cm H2O/L/s), ratio of mean to maximum inspiratory pressure (0.46 +/- 0.1 versus 0.31 +/- 0.08), tension time index (TTI, 0.162 +/- 0.032 versus 0.102 +/- 0.023) and power (315 +/- 153 versus 215 +/- 75 cm H2O x L/min), less maximum inspiratory pressure (42.3 +/- 12.7 versus 53.8 +/- 15.1 cm H2O), and a breathing pattern that was more rapid and shallow (ratio of frequency to tidal volume, f/VT 98 +/- 38 versus 62 +/- 21 breaths/min/L). To clarify on pathophysiologic grounds what determines inability to wean from mechanical ventilation, we performed multiple logistic regression analysis with the weaning outcome as the dependent variable. The TTI and the f/VT ratio were the only significant variables in the model. We conclude that the TTI and the f/VT are the major pathophysiologic determinants underlying the transition from weaning failure to weaning success.

Adult↗
PubMed1997

Changes in thoracopulmonary compliance and hemodynamic effects of positive end-expiratory pressure in patients with or without heart failure.

PURPOSE: The purpose of this study was to confirm that positive end-expiratory pressure (PEEP) has a different effect on cardiac index (CI) in patients with or without heart failure, even after controlling for differences in thoracopulmonary compliance (Ctp) and minimizing the secondary effects of PEEP related changes in oxygenation and breathing effort. MATERIALS AND METHODS: The hemodynamic effects of PEEP were evaluated in two groups of sedated and paralyzed patients with a low Ctp at 0 PEEP: 12 patients with normal pulmonary artery occlusion pressure (Ppao) and a CI > 2.5 L/min and 12 patients with a CI < 2.5 L/min and increased oxygen extraction ratio, despite a Ppao > 15 mm Hg. RESULTS: In patients with low CI and high Ppao, PEEP had no hemodynamic effect and Ctp remained low at all PEEP levels. However, PEEP-induced CI reduction in patients with normal cardiovascular function was associated with an increase in Ctp with incremental PEEP. Concerning PEEP-related hemodynamic effects, the significance between group differences persisted when data were analyzed after controlling for Ctp changes. However, Ctp changes with PEEP were the most significant correlators and discriminators of the magnitude and direction of PEEP-induced CI change. CONCLUSIONS: We conclude that (1) the observed different effect of PEEP on CI in patients with and without heart failure persists after the elimination of secondary effects due to underlying differences in Ctp, oxygenation, and breathing effort; and (2) PEEP-related changes in Ctp should be taken into consideration when dealing with the cardiovascular effects of PEEP. Our data support the hypothesis that, in addition to the transmission of PEEP to the pleural space, changes in lung volume are a significant determinant of PEEP-induced CI changes.

Adult↗
PubMed1997

Inspiratory maneuver effects on peak expiratory flow. Role of lung elastic recoil and expiratory pressure.

We investigated the effects of two different inspiratory maneuvers (fast or slow) on the ability of normal subjects to generate peak expiratory flows (PEF) and maximal dynamic expiratory pressures (Pexp) during the performance of a forced vital capacity maneuver. During the fast maneuver (F), the subject inspired rapidly to total lung capacity (TLC) and immediately performed a maximal expiration, whereas in the slow maneuver (S) the subject inspired slowly to TLC, paused for 4-5 s at TLC and then performed a maximal expiration. Ten normal subjects performed a series of such maneuvers. In addition to PEF and Pexp, we measured EMG activity of abdominal (EMGabd) and rib cage muscles, and lung elastic recoil pressure (PesL). Overall, F yielded higher PEF values than S (by approximately 7%); in addition, PesL, Pexp, rate of rise of Pexp (dPexp/dt), and EMGabd were similarly higher with F than with S (p < 0.05 for all). Analysis of individual data showed that the intermaneuver differences in PEF were largely explained by differences in PesL, Pexp or dPexp/dt. Our data suggest that, in comparison with the slow maneuver, the fast maneuver induces a greater change in both the lung elastic recoil and expiratory muscle activation which account for differences in PEF between the two maneuvers. The enhanced expiratory muscle activation with the fast maneuver suggests a specific inspiratory-expiratory muscle interaction analogous to agonist-antagonist interactions described for skeletal muscles.

Adult↗
PubMed1996

Respiratory muscles and weaning failure.

Weaning failure is, unfortunately, a rather common phenomenon for mechanically-ventilated patients (especially those with chronic obstructive pulmonary disease (COPD)), and the respiratory muscles play a pivotal role in its development. Weaning fails whenever an imbalance exists between the ventilatory needs and the neurocardiorespiratory capacity. This can happen if there is an increase in the energy demands of the respiratory muscles, a decrease in the energy available, a decrease in neuromuscular competence, or if the respiratory muscles pose an impediment to the heart and blood flow. The imbalance created will lead to weaning failure through the development of respiratory muscle fatigue, hypercapnia, dyspnoea, anxiety and organ dysfunction.

Anxiety↗
PubMed1993

Effect of diaphragmatic fatigue on control of respiratory muscles and ventilation during CO2 rebreathing.

