Resonancia magnética de próstata: lectura con el sistema PI-RADS V2 / Magnetic resonance imaging of the prostate: interpretation using the PI-RADS V2

Objetivo. El sistema de datos e informe en imagen prostática (Prostate Imaging and Reporting and Data System, PI-RADS) en su versión 2 fue creado con el fin de ayudar en la detección, localización y caracterización del cáncer de próstata con resonancia magnética (RM). Sus recomendaciones de estandarización de parámetros de adquisición de imágenes pretenden disminuir la variabilidad en la interpretación de los estudios de RM prostática, lo que, junto con la realización de un informe estructurado, tiene el valor añadido de mejorar la comunicación entre los radiólogos, y entre estos y los urólogos. El objetivo de nuestro trabajo es explicar de manera sencilla el sistema de clasificación PI-RADS v2 mediante imágenes ilustrativas de cada una de las categorías, así como recomendar el uso de una técnica estándar que ayude en la reproducibilidad de los estudios de RM multiparamétrica. Conclusión. El documento PI-RADS v2 es sencillo de aplicar a la lectura de la RMmp de próstata. Es importante que los radiólogos dedicados a la imagen prostática lo incluyamos en la práctica diaria para realizar informes claros y concisos que mejoren la comunicación entre radiólogos y urólogos (AU)

Objective. Version 2 of the Prostate Imaging and Reporting and Data System (PI-RADS) was developed to help in the detection, location, and characterization of prostate cancer with magnetic resonance imaging (MRI). Its recommendations for standardizing image acquisition parameters aims to reduce variability in the interpretation of MRI studies of the prostate; this approach, together with structured reporting, has the added value of improving communication among radiologists and between radiologists and urologists. This article aims to explain the PI-RADS v2 classification in a simple way, using illustrative images for each of the categories, as well as to recommend the use of a standard technique that helps ensure the reproducibility of multiparametric MRI. Conclusion. The PI-RADS v2 is simple to appy when reading multiparametric MRI studies of the prostate. It is important for radiologists doing prostate imaging to use the PI-RADS v2 in daily practice to write clear and concise reports that improve communication between radiologists and urologists (AU)

Magnetic resonance imaging of the prostate: interpretation using the PI-RADS V2. / Resonancia magnética de próstata: lectura con el sistema PI-RADS V2.

OBJECTIVE: Version 2 of the Prostate Imaging and Reporting and Data System (PI-RADS) was developed to help in the detection, location, and characterization of prostate cancer with magnetic resonance imaging (MRI). Its recommendations for standardizing image acquisition parameters aims to reduce variability in the interpretation of MRI studies of the prostate; this approach, together with structured reporting, has the added value of improving communication among radiologists and between radiologists and urologists. This article aims to explain the PI-RADS v2 classification in a simple way, using illustrative images for each of the categories, as well as to recommend the use of a standard technique that helps ensure the reproducibility of multiparametric MRI. CONCLUSION: The PI-RADS v2 is simple to appy when reading multiparametric MRI studies of the prostate. It is important for radiologists doing prostate imaging to use the PI-RADS v2 in daily practice to write clear and concise reports that improve communication between radiologists and urologists.

Immediate and long-term outcome of left-sided infective endocarditis. A 12-year prospective study from a contemporary cohort in a referral hospital.

