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Here, we assessed the efficacy of a short-course multimodal therapy (enrofloxacin, azithromycin, fenbendazole, and paromomycin) to eliminate common macaque endemic pathogens (EPs) and evaluated its impact on gastrointestinal (GI) microbiota, mucosal integrity, and local and systemic inflammation in sixteen clinically healthy macaques. Treatment combined with expanded practices resulted in successful maintenance of rhesus macaques (RM) free of common EPs, with no evidence of overt microbiota diversity loss or dysbiosis and instead resulted in a more defined luminal microbiota across study subjects. Creation of a GI pathogen free (GPF) status resulted in improved colonic mucosal barrier function (histologically, reduced colonic MPO+, and reduced pan-bacterial 16s rRNA in the MLN), reduced local and systemic innate and adaptive inflammation with reduction of colonic Mx1 and pSTAT1, decreased intermediate (CD14+CD16+) and non-classical monocytes (CD14-CD16+), reduced populations of peripheral dendritic cells, Ki-67+ and CD38+ CD4+ T cells, Ki-67+IgG+, and Ki-67+IgD+ B cells indicating lower levels of background inflammation in the distal descending colon, draining mesenteric lymph nodes, and systemically in peripheral blood, spleen, and axillary lymph nodes. A more controlled rate of viral acquisition resulted when untreated and treated macaques were challenged by low dose intrarectal SIVmac239x, with an ~100 fold increase in dose required to infect 50% (AID50) of the animals receiving treatment compared to untreated controls. Reduction in and increased consistency of number of transmitted founder variants resulting from challenge seen in the proof of concept study directly correlated with post-treatment GPF animal's improved barrier function and reduction of key target cell populations (Ki-67+ CD4+T cells) at the site of viral acquisition in the follow up study. These data demonstrate that a therapeutic and operational strategy can successfully eliminate varying background levels of EPs and their associated aberrant immunomodulatory effects within a captive macaque cohort, leading to a more consistent, better defined and reproducible research model., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To explore the relationship between in-hospital mortality following adult cardiac surgery and the time since primary clinical qualification for the responsible consultant cardiac surgeon (a proxy for experience)., Design: Retrospective analysis of prospectively collected national registry data over a 10-year period using mixed-effects multiple logistic regression modelling. Surgeon experience was defined as the time between the date of surgery and award of primary clinical qualification., Setting: UK National Health Service hospitals performing cardiac surgery between January 2003 and December 2012., Participants: All patients undergoing coronary artery bypass grafts and/or valve surgery under the care of a consultant cardiac surgeon., Main Outcome Measures: All-cause in-hospital mortality., Results: A total of 292,973 operations performed by 273 consultant surgeons (with lengths of service from 11.2 to 42.0 years) were included. Crude mortality increased approximately linearly until 33 years service, before decreasing. After adjusting for case-mix and year of surgery, there remained a statistically significant (p=0.002) association between length of service and in-hospital mortality (odds ratio 1.013; 95% CI 1.005-1.021 for each year of 'experience')., Conclusions: Consultant cardiac surgeons take on increasingly complex surgery as they gain experience. With this progression, the incidence of adverse outcomes is expected to increase, as is demonstrated in this study. After adjusting for case-mix using the EuroSCORE, we observed an increased risk of mortality in patients operated on by longer serving surgeons. This finding may reflect under-adjustment for risk, unmeasured confounding or a real association. Further research into outcomes over the time course of surgeon's careers is required., (© The Royal Society of Medicine.)

