Biomedical subjects

M Holzer

Publications and source records attributed to M Holzer.

At least 37 records · Page 2Linked to original sources

PubMed2000

Pulmonary embolism as a cause of cardiac arrest: presentation and outcome.

BACKGROUND: Pulmonary embolism (PE) is a possible noncardiac cause of cardiac arrest. Mortality is very high, and often diagnosis is established only by autopsy. METHODS: In a retrospective study, we analyzed clinical presentation, diagnosis, therapy, and outcome of patients with cardiac arrest after PE admitted to the emergency department of an urban tertiary care hospital. RESULTS: Within 8 years, PE was found as the cause in 60 (4.8%) of 1246 cardiac arrest victims. The initial rhythm diagnosis was pulseless electrical activity in 38 (63%), asystole in 19 (32%), and ventricular fibrillation in 3 (5%) of the patients. Pronounced metabolic acidosis (median pH, 6.95, and lactate level, 16 mmol/L) was found in most patients. In 18 patients (30%), the diagnosis of PE was established only postmortem. In 42 (70%) it was diagnosed clinically, in 24 of them the diagnosis of PE was confirmed by echocardiography. In 21 patients, 100 mg of recombinant tissue-type plasminogen activator was administered as thrombolytic treatment, and 2 (10%) of these patients survived to hospital discharge. Comparison of patients of the thrombolysis group (n = 21) with those of the nonthrombolysis group (n = 21) showed a significantly higher rate of return of spontaneous circulation (81% vs 43%) in the thrombolysis group (P=.03). CONCLUSIONS: Mortality related to cardiac arrest caused by PE is high. Echocardiography is supportive in determining PE as the cause of cardiac arrest. In view of the poor prognosis, thrombolysis should be attempted to achieve return of spontaneous circulation and probably better outcome.

Aged↗

PubMed2000

Aberrant expression of nNOS in pyramidal neurons in Alzheimer's disease is highly co-localized with p21ras and p16INK4a.

Aberrancies of growth and proliferation-regulating mechanisms might be critically involved in the processes of neurodegeneration in Alzheimer's disease (AD). Expression of p21ras and further downstream signalling elements involved in regulation of proliferation and differentiation as, for example, MEK, ERK1/2, cyclins, cyclin-dependent kinases and their inhibitors such as those of the p16INK4a family, are elevated early during the course of neurodegeneration. Activation of p21ras can also directly be triggered by nitric oxide (NO), synthesized in the brain by various isoforms of nitric oxide synthase (NOS) that might be differentially involved into the pathomechanism of AD. To study the potential link of NO and critical regulators of cellular proliferation and differentiation in the process of neurofibrillary degeneration, we analyzed the expression pattern of NOS-isoforms, p21ras and p16INK4a compared to neurofibrillary degeneration in AD. Additionally to its expression in a subtype of cortical interneurons that contain the nNOS-isoform also in normal brain, nNOS was detected in pyramidal neurons containing neurofibrillary tangles or were even unaffected by neurofibrillary degeneration. Expression of nNOS in these neurons was highly co-localized with p21ras and p16INK4a. Because endogenous NO can activate p21ras in the same cell which in turn leads to cellular activation and stimulation of NOS expression [H.M. Lander, J.S. Ogiste, S.F.A. Pearce, R. Levi, A. Novogrodsky, Nitric oxide-stimulated guanine nucleotide exchange on p21 ras, J. Biol. Chem. 270 (1995) 7017-7020], the high level of co-expression of NOS and p21ras in neurons vulnerable to neurofibrillary degeneration early in the course of AD thus provides the basis for an autocrine feedback mechanism that might exacerbate the progression of neurodegeneration in a self-propagating manner.

Aged↗

PubMed2000

Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia.

