Myoglobin Release Research Articles

Drug-Induced Rhabdomyolysis

The syndrome of rhabdomyolysis is the result of skeletalmuscle injury that alters the integrity of the sarcolemmaand leads to the eventual release of intracellular contentsinto the plasma. The causes are diverse, and includemuscle trauma (for instance, from vigorous exercise, crushinjuries, battering, or seizures), inadequate bloodperfusion, heat stroke, electrolyte imbalance, hereditaryenzyme deficiencies, infections and ingestion of drugs andtoxins. Various serious medical disorders, particularlythose resulting in states of disordered energy production,are also associated with rhabdomyolysis.In general, drug toxicity involves organs, such as thekidney, liver, gastrointestinal tract and the central nervoussystem, with skeletal muscle being usually less readilyaffected. Although drug-induced rhabdomyolysis wasuncommon in the past, it is no longer rare, due to theintroduction of more and increasingly potent drugs intoclinical practice.The incidence of drug-induced rhabdomyolysis isuncertain, largely because most of it is unreported.Similarly, the mortality rates are unknown. However, ithas been suggested that rhabdomyolysis from all causesleads to 5%-25% of cases of acute renal failure.

Beneficial effect of ischemic preconditioning on Ca 2+ paradox in the rat heart

The effect of ischemic preconditioning ( IP; 3 min ischemia plus 3 min reperfusion) on the recovery of cardiac function after Ca 2+ depletion was investigated. Isolated rat hearts were subjected to different cycles of IP episodes followed by Ca 2+ free perfusion and repletion. Perfusion of control hearts with Ca 2+ free medium for 5 min followed by repletion of Ca 2+ for 30 min resulted in a marked decrease in the left ventricular (LV) developed pressure and an increase in LV end-diastolic pressure (Ca 2+ paradox). The depressed function due to Ca 2+ paradox recovered with three cycles of IP. Myoglobin release during Ca 2+ repletion also decreased significantly by three cycles of IP. The beneficial effects of IP were also evident when the hearts were subjected to a mild form of Ca 2+ paradox involving 3 min Ca 2+ depletion. The protective effect rendered by IP disappeared when 10 μM of 8-(p-sulfophenyl)-theophylline, adenosine antagonist was perfused for 10 min before IP. These results suggest that IP exerts beneficial effects on Ca 2+ paradox which may be mediated by adenosine.

Stability of a Control Material Suitable for Quantitative Measurement of Urine Myoglobin

Myoglobin is a 17-kDa single-chain hemoprotein found in skeletal and cardiac muscle. This heme protein facilitates the movement of oxygen into cells and provides for local storage of oxygen. Myoglobin is found in the circulation as a result of muscle damage. Several conditions are associated with the release of myoglobin into the circulation, including myocardial infarction, trauma, ischemia, surgery, exercise, rhabdomyolysis, and other myopathy-associated disease states [1–3] . The quantitative measurement of myoglobin in urine is clinically important in diagnosing myoglobinuria, which can subsequently induce acute renal failure, particularly in posttrauma, surgery, and rhabdomyolysis patients. Recent studies have suggested that patients with a urine myoglobin concentration >20 000 μg/L, particularly with a decreased myoglobin clearance rate (<4 mL/min), are at increased risk for decreased renal function (4)(5). Although the mechanism for myoglobin-induced acute renal failure has not yet been elucidated, large amounts of myoglobin present in the tubules may precipitate, particularly under acidic conditions, resulting in increased intratubular pressure and, subsequently, the decreased glomerular filtration rate (6) and (or) free-radical generation from inorganic iron may cause renal damage (7). The identification of the early clinical sequelae of myoglobinuria is important for enabling administration of prophylactic treatment for acute renal failure (8). Quantitative methodologies, including automated immunoassays, …

Collagen scar formation after acute myocardial infarction: relationships to infarct size, left ventricular function, and coronary artery patency.

