[Chronic hypoxia and cardiovascular risk : Clinical significance of different forms of hypoxia]. / Chronische Hypoxie und kardiovaskuläres Risiko : Klinische Bedeutung verschiedener Hypoxieformen.

It is of fundamental importance to differentiate whether chronic hypoxia occurs intermittently or persistently. While chronic intermittent hypoxia (CIH) is found typically in patients with obstructive sleep apnea (OAS), chronic persistent hypoxia (CPH) is typically diagnosed in patients with chronic lung disease. Cardiovascular risk is markedly increased in patients with CIH compared to patients with CPH. The frequent change between oxygen desaturation and reoxygenation in patients with CIH is associated with increased hypoxic stress, increased systemic inflammation, and enhanced adrenergic activation followed by endothelial dysfunction and increased arteriosclerosis. The pathophysiologic consequences of CPH are less well understood. The relationship between CPH and the development of pulmonary hypertension, pulmonary heart disease as well as polycythemia has been established.

[Recognizing rare cardiac diseases by electrocardiogram]. / Seltene Herzerkrankungen am Elektrokardiogramm erkennen.

A number of rare cardiac diseases can be recognized by electrocardiogram (ECG). This article illustrates the clinical importance of ECG as a key diagnostic tool to detect Wolff-Parkinson-White syndrome and channelopathies, which are frequently diagnosed late after one or more affected family members have become victims of sudden cardiac death. These channelopathies include long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. In addition, typical ECG findings are frequently present in patients with idiopathic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, digitalis intoxication, hyperkalemia, acute cor pulmonale due to pulmonary embolism, as well as severe left ventricular hypertrophy as in hypertrophic cardiomyopathy.

Characterization and analysis of migration patterns of dentospheres derived from periodontal tissue and the palate.

BACKGROUND AND OBJECTIVE: Stem cells derived from periodontal and palatal tissues may be useful for regenerative therapies of periodontal tissues. In addition to the use of single periodontium-derived stem cells (pdSCs) and palatal-derived stem cells (paldSCs), the application of pdSC and paldSC dentospheres, providing a pool of vital stem cells, may be a useful approach. As cell migration is a prerequisite for stem cells to regenerate a three-dimensional tissue environment, we characterized pdSCs and paldSCs and investigated the migratory activity of dentospheres within a three-dimensional environment. We also investigated the capacity of the dentospheres to grow on zirconium dioxide surfaces. MATERIAL AND METHODS: The capacity of pdSCs and paldSCs to differentiate into the neuronal and osteogenic lineages was proved by RT-PCR and immunohistochemistry through the detection of specific lineage markers, such as alkaline phosphatase, glutamate decarboxylase 1 (also known as GAD67, the 67-kDa isoform of glutamate decarboxylase), neurofilament-M and ß-III-tubulin. The expression profile of surface molecules on pdSCs and paldSCs was analyzed by flow cytometry. Adhesion and growth of pdSC/paldSC dentospheres on zirconium dioxide surfaces were determined using confocal laser-scanning microscopy. The migratory behavior of the cells was analyzed using a three-dimensional collagen matrix migration assay. RESULTS: Both pdSCs and paldSCs were positive for epidermal growth factor receptor, CC chemokine receptor 2 and CXC chemokine receptor 4 expression and were able to grow on zirconium dioxide surfaces. Cell-migration experiments revealed that both stem-cell populations responded similarly to epidermal growth factor (EGF), monocyte chemotactic protein 1 (MCP-1) and stromal cell-derived factor 1alpha (SDF-1α). Stimulation with EGF resulted in an increased migratory activity of both stem-cell types, whereas the locomotory behavior of the cells was impaired by both MCP-1 and SDF-1α. CONCLUSION: Dentospheres represent a pool of vital pdSCs/paldSCs. As a result of the migratory activity demonstrated, along with the capacity to grow on zirconium dioxide surfaces, dentospheres may be useful for regenerative purposes in periodontal tissues.

Prophylactic implantable defibrillators in dilated cardiomyopathy.

Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator (ICD) therapy was investigated in the Marburg Cardiomyopathy Study, which revealed left ventricular ejection fraction to be the only significant independent arrhythmia risk predictor in a relatively large dilated cardiomyopathy (DCM) patient population. Based of the favorable results of the SCD-HeFT Trial, prophylactic ICD therapy became a class I indication for patients with DCM, NYHA class II or III heart failure and a left ventricular ejection fraction ≤ 35% despite optimized medical therapy. In addition, prophylactic ICD therapy combined with cardiac resynchronization became standard treatment in DCM patients with complete left bundle branch block and an ICD indication according to SCD-HeFT criteria. Unresolved issues of prophylactic ICD therapy in DCM include a high number to treat in order to save one patient from sudden death due to difficult arrhythmia risk stratification which is largely based on reduced left ventricular ejection fraction. Second, optimal timing of prophylactic ICD implant remains difficult, because a significant but unpredictable number of DCM patients show a marked improvement of left ventricular function during follow-up, thus, averting the need prophylactic ICD therapy. Finally, prophylactic ICD therapy is associated with a considerable complication rate with painful inappropriate shocks and lead-related problems being the most frequent complications during long-term follow-up.

Clinical and Pathogenetic Significance of Amylase Level and Microtomographic Index of Synovial Fluid in Various Joint Lesions.

The aim of the investigation was to study the level of amylolytic activity and microtomographic index of synovial fluid density as well as to substantiate their clinical and pathogenetic significance by identifying correlations with the known informative indicators reflecting characteristic features of the pathological process in various joint diseases. Materials and Methods: Samples of synovial fluid from 95 patients with various joint pathologies at the stage of the disease progression characterized by copious effusion into articular cavities have been examined. Synovial fluid samples obtained by knee arthrocentesis served as a material for the investigation. Conventional methods were used to determine the concentration of uric acid, inorganic phosphorus, total protein, and amylolytic activity level in the selected samples while X-ray density was identified by computed microtomography. Results: All samples of pathological joint fluid have shown a high level of amylolytic activity as compared to the synovial fluid from healthy joints. The relationship between the level of amylolytic activity in synovia and specific joint pathology has been identified. It has also been found that uric acid values, inorganic phosphorus concentrations, and total protein in various types of joint damage may influence X-ray density of the synovial fluid. Correlations between the studied indices have been established. Conclusion: New data on the level of synovia amylolytic activity has been obtained in one non-inflammatory and six different inflammatory diseases. Pathogenically determined correlation between the microtomographic index of synovial fluid density and concentrations of uric acid, inorganic phosphorus, total protein has been confirmed. Specific indicators of X-ray density of synovia in various joint pathologies as well as unidirectional and multidirectional data in comparison with the norm allow us to consider X-ray microtomography as a method that reveals additional details during investigation of synovial fluid density and brings new surrogate markers for the study of pathogenetic mechanisms of the development, differentiation, and treatment of various joint pathologies.

Agonist- and mitogen-induced desensitization of isoproterenol-stimulated cyclic AMP formation in mouse epidermis in vivo.

Injection of the beta-adrenergic agonist isoproterenol causes a rapid desensitization of cyclic AMP formation to subsequent beta-adrenergic challenge in mouse epidermis. Long-lasting catecholamine refractoriness is also observed after prolonged treatment of mouse skin with certain mitogens such as the phorbol ester TPA (tumor promoter), 12-retinoylphorbol-acetate, the TPA-analogue C14:4phorbol acetate or the divalent cation ionophore A 23187 but not after mitogenic stimulation by phorbol-12,13-dibenzoate and 4-O-methyl-TPA or by means of chemical depilation, removal of the horny layer or skin massage. Thus no clear-cut correlation exists between the desensitizing efficacy of a given treatment and its ability to provoke epidermal hyperplasia and to promote skin tumor formation. Both, agonist- and mitogen-induced desensitization are dependent on protein synthesis in epidermis, the mitogen-induced effect is in addition dependent on RNA synthesis. The putative desensitizing protein is not cyclic AMP phosphodiesterase but could be a feedback inhibitor of receptor-cyclase interaction ("refractoriness protein") which has recently been proposed to be responsible for catecholamine tachyphylaxis in certain in vitro systems. In contrast to epidermal hyperproliferation mitogen-induced tachyphylaxis is not mediated by prostaglandin synthesis and is apparently also independent of initial cyclic AMP formation. It can be prevented, however, by the antimitotic synthetic corticoid fluocinolone acetonide but not by colchicine, vincristine cytochalasin B or adrenergic blockers.

Programmed ventricular stimulation for arrhythmia risk prediction in patients with idiopathic dilated cardiomyopathy and nonsustained ventricular tachycardia.