Abnormal phosphorylation of the tau-protein is regarded as a crucial step in the formation of neurofibrillary tangles in the neuronal cell body and neuropil threads in dendrites. We studied the effects of tau-pathology on the clinical expression of dementia in 106 autopsy cases in the entorhinal region, the hippocampal stratum oriens, the stratum radiatum, and the perforant path target zone. The first cytoskeletal lesions were located in the perikarya and dendrites of the pre-alpha cells of the transentorhinal and entorhinal region. Next, abnormally phosphorylated tau-protein (PHF-tau) was found in the neuropil of the CA1-subiculum region. Thereafter, the stratum radiatum and stratum oriens began to be involved in PHF-tau pathology in Braak stage II. In the Braak stages IV and V, the stratum radiatum was completely involved, the stratum oriens increasingly so. Beginning in Braak stage III, we noted cases having PHF-tau pathology in the perforant path target zone of the outer molecular layer of the dentate gyrus. The increase of this pathology with ever greater involvement on the part of the entorhinohippocampal circuit correlated significantly not only with the Braak stages and with the neurochemically determined hippocampal content of PHF-tau but also with the degree of dementia as defined by the clinical dementia rating (CDR) scale. The affection of the stratum oriens in combination with PHF-tau pathology in the stratum radiatum and in the outer molecular layer of the dentate gyrus was encountered almost exclusively in demented individuals (CDR 1-3). These results indicate that axonal PHF-tau pathology in hippocampal pathways presumably is critical for the clinical expression of dementia and may constitute an anatomical substrate of clinically verifiable memory dysfunction in Alzheimer's disease.

Aged↗

PubMed2000

Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons.

Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.

Amyloid beta-Peptides↗

PubMed2000

The attitudes of cardiac arrest survivors and their family members towards CPR courses.

OBJECTIVES: to evaluate self-assessment of first aid knowledge, readiness to make use of it in case of a medical emergency and judgement of a 1-day CPR course by cardiac arrest survivors, their family members and friends as compared to the general public. BACKGROUND: the recurrence rate of a cardiac arrest after successful resuscitation is high and most of out-of-hospital cardiac arrests occur at the patient's home. METHODS: medical students trained in basic and advanced life support provided 101 members of the target group and 94 of a sex and age matched control group with a 1-day course in CPR. RESULTS: after the course, half of the participants in both groups considered their knowledge of first aid to be very good or good. The readiness to perform first aid in a medical emergency increased significantly. Of the target group 96% of the participants as compared with the control group where 91% felt confident to recognise a cardiac arrest; 79 versus 68% considered themselves capable to perform CPR if needed. The course was judged as very good in 71 versus 69% and as good in 25 versus 27% with no differences between groups. CONCLUSION: one-day CPR courses are well accepted by cardiac arrest survivors, their family members and friends and help to reduce fears of reacting in medical emergencies. They seem to be more motivated to gain and use first aid knowledge than others.

Adolescent↗

PubMed2000

A novel wavelet transform based analysis reveals hidden structure in ventricular fibrillation.

We report a new method of interrogating the surface ECG signal using techniques developed in the field of wavelet transform analysis. Previously unreported structure within the ECG during ventricular fibrillation (VF) is found using a high-resolution decomposition of the signal employing the continuous wavelet transform. We believe that wavelet transform methods could lead to the development of powerful tools for use in the resuscitation of patients with cardiac arrest.

Animals↗

PubMed2000

Guinea-pig primary cell cultures provide a model to study expression and amyloidogenic processing of endogenous amyloid precursor protein.

Until now guinea-pigs have been rarely used to investigate formation and deposition of Alzheimer's disease-associated amyloid beta peptides despite the sequence identity of human and guinea-pig amyloid beta peptides being known, and the overall similarity of human and guinea-pig amyloid precursor protein. We now describe a primary cell culture system of mixed fetal guinea-pig brain cells, which we have applied to characterize endogenous amyloid precursor protein processing and amyloid beta formation. These cell cultures were established at embryonic day 24 of guinea-pigs after comparison of selected stages of guinea-pig ontogenetic development with the known ontogeny of rats, and were characterized by immunocytochemical detection of neuronal and glial marker proteins. Amyloid precursor protein expression, processing and amyloid beta formation increased in parallel with cellular maturation during cultivation and reached a stable phase after approximately 14 days in vitro therefore providing a suitable time for analysis. Aged cultures display strong neuronal amyloid precursor protein immunoreactivity and an altered profile of amyloid precursor protein isoform messenger RNA expression due to glial proliferation as single neurons were shown to retain their typical pattern of amyloid precursor protein expression. We show that amyloid precursor protein in guinea-pig cells is processed by different protease activities which most likely represent alpha- and beta-secretase, leading to the generation of soluble amyloid precursor protein derivatives. Furthermore, endogenous amyloid precursor protein processing leads to production of substantial amounts of amyloid beta-peptides which accumulate in conditioned culture medium. Amyloid beta was readily detectable by western blot analysis and was shown to consist of approximately 80-90% amyloid beta(1-40). We suggest that primary guinea-pig cell cultures provide a valuable tool in amyloid research that resembles amyloid precursor protein processing under physiological concentrations and, therefore, the situation in humans more closely than current rodent models. It should be especially useful in screening experiments for secretase inhibiting compounds.

