Lower body negative pressure reduces jugular and portal vein volumes and counteracts the elevation of middle cerebral vein velocity during long-duration spaceflight.

Cephalad fluid shifts in space have been hypothesized to cause the spaceflight-associated neuro-ocular syndrome (SANS) by increasing the intracranial-ocular translaminal pressure gradient. Lower body negative pressure (LBNP) can be used to shift upper-body blood and other fluids toward the legs during spaceflight. We hypothesized that microgravity would increase jugular vein volume (JVvol), portal vein cross-sectional area (PV), and intracranial venous blood velocity (MCV) and that LBNP application would return these variables toward preflight levels. Data were collected from 14 subjects (11 males) before and during long-duration International Space Station (ISS) spaceflights. Ultrasound measures of JVvol, PV, and MCV were acquired while seated and supine before flight and early during spaceflight at day 45 (FD45) and late at day 150 (FD150) with and without LBNP. JVvol increased from preflight supine and seated postures (46 ± 48% and 646 ± 595% on FD45 and 43 ± 43% and 702 ± 631% on FD150, P < 0.05), MCV increased from preflight supine (44 ± 31% on FD45 and 115 ± 116% on FD150, P < 0.05), and PV increased from preflight supine and seated (51 ± 56% on FD45 and 100 ± 74% on FD150, P < 0.05). Inflight LBNP of -25 mmHg restored JVvol and MCV to preflight supine level and PV to preflight seated level. Elevated JVvol confirms the sustained neck-head blood engorgement inflight, whereas increased PV area supports the fluid shift at the splanchnic level. Also, MCV increased potentially due to reduced lumen diameter. LBNP, returning variables to preflight levels, may be an effective countermeasure.NEW & NOTEWORTHY Microgravity-induced fluid shifts markedly enlarge jugular and portal veins and increase cerebral vein velocity. These findings demonstrate a marked flow engorgement at neck and splanchnic levels and may suggest compression of the cerebral veins by the brain tissue in space. LBNP (-25 mmHg for 30 min) returns these changes to preflight levels and, thus, reduces the associated flow and tissue disturbances.

Calcium blockade reduces renal apoptosis during ischemia reperfusion.

Apoptosis is well described in invertebrates and recently documented in mammals. The prevalence and pathophysiology of mammalian apoptosis is unknown and may have clinical ramifications. The aim of this study is to investigate the apoptotic response during kidney ischemia-reperfusion (I/R) injury. Kidney I/R was initiated in anesthetized rats by occlusion of the renal pedicle for 45 min with or without pretreatment with .2 mg/kg verapamil: control animals received sham exposure. Flow was re-established after ischemia and the animals were allowed to recover for 24 h. Bilateral kidneys were harvested for DNA electrophoresis, Western analysis for p53, Northern analysis for c-myc expression, and light and electron microscopic analysis. Kidney I/R caused characteristic DNA laddering in the clamped kidney, and less extensive laddering was seen in the contralateral kidney. Light and electron microscopic analysis confirmed apoptotic morphology in the reperfused tissues. Verapamil pretreatment completely abolished DNA laddering and attenuated the microscopic evidence of apoptosis. p53 levels were increased by I/R in the ischemic kidney and moderately increased in the contralateral organ. c-myc mRNA levels were increased by the I/R insult. Kidney I/R injury may induce global apoptosis, which seems to be associated with an alteration in calcium homeostasis. The increase in p53 and c-myc mRNA levels seen with I/R may facilitate apoptosis. Calcium modulation seems to reduce apoptosis during I/R and may have therapeutic implications.

Triiodothyronine treatment maintains surfactant synthesis during sepsis.

BACKGROUND: Pulmonary compromise with altered surfactant metabolism is frequently noted during sepsis; triiodothyronine is necessary for normal surfactant synthesis. We evaluated the role of physiologic replacement of triiodothyronine during sepsis-induced hypothyroidism on surfactant synthesis and lung structural integrity. METHODS: Male Sprague Dawley rats (average weight, 330 gm) underwent sham laparotomy or cecal ligation and puncture; treatment was administered to rats that underwent cecal ligation and puncture by Alzet osmotic pump consisting of triiodothyronine (3 ng/hr) or saline control. The rats were killed 24 hours after serum triiodothyronine determination by radioimmunoassay (normal, 60 to 160 ng/dl). Surfactant was obtained by saline lavage. Lipid content was determined by Folch extraction; phospholipid content was verified by chromatography. Blinded histologic analysis of lung confluence and alveolar sparing was done in separate subgroups. Results are +/- SE. RESULTS: Control rats with sepsis were hypothyroid at 24 hours; rats given triiodothyronine were euthyroid (rats that underwent sham laparotomy, 67.7 +/- 4.9 ng/dl; control rats, 37.6 +/- 5.7 ng/dl; and triiodothyronine, 85.7 +/- 19 ng/dl; p less than 0.05 compared with triiodothyronine by analysis of variance). Surfactant production was significantly improved by triiodothyronine compared with control (60.7 +/- 22.6 mg vs 23.2 +/- 11.3 mg; p less than 0.05 by analysis of variance). Lung histologic integrity was maintained by triiodothyronine treatment during sepsis. CONCLUSIONS: Triiodothyronine supplementation may be beneficial in septic-induced pulmonary dysfunction.