Feeding 56 versus 0 g/d of Saccharomyces cerevisiae fermentation product (SCFP; Diamond V Original XP; Diamond V, Cedar Rapids, IA) can increase feed intake and milk production in transition dairy cows. To evaluate the effects of various dosages of SCFP, Holstein cows were given individually a supplement containing 0 (n=14), 56 (n=15), or 112 g (n=13) of SCFP daily during morning lockup as a topdressing to their total mixed ration. The supplement consisted of 0, 56, or 112 g of SCFP mixed with 84 g of molasses and 168, 112, or 56 g of corn meal, respectively. Supplement feeding began 28 d before predicted calving date (no less than 14 d) and ended 28 d postpartum, and supplement intake was evaluated daily. Blood samples were collected at d -21, -14, -7, -3, -1, 0, 1, 3, 7, 14, 21, and 28 to measure serum concentrations of macrominerals, metabolites, acute-phase proteins, immunoglobulin, and hormones. Milk weights were measured and milk samples were collected 2 times/wk on nonconsecutive days and analyzed for milk fat, protein, lactose, and somatic cell count (SCC). During the first day after calving, feeding SCFP versus no SCFP decreased serum cortisol concentrations and at least tended to increase supplement intake and serum concentrations of calcium, glucose, urea N, and serum amyloid A. During the first 4 wk postpartum, feeding SCFP versus no SCFP decreased milk SCC and increased milk production and serum phosphorus concentrations. Feeding 112 versus 56 g of SCFP/d did not show additional effects. Feeding SCFP may have a dosage-independent beneficial effect in supporting the physiologic adaptations after parturition, resulting in higher milk production and lower milk SCC., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

We report what is believed to be the first case of late-onset prosthetic valve endocarditis caused by Mycoplasma hominis in a case of blood culture-negative endocarditis. The objective of this report is to emphasize the use of a broad-range PCR technique for bacterial 16S rRNA genes in identifying the causative pathogen, thus enabling targeted antimicrobial treatment.

Stromal interaction molecule 1 (STIM1) is a predicted single membrane-spanning protein involved in store-operated calcium entry and interacting with ion channels including TRPC1. Here, we focus on endogenous STIM1 of modulated vascular smooth muscle cells, which exhibited a nonselective cationic current in response to store depletion despite strong buffering of intracellular calcium at the physiological concentration. STIM1 mRNA and protein were detected and suppressed by specific short interfering RNA. Calcium entry evoked by store depletion was partially inhibited by STIM1 short interfering RNA, whereas calcium release was unaffected. STIM1 short interfering RNA suppressed cell migration but not proliferation. Antibody that specifically bound STIM1 revealed constitutive extracellular N terminus of STIM1 and extracellular application of the antibody caused fast inhibition of the current evoked by store depletion. The antibody also inhibited calcium entry and cell migration but not proliferation. STIM1 interacted with TRPC1, and TRPC1 contributed partially to calcium entry and cationic current. However, the underlying processes could not be explained only by a STIM1-TRPC1 partnership because extracellular TRPC1 antibody suppressed cationic current only in a fraction of cells, TRPC1-containing channels were important for cell proliferation as well as migration, and cell surface localization studies revealed TRPC1 alone, as well as with STIM1. The data suggest a complex situation in which there is not only plasma membrane-spanning STIM1 that is important for cell migration and TRPC1-independent store-operated cationic current but also TRPC1-STIM1 interaction, a TRPC1-dependent component of store-operated current, and STIM1-independent TRPC1 linked to cell proliferation.

Radio-labeled red cell perfusion scan of the non-donor/donor forearm/hand was undertaken, 1- and 5-years post operation, in 12 patients who had received a radial artery graft during myocardial revascularisation. Results were analysed using a Wilcoxon Signed Rank test (P-value <0.05 was taken as statistically significant). Mean tissue perfusion (in milliliters/100 ml tissue/min) declined in the non-donor (-10.06%, P=0.07) and donor (-6.65%, P=0.15) forearm, respectively, compared to 1 year post radial artery harvest. The statistically significant observed difference in tissue perfusion between the non-donor (21.9+/-5.1) and donor (17.5+/-3.7) forearm (P=0.0007) at 1 year was maintained at 5 years, non-donor and donor, 19.5+/-3.7 and 16.2+/-3.4 (P=0.001), respectively. The same pattern in tissue perfusion was observed in the non-donor/donor hand. This study demonstrates that, over time, there is little recovery in perfusion in the donor forearm/hand from ulnar artery collateral circulation. There is a significant and persistent difference in tissue perfusion between the non-donor/donor forearm/hand at 5 years post radial artery harvest. Although no functional deficit or overt ischaemic events were recorded, these findings may influence the choice of conduit and the information given when obtaining consent in patients undergoing myocardial revascularisation.