The aim of this study was to describe the immediate and long-term prognosis of a contemporary cohort of patients with left-sided infective endocarditis (LSIE). A prospective observational cohort study was conducted in a referral centre. Between January 2000 and December 2011, all consecutive adult patients with LSIE were followed-up until death, relapse, recurrence, need for late surgery, or last control. During the active phase of IE, 174 of 438 patients underwent surgery (40% overall; 43% native valve (NVIE), 30% prosthetic valve (PVIE)) and 125 died (29% overall; 26% NVIE, 39% PVIE). The median follow-up in survivors was 3.2 years (interquartile range (IQR) 1.0-6.0 years). Relapses occurred in seven patients (2.2%; 95% CI, 1.1-4.5) and recurrences in eight (2.6%; 95% CI, 1.3-5.0), with an incidence density of 0.0067 per patient-year (95% CI, 0.0029-0.0133) and high mortality (75% of recurrences). Only four of 130 survivors (3.1%; 95% CI, 1.2-7.6) who were treated surgically during the active phase of the disease, and 14/183 (7.7%; 95% CI, 4.6-12.4) of those not undergoing surgery needed operation during follow-up (p 0.09). In the 313 survivors, actuarial survival was 86% at 1 year (87% NVIE, 83% PVIE), 79% at 2 years (81% NVIE, 72% PVIE) and 68% at 5 years (71% NVIE, 57% PVIE). At 1 year, 115 of 397 patients (29.0%; 95% CI, 24.7-33.6) remained alive, with no surgery requirement, relapse or recurrence. LSIE is associated with considerable in-hospital and long-term mortality, especially PVIE. However, relapses, recurrences and the need for late surgery are uncommon.

MitroFast® annuloplasty ring for complete posterior mitral leaflet destruction: a novel approach in active endocarditis.

We report the successful use of MitroFast® annuloplasty ring in the setting of active endocarditis to preserve the native valve mechanism despite complete posterior leaflet destruction. This patient remained well at 20 month follow-up after her surgery.

Relationship between reduced elasticity of extracardiac vessels and left main stem coronary artery disease.

OBJECTIVES: To investigate the elastic properties of medium-size extracardiac arteries and veins between patients with and without left main stem coronary artery disease. METHODS: The compliance, distensibility, and incremental elastic modulus (iEmod) of the internal thoracic arteries (n=53), long saphenous veins (n=38), and radial arteries (n=35) from 74 patients undergoing coronary surgery were studied in organ baths. Twenty-four patients had left main stem (LMS) disease and 50 non-LMS coronary disease. RESULTS: Internal thoracic arteries from patients with LMS presented significantly lower compliance (-17%) and distensibility (-18%) and significantly higher iEmod (19%) than internal thoracic arteries from patients with non-LMS disease. Radial arteries from patients with LMS presented higher iEmod (50%) than radial arteries from patients with non-LMS disease. Furthermore, long saphenous veins from patients with LMS had reduced compliance (-45%), reduced distensibility (-40%) and increased iEmod (34%) compared to those from patients with non-LMS disease. CONCLUSIONS: LMS coronary disease is associated with a significantly reduced elasticity of extracardiac arteries and veins compared to non-LMS coronary disease. This finding suggests that widespread vascular elasticity defects may play a role in the development of LMS disease and be responsible for the higher incidence of early and late cardiovascular morbidity observed in this condition.

The radial hyperaemic response: a new and objective assessment of ulnar collateral supply to the hand.

The assessment of adequate ulnar collateral supply to the hand is mandatory prior to the harvest of the radial artery as a conduit for coronary artery bypass grafting. However, there is currently no one test which is widely used in all centres. We report a new and objective method of assessing ulnar collateral supply to the hand prior to harvest of the radial artery. This technique involves assessing the presence of a hyperaemic flow response to occlusion of the radial artery using an intraoperative transit time flowmeter. We found this technique to be objective and reliable, and would advocate its use in patients with a positive Allen's test.

Effect of diabetes on nitric oxide metabolism during cardiac surgery.

