Reduction of spectral interferences using ultraclean gold nanowire arrays in the LDI-MS analysis of a model peptide.

The surface chemistry of gold nanowires (AuNWs) has been systematically assessed in terms of contamination and cleaning processes. The nanomaterial's surface quality was correlated to its performance in the matrix-free laser desorption ionization mass spectrometry (LDI-MS) analysis of low molecular weight analytes. Arrays of AuNWs were deposited on glass slides by means of the lithographically patterned nanowire electrodeposition technique. AuNWs were then characterized in terms of surface chemical composition and morphology using X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy. AuNWs were subjected to a series of well-known cleaning procedures with the aim of producing the best performing surfaces for the LDI-MS detection of leucine enkephalin, chosen as a model analyte with a molar mass below 1,000 g/mol. Prolonged cyclic voltammetry in 2 M sulfuric acid and, most of all, oxygen plasma cleaning for 5 min provided the best results in terms of simpler (interference-free) and more intense mass spectrometry spectra of the reference compound. The analyte always ionized as the sodiated adduct, and leucine enkephalin limits of detection of 0.5 and 2.5 pmol were estimated for the positive and negative analysis modes, respectively. This study points out the tight correlation existing between the chemical status of the nanostructure surface and the AuNW-assisted LDI-MS performance in terms of reproducibility of spectra, intensity of analyte ions and reduction of interferences.

Polycyclic aromatic hydrocarbons in residential dust and risk of childhood acute lymphoblastic leukemia.

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.

Pathological features of oxalate nephrosis in a population of koalas (Phascolarctos cinereus) in South Australia.

The wild and captive koala population of the Mt Lofty Ranges in South Australia has a high level of renal dysfunction in which crystals consistent with calcium oxalate have been observed in the kidneys. This study aimed to describe the pathological features of the renal disease in this population, confirm the composition of renal crystals as calcium oxalate, and determine whether any age or sex predispositions exist for this disease. A total of 51 koalas (28 wild rescues, 23 captive) were examined at necropsy, of which 28 (55%) were found to have gross and/or histological evidence of oxalate nephrosis. Histopathological features included intratubular and interstitial inflammation, tubule dilation, glomerular atrophy, tubule loss, and cortical fibrosis. Calcium oxalate crystals were demonstrated using a combination of polarization microscopy, alizarin red S staining, infrared spectroscopy, and energy-dispersive X-ray analysis with scanning electron microscopy. Uric acid and phosphate deposits were also shown to be present but were associated with minimal histopathological changes. No significant differences were found between the numbers of affected captive and wild rescued koalas; also, there were no sex or age predispositions identified, but it was found that oxalate nephrosis may affect koalas <2 years of age. The findings of this study suggest that oxalate nephrosis is a leading disease in this koala population. Possible causes of this disease are currently under investigation.

The impact of off-pump coronary artery bypass surgery on postoperative renal function.

OBJECTIVES: A number of risk factors have been recognised for postoperative renal dysfunction following on-pump coronary artery bypass surgery (CABG). There are, however, few studies that have evaluated the potential reno-protective effects of off-pump CABG in the presence of other confounding risk factors. The aim of this study was to determine if off-pump CABG reduces the risk of renal injury. METHODS: Serum creatinine values (preoperatively and day 1, 2 and 4 postoperatively) and other clinical data were prospectively collected on 1580 consecutive patients who underwent first-time CABG from 2002 to 2005. Creatinine clearance was calculated using the Cockcroft and Gault equation. The effect of on-pump vs. off-pump CABG on renal function was analysed, adjusting for age, gender, diabetes mellitus, left ventricular (LV) function and preoperative creatinine clearance, using multiple regression analysis. RESULTS: One thousand one hundred and forty-five (73%) patients underwent on-pump CABG and 435 (27%) underwent off-pump CABG. The two groups were similar with respect to age, gender and diabetes. Two hundred and seventy-four (17%) patients were females and 274 (17%) patients had diabetes. Multivariate analysis demonstrated significantly lower creatinine clearance postoperatively in patients with diabetes (P<0.001) and advanced age (P<0.001). The on-pump group had significantly lower postoperative creatinine clearance in comparison to the off-pump group (P= 0.01). The effect remained consistent after adjusting for potential risk factors (age, diabetes, gender, LV function and preoperative creatinine clearance) in the multivariate analysis. CONCLUSION: Off-pump surgery is associated with a reduction in postoperative renal injury.