In a screen of potential lipid regulators of transient receptor potential (TRP) channels, we identified sphingosine-1-phosphate (S1P) as an activator of TRPC5. We explored the relevance to vascular biology because S1P is a key cardiovascular signaling molecule. TRPC5 is expressed in smooth muscle cells of human vein along with TRPC1, which forms a complex with TRPC5. Importantly, S1P also activates the TRPC5-TRPC1 heteromultimeric channel. Because TRPC channels are linked to neuronal growth cone extension, we considered a related concept for smooth muscle. We find S1P stimulates smooth muscle cell motility, and that this is inhibited by E3-targeted anti-TRPC5 antibody. Ion permeation involving TRPC5 is crucial because S1P-evoked motility is also suppressed by the channel blocker 2-aminoethoxydiphenyl borate or a TRPC5 ion-pore mutant. S1P acts on TRPC5 via two mechanisms, one extracellular and one intracellular, consistent with its bipolar signaling functions. The extracellular effect appears to have a primary role in S1P-evoked cell motility. The data suggest S1P sensing by TRPC5 calcium channel is a mechanism contributing to vascular smooth muscle adaptation.

Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure.

Background: Since 1999 our institution has adopted offpump coronary artery bypass grafting (OPCABG) for treating the majority of our patients. In the year 2001, 96% of our isolated coronary bypass procedures were performed on the beating heart. Routine use of intracoronary shunts in OPCABG has been a controversial topic. We use routine intracoronary shunting in all cases to maintain distal perfusion and to help achieve hemostasis., Methods: We reviewed the first 550 OPCABG procedures performed at our institution (July 1998-December 2001) by 2 surgeons currently performing >95% of all coronary bypasses off-pump. All cases were completed with routine intracoronary shunting using Flo-Coil (Guidant, Santa Clara, CA, USA) or Flo-Thru (Bio-Vascular, St Paul, MN, USA) shunts. The mean number of grafts was 3.7. (range, 1-8). In-hospital outcomes in this series of patients were compared to outcomes in 485 patients operated on by the same 2 surgeons using traditional cardiopulmonary bypass (CPB) and aortic cross-clamping prior to adopting routine OPCABG. Statistical significance was calculated using Pearson chisquare analysis and reported for P values of <.05., Results: The rates of occurrence of postoperative cardiovascular accident, atrial fibrillation, prolonged ventilator time, renal failure, and blood product use and the length of postoperative stay were significantly less in the off-pump group (P <.05). Predicted risk of mortality, observed mortality, and perioperative myocardial infarction rates were not significantly different in the 2 groups (P <.05). The conversion rate was 3.1%., Conclusion: We conclude that routine intracoronary shunting in OPCABG is a safe technique that is associated with good myocardial preservation and allows for total revascularization with a low rate of conversion to CPB.

There are many functions in an integrated delivery system charged with focused, clinical excellence and process improvement based on data. Information system complexity, enhanced technology and software, and increased demand for data have created the need for one healthcare organization to look at an alternative system for data support of these key functions. This article describes a clinical data department model that has been implemented successfully in an integrated delivery system. It describes the structure and function of this department and its relationship in supporting the areas where clinical data is needed.

