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1.
Minerva Anestesiol ; 77(11): 1043-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21602755

ABSTRACT

BACKGROUND: The need for a cesarean delivery may interfere negatively with the overall experience of childbirth. Several factors related to anesthesiological management such as postoperative pain and discomfort, nausea and pruritus, and postdural puncture headache (PDPH), may lead to dissatisfaction and have a negative impact on early mobilization and a new mother's ability to care for her newborn baby. Optimal prophylaxis and treatment decrease these complications, increase satisfaction, and prevent chronic pain. This survey determined how prophylaxis and treatment of pain, PDPH, nausea, and pruritus after cesarean section (CS) is managed. METHODS: A questionnaire was sent to 709 departments of anesthesiology serving an obstetric unit in Germany. The questionnaire asked about different aspects of pain management, the management of accidental dural puncture (ADP), and treatment of PDPH. Further we asked about therapy and prophylaxis of nausea and pruritus in the peripartal setting. RESULTS: In all, 360 questionnaires (50.8%) were returned; 346 were complete and analyzed (accounting for 330000 births per year). Paracetamol (77.5%) and piritramide (85.6%) are the most common analgesics used. If epidural catheters were used for anesthesia for CS, 47.7% were used for postoperative pain therapy. However, 92.7% of the departments removed catheters in less than 24 hours after delivery. In case of an ADP most departments (69.9%) repeated puncture, 2.6% placed catheters intrathecally. Median blood volume for an epidural blood patch was 10ml. CONCLUSION: Apart from conservative treatment of PDPH, prophylaxis and treatment of pain after cesarean delivery, PDPH, nausea, and pruritus varied widely, indicating the need for the qualitative evaluation of overall management.


Subject(s)
Cesarean Section/adverse effects , Pain, Postoperative/etiology , Pain, Postoperative/therapy , Post-Dural Puncture Headache/etiology , Post-Dural Puncture Headache/therapy , Postoperative Nausea and Vomiting/etiology , Postoperative Nausea and Vomiting/therapy , Pruritus/etiology , Pruritus/therapy , Adult , Analgesia, Epidural , Analgesics/therapeutic use , Dura Mater/injuries , Female , Germany/epidemiology , Humans , Infant, Newborn , Medical Errors , Pain Management/methods , Pain, Postoperative/prevention & control , Post-Dural Puncture Headache/prevention & control , Postoperative Nausea and Vomiting/prevention & control , Pregnancy , Pruritus/prevention & control , Surveys and Questionnaires , Treatment Outcome
2.
Anaesthesist ; 58(10): 1010-26, 2009 Oct.
Article in German | MEDLINE | ID: mdl-19816662

ABSTRACT

In recent years a new understanding of trauma-associated hemorrhaging and trauma-induced coagulopathy has been achieved. This coagulopathy is multifactorial with the predominant mechanisms being tissue trauma, shock and hypoperfusion which can lead to hyperfibrinolysis by activation of the endothelium. Routinely tested coagulation parameters, such as prothrombin time and partial thromboplastin time, are frequently employed for decision making but remain problematic as they do not give any information on clot stability, lysis or platelet function. Thrombelastometry seems to be a useful alternative. A pro-active anticipatory approach is required for a successful outcome to be achieved as rescue correction is more difficult than prevention. While the pathophysiological conception of causal relationship of the mentioned therapeutic options is conclusive, an evidence-based validation by randomized controlled studies is mostly lacking. The emergency and anesthesiological concept of damage control resuscitation consists of limiting volume therapy with crystalloids and colloids to reach a mean arterial pressure > or =65 mmHg (higher for head injuries), active (re-)warming management, the prevention of a pH< or =7.2 and a base excess (BE) < or =-6 mmol/l. The early and sufficient application of hemostatic drugs is essential. Because erythrocytes play a substantial role in the coagulation process, hemoglobin (Hb) values of around 6. 2 mmol/l (10 g/dl) and/or a hematocrit of 30% should be strived for when massive non-arrested hemorrhaging occurs. After severe multiple trauma a fibrinogen deficit develops and must be adequately compensated. If coagulation therapy is carried out using fresh frozen plasma sufficient quantities (20-30 ml/kgBW) must be administered to correspondingly raise the coagulation factors. Prothrombin complex concentrates can be helpful to optimize thrombin generation during severe hemorrhaging. Because hyperfibrinolysis occurs more often than previously assumed during severe trauma, an anti-fibrinolytic therapy should be used especially for patients with an instable circulation. The platelet count should not go below 100,000/microl when hemorrhaging occurs after multiple trauma. For thrombocytopathic patients with diffuse bleeding desmopressin (DDAVP) is a therapeutic option and the "off label" use of recombinant activated factor VIIa (rFVIIa) remains an option for individual situations with stringent indications and when the above named measures to optimize the coagulation situation have been taken.