Prevention and early treatment of the long-term physical effects of COVID-19 in adults: design of a randomised controlled trial of resistance exercise-CISCO-21.

BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection. METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea. DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals. TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.

Generation of sex ratio biases in the red-tailed phascogale (Phascogale calura).

Male semelparous dasyurid species are annual breeders that use a promiscuous mating system. These species have shown biases in litter sex ratios and, with females producing more young than they have available teats, this provides an opportunity for the manipulation of the sex ratio at birth. The sex ratio of embryos and pouch young, and the degree of embryonic overproduction, in red-tailed phascogales (Phascogale calura) was investigated to gain an understanding of the mechanism by which sex biases may be generated. The sex ratio of embryos did not differ from parity, but a male bias was observed in young attaching to teats. Females produced an average of 15.1 +/- 1.9 corpora lutea and 10.5 +/- 3.5 viable embryos, with no difference in fecundity observed with female age or weight. Because females only have eight teats, the overproduction of young, and male-biased attachment, was sufficient to explain the observed male bias in pouch young. No relationship was observed between maternal weight and sex ratio, but heavier females did tend to produce more ova. Meta-analysis of studies providing information on litter sex ratios in male semelparous dasyurid species did not show any consistent trend.

Eimeria taggarti N. Sp., a Novel Coccidian (Apicomplexa: Eimeriorina) in the Prostate of an Antechinus flavipes.

A novel coccidian species was discovered in the prostate of an Antechinus flavipes (yellow-footed antechinus) in South Australia during the period of postmating male antechinus immunosuppression and mortality. This novel coccidian is unusual because it develops extraintestinally and sporulates endogenously within the prostate gland of its mammalian host. Histological examination of prostatic tissue revealed dense aggregations of spherical and thin-walled tetrasporocystic, dizoic, sporulated coccidian oocysts within tubular lumina, with unsporulated oocysts and gamogonic stages within the cytoplasm of glandular epithelial cells. This coccidian was observed occurring concurrently with dasyurid gammaherpesvirus 1 infection of the antechinus' prostate. Eimeria-specific 18S small-subunit ribosomal (r)DNA polymerase chain reaction amplification was used to obtain a partial 18S rDNA nucleotide sequence from the antechinus coccidian. Bayesian phylogenetic analysis based on 18S rDNA gene sequences revealed that the novel coccidian clusters with reptile-host coccidians, forming an ancestral basal lineage of the eimeriid clade. The species has been named Eimeria taggarti n. sp. on the basis of both sporulated oocyst morphology and molecular characterization. It is suspected that E. taggarti is sexually transmitted via excretion of sporulated oocysts or free sporocysts with prostatic secretions in semen.

On the adaptation in potassium excretion associated with nephron reduction in the dog.

An effort to examine certain aspects of the adaptation in potassium excretion associated with nephron reduction was made in dogs with unilateral remnant kidneys. A constant intake of potassium was maintained by tube feeding and studies were performed before and after removal of the intact control kidney. The removal of the intact kidney created the need for the remaining nephrons of the remnant kidney to increase their rate of potassium excretion markedly. Sodium intake was held constant either at a normal or a low level. Mineralocorticoid hormone activity was maintained either at a high level by the administration of 0.2 mg 9-alpha-fluorohydrocortisone daily or at a low level by performing bilateral adrenalectomy and administering a minimal maintenance dose of deoxycorticosterone acetate (DOCA) and cortisol. Potassium excretion per nephron increased strikingly within 18 hr of contralateral nephrectomy and by 7 days, excretion rates were 600% of control values for the remnant kidney. More potassium was excreted in the first 5 hr after administration of a test dose of potassium by the remnant kidney alone in the postnephrectomy state than by both the remnant and intact kidneys in the prenephrectomy state. 24 hr excretion of potassium by the remnant kidney postnephrectomy averaged 92% of the administered load of potassium. The adaptation in potassium excretion was independent of the concurrent rate of sodium excretion and of mineralocorticoid hormone activity and persisted during constriction of the renal artery, a stimulus which presumably decreased distal delivery of sodium. The adaptation and the continued modulation of potassium excretion could not be explained adequately by an increase in impermeant anion excretion per nephron. Finally, known changes in hydrogen ion excretion per nephron associated with nephron reduction are in a direction opposite to those which would explain the acquired kaliuresis per nephron.