1. Vasospasm of arterial conduits used for coronary artery surgery is an important cause of graft failure and is likely to result partly from raised levels of vasoconstrictor substances such as thromboxane A(2) and endothelin-1. Our aim was to find pharmacological agents that could prevent agonist-induced vasospasm. 2. Isometric tension was recorded from discarded segments of human left internal mammary artery (LIMA). Submaximal contraction evoked by the thromboxane A(2) mimetic U46619 (10 nM) was not inhibited by a blocker of store- and receptor-operated Ca(2+) channels (30 microM SKF96365) in the presence of diltiazem. Furthermore, contractions to < or =1 nM U46619 were preserved when extracellular Ca(2+) was reduced from 2.5 mM to 60 nM. Thus, sustained U46619-evoked contraction occurred without Ca(2+) influx. 3., We hypothesized that contraction might occur via Rho-kinase-mediated Ca(2+)-sensitization of myofilaments. Inhibitors of Rho-kinase (Y27632 and HA1077) were profound relaxants. If contraction was pre-evoked by 10 nM U46619, Y27632 and HA1077 caused full relaxation with EC(50)s of 1.67+/-0.22 microM and 3.58+/-0.35 microM respectively. Y27632 was also effective if applied before U46619, but was less potent. 4. Y27632 abolished contraction evoked by endothelin-1 and significantly reduced resting tone in the absence of a vasoconstrictor. 5. Rho-kinase-mediated Ca(2+)-sensitization appears to be a major mechanism of vasoconstriction in human LIMA. Rho-kinase inhibitors may have an important role in preventing vasospasm in arterial grafts used for coronary artery surgery.

Although Jehovah's Witnesses present a particular problem when undergoing surgery because of their refusal to accept stored blood, it is now quite common to undertake uncomplicated cardiac surgery in these patients. Complex or redo cardiac surgery however, is often associated with major blood loss, and is conventionally contraindicated in Jehovah's Witnesses. We describe the perioperative management of a Jehovah's Witness who underwent a resternotomy for mitral valve replacement and coronary artery bypass grafting having previously had an aortic valve replacement and mitral valve repair. The importance of a multidisciplinary approach to blood conservation is discussed.

A review of the management of isolated sternal fractures in a regional cardiothoracic unit reveals that, in a 2 year period, 37 consecutive patients were admitted for observation and further investigation, including echocardiography and cardiac enzyme measurements to exclude blunt cardiac injury. Minor blunt cardiac injury was detected in only one patient, and was associated with an acutely abnormal electrocardiogram (ECG). ECG showed acute changes in 8 further patients, whilst 3 patients had an abnormal chest X-ray (CXR) due to widening of the mediastinum (1 patient had abnormal CXR and ECG), but none had evidence of cardiac injury. CXR and ECG were both normal in 23 patients, and were predictive of the absence of significant complications. A survey of 22 other cardiothoracic units around the UK confirms that the management of patients with isolated sternal fractures varies considerably from hospital to hospital. As suggested by previous reports, we believe that patients, who are otherwise fit and have normal ECG and CXR on presentation, can be safely discharged home on oral analgesics. The routine use of echocardiography and creatinine kinase (CK) assays in the assessment of isolated sternal fractures is not indicated. The introduction of these guidelines has resulted in a dramatic reduction in the number of patients admitted with isolated sternal fractures to our unit.

A case is reported of a 59 year old woman who presented with palpitations. Electrocardiographic studies revealed atrial fibrillation and atrioventricular block. Echocardiography and magnetic resonance imaging showed a right atrial cystic mass attached to the interatrial septum. The patient underwent surgical excision of the mass. Histopathological findings were of a cystic tumour of the atrioventricular nodal region. This is the second report of this condition diagnosed antemortem and treated successfully with surgical excision.

