Atrial overdrive pacing compared to CPAP in patients with obstructive sleep apnoea syndrome.

AIMS: Obstructive sleep apnoea (OSA) is associated with oxygen desaturation, blood pressure increase, and neurohumoral activation, resulting in possible detrimental effects on the cardiovascular system. Continuous positive airway pressure (CPAP) is the therapy of choice for OSA. In a recent study, nocturnal atrial overdrive pacing (pacing) reduced the severity of sleep apnoea in pacemaker patients. We compared the effects of CPAP with those of pacing in patients with OSA but without pacemaker indication or clinical signs of heart failure. METHODS AND RESULTS: Ten patients with OSA on CPAP therapy were studied for three nights by polysomnography. During the nights that followed a night without any treatment (baseline), the patients were treated with CPAP or pacing in a random order. Pacing was performed with a temporary pacing lead. The pacing frequency was 15 b.p.m. higher than the baseline heart rate. The apnoea-hypopnoea index was 41.0 h(-1) (12.0-66.6) at baseline and was significantly lower during CPAP [2.2 h(-1) (0.3-12.4)] compared with pacing [39.1 h(-1) (8.2-78.5)]. Furthermore, duration and quality of sleep were significantly improved during CPAP when compared with pacing. CONCLUSION: Nocturnal atrial overdrive pacing is no alternative therapeutic strategy to CPAP for the treatment of OSA in patients without clinical signs of heart failure and without conventional indication for anti-bradycardia pacing.     

Brain tissue oxygen monitoring and hyperoxic treatment in patients with traumatic brain injury

Abstract Cerebral ischemia is a well-recognized contributor to high morbidity and mortality after traumatic brain injury (TBI). Standard of care treatment aims to maintain a sufficient oxygen supply to the brain by avoiding increased intracranial pressure (ICP) and ensuring a sufficient cerebral perfusion pressure (CPP). Devices allowing direct assessment of brain tissue oxygenation have showed promising results in clinical studies, and their use was implemented in the Brain Trauma Foundation Guidelines for the treatment of TBI patients in 2007. Results of several studies suggest that a brain tissue oxygen-directed therapy guided by these monitors may contribute to reduced mortality and improved outcome of TBI patients. Whether increasing the oxygen supply to supraphysiological levels has beneficial or detrimental effects on TBI patients has been a matter of debate for decades. The results of trials of hyperbaric oxygenation (HBO) have failed to show a benefit, but renewed interest in normobaric hyperoxia (NBO) in the treatment of TBI patients has emerged in recent years. With the increased availability of advanced neuromonitoring devices such as brain tissue oxygen monitors, it was shown that some patients might benefit from this therapeutic approach. In this article, we review the pathophysiological rationale and technical modalities of brain tissue oxygen monitors, as well as its use in studies of brain tissue oxygen-directed therapy. Furthermore, we analyze hyperoxia as a treatment option in TBI patients, summarize the results of clinical trials, and give insights into the recent findings of hyperoxic effects on cerebral metabolism after TBI.     

Schweres Sch?del-Hirn-Trauma

Traumatic brain injury is a leading cause of morbidity and mortality, especially under 45 years of age. The primary brain injury occurs at the moment of trauma and is defined by the direct damage to tissue. In contrast, secondary brain injury develops over time and is accessible to therapeutic interventions. Patients with severe traumatic brain injury have to be transferred to a specialized trauma centre in order to perform appropriate diagnostic and therapeutic procedures. These include surgical management of lesions (e.g. haematoma evacuation) as well as specific neurointensive care. Neurointensive care medicine principles such as treatment of increased intracranial pressure and advanced invasive neuromonitoring of brain tissue have to be followed.     

Further studies on proctolin analogues modified in position 2 of the peptide chain and their influence on heart-beat frequency of insects

Seven proctolin analogues (I-VII) modified in position 2 of the peptide chain by Phe (p-guanidino) (I), Phe (p-OEt) (II), Tyr (3′-NH₂) (III), Tyr (3′-NO₂) (IV), Afb (p-OH) (V) (Afb = 3-amino-4-phenyl-l -butyric acid), Afb (p-NH₂) (VI), Afb (p-NO₂) (VII), and the tetrapeptide Tyr (3′-NH₂)-Leu-Pro-Thr (VIII) were synthesized by the classic liquid-phase method. The biological effects of the peptides were investigated in cardioexcitatory tests on two insect species, the cockroach Periplaneta americana L., and the yellow mealworm, Tenebrio molitor L. Within physiological concentrations (10⁻⁹ - 10⁻⁷ M) peptides II, III, and IV stimulated the heart action of P. americana like proctolin itself. Under identical conditions, in the case of T. molitor, only peptide III showed cardiostimulatory properties, whereas other compounds (including II and IV) were inactive at concentrations up to 10⁻⁷m . Results reported here reflect, with reference to the analogues I-VII, selective recognition of receptors on myocardium of both insect species. The tetrapeptide VIII revealed a weak deacceleratory effect on P. americana and T. molitor heart action.     

