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Axel Kleinsasser

Publications and source records attributed to Axel Kleinsasser.

14 recordsLinked to original sources
PubMed2005

Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration.

Acute pulmonary arterial hypertension in acute lung injury aggravates the clinical course and complicates treatment. Increased release and turnover of endogenous endothelin-1 is known to be a major determinant in the pathophysiology of pulmonary arterial hypertension of various etiologies. We tested whether intravenous tezosentan, a dual endothelin receptor antagonist, reduced pulmonary artery pressure in a pig model of acute lung injury induced by meconium aspiration. Acute pulmonary arterial hypertension was induced in 12 anesthetized and instrumented pigs by instillation of human pooled meconium in a 20% solution. Hemodynamic and gas exchange parameters were recorded every 30 min. Six animals received tezosentan 5 mg/kg after 0 and 90 min; six animals served as controls. Tezosentan led to a decrease of mean pulmonary artery pressure (PAP) from 33.4 +/- 4.0 mm Hg to 24.7 +/- 2.1 mm Hg and pulmonary vascular resistance (PVR) from 7.8 +/- 1.4 mm Hg.L(-1).min.m2 to 5.2 +/- 0.7 mm Hg.L(-1).min.m2. All animals treated with tezosentan survived, whereas in the control group four out of six animals died. Tezosentan improved survival and decreased pulmonary artery pressure in a porcine model of acute pulmonary arterial hypertension after meconium aspiration. Tezosentan has the potential for effective pharmacological treatment of pulmonary arterial hypertension following acute lung injury.

Animals↗
PubMed2004

Does gender affect human pulmonary gas exchange during exercise?

Women may experience greater pulmonary gas exchange impairment during exercise than men. To test this we used the multiple inert gas elimination technique to study eight women and seven men matched for age, height and (O(2) max) ( approximately 48 ml x kg(-1) min(-1)) during normoxic and hypoxic (inspired P(O(2))= 95 Torr) cycle exercise. Resting lung function was similar between the sexes, except for a lower carbon monoxide diffusing capacity (DL(CO)) in women (P < 0.05). Arterial P(O(2)),P(CO(2)) and alveolar-arterial O(2) difference (A-aD(O(2))) were not significantly different in men and women. Despite a lower diffusing capacity for O(2) (DL(O(2))) in women, the ratio DL(O(2))/beta (which estimates pulmonary end-capillary diffusion equilibrium) was similar between men and women and estimates of diffusion limitation during hypoxic exercise were not different between the sexes. Ventilation-perfusion inequality (described by the second moment of the perfusion distribution, logSD increased during both normoxic and hypoxic exercise. Surprisingly, logSD values were slightly lower for women under all conditions (P < 0.05), but this did not significantly affect gas exchange. These data indicate that these active women, despite a lower DL(CO) and DL(O(2)), do not experience greater exercise-induced abnormalities in gas exchange than men matched for age, height, aerobic capacity and lung size. Possibly fitness level and lung size are more important in determining whether or not pulmonary gas exchange impairment occurs during exercise than sex per se.

Adult↗
PubMed2004

Proportional assist ventilation reduces the work of breathing during exercise at moderate altitude.

Reducing the work of breathing (WOB) during exercise and thus the oxygen required solely for ventilation may be an option to increase the oxygen available for nonventilatory physiological tasks at altitude. This study evaluated whether pressure support ventilation (PSV) and proportional assist ventilation (PAV) may partially reduce WOB during exercise at altitude. Seven volunteers breathing with either PSV or PAV or without support (control) were examined for WOB, inspiratory pressure time product (iPTP), and (O(2)) before and during pedaling at 160 W for 4 min on an ergometer at an altitude of 2860 m, where barometric pressure and oxygen partial pressure are approximately 30% less than at sea level. PSV and PAV reduced WOB from 4.5 +/- 0.9 J/L(-1)/min(-1) during unsupported breathing to 3.7 +/- 0.4 (p < 0.05) and 3.2 +/- 0.7 (p < 0.01), respectively. iPTP was reduced during PAV (570 +/- 151 cm H(2)O/sec/min(-1), p < 0.01), but not during PSV (727 +/- 116, p = 0.58) compared with unsupported ventilation during exercise (763 +/- 90). During PSV and PAV breathing, higher arterial oxygen saturations (84 +/- 2%, p < 0.05, and 86 +/- 1%, p < 0.01, respectively) were observed compared with control (80 +/- 3%), indicating that PSV and PAV attenuated hypoxemia during exercise at altitude. Total body (O(2)), however, was not reduced during PSV or PAV. In conclusion, both PSV and PAV reduced the WOB during exercise at altitude, but only PAV reduces iPTP. Both modes reduce hypoxemia, which may be due to higher alveolar ventilation or decreased ventilation-perfusion heterogeneity compared to unsupported breathing.