Left ventricular function after acute myocardial infarction (AMI) is determined by the expansion of the infarct zone and remodeling of the noninfarcted myocardium. An occluded infarct-related artery (IRA) is an independent risk factor for remodeling. Changes in myocardial collagen metabolism were evaluated in 36 patients with suspected AMI. The plasma creatine kinase MB fraction and myoglobin release curves were analyzed for assessment of early reperfusion and infarct size. Collagen scar formation was evaluated by measurement of serum concentrations of the aminoterminal propeptide of type III procollagen (PIIINP), the aminoterminal propeptide of type I procollagen (intact PINP), and the carboxyterminal propeptide of type I procollagen (PICP). Plasma renin activity and urine excretion of cortisol and aldosterone were also measured. Coronary angiography and left ventricular cineangiography were performed during early hospitalization. The serum concentration of PIIINP increased from 3.50+/-0.20 to a maximum of 5.08+/-0.36 microg/L (n=32) in the patients with AMI, whereas the concentrations of intact PINP and PICP tended to decrease. The area under the curve (AUC) of PIIINP during the first 10 postinfarction days was larger in patients with severe heart failure or ejection fractions < or = 40% than in those with no heart failure or with an ejection fraction > 40% (P<.05 and P<.01, respectively), and it was also larger in the patients with TIMI grade 0 to 2 flows than in those with TIMI 3 flows (P<.05), despite similar enzymatically determined infarct sizes. No significant correlations between PIIINP and neurohumoral parameters were observed. The AUC of PIIINP and the change in PIIINP during the first 4 days were significantly correlated with indices of cardiac function. Collagen scar formation after AMI can be quantified by measurement of serum PIIINP concentrations. Scar formation is more prominent in large infarctions causing left ventricular dysfunction and in patients with occluded IRAs.

Thrombolysis-induced coronary reperfusion causes acute and massive interstitial release of cardiac muscle cell proteins

Reperfusion of the infarct-related artery in patients with acute myocardial infarction limits infarct size, but also causes accelerated release into plasma of cardiac tissue proteins. The latter effect could reflect either enhanced protein washout from the heart or abrupt disruption of myocyte membranes. The present study indicates that the latter mechanism prevails. In 26 patients, patency of the infarct-related artery was determined by coronary angiography 90 min and 5-7 days after thrombolytic treatment. Continuous electrocardiography was performed during the first 24 h after admission. Cumulative release of myoglobin (Mb) and creatine kinase (CK) into plasma was calculated from frequently sampled plasma concentrations. In patients with a patent infarct-related artery after 90 min, onset of a rapid (> 50%) decrease in ST-vector magnitude coincided with an equally rapid increase in QRS-vector magnitude, and with a sudden onset of release into plasma of Mb as well as CK. In these patients, a maximal initial release rate was observed and cumulative release conformed closely to a simple model for sudden interstitial liberation of proteins. In contrast, protein release started more gradually and could not be fitted to this model, in patients with persistent occlusion of the infarct-related artery at 90 min and absence of ST-vector normalisation. Previous studies have demonstrated significant myocardial salvage by timely reperfusion therapy. Nevertheless, this study indicates that the moment of recanalisation of the infarct-related artery coincides with sudden and massive disruption of myocyte membranes. Attenuation of this effect, if possible, could further improve the benefits of reperfusion therapy.

Acute salinomycin toxicosis of pigs.

Acute salinomycin toxicosis of pigs.

Cardiac and skeletal muscle myoglobin release after reperfusion of injured myocardium in dogs with systemic hypotension.

