Estimating Arterial Cyclic Strain from the Spacing of Endothelial Nuclei.

BACKGROUND: The non-uniform distribution of atherosclerosis within the arterial system is widely attributed to variation in haemodynamic wall shear stress. It may also depend on variation in pressure-induced stresses and strains within the arterial wall; these have been less widely investigated, at least in part because of a lack of suitable techniques. OBJECTIVES: Here we show that local arterial strain can be determined from impressions left by endothelial cells on the surface of vascular corrosion casts made at different pressures, even though only one pressure can be examined in each vessel. The pattern of pits in the cast caused by protruding endothelial nuclei was subject to "retro-deformation" to identify the pattern that would have occurred in the absence of applied stresses. METHODS: Retaining the nearest-neighbour pairs found under this condition, changes in nearest-neighbour vectors were calculated for the pattern seen in the cast, and the ratio of mean changes at different pressures determined. This approach removes errors in simple nearest-neighbour analyses caused by the nearest neighbour changing as deformation occurs. RESULTS: The accuracy, precision and robustness of the approach were validated using simulations. The method was implemented using confocal microscopy of casts of the rabbit aorta made at systolic and diastolic pressures; results agreed well with the ratio of the macroscopic dimensions of the casts. CONCLUSIONS: Applying the new technique to areas around arterial branches could support or refute the hypothesis that the development of atherosclerosis is influenced by mural strain, and the method may be applicable to other tissues.

Universal features of counting statistics of thermal and quantum phase slips in nanosize superconducting circuits.

We perform measurements of phase-slip-induced switching current events on different types of superconducting weak links and systematically study statistical properties of the switching current distributions. We employ two types of devices in which a weak link is formed either by a superconducting nanowire or by a graphene flake subject to proximity effect. We demonstrate that independently of the nature of the weak link, higher moments of the distribution take universal values. In particular, the third moment (skewness) of the distribution is close to -1 both in thermal and quantum regimes. The fourth moment (kurtosis) also takes a universal value close to 5. The discovered universality of skewness and kurtosis is confirmed by an analytical model. Our numerical analysis shows that introduction of extraneous noise into the system leads to significant deviations from the universal values. We suggest using the discovered universality of higher moments as a robust tool for checking against undesirable effects on noise in various types of measurements.

Contrast Agent-Free Assessment of Blood Flow and Wall Shear Stress in the Rabbit Aorta using Ultrasound Image Velocimetry.

Blood flow velocity and wall shear stress (WSS) influence and are influenced by vascular disease. Their measurement is consequently useful in the laboratory and clinic. Contrast-enhanced ultrasound image velocimetry (UIV) can estimate them accurately but the need to inject contrast agents limits utility. Singular value decomposition and high-frame-rate imaging may render contrast agents dispensable. Here we determined whether contrast agent-free UIV can measure flow and WSS. In simulation, accurate measurements were achieved with a signal-to-noise ratio of 13.5 dB or higher. Signal intensity in the rabbit aorta increased monotonically with mechanical index; it was lowest during stagnant flow and uneven across the vessel. In vivo measurements with contrast-free and contrast-enhanced UIV differed by 4.4% and 1.9% for velocity magnitude and angle and by 9.47% for WSS. Bland-Altman analysis of waveforms revealed good agreement between contrast-free and contrast-enhanced UIV. In five rabbits, the root-mean-square errors were as low as 0.022 m/s (0.81%) and 0.11 Pa (1.7%). This study indicates that with an optimised protocol, UIV can assess flow and WSS without contrast agents. Unlike contrast-enhanced UIV, contrast-free UIV could be routinely employed.

The effect of the endothelial glycocalyx layer on concentration polarisation of low density lipoprotein in arteries.