Adult↗
PubMed2004

External cardiac defibrillation does not cause acute histopathological changes typical of thermal injuries in pigs with in situ cerebral stimulation electrodes.

UNLABELLED: Parkinson's disease patients with long-term L-dopa syndrome may benefit from an implanted cerebral stimulation device. When advanced life support demands cardioversion or defibrillation in these patients, undesired effects of monophasic electroshocks might occur in brain tissue adjacent to the stimulation electrodes (e.g., thermal injury), but also in the stimulation device itself. Thus, in this animal study (n = 6 pigs), we investigated the effects of repeated defibrillation (2 x 200 J [n = 1] and 2 x 360 J [n = 5]) at the implantation site of cerebral stimulation electrodes and on stimulation device function. Repeated external cardiac defibrillation did not cause acute histopathologic changes typical of thermal injury to brain tissue adjacent to the cerebral stimulation electrodes. Functionality of the stimulator device after defibrillation, however, ranged from normal to total loss of function. Therefore, when defibrillation is performed, the greatest possible distance between the defibrillation site and the stimulator device implantation site should be considered. Subsequent testing of the stimulator device's function is mandatory. IMPLICATIONS: Repeated cardiac defibrillation did not cause histopathologic changes typical of thermal injury at the implantation site of cerebral stimulation electrodes. The function of the stimulator device after defibrillation, however, ranged from normal to total loss of function.

Adenosine↗
PubMed2003

A pig model of high altitude pulmonary edema.

High altitude pulmonary edema (HAPE) affects unacclimatized individuals ascending rapidly to high altitude. The pathogenesis of HAPE is not fully elucidated, and many investigative techniques that could provide valuable information are not suitable for use in humans; thus, an animal model is desirable. Rabbits, sheep, dogs, and ferrets have been shown not to consistently develop HAPE, and studies in rats are limited by the animal's small size and inconsistent response. Pigs develop a marked pulmonary vasoconstrictive response to hypoxia, and preliminary studies of HAPE in pigs have been promising. To determine the suitability of pigs as an animal model of HAPE, we exposed six subadult (20 to 25 kg) pigs to normobaric hypoxia (10% oxygen) for 48 hr. One week before, and immediately after exposure to hypoxia, under anesthesia, arterial blood gases were obtained and bronchoalveolar lavage (BAL) and chest x-ray were performed. Hypoxia increased alveolar-arterial pressure difference for oxygen from 22 +/- 9 to 38 +/- 5 torr, p < 0.01) and red cell (from 12.3 +/- 5.9 to 27.4 +/- 5.3 cells x 10(5)/mL(-1), p < 0.001) and white cell (from 1.59 +/- 0.90 to 7.88 +/- 3.36 cells x 10(5)/mL(-1), p < 0.05) concentrations in BAL in all animals. Total BAL protein concentration increased by 64% and fractional albumin by 38% (both p < 0.05) posthypoxia. One animal had evidence of pulmonary edema on X ray. Some pigs develop findings consistent with early HAPE when exposed to normobaric hypoxia. Increasing the duration of hypoxic exposure or exercising the animals in hypoxia may better model the disease process observed in humans with clinically significant HAPE.

Altitude Sickness↗
PubMed2003

Sustained prolongation of the QTc interval after anesthesia with sevoflurane in infants during the first 6 months of life.