Effect of hypertonic saline solution and dextran on ventricular blood flow and heart-lung interaction after hemorrhagic shock.

BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects in the resuscitation of hemorrhagic shock. The effects on cardiac function and potential interaction with lung function are controversial and served as the basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5% NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock, and after resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time (dP/dt) were used to index contractility. Regional myocardial blood flow was determined with microspheres. Lung water was determined gravimetrically. RESULTS: There were no differences in the ability to restore hemodynamic parameters with equivalent sodium loads of LR and HSD resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time were only transiently affected by shock and resuscitation. Regional myocardial blood flow was increased above baseline values after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally effective in the early resuscitation of hemorrhagic shock, this occurred at the expense of significantly greater volume requirements for resuscitation with LR. This may contribute to cardiac dysfunction in this setting. Enhanced regional myocardial blood flow after HSD resuscitation may be beneficial against ongoing myocardial stress.

Gallbladder and biliary tract candidiasis.

BACKGROUND: The clinical significance of Candida spp isolated from the gallbladder on the biliary tract is relatively unknown. METHODS: To provide this information, patients with Candida spp isolated from gallbladder and other biliary tract sources during a 10-year period were identified through the records of our clinical microbiology laboratory. Medical records were analyzed for biliary disease causes, culture data, treatment, and outcome. RESULTS: Twenty-seven patients were identified. Five of seven patients with cholecystitis were critically ill intensive care unit (ICU) patients in whom the mortality rate was 100%. Gallstone pancreatitis was found in four patients and was fatal in one patient with a pancreatic abscess and ongoing retroperitoneal sepsis. An external biliary shunt/endoprosthesis was placed in 16 patients to relieve biliary obstruction. Cholangitis was present in 14 patients, and most bile cultures contained Candida as part of a mixed flora. Only 3 of 27 patients had candidemia, and 22 of 27 patients were colonized with Candida at other sites. CONCLUSIONS: (1) The ICU patient with Candida cholecystitis has a grave prognosis. (2) Patients with Candida isolated from biliary stents placed for obstruction and cholangitis should be treated with both antifungal and broad spectrum antimicrobial agents. (3) Candidemia is not frequently seen in this setting.

Effect of triiodothyronine augmentation on rat lung surfactant phospholipids during sepsis.

Surfactant functional effectiveness is dependent on phospholipid compositional integrity; sepsis decreases this through an undefined mechanism. Sepsis-induced hypothyroidism is commensurate and may be related. This study examines the effect of 3,3',5-triiodo-L-thyronine (T3) supplementation on surfactant composition and function during sepsis. Male Sprague-Dawley rats underwent sham laparotomy (Sham) or cecal ligation and puncture (CLP) with or without T3 supplementation [CLP/T3 (3 ng/h)]. After 6, 12, or 24 h, surfactant was obtained by lavage. Function was assessed by a pulsating bubble surfactometer and in vivo compliance studies. Sepsis produced a decrease in surfactant phosphatidylglycerol and phosphatidic acid, with an increase in lesser surface-active lipids phosphatidylserine and phosphatidylinositol. Phosphatidylcholine content was not significantly changed. Sepsis caused an alteration in the fatty acid composition and an increase in saturation in most phospholipids. Hormonal replacement attenuated these changes. Lung compliance and surfactant adsorption were reduced by sepsis and maintained by T3 treatment. Thyroid hormone may have an active role in lung functional preservation through maintenance of surfactant homeostasis during sepsis.

Impact of trauma stress ulcer prophylaxis guidelines on drug cost and frequency of major gastrointestinal bleeding.

