Low-dose aspirin for secondary cardiovascular prevention - cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation - review and meta-analysis.

OBJECTIVES: Low-dose aspirin given for secondary prevention of cardiovascular disease is frequently withdrawn prior to surgical or diagnostic procedures to reduce bleeding complications. This may expose patients to increased cardiovascular morbidity and mortality. Aim of the study was to review and quantify cardiovascular risks because of periprocedural aspirin withdrawal and bleeding risks with the continuation of aspirin. METHODS: We screened MEDLINE (January 1970-October 2004) with additional manual cross-referencing for clinical studies, surveys on the opinions of doctors and guidelines. RESULTS: Studies reporting the relative risk of acute cardiovascular events after aspirin withdrawal when compared with its continuation were not found. However, retrospective investigations revealed that aspirin withdrawal precedes up to 10.2% of acute cardiovascular syndromes. The time interval between discontinuation and acute cerebral events was 14.3 +/- 11.3 days, 8.5 +/- 3.6 days for acute coronary syndromes, and 25.8 +/- 18.1 days for acute peripheral arterial syndromes (P < 0.02 versus acute coronary syndromes). On aspirin-related bleeding risks, we obtained 41 (12 observational retrospective, 19 observational prospective, 10 randomized) studies, reporting on 49 590 patients (14 981 on aspirin). Baseline frequency of bleeding complications varied between 0 (skin lesion excision, cataract surgery) and 75% (transrectal prostate biopsy). Whilst aspirin increased the rate of bleeding complications by factor 1.5 (median, interquartile range: 1.0-2.5), it did not lead to a higher level of the severity of bleeding complications (exception: intracranial surgery, and possibly transurethral prostatectomy). Surveys amongst doctors on the management of this problem demonstrate wide variations. Available guidelines are scarce and in part contradictory. CONCLUSIONS: Only if low-dose aspirin may cause bleeding risks with increased mortality or sequels comparable with the observed cardiovascular risks after aspirin withdrawal, it should be discontinued prior to an intended operation or procedure. Controlled clinical studies are urgently needed.

[Etiology of initially unexplained confusion of excitability in deadly nightshade poisoning with suicidal intent. Symptoms, differential diagnosis, toxicology and physostigmine therapy of anticholinergic syndrome]. / Atiologisch zunächst unklare Verwirrtheit und Exzitation im Verlauf einer Tollkirschenvergiftung mit suizidaler Absicht. Symptomatik, Differentialdiagnose, Toxikologie und Physostigmin-Therapie des anticholinergen Syndroms.

HISTORY AND ADMISSION FINDINGS: After a walk in a wood a 55-year-old teacher was admitted to the emergency unit of a university hospital because of somnolence and excitability. Her rectal temperature was 37.8 degrees C, she had sinus tachycardia (rate of 130/min) but no other significant findings. INVESTIGATIONS: With the exception of C-reactive protein (10 mg/dl), MCV (101 fl), MCH (34 pg) and arterial blood gases (pH 7.483, pCO2 35.5 mmHg, base excess 5.1 mmp/l) laboratory tests were within normal limits. Qualitative screening of serum for benzodiazepines, barbiturates and antidepressives was negative. Neurological examination, including lumbar puncture and cranial computed tomography were noncontributory. TREATMENT AND COURSE: 10 hours after admission the patient developed signs of an anticholinergic syndrome with mydriasis, dry mouth, tachycardia, hot skin and an atonic bladder. Physostigmine 2 mg completely reversed the neurological and mental symptoms. After gas chromatography, mass-spectrometry of a urine sample showed an atropine molecular fragment with a molecular weight of 271. At intervals of 3 to 5 hours the recurrence of confusion and excitability required 4 further i.v. injection of physostigmine. The patient subsequently became accessible to psychiatric examination and reported that during the walk she had swallowed 8-10 berries of deadly nightshade with suicidal intent. CONCLUSION: In case of excitability and confusion as well as somnolence or coma of uncertain aetiology an anticholinergic syndrome caused by ingestion of atropine-containing plants or psychoactive drugs (phenothiazines, butyrophenones, tri- or tetracyclic antidepressants) should be included in the differential diagnosis. If there are suggestive clinical findings (tachycardia, somnolence, coma or threatened respiratory arrest, physostigmine should be given if there are no contraindications.