BACKGROUND: Sevoflurane, an inhalational anesthetic frequently administered to infants, prolongs the QT interval of the electrocardiogram in adults. A long QT interval resulting in fatal arrhythmia may also be responsible for some cases of sudden death in infants. As the QT interval increases during the second month of life and returns to the values recorded at birth by the sixth month, we evaluated the effect of sevoflurane on the QT interval during and after anesthesia in this particular population. METHODS: In this prospective two-group trial we examined pre-, peri-, and postoperative electrocardiograms of 36 infants aged 1 to 6 months scheduled for elective inguinal or umbilical hernia repair. Anesthesia was induced and maintained with either sevoflurane, or the well-established pediatric anesthetic halothane. Heart rate corrected (c) QTc and JTc interval (indicator of intraventricular conduction delays) were recorded from electrocardiograms before and during anesthesia, and at 60 min after emergence from anesthesia. RESULTS: Prolonged QTc was observed during sevoflurane anesthesia (mean [+/-SD], 473 +/- 19 ms, P< 0.01). Sixty minutes after emergence from anesthesia, QTc was still prolonged (433 +/- 15 ms) in infants treated with sevoflurane compared with those treated with halothane (407 +/- 33 ms, P< 0.01). Analogous differences were found for the JTc interval. CONCLUSIONS: Despite a shorter elimination time than better known inhalational anesthetics, sevoflurane induction and anesthesia results in sustained prolongations of QTc and JTc interval in infants in the first 6 months of life. Electrocardiogram monitoring until the QTc interval has returned to preanesthetic values may increase safety after sevoflurane anesthesia.

Anesthetics, Inhalation↗
PubMed2002

Decompression-triggered positive-pressure ventilation during cardiopulmonary resuscitation improves pulmonary gas exchange and oxygen uptake.

BACKGROUND: Intermittent positive-pressure ventilation (IPPV) is the "gold standard" of ventilation during cardiopulmonary resuscitation (CPR), but continuous positive airway pressure (CPAP) is increasingly discussed as an alternative. This study investigated hemodynamics and pulmonary gas exchange applying CPAP enhanced with pressure support ventilation (CPAP(PSV)) during CPR. METHODS AND RESULTS: Twenty-four pigs were subjected to ventricular fibrillation and CPR with CPAP(PSV), CPAP, or IPPV. Measurements were taken before (hemodynamics, blood gases, inert gas measurements) and 10 (hemodynamics, blood gases) and 20 (hemodynamics, blood gases, inert gas measurements) minutes after induction of ventricular fibrillation. Although no significant intergroup differences in hemodynamics were found, arterial partial pressure of oxygen (PaO(2)) was significantly higher during CPAP(PSV) compared with CPAP or IPPV (98+/-10, 61+/-27, and 71+/-30 mm Hg, respectively, P<0.05). CPAP(PSV) resulted in an alveolar-arterial partial pressure of oxygen difference of 56+/-17 mm Hg, whereas during CPAP, 83+/-21 mm Hg was detected, and during IPPV, 98+/-29 mm Hg was detected (P<0.05). Pulmonary blood flow to lung units with a normal VA/Q ratio in percent of cardiac output was 76+/-17% during CPAP(PSV), 61+/-21% during CPAP (P<0.01), and 54+/-13% during IPPV (P<0.01). Oxygen uptake (VO(2)) was significantly higher during CPAP(PSV) than with the other ventilation modes (P<0.05) and comparable to the baseline value in intragroup comparison. Return of spontaneous circulation was recorded in 8 of 8 animals in the CPAP(PSV) group, in 6 of 8 in the CPAP group, and in 3 of 8 in the IPPV group. CONCLUSIONS: CPAP(PSV) provides a straightforward and effective alternative to IPPV or CPAP during CPR that provides significantly higher PaO(2) and VO(2).

Animals↗
PubMed2002

Are sildenafil and theophylline effective in the prevention of high-altitude pulmonary edema?

High-altitude pulmonary edema reflects a potentially life-threatening condition affecting susceptible persons in the second night after ascent to altitudes above 2500 m. Currently, nifedipine is the only pharmacological intervention approved for both, prevention and treatment of high-altitude pulmonary edema. We evaluated the application of the phosphodiesterase-V inhibitor sildenafil combined with the non-selective phosphodiesterase-inhibitor theophylline as preventive agents. In theory, the proposed regimen can impede the two main pathophysiological features of high-altitude pulmonary edema: the deleteriously high pulmonary artery pressure (sildenafil's task) on the one hand, and the activation of an inflammatory cascade (theophylline's task) on the other hand. We suggest that these orally applicable phosphodiesterase inhibitors might be useful in the prevention of high-altitude pulmonary edema.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2002

Brief report: pressure support ventilation during an ascent and on the summit of Mt. Everest? A theoretical approach.