Subject(s)
Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/therapy , Multiple Trauma/blood , Multiple Trauma/therapy , Acidosis/etiology , Acidosis/therapy , Blood Coagulation Disorders/diagnosis , Blood Component Transfusion , Fibrinolysis , Hemostasis , Hemostatics/therapeutic use , Humans , Hypotension, Controlled , Hypothermia, Induced , Inflammation/etiology , Inflammation/therapy , Partial Thromboplastin Time , Plasma , Shock, Hemorrhagic/therapy , Thrombelastography
3.
Anaesthesist ; 58(9): 891-6, 2009 Sep.
Article in German | MEDLINE | ID: mdl-19730795

ABSTRACT

This case report reviews the anesthesiological complications of intrathecal baclofen (ITB) therapy. An 11-year-old boy with spasticity and apallic syndrome needed general anesthesia for exchange of a baclofen pump but 2 h later he became increasingly hypothermic, hypotonic with bradycardy and dyspnea. The cause was an intra-operative bolus of ITB. Reduction of the baclofen administration rate caused disappearance of all symptoms without any residual effects. The ITB is an increasingly used therapeutic option for multiple sclerosis and cerebral palsy. Therefore, emergency personal and anesthesiologists must be aware of the possible side effects of this medication.


Subject(s)
Baclofen/administration & dosage , Baclofen/therapeutic use , Infusion Pumps, Implantable , Muscle Relaxants, Central/administration & dosage , Muscle Relaxants, Central/therapeutic use , Anesthesia, General , Baclofen/adverse effects , Cerebral Palsy/drug therapy , Child , Drug Overdose , Humans , Injections, Spinal , Intraoperative Complications/chemically induced , Intraoperative Complications/physiopathology , Male , Muscle Relaxants, Central/adverse effects , Muscle Spasticity/drug therapy
4.
Anaesthesist ; 57(6): 582-8, 2008 Jun.
Article in German | MEDLINE | ID: mdl-18446523

ABSTRACT

Survival rates after cardiac arrest remain poor despite substantial efforts to advance the cardiopulmonary resuscitation algorithm in the last decades. Recent changes in the resuscitation guidelines in 2005 focused on minimizing interruptions during chest compressions. The aim to provide optimal chest compressions led to the development of automated mechanical chest compression devices, one of which is the AutoPulse resuscitation system. A case of successful use of the AutoPulse system in a 66-year-old patient with sudden cardiac arrest is presented and a review is given of more than 3 years experience in the routine use of this mechanical device for CPR in the emergency medical system in Bonn. Based on this experience, the AutoPulse system is considered to be a safe and effective technical advancement that under certain CPR conditions can be a helpful tool and provide an increased quality of chest compressions.


Subject(s)
Cardiopulmonary Resuscitation/instrumentation , Emergency Medical Services/methods , Physicians , Pulse/methods , Aged , Cardiopulmonary Resuscitation/adverse effects , Coronary Angiography , Death, Sudden, Cardiac , Electrocardiography , Guidelines as Topic , Humans , Male
5.
Anaesthesist ; 57(2): 143-6, 2008 Feb.
Article in German | MEDLINE | ID: mdl-18038119

ABSTRACT

A 71-year-old female patient developed acute myocardial failure immediately after cataract surgery under general anesthesia. Subsequently performed laevocardiography demonstrated a basal ballooning of the left ventricle characteristic of basal tako-tsubo cardiomyopathy. The basal tako-tsubo cardiomyopathy was induced by a previously asymptomatic pheochromocytoma. The left ventricular function recovered completely within 4 days without specific treatment.