We studied the influence of diaphragmatic fatigue on the control of ventilation and respiratory muscle contribution to pressure swings in six normal seated subjects. CO2 was rebreathed before and after diaphragmatic fatigue induced by breathing against an inspiratory resistance requiring 60% maximal transdiaphragmatic pressure with each breath until exhaustion. After diaphragmatic fatigue for a given level of end-tidal PCO2, we found that tidal volume, breathing frequency, minute ventilation, duty cycle, and mean inspiratory flow did not change; esophageal pressure swings were the same, but gastric and transdiaphragmatic pressure swings were decreased; and the slope of the transpulmonary pressure-gastric pressure relationship determined at zero flow points at end expiration and end inspiration was increased. End-expiratory transpulmonary pressure progressively decreased and end-expiratory gastric pressure progressively increased with increasing end-tidal PCO2 by the same magnitude before and after diaphragmatic fatigue. We conclude that diaphragmatic fatigue induces proportionately greater contributions of inspiratory rib cage muscles than of the diaphragm, which results in the preservation of ventilatory response to CO2 despite impaired diaphragmatic contractility.

Adult↗
PubMed1993

Effect of global inspiratory muscle fatigue on ventilatory and respiratory muscle responses to CO2.

We evaluated the effect of global inspiratory muscle fatigue on ventilation and respiratory muscle control during CO2 rebreathing in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. CO2 response curves were measured before and after fatigue. During CO2 rebreathing, global fatigue caused a decreased tidal volume (VT) and an increased breathing frequency but did not change minute ventilation, duty cycle, or mean inspiratory flow. Both esophageal and transdiaphragmatic pressure swings were significantly reduced after global fatigue, suggesting decreased contribution of both rib cage muscles and diaphragm to breathing. End-expiratory transpulmonary pressure for a given CO2 was lower after fatigue, indicating an additional decrease in end-expiratory lung volume due to expiratory muscle recruitment, which leads to a greater initial portion of inspiration being passive. This, combined with the reduction in VT, decreased the fraction of VT attributable to inspiratory muscle contribution; therefore the inspiratory muscle elastic work and power per breath were significantly reduced. We conclude that respiratory control mechanisms are plastic and that the respiratory centers alter their output in a manner appropriate to the contractile state of the respiratory muscles to conserve the ventilatory response to CO2.

Adult↗
PubMed1989

Effects of furosemide on pulmonary shunts.

In 23 mechanically ventilated anuric (six) or oliguric (17) patients (less than 16 ml/h of urine output) with severe gas exchange abnormality, we investigated the effect of furosemide on intrapulmonary shunt (Qs/QT). Before and after 0.5, 1, and 2 h of IV administration of 200 mg of furosemide, we assessed the intrapulmonary shunt and PaO2 while patients' hemodynamic measurements were monitored. Ventilatory parameters remained constant throughout the study. While the urine output was minimal and no alteration in hemodynamic values was found, the Qs/QT decreased from 27.7 +/- 2.3 percent (mean +/- SEM) at control to 24.3 +/- 2.1 percent (p less than 0.01) at 0.5 h, 21.7 +/- 2.1 percent (p less than 0.001) at 1 h, and 18.1 +/- 1.8 percent (p less than 0.001) at 2 h. The PaO2 showed no significant difference at 0.5 h but rose significantly from 96 +/- 14 to 105 +/- 14 mm Hg (p less than 0.05) and 111 +/- 14 mm Hg (p less than 0.01) at 1 and 2 h, respectively. Since we observed no changes in hemodynamics, we speculate a direct effect of furosemide in the pulmonary vasculature affecting the ventilation-perfusion mismatch and, therefore, the Qs/QT and PaO2.

Acute Kidney Injury↗
PubMedDate not supplied

Losartan reduces left ventricular hypertrophy proportionally to blood pressure reduction in hypertensives, but does not affect diastolic cardiac function.

In contrast to the well-recognized salutary effects of angiotensin-converting enzyme inhibition, the value of angiotensin II type I (ATl)-receptor blockade on left ventricular hypertrophy (LVH) is controversial. In addition, the data on the influence of this therapy on cardiac diastolic function are scarce. Thirty-nine patients with moderate primary hypertension, LVH, and normal systolic function received losartan, 50 to 100 mg daily. Transthoracic echocardiography was performed at baseline and after 6 months of treatment. Thirty-one patients completed and were included in the study (16 males, 61.1 +/- 1.0 years). The patients were divided into responders if mean blood pressure (BP) decreased > 5 mm Hg at the end of the study (20 patients) and non-responders (mean BP decrease < or = 5 mm Hg, 11 patients). The BP and the LVH were significantly reduced (systolic BP by 10.0%, diastolic BP 6.5%, mean BP 8.2%, left ventricular mass index [LVMI] 6.2%, interventricular septum 5.8%, posterior wall 3.0%) (p< or =0.02), attributed to the reduction of BP and LVH in responders; the LVH in non-responders did not alter with treatment. A significant correlation was noted between changes in BP and LVMI (r=0.60, p<0.001). The systolic cardiac function remained normal. The Doppler parameters usually used to assess the diastolic function of the LV (early diastolic filling velocity [E wave], late diastolic filling velocity [A wave], ratio of E/A waves, isovolumic relaxation time), which were abnormal at baseline, did not change with treatment. The size of the left atrium increased (p<0.05) at the end of the study. In conclusion, a 6-month course with losartan decreased BP and LVH. However, the LVH regression was rather associated with the reduction of the hemodynamic stimulus per se, than any trophic effect of the drug in the myocardium. The diastolic cardiac function remained abnormal with treatment.

Antihypertensive Agents↗