Organophosphate inhibition of human heart muscle cholinesterase isoenzymes.

The rate of acetylcholine hydrolysis of mammalian heart muscle influences cardiac responses to vagal innervation. We characterized cholinesterases of human left ventricular heart muscle with respect to both substrate specificity and irreversible inhibition kinetics with the organophosphorus inhibitor N,N'-di-isopropylphosphorodiamidic fluoride (mipafox). Specimens were obtained postmortem from three men and four women (61 +/- 5 years) with no history of cardiovascular disease. Myocardial choline ester hydrolyzing activity was determined with acetylthiocholine (ASCh; 1.25 mM), acetyl-beta-methylthiocholine (AbetaMSCh; 2.0 mM), and butyrylthiocholine (BSCh; 30 mM). After irreversible and covalent inhibition (60 min; 25 degrees C) with a wide range of mipafox concentrations (50 nM-5 mM), residual choline ester hydrolyzing activities were fitted to a sum of up to five exponentials using weighted least-squares non-linear curve fitting. In each ease, quality of curve fitting reached its optimum on the basis of a four component model. Final classification of heart muscle cholinesterases was achieved according to substrate hydrolysis patterns (nmol/min per g wet weight) and to second-order organophosphate inhibition rate constants k2 (1/mol per min); one choline ester hydrolyzing enzyme was identified as acetylcholinesterase (AChE; k2/mipafox = 6.1 (+/- 0.8) x 10(2)), and one as butyrylcholinesterase (BChE; k2/mipafox = 5.3 (+/- 1.1) x 10(3)). An enzyme exhibiting both ChE-like substrate specificity and relative resistance to mipafox inhibition (k2/mipafox = 5.2 (+/- 1.0) x 10(-1)) was classified as atypical cholinesterase.

Paraoxonase polymorphism in rabbits.

Paraoxonase in serum and liver of rabbits and cattle was investigated. In serum the two substrates paraoxon and phenylacetate are exclusively hydrolyzed by alpha-lipoprotein-bound paraoxonase. In rabbit liver paraoxon is hydrolyzed only by paraoxonase, while phenylacetate is hydrolyzed by paraoxonase (20%) and additionally by an organophosphate sensitive carboxylesterase (B-Esterase), which is responsible for 80% of total liver phenylacetate hydrolysis. Phenyl acetate hydrolysis by B-Esterase of rabbit liver was shown to be inhibited by paraoxon and by mipafox covalently in a time and concentration dependent manner. Rabbit serum exhibits by far the highest serum paraoxonase activity (2.6 +/- 0.66 U/ml) of all vertebrate species tested up to now, while rabbit liver contains only 0.5 +/- 0.2 U/g fresh weight. In cattle extremely high paraoxonase activity is found in liver (2.8 U/g), while bovine serum contains only 0.2 U/g. The paraoxonase activity ratio (hydrolysis rate paraoxon: phenylacetate x 1000) in cattle does not show interindividual variation (activity ratio 4.0 +/- 0.4, correlation coefficient 0.996, P < 0.001). In contrast, the paraoxon/phenylacetate hydrolysis ratio of rabbit paraoxonase in serum as well as in liver does vary considerably between individuals. In cross-bred rabbits paraoxonase activity ratios from three to ten are found. In a strain of pure-bred New Zealand White rabbits three polymorphic serum paraoxonase phenotypes could be clearly differentiated by the activity ratio. By analogy with the human paraoxonase polymorphism, the rabbit paraoxonase isotypes were classified as paraoxonase A (activity ratio 3.8-4.3), AB (ratio 5.5-6.0) and B (ratio 7.3-8.6). The corresponding frequencies of the three isotypes were 40, 35 and 25%.