Subject(s)
Anesthesia, General/adverse effects , Pheochromocytoma/etiology , Postoperative Complications/physiopathology , Takotsubo Cardiomyopathy/etiology , 3-Iodobenzylguanidine , Aged , Cataract Extraction , Electrocardiography , Female , Heart Failure/diagnostic imaging , Heart Failure/etiology , Heart Failure/physiopathology , Humans , Pheochromocytoma/diagnostic imaging , Pheochromocytoma/therapy , Positron-Emission Tomography , Radiopharmaceuticals , Takotsubo Cardiomyopathy/diagnostic imaging , Takotsubo Cardiomyopathy/physiopathology , Ultrasonography , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
6.
Anaesthesist ; 55(7): 773-7, 2006 Jul.
Article in German | MEDLINE | ID: mdl-16670903

ABSTRACT

We report the use of the non-specific adenosine antagonist theophylline (aminophylline) during a prolonged intraoperative cardiopulmonary resuscitation (CPR) due to myocardial infarction. In the 2005 guidelines of the European Resuscitation Council the general use of theophylline during CPR is not recommended, but in the case of an atropine and epinephrine resistant asystole, especially as a result of inferior myocardial infarction, theophylline might be a useful adjunct during CPR.


Subject(s)
Heart Arrest/drug therapy , Theophylline/therapeutic use , Vasodilator Agents/therapeutic use , Aged, 80 and over , Anesthesia, General , Atropine/therapeutic use , Cardiopulmonary Resuscitation , Electrocardiography , Epinephrine/therapeutic use , Heart Arrest/etiology , Humans , Male , Muscarinic Antagonists/therapeutic use , Myocardial Infarction/complications , Ophthalmologic Surgical Procedures , Vasoconstrictor Agents/therapeutic use
7.
Article in German | MEDLINE | ID: mdl-14508702

ABSTRACT

OBJECTIVE: Due to rising health care costs there is a need to verify that the treatment by Emergency Medical Services (EMS) systems is efficient and cost effective. The integration of emergency physicians is inherent part of out-of-hospital emergency care and regulated by law in Germany but not in England and the United States of America. Aim of this study therefore was to conduct a cost performance analysis by evaluating the underlying structure, the costs incurred and the achieved performance in two EMS systems with paramedics or emergency physicians on scene. METHODS: The study was carried out in West-Birmingham, a part of the West-Midlands-Ambulance-Service (WMAS), and the EMS of Bonn. Pre defined questionnaires, EMS protocols, calculations of purchasing power parity and recent publications concerning out-of-hospital resuscitation (CPR) were used to evaluate the operating costs, to describe the structure and to measure the quality of performance. Significance was assumed at p < 0.01 for CHI(2)- or t-test, respectively. RESULTS: Birmingham used state of the art technology for dispatch and logistics whereas Bonn trusted in high qualified personnel. In the 1st quarter 1997 the Mainz-Emergency-Evaluation Score could be achieved before (MEES A) and after preclinical treatment (MEES B) in 3502 and 3422 patients in Birmingham and Bonn, respectively. In Birmingham 7.5 % and in Bonn 17 % of all patients could be improved by the EMS treatment, respectively (p < 0.01). Looking at severely ill patients (MEES A < 22) the EMS in West-Birmingham achieved an improvement in 27.9 % of these patients with an averaged change in MEES of 0.9 +/- 1.7 points in all of them. In contrast the Bonn EMS improved the status in 47.8 % of these patients and MEES A could be improved considerably by 2.3 +/- 3.4 points (p < 0.01). Pharmacological treatment was less frequently used in Birmingham than in Bonn (12.9 % vs. 32.4 %, respectively; p < 0.01). At equal incidences of CPR attempts discharge rate after CPR was only 4 % in WMAS compared to 14.7 % in Bonn-North (p < 0.01). Per inhabitant and year total costs amounted to 10.43 euro for the EMS system in Birmingham, which is 42 % less than in Bonn. Unit hour utilisation reached 0.6 in Birmingham and only 0.33 in Bonn. In severely ill patients the improvement of MEES A by 0.1 points cost per inhabitant and year 1.16 euro in Birmingham and only 0.65 euro in Bonn. The survival of one patient after CPR was calculated to 0.7 euro in Birmingham and 0.17 euro in Bonn. CONCLUSIONS: The provider of the EMS in West-Birmingham--WMAS--organised a reliable system with high efficiency concerning unit hour utilisation and response time reliability. In the EMS of Bonn, in contrast, the complex therapy by the emergency physicians improved MEES considerably and increased probability of survival after CPR at a higher level of efficiency. Further investigations however are necessary to evaluate the presented parameter of efficiency.