Objective: The radial artery is becoming popular as a conduit for coronary artery surgery but there is concern about its tendency to vasospasm. Diltiazem is used clinically in an effort to prevent vasospasm but there are suggestions that it is relatively ineffective. The first aim of the study was to test the effectiveness of Ca(2+) antagonists against vasospasm evoked by vasoconstrictor agonists. Because a large component of vasospasm was resistant to Ca(2+) antagonists, the second aim was to test if a different class of vasodilator, nicorandil, might relax the residual tone., Methods: Isometric tension was recorded in human radial artery segments harvested from patients undergoing myocardial revascularization surgery., Results: Diltiazem at 10 microM, which strongly inhibits L-type voltage-gated Ca(2+) channels, induced partial relaxation (mean+/-SEM, 44.6+/-3.5%, n=31) of phenylephrine-evoked contraction, but only 14.0+/-4.1% (n=10) and 12. 2+/-4.2% (n=10) relaxation of U46619- (a thromboxane A(2) analogue) or endothelin-1-evoked contraction. Strikingly, nicorandil relaxed agonist-evoked contractions that were resistant to diltiazem or nicardipine. In the absence of a Ca(2+) antagonist, nicorandil (30 microM) evoked 74.1+/-5.6% (n=24), 36.8+/-9.3% (n=10) and 64.5+/-7. 9% (n=14) relaxation of phenylephrine-, U46619- and endothelin-1-evoked contractions., Conclusions: Nicorandil has a marked relaxant effect on contractions evoked by three different vasoconstrictor agonists, and relaxes vasospasm that is resistant to conventional Ca(2+) antagonists. These in vitro data suggest that nicorandil might be a useful drug for the inhibition of radial artery vasospasm in myocardial revascularization surgery.

Liver blood flow is reduced after cardiopulmonary bypass (CPB) and both dopamine and dopexamine are used to overcome this. This study compares the effects of these agents on liver blood flow. Thirty patients undergoing elective coronary artery bypass graft surgery were randomized into three groups (n = 10 per group). Six hours after surgery baseline liver blood flow was determined by the percentage disappearance rate of indocyanine green measured by dichromatic auricular densitometery. Patients then received infusions of either: (1) placebo (dextrose 5%); (2) dopamine (4 micrograms/kg/min); (3) dopexamine (1 microgram/kg/min increasing to 2 micrograms/kg/min). One hour after infusion, liver blood flow measurements were repeated. In the dopexamine group the infusion was increased and the measurements repeated another hour later. We found that patient-specific variables and operative details were similar for all groups. Postoperative cardiac index and heart rate were increased significantly by dopamine (cardiac index 2.82 +/- 0.46 l/m/m2 vs 3.28 +/- 0.67 l/m/m2: p < 0.001 and heart rate 87.5 +/- 13.2 vs 96 +/- 16: p < 0.05) and dopexamine at 2 micrograms/kg/min (cardiac index 2.71 +/- 0.53 l/m/m2 vs 3.45 +/- 0.67 l/m/m2: p < 0.05 and heart rate 89.0 +/- 18.9 vs 107.4 +/- 13.6: p < 0.001) compared to placebo (cardiac index 2.97 +/- 0.8 l/m/m2 vs 3.18 +/- 0.9 l/m/m2: p > 0.05 and heart rate 77.2 +/- 7.4 vs 77.3 +/- 8: p > 0.05) despite similar atrial and systemic arterial pressures. The disappearance rate of indocyanine green was not altered during infusion of placebo group (9.0 +/- 3.2%/min vs 7.9 +/- 3.0%/min: p > 0.05) or dopexamine at 1 microgram/kg/min (9.7 +/- 3.1%/min vs 11.2 +/- 4.1%/min: p > 0.05). The disappearance rate was increased with dopamine (6.7 +/- 3.7%/min vs 11.8 +/- 3.0%/min: p < 0.05) and dopexamine 2 micrograms/kg/min (9.7 +/- 3.1%/min vs 13.5 +/- 3.2%/min: p < 0.05). This indicates a 76% increase in liver blood flow with dopamine and a 38% increase with dopexamine. We conclude that dopamine 4 micrograms/kg/min and dopexamine 2 micrograms/kg/min increase liver blood flow, although this may, in part, be related to an increase in cardiac output. Dopexamine shows no advantage over dopamine in enhancing liver blood flow after CPB.