The metabolism of nitric oxide (NO) during cardiac surgery is unclear. We studied the effect of diabetes on NO metabolism during cardiac surgery in 40 subjects (20 with diabetes and 20 without diabetes). The patients were randomized to receive an infusion of physiological saline or nitroglycerin (GTN) at 1 microg. kg(-1). min(-1) starting 10 min before the initiation of cardiopulmonary bypass and then continuing for a period of 4 h. Blood and urine samples were collected at several time points for up to 8 h. NO metabolites were determined by the measurement of nitrate/nitrite (NOx, micromol/mmol creatinine) and cyclic guanosine monophosphate (cGMP, nmol/mmol creatinine) in plasma and urine. Plasma insulin levels were also determined at selected time points. Plasma NOx levels before surgery were significantly elevated in the group with diabetes compared with the group without diabetes (P < 0.001), and values were further increased during surgery in the former (P = 0.005) but not in the latter (P = 0.8). The greater plasma NOx values in patients with diabetes were matched by commensurate elevations in plasma cGMP levels (P = 0.01). Interestingly, infusion of GTN, an NO donor, significantly reduced plasma NOx (P < 0.001) and its urine elimination (P < 0.001) in patients with diabetes without reducing plasma cGMP levels (P = 0.89). Cardiac surgery increased plasma insulin in patients with and without diabetes; this increase was delayed by the infusion of GTN, but it was not related to the changes in NO production. In conclusion, NO production during cardiac surgery is increased in patients with diabetes, and this elevation can be blunted by the infusion of GTN in a rapid and reversible manner.

Pituitary gland macroadenoma: a cause of transient blindness after cardiac surgery.

Pituitary gland macroadenoma complicating cardiac surgery is an uncommon condition of spectacular clinical presentation that is generally treated by surgery. We report here on an unusual presentation of this condition that was successfully managed by medical treatment.

alpha1-Adrenoceptors during simulated ischemia and reoxygenation of the human myocardium: effect of the dose and time of administration.

OBJECTIVE: We sought to investigate the effect of alpha1-adrenoceptor activity on the ischemic and reoxygenated human myocardium. METHODS: Right atrial appendages (n = 6 per group) obtained during elective cardiac operations were sliced and stabilized in normoxic normothermic buffer solution for 30 minutes and then subjected to 90 minutes of simulated ischemia, followed by 120 minutes of reoxygenation. In study 1 the dose responses to the alpha1-adrenoceptor agonist phenylephrine (0.01, 0.1, 1, 10, and 100 micromol/L) and to the alpha1-adrenoceptor antagonist prazosin (0.1, 1, 10, and 100 micromol/L) when administered for 10 minutes before ischemia, during ischemia, and during reoxygenation were examined. The influence of the time of administration (ie, before ischemia, during ischemia, or during reoxygenation) of phenylephrine (0.1 micromol/L) and prazosin (10 micromol/L) was then investigated in study 2. In study 3 the effect of the combined administration of phenylephrine given before ischemia and prazosin given during ischemia was investigated. In study 4 the protective effect of phenylephrine given before ischemia (for 10 minutes or for 5 minutes with a 5-minute washout period) was compared with that of ischemic preconditioning (5 minutes of ischemia and 5 minutes of reoxygenation). At the end of each protocol, the leakage of creatine kinase (in units per gram of wet weight) and the reduction of 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide to insoluble formazan dye (in millimoles per gram of wet weight) were measured. RESULTS: Phenylephrine is maximally beneficial at 0.1 and 1 micromol/L (creatinine kinase, 0.97 +/- 0.06 and 0.95 +/- 0.03 U/g, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 153.0 +/- 7.8 and 156.2 +/- 6.7 mmol/g, respectively) compared with ischemic control (creatine kinase, 1.87 +/- 0.03 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 108.5 +/- 6.8 mmol/g; P <.05) but prazosin is detrimental at concentrations above 10 micromol/L (creatine kinase, 5.22 +/- 0.29 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 69.8 +/- 2.9 mmol/g; P <.05 vs ischemic control). In addition, phenylephrine (0.1 micromol/L) is protective when given before ischemia (creatine kinase, 2.06 +/- 0.21 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 148.5 +/- 4.5 mmol/g; P <.05 vs ischemic control) but is detrimental when given during ischemia alone (creatine kinase, 4.49 +/- 0.98 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 70.5 +/- 6.1 mmol/g; P <.05 vs ischemic control) and has no significant effect during reoxygenation. In contrast, prazosin (10 micromol/L) is beneficial when given during ischemia alone (creatine kinase, 1.34 +/- 0.10 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 148.5 +/- 4.5 mmol/g; P <.05 vs ischemic control), is detrimental when given during reoxygenation alone (creatine kinase, 1.5 +/- 0.16 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 85.0 +/- 4.7 mmol/g; P <.05 vs ischemic control), and has no effect when given before ischemia. The use of phenylephrine before ischemia alone is as protective as prazosin given during ischemia alone, but the combination of the two drugs does not cause additional benefit. Interestingly, the protection afforded by phenylephrine when given before ischemia is similar to that obtained with ischemic preconditioning. CONCLUSIONS: In the human myocardium activation of alpha1-adrenoceptors before ischemia is protective but is detrimental during ischemia, whereas blockade of alpha1-adrenoceptors is beneficial during ischemia but detrimental during reoxygenation. The degree of protection achieved by activation of the alpha1-adrenoceptors before ischemia is similar to that obtained with blockade of alpha1-adrenoceptors during ischemia and that of ischemic preconditioning.