Subject(s)
Emergency Medical Services/economics , Emergency Medical Services/standards , Allied Health Personnel/economics , Allied Health Personnel/standards , Cardiopulmonary Resuscitation , Cost-Benefit Analysis , Drug Therapy/statistics & numerical data , Efficiency, Organizational , Germany , Humans , Physicians/economics , Physicians/standards , Quality Assurance, Health Care , Surveys and Questionnaires , Survival , United Kingdom
8.
Acta Neuropathol ; 101(2): 101-13, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11271364

ABSTRACT

Rats were submitted to 10-min cardiac arrest, followed by resuscitation and survival for 1 day, 3 days or 1 week. Five regions of interest (CA1 and CA3 sector of hippocampus, dentate gyrus, reticular nucleus of thalamus and parietal cortex) where studied by light and electron microscopy at each of the survival times, and compared with non-ischemic control rats. Cell counts revealed delayed neuronal loss of about 30% after 3 days in both CA1 and CA3 sectors. Ischemic cell changes consisting of cytoplasmic condensation and nuclear pyknosis appeared in these regions on day 7 and --to a lesser degree-- also affected dentate gyrus, the reticular nucleus of thalamus and cerebral cortex. Ultrastructural alterations were evaluated using an ultrastructural injury catalogue. In all brain regions similar, although quantitatively differently expressed, changes occurred except ribosomal disaggregation, which was restricted to neurons of hippocampal CA1 sector on the first day after cardiac arrest. Progressive alterations included swelling of mitochondria and endoplasmic reticulum, which was most pronounced in CA1 and CA3 sectors of hippocampus, as well as chromatin aggregation and alterations of neuronal volume, which affected mainly the granule cells of dentate gyrus. Other alterations, such as osmiophilic inclusions or the formation of nuclear pore complexes, were transient with a maximum on the first day after cardiac arrest. Treatment with the free-radical scavenger alpha-phenyl-N-tert-butyl nitrone (PBN) suppressed the formation of nuclear pores but otherwise did not markedly change the morphological outcome. In comparison to previous studies of global brain ischemia induced by arterial inflow occlusion of the same duration, the present data demonstrate remarkable preservation of tissue integrity in CA1 sector but also distinct changes in brain regions considered to be resistant to ischemic injury. Morphological alterations of brain after cardiac arrest do not follow the established pattern of selective vulnerability.


Subject(s)
Brain Ischemia/pathology , Brain/pathology , Heart Arrest/complications , Nerve Degeneration/pathology , Neurons/pathology , Animals , Brain/ultrastructure , Brain Ischemia/drug therapy , Capillaries/pathology , Capillaries/ultrastructure , Cardiovascular Physiological Phenomena , Cell Nucleus/pathology , Cell Nucleus/ultrastructure , Cell Size/physiology , Chromatin/pathology , Chromatin/ultrastructure , Cyclic N-Oxides , Microscopy, Electron , Nerve Degeneration/drug therapy , Neuroglia/pathology , Neuroglia/ultrastructure , Neurons/ultrastructure , Neuroprotective Agents/pharmacology , Nitrogen Oxides/pharmacology , Nuclear Envelope/pathology , Nuclear Envelope/ultrastructure , Organelles/pathology , Organelles/ultrastructure , Rats
9.
Crit Care Med ; 28(8): 2866-72, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10966263