Myoglobin (Mb) is an intramyocardial protein that is released into the systemic circulation and rapidly cleared via the kidneys after myocardial injury. Arterial Mb concentration-time curves have been studied in humans and dogs in the setting of acute coronary artery occlusion, and the rate of rise of Mb is both sensitive and specific as an indicator of successful coronary artery reperfusion. Systemic hypotension may alter Mb kinetics and impact on the utility of this method by causing Mb release from ischemic skeletal muscle and by decreasing renal Mb clearance. This study was undertaken to determine whether analysis of Mb kinetics remains accurate in identifying coronary reperfusion in the setting of systemic hypotension. Eighteen chronically instrumented dogs were made hypotensive by being bled via a large-bore femoral artery catheter into a reservoir adjusted to maintain a constant mean arterial pressure of 50 mm Hg for 8 hours. After the first hour of hypotension, each dog was studied under one of the following three protocols: group 1, 2 hours of mid-left anterior descending artery (LAD) occlusion followed by 5 hours of unlimited reperfusion; group 2, 7 hours of mid-LAD occlusion without reperfusion; or group 3, 7 additional hours of hypotension alone. Systemic lactate extractions demonstrated a shift to anaerobic metabolism in skeletal muscle and confirmed that shock was established in all animals. Regional arteriovenous Mb differences in group 1 animals demonstrated release of large amounts of Mb from reperfused myocardium; in contrast, smaller amounts of Mb were released both from skeletal muscle rendered ischemic by hypotension and from myocardium rendered ischemic by coronary occlusion without reperfusion. In group 1 dogs, arterial Mb rose rapidly immediately after reperfusion, with peak Mb occurring 108 +/- 24 minutes (mean +/- SEM) after vessel reopening. In group 2 and group 3 dogs, arterial Mb rose more slowly, such that peak Mb was not reached within 8 hours in 11 of 12 animals. The linear rate of rise of arterial Mb over the first hour of reperfusion in group 1 dogs was 51 +/- 16 ng.mL-1.min-1. This slope was significantly greater than slopes determined over the same time period in dogs occluded and not reperfused (group 2, 1.2 +/- 0.6 ng.mL-1.min-1) and in those hypotensive alone (group 3, 0.8 +/- 0.5 ng.mL-1.min-1). All the slopes of group 2 and group 3 dogs fell below the range of slopes of group 1 dogs. In contrast to slopes of the Mb concentration-time curves, linear creatine kinase slopes were significantly less sensitive in predicting reperfusion. Analysis of plasma Mb kinetics allows early identification of coronary reperfusion after myocardial injury even in the presence of significant systemic hypotension.

Inhibition of the calcium paradox in isolated rat hearts by high perfusate sucrose concentrations

If a colloid osmotic (oncotic) pressure gradient develops across the myocyte membrane during the calcium paradox, adding an oncotic agent to the perfusate should be inhibitory. After 10-min perfusion with Ca(2+)-free Krebs-Henseleit (KH) buffer under constant flow at 34 degrees C, myoglobin release was measured from Langendorff hearts reperfused with Ca(2+)-containing KH buffer. When the Ca(2+)-free medium contained 200 mM sucrose, myoglobin release was reduced to 5% of that observed in the absence of sucrose, a change that was not seen when 200 mosM NaCl, choline chloride, LiCl, or glycerol was added. Replacement of 75 mM NaCl in the perfusate with 150 mM sucrose resulted in myoglobin release values that were 4% of the control. Plots of myoglobin release against sucrose concentration under these hypertonic and isotonic conditions yielded similar though separate curves. Sucrose also inhibited increases in wet weight-to-dry weight ratio and decreases in ATP and phosphocreatine contents. These results support the hypothesis that an oncotic pressure gradient arises during the calcium paradox at the moment of increased membrane permeability and plays a major role in its development.

Ascorbyl free radical: A noninvasive marker of oxidative stress in human open-heart surgery

To assess the development of oxidative stress in cardiac ischemia/reperfusion, the resulting depletion of plasma ascorbate was monitored by electron spin resonance spectroscopic detection of ascorbyl free radical (AFR) in a homogeneous group of 12 patients undergoing aortic valve replacement. Dimethyl sulfoxide (DMSO) was used as an enhancer and stabilizer for AFR in plasma separated from blood samples collected 15 min before incision, 10 min before aortic declamping, and sequentially during the initial 30 min of reperfusion. Plasma DMSO/AFR levels of patients were found to be significantly lower than in healthy subjects (−25%), further decreased upon ischemia (−35%), dropped to their lowest values within the first 10 min of reperfusion (−46%), and did not recover their initial values within 30 min following reflow. Cardiac index measurements revealed a still depressed heart function 4 h postdeclamping and a more delayed tissue injury was evidenced by cardiac myosin and myoglobin release in plasma. DMSO/AFR levels at early reperfusion were slightly (+12%) higher in plasma obtained from coronary sinus samples than in plasma from peripheral blood, suggesting an extra ascorbate release from the injured heart tissue. The close analogy between these results and the reported measurements of other plasma markers of oxidative stress, including ascorbate, indicates that the present method could be of great value in clinical practice.