Role of the L-arginine/nitric oxide pathway in ischaemic/reoxygenation injury of the human myocardium.

The role of the L-arginine/nitric oxide (NO) pathway in myocardial ischaemic/reperfusion injury remains controversial in experimental animal models. The aim of the present studies was to investigate the role of this pathway in the human myocardium. Myocardial specimens from right atrial appendages of patients undergoing elective coronary bypass graft surgery were incubated in crystalloid buffer at 37 degrees C and subjected to 120 min of simulated ischaemia followed by 120 min of reoxygenation. Tested drugs were added 15 min before ischaemia, and maintained during ischaemia and throughout reoxygenation. Ischaemia resulted in severe myocardial damage, as assessed by the leakage of lactate dehydrogenase (LDH) into the incubation medium and by the capacity of the tissue to reduce 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan product. L-Arginine (10 mM), a precursor of NO, significantly decreased LDH leakage (from 9.0+/-0.6 to 5.3+/-0.3 units/g wet wt; P<0.05), but had no effect on MTT reduction or oxygen consumption. D-Arginine (10 mM), N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5 mM), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (at 1, 100, 500 and 1000 microM), an NO donor, had no significant effects on the measured indices, and L-NAME did not reverse the protection afforded by L-arginine against LDH leakage. In addition, the formation of nitrotyrosine was not influenced by ischaemia/reoxygenation alone or by the agents investigated. In conclusion, these data suggest that L-arginine affords modest protection against ischaemic/reoxygenation injury of the human myocardium, an action that is NO-independent, and that NO metabolism does not play a significant role in this model.

Cardiotrophin-1 protects the human myocardium from ischemic injury. Comparison with the first and second window of protection by ischemic preconditioning.