[Age related decrease of high density lipoproteins (HDL) in women after menopause. Quantification of HDL with genetically determined HDL arylesterase in women with healthy coronary vessels and in women with angiographically verified coronary heart disease]. / Zur altersabhängigen Verminderung von Lipoproteinen hoher Dichte (HDL) bei Frauen nach der Menopause. Quantifizierung von HDL über die genetisch determinierte HDL-Arylesterase bei koronargesunden Frauen und bei Frauen mit angiographisch gesicherter koronarer Herzkrankheit.

BACKGROUND: The decline in the concentration of high density lipoproteins (HDL) observed in postmenopausal women is thought to contribute to the increasing incidence of coronary artery disease (CAD) after menopause. Human serum arylesterase (EC 3.1.1.2) is exclusively associated with HDL. We therefore investigated possible differences in the decline of HDL-levels and of HDL-subfractions HDL2 and HDL3 between postmenopausal women without and with angiographically documented CAD. PATIENTS AND METHODS: HDL-, HDL2-and-HDL3- concentrations were studied in postmenopausal women with angiographically documented CAD (n = 24; 51 to 72 years mean: 62 years) and compared to HDL-parameters of women without CAD (n = 22; 51 to 81 years, mean: 58 years). Arylesterase activities of HDL2-and HDL3-subfractions and HDL2-cholesterol concentrations were determined after differential precipitation with polyethylene glycol (4.7 mM PEG). Phenotyping of HDL-arylesterase was achieved in CAD patients and in women without CAD after determining hydrolysis of arylesterase substrates paraoxon (PO) and phenylacetate (PA) by calculating paraoxonase/arylesterase activity ratios R (R = [PO]/[PA] x 1000): phenotype A (n = 26) with R < 2.5, phenotype AB (n = 16) with 5.0 < R < 10.7, and phenotype B (n = 4) with R > 13.5. RESULTS: In postmenopausal women with documented CAD, as compared to women without CAD, HDL-cholesterol (55 +/- 3 mg/dl vs. 69 +/- 3 mg/dl HDL2-arylesterase (25 +/- 1 kU/l vs. 33 +/- 2 kU/l), and HDL3-arylesterase (89 +/- 4 kU/l vs. 106 +/- 5 kU/I) were found to be significantly reduced. Analysis of the correlation of lipid parameters and age revealed in CAD patients, but not in postmenopausal women without CAD, a significant increase of total cholesterol (r = 0.42), and significant reductions of both HDL2-arylesterase (r = -0.47) and HDL3-arylesterase (r = 0.74) with increasing age. In contrast, HDL-cholesterol (r = -0.14) and HDL2-cholesterol (r = -0.06) of CAD patients showed only slight and non-significant reductions with age. Since HDL3-arylesterase was found to be age-dependently reduced in women without CAD (r = 0.17), HDL2-arylesterase of postmenopausal women, among all lipid parameters showed the most pronounced differences between women without CAD and CAD patients. The age-dependent decrease of HDL2-arylesterase in postmenopausal women with CAD does not result from an increased frequency of B-allele carriers in the subgroup of CAD patients with an age above the median (64 years). CONCLUSION: Genetically determined serum HDL-arylesterase is well suited to quantify HDL in postmenopausal women without and with CAD. HDL2-arylesterase of postmenopausal women should be evaluated as a screening parameter for both primary and secondary CAD prevention.

Mipafox differential inhibition assay for heart muscle cholinesterases: substrate specificity and inhibition of three isoenzymes by physostigmine and quinidine.