Oxygen free radical damage of isolated cardiomyocytes: comparative protective effect of radical scavengers and calcium antagonists

Summary Oxygen free radicals have been shown to play a major role in the development of perfusion abnormalities, contractile dysfunction, and irreversible injury in ischemic-reperfused myocardium. The aim of this study was to assess the direct protective effects of radical scavengers, calcium antagonists, and combination of these substances against free radical induced myocyte damage. Viability (% of rod-shaped cells) and adenine nucleotide content (AdN, high-pressure liquid chromatography) of isolated adult rat cardiomyocytes were measured after exposure to hypoxanthine (2 mM) and xanthine oxidase (25 mU/ml). After 90 min, viability of myocytes decreased to 4.2±3.4 % (mean±SEM) of pre-exposure control, and AdN decreased from 28.2±1.8 to 8.09±1.1 nmol/mg protein. Addition of catalase (1500 U/ml) resulted in the preservation of viability (77±6% of pre-exposure control, n=6, mean±SEM), and AdN 84±6%, p<0.001. These values are not significantly different from those measured in myocytes not exposed to free radicals (88±9% and 79±6%, respectively). Superoxide dismutase (2400 U/ml), dimethylthiourea (10 mM), and desferrioxamine (1 mM) did not preserve either viability or AdN. The calcium antagonist verapamil (10 M) also preserved myocyte viability significantly (23±9.7%, p<0.05 vs unprotected cells), but failed to prevent the loss of AdN (13.2±4%, not significant as compared to unprotected cells). Viability and AdN in myocytes treated with nifedipine (10 M) or diltiazem (10 M) were not higher than in unprotected cells. All combined treatment forms which included catalase resulted in the preservation of myocyte viability as well as AdN. These data show that only the hydrogen peroxide scavenger catalase protects isolated cardiomyocytes against free radicals generated in the purine catabolic pathway.     

Visualization of rat pial microcirculation using the novel orthogonal polarized spectral (OPS) imaging after brain injury.

Recently, the novel optical system, orthogonal polarized spectral (OPS) imaging was developed to visualize microcirculation. Investigation of changes in microcirculation is essential for physiological, pathophysiological, and pharmacological studies. In the present study applicability of OPS imaging was assessed to study pial microcirculation in normal and traumatized rat brain. High quality images of rat pial microcirculation in normal and traumatized rats were generated with the OPS imaging, allowing to easily differentiate arterioles and venules with the dura remaining intact. In non-traumatized rats, mean vessel diameter of arterioles and venules of five different cortical regions was 19.1+/-2.7 and 22.2+/-1.4 microm, respectively. In the early phase following focal cortical contusion vessel diameter was significantly decreased in arterioles by 28% while diameter in venules was significantly increased by 27%. For technical reasons velocity in arterioles was not measurable. In venules, mean flow velocity of 0.68+/-0.08 mm/s was significantly decreased by 50% at 30 min after trauma. OPS imaging is an easy to use optical system allowing to generate high quality images and to reliably investigate pial microcirculation without having to remove the dura. This technique opens the possibility to perform longitudinal studies investigating changes in pial microcirculation.     

Relation of cerebral energy metabolism and extracellular nitrite and nitrate concentrations in patients after aneurysmal subarachnoid hemorrhage.

In a prospective clinical investigation on neurochemical intensive care monitoring, the authors' aim was to elucidate the temporal profile of nitric oxide metabolite concentrations-that is, nitrite and nitrate (NO(x))--and compounds related to energy-metabolism in the cerebral interstitium of patients after aneurysmal subarachnoid hemorrhage (SAH). During aneurysm surgery, microdialysis probes were implanted in cerebral white matter of the vascular territory most likely affected by vasospasm. Temporal profiles of NO(x) were analyzed in a subset of 10 patients (7 female, 3 male, mean age = 47 +/- 14 years). Microdialysis was performed for 152 +/- 63 hours. Extracellular metabolites (glucose, lactate, pyruvate, glutamate) were recovered from the extracellular fluid of the cerebral parenchyma. NO(x) was measured using a fluorometric assay. After early surgery, SAH patients revealed characteristic decreases of NO(x) from initial values of 46.2 +/- 34.8 micromol/L to 23.5 +/- 9.0 micromol/L on day 7 after SAH (P < 0.05). Decreases in NO(x) were seen regardless of development of delayed ischemia (DIND). Overall NO(x) correlated intraindividually with glucose, lactate, and glutamate (r = 0.58, P < 0.05; r = 0.32, P < 0.05; r = 0.28, P < 0.05; respectively). After SAH, cerebral extracellular concentrations of NO metabolites decrease over time and are associated with concomitant alterations in energy-or damage-related compounds. This could be related to reduced NO availability, potentially leading to an imbalance of vasodilatory and vasoconstrictive factors. On the basis of the current findings, however, subsequent development of DIND cannot be explained by a lack of vasodilatory NO alone.     

Hypermedia techniques for diagnostic imaging instruction: videodisk echocardiography encyclopedia

Because of the visual complexity of medical images and the intensive tutorial experience required to develop image recognition expertise, professional training programs have concentrated on educating limited numbers of experts. Videodisk and CD-ROM (compact disk read only memory) image storage media now make it possible for a microcomputer workstation to provide a learning environment substantially equivalent to that of conventional time-consuming tutorial methods. A demonstration hypermedia program on echocardiography was constructed that provides a user-controlled learning environment with instant access to 54,000 video frames encompassing 1,200 clinical items. The instructional module is controlled by a microcomputer, which provides electronic linkage to relevant graphics, animations, text, categorized data bases, and digitized sound. The system has been successfully used in a residency program as the primary instructional tool for achieving an intermediate level of clinical expertise. Hypermedia offer substantial advantages over conventional books as a clinical reference source.     

Pharmacokinetics of human granulocyte-macrophage colony-stimulating factor using a sensitive immunoassay

A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.