BACKGROUND: There are reports suggesting that cardiotrophin 1 (CT-1) is cytoprotective. We investigated the cardioprotective effects of CT-1 on the human myocardium and compared this benefit with the early and delayed protection afforded by ischemic preconditioning (PC). METHODS: Right atrium specimens were prepared and incubated in buffer solution at 37 degrees C for 30 min stabilisation, before entering one of the three following studies. In study 1, muscles (n=6/group) were allocated to one of four groups: (i) aerobic control - incubated in oxygenated media for 210 min, (ii) ischemia alone - 90 min ischemia followed by 120 min reoxygenation, (iii) PC by 5 min ischemia-5 min reoxygenation before 90 min ischemia-120 min reoxygenation and (iv) CT-1 (1 nM) - 90 min ischemia-120 min reoxygenation with exposure to CT-1 throughout the protocol. In study 2, muscles (n=6/group) were allocated to one of four protocols as in study 1with the exception that were incubated for 24 h followed by 30 or 90 min ischemia-120 min reoxygenation on day 2. In study 3, the same groups were employed as in study 2 with the exception that only a 30-min period of ischemia was used and that CT-1 antibody (5 microg/ml) was added to all groups throughout the experimental protocol. Creatine kinase (CK, U/g wet wt.) leakage into the medium and MTT reduction (OD/mg wet wt.), an index of cell viability, were assessed at the end of the experiment. RESULTS: In study 1, a first window of cardioprotection was observed with PC (CK=4.39+/-0.34; MTT=0.58+/-0.03 vs. CK=7.11+/-0.4;MTT=0.32+/-0.02 in the ischemic alone group; P<0.001) but not with CT-1(CK=6.65+/-0. 67; MTT=0.31+/-0.03, P=NS vs. ischemia alone). In study 2, PC applied on day 1 was protective against 30-min ischemia (CK=3.28+/-0. 43; MTT=0.68+/-0.046, P<0.001 vs. ischemia alone) but not against 90-min ischemia (CK=7.13+/-0.66; MTT=0.24+/-0.03, P=NS vs. ischemia alone) induced on day 2 (second window). However, when the tissue was exposed to CT-1 for 24 h, protection was similar to that of PC when subjected to 30 min of ischemia (CK=2.95+/-0.71; MTT=0.77+/-0. 05, P=NS vs. PC) and greater than PC when subjected to 90 min of ischemia (CK=4.56+/-0.51; MTT=0.39+/-0.03, P=0.002 vs. PC). In study 3, the CT-1 antibody did not affect the protection induced by PC (CK=3.36+/-0.6; MTT=0.69+/-0.06) but it abolished the protection obtained with CT-1(CK=5.15+/-0.81; MTT=0.42+/-0.06, P=NS vs. ischemia alone group). CONCLUSIONS: CT-1 exhibits a significant protection of the human myocardium against ischemic injury when tissue is exposed to this factor for a long period (e.g. 24 h) but not when exposed for a short period (e.g. 2 h). In addition, the protection afforded by long exposure to CT-1 is as potent or even greater than the one obtained by the second window of PC. The protection induced by CT-1 but not that induced by PC can be abolished by CT-1 antibody suggesting that their beneficial action is attained by different mechanisms.

Characterization of an in vitro model for the study of the short and prolonged effects of myocardial ischaemia and reperfusion in man.

The mechanisms underlying myocardial ischaemia and reperfusion-induced injury have been investigated, mainly by using animal experimental preparations in vitro and in vivo, but little is known of the process in human myocardium. The present studies characterize an in vitro model using human myocardium for the study of early and delayed effects of ischaemia and reperfusion. The right atrial appendage was manually sliced and incubated in buffer through which was bubbled O(2)/CO(2) (19:1, v/v) for various time periods. Lactate dehydrogenase (LDH) leakage, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-2H-tetrazolium bromide (MTT) reduction, oxygen consumption, nucleotide levels and tissue morphology were all investigated as markers of myocardial injury. The specimens remained stable and viable up to 24 h, but had significantly deteriorated by 48 h. The preparation responded to ischaemia in a time-related manner. Tissue viability was reduced by 25% after 30 min ischaemia, declined to 60% after 60 min ischaemia and to 75% after 120 min ischaemia. Interestingly, the tissue was more susceptible when ischaemia was induced after 24 h of aerobic incubation. The effects of the duration of reperfusion were investigated after a fixed 60 min ischaemic insult. The results of LDH leakage suggest that reperfusion injury is mainly sustained within the first 2 h of reperfusion. However, the results of MTT reduction show that there is a progressive decrease in tissue viability over the 24 h reperfusion period, possibly reflecting the occurrence of tissue necrosis and apoptosis at different reperfusion times. In conclusion, the data provide evidence that the incubation of human atrial tissue in vitro is stable, and slices are viable for at least 24 h, which permits the study of early and delayed consequences of ischaemia and reperfusion in the human myocardium.

Residual atrial fibrillation and clinical consequences following postoperative supraventricular arrhythmias.