Trauma patients are routinely prescribed stress ulcer prophylaxis despite evidence suggesting such therapy be limited to patients with identifiable risk factors for bleeding. With surgeons' consensus, we developed and implemented trauma stress ulcer prophylaxis guidelines, and measured the impact of clinical pharmacists on implementing the guidelines and the effect of the guidelines on drug cost and frequency of major gastrointestinal bleeding. Two groups of 150 consecutive patients admitted with multiple trauma were evaluated before and after guideline implementation and stratified by Injury Severity Score (ISS) to minor (ISS < 9) or moderate to severe (ISS > or = 9) trauma groups. The number of patients prescribed stress ulcer prophylaxis, length and cost of this therapy, and number of patients experiencing major gastrointestinal bleeding (decrease in consecutive hemoglobin > or = 2 g/dl in conjunction with coffee-ground emesis, hematemesis, melena, or hematochezia) were measured. All pharmacist interventions pertaining to stress prophylaxis were collected. Fewer patients were prescribed stress ulcer prophylaxis after guideline implementation (105/150, 70% vs 39/150, 26%, p<0.0001), leading to a decrease in total drug cost of $4558. Use decreased more in patients with minor (40/54, 74% vs 9/59, 15%, p<0.0001) than moderate to severe (65/96, 68% vs 30/91, 33%, p<0.0001) trauma. Neither length of therapy nor agent of choice (> 95% cimetidine) differed between groups. Fifteen (38%) of 38 postguideline prophylaxis orders were determined by the pharmacist not to meet guideline criteria. Recommendations to discontinue therapy were accepted in 9 (60%) of 15 instances. The frequency of major gastrointestinal bleeding remained unchanged between groups (1/150 vs 0/150, p=1.0). Implementation of trauma stress ulcer prophylaxis guidelines limiting therapy to patients with risk factors for bleeding led to a 80% decrease in drug cost and did not affect the frequency of major gastrointestinal bleeding.

Endoscopic surgery in weightlessness: the investigation of basic principles for surgery in space.

BACKGROUND: Performing a surgical procedure in weightlessness, also called 0-gravity (0-g), has been shown to be no more difficult than in a 1-g environment if the requirements for the restraint of the patient, operator, surgical hardware, are observed. The performance of laparoscopic and thorascopic procedures in weightlessness, if feasible, would offer several advantages over the performance of an open operation. Concerns about the feasibility of performing minimally invasive procedures in weightlessness have included impaired visualization from the absence of gravitational retraction of the bowel (laparoscopy) or thoracic organs (thoracoscopy) as well as obstruction and interference from floating debris such as blood, pus, and irrigation fluid. The purpose of this study was to determine the feasibility of performing laparoscopic and thorascopic procedures and the degree of impaired surgical endoscopic visualization in weightlessness. METHODS: From 1993 to 2000, laparoscopic and thorascopic procedures were performed on 10 anesthetized adult pigs weighing approximately 50 kg in the National Aeronautics and Space Administration (NASA) Microgravity Program using a modified KC-135 airplane. The parabolic simulation system for advanced life support was used in this project, and 20 to 40 parabolas were used for laparoscopic or thorascopic investigation, each containing approximately 30 s of 0-g alternating with 2-g pullouts. The animal model was restrained in the supine position on a floor-level Crew Medical Restraint System, and the abdominal cavity was insufflated with carbon dioxide. The intraabdominal and intrathoracic anatomy was visualized in the 1-g, 0-g, and 2-g periods of parabolic flight. Bleeding was created in the animals, and the behavior of the blood in the abdominal and thoracic cavities was observed. In the thoracic cavity, gas insufflation and mechanical retraction was used at times unilaterally to decrease pulmonary ventilation enough to increase the thoracic domain. RESULTS: Visualization was improved in laparoscopy, from tethering of the bowel by the elastic mesentery, and from the strong tendency for debris and blood to adhere to the abdominal wall because of surface tension forces. The lack of adequate thoracic domain made thorascopy more difficult. Fluid in the thoracic cavity did not impair visualization because the fluid at 0-g does not loculate posteriorly, but disperses along the thoracic wall and mediastinal reflections. CONCLUSIONS: Performing minimally invasive procedures instead of open surgical procedures in a weightless environment has theoretical advantages, especially in the ability to prevent cabin atmosphere contamination from surgical fluids (blood, pus, irrigation). Visualization will become more important and practical as the endoscopic hardware is miniaturized from its current form, as endoscopic technology becomes more advanced, and as more surgically capable medical crew officers are present in future long-duration space exploration missions.

Peripheral vascular cutdown.