ABSTRACT

OBJECTIVE: Successful resuscitation of the brain after cardiac arrest requires unimpaired microcirculatory reperfusion. Postischemic cerebral hypoperfusion presumably is mediated through activation of endothelin type A receptors (ET(A)). The effect of the selective ET(A) antagonist BQ123 on cerebral blood flow and function was studied in a rat model of cardiac arrest. DESIGN: Prospective, randomized trial. SETTING: Experimental animal laboratory. SUBJECTS: Twelve male Sprague-Dawley rats (290-350 g). INTERVENTIONS: Cardiac arrest for 12 mins was induced by electrical fibrillation of the heart, followed by standardized cardiopulmonary resuscitation. BQ123 (0.8 mg/kg; n = 6) or its vehicle (saline; n = 6) was injected intravenously at 15 mins after the return of spontaneous circulation. MEASUREMENTS: Cortical blood flow was measured by laser-Doppler flowmetry, electrophysiological function by recording the amplitude of somatosensory evoked potentials, vascular reactivity by ventilation with 6% CO2, and the functional coupling of blood flow by recording the laser-Doppler flow (LDF) changes during somatosensory stimulation. Hemodynamic and functional cerebral recovery was monitored for 3 hrs after the return of spontaneous circulation. MAIN RESULTS: Forty-five minutes after the return of spontaneous circulation, postischemic hypoperfusion developed in both groups, as reflected by a decrease of the LDF signal to about 60% of the preischemic level. In untreated animals, hypoperfusion persisted throughout the observation time, but in animals receiving BQ123, LDF gradually returned to normal. CO2 reactivity in untreated animals was severely reduced for 2-3 hrs after the onset of recirculation, whereas after BQ123 treatment it returned to normal and after 2 hrs even above normal. The ET(A) antagonist also induced a more rapid recovery of the somatosensory evoked potentials amplitude and of the functional blood flow response to somatosensory stimulation, but these parameters did not recover completely within the observation period. CONCLUSIONS: Application of the ET(A) antagonist BQ123 during the early reperfusion period after cardiac arrest shortens postischemic cerebral hypoperfusion and accelerates the restoration of the cerebrovascular CO2 reactivity and the recovery of electrophysiologic function.


Subject(s)
Cardiopulmonary Resuscitation , Cerebrovascular Circulation/drug effects , Endothelin Receptor Antagonists , Heart Arrest/therapy , Peptides, Cyclic/therapeutic use , Animals , Carbon Dioxide/pharmacology , Heart Arrest/physiopathology , Hemodynamics , Male , Prospective Studies , Random Allocation , Rats , Rats, Sprague-Dawley
10.
Crit Care Med ; 28(8): 2873-80, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10966264

ABSTRACT

OBJECTIVE: Antagonists of endothelin (ET(A)) receptors improve postischemic hypoperfusion. In this study we investigated whether the selective ET(A)-antagonist BQ123 also improves postischemic functional recovery. STUDY DESIGN: Cardiac arrest of 12 mins duration was induced in rats by electrical fibrillation of the heart, followed by advanced cardiopulmonary resuscitation. BQ123 (0.8 mg/kg; n = 9) or its vehicle (saline; n = 9) was injected intravenously at 15 mins after the return of spontaneous circulation. The neurologic deficit was scored daily for 7 days after resuscitation by rating consciousness, various sensory and motor functions, and coordination tests. On day 7, we measured functional coupling of cerebral blood flow under halothane anesthesia by recording laser-Doppler flow during electrical forepaw stimulation, and we measured vascular reactivity to CO2 by measuring the laser-Doppler flow change during ventilation with 6% CO2. The brains were perfusion-fixated with 4% paraformaldehyde, and the histopathologic damage was evaluated in the CA1 sector of hippocampus, in the motor cortex, and in the cerebellum. RESULTS: Treatment with BQ123 had no effect on histopathologic damage, but it significantly improved neurologic recovery. In all nine treated rats, neurologic performance returned to near normal within 2 days whereas four of nine untreated animals developed spastic paralysis of the hind limbs and severe coordination deficits. BQ123 also normalized CO2 reactivity and improved the functional cerebral blood flow response to somatosensory stimulation. CONCLUSIONS: The ET(A)-antagonist BQ123 significantly improves neurologic outcome after 12 mins of cardiac arrest. The apparent restoration of vascular reactivity demonstrates a correlation between hemodynamic factors and functional recovery.


Subject(s)
Cardiopulmonary Resuscitation , Endothelin Receptor Antagonists , Heart Arrest/physiopathology , Heart Arrest/therapy , Nervous System/drug effects , Nervous System/physiopathology , Peptides, Cyclic/therapeutic use , Animals , Brain/drug effects , Brain/pathology , Electrophysiology , Hemodynamics , Male , Rats , Rats, Sprague-Dawley , Recovery of Function , Time Factors
11.
Magn Reson Med ; 41(3): 469-73, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10204868