AIMS: This retrospective study investigated whether the supraventricular arrhythmias (SVA) observed during cardiac surgery are limited to or persist beyond the postoperative period, their clinical consequences and whether they are influenced by preoperative and postoperative factors. METHODS: A total of 375 patients undergoing elective bypass graft surgery over a 15-month period by three surgeons were included. All patients had their preoperative medications continued to the day of surgery and prophylactic anti-arrhythmic medications were not used in any of the cases. Standard anaesthetic techniques were used. Rhythm disturbances were diagnosed by ECG. The arrhythmias were treated medically or by cardioversion. All patients were followed up for 6 months. RESULTS: Postoperative SVA occurred in 25% of patients. The commonest arrhythmia was atrial fibrillation (89.4%), followed by atrial flutter (6.4%) and supraventricular tachycardia (4.2%). In 89. 8% of the cases, the arrhythmias occurred within the first four postoperative days with a maximum incidence on the second day (27. 7%). Atrial fibrillation was still present in 50% of patients at hospital discharge and in 39% at 6 months follow up. Patients with arrhythmias had a prolonged hospital stay (7.7+/-2.6 vs. 6.0+/-2.6 days; P<0.05). There was no hospital mortality in the study and the incidence of postoperative stroke was equal in the sinus rhythm and arrhythmia patients (1.1%). SVA were more frequent when cardioplegia was used to protect the heart (32%) than with intermittent ischaemia (9%; P<0.001). At 6 months follow up, the patients receiving cardioplegia also had a higher prevalence of atrial fibrillation than those operated with intermittent ischaemia (41% vs. 22%; P<0. 05). The incidence of SVA and persistence of atrial fibrillation was unrelated to other preoperative and intraoperative factors. CONCLUSION: Postoperative supraventricular arrhythmias have a long-lasting effect on cardiac rhythm: patients with SVA have a high probability of remaining in atrial fibrillation at hospital discharge and 6 months after surgery. The occurrence of atrial fibrillation seems to be influenced by the type of myocardial protection used but this does not appear to exert harmful effects.

Cardiopulmonary bypass exacerbates oxidative stress but does not increase proinflammatory cytokine release in patients with diabetes compared with patients without diabetes: regulatory effects of exogenous nitric oxide.

BACKGROUND: Cardiopulmonary bypass induces oxidative stress and a whole-body inflammatory reaction that are believed to increase surgical morbidity. OBJECTIVES: Our goal was to investigate the effect of nitric oxide supplementation on bypass-induced oxidative stress and inflammatory reaction in patients with and without diabetes undergoing elective coronary bypass graft surgery. METHODS: Patients with and without diabetes were randomized to receive an infusion of saline solution or the nitric oxide donor nitroglycerin at 1 microg. kg(-1). min(-1) starting 10 minutes before the initiation of cardiopulmonary bypass and then maintained for 4 hours (n = 10 per group). Serial blood samples were taken at various intervals and plasma was analyzed for markers of oxidative stress (lipid hydroperoxides, protein carbonyls, and protein nitrotyrosine) and inflammation (complement C3a, elastase, interleukin 8, and tumor necrosis factor alpha). RESULTS: Cardiopulmonary bypass significantly increased lipid hydroperoxides, protein carbonyls, protein nitrotyrosine, complement C3a, elastase, soluble E-selectin, interleukin 8, and tumor necrosis factor alpha in both groups. Infusion of nitroglycerin significantly reduced the increase in lipid hydroperoxides and protein carbonyls in patients who have diabetes without affecting levels in patients without diabetes. Nitroglycerin infusion markedly reduced protein nitrotyrosine and tumor necrosis factor alpha levels in both groups. In contrast, nitroglycerin infusion significantly increased C3a in patients without diabetes and increased elastase and interleukin 8 levels in patients with diabetes. CONCLUSIONS: Cardiopulmonary bypass induces a greater oxidative stress in patients with diabetes than in those without diabetes, and the inflammatory reaction is qualitatively different in the 2 groups of patients. In addition, nitroglycerin reduces oxidative stress in patients with diabetes and differentially affects the inflammatory response to bypass both in patients with and in those without diabetes. The results have important implications with respect to the use of nitric oxide donors during cardiopulmonary bypass.

Early discharge following coronary bypass surgery: is it safe?