It has been postulated that a flow-dependent (and hence spatially varying) low density lipoprotein (LDL) concentration polarisation layer forms on the luminal surface of the vascular endothelium. Such a layer has the potential to cause heterogeneity in the distribution of atherosclerotic lesions by spatially modulating the rate of LDL transport into the arterial wall. Theoretical analysis suggests that a transmural water flux which is spatially heterogeneous at the cellular scale can act to enhance LDL concentration polarisation in a shear dependent fashion. However, such an effect is only observed if a relevant Peclet number (i.e. the ratio of LDL convection to LDL diffusion) is of order unity or greater. Based on the diffusivity of LDL in blood plasma, such a Peclet number is found to be far less than unity, implying that the aforementioned enhancement and shear dependence will not occur. However, this conclusion ignores the existence of the endothelial glycocalyx layer (EGL), which may inhibit the diffusion of LDL near the luminal surface of the endothelium, and hence raise any Peclet number associated with the transport of LDL. The present study numerically investigates the effect of the EGL, as well as a heterogeneous transmural water flux, on arterial LDL concentration polarisation. Particular attention is paid to measures of LDL concentration polarisation thought relevant to the rate of transendothelial LDL transport. It is demonstrated that an EGL is unlikely to cause any additional shear dependence of such measures directly, irrespective of whether or not LDL can penetrate into the EGL. However, it is found that such measures depend significantly on the nature of the interaction between LDL and the EGL (parameterized by the height of the EGL, the depth to which LDL penetrates into the EGL, and the diffusivity of LDL in the EGL). Various processes may regulate the interaction of LDL with the EGL, possibly in a flow dependent and hence spatially non-uniform fashion. It is concluded that any such processes may be as important as vascular scale flow features in terms of spatially modulating transendothelial LDL transport via an LDL concentration polarisation mechanism.

Determining Haemodynamic Wall Shear Stress in the Rabbit Aorta In Vivo Using Contrast-Enhanced Ultrasound Image Velocimetry.

Abnormal blood flow and wall shear stress (WSS) can cause and be caused by cardiovascular disease. To date, however, no standard method has been established for mapping WSS in vivo. Here we demonstrate wide-field assessment of WSS in the rabbit abdominal aorta using contrast-enhanced ultrasound image velocimetry (UIV). Flow and WSS measurements were made independent of beam angle, curvature or branching. Measurements were validated in an in silico model of the rabbit thoracic aorta with moving walls and pulsatile flow. Mean errors over a cardiac cycle for velocity and WSS were 0.34 and 1.69%, respectively. In vivo time average WSS in a straight segment of the suprarenal aorta correlated highly with simulations (PC = 0.99) with a mean deviation of 0.29 Pa or 5.16%. To assess fundamental plausibility of the measurement, UIV WSS was compared to an analytic approximation derived from the Poiseuille equation; the discrepancy was 17%. Mapping of WSS was also demonstrated in regions of arterial branching. High time average WSS (TAWSSxz = 3.4 Pa) and oscillatory flow (OSIxz = 0.3) were observed near the origin of conduit arteries. In conclusion, we have demonstrated that contrast-enhanced UIV is capable of measuring spatiotemporal variation in flow velocity, arterial wall location and hence WSS in vivo with high accuracy over a large field of view.

Ensiling olive cake with and without molasses for ruminant feeding.

The purpose of the current experiment was to study the ensiling properties of olive cake with and without added molasses at 2-6% (w/w). The results indicate that molasses enhanced the ensiling fermentation of olive cake, as evidenced from higher lactic acid content and higher lactic acid bacteria numbers at 4% and 6% added molasses. However, when applied at 4% and 6% molasses increased fermentation losses up to 9.4%, probably due to larger yeast population. Polyphenols which could interfere with protein utilization by ruminants, decreased during ensiling by about 40%. It is concluded that molasses added at 3% could improve the ensiling fermentation of olive cake without substantial losses.

Noradrenaline has opposing effects on the hydraulic conductance of arterial intima and media.

The uptake of circulating macromolecules by the arterial intima is thought to be a key step in atherogenesis. Such transport is dominantly advective, so elucidating the mechanisms of water transport is important. The relation between vasoactive agents and water transport in the arterial wall is incompletely understood. Here we applied our recently-developed combination of computational and experimental methods to investigate the effects of noradrenaline (NA) on hydraulic conductance of the wall (Lp), medial extracellular matrix volume fraction (ϕECM) and medial permeability (K11) in the rat abdominal aorta. Experimentally, we found that physiological NA concentrations were sufficient to induce SMC contraction and produced significant decreases in Lp and increases in ϕECM. Simulation results based on 3D confocal images of the extracellular volume showed a corresponding increase in K11, attributed to the opening of the ECM. Conversion of permeabilities to layer-specific resistances revealed that although the total wall resistance increased, medial resistance decreased, suggesting an increase in intimal resistance upon application of NA.

Intimal and medial contributions to the hydraulic resistance of the arterial wall at different pressures: a combined computational and experimental study.