OBJECTIVES: This study investigated the role of programmed ventricular stimulation (PVS) for arrhythmia risk prediction in patients with idiopathic dilated cardiomyopathy (IDC) and spontaneous nonsustained ventricular tachycardia (VT). BACKGROUND: Nonsustained VT in patients with IDC has been associated with a high incidence of sudden cardiac death. METHODS: Over the course of 4 years, 34 patients with IDC, a left ventricular (LV) ejection fraction < or = 35%, and spontaneous nonsustained VT underwent PVS. All patients were prospectively followed for 24+/-13 months. RESULTS: Sustained ventricular arrhythmias were induced in 13 patients (38%). Sustained monomorphic VT was induced in three patients (9%), and polymorphic VT or ventricular fibrillation (VF) in another 10 patients (29%). No sustained ventricular arrhythmia could be induced in 21 study patients (62%). Prophylactic implantation of third-generation defibrillators (ICDs) with electrogram storage capability was performed in all 13 patients with inducible sustained VT or VF, and in nine of 21 patients (43%) without inducible sustained VT or VF. There were no significant differences between the additional use of amiodarone, d,I-sotalol, and beta-blocker therapy during follow-up in patients with and without inducible VT or VF. During 24+/-13 months of follow-up, arrhythmic events were observed in nine patients (26%) including sudden cardiac deaths in two patients and ICD shocks for rapid VT or VF in seven patients. Arrhythmic events during follow-up occurred in four of 13 patients with inducible ventricular arrhythmias compared with five of 21 patients without inducible ventricular arrhythmias at PVS (31% vs. 24%, p=NS). CONCLUSION: PVS does not appear to be helpful for arrhythmia risk stratification in patients with IDC, a left ventricular ejection fraction < or =35%, and spontaneous nonsustained VT. Due to the limited number of patients, however, the power of this study is too small to exclude moderately large differences in outcome between patients with IDC with and without inducible VT or VF.

Human corticotropin-releasing hormone in depression--correlation with thyrotropin secretion following thyrotropin-releasing hormone.

Twenty-two subjects (11 patients with major endogenous depression and 11 controls) received an intravenous test dose of 100 micrograms human corticotropin-releasing hormone (h-CRH). Corticotropin (ACTH), but not cortisol, responses were blunted in depressives. Basal cortisol secretion was higher in depressives than in controls and was negatively correlated to the corticotropin response following h-CRH. This finding indicates the integrity of the glucocorticoid-dependent negative feedback regulation in depression and supports the view that hypercortisolism in depression is primarily due to a suprapituitary disturbance. Comparison of ACTH responses after h-CRH with thyrotropin (TSH) output following thyrotropin-releasing hormone (TRH) revealed a positive correlation (r = 0.65, p less than 0.001). The concordance between ACTH and TSH responses after specific challenges suggests that regulation of both systems is at least in part under a common control.

A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infections.

PURPOSE: Fluid extracts of Echinacea purpurea are widely used for the prevention and treatment of colds and respiratory infections, although the clinical efficacy of this agent has not been proven. PATIENTS AND METHODS: A total of 109 patients with a history of more than 3 colds or respiratory infections in the preceding year were randomly assigned to receive 4 mL fluid extract of Echinacea purpurea or 4 mL placebo-juice twice a day in a double-blind manner. (One patient withdrew his consent before taking the first dose of the allocated medication; thus, only 108 patients were included for analysis.) The incidence and severity of colds and respiratory infections were determined during 8 weeks of follow-up, based on patient reported symptoms together with findings on physical exam. The severity of each infection was graded by the investigators. Relative risks (RR) and 95% confidence intervals (CI) were estimated. RESULTS: During the 8-week treatment period, 35 (65%) of 54 patients in the Echinacea group and 40 (74%) of 54 patients in the placebo group had at least one cold or respiratory infection [RR = 0.88; 95% CI (0.60, 1.22)]. The average number of colds and respiratory infections per patient was 0.78 in the Echinacea group, and 0.93 in the placebo group [difference = 0.15; 95% CI (-0.12, 0.41), P = 0.33]. Median duration of colds and respiratory infections was 4.5 days in the Echinacea group and 6.5 days in the placebo group (95% CI: -1, +3 days; P = 0.45). There were no significant differences between treatment groups in the number of infections in each category of severity. Side effects were observed in 11 patients (20%) of the Echinacea group and in seven patients (13%) of the placebo group (P = 0.44). CONCLUSION: Treatment with fluid extract of Echinacea purpurea did not significantly decrease the incidence, duration or severity of colds and respiratory infections compared to placebo.