Cardiopulmonary bypass (CPB) involves the use of either an occlusive roller pump or centrifugal pump. Damage to blood elements, including haemolysis, may arise from occlusion when using a roller pump; the appropriate degree of occlusion has not yet been determined scientifically. Centrifugal and nonocclusive roller pumps are reputed to reduce haemolysis. The objective of this study was to compare haemolysis caused by a standard roller pump with a dynamically set nonocclusive roller pump and with a centrifugal pump. We prospectively randomized 60 patients undergoing routine coronary artery surgery into three groups: standard roller pump (STD, n = 20), dynamically set roller pump (DYN, n = 20), or centrifugal pump (CEN, n = 20). The level of plasma free haemoglobin (FHb) was measured preoperatively, and the rate of formation of FHb (in mg/dl/min) was determined at the end of the ischaemic phase and at the end of CPB. Cardiotomy suction blood was isolated for the ischaemic phase and returned before the end of CPB. It was found that there were no differences between the groups in demographic or operative variables. The rate of formation of FHb at the end of the ischaemic phase was similar for all groups (STD 0.108 +/- 0.10, DYN 0.117 +/- 0.08, CEN 0.129 +/- 0.07). At the end of CPB, after return of the cardiotomy suction blood, there was a significant (< 0.001) increase in the rate of formation of FHb in all groups. The increase was similar for each of the groups (STD 0.424 +/- 0.17, DYN 0.481 +/- 0.20, CEN 0.471 +/- 0.18). We conclude that the rates of haemolysis are similar for each of the pump types, and no benefit is conferred by the use of either a dynamically set roller pump or a centrifugal pump compared with the standard roller pump. The return of the cardiotomy suction blood to the circulation is the principal source of plasma free haemoglobin.

Gastric mucosal tonometry was used to determine the adequacy of gastrointestinal perfusion in 10 patients undergoing elective myocardial revascularization. Patients were prospectively randomized to receive either pulsatile or nonpulsatile flow during cardiopulmonary bypass. All patients showed a reduction in gastric mucosal perfusion during bypass, manifested by a reduction in the gastric mucosal pH, which occurred independently of variations in the arterial pH. In the group of patients receiving nonpulsatile flow, this reduction was significantly greater (p < 0.05). Cardiopulmonary bypass using nonpulsatile flow is associated with the development of a gastric mucosal acidosis, which may have implications for the development of postoperative complications.

1. Adenine nucleotide concentrations in normal and one day hypertrophied hearts of untreated, orotic acid (OA), uridine, uracil, dihydroorotate and reserpine pretreated rats were measured. OA treatment increased the ADP concentration 5-fold in one day hypertrophied hearts. Neither uracil, uridine, dihydroorotate nor reserpine treatments changed ADP or total adenylate concentrations at one day of hypertrophy. 2. The adenine nucleotide ratio (ANR) at 0.263 x 10(3) M-1 and the energy charge (0.66) were at their lowest values in OA and in reserpine treated one day hypertrophying hearts. The temporal decline in the indices of energy metabolism corresponded with the OA induced maximum stimulation of contractility and maximum rates of protein, RNA and glycogen synthesis. 3. The phosphorylation state of the adenine nucleotides (PSAN) was both the most sensitive and the best predictive index of the cellular energy status in normal and hypertrophying hearts. The pronounced ability of OA treatment to energize myocyte cytoplasm was shown by the 9- and 6-fold greater values of PSAN over ANR in one and three day hypertrophied hearts. The enhanced PSAN may be the key factor in the mechanism of OA induced enhancement of contractile and synthetic functions of the heart in compensatory hypertrophy. 4. The development of myocardial hypertrophy in untreated rats resulted in a 36% reduction in the cytoplasmic NAD/NADH ratio. In rats treated with OA this redox couple of the hypertrophying heart was more oxidized and was increased by 30% to restore it to the value range of normal heart. 5. The regulatory status of the glycolytic pathway in untreated and OA treated hypertrophying hearts was assessed by comparisons of the mass action ratio (MAR) and equilibrium constants for each of the individual glycolytic reactions. There was an OA induced 2.7-fold increase in glycogen, UDP-glucose and total uridine nucleotides in hypertrophied hearts. The concentrations of seven out of ten glycolytic intermediates, including pyruvate and lactate were increased as a consequence of OA treated hypertrophy. Glycolytic flux was not stalled, rather the pathway was "more open" permitting greater throughput of intermediates with individually increased levels of selected metabolites. OA stimulated hypertrophy did not change the canonical control of glycolysis by the activities and individual MAR values of phosphofructokinase and pyruvic kinase. 6. Elevated levels of Glu 6-P, Fru 6-P and DHAP can force glycolytic intermediate entry into the non-oxidative reaction segment of the pentose pathway (PP), thereby elevating Rib 5-P concentration by reversal of the conventional flux direction of PP.(ABSTRACT TRUNCATED AT 400 WORDS)