Amyloid↗

PubMed2000

Analysis of the molecular heterogeneity of the microtubule-associated protein tau by two-dimensional electrophoresis and RT-PCR.

The microtubule-associated protein tau is a member of a group of proteins, promoting assembly and stabilization of microtubules. In several tauopathic neurodegenerative disorders, namely Alzheimer's and Pick's disease and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP 17) this protein is converted into fibrilar polymers which form the component of insoluble proteanous deposits such as neurofibrillary tangles. The formation of these fibrils is believed to interrupt the physiological function of neurons resulting in degeneration and cell death. Tau protein exists as a family of heterogeneous isoforms derived by both, differential splicing of tau-mRNA and posttranslational modification of the protein. Since the role of the different isoforms during the process of neurodegeneration is not well understood and as their balance might be altered in some cases of tauopathies (Spillantini et al., Proc. Natl. Acad. Sci. USA 1998;95:7737-7741), the detailed analysis of the molecular heterogeneity gained outstanding interest. The method presented here allows the analysis of both, differential splicing and phosphorylation of tau protein by the application of two-dimensional (2D) electrophoresis and Western blot detection. Tau protein isoforms could be identified from the 2D pattern of dephosphorylated tau in concordance with the results of tau-mRNA analysis by RT-PCR. The protocol presented was successfully applied to analysis of tau isoforms of human brain (Janke et al., FEBS Lett. 1996;379:222-226) and of several species, revealing a phylogenetic correlation of tau protein patterns in mammals (Janke et al., Mol. Brain Res. 1999;68:119-128). The present paper provides a detailed description of the technique and discusses its prospects and limits.

Animals↗

PubMed2000

Activated mitogenic signaling induces a process of dedifferentiation in Alzheimer's disease that eventually results in cell death.

Neurodegeneration in Alzheimer's disease (AD) is associated with the appearance of dystrophic neuronal growth profiles that most likely reflect an impairment of neuronal reorganization. This process of morphodysregulation, which eventually goes awry and becomes a disease itself, might be triggered either by a variety of life events that place an additional burden on the plastic capability of the brain or by genetic pertubations that shift the threshold for decompensation. This paper summarizes recent evidence that impairment of the p21ras intracellular signal transduction, which is is mediated by a hierarchy of phosphorylation signals and eventually results in loss of differentiation control and an attempt of neurons to re-enter the cell-cycle, is critically involved in this process. Neurodegeneration might thus be viewed as an alternative effector pathway of those events that in the dividing cell would lead to cellular transformation. This hypothesis might be of heuristic value for the development of a therapeutic strategy.

Alzheimer Disease↗

PubMed2000

Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group.

BACKGROUND AND PURPOSE: Recent animal studies showed that mild resuscitative hypothermia improves neurological outcome when applied after cardiac arrest. In a 3-year randomized, prospective, multicenter clinical trial, we hypothesized that mild resuscitative cerebral hypothermia (32 degrees C to 34 degrees C core temperature) would improve neurological outcome after cardiac arrest. METHODS: We lowered patients' temperature after admission to the emergency department and continued cooling for at least 24 hours after arrest in conjunction with advanced cardiac life support. The cooling technique chosen was external head and total body cooling with a cooling device in conjunction with a blanket and a mattress. Infrared tympanic thermometry was monitored before a central pulmonary artery thermistor probe was inserted. RESULTS: In 27 patients (age 58 [interquartile range [IQR] 52 to 64] years; 7 women; estimated "no-flow" duration 6 [IQR 1 to 11] minutes and "low-flow" duration 15 [IQR 9 to 23] minutes; admitted to the emergency department 36 [IQR 24 to 43] minutes after return of spontaneous circulation), we could initiate cooling within 62 (IQR 41 to 75) minutes and achieve a pulmonary artery temperature of 33+/-1 degrees C 287 (IQR 42 to 401) minutes after cardiac arrest. During 24 hours of mild resuscitative hypothermia, no major complications occurred. Passive rewarming >35 degrees C was accomplished within 7 hours. CONCLUSIONS: Mild resuscitative hypothermia in patients is feasible and safe. A clinical multicenter trial might prove that mild hypothermia is a useful method of cerebral resuscitation after global ischemic states.