On the pathogenesis of hyperparathyroidism in chronic experimental renal insufficiency in the dog.

Healthy adult dogs were subjected to stepwise reduction of nephron population so as to create the transition from normal renal function to advanced renal insufficiency. Studies were performed at each level of renal function. Glomerular filtration rate (GFR), renal phosphate clearance, and serum radioimmunoassayable parathyroid hormone (PTH) levels were measured. Two groups of animals were studied. In one, phosphorous intake was maintained at 1200 mg/day. As GFR declined, fractional phosphate excretion rose reciprocally, and PTH levels increased over 20-fold. In the second group, phosphorous intake was maintained at less than 100 mg/day. As GFR fell, fractional phosphate excretion changed little, and no increment in PTH levels occurred. The data suggest that the control system regulating phosphate excretion contributes importantly to the pathogenesis of secondary hyperparathyroidism in advancing renal insufficiency.

Ovarian follicular superstimulation and oocyte maturation in the anoestrous southern hairy-nosed wombat, Lasiorhinus latifrons.

This study investigates the effect of three exogenous gonadotrophin regimens on ovarian follicular development in southern hairy-nosed wombats during the non-breeding season. Females were given either porcine follicle stimulating hormone (pFSH; total of 200 mg at 12 h intervals over 7 (Group 1), or 4 days (Group 2)), or pregnant mares' serum gonadotrophin (PMSG; single dose of 150 I.U. (Group 3)). In all treatment groups 25 mg of porcine luteinising hormone (pLH) was used to trigger maturation; Groups 1 and 2 received pLH 12 h after the final pFSH injection and Group 3 received pLH 72 h after PMSG. The results showed Group 1 produced significantly more follicles per ovary (5.91+/-1.28) than Group 2 (1.67+/-0.62), or Group 3 (2.17+/-1.16) at p<0.05. Control females received saline injections concurrently with the three treatment groups (n=6; 2 control animals for each treatment group). No follicular development occurred in any control female. Analysis of oocyte nuclear status revealed that while oocytes from all three treatment groups had resumed meiosis, only those in Group 1 (7-day pFSH/pLH treatment) progressed to metaphase II. These results have implications for the development of assisted breeding strategies in this species.

Pouch young removal and return to oestrus in wild southern hairy-nosed wombats (Lasiorhinus latifrons).

The southern hairy-nosed wombat (Lasiorhinus latifrons) is a seasonal breeding, burrowing marsupial adapted to a semi-arid environment and the closest relative of the endangered northern hairy-nosed wombat (Lasiorhinus krefftii). Females typically give birth to one to two young every 3 years with young weaned at 360-400 days. This study examined the occurrence of polyoestry in a wild population of southern hairy-nosed wombats, and in particular the ability of this species to produce additional offspring in the same breeding season if a young was prematurely lost or removed. Pouch young were removed during the breeding seasons of 1996/1997 and 2003. No females from the 1996 (n=3)/1997 (n=3) group gave birth to a second pouch young in the same breeding season. However, two females in this group gave birth to young the following season. In contrast, all the 2003 group of females (n=6) produced a second offspring in the same breeding season after removal of pouch young (RPY). The reason for the different response to RPY between the two groups is unknown. These studies confirm that southern hairy-nosed wombats are polyoestrus in the wild and are capable of producing more than one offspring in a single breeding season. Females that failed to return to oestrus in the breeding season that pouch young were removed bred again in the following season. Rapid replacement of southern hairy-nosed wombat pouch young in the same breeding season as RPY suggests that this procedure, linked to either hand-rearing or interspecific cross-fostering, should be seriously considered as a priority conservation action to increase the population size of the critically endangered sister species, the northern hairy-nosed wombat.

Effect of exogenous gonadotrophins on ovarian morphology and oocyte maturation in the southern hairy nosed wombat Lasiohinus latifrons during the breeding season.