Postischemic dysfunction of the heart induced by small numbers of neutrophils via formation of hypochlorous acid.

The role of polymorphonuclear neutrophils (PMN) in the injury of the heart following ischemia and reperfusion is still controversial. The aim of this study was to investigate whether small numbers of PMN may cause myocardial dysfunction in an isolated system, how the resulting loss of function can be characterized and whether the formation of hypochlorous acid (HOCl) can be responsible for the PMN-mediated effect. Isolated working guinea pig hearts were subjected to a 90% reduction of coronary flow for 30 min, with or without intracoronary infusion of homologous PMN (approximately 1-2 x 10(5) cells/min, i.e. about 5-10% of normal blood count). This ischemia was followed by a 15 min reflow period in a non-working ("Langendorff") mode before work was resumed. In hearts perfused only with buffer, post-hypoxic heart function recovered to 75-80% of the initial value. Inclusion of unstimulated PMN did not further attenuate cardiac function. However, cardiac output was decreased to 42% of the initial value, provided thrombin (0.3 U/ml) and H2O2 (10(-5) M) were also present, and the retained PMN (about 10% of those infused) were additionally stimulated during reflow by application of FMLP (10(-6) M for 1 min). In these instances, coronary flow at any time of the experiment and release of lactate or purines during ischemia and reflow did not differ significantly between hearts perfused with or without PMN. There was no substantial release of myoglobin in controls and in PMN-treated hearts. Inotropic stimulation of the hearts with noradrenaline or exogenous Ca2+ caused a sustained increase in contractile force. However, the response was significantly reduced in PMN-perfused hearts in comparison to control hearts. The myocardial contents of high-energy phosphates with and without inotropic stimulation proved to be identical irrespective of whether experiments had been performed in the absence or presence of PMN. A similar loss of myocardial function as mediated by PMN could be produced by infusing chemically generated hypochlorous acid (HOCl, 5 x 10(-7) M for 10 min). Strikingly, that portion of the infused HOCl which actually reacted with cardiac tissue was comparable to the amount shown to be generated by stimulating 10(6) PMN retained in the coronary system (about 7 nmoles). Supplementing the perfusate with the scavengers L-methionine (10(-4) M) or uric acid (5 x 10(-4) M) prevented the attenuation of heart function provoked by PMN. The results indicate that small numbers of PMN, sufficiently activated, can depress cardiac function after 30 min of ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Continuous ST- and QRS-vector changes and myoglobin release during streptokinase-treated acute myocardial infarction.

Twenty-two consecutive patients with a first myocardial infarction treated with streptokinase (SK) were compared to a group of 33 consecutive patients who did not receive SK. Age, infarct localization, duration of symptoms and infarct size, as estimated by cumulative creatine kinase (CK) release, did not differ between the two groups. Myoglobin (MG) release stopped after 5.5 +/- 3.3 h in SK-treated patients, which was 11 h earlier than in the controls (P less than 0.0001). CK release ceased after 15 +/- 7.8 h, about 13 h earlier than in the controls (P less than 0.0001). ST and QRS vector changes, registered by continuous vectorcardiography, were completed after 2.9 +/- 2.0 and 4.4 +/- 2.5 h respectively, about 2 and 4 earlier than in the controls (P less than 0.005 and P less than 0.0001 respectively). With SK, the termination of ST and QRS vector changes occurred more uniformly than corresponding vector changes in the controls, in whom a longer time interval between the termination of ST and the end of QRS vector changes was observed. With SK, the difference between the end of ST and QRS vectors decreased by about 3 h to 1.6 +/- 1.5 h (P less than 0.0001). Temporal relations between MG release and ST and QRS vector changes were similar but more uniform than in those of the reference group. In conclusion, we found that SK resulted in an accelerated and more uniform development of the infarct process, ending about 10 h after onset of therapy, compared with 20-30 h in the reference group.