At extreme altitude, air has an almost identical composition compared to air at sea level, while its pressure is altitude-dependently lower. When supplementary oxygen is used to achieve an acceptable inspiratory pressure of oxygen (PI(O2)) during climbing, the barometric pressure difference to lower altitudes is not compensated for. In this report, we tried theoretically to apply pressure support ventilation (PSV) to partially compensate for low barometric pressures. PSV is widely used for respiratory home care and is applicable via a nasal mask. Since there are light-weight units with long battery lives on the market, we speculated that these units may to some extent replace bottled oxygen. PSV was in theory applied at barometric pressures of 400 torr (Everest Base Camp), 284 torr (South Col), and 253 torr (summit of Mt. Everest). We found that during PSV at a mean airway pressure of 16.5 torr on the summit of Mt. Everest, a fraction of inspired oxygen (FI(O2)) of 0.34 sufficed to achieve an alveolar partial pressure (PA(O2)) of 67 torr. PSV increases PI(O2) by 3.5 torr, which in theory elevates the maximum oxygen consumption (V(O2max)) by 218 mL.min(-1) in an acclimatized climber in this setting. An additional benefit of PSV at extreme altitude may come from the unloading of the respiratory muscles.

Air Pressure↗
PubMed2002

The Laryngeal Mask Airway ProSeal(TM) as a temporary ventilatory device in grossly and morbidly obese patients before laryngoscope-guided tracheal intubation.

UNLABELLED: We determined the efficacy of the laryngeal mask airway ProSeal(TM) (PLMA) as a temporary ventilatory device in morbidly obese patients before laryngoscope-guided tracheal intubation. Sixty patients (body mass index 35--60 kg/m(2)) scheduled for elective surgery, who preferred airway management under general anesthesia, were studied. The induction of anesthesia was with midazolam/fentanyl/propofol and maintenance was with sevoflurane 1%--3% in oxygen 100%. The PLMA was inserted and an effective airway established. Rocuronium was given IV for paralysis. Oropharyngeal leak pressure, ease of gastric tube placement, residual gastric volume, fiberoptic position of the airway/drainage tube, and ease of ventilation at a tidal volume of 8 mL/kg was determined. The PLMA was then removed and laryngoscope-guided tracheal intubation attempted. The number of insertion/intubation attempts (maximum two each) and time taken to establish an effective airway with each device were recorded. An effective airway was obtained at the first insertion attempt in 90% of patients (54/60) and at the second attempt in 10% (6/60). The time taken to provide an effective airway was 15 plus minus 7 s (7--42 s). Oropharyngeal leak pressure was 32 plus minus 8 cm H(2)O (12--40 cm H(2)O). The residual gastric volume was 36 plus minus 46 mL (0--240 mL). Positive pressure ventilation without air leaks was possible in 95% of patients (57/60). The vocal cords were seen from the airway tube in 75% of patients (45/60), but the esophagus was not seen. The fiberoptic view from the drainage tube revealed mucosa in 93% of patients (56/60) and an open upper esophageal sphincter in 7% (4/60). Tracheal intubation was successful at the first attempt in 90% of patients (54/60), at the second attempt in 7% (4/60), and failed in 3% (2/60). In these latter two patients, the PLMA was reinserted and surgery performed uneventfully with the PLMA. The time taken to tracheally intubate the patient was 13 plus minus 10 s (8--51 s). There were no episodes of hypoxia (SpO(2) <90%) or other adverse events. There were no differences in insertion success rate, or the time to successful insertion between the PLMA and laryngoscope-guided intubation. We conclude that the PLMA is an effective temporary ventilatory device in grossly or morbidly obese patients before laryngoscope-guided tracheal intubation. IMPLICATIONS: The laryngeal mask airway ProSeal(TM) is an effective temporary ventilatory device in grossly and morbidly obese patients before laryngoscope-guided tracheal intubation.

Adult↗
PubMed2002

Pulmonary gas exchange in coronary artery surgery patients during sevoflurane and isoflurane anesthesia.