Emergency cardiac surgery after recent thrombolytic therapy is associated with increased blood loss. A patient underwent emergency repair of a ruptured left ventricle after intravenous streptokinase treatment for acute coronary occlusion. High dose aprotinin was given during the operation to reduce the expected blood loss. Surgical repair was successful without bleeding complications. Total postoperative blood loss was 365 ml.

Patients with a recent myocardial infarction have a higher morbidity and mortality than comparable patients with chronic myocardial ischaemia. We postulated that this might be due to a reduced overall tolerance of the heart to cardioplegic arrest in the presence of a recent infarct. We postulated that orotic acid, a pyrimidine precursor which augments the rate of protein synthesis, might improve the response of the recently infarcted heart to cardioplegic arrest. Myocardial infarction was produced in rats by coronary ligation. The rats were then divided into two groups according to whether they were treated with oral orotic acid (10 mg/kg per day) or untreated. A sham-operated (non-infarcted) group served as normal controls. After 2 days, the hearts (n = 12 per group) underwent 1 h of cardioplegic arrest at 23 degrees C on the isolated working heart apparatus. Before arrest, maximum cardiac function in the untreated infarct group was lower than in the normal group (P less than 0.05), whereas in the treated group, function was similar to the normal group. After arrest there was severe depression of cardiac function in the untreated infarct group: only 57% recovery of the pre-arrest value compared with 86% in the normal group (P less than 0.001). In the orotic acid treated group, recovery (90%) was significantly greater than in the untreated group (P less than 0.001) and equivalent to the normal group. Oxygen utilisation, when corrected for external work, was higher in both infarct groups than in the normal group before and after arrest (P less than 0.05 in both cases). Total uridine nucleotide content of the infarcted and non-infarcted zones of the heart was increased. Treatment with orotic acid produced a further upward trend in uridine nucleotide levels. We conclude that an established, recent infarct reduces the overall tolerance of the heart to hypothermic cardioplegia. Treatment with orotic acid improves the function of the infarcted heart following cardioplegic arrest, and may therefore improve the results of urgent cardiac surgery in patients with myocardial infarction.

Hydroxyethyl starch (HES) is a recently developed synthetic volume expander. Forty patients undergoing coronary artery surgery were randomized to receive either HES or plasma protein fraction (PPF) as non-blood volume replacement according to standard haemodynamic criteria. The two groups were comparable in all respects. The median colloid use in the first 24 h was 950 ml (range 500-1500) in the HES group and 975 ml (350-2000) in the PPF group (not significant). There was no difference in blood use, urine output or blood loss between the two groups. Tests of coagulation showed the postoperative changes usual in cardiac surgical patients. There was no difference between the two groups in thrombin time, prothrombin time, activated partial thromboplastin time, or fibrinogen concentration. Similarly, tests of platelet function and Factor VIII and von Willebrand Factor activity showed no difference between the two groups. We conclude that HES is a safe and effective volume expander, and its relative lack of expense and ease of availability make its routine use after cardiac surgery an attractive proposition.