Reduced free radical generation during reperfusion of hypothermically arrested hearts.

Several studies indicate the presence of hydroxyl radical (OH.) as well as its involvement in the myocardial reperfusion injury. A transition metal-like iron is necessary for the conversion of superoxide anion (O2-) to a highly reactive and cytotoxic hydroxyl radical (OH.). In the present study, we have examined the generation of OH. and free iron in reperfused hearts following either normothermic (37 degrees C) or hypothermic ischemia (5 degrees C). Employing the Langendorff technique, isolated rat hearts were subjected to global ischemia for 30 min at 37 degrees C or 5 degrees C and were then reperfused for 15 min at 37 degrees C. The results of the study suggest that both the OH. generation in myocardium and free iron release into perfusate were significantly lower in hearts made ischemic at 5 degrees C as compared to 37 degrees C. Release of myoglobin and lactic acid dehydrogenase into perfusate also followed a similar pattern. Furthermore, in in vitro studies, chemically generated O2- at 5 degrees C caused a significantly lower rate of oxidation of oxymyoglobin as well as generation of OH. and free iron as compared to 37 degrees C. These results suggest that (1) reperfusion of hypothermic ischemic heart is associated with a reduction in the generation of OH. and cellular damage compared to that of normothermic ischemic heart, and (2) myoglobin, an intracellular protein, is a source of free iron and plays a role in the reperfusion injury mediated by free radicals.

Blends of PVA and PGLA: control of the permeability and degradability of hydrogels by blending

Blends of poly vinyl alcohol (PVA) and polyglycolic acid-co-lactic acid (1:1), PGLA, were shown by DSC and electron microscopy to be miscible when the PVA content was 70wt-% or greater. The permeability coefficients of naltrexone, naltrexone hydrochloride, cytochrome C, myoglobin and somatotropin in PVA and PVA-PGLA blends ( 80:20 and 40:60 ) were measured. The permeability was proportional to the water content of the blends, which increased monotonically with the PVA content. Controlled release of myoglobin and cytochrome C from spheres coated with a PVA-PGLA (80:20) blend was achieved. The rate of hydrolytic chain scission of PGLA was relatively insensitive to the water content of immiscible blends, but increased exponentially after the blends became miscible.

Lack of indication of myocardial cell damage after myocardial ischaemia in patients with severe stable angina.

To evaluate myocardial cell damage in relation to spontaneous and exercise-induced ischaemia, release of myoglobin, creatine kinase (CK) and its isoenzyme MB (CK-MB) into the serum was estimated in 10 patients with severe stable angina. All patients had a positive exercise test, significant stenosis of one or more of the main coronary arteries and more than five ischaemic attacks per week. ST-segment monitoring was performed for 36 h. During the last 24 h of that period (period A) serial blood samples were analysed for myoglobin, CK and CK-MB using sensitive assays. Three days later (period B) the patients performed an exercise test at 0815 h, with ST-segment monitoring and blood sampling carried out as described for period A. During period A, 47 ischaemic episodes (100% silent) with a total duration of 599 min were noted in four patients. Forty-seven ischaemic episodes (94% silent) with a total duration of 804 min, were observed in seven patients during period B. Release of myoglobin, CK, and CK-MB did not increase in relation either to spontaneous or exercise-induced ischaemia. Thus even frequent and prolonged episodes of transient myocardial ischaemia (symptomatic or asymptomatic) in patients with severe stable angina pectoris does not seem to cause irreversible myocardial damage.

Effects of exercise on plasma myosin heavy chain fragments and MRI of skeletal muscle.