Critically ill patients who are not candidates for percutaneously placed arterial and venous lines require surgical cutdown. Although significant complications may arise from inadvertent injury to the vessel or associated structures during arterial and venous cutdown, these complications can be minimized by meticulous technique. With attention to site selection and catheter care, the useful life of these complex catheters approaches that of percutaneously placed devices. Finally, although the sequelae of placement by these techniques--including wound and catheter infection, distal ischemia, and vessel ligation--are increased, the need for appropriate intravascular access in these patients far outweighs the potential risks.

Problems with 20 or more blood transfusions in 24 hours.

The case records of 128 patients receiving 129 transfusions of 20 or more units of blood within a 24-hour period at Detroit Receiving Hospital, between August 1980 and August 1985, were reviewed. In patients receiving 20 to 49 units of blood, without pre-existing disease or prolonged shock, the mortality rate was 36 per cent (15/42). In similar patients who had prolonged shock, the mortality rate was 61 per cent (27/44). If the patient had pre-existing disease and prolonged shock, the mortality rate with 20 to 49 units of blood was 92 per cent (12/13). All 13 patients receiving 50 or more units of blood died. Platelet counts were less than 50,000/microL in 50 per cent (51/102). The prothrombin time (PT) was prolonged by 5 or more seconds in 54 per cent (51/92). The partial thromboplastin time (PTT) was prolonged to more than 60 seconds in 45 per cent (42/94). There was no correlation between the PT, PTT, and amount of fresh frozen plasma (FFP) given. A coagulopathy was diagnosed clinically in 43 patients, but this did not correlate well with laboratory coagulation studies. The average core temperature of the patients was 32.9 +/- 1.7 C. Severe hypocalcemia with total calcium levels less than 6.0 mg/dL was found in 53 per cent (33/62). Ionized calcium levels Ca++ were less than 0.70 mmol/L in 56 per cent (24/43). Of the 82 deaths, 32 (38%) occurred in the operating room and 31 (38%) occurred within 48 hours from continued bleeding and/or shock. Twelve deaths (15%), from severe infections, occurred after 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Inflammatory complications following penetrating cardiac trauma.

Two cases with pericardial and myocardial inflammatory complications following penetrating cardiac trauma are presented. A high index of suspicion with liberal usage of echocardiography, serial electrocardiograms, and careful patient follow-up will preclude this diagnostic oversight.

Fibrin gel limits intra-abdominal adhesion formation.

Autologous fibrin gel (FG) has recently been reported efficacious in hepatic injury; the effects of fibrin compounds on intra-abdominal adhesion formation is controversial. This study evaluated intra-abdominal adhesion formation in a rabbit devascularization model. Seventeen New Zealand rabbits were anesthetized and laparotomy was done. The uterine horns were abraded to punctate bleeding followed by bilateral uterine devascularization. Treatment consisted of 10 cc saline control (c) or FG applied to the uterine horns. Peritoneal lavage was done at 15 minutes for red blood cell (RBC) analysis. Autopsy was performed at 1 week. Adhesions were graded from grade 0 (no adhesions) to grade III (dense adhesions). Adhesion grading revealed no difference in average adhesion grade between FG and C with small bowel (1.0 +/- 1.3 vs 0.5 +/- 1.0); bladder (2.1 +/- 1.1 vs 2.4 +/- 1.2); or uterus (1.2 +/- vs 2.0 +/- 1.2). Adhesion grade was significantly less in FG compared to C for the colon and the abdominal incision (0.4 +/- 0.5 vs 1.7 +/- 1.1 and 1.2 +/- 1.1 vs 3.0 +/- 1.2; P less than 0.05 by t-test). There were no differences in lavage RBC count between FG and C (13.1 x 106 +/- 4.1 x 10(6) vs 8.7 x 106 +/- 3.2 x 10(6)). Fibrin gel significantly decreased incisional and colonic adhesions and reduced other abdominal adhesion formation by a nonhemostatic dependent mechanism.

Nonoperative management of gunshot wounds of the abdomen.

Nonoperative management of stab wounds of the abdomen is currently practiced in many trauma centers; this report examines the role of expectant management of gunshot wounds to the abdomen in a select patient population. Patients presenting to a single trauma service from 5/91 to 1/94 at Detroit Receiving Hospital with a gunshot wound (GSW) to the abdomen fulfilling the following criteria were observed: 1) single GSW to the right upper quadrant, 2) stable vital signs, 3) reliable examination with minimal abdominal tenderness and available team/operating room, and 4) minimal or no abdominal tenderness. There were 12 patients fulfilling the study criteria; all were successfully observed. One nontherapeutic laparotomy was done due to abdominal tenderness. The role of expectant therapy of abdominal gunshot wounds is cautiously advanced. With appropriate criteria, this technique appears safe and efficacious.