Intermittent regional therapy with rt-PA is not superior to systemic thrombolysis in deep vein thrombosis (DVT)--a German multicenter trial.

In a prospective and randomized multicenter trial the efficacy of intermittent regional and systemic thrombolytic therapy for DVT was evaluated. 137 patients with phlebographically confirmed acute DVT above the calf region were treated with 20 mg of rt-PA for 4 h each day. Thrombolysis was applied either locally via a dorsal pedal vein of the firmly bandaged affected leg or systemically using a cubital vein. Treatment lasted for 4-7 days, and during this time unfractionated heparin was applied continuously with the dosage adjusted according to aPTT (1.5-2.0 times the normal value). A second phlebography was performed within 24 h after the end of treatment. Results were evaluated by an independent radiologist who was unaware of the treatment given. Significant thrombolytic results (e.g. lysis of more than 50% of the original thrombus and complete recanalization of all affected veins) were reached in only 1/3 of all patients. Rates of recanalization did not differ in both groups and bleeding complications occurred in 26.5%. We conclude that intermittent local or systemic application of 20 mg rt-PA seems to be ineffective in the treatment of DVT.

Symptoms and electrocardiographically documented rhythm preceding spontaneous shocks in patients with implantable cardioverter-defibrillator.

During a follow-up of 24 +/- 20 months after treatment with an implantable cardioverter-defibrillator (ICD), 101 of 241 patients (42%) received > or = 1 spontaneous ICD shocks with documentation of the rhythm leading to shock by Holter or telemetry monitoring or stored electrograms by the device. Sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) was documented in 67 of the 101 patients (66%) with electrocardiographically documented shocks, nonsustained VT in 4 patients (4%), supraventricular tachyarrhythmias in 41 patients (41%), and normal sinus or pacemaker rhythm in 10 patients (10%). No, mild (palpitations and/or mild dizziness) and severe symptoms (presyncope/syncope) preceded spontaneous ICD shocks in 20 (30%), 33 (49%) and 27 (42%) of the 67 patients, respectively, with electrocardiographically documented VT or VF, and in 23 (56%), 16 (39%) and 1 (2%) of the 41 patients, respectively, with electrocardiographically documented supraventricular tachyarrhythmias. Three of the 4 patients with nonsustained VT had mild symptoms, and 1 patient with nonsustained VT had presyncope. None of the 10 patients with spurious discharges during normal sinus or pacemaker rhythm had symptoms preceding the ICD shocks. It is concluded that (1) most patients with either electrocardiographically documented VT/VF or a non-VT/VF rhythm preceding spontaneous ICD shocks have no or mild symptoms preceding the shock, and (2) severe symptoms preceding ICD shocks suggest sustained VT or VF as the underlying rhythm, although severe symptoms rarely occur in patients with supraventricular tachyarrhythmias or nonsustained VT.

QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy.

QT dispersion was measured in the 12-lead standard electrocardiogram in 107 patients with idiopathic dilated cardiomyopathy (IDC) and 100 age- and sex- matched controls without structural heart disease. All 107 study patients with IDC were prospectively followed in order to determine possible associations between QT dispersion and arrhythmic events, i.e., sustained ventricular tachycardia, ventricular fibrillation, or sudden death. QT dispersion, rate-corrected QT dispersion, and adjusted QTc dispersion, which takes account of the number of leads measured, were significantly greater in patients with IDC than in controls. During 13 +/- 7 months follow-up, arrhythmic events occurred in 12 of 107 study patients with IDC (11%). QT dispersion was increased in patients with versus without arrhythmic events during follow-up (76 +/- 17 vs 60 +/- 26 ms; p=0.03). QTc dispersion and adjusted QTc dispersion were not significantly different between patients with and without arrhythmic events (80 +/- 21 vs 75 +/- 35 ms, and 27 +/- 6 vs 24 +/- 10 ms, respectively). Thus, although QT dispersion was increased in patients with IDC and arrhythmic events during follow-up, its usefulness for arrhythmia risk prediction was limited by the large overlap of QT dispersion between patients with and without arrhythmic events.

Significance of accelerated idioventricular rhythm in idiopathic dilated cardiomyopathy.