The hydraulic resistances of the intima and media determine water flux and the advection of macromolecules into and across the arterial wall. Despite several experimental and computational studies, these transport processes and their dependence on transmural pressure remain incompletely understood. Here, we use a combination of experimental and computational methods to ascertain how the hydraulic permeability of the rat abdominal aorta depends on these two layers and how it is affected by structural rearrangement of the media under pressure. Ex vivo experiments determined the conductance of the whole wall, the thickness of the media and the geometry of medial smooth muscle cells (SMCs) and extracellular matrix (ECM). Numerical methods were used to compute water flux through the media. Intimal values were obtained by subtraction. A mechanism was identified that modulates pressure-induced changes in medial transport properties: compaction of the ECM leading to spatial reorganization of SMCs. This is summarized in an empirical constitutive law for permeability and volumetric strain. It led to the physiologically interesting observation that, as a consequence of the changes in medial microstructure, the relative contributions of the intima and media to the hydraulic resistance of the wall depend on the applied pressure; medial resistance dominated at pressures above approximately 93 mmHg in this vessel.

The effect of osmotic and mechanical pressures on water partitioning in articular cartilage.

X-ray diffraction measurements on native and proteoglycan-free articular cartilage have been made in order to test the dependence of the lateral packing of the collagen molecules on the osmotic pressure gradient, either naturally occurring or externally applied, between the intra- and extrafibrillar compartments. From the information on collagen packing we have been able to calculate, albeit with several assumptions, the amount of intrafibrillar water as a function of pressure. In parallel with the above measurements, we have quantitated, using serum albumin partitioning, the intrafibrillar water in proteoglycan-free cartilage, as a function of mechanically applied pressure. The results of both sets of experiments lead to the conclusion that the molecular packing density, and hence the intrafibrillar water content, are a function of the osmotic pressure difference between the extrafibrillar and intrafibrillar spaces or the equivalent mechanically applied pressure. The determination of intrafibrillar water has enabled us to calculate, from measured values of fixed charge density, the internal osmotic pressure of cartilage specimens, both in compressed and uncompressed states.

Diastolic biomechanics in normal infants utilizing MRI tissue tagging.

BACKGROUND: Most of what is known about diastolic function in normal infants is derived from flow and pressure measurements. Little is known about regional diastolic strain and wall motion. METHODS AND RESULTS: Magnetic resonance tissue tagging was performed in 11 normal infants to determine regional diastolic strain and wall motion. Tracking diastolic motion of the intersection points and finite strain analysis yielded regional rotation, radial displacement, and E(1) and E(2) strains at 3 short-axis levels (significance was defined as P<0.05). E(2) "circumferential lengthening" strains were significantly greater at the lateral wall, regardless of short-axis level, whereas E(1) "radial thinning" strains were similar in all wall regions at all short-axis levels. In general, no differences were noted in strain dispersion within a wall region or in endocardial/epicardial strain at all short-axis levels. At all short-axis levels, septal radial motion was significantly less than in other wall regions. No significant differences in radial wall motion between short-axis levels were noted. Rotation was significantly greater at the apical short-axis level in all wall regions than in other short-axis levels, and it was clockwise. At the atrioventricular valve, septal and anterior walls rotated slightly clockwise, whereas the lateral and inferior walls rotated counterclockwise. CONCLUSIONS: Diastolic biomechanics in infants are not homogeneous. The lateral walls are affected most by strain, and the septal walls undergo the least radial wall motion. Apical walls undergo the most rotation. These normal data may help in the understanding of diastolic dysfunction in infants with congenital heart disease.

Fetal hydrops in a newborn with hypoplastic left heart syndrome: tricuspid valve "stopper".

Fetal hydrops in a newborn infant with hypoplastic left heart syndrome led to the discovery of tricuspid stenosis and insufficiency from an unusual malformation of the right venous valve of the embryonic sinus venosus. This unfortunate combination of lesions precluded surgical palliation for the hypoplastic left heart.

Subcostal two-dimensional echocardiographic identification of anomalous attachment of septum primum in patients with left atrioventricular valve underdevelopment.