The effect of the exogenous administration of porcine follicle-stimulating hormone (pFSH) and pregnant mare serum gonadotrophin (PMSG) on ovarian follicular development and oocyte maturation in the southern hairy nosed wombat Lasiorhinus latifrons was investigated. Three experimental groups were administered pFSH at various doses and for different treatment lengths, followed by 25 mg porcine luteinising hormone (pLH) 12 h after the last dose of pFSH. Another group was given PMSG followed 72 h later by 25 mg pLH. Animals were killed 24 h after pLH. The left ovary was fixed for histology and the morphology of the antral follicles was determined, whereas follicular oocytes in the right ovary were aspirated, fixed, stained with 42,62-diamidino-2-phenylindole, and viewed for nuclear maturation. There was no significant difference in the mean number of ovarian follicles >1 mm, or in the size class of follicles assessed between control and experimental groups. However, a trend was observed suggesting a possible increase in follicles >3.0 mm in experimental groups compared with control animals. In all females administered exogenous porcine gonadotrophins, but not controls, some of the mural granulosa cells of large tertiary antral follicles had markedly enlarged nuclei (approximately 14 microm in diameter). All oocytes from the control group remained at the germinal vesicle stage, whereas approximately 40% of oocytes retrieved from the pFSH groups and 82.4% retrieved from the PMSG-primed animals had undergone germinal vesicle break down, with a small number reaching meiosis II. The present study shows that exogenous administration of either pFSH or PMSG to hairy nosed wombats can induce follicular growth and oocyte maturation. Such findings could be useful in the development of reproductive technology in this species.

Oestrous cycle of captive southern hairy-nosed wombats (Lasiorhinus latifrons) in South Australia, Australia.

There is limited information available on the oestrous cycle of female southern hairy-nosed wombats (Lasiorhinus latifrons). This is mainly due to an extremely poor breeding success in captivity and the difficulty in routine recapturing of these cryptic, semi-fossorial animals in the wild. The aim of this study was to characterise the oestrous cycle of this species by monitoring peripheral plasma concentrations of progesterone and oestradiol, assessing changes in vaginal cytology, pouch condition and the urogenital sinus. Eight adult female wombats were monitored during the breeding season (July-December) over 2 years (2002-2003). Samples were collected up to three times a week. Vaginal smears contained several cell types, categorised by morphology, as either superficial epithelial cells or parabasal-intermediate cells. Leucocytes were also counted. Plasma progesterone profiles showed a mean oestrous cycle length of 36.33+/-0.67 days with a peak progesterone concentration of 139.53+/-10.62nmol/L. Levels of oestradiol peaked at a mean level of 467.33+/-44.32pmol/L on average 5 days before a rise in plasma progesterone values. The proportion of epithelial cells in vaginal smears varied throughout the cycle, with a high percentage of superficial epithelial cells observed during the follicular phase. During periods when progesterone concentrations were high, a greater percentage of parabasal-intermediate cells was observed. In conclusion, this study has characterised the oestrous cycle of the southern hairy-nosed wombat and confirmed that changes in vaginal smears together with pouch and urogenital sinus details could be used to determine signs of oestrus in this species.

Cell therapy for heart disease: Trial sequential analyses of two Cochrane reviews.

Meta-analyses of cell therapy trials for heart disease have yielded discrepant results. To resolve limitations associated with meta-analyses, such as imprecision and accumulation of random errors, we conducted trial sequential analysis (TSA). Randomized controlled trials that administered autologous bone marrow-derived cells to patients who suffered acute myocardial infarction (AMI) or heart failure (HF) were included. TSA has been applied to two clinical outcomes, all-cause mortality and hospitalization for HF, and to left ventricular ejection fraction (LVEF), as a surrogate of heart function. The results suggest that there is evidence of reduction of the risk of mortality and hospitalization in HF, but insufficient evidence to determine treatment effect in AMI. Moreover, the treatment does not improve LVEF by more than a mean difference of 4% when administered to either AMI or HF patients. The required number of participants to include in a meta-analysis to detect treatment effect was also estimated.

Biochemical assessment of myocardial injury after cardiac surgery: effects of a platelet activating factor antagonist, bilateral internal thoracic artery grafts, and coronary endarterectomy.