1. A differential inhibition assay was developed for the quantitative determination of cholinesterase isoenzymes acetylcholinesterase (AChE; EC 3.1.1.7), cholinesterase (BChE; EC 3.1.1.8), and atypical cholinesterase in small samples of left ventricular porcine heart muscle. 2. The assay is based on kinetic analysis of irreversible cholinesterase inhibition by the organophosphorus compound N,N'-di-isopropylphosphorodiamidic fluoride (mipafox). With acetylthiocholine (ASCh) as substrate (1.25 mM), hydrolytic activities (A) of cholinesterase isoenzymes were determined after preincubation (60 min, 25 degrees C) of heart muscle samples with either saline (total activity, A tau), 7 microM mipafox (AM1), or 0.8 mM mipafox (AM2): (BChE) = A tau-AM1, (AChE) = AM1-AM2, (Atypical ChE) = AM2. 3. The mipafox differential inhibition assay was used to determine the substrate hydrolysis patterns of myocardial cholinesterases with ASCh, acetyl-beta-methylthiocholine (A beta MSCh), propionylthiocholine (PSCh), and butyrylthiocholine (BSCh). The substrate specificities of myocardial AChE and BChE resemble those of erythrocyte AChE and serum BChE, respectively. Michaelis constants KM with ASCh were determined to be 0.15 mM for AChE and 1.4 mM for BChE. 4. Atypical cholinesterase, in respect to both substrate specificity and inhibition kinetics, differs from cholinesterase activities of vertebrate tissue and, up to now, could be identified exclusively in heart muscle. The enzyme's Michaelis constant with ASCh was determined to be 4.0 mM. 5. The reversible inhibitory effects of physostigmine (eserine) and quinidine on heart muscle cholinesterases were investigated using the differential inhibition assay. With all three isoenzymes, the inhibition kinetics of both substances were strictly competitive. The physostigmine inhibition of AChE was most pronounced (Ki = 0.22 microM). Quinidine most potently inhibited myocardial BChE (Ki = 35 microM).

Indirect parasympathomimetic activity of the class III antiarrhythmic substance D/L-sotalol in vitro: reversible inhibition of cholinesterase isoenzymes from blood and the human central nervous system.

Inhibitory effects of the class III antiarrhythmic compound D/L-sotalol on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and the human caudate nucleus and on serum cholinesterase (ChE; EC 3.1.1.8) were studied in vitro using a spectrophotometric kinetic assay with acetylthiocholine (ASCh) as substrate. Sotalol concentrations in the assays varied from 0.32 to 3.2 mM. All isoenzymes studied were inhibited by D/L-sotalol in a reversible and concentration-dependent manner. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that D/L-sotalol reduced substrate affinity (apparent Michaelis constant, KM, increased) of serum ChE, but did not change the enzyme's maximal rate of ASCh hydrolysis (Vmax). Thus, D/L-sotalol inhibition of serum ChE was of the competitive type (rate constant for reversible competitive inhibition: Ki = 0.51 mM). In contrast, D/L sotalol reduced the maximal reaction velocity of the AChE isoenzyme from the central nervous system (caudate nucleus), but had no influence on substrate affinity of the enzyme (KM with ASCh unchanged) indicating purely non-competitive inhibition kinetics (rate constant of reversible non-competitive inhibition: Ki = 0.44 mM). D/L-sotalol inhibition of erythrocyte AChE was of mixed competitive/non-competitive type (Ki = 0.31 mM, Ki = 0.49 mM). Non-competitive D/L-sotalol inhibition of caudate nucleus AChE and the non-competitive component of erythrocyte AChE inhibition cannot be overcome by increased concentrations of the cholinergic transmitter acetylcholine (ACh). Peak D/L-sotalol plasma levels as described in the literature for both humans (15 microM) and experimental animals (dogs: 18 microM; rats: 260 microM) as well as maximal myocardial concentrations of the substance (dogs: 46 microM; rats: 478 microM) are in the range of about 2% to 100% of the sotalol inhibition rate constants determined in the present paper for cholinesterase isoenzymes in vitro. Thus, D/L-sotalol inhibition of ACh hydrolysis in vivo may contribute to both the well known antiarrhythmic potential and proarrhythmic side effects of the compound.

Indirect parasympathomimetic activity of metoclopramide: reversible inhibition of cholinesterases from human central nervous system and blood.