Holter monitoring was performed in 202 patients with idiopathic dilated cardiomyopathy, which revealed accelerated idioventricular rhythm in 16 patients (8%) and nonsustained ventricular tachycardia in 70 patients (35%). During 32 +/- 15-month prospective follow-up, no significant difference was observed for major arrhythmic events and transplant-free survival between patients with and without accelerated idioventricular rhythm, whereas patients with nonsustained ventricular tachycardia had a significantly higher incidence of major arrhythmic events and a lower transplant-free survival rate.

Heart rate variability in carcinoid heart disease.

Time domain heart rate variability measurements and echocardiographic studies were performed in 35 patients with carcinoid syndrome. Carcinoid heart disease was present in 18 patients (51%). Heart rate variability parameters (standard deviation of all normal RR intervals, percentage of the number of pairs of adjacent normal RR intervals differing by >50 ms) were significantly reduced in patients with than in those without carcinoid heart disease.

Simplified implantation of single-lead pectoral cardioverter defibrillators using device-based testing.

Device-based testing of single-lead pectoral defibrillators (defibrillation efficacy testing without an external defibrillation system after complete implantation of the device) resulted in an adequate defibrillation threshold (< or = 20 J) in 45 of 50 study patients (90%). Mean surgical implantation time (skin to skin) was 62 +/- 29 minutes without perioperative mortality and without implantable cardioverter defibrillator infection during follow-up. Thus, device-based testing appears to be a simple and safe method to test defibrillation efficacy of single-lead pectoral defibrillators.

Electrophysiologic evaluation of sinus node function and atrioventricular conduction in patients with prolonged ventricular asystole during obstructive sleep apnea.

In 15 patients with ventricular asystole of 8.5 +/- 3.5 seconds (range 5.0 to 16.8) occurring exclusively during obstructive sleep apnea, electrophysiologic study of sinus node function and atrioventricular conduction before and after administration of intravenous atropine (0.02 mg/kg) was performed. Electrophysiologic parameters of sinus node function were normal in 12 of 15 patients (80%) and atrioventricular (AV) nodal function was normal in 7 patients (47%). Almost all abnormal findings of sinus node function and AV nodal function were reversible by administration of atropine. The HisPurkinje system function was normal in 6 patients (40%). Prolonged HV intervals (57 to 73 ms) were found in 9 patients (60%). Intra- or infra-His block was not observed in any patient. In summary, electrophysiologic parameters of sinus node function and AV conduction were normal or only slightly abnormal in all 15 study patients, which suggests that prolonged ventricular asystole during obstructive sleep apnea is not due to fixed or anatomic disease of the sinus node or the AV conduction system.

Outcome of patients with sleep apnea-associated severe bradyarrhythmias after continuous positive airway pressure therapy.

Twenty-nine patients in whom severe bradyarrhythmias occurred exclusively during obstructive sleep apnea and in whom advanced sinus node disease or atrioventricular conduction system dysfunction had been excluded by invasive electrophysiologic evaluation were prospectively followed on nasal continuous positive airway pressure. During 54 +/- 10 months follow-up, no syncope and no sudden deaths were observed, suggesting that patients with sleep apnea-associated bradyarrhythmias and a normal electrophysiologic study appear to have a favorable prognosis with continuous positive airway pressure.

Induction of DNA single-strand breaks by 131I and 99mTc in human mononuclear blood cells in vitro and extrapolation to the in vivo situation.