The effects of a single series of high-force eccentric contractions involving the quadriceps muscle group (single leg) on plasma concentrations of muscle proteins were examined as a function of time, in the context of measurements of torque production and magnetic resonance imaging (MRI) of the involved muscle groups. Plasma concentrations of slow-twitch skeletal (cardiac beta-type) myosin heavy chain (MHC) fragments, myoglobin, creatine kinase (CK), and cardiac troponin T were measured in blood samples of six healthy male volunteers before and 2 h after 70 eccentric contractions of the quadriceps femoris muscle. Screenings were conducted 1, 2, 3, 6, 9, and 13 days later. To visualize muscle injury, MRI of the loaded and unloaded thighs was performed 3, 6, and 9 days after the eccentric exercise bout. Force generation of the knee extensors was monitored on a dynamometer (Cybex II+) parallel to blood sampling. Exercise resulted in a biphasic myoglobin release profile, delayed CK and MHC peaks. Increased MHC fragment concentrations of slow skeletal muscle myosin occurred in late samples of all participants, which indicated a degradation of slow skeletal muscle myosin. Because cardiac troponin T was within the normal range in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for an injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Muscle action revealed delayed reversible increases in MRI signal intensities on T2-weighted images of the loaded vastus intermedius and deep parts of the vastus lateralis. We attributed MRI signal changes due to edema in part to slow skeletal muscle fiber injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the incorporation of amino groups in a glucose‐responsive polymer complex having phenylboronic acid moieties

AbstractA novel polymer complex system sensitive to glucose was studied as a candidate material for formulating a chemically regulated insulin release system. A ternary copolymer of N‐vinyl‐2‐pyrrolidone (NVP), 3‐acrylamidophenylboronic acid (AAm‐PBA) and N,N‐dimethylaminopropylacrylamide (DMAPAA) (poly(NVP‐co‐PBA‐co‐DMAPAA)) was synthesized by radical copolymerization. The phenylboronic acid group in this copolymer serves as a glucose sensor moiety. Poly(NVP‐co‐PBA‐co‐DMAPAA) was soluble in water in the pH range of 3–12, in sharp contrast to a binary copolymer of NVP and AAm‐PBA (poly(NVP‐co‐PBA)) which showed solubility only under alkaline aqueous conditions, where the boronic acid group is in a tetrahedral ionized form. The protonated amino group in poly(NVP‐co‐PBA‐DMAPAA) contributed to increase the solubility of the polymer under physiological and acidic aqueous conditions. Furthermore, poly(NVP‐co‐PBA‐co‐DMAPAA) formed a stable polymer complex gel with poly(vinyl alcohol) (PVA) in pH 7.4 phosphate buffered solution due to the formation of a covalent linkage between the boronic acid groups in ternary copolymer and diol units in PVA. The release of myoglobin as model protein from the complex gel was increased immediately after the addition of glucose, due to the transition of gel into sol state, indicating the feasibility of this complex gel as a candidate material for a glucose‐responsive delivery system for insulin.

Muscle ATP and lactate and the release of myoglobin and carbanhydrase III in acute lower-limb ischaemia

Serum-myoglobin and carbanhydrase III (S-CAIII), a specific muscle enzyme, were measured on admission, during surgery and in the postoperative period in 23 patients with acute lower-limb ischaemia and in 21 patients with chronic limb ischaemia in order to evaluate these molecules as possible markers of the degree of clinical ischaemia. The muscle contents of ATP and lactate were determined in muscle biopsies from patients with acute ischaemia on admission. Unlike S-myoglobin and S-CAIII they discriminated between cases which required subsequent amputation from those which did not. Clinical signs of ischaemia were, however, of no value in this respect and there were no correlations between clinical signs or the duration of ischaemia and S-myoglobin or S-CAIII or the contents of ATP or lactate in muscle tissue. The levels of S-myoglobin and S-CAIII correlated well (r = 0.95, p less than 0.0001). In patients who subsequently required an amputation S-myoglobin increased ten-fold (i.e., from 24-48 h postoperatively in acute arterial ischaemia and from 3 h postoperatively in patients with chronic limb ischaemia). In patients with a successful revascularisation S-myoglobin returned to normal levels. It is concluded that in this investigation S-myoglobin had no prognostic value on admission and that S-myoglobin analyses in the postoperative course may be useful for making clinical decisions concerning impending recirculation failures.