UNLABELLED: As the surgical population ages, the number of patients presenting with coronary artery disease and age-related loss of pulmonary recoil will increase. Although their influence on gas exchange in this population remains unknown, sevoflurane and isoflurane are used for an increasing variety of surgical procedures. We examined pulmonary gas exchange (multiple inert gas elimination technique) in 30 patients presenting for coronary artery bypass grafting. After a baseline measurement taken during midazolam anesthesia, patients were continued on sevoflurane (n = 10), isoflurane (n = 10), or midazolam (n = 10) for 20 min, then a second measurement was taken. During sevoflurane and isoflurane anesthesia, blood flow to lung areas with a low ventilation/perfusion ratio (Va/Q) was significantly increased in comparison with control. During sevoflurane anesthesia, blood flow to lung areas with a normal Va/Q ratio (76 +/- 12 versus control: 89 +/- 5, mean +/- SD) and PaO(2) (138 +/- 31 versus control: 156 +/- 35 mm Hg, mean +/- SD) were depressed, whereas an increase in Va/Q-dispersion (log SD(Q)) was observed during isoflurane anesthesia. We conclude that both sevoflurane and isoflurane alter the distribution of perfusion in the lung, but only sevoflurane significantly depresses PaO(2). IMPLICATIONS: Both sevoflurane and isoflurane modified pulmonary blood flow in patients with coronary artery disease, but only sevoflurane depresses arterial oxygenation in this population.

Aged↗
PubMed2002

Administration of oxygen before tracheal extubation worsens gas exchange after general anesthesia in a pig model.

UNLABELLED: Administration of 100% oxygen before tracheal extubation is common clinical practice. We determined the effect of this technique on postoperative gas exchange in a porcine model using the multiple inert gas elimination technique. After general anesthesia with mechanical ventilation for a period of 30 min (inspiratory fraction of oxygen of 0.3), anesthesia was discontinued, and the pigs were randomized to an inspiratory fraction of oxygen of 0.3 or 1.0 until they could be safely extubated. Thirty minutes after extubation while breathing air, blood flow to poorly ventilated units had significantly increased in pigs that had been administered 100% oxygen as compared with those receiving 30% oxygen (17% +/- 15% versus 7% +/- 5%; P = 0.009). We conclude that exposure to 100% oxygen before extubation may cause an undesirable alteration in gas exchange. IMPLICATIONS: Blood flow to lung units with a low V(A)/Q ratio was significantly larger in pigs that had been exposed to 100% oxygen before extubation as compared with those exposed to 30% oxygen before extubation.

Anesthesia, General↗
PubMed2002

Pulmonary gas exchange after cardiopulmonary resuscitation with either vasopressin or epinephrine.

OBJECTIVE: It is well established that epinephrine administered during cardiopulmonary resuscitation results in pulmonary gas exchange disturbances. It is uncertain how vasopressin affects gas exchange after cardiopulmonary resuscitation. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Twenty domestic pigs. INTERVENTIONS: Animals were subjected to ventricular fibrillation and cardiopulmonary resuscitation by using either vasopressin or epinephrine. Hemodynamic and pulmonary gas exchange (multiple inert gas elimination technique) variables were recorded before cardiopulmonary resuscitation and 10, 30, 60, and 120 mins after return of spontaneous circulation when either epinephrine (control) or vasopressin was used. MEASUREMENTS AND MAIN RESULTS: At 10 mins after return of spontaneous circulation, blood flow to low V /Q lung units was increased in animals treated with epinephrine (17.8 +/- 6 vs. 2.6 +/- 3%, mean +/- sd, p<.01). Resulting carbon dioxide elimination was impaired in animals treated with epinephrine but not in animals treated with vasopressin (PaCO2, 55 +/- 2 vs. 46 +/- 4 torr, p<.05). Thirty minutes after return of spontaneous circulation, blood flow to lung units with a normal VA /Q ratio was reduced in animals treated with epinephrine (79 +/- 1 vs. 84 +/- 12%, p<.05), resulting in a depressed PaO2 (147 +/- 4 vs. 127 +/- 10 torr, p<.05). CONCLUSION: Vasopressin compared with epinephrine for cardiopulmonary resuscitation resulted in better gas exchange variables in the early postresuscitation phase.

Animals↗