OBJECTIVE: Platelet activating factor antagonists reduce ischemia-reperfusion injury in experiments, but there is no supportive clinical evidence. METHODS: A single-center, double-blind, minimized, placebo-controlled, randomized trial of low-dose (10 mg) or high-dose (100 mg) platelet activating factor antagonist was conducted in 150 patients undergoing coronary artery bypass grafting. Myocardial injury was determined by serial measurements of the MB isoenzyme of creatine kinase and cardiac troponin T. The effects of single or bilateral internal thoracic artery grafting and coronary endarterectomy on myocardial injury were also assessed. RESULTS: The placebo and platelet activating factor antagonist groups were similar with respect to preoperative, intraoperative, and postoperative factors. Four patients (2.7%) died before discharge, 3 from cardiac events. Thirteen patients (9%) had biochemical evidence of myocardial infarction, of whom 3 died. Stepwise multiple regression analysis demonstrated that duration of cardiopulmonary bypass was the most important determinant of elevations in creatine kinase MB isoenzyme and cardiac troponin T up to 6 hours after the operation and that the use of a platelet activating factor antagonist and the number of internal thoracic artery grafts did not influence myocardial injury at any time. Endarterectomy was performed in 11 patients (7%), of whom 6 (55%) had biochemically defined myocardial infarction and of whom 1 died (9%). Endarterectomy was the most important determinant of elevated levels of creatine kinase MB isoenzyme and cardiac troponin T 24 and 48 hours after the operation. CONCLUSION: Platelet activating factor antagonists do not reduce perioperative myocardial injury. Bilateral and single internal thoracic artery grafting results in similar levels of myocardial injury, whereas endarterectomy is frequently associated with biochemical evidence of myocardial injury.

The Jarvik 2000 Oxford system: increasing the scope of mechanical circulatory support.

METHODS: We developed a system for mechanical circulatory support based on the Jarvik 2000 intraventricular axial flow impeller pump (Jarvik Research, Inc., New York, N.Y.) and percutaneous electric power. The adult pump provides flow at a rate up to 10 L/min with an energy requirement of 7 to 10 watts. The device was implanted into the apex of the left ventricle through a left thoracotomy without cardiopulmonary bypass. A Dacron graft conveyed blood to the descending thoracic aorta. In patients, we will use a skull-mounted carbon pedestal to transmit fine electric wires through the scalp skin. Being highly vascular, the scalp skin is resistant to infection. RESULTS: We tested 16 adult systems and one pediatric system in 17 adult ewes weighing between 60 and 90 kg. Five died of perioperative complications. Twelve survived between 3 and 198 days (mean 44 days) with a functioning device. None of the sheep could receive adequate anticoagulation with warfarin (INR 1.0 to 1.5). Acute thrombotic occlusion occurred after a 3-hour power loss in one device (46 days) but was cleared with streptokinase. In a second animal with endocarditis, the pump inflow became occluded with vegetations. No other device-related problems or important hemolysis developed despite pump speeds between 10,000 and 18,000 rpm. Renal function remained normal in all animals. Autopsy studies showed no pannus ingrowth at the device inflow despite the restrictive left ventricular cavity size. No sign of thromboembolism could be detected in the brains or kidneys. CONCLUSION: Our findings indicate the Jarvik 2000 Oxford System to be a safe and effective circulatory assist device. Potential uses include permanent circulatory support, bridge to transplantation, or bridge to myocardial recovery in acute or chronic left ventricular failure.

Postoperative hypoxia is a contributory factor to cognitive impairment after cardiac surgery.

OBJECTIVE: Cognitive dysfunction and postoperative hypoxia are common sequelae of coronary artery bypass grafting, but there has been no study to determine whether there is any relationship between them. METHODS: Arterial blood gas measurements were performed before surgical intervention and on the second and fifth postoperative day, and neuropsychological assessments were performed before surgical intervention and 5 days and 3 months postoperatively by using a battery of 10 psychometric tests in 175 patients undergoing coronary artery bypass grafting. An estimate of overall performance on the battery at each assessment point was provided by a simple aggregate cognitive index score calculated from the mean z scores of 4 normally distributed test variables. Multiple regression analysis was performed by using the cognitive index score at day 5 as the dependent variable, with age, sex, duration of the operation, presence or absence of cardiopulmonary bypass, preoperative cognitive index score, and arterial oxygenation and percentage of saturation at day 5 as independent variables. RESULTS: The mean cognitive index score decreased significantly in 115 (66%) patients who agreed to neuropsychological test battery assessment on the fifth postoperative day but improved significantly beyond baseline at 3 months. Mean arterial oxygen tension and percentage of saturation decreased significantly 2 days after the operation and, although improving over the following 3 days, remained decreased at day 5. Decreased cognitive index scores at day 5 strongly predicted cognitive impairment at 3 months (r = 0.36). The only significant independent predictors of the day 5 cognitive index score in the multiple regression analysis were preoperative cognitive index score and arterial oxygenation tension at day 5 (r = 0.24, P <.03). CONCLUSIONS: We report a significant correlation between postoperative cognitive dysfunction and hypoxia 5 days after coronary artery bypass grafting. This finding might have therapeutic implications because early postoperative cognitive dysfunction influences long-term impairment.