Hypertonic saline/dextran improves septic myocardial performance.

An isolated perfused heart preparation was used to determine the effects of hypertonic saline dextran on contractile performance in both control and septic animals. Myocardial performance was assessed by developed pressure (DP), maximal rate of tension development (dp/dtmax) and relaxation (-dp/dt). Coronary flow rate was measured and myocardial oxygen consumption (MVO2) determined in the septic preparations. The hypertonic perfusate had negligible effects on contraction and relaxation in the control group. In the septic group, perfusion with the hypertonic solution improved myocardial contractility to 150 per cent of baseline DP and +dp/dt and 134 per cent of baseline -dp/dt. These improvements in myocardial performance were unrelated to changes in coronary flow or MVO2.

Splanchnic mucosal perfusion effects of hypertonic versus isotonic resuscitation of hemorrhagic shock.

A porcine hemorrhagic shock (HS) model was used to assess the splanchnic mucosal and systemic effects of hypertonic versus isotonic crystalloid resuscitation. Animals were bled to a mean arterial pressure of 40 mm Hg for 1 hour and then resuscitated with equivalent sodium loads of LR, 7.5 per cent hypertonic saline (HSS), or 7.5 per cent HSS with 6 per cent Dextran (HSD). Intestinal mucosal blood flow (IMBF) was measured by a laser Doppler flow probe placed on the mucosa of the small bowel. Following resuscitation the cardiac output (CO) (relative to baseline values) was significantly higher with HSD (158 17 per cent) and HSS (137 24 per cent) than with LR (84 27 per cent) (P < 0.005). There was prompt restoration of IMBF with both HSD (126 31 per cent) and HSS (106 22 per cent) (vs baseline). Resuscitation with LR was associated with a persistent reduction in IMBF (52 16 per cent) despite restoration of mean arterial pressure and cardiac output to baseline levels (P < 0.05). Thus, hypertonic saline solutions may serve an adjunctive role in the resuscitation of hemorrhagic shock by restoring intestinal nutrient blood flow and, thereby, preventing gut barrier impairment, bacterial translocation, and organ failure.

Hemorrhagic shock impairs mucosal immunity to gut-derived antigens.

Secretory immunoglobulin A (sIgA) is the principal antibody protecting against pathogens in the respiratory tract and other mucosal surfaces. Nosocomial pneumonias are frequent after injury and critical illness and are often due to enteric pathogens. The aim of this study was to assess the relative effect of hemorrhagic shock (HS) on mucosal immunity at intestinal and respiratory mucosal sites. Fisher rats were immunized intragastrically with dinitrophenylated (DNP) Pneumococcus (Pn). Three weeks later, animals were subjected to sham treatment or HS. The animals were then rechallenged with DNP-Pn 1 or 3 days later. Animals were sacrificed 7 days later, and bronchoalveolar and gastric lavage was performed. Total and anti-DNP-specific sIgA were quantitated from these secretions by enzyme-linked immunosorbent assay. There was a significant decrease in DNP-Pn-specific sIgA at 72 hours after HS, which was not present in animals at 24 hours after HS. This was most profound in bronchoalveolar lavage specimens. We conclude that impaired mucosal defense against gut-derived antigens after HS may be important mechanistically for the development of posttraumatic pneumonia and other mucosally related infectious complications.

Electrolyte and acid-base changes with massive blood transfusions.

The case records of 471 patients with massive transfusions of ten or more units of bank blood within 24 hours were reviewed to analyze the electrolyte and acid-base changes. The patients who lived had a less severe acidosis (7.23 +/- 0.15 vs 7.11 +/- 0.17) and the HCO3 was higher (19.8 +/- 15.2 vs 13.4 +/- 6.8) (P less than 0.001). The mean anion gap, despite the low HCO3, was 11.8 +/- 7.8 mEq/L. A combined metabolic and respiratory acidosis, often following bicarbonate therapy, was fetal in 83 per cent (39/47). Serum potassium values (K) were high in 22 per cent and low in 18 per cent of patients. If potassium levels were "corrected" by subtracting 0.5 mEq/L for each 0.1 pH of metabolic acidosis, only 5 per cent of patients were hyperkalemic. Patients dying within 48 hours of the massive transfusions had higher potassium levels (4.9 +/- 1.1 vs 4.4 +/- 0.9; P less than 0.001). Ionized calcium levels (Ca++) were less than normal (1.13-1.32 mmol/L) in 94 per cent of patients and were very low (less than 0.70 mmol/L) in 46 per cent (108/234). The mortality rate with severe ionic hypocalcemia was 71 per cent (vs 40% in patients with more normal values); P less than 0.0001. pH, PCO2, K, and Ca++ must be followed closely with massive transfusions. Rapid correction of volume and pH, without overcorrection, is essential.