ABSTRACT

Somatosensory evoked potentials (SEP) and T2*-weighted nuclear magnetic resonance (NMR) images were recorded simultaneously during somatosensory stimulation of rat to investigate the relationship between electrical activation of the brain tissue and the signal intensity change in functional NMR imaging. Electrical forepaw stimulation was performed in Wistar rats anesthetized with alpha-chloralose. SEPs were recorded with calomel electrodes at stimulation frequencies of 1.5, 3, 4.5, and 6 Hz. At the same time, T2*-weighted imaging was performed, and the signal intensity increase during stimulation was correlated with the mean amplitude of the SEP. Both the stimulation-evoked signal intensity increase in T2*-weighted images and the amplitude of SEPs were dependent on the stimulation frequency, with the largest signals at a stimulation frequency of 1.5 Hz and decreasing activations with increasing frequencies. The feasibility of simultaneous, artifact-free recordings of T2*-weighted NMR images and of evoked potentials is proved. Furthermore, the study demonstrates-in the intact brain-the validity of functional magnetic resonance imaging for estimating the intensity of electrocortical activation.


Subject(s)
Brain/anatomy & histology , Brain/physiology , Evoked Potentials, Somatosensory , Magnetic Resonance Imaging , Animals , Cerebrovascular Circulation/physiology , Electric Stimulation , Electrophysiology , Male , Rats , Rats, Wistar , Reproducibility of Results , Sensitivity and Specificity
12.
NMR Biomed ; 11(3): 115-9, 1998 May.
Article in English | MEDLINE | ID: mdl-9699494

ABSTRACT

T2*-weighted imaging at 4.7 T was used to identify the cortical areas activated by electrical stimulation of the forepaw and hindpaw of alpha-chloralose anesthetized rats. Variation of the coronal slice position relative to the bregma, showed that the forepaw representation in the somatosensory cortex is more frontal and lateral than that of the hindpaw. Overlap between both activation areas was observed only in a small region in the slice at the level of the bregma. Documented localizations of both representations are in good agreement with earlier observations using invasive techniques. The determination of the separate areas of both paws indicates the feasibility of more complex activation studies in anesthetized animals, such as combined stimulations for the investigation of potentiation or depression effects on individual stimuli.


Subject(s)
Anesthetics, Intravenous/pharmacology , Brain Mapping , Chloralose/pharmacology , Magnetic Resonance Imaging/methods , Somatosensory Cortex/physiology , Animals , Electric Stimulation , Forelimb/physiology , Hindlimb/physiology , Rats , Rats, Sprague-Dawley
13.
Neuroscience ; 84(1): 81-8, 1998 May.
Article in English | MEDLINE | ID: mdl-9522364

ABSTRACT

Administration of inhibitors of neuronal nitric oxide synthase or deletion of the encoding gene in rodents provided evidence that neuronal nitric oxide synthase activity may contribute to neuronal cell death following global and focal cerebral ischemia. In the present study, we investigated by in situ hybridization the expression of an endogenous inhibitor of neuronal nitric oxide synthase activity, designated protein inhibitor of neuronal nitric oxide synthase and homologous to cytoplasmic dynein light chain, in the post-ischemic rat brain. Following global ischemia induced by cardiac arrest, messenger RNA expression of protein inhibitor of neuronal nitric oxide synthase was rapidly induced in pyramidal neurons of the hippocampal CA3 region and granule cell of the dentate gyrus which are resistant to ischemic damage. In vulnerable CA1 pyramidal neurons however, protein inhibitor of neuronal nitric oxide synthase expression remained at basal level after global ischemia and was associated with an increase in nicotinamide adenine dinucleotide phosphate-diaphorase activity and subsequent DNA fragmentation indicating ischemia-mediated neuronal cell death. Following focal cerebral ischemia induced by permanent occlusion of the middle cerebral artery, transcripts of protein inhibitor of neuronal nitric oxide synthase progressively accumulated in cortical neurons bordering the infarct area. After transient middle cerebral artery occlusion however, messenger RNA levels of protein inhibitor of neuronal nitric oxide synthase increased in the reperfused neocortex. Our findings indicate that cerebral ischemia leads to an increase in neuronal expression of protein inhibitor of neuronal nitric oxide synthase in brain regions where sustained or "uncoupled" nitric oxide synthase activity may be detrimental to neurons. Lack of post-ischemic induction of protein inhibitor of neuronal nitric oxide synthase in CA1 pyramidal neurons may result in high nitric oxide synthase activity after global ischemia and could contribute to delayed neuronal cell death.