Brain↗

PubMed2000

Apolipoprotein E polymorphism: survival and neurological outcome after cardiopulmonary resuscitation.

BACKGROUND AND PURPOSE: The apolipoprotein E 3/3 (apoE 3/3) genotype is associated with a reduced risk of developing Alzheimer's disease and with a favorable neurological outcome after traumatic head injury. In vitro studies suggest that the most common genotype, apoE 3/3, may be involved in neuroprotective and neuroregenerative mechanisms. The aim of this study was to determine whether the apoE 3/3 genotype has an impact on survival and neurological outcome after cardiopulmonary resuscitation. METHODS: Eighty patients with cardiac arrest were investigated prospectively for their apoE genotype. Epidemiological data were assessed according to recommended guidelines. Patients were divided into 2 groups, ie, with the apoE 3/3 genotype present or absent, and tested for differences in survival and neurological outcome. Further statistical analysis with respect to survival and neurological outcome was performed by using a stepwise logistic regression analysis. RESULTS: Patients with the apoE 3/3 genotype had a significantly higher survival rate (64% versus 33%, P:=0.007) and more often a favorable neurological outcome (55% versus 27%, P:=0. 013) compared with patients with other apoE genotypes. The apoE 3/3 genotype was shown to be a substantial predictive factor for a favorable neurological outcome (odds ratio 3.2) and was, apart from other essential factors, predictive for survival (odds ratio 4.4) after cardiopulmonary resuscitation. CONCLUSIONS: These data give evidence that patients with the apoE 3/3 genotype have a better chance of recovery after cardiopulmonary resuscitation than do patients with apoE genotypes other than 3/3.

Alleles↗

PubMed1999

Two distinct populations of cholinergic neurons in the septum of raccoon (Procyon lotor): evidence for a separate subset in the lateral septum.

The present study focused on cholinergic neurons in the lateral septal region of the raccoon detected by choline acetyltransferase (ChAT)-immunostaining. For comparison of the cholinergic neurons of the medial and lateral septal nuclei, soma sizes were measured, and several antibodies were applied that differentially characterize these cells in several species: low-affinity neurotrophin receptor p75 (p75(NTR)), calbindin-D(28k) (CALB), and constitutive nitric oxide synthase (cNOS). To compare the basic organization of the raccoon septum with that in other mammals, parvalbumin (PARV) immunocytochemistry and Wisteria floribunda-agglutinin (WFA) lectin histochemistry also were used in double-staining experiments. The ChAT-immunoreactive neurons of the rostral lateral septum are arranged in laminae. Accumulations of cholinergic varicosities, often clearly ensheathing noncholinergic neurons, occupy small territories of the rostral septum. Such regions become larger in the caudal septum. They are assumed to correspond to the septohippocampal and septofimbrial nuclei of the rat. In contrast to the large medial septal cholinergic neurons of the raccoon that contain p75(NTR), CALB, and cNOS, the cholinergic neurons of the lateral septum are smaller and do not express these markers. A further peculiarity is that the region of the lateral septum that contains cholinergic neurons corresponds to WFA-labelled extracellular matrix zones that contain chondroitin sulfate proteoglycans. In addition to clustered thread- or ring-like accumulations of the WFA, sparsely labelled perineuronal nets surround the lateral septal cholinergic neurons. Similar to other species that have been investigated, perineuronal nets are completely absent around cholinergic cells of the medial septum. The PARV-containing neurons of this region, however, are enwrapped by perineuronal nets as they are in the rat. Within the medial septum, the PARV-containing neurons are restricted to ventral bilateral territories that are devoid of cholinergic cells. In this respect, they differ from the more vertically arranged PARV-containing medial septal cells in rodents and primates. Apart from striking differences in numbers and distribution patterns, the raccoon lateral septal cholinergic neurons resemble those detected by Kimura et al. (Brain Res [1990] 533:165-170) in the ventrolateral septal region of rat and monkey. Their participation in the functions of the lateral septum remains to be elucidated.