Five variations of atrial septal morphology occur in hypoplastic left heart syndrome. One variety, termed anomalous attachment of septum primum, has been described only in necropsy series. Two-dimensional echocardiography was utilized to determine the incidence of this anomaly in patients with left atrioventricular (AV) valve underdevelopment, including those with other ventriculoarterial alignments, such as transposition of the great arteries. Forty-eight (37%) of 129 patients with normally aligned great arteries (and two ventricles) had anomalous attachment of septum primum. Ten (34%) of 29 patients with double outlet right ventricle and left AV valve underdevelopment had this anomaly. Four (50%) of eight patients with single ventricle exhibited this atrial septal variant. The most reliable view to identify anomalous attachment was the subcostal left oblique-equivalent cut. Recognition of atrial septal morphology has implications for preoperative and intraoperative management of patients with left AV valve underdevelopment. The similar prevalence of this atrial septal variant in patients with normally aligned great arteries, double outlet right ventricle and transposed great arteries suggests that there may be a common mechanism for left AV valve underdevelopment that is independent of the development of the arterial portion of the heart.

Morphometric analysis of unbalanced common atrioventricular canal using two-dimensional echocardiography.

OBJECTIVES: This study was designed to define morphometric echocardiographic variables of unbalanced common atrioventricular canal (CAVC) that could aid in appropriate referral for surgical repair. BACKGROUND: Unbalanced CAVC has a high surgical mortality rate. This may be secondary to inappropriate referral of some patients for two-ventricle repair (closure of septal defects) instead of single-ventricle repair (Norwood palliation and Fontan operation). METHODS: The echocardiograms of 103 patients with CAVC were retrospectively reviewed. In the subcostal left anterior oblique view, the area of the atrioventricular (AV) valve aportioned over each ventricle was measured, and an AV valve index (AVVI) was calculated as left/right valve area. The ventricular cavity ratio between the two ventricles was estimated as left ventricular length times width divided by right ventricular length times width. These variables were correlated with surgical referral and outcome. RESULTS: Patients previously categorized as having balanced CAVC all had AVVI > 0.67 (n = 77). Of the patients with unbalanced CAVC (n = 26), 11 had ductal-dependent circulation and underwent Norwood palliation (AVVI 0.21 +/- 0.13, mean +/- SD), and 15 had two-ventricle repair (AVVI 0.51 +/- 0.12, p < 0.0001). Of these 15 patients, 9 have survived, with no difference in mean AVVI between survivors and nonsurvivors (0.52 +/- 0.11 versus 0.49 +/- 0.13, p = 0.72). For all 103 patients, AVVI correlated with ventricular cavity ratio. However, of the unbalanced CAVC group who underwent two-ventricle repair, three nonsurvivors had a discrepancy between AVVI and ventricular cavity ratio (low AVVI but normal ventricular size). A large ventricular septal defect was present in all six nonsurvivors but in only four of nine survivors (p < 0.05). CONCLUSIONS: Echocardiographic morphometry is useful in defining unbalance in CAVC. If AVVI is < 0.67 in the presence of a large ventricular septal defect, a single-ventricle approach to repair should be considered.

Growth characteristics of the aortic arch after the Norwood operation.

OBJECTIVES: We sought to characterize the growth of the reconstructed aortic arch after the Norwood operation (NO). BACKGROUND: The first stage of surgical palliation of hypoplastic left heart syndrome (HLHS), the NO, includes augmentation of the aortic arch with homograft. Growth characteristics of the reconstructed aortic arch, which is comprised of both native aortic tissue and homograft, have not been characterized. METHODS: Retrospectively, we examined the serial echocardiograms of 50 patients with HLHS who underwent NO to determine the diameter of the reconstructed transverse arch. Measurements were taken immediately after NO and at two other points (1 to 11 years of age). In addition, the autopsy specimens of 10 other patients with HLHS who underwent NO were examined to determine the contribution of native aortic tissue to the overall size of the reconstructed arch at the time of death (12 to 34 months). RESULTS: The diameter of the transverse aorta increased after NO in all subjects. Its rate of growth paralleled that seen in the normal population, though the reconstructed arch had a significantly larger diameter throughout childhood. Examination of autopsy specimens demonstrated a mean increase in circumference of the native aortic tissue of 0.67 cm (p value <0.01), whereas there was no significant change in homograft circumference. CONCLUSIONS: After reconstruction of the aortic arch in HLHS, the diameter of the arch continues to increase throughout childhood, and this increase is due to growth of the native aortic tissue.

Origin of the left coronary artery from the right pulmonary artery.

Origin of the left coronary artery from the right pulmonary artery has rarely been documented. This is the first such case in a heart with an intact ventricular septum and paraductal coarctation of the aorta. Although an antemortem diagnosis was made and the anomalous left coronary artery was ligated, the patient, a 3 1/2 month old infant, died 1 day after surgery. Autopsy confirmed the diagnosis, but revealed that the left coronary artery was dominant. It is believed that the fatal outcome in the infant was, in part, due to the dominance of the left coronary artery and the effects of the coarctation on the already ischemic left ventricle.