OBJECTIVES: Early discharge has been proposed as a means of containing the escalating cost of health care in cardiac surgery. The aim of this study was to investigate whether shortening the length of hospital stay after coronary artery bypass surgery is safe and cost effective. METHODS: Patients (n=198) undergoing elective bypass surgery by two surgeons for a period of 12 months were prospectively entered into the study but not randomized. The anaesthetic and surgical treatments were identical in all patients with the exception that one of the surgeons used intermittent cold crystalloid cardioplegia ('normal discharge' group; n=119) and the other used intermittent ischaemia without cardioplegia ('early discharge' group; n=79). Previous to the study both surgeons discharged patients on the 7th-8th postoperative day. For the present study, one of the two surgeons adopted the new policy of discharging patients on the 4th postoperative day ('early discharge' group). The criteria for hospital discharge included: presence of sinus rhythm, absence of pyrexia and wound infection, normal routine blood tests, satisfactory chest X-ray and ECG and full mobility. RESULTS: The clinical characteristics were identical in the two groups. The number of grafts per patient was 2.8+/-0.8 and 3.2+/-1.0, and the total ischaemic time 47+/-13 and 46+/-14 min in the normal and early discharge groups, respectively (P=NS in each instance). In the normal discharge group the mean hospital stay was 7.7+/-3.3 days whereas in the early discharge group it was 4.7+/-2.0 days (P<0. 0001) with 73.5% of the patients being discharged within the first 4 days following surgery. The shortening of hospital stay resulted in a mean reduction of costs of pound750/patient. There was no operative mortality (<30 days following surgery) and the incidence of non-fatal perioperative complications were similar in the two groups, with the exception that the incidence of supraventricular arrhythmias was significantly higher in the normal discharge group than in the early discharge group (33% vs. 6.3% respectively; P<0. 0001). These rhythm abnormalities occurred within the first 4 days in 89% of patients following surgery and were the cause of readmission in only one patient in the normal discharge group. There were a total of ten (8.4%) readmissions in the normal discharge group and three (3.8%) in the early discharge group. CONCLUSION: Shortening the postoperative hospital stay to 4 days following elective coronary bypass surgery appears to be safe and can be a means of reducing the cost of care. This in turn may result in a greater availability of resources and in an effective way of reducing waiting lists.

Off-pump bypass graft operation significantly reduces oxidative stress and inflammation.

BACKGROUND: This study investigated whether off-pump coronary bypass graft operations on the beating heart under normothermic conditions reduces the systemic oxidative stress and inflammatory reaction seen in patients operated under cardiopulmonary bypass (CPB). METHODS: A cardiac stabilizer (Octopus Tissue Stabilizer; Medtronic Inc, Minneapolis, MN) was used to perform the coronary anastomoses on the normothermic beating heart with or without CPB. Serial blood samples were taken at various intervals. Plasma was analyzed for several oxidative stress and inflammatory markers. RESULTS: Significant increases from prior anesthesia values of lipid hydroperoxides (190% at 4 hours), protein carbonyls (250% at 0.5 hours) and nitrotyrosine (510% at 0.5 hours) were seen in the CPB group, but they were abolished or significantly reduced in the off-pump group. Complement C3a and elastase levels were rapidly increased upon the institution of CPB, and this was followed by increases in IL-8, TNF-alpha, and sE-selectin. In contrast, the rise of these factors was blunted in patients operated without CPB. CONCLUSIONS: Off-pump coronary bypass graft operation on a beating heart significantly reduces oxidative stress and suppresses the inflammatory reaction associated with the use of CPB.

Preconditioning the human myocardium by simulated ischemia: studies on the early and delayed protection.