Subject(s)
Brain Ischemia/metabolism , Carrier Proteins/metabolism , Drosophila Proteins , Animals , Autoradiography , Blotting, Northern , Brain/metabolism , Brain/pathology , Brain Ischemia/pathology , Carrier Proteins/genetics , Cell Death/physiology , Dyneins , In Situ Hybridization , Male , NADPH Dehydrogenase/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Tissue Distribution
14.
Am J Hypertens ; 10(5 Pt 1): 525-34, 1997 May.
Article in English | MEDLINE | ID: mdl-9160763

ABSTRACT

The renal sodium pump participates in sodium homeostasis and has been predicted to have a role in salt dependent forms of hypertension. However, the status of the renal sodium pump in volume-dependent hypertension is unclear. We assessed the renal sodium pump and its activity in the deoxycorticosterone acetate (DOCA)-salt model in rats, a model of volume-dependent hypertension. Sprague-Dawley rats on ad libitum diet were compared with four groups of litter mates receiving high or low salt diets, with or without DOCA administration. The renal sodium pump evaluation included measurement of hydrolytic activity, ouabain binding capacity and affinity, sodium activation, active pump units (determined by phosphoenzyme level), dephosphorylation rate, and isoform specific molecular expression. Intrinsic enzyme properties, including sodium and ouabain affinities, as well as turnover rate per sodium pump, were identical among the five groups. In contrast, the combination of DOCA and high salt intake (DOCA high salt) produced marked, significant increases in hydrolytic activity, ouabain binding capacity, phosphoenzyme level, and alpha1-isoform expression. DOCA low salt animals showed much smaller but significant increases in pump number. We conclude that DOCA and volume expansion may each alter renal sodium pump regulation, but volume expansion is clearly dominant. Increased renal sodium pump activity in DOCA high salt animals would, if unmitigated, favor sodium reabsorption and may contribute to hypertension.


Subject(s)
Hypertension, Renal/physiopathology , Sodium-Potassium-Exchanging ATPase/physiology , Animals , Desoxycorticosterone/administration & dosage , Diet, Sodium-Restricted , Disease Models, Animal , Homeostasis , Hypertension, Renal/enzymology , Hypertension, Renal/veterinary , Male , Plasma Volume/physiology , Rats , Rats, Sprague-Dawley , Sodium Chloride, Dietary
15.
Am J Physiol ; 271(2 Pt 2): H514-20, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8770091

ABSTRACT

The Na pump in vascular smooth muscle (VSM) is likely to influence not only intracellular Na content but also the content and distribution of other cations and anions measured by electron probe X-ray microanalysis (EPXMA). The hypothesis we tested was that EPXMA of pump-inhibited VSM would yield a characteristic cellular elemental profile, providing insight into the contribution of the Na pump to the intracellular milieu and an approach to identifying when VSM operates under the constraints of pump inhibition. We assessed the contractile state and elemental EPXMA profile of rabbit aorta that was either quiescent or contracted by serotonin (10(-6) M) or ouabain (10(-6) M). VSM cytoplasm showed the anticipated low Na (28 +/- 2 mM) and high K (182 +/- 5 mM) content. With ouabain, Na rose and K fell to reverse the Na-to-K ratio (0.15 +/- 0.01 vs. 6.6 +/- 0.3; P < 0.01). With serotonin, the ratio rose slightly (0.28 +/- 0.2; P < 0.05). Nuclei and mitochondria showed a similar pattern. CI showed a small increase (56 +/- 2 to 102 +/- 4 mM) with ouabain, a shift that could not be accounted for on the basis of charge redistribution to maintain neutrality because the change in Na and K were essentially offsetting. EPXMA measures total and not ionized Ca. If changes in cytoplasmic Ca occurred, they were too small to be measured by the imaging methods employed. The sustained, myogenic contractile response of VSM to Na pump inhibition shows a characteristic elemental profile that could prove useful in its identification. Direct measurement of membrane potential during the myogenic response to Na pump inhibition should have a high priority.