Coronary artery abnormalities and right ventricular histology in hypoplastic left heart syndrome.

OBJECTIVES: To determine whether right ventricular preservation is compromised in any anatomic subgroup of hypoplastic left heart syndrome, we assessed the coronary artery anatomy and myocardial histologic features of 151 postmortem specimens with hypoplastic left heart syndrome. BACKGROUND: Although previous studies have shown that coronary artery abnormalities are more prominent in the subgroup of patients who have a patent mitral valve and obstructed aortic valve, it has not been established that these abnormalities compromise right ventricular perfusion. METHODS: Eighty-nine specimens with a patent mitral valve and aortic atresia, 52 with mitral and aortic atresia and 10 with patent mitral and aortic valves were examined. Histologic sections of the right ventricle, left ventricle and coronary arteries were obtained from 64 study hearts and 5 control hearts. RESULTS: Gross coronary anomalies included coronary-cameral communications (n = 29), single left coronary artery (n = 2), single right coronary artery (n = 1) and tortuosity (n = 19). Coronary-cameral communications and tortuosity were significantly associated with the subgroup that had mitral hypoplasia and aortic atresia. Coronary artery wall thickness relative to lumen diameter was not different among the subgroups. No areas of coronary artery stenosis or interruption were discovered. Although endocardial fibroelastosis of the left ventricle was strongly associated with the mitral hypoplasia and aortic atresia group, the right ventricular histologic findings were similar in all subgroups and were not differentially affected by older age. CONCLUSIONS: Although the incidence of coronary abnormalities is greater in patients with mitral hypoplasia and aortic atresia, in this study there was no apparent difference in perfusion of the right ventricle among the anatomic subgroups of hearts with hypoplastic left heart syndrome.

Late ventricular geometry and performance changes of functional single ventricle throughout staged Fontan reconstruction assessed by magnetic resonance imaging.

OBJECTIVES: We sought to test the hypothesis that late ventricular geometry and performance changes occur in functional single ventricles as they progress through staged Fontan reconstruction. BACKGROUND: Indexes of ventricular geometry and performance are important in evaluating the functional state of the heart. Magnetic resonance imaging determines these indexes in complex ventricular shapes with minimal geometric assumptions. Previous studies have shown that 1 week after hemiFontan, the mass/volume ratio markedly increases. METHODS: Multiphase, multislice, spin echo (n = 5) and cine (n = 30) magnetic resonance imaging was performed in 35 patients with a functional single ventricle (1 week to 12 years old) at various stages of Fontan reconstruction (15 in the pre hemiFontan stage, 11 after [6 to 9 months] the hemiFontan procedure and 9 after [1 to 2 years] the Fontan procedure). Volume and mass were calculated at end-systole and end-diastole. Ventricular output was then obtained. Ventricular centroid motion was also calculated. RESULTS: No difference was noted (power > 72%) from the pre hemiFontan stage to 6 to 9 months after the hemiFontan procedure in (mean +/- SD) end-diastolic volume (104 +/- 24 vs. 123 +/- 40 cc/m2), mass (171 +/- 46 vs. 202 +/- 61 g/m2), ventricular output (7.9 +/- 2.2 vs. 6.6 +/- 2.4 liters/min per m2) or centroid motion (6.9 +/- 2.8 vs. 6.7 +/- 2. mm/m2). Patients in the Fontan group demonstrated a marked decrease in all indexes, indicating significant volume unloading and decrease in mass and ventricular performance. Mass/volume ratio was not significantly different among all three groups. CONCLUSIONS: No geometric and performance changes from the volume-loaded stage are noted 6 to 9 months after the hemiFontan procedure; however, major changes occur 1 to 2 years after the Fontan procedure. The dramatic changes in the mass/volume ratio seen early after the hemiFontan procedure were not detected at 6 to 9 months. Furthermore diminution of mass, volume and ventricular performance are present at least 2 years after the Fontan procedure.

Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching.