Animals↗

PubMed1999

Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders.

The microtubule-associated protein tau regulates the dynamic stability of the neuronal cytoskeleton by interacting with microtubules. It is encoded by a single gene, but expressed in a variety of isoforms due to differential RNA splicing. Six isoforms can be found in the human central nervous system. These isoforms differ in their ability to promote the assembly of microtubules as well as in their capacity to stabilize existing microtubule structures. Furthermore, some of the isoforms of tau are specifically involved in the pathogenesis of neurodegenerative disorders. Thus, splicing of tau might critically influence the physiological functions of tau protein as well as the pathogenesis of neurodegenerative diseases with tauopathy. The present study addresses the differential expression of the six isoforms of tau in the central nervous system of 12 mammalian species including Homo sapiens. The occurrence of each of the six tau isoforms was highly variable. However, species that were phylogenetically related expressed a similar pattern of tau isoforms. These results suggest a phylogenetic descent of splicing paradigms, which can be matched with known phylogenetic concepts based on morphological and molecular genetical studies. Especially, the unique expression pattern of tau isoforms in the human central nervous system implicates a possible link to the particular vulnerability of humans to neurodegenerative disorders with tauopathy, namely Alzheimer's disease, frontotemporal dementia and Pick's disease.

Animals↗

PubMed1999

Cortical load of PHF-tau in Alzheimer's disease is correlated to cholinergic dysfunction.

To assess a potential relationship between cortical neurofibrillary degeneration and cortical cholinergic deafferentation, the load of PHF-tau was analysed in eight cortical regions and in the basal nucleus of Meynert in 12 cases with Alzheimer's disease by means of a sensitive ELISA employing the monoclonal antibody B5-2. The activity of choline acetyltransferase was determined on identical tissue samples. The results demonstrate a highly correlative relationship between the cortical distribution of the amount of PHF-tau, mainly present in neuropil threads, and cholinergic depletion early during the course of the disease. This relationship was less strong in more advanced stages. The results support the suggestion that the formation of PHF-tau in cholinergic axon terminals which might result in a loss of cholinergic synapses and a cholinergic dysconnection of the cortex, is an early event in AD. During the progression of the disease, formation of PHF-tau appears to spread over the cortex which results in a more even distribution of neuropil threads and a progressive involvement of non-cholinergic neurons.

Aged↗

PubMed1999

Alterations in content and phosphorylation state of cytoskeletal proteins in the sciatic nerve during ageing and in Alzheimer's disease.

Paired helical filaments containing the microtubule-associated protein tau in an abnormally high phosphorylated state are one of the major hallmarks of Alzheimer's disease. In the central nervous system, this neurofibrillar degeneration preferentially affects long-axon projection neurons. In the peripheral nervous system largely made up by long-axon neurons, formation of paired helical filaments, however, has only rarely been described. In the present study, we have analysed alterations in the content and phosphorylation state of tau and neurofilament protein in the sciatic nerve during ageing and in Alzheimer's disease. The amount of both cytoskeletal proteins remained constant during ageing but was significantly reduced in Alzheimer's disease. The phosphorylation state of tau protein was elevated during ageing as well as in Alzheimer's disease. No indications of a paired helical filament-like aggregation of tau were found. It is concluded that during normal ageing and in Alzheimer's disease, processes are activated in the peripheral nervous system that induce a hyperphosphorylation of tau. Increased phosphorylation of tau in peripheral neurons, however, is not necessarily accompanied by the formation of paired helical filaments. Analysing principal differences in the expression, posttranslational modification and metabolism of tau between central and peripheral neurons might, therefore, help to get a better insight into the mechanism of paired helical filament formation.

Aged↗

PubMed1999

Sustained ventricular tachycardia in the emergency department.