Applicability of intermittent global ischemia for repeat coronary artery operations.

Despite the increasing popularity of cardioplegic techniques there is no consensus as to the optimal myocardial protective technique for first-time or repeat coronary artery bypass grafting. Intermittent global ischemia was used in 159 consecutive patients (142 male; 17 female) undergoing repeat coronary artery bypass grafting during a 6-year period (1987 to 1992). The median age of the patients was 60 years (90% confidence interval: 47 to 70 years) and the median interval from the first operation was 9 years (90% confidence interval: 2 to 14 years). One third of the patients required emergency (within 24 hours) or urgent (within 7 days) operations because of failure of symptoms to resolve with medical therapy. Compared with events at the initial operation there was an increased prevalence of impaired ventricular function (ejection fraction < 50%) and increased use of the internal thoracic artery (48% versus 9%). Two of 12 patients who required emergency operations died in the hospital, which resulted in an overall mortality rate at 30 days of 1%. Intraaortic balloon pump support was required in five patients (3%) and cardiac dose inotropic support in 21% of patients for up to 24 hours after operation. There was definite electrocardiographic evidence of infarction in 11 patients (7%). The mean postoperative blood loss, without aprotinin, was 627 ml (standard deviation 327 ml) and two patients required reexploration because of bleeding. Five patients had a hemiparesis (3%) and a further four patients (3%) had a mild or transient postoperative focal neurologic deficit. The median postoperative hospital stay was 9 days (90% confidence interval: 7 to 20 days) although 10% of patients required a hospital stay in excess of 21 days. No patient was lost to follow-up. The median (and interquartile range) period of follow-up was 1.6 (1 to 3) years. Eight patients died in the follow-up period, which resulted in an estimated survival of 80% at 5 years. At a mean follow-up period of 2 years (and with or without antianginal medication) 83% of patients had no or minimal angina, 12% had angina on moderate exertion, and 5% had angina on minimal exertion. In comparison with other current series of repeat coronary revascularization our results suggest that repeat coronary artery bypass grafting can be done with intermittent global ischemia with early and intermediate results at least equivalent to those obtained with cardioplegic methods.

Is cardiopulmonary bypass still the cause of cognitive dysfunction after cardiac operations?

OBJECTIVE: The purpose of this study was to determine whether cognitive impairment is related to cardiopulmonary bypass. METHODS: Twenty-five patients undergoing coronary artery bypass grafting without cardiopulmonary bypass were matched with 50 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. All patients received the same anesthetic regimen, and one surgeon performed all the operations. A battery of 10 standard tests of neuropsychologic function were performed before, at discharge, and 3 months after the operation. A comprehensive multidimensional measure of subjective health status was used as the primary clinical measure of functional outcome. RESULTS: The groups were similar with respect to age, sex, and ventricular function and differed only in the need for a circumflex artery graft. Both groups showed significant improvement in the comprehensive multidimensional measure of subjective health status at 3 months. At discharge most neuropsychologic tests had deteriorated in both groups (the same 4 tests had deteriorated significantly in both groups, and an additional test had deteriorated significantly in the cardiopulmonary bypass group). At 3 months all but one test in the cardiopulmonary bypass group had returned to or exceeded baseline performance. The same 2 tests had improved significantly in both groups, and a further test had improved significantly in the group without cardiopulmonary bypass. At no specific time point was there a significant difference between the absolute or change scores between the groups on any of the tests. CONCLUSIONS: The similar pattern of early decline and late recovery of cognitive function in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass suggests that cardiopulmonary bypass is not the major cause of postoperative cognitive impairment. This merits consideration in deciding optimal treatment strategies in coronary revascularization.