Subject(s)
Aorta/metabolism , Muscle, Smooth, Vascular/metabolism , Sodium-Potassium-Exchanging ATPase/chemistry , Sodium-Potassium-Exchanging ATPase/physiology , Animals , Aorta/cytology , Aorta/drug effects , Cytoplasm/metabolism , Electron Probe Microanalysis , Female , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Ouabain/pharmacology , Potassium/metabolism , Rabbits , Serotonin/pharmacology , Sodium/metabolism , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Subcellular Fractions/metabolism , Vasoconstriction , Vasoconstrictor Agents/pharmacology
16.
Am J Hypertens ; 9(1): 39-46, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8834705

ABSTRACT

The possibility that a circulating sodium pump inhibitor contributes to the pathogenesis of volume-dependent hypertension via an action on vascular smooth muscle (VSM) is supported by multiple lines of investigation, but remains controversial. We had two goals in this study. The first was to compare the pattern of contractile response of rabbit aorta induced by two candidates, ouabain and a labile sodium pump inhibitor that we have identified in the peritoneal dialysate of volume-expanded hypertensive patients with chronic renal failure. Our second goal was to examine the ability of Digibind, a Fab fragment of antisera directed against digoxin, to reverse VSM contraction induced by both agents. Ouabain induced a concentration-dependent contraction, which was delayed in onset, was gradual, and reached a stable plateau after many hours. The labile sodium pump inhibitor induced a qualitatively similar series of responses. Digibind rapidly reversed the contractile responses to both sodium pump inhibitors, with a rate of relaxation that matched that induced by physical removal of the pump inhibitor from the bath. For ouabain, the Digibind:ouabain stoichiometry was highly predictable. When Digibind was present in a molar concentration equivalent to that of ouabain, or less, it had no effect. When the Digibind concentration was twice that of ouabain, complete relaxation occurred. Although the concentration:VSM response relationship for ouabain was steep, the concentration:effect interaction with Digibind was even more steep. The molar concentration of Digibind required to reverse the effects of the labile endogenous inhibitor from peritoneal dialysate was consistently lower than that for ouabain, which is compatible with either greater potency of the labile factor in VSM or greater affinity for Digibind. These findings are compatible with a role for one or more endogenous sodium pump inhibitors as the determinant of vascular smooth muscle tone in the volume-sensitive hypertension of renal disease.


Subject(s)
Enzyme Inhibitors/pharmacology , Hypertension/physiopathology , Muscle, Smooth, Vascular/physiology , Ouabain/pharmacology , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Animals , Aorta/drug effects , Aorta/physiology , Digoxin/immunology , Female , Humans , Immunoglobulin Fab Fragments/pharmacology , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Rabbits
17.
Am J Hypertens ; 8(9): 921-7, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8541008

ABSTRACT

Although volume and vasoconstriction have been considered polar elements in a useful pathogenetic hypertension model, many observations suggest that vasoconstriction is involved in volume-dependent hypertension, reflecting the effect of a digitalis-like factor. To examine that possibility, we assessed the depressor responses to Digibind, an antibody Fab directed against digoxin, in a volume-dependent model--DOCA-salt-induced hypertension in rats. Digibind (10 mg/kg, intravenously) induced a gradual blood pressure fall over 2 h that was sustained for 4 h (P < .001). Blood pressure did not fall with Digibind when DOCA was administered without salt or a high-salt intake was provided without DOCA. The intracellular sodium content of the rat aorta, measured by atomic absorption spectroscopy after cold choline wash, was increased in the DOCA-high-salt rats (23.3 +/- 2.7 mEq/L) compared to control rats (12.1 +/- 0.8 mEq/L; P < .001). Aorta sodium content, in parallel with blood pressure, was not increased either by dietary salt supplementation without DOCA, or by DOCA with a low-salt diet. Sodium pump activity was measured as 86Rb uptake into vascular smooth muscle (VSM). Both ouabain-sensitive and ouabain-resistant 86Rb uptake were significantly higher in VSM from DOCA-high-salt animals (P < .01). Despite its effectiveness in reducing blood pressure in this model, Digibind influenced neither VSM sodium content nor 86Rb uptake. The results are consistent with a role for a circulating digitalis-like factor in this volume-dependent model, but events at the VSM level are complex.


Subject(s)
Digoxin/immunology , Hypertension/drug therapy , Hypertension/physiopathology , Immunoglobulin Fab Fragments/administration & dosage , Animals , Aorta/drug effects , Aorta/metabolism , Blood Pressure/drug effects , Desoxycorticosterone , Diet , Hypertension/metabolism , Infusions, Intravenous , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Rats , Rats, Sprague-Dawley , Sodium/metabolism , Sodium-Potassium-Exchanging ATPase/drug effects , Sodium-Potassium-Exchanging ATPase/metabolism
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