Inhibitory effects of the dopamine D2-receptor antagonistic benzamide compound metoclopramide (MCP) on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and human caudate nucleus and on human serum cholinesterase (ChE; EC 3.1.1.8) were studied in vitro using a spectrophotometric assay with acetylthiocholine (ASCh) as substrate. MCP concentrations in the assays varied from 0.30 microM to 0.15 mM. All isoenzymes studied were inhibited by metoclopramide in a concentration-dependent manner. MCP inhibition of AChE and ChE isoenzymes was not time-dependent and of the reversible type. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that, for AChE isoenzymes of erythrocytes and of the caudate nucleus, MCP reduced both maximal reaction velocity (Vmax) and substrate affinity (apparent Michaelis constant, KM, increased). Thus, MCP inhibition of both AChE isoenzymes was of mixed competitive/non-competitive type. MCP constants for reversible competitive (Ki) and non-competitive (Ki) inhibition could be determined for erythrocyte AChE (Ki = 10 microM; Ki = 70 microM) and caudate nucleus AChE (Ki = 9.3 microM; Ki = 82 microM). In contrast to MCP inhibition of AChE isoenzymes, the type of reversible MCP inhibition of human serum ChE depended on substrate concentration. If substrate concentration exceeded 0.2 mM, MCP inhibition was of mixed competitive/non-competitive type (Ki = 0.19 microM; Ki = 1.4 microM). MCP inhibition was of uncompetitive type, if substrate concentration was below 0.2 mM (Ki(u) = 1.0 microM). The mixed-type MCP inhibition of cholinesterase isoenzymes, because of its non-competitive component, can only partially be overcome by increased concentrations of the cholinergic transmitter acetylcholine (ACh). Since, with intravenous infusions, peak MCP plasma concentrations in humans reach 4 microM, MCP inhibition of ACh hydrolysis in vivo may contribute both to prokinetic and anti-emetic actions of the substance and to its extrapyramidal side effects.

Fasting, lactate, and insulin improve ischemia tolerance in rat heart: a comparison with ischemic preconditioning.

We tested the hypothesis that improved ischemia tolerance in an isolated working rat heart preparation can be achieved by interventions other than ischemic preconditioning. Hearts were perfused at near-physiological workload with bicarbonate buffer containing glucose (10 mM). A preischemic period of 25 min was followed by 15 min of global ischemia and 30 min of reperfusion under preischemic conditions. Hearts came from either fed or fasted animals (groups 1 and 2). In group 3 lactate (10 mM) and insulin (10 mU/ml) were added to the perfusate of fasted animals. In group 4 hearts from fed animals were perfused with glucose (10 mM) and were ischemically preconditioned by one cycle of ischemia between 10 and 15 min of the preischemic perfusion. Cardiac power and glucose uptake were measured continuously to assess functional and metabolic recovery. In addition, we measured the time to return of aortic flow. Glucose metabolites and the ratio of latent of free citrate synthase activity (citrate synthase ratio, a marker for the structural integrity of mitochondria) were determined at selected time points. Groups 2, 3, and 4 recovered significantly faster than group 1, whereas recovery of power showed an improvement in groups 3 and 4 only. In addition, there was an early increase in glucose uptake during reperfusion in these two groups, suggesting an early need for glucose substrate. Glycogen levels decreased with ischemia in all groups and returned to preischemic levels in groups 2, 3, and 4. The citrate synthase ratio was low in the control group and preserved in the groups showing improved functional recovery. We conclude that metabolic interventions may be as effective as ischemic preconditioning in protecting the heart from ischemic injury.

Need for active left-ventricular decompression during percutaneous cardiopulmonary support in cardiac arrest.

During ventricular fibrillation, myocardial hemodynamic and metabolic effects of percutaneous cardiopulmonary support (PCPS) were analyzed in 11 adult sheep (body weight 77-112 kg). During supported fibrillation, an abrupt increase in left-ventricular pressures with alignment to aortic pressures was observed in 2 animals, which was probably due to spontaneous aortic regurgitation, and resulted in deterioration of coronary perfusion. In 9 animals, left-ventricular pressures rose from 22.9 +/- 4.9 to 31.2 +/- 7.9 mm Hg elevating left ventricular wall stress from 16,750 +/- 8,745 to 28,835 +/- 8,892 dyn/cm2 after 10 min of PCPS-supported fibrillation (mean flow rate 4.5 +/- 0.7 liters/min). Simultaneously, myocardial perfusion pressures decreased from an average of 32.4 +/- 11.7 to 22.3 +/- 9.4 mm Hg and myocardial lactate release was observed. Additional transapical LV venting using a 9-Fr catheter led to a decrease in both LV pressure (to 25.7 +/- 5.3 mm Hg) and wall stress (to 20,612 +/- 7,499 dyn/cm2). Left-ventricular decompression decreased myocardial oxygen consumption (from 5.3 +/- 1.4 to 4.8 +/- 0.9 ml/min.100 g), and reduced myocardial lactate release, which indicates myocardial protection. Protective effects were most pronounced using 12-Fr-, and 21-Fr-venting cannulas (with 21 Fr: decrease in myocardial oxygen consumption to 2.7 +/- 0.6 ml/min.100 g, and reversal of myocardial lactate release to lactate uptake during fibrillation). Conclusions. Hemodynamic and metabolic data clearly demonstrate the deleterious effects of PCPS to the unvented left ventricle during cardiac arrest. The results emphasize the need for active left-ventricular decompression during PCPS in ventricular fibrillation.