The aim of the study was to evaluate the demographics, haemodynamics, ECG characteristics, underlying disease, tachycardia termination and outcome of patients with sustained ventricular tachycardia (VT). We registered 75 patients presenting with VT (51 male, median age 63) from December 1993 to August 1998 in our emergency department (ED). Seventeen of these patients were haemodynamically unstable (23%), and 58 patients were stable (77%); there was no difference in the tachycardia cycle length (median 320 ms) and QRS width (median 140ms) between the two groups; however, five of the seven patients with polymorphic VT pattern were in the unstable group. Ischaemic heart disease was the underlying disorder in 57 patients (76%). Acute myocardial infarction (AMI) was present in 12 of the 58 stable (21%) compared to 11 of the 17 unstable (65%) patients. In three patients (4%) VT terminated spontaneously, in 34 patients (45%) VT was terminated by first-line intravenous drug therapy, and in 38 patients (51%) including all 17 unstable and 22 stable who failed to respond to the intravenous antiarrhythmic therapy challenge out of 55 patients, VT was terminated by electrical therapy. Within 2 days, 48 patients (64%) were transferred to an open ward, 13 (17%) still needed intensive care, nine (12%) were discharged to home and five (7%) died. Death occurred due to cardiac failure from AMI with extensive anterior wall infarction in three patients, and due to constrictive pericarditis and reocclusion of stented LAD each in one patient. At presentation in the emergency department, the majority of the patients with VT were haemodynamically stable, thus allowing first-line antiarrhythmic drug administration. However, in the course of the disease, half needed electrical therapy for definitive termination of the tachycardia. Therefore, direct current cardioversion must be available in the emergency department. Haemodynamic instability and death occurs significantly more often if VT occurs during the course of AMI.

Aged↗

PubMed1999

Elevated expression of p21ras is an early event in Alzheimer's disease and precedes neurofibrillary degeneration.

Alzheimer's disease is a chronic degenerative disorder characterized by the intracellular accumulation of "paired helical filaments" consisting of highly phosphorylated tau and by extracellular deposits of aggregated Abeta-peptide. Furthermore, neurodegeneration in Alzheimer's disease is associated with the appearance of neuritic growth profiles that are aberrant with respect to their localization, morphological appearance, and composition of cytoskeletal elements. During early stages of Alzheimer's disease, a variety of growth factors and mitogenic compounds are elevated. Most of these factors mediate their cellular effects through activation of the p21ras-dependent mitogen-activated protein kinase cascade, a pathway that is also involved in the regulation of expression and post-translational modification of the amyloid precursor protein and tau protein. We previously reported on the elevated expression of p21ras associated with paired helical filament formation and Abeta-deposits. However, the question arises as to whether induction of p21ras and the downstream mitogen-activated protein kinase cascade is an early event with rather primary importance in the pathogenetic chain or simply occurs as a cellular response to neurodegeneration. The present study shows that expression of p21ras is clearly elevated in very early stages of the disease, preceding both neurofibrillary pathology and formation of Abeta.

Aged↗

PubMed1999

Successful resuscitation of a verapamil-intoxicated patient with percutaneous cardiopulmonary bypass.

OBJECTIVE: To describe our experience with the use of percutaneous cardiopulmonary bypass as a therapy for cardiac arrest in an adult patient intoxicated with verapamil. DESIGN: Case report. SETTING: Emergency department of a university hospital. PATIENT: A patient with cardiac arrest after severe verapamil intoxication. INTERVENTIONS: Percutaneous cardiopulmonary bypass and theophylline therapy. CASE REPORT: A 41-yr-old white male had taken 4800-6400 mg of verapamil in a suicide attempt. On arrival of the ambulance physician, the patient was conscious with weak palpable pulses and was transported to a nearby hospital. The patient developed a pulseless electrical activity, and cardiopulmonary resuscitation was started. Despite all advanced life support efforts, the patient remained in cardiac arrest. Therefore, he was transferred under ongoing cardiopulmonary resuscitation to our department, where percutaneous cardiopulmonary bypass was initiated immediately (2.5 hrs after cardiac arrest). The first verapamil serum concentration obtained at admittance to our institution was 630 ng/mL. After several ineffective intravenous epinephrine applications, the administration of 0.48 g of theophylline as an intravenous bolus 6 hrs and 18 mins after cardiac arrest led to the return of spontaneous circulation. The patient remained stable and was transferred to an intensive care unit the same day. He woke up on the 12th day and was extubated on the 18th day. After transfer to a neuropsychiatric rehabilitation hospital, he recovered totally. CONCLUSION: In patients with cardiac arrest attributable to massive verapamil overdose, percutaneous extracorporeal cardiopulmonary bypass can provide adequate tissue perfusion and sufficient cerebral oxygen supply until the drug level is reduced and restoration of spontaneous circulation can be achieved.

Adult↗