Diet, diabetes, and male chauvinism.

Massive muscle breakdown Tests of renal function were taken four days after the incident. All electrolyte concentrations were normal, but the measurements of muscle breakdown aspartate transaminase and creatinine kinase were 1540 IU/l (normal 2-40 IU/l) and 45 860 IU/l (normal <170 IU/l) respectively, indicating massive muscle breakdown. Death from acute tubular necrosis because oftraumatic myolysis has resulted following concentrations of creatinine kinase as low as 3500 IU/1.5 The creatinine clearance as a result was 148 ml/min. Friday saw some recovery as I was now able to stand unsupported for up to five minutes at a time. The urine had returned to a normal colour and I was able to put my socks on (with difficulty). I had clearly a large mass of muscles in my chest, shoulders, and abdomen caused by my strenuous efforts to stand on the water and the prolonged high speed battering while'in the water. Massive release of myoglobin occurred as it does in the crush syndrome,6 and there was a risk of blocking the glomerulus of the kidney with the sequelae of acute tubular necrosis. Fortunately, this was avoided. This potentially severe injury has not been previously reported in barefoot waterskiing yet is a real possibility given the speed and trauma that the torso suffers as it is pulled through the water. Adequate body protection must be worn and repeated exposure to many high speed attempts should not be permitted. Doctors are often accused of playing God in their dealings with patients. This is one orthopaedic surgeon who will no longer attempt to walk on water.

Rhabdomyolysis Due to Pulsed Electric Fields

High-voltage electrical trauma frequently results in extensive and scattered destruction of skeletal muscle along the current path. The damage is commonly believed to be mediated by heating. Recent experimental and theoretical evidence suggests, however, that the rhabdomyolysis and secondary myoglobin release that occur also can result from electroporation, a purely nonthermal mechanism. Based on the results of a computer simulation of a typical high-voltage electric shock, we have postulated that electroporation contributes substantially to skeletal muscle damage and could be the primary mechanism of damage in some cases of electrical injury. In this study, we determined the threshold field strength and exposure duration required to produce rhabdomyolysis by the electroporation mechanism. The change in the electrical impedance of intact skeletal muscle tissue following the application of short-duration, high-intensity electric field pulses is used as an indicator of membrane damage. Our experiments show that a decrease in impedance magnitude occurs following electric field pulses that exceed threshold values of 60 V/cm magnitude and 1-ms duration. The field strength, pulse duration, and number of pulses are factors that determine the extent of damage. The effect does not depend on excitation-contraction coupling. Electron micrographs confirm structural defects created in the membranes by the applied electric field pulses, and these represent the first clear demonstration of rhabdomyolysis in intact muscle due to electroporation. These results provide compelling evidence in support of our postulate.

Clinical and laboratory features of South American rattlesnake ( Crotalus durissus terrificus) envenomation in children

The venom of the South American rattlesnake Crotalus durissus terrificus was first reported to have mainly haemolytic and neurotoxic physiopathological activities. Later studies demonstrated the systemic myotoxic action of the venom, characterized by the release of myoglobin from damaged skeletal muscle into serum and urine, and a recent report ruled out the presence of intravascular haemolysis in 3 patients, one child and 2 adults. The present paper describes the clinical-laboratory evolution of 10 children bitten by C. durissus terrificus; 2 developed acute renal failure and one died. The myotoxic activity of the venom was evaluated by measuring serum lactic dehydrogenase, creatine kinase and aspartate aminotransferase, by detection of myoglobin in serum and urine, and by muscle biopsy. Haemolytic activity was evaluated by serial measurements of serum haemoglobin and haptoglobin and by detection of urine haemoglobin. We conclude that the signs and symptoms exhibited by patients bitten by C. durissus terrificus are due only to the myotoxic and neurotoxic action of the venom. The only patients with major morbidity were those who initially received subcutaneous antivenin and did not receive definitive antivenin therapy until later.