Computerized analysis of covalent inhibition kinetics for identification of heart muscle cholinesterase and brain carboxylesterase isoenzymes. Design of differential inhibition assays.

The kinetics of time- and concentration-dependent covalent organophosphorus inhibition of carboxylesterase isoenzymes (EC 3.1.1.1) and cholinesterase isoenzymes (EC 3.1.1.7 and EC 3.1.1.8) were investigated using a wide range of organophosphate inhibitor concentrations (10(-10)-10(-3) mol/l) and different inhibition times. Computerized analysis of inhibition curves by weighted non-linear least-squares curve fitting was compared to graphic analysis by iterative elimination of exponential functions. Possible experimental errors due to inhibitor saturation kinetics and enzymatic organophosphate hydrolysis were thoroughly investigated. In mammalian heart muscle, three different cholinesterase isoenzymes were identified. High sensitivity and specificity of the classic differential inhibition test for carboxylesterase activity of hen brain neuropathy target esterase (NTE) could be confirmed independently with both methods of inhibition curve analysis.

Lipoproteins and hydrolysis of organophosphorus compounds.

Paraoxonase of human and animal sera was shown to be a structural part of high density lipoproteins (HDL) by immunoprecipitation, heparin- or polyethyleneglycol fractionation, ultracentrifugation and gel chromatography. Frequency distribution of paraoxonase activity in human sera is trimodal. Human individuals, with respect to paraoxon detoxication, can be distinguished into low and high detoxicators using ratios of phenylacetate and paraoxon hydrolysis as well as activation with ethanolamine and sodium chloride. With conversion of alpha-lipoprotein subtype HDL3 to HDL2, specific activities of paraoxonase and arylesterase are increasing about 3.5-fold in low detoxicator individuals and 1.9-fold in high detoxicators, indicating that more than 90% of HDL2 particle-bound paraoxonase and arylesterase activity are incorporated during the HDL conversion process. HDL cholesterol concentrations in individual sera were shown to be positively correlated to both serum paraoxonase and arylesterase activities.

Rapid preparation of subsarcolemmal and interfibrillar mitochondrial subpopulations from cardiac muscle.

1. Subsarcolemmal and interfibrillar mitochondria were prepared with complete recovery from rabbit and porcine heart muscle by upward-flotation during 60 sec of Percoll density gradient centrifugation. 2. Mitochondrial subpopulations were identified and characterized according to buoyant density, electron-microscopy, marker enzyme activities and respiratory performance. 3. ADP-induced state 3-respiration related to latent citrate synthase activity as a marker for structurally intact mitochondria was not significantly different in both mitochondrial subtypes.

Aorto-coronary artery to coronary vein fistula with the potential of coronary steal as complication of saphenous vein jump bypass graft.

We report the first documented case of an iatrogenic aorto-coronary artery to coronary vein fistula secondary to an aortocoronary saphenous vein jump bypass graft inadvertently anastomosed to a coronary vein. Angiographic and oximetric results of left and right cardiac catheterization--including direct catheterization of the anastomosed coronary vein--as well as clinical data with a four-year follow-up are presented. The role of surgery, percutaneous transcatheter embolization, and conservative treatment is discussed in this unique case with the potential of a coronary steal phenomenon.