Detection of surgical glove integrity.

Surgical glove integrity is essential for universal precautions; glove safety is verified by the water load test (WLT). Concerns regarding glove injury have prompted newer testing methodologies, including electrical conductance testing (ECT); however, the sensitivities of these tests are not known. We compared the sensitivity of WLT and ECT in detecting glove needle-stick injury in two commonly used brands of surgical gloves. Punctures were made with hollow-bore and solid surgical needles of various configurations. The WLT failed to detect glove holes from the smallest-caliber needles and only detected the injury in 60 per cent for the largest caliber. The ECT provided a graded index of glove injury in all holes made by both solid surgical needles and hollow-bore needles. The WLT is a poor test for clinical defects in latex surgical gloves; the ECT is significantly more sensitive and provides a gauge of the cross-sectional area of the defect. Interbrand differences in self-sealing properties of surgical gloves were evidenced and may be clinically relevant after glove perforation.

Ultrasound evaluation of the magnitude of pneumothorax: a new concept.

Pneumothorax is commonly seen in trauma patients; the diagnosis is confirmed by radiography. The use of ultrasound where radiographic capabilities are absent, is being investigated by the National Aeronautics and Space Administration. We investigated the ability of ultrasound to assess the magnitude of pneumothorax in a porcine model. Sonography was performed on anesthetized pigs in both ground-based laboratory (n = 5) and microgravity conditions (0 x g) aboard the KC-135 aircraft during parabolic flight (n = 4). Aliquots of air (50-100 cm3) were introduced into the chest to simulate pneumothorax. Results were videorecorded and digitized for later interpretation. Several distinct sonographic patterns of partial lung sliding were noted including the combination of a sliding zone with a still zone and a "segmented" sliding zone. These "partial lung sliding" patterns exclude massive pneumothorax manifested by a complete separation of the lung from the parietal pleura. In 0 x g, the sonographic picture is more diverse; one x g differences between posterior and anterior aspects are diminished. Modest pneumothorax can be inferred by the ultrasound sign of "partial lung sliding." This finding, which increases the negative predictive value of thoracic ultrasound, may be attributed to intermittent pleural contact, small air spaces, or alterations in pleural lubricant. Further studies of these phenomena are warranted.

Effect of Maharishi AK-4 on H2O2-induced oxidative stress in isolated rat hearts.

Oxidative damage to crucial biomolecules due to excess generation of reactive oxygen species has been implicated as a major cause of organ damage and hence compounds capable of negating such damage have potential benefits. Using hydrogen peroxide (H2O2) as a model pro-oxidant to induce oxidative stress, we have examined the ability of natural food supplement Maharishi Amrit Kalash (MAK-4) to decrease oxidative damage in potassium-arrested isolated rat hearts. The protocol was that hearts isolated from male Sprague-Dawley rats were retrograde-perfused with Krebs-Henseleit (K-H) solution for 30 min for equilibration. After this period, the hearts were subjected to cardioplegia with high potassium (26-30 mM), followed by reperfusion with K-H solution in the presence or absence of 200 microM H2O2. As expected, H2O2 treatment following cardioplegia induced a high degree of oxidative stress as assessed by release of lactate dehydrogenase (LDH, a marker of plasma membrane damage) and total glutathione (GSH + GSSG). H2O2 also impaired the ability of heart to regain developed tension during the testing period. However, addition of MAK-4 in the perfusate containing H2O2 decreased oxidative stress in terms of release of LDH and glutathione. In parallel with these biochemical studies, in a few experiments the cardiac function was assessed by measuring developed contractile tension. These preliminary studies also showed that in the presence of MAK-4 the H2O2-treated hearts were able to regain better developed tension. Further in vitro studies to examine the possible mechanisms of MAK-4 action reveal that this formulation contains H2O2 binding activity which resulted in the decreased availability of H2O2 itself. Our studies hence reveal that the ayurvedic food supplement MAK-4 may have potential benefits in reducing oxidative stress.