OBJECTIVES: The purpose of this study was to determine the frequency of chromosome 22q11 deletions in patients with isolated anomalies of the aortic arch and its branches. BACKGROUND: Chromosome 22q11 deletions are often present in patients with certain forms of congenital cardiovascular disease, including tetralogy of Fallot, truncus arteriosus and interruption of the aortic arch. Among patients with these anomalies, chromosome 22q11 deletion is more common in those with abnormal aortic arch laterality or branching. METHODS: We studied 66 patients with isolated anomalies of the aortic arch and no associated intracardiac defects for deletions within chromosome 22q11, using fluorescence in situ hybridization with the cosmid probe N25 (D22S75). Arch anomalies included: double aortic arch (n = 22); right aortic arch with aberrant left subclavian artery (n = 28); right aortic arch with mirror-image branching and a vascular ring formed by a left-sided ductus from the descending aorta (n = 5); right aortic arch with mirror-image branching and no vascular ring (n = 4); and left aortic arch with aberrant right subclavian artery (n = 7). In addition, four patients had a cervical aortic arch, four had aortic coarctation and six had hypoplasia/atresia of the proximal pulmonary arteries. RESULTS: Chromosome 22q11 deletions were found in 16 patients (24%) across the full spectrum of anomalies studied. Among the morphologic variables analyzed, only hypoplasia/atresia of the proximal pulmonary arteries correlated with the deletion (p = 0.03). Among patients with a double arch, the frequency of chromosome 22q11 deletion was higher in those with an atretic minor arch than it was in those with a patent minor arch (p = 0.02). CONCLUSIONS: Chromosome 22q11 deletion is associated with isolated anomalies of laterality or branching of the aortic arch in 24% of cases in our series. These findings should alert the clinician to consider deletion screening in patients with isolated anomalies of the aortic arch.

Distribution of lipid deposits around aortic branches of mice lacking LDL receptors and apolipoprotein E.

Mice with inactivated genes are increasingly used as models of human atherosclerosis. The aim of the present study was to determine whether the characteristic age-related distributions of lipid deposition seen around human arterial branches are replicated in such mice. Lesions occur downstream of branch ostia in immature human aortas, but these regions are spared in adult vessels, with lesions occurring more frequently at the sides or upstream of the branches. We determined the pattern of lipid staining around 102 intercostal branch ostia from apolipoprotein E/low density lipoprotein receptor double-knockout mice aged 9 to 20 weeks by using en face microscopy and a frequency-mapping technique. Lesion prevalence was high in the ostium and the region immediately surrounding it. Frequencies were 2.12+/-0.30 (mean+/-SEM, n=11) times higher upstream than downstream (P<0.01), but the pattern did not resemble the adult human pattern: there were no peaks in frequency at the sides or upstream of the branch, and there was no sparing downstream. Furthermore, a patch of sparing upstream of the branch was seen, which has not been reported for human vessels, and there was no trend toward a more upstream pattern with age. We conclude that knockout mice may not be a suitable model in which to investigate localizing factors.

The metabolic and respiratory alterations of heat stroke.

The metabolic and respiratory changes of 21 patients with heat stroke were studied. Admission arterial blood gas levels were measured, and serum bicarbonate, lactate, calcium, phosphorus, and anion gap determinations were performed. Seven patients had a metabolic acidosis (pH 7.20 +/- 0.04, PCO2 32 +/- 2 mm Hg, and bicarbonate 12 +/- 1 mEq/L), seven a combined metabolic acidosis and respiratory alkalosis (pH 7.39 +/- 0.01, PCO2 25 +/- 1 mm Hg, and bicarbonate 15 +/- 1 mEq/L), four a respiratory alkalosis (pH 7.45 +/- 0.01, PCO2 30 +/- 1 mm Hg, and bicarbonate 20 +/- 1 mEq/L), one a metabolic and respiratory acidosis (pH 7.13, PCO2 52 mm Hg, and bicarbonate 17 mEq/L), and one a respiratory acidosis (pH 7.30, PCO2 56 MM Hg, and bicarbonate 27 mEq/L). The 15 patients with a metabolic acidosis had a pH of 7.28 +/- 0.03, PCO2 of 30 +/- 2 mm Hg, bicarbonate level of 14 +/- 1 mEq/L, lactate concentration of 6.5 +/- 1.0 mEq/L, and an anion gap of 26 +/- 4 mEq/L. Nine patients were hypocalcemic (7.8 +/- 0.3 mg/dL), and five patients were hypophosphatemic (2.0 +/- 0.2 mg/dL). The predominant metabolic change in heat stroke is a metabolic acidosis secondary to increased lactate content and/or a respiratory alkalosis. Hypocalcemia is common and hypophosphatemia is not infrequent.