Myocardial infarction in young patients with Hodgkin's disease--potential pathogenic role of radiotherapy, chemotherapy, and splenectomy.

Among a total of 2147 patients admitted to our hospital for acute myocardial infarction between 1978 and 1987, three young patients aged 24, 29, and 39 years had previously been treated for Hodgkin's disease. Staging laparotomy, including splenectomy, had been performed in all three patients. Two patients had both mediastinal irradiation (21 and 27 months before infarction) and chemotherapy. In the first patient, postmortem histologic examination of the coronary arteries revealed fibrotic changes, which were probably induced by radiotherapy. In our second patient, myocardial infarction developed 5 days after vinblastine treatment; early angiography showed thrombotic occlusion of the proximal right coronary artery, which was recanalized using the diagnostic Sones catheter. Subsequent angiography revealed normal coronary arteries. This is, to our knowledge, the first case of documented coronary artery thrombosis after treatment with vinca-alkaloids. In our third patient, neither mediastinal irradiation nor chemotherapy had been performed prior to myocardial infarction. However, a marked increase in platelet counts following splenectomy was observed in this patient. The role of radiotherapy, chemotherapy, and splenectomy with consecutive thrombocytosis as a third possible pathogenic factor for subsequent development of myocardial infarction is discussed.

Frequency of complications of cardiopulmonary resuscitation after thrombolysis during acute myocardial infarction.

Prolonged external cardiac massage is often regarded as a contraindication for thrombolytic therapy because of the risk of fatal hemorrhage. The influence of cardiopulmonary resuscitation on complications of thrombolytic bleeding was assessed analyzing data of all patients with myocardial infarction admitted to our clinic during the 10-year period between 1978 and 1987. From the total of 2,147 patients with acute myocardial infarction, 590 received thrombolytic therapy (intracoronary in 229, intravenous in 400). Of these, 43 patients underwent prolonged cardiopulmonary resuscitation and received thrombolysis within a time interval of less than 24 hours. In 21 patients, resuscitation was performed within a short period of time (5 minutes to 20 hours) after thrombolysis (10 intracoronary, 10 intravenous, 1 intravenous + intracoronary) had been initiated; 9 of these patients survived (43%). In the other 22 patients, thrombolytic therapy was initiated during ongoing resuscitation (n = 6: intravenous in 5, intravenous + intracoronary in 1) or in the early phase (10 to 120 minutes) after successful resuscitation (n = 16: intracoronary in 10, intravenous in 4, intravenous + intracoronary in 2). From this group, 14 patients survived (in-hospital mortality 36%). The mean duration of cardiopulmonary resuscitation was 36 +/- 32 minutes (range 4 to 120). Autopsy studies were performed in 16 of 20 decreased patients. Bleeding complications occurred in 8 of 43 patients. No case of bleeding was directly related to cardiocompression despite the often traumatic procedure with rib fractures verified in 17 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholinesterases of heart muscle. Characterization of multiple enzymes using kinetics of irreversible organophosphorus inhibition.

Cholinesterases of porcine left ventricular heart muscle were characterized with respect to substrate specificity and inhibition kinetics with organophosphorus inhibitors N,N'-di-isopropyl-phosphorodiamidic fluoride (Mipafox), di-isopropylphosphorofluoridate (DFP), and diethyl p-nitro-phenyl phosphate (Paraoxon). Total myocardial choline ester hydrolysing activity (234 nmol/min/g wet wt with 1.5 mM acetylthiocholine, ASCh; 216 nmol/min/g with 30 mM butyrylthiocholine, BSCh) was irreversibly and covalently inhibited by a wide range of inhibitor concentrations and, using weighted least-squares non-linear curve fitting, residual activities as determined with four different substrates in each case were fitted to a sum of up to four exponential functions. Quality of curve fitting as assessed by the sum of squares reached its optimum on the basis of a three component model, thus, indicating the presence of three different enzymes taking part in choline ester hydrolysis. Final classification of heart muscle cholinesterases was obtained according to both substrate hydrolysis patterns with ASCh, BSCh, acetyl-beta-methylthiocholine and propionylthiocholine, and second-order rate constants for the reaction with organophosphorus inhibitors Mipafox, DFP, and Paraoxon. One choline ester-hydrolysing enzyme was identified as acetylcholinesterase (EC 3.1.1.7), and one as butyrylcholinesterase (EC 3.1.1.8). The third enzyme with relative resistance to organophosphorus inhibition was classified as atypical cholinesterase.