The radionuclides (131)I and (99m)Tc are frequently used for therapy of benign and malignant thyroid disease ((131)I) and for diagnosis of thyroid and other diseases ((99m)Tc). However, the levels of DNA single-strand breaks (SSBs) induced in cells of patients after administration of (131)I and (99m)Tc are not known. In this study, we measured the number of SSBs per cell induced by (131)I and (99m)Tc in vitro, extrapolated the results to the clinical situation, and assessed their biological relevance by comparing levels of SSBs induced after therapeutic administration of (131)I and (99m)Tc to those induced by endogenous processes or by occupational exposure to genotoxic substances. A linear dose-response relationship between the radioactivity concentrations of (131)I and (99m)Tc and SSBs in human mononuclear blood cells (determined by alkaline elution) was obtained after incubation at 4 and 37 degrees C. At 4 degrees C, where almost no repair of SSBs takes place, (131)I and (99m)Tc induced 81 and 7 SSBs per cell per hour/(MBq/ml), respectively. At 37 degrees C, only 20 and 1.6 SSBs per cell per hour/(MBq/ml) were observed after incubation with (131)I and (99m)Tc. To estimate the induction of SSBs in vivo in cells of patients after administration of 3700 MBq (131)I (oral) or 60 MBq (99m)Tc (i.v.), the rates of induction of SSBs obtained in vitro were extrapolated to the concentrations of (131)I and (99m)Tc measured in blood of patients. The total number of SSBs (mean +/- standard deviation) accumulated after oral administration of 3700 MBq (131)I up to 70 h after administration was calculated as 200 +/- 59 SSBs/cell. After administration of 60 MBq (99m)Tc (i.v.), 0.032 +/- 0.009 SSBs per cell (total SSBs up to 2 h after administration) were cumulated. The induction of SSBs by endogenous processes (estimated 2,000 SSBs per cell per hour) and by occupational exposure to genotoxic substances (125-430 SSBs per cell) has been estimated in earlier studies. In conclusion, the frequency of SSBs induced by thyroid diagnosis with 60 MBq (99m)Tc is approximately 5 orders of magnitude smaller than the frequency of spontaneous SSBs and thus is most probably without biological relevance. Since the frequency of induction of SSBs by therapy with (131)I (3700 MBq) is about 6000-fold higher compared to thyroid diagnosis by (99m)Tc, its biological relevance is more difficult to assess. Nevertheless, the number of SSBs induced by therapy with (131)I is substantially lower than that induced by endogenous processes.

Invasive electrophysiological evaluation of patients with sleep apnoea-associated ventricular asystole-methods and preliminary results.

Twelve patients (aged 48 +/- 12 y) with ventricular asystole of >3 s due to complete atrioventricular (AV) block (n = 8), sinoatrial (SA) block or sinus node arrest (n = 3) or both (n = 1) associated with obstructive sleep apnoea underwent invasive electrophysiological evaluation of sinus node function and AV conduction properties before and after administration of atropine (0.02 mg kg-1). Ventricular asystole lasted for 5.9 +/- 2.8 s (range 3.1-13 s). Sinus node function was assessed by measurement of sinus node recovery time, sinoatrial conduction time, and the response of sinus rate to atropine. Parameters of AV-conduction assessment included AH- and HV-intervals, AV- and VA-Wenckebach periods, and effective refractory period of the AV node before and after atropine. Sinus node function was normal in 11 of the 12 study patients and moderately abnormal in 1 patient. AV-nodal function was normal in 8 patients and moderately abnormal in 4 patients. A slightly prolonged HV-interval (59-63 ms) was present in 6 patients. Intra- or infra His block was not observed in any patient. In conclusion, normal or only moderately abnormal electrophysiological findings in patients with sleep apnoea-associated ventricular asystole suggest that a neurally mediated cardioinhibitory reflex may cause ventricular asystole in these patients. This sleep apnoea-triggered 'vasovagal' reflex may unmask pre-existing mild to moderate structural abnormalities of the AV conduction system.

High dose naloxone does not improve cerebral or myocardial blood flow during cardiopulmonary resuscitation in pigs.

In a prospective, randomized, placebo-controlled, double-blind trial we tested the hypothesis that naloxone given during cardiopulmonary resuscitation (CPR) enhances cerebral and myocardial blood flow. Twenty-one anesthetized, normoventilated pigs were instrumented for measurements of right atrial and aortic pressures, and regional organ blood flow (radiolabeled microspheres). After 5 min of untreated fibrillatory arrest, CPR was commenced using a pneumatic chest compressor/ventilator. With onset of CPR, an i.v. bolus of 40 micrograms/kg b.w. of epinephrine was given, followed by an infusion of 0.4 micrograms/kg per min. After 5 min of CPR, either naloxone, 10 mg/kg b.w. (group N, n = 11) or normal saline (group S, n = 10) was given i.v. Prior to, and after 1, 15, and 30 min of CPR, hemodynamic and blood flow measurements were obtained. After 30 min of CPR, mean arterial pressure was significantly higher in group N (26 +/- 5 vs. 13 +/- 3 mmHg, P < 0.05). Groups did not differ with respect to myocardial perfusion pressure or arterial blood gases at any time during the observation period. Regional brain and heart blood flows were not different between N and S at any point of measurement. We conclude that high-dose naloxone does not augment cerebral or myocardial blood flow during prolonged closed-chest CPR.