Successful surgical management of left ventricular free wall rupture in the course of myocardial infarction.

The case of a 49-year-old patient is described who presented with cardiogenic shock and electrocardiographic signs of an inferolateral Q-wave infarction, and who received systemic lysis with anisoylated plasminogen streptokinase activator complex (Eminase). After coronary angiography had revealed only peripheral occlusion of a posterolateral branch of the left circumflex coronary artery, a pericardial effusion surrounding both right and left ventricular cavity was identified by echocardiography and was successfully drained via an inferior pericardiotomy with an immediate rise of blood pressure. Upon thoracotomy myocardial rupture was detected in the infarct area and was closed with mattress sutures. A total of 39 cases of successful surgical repair of myocardial free wall rupture reported in the literature is discussed. The mean age of patients was 59.6 +/- 1.3 years. Posterior and anterolateral infarctions were the preferred locations of myocardial rupture. Rupture occurred with a mean delay of 5.0 +/- 1.0 days after the onset of clinical infarct signs. Among patients saved by surgical means were 33 males and 6 females.

[Percutaneous transluminal coronary angioplasty in patients over 75 years old with acute myocardial infarct or unstable angina pectoris]. / Perkutane transluminale Koronarangioplastie bei Patienten über 75 Jahre mit akutem Myokardinfarkt oder instabiler Angina pectoris.

Both increasing frequency and technical improvements of percutaneous transluminal coronary angioplasty (PTCA) have focussed attention on possible applications of PTCA in elderly patients with coronary artery disease. From January 1986 to June 1989, among 1872 patients treated with PTCA in our hospital, 42 patients (2.3%) were 75 or more years old. Of these patients, 14 presented with unstable angina, 28 patients suffered from acute myocardial infarction. PTCA was performed on stenoses of left anterior descending artery (43%), circumflex coronary artery (18%), and right coronary artery (39%), respectively. In patients with unstable angina, PTCA in 81% could reduce diameter stenoses of culprit lesions to 50% or less. 43% of patients with acute myocardial infarction had received previous thrombolytic therapy with streptokinase or urokinase applied either systemically or intracoronarily. On cardiac catheterization, 39% of patients presenting with acute myocardial infarction showed total occlusion of the infarct-related vessel. In 75% of patients with acute myocardial infarction, after PTCA, patency of the infarct-related artery (diameter stenoses 50% or less) was observed. In-hospital mortality of patients with acute myocardial infarction subjected to PTCA was 10%, two patients dying in prolonged cardiogenic shock, one in septic shock. In 20% of cases, coronary dissection was observed after PTCA. Non-Q-wave infarction developed in one patient. Three patients had a peripheral vascular complication, and in one patient a transient ischemic attack was observed. No severe catheter-related complications occurred after thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of the organophosphorus compound DFP on inhibitory motor systems and esterase activity in the spinal cord of cats.

In high spinal cats, the acute time-dependent changes of both the activity of spinal reflex pathways and the activity of three different esterases (acetylcholinesterase, carboxylesterase and neurotoxicant target enzyme) in the spinal cord were investigated after intravenous application of the organophosphorus compound di-isopropyl phosphofluoridate (DFP). There is no general depression of spinal reflexes by DFP. While the recurrent inhibition is completely abolished for a long time and the reflexes to a flexor (PBSt) are depressed but with a shorter recovery time, the reflexes to an extensor (GS) are distinctly less depressed or even facilitated. Reflex pathways from skin afferents to motoneurones did not react in a uniform way to DFP, e.g. inhibitory nociceptive pathways were less affected than excitatory ones. Esterase activities were heavily depressed and recovered with different time courses. The acute DFP action cannot be explained by a uniform intoxication of all spinal functions but probably emerges from a differential action on different interneuronal systems.