BACKGROUND: There are data supporting the existence of ischemic preconditioning in man. This study investigated the most effective preconditioning protocol for the human myocardium and whether the second window of ischemic preconditioning (24 h) is as protective as the first window (< or = 2 h). METHODS AND RESULTS: Right atrial appendages (n = 6/group) obtained during coronary bypass surgery were prepared and superfused with normoxic and normothermic Krebs-Henseleit solution. After 30 min stabilisation, muscles were subjected to various preconditioning protocols followed by 90 min ischemia and 120 min reperfusion. At the end of each protocol, the leakage of creatinine kinase (CK, U/g wet wt) and the reduction of MTT to insoluble formazan dye (OD/mg wet wt), an index of cell viability, were measured. In study 1, preconditioning was induced by 2, 3, 5 and 10 min of ischemia followed by 5 min reperfusion. In study 2, 1-4 cycles of 2 or 5 min ischemia-5 min reperfusion were applied. In study 3, preconditioning was induced by 5 min ischemia-5 min reperfusion followed by 1, 2, 3 or 4 h reperfusion before the subsequent 90 min ischemia. In study 4, preconditioning with 5 min ischemia followed by 5 min reperfusion either immediately preceded 30 or 90 min ischemia/120 min reperfusion or was applied 24 h before. In study 1 and 2, optimal protection was achieved with 5 min or two cycles of 2 min preconditioning ischemia (CK = 3.06 +/- 0.31 and 2.89 +/- 0.02; MTT = 0.56 +/- 0.05 and 0.47 +/- 0.09, respectively vs. CK = 5.56 +/- 0.52 and MTT = 0.18 +/- 0.04 in ischemia alone group; P < 0.05). In study 3, protection was observed 2 h after preconditioning (CK = 3.43 +/- 0.22 and MTT = 0.46 +/- 0.09; P < 0.01 vs. ischemia alone group) but it was lost beyond 2 h (CK = 6.30 +/- 0.56 and MTT = 0.16 +/- 0.02 after 3 h; P = NS vs. ischemia alone group). In study 4, protection was observed 24 h following preconditioning when the atrial specimens were exposed to 30 min ischemia (CK = 2.96 +/- 0.38 and MTT = 0.61 +/- 0.01 vs. CK = 4.56 +/- 0.26 and MTT = 0.43 +/- 0.02 in ischemia alone group, P < 0.05); however, when the period of ischemia was extended to 90 min the beneficial effect of preconditioning was lost (CK = 10.28 +/- 0.05 and MTT = 0.11 +/- 0.05 vs. CK = 9.56 +/- 0.62 and MTT = 0.104 +/- 0.05 in ischemia alone group, P = NS). CONCLUSIONS: In the isolated human myocardium maximal protection induced by preconditioning is achieved by a total 4-5 min ischemic stimulus, an effect that is lost beyond 2 h of its application. Two windows of protection were identified, the first (< or = 2 h) being more potent than the second (24 h).

Evidence for mitochondrial K ATP channels as effectors of human myocardial preconditioning.

BACKGROUND: Sublethal periods of ischemia preceding a prolonged interval of ischaemia protect the myocardium. This myocardial preconditioning (PC) appears to be effected by KATP channels. These channels occur both in the sarcolemma and the mitochondrial membrane. We investigated whether mitochondrial KATP channels are the end-effector of PC in the human myocardium. METHODS: Right atrium specimens obtained from patients undergoing cardiac surgery were prepared and incubated in buffer solution at 37 degrees C. After 30-min stabilisation, the muscles were made ischemic for 90 min and then reperfused for 120 min. The preparations were randomised into eight experimental groups (n = 6/group): (1) Aerobic control--incubated in oxygenated buffer for 210 min, (2) ischemia alone--90 min ischemia followed by 120 min reperfusion, (3) PC--preconditioned with 5 min ischemia/5 min reperfusion, (4) Glibenclamide (10 microM) in the incubation media for 10 min before PC, (5) 5-hydroxydecanoate (5-HD, MitoKATP blocker, 1 mM) in the incubation media for 10 min before PC, (6) HMR 1883 (SarcKATP blocker, 10 microM) in the incubation media for 10 min before PC, (7) Pinacidil (0.5 mM) in the incubation media for 10 min before ischemia, and (8) Diazoxide (MitoKATP opener, 0.1 mM) in the incubation media for 10 min before ischemia. Creatinine kinase leakage into the medium (CK, IU/g wet wt) and MTT reduction (OD/mg wet wt.), an index of cell viability, were assessed at the end of the experiment. RESULTS: Ischemia alone resulted in a significant increase in CK leakage (8.01 +/- 0.35) and decrease in MTT (0.15 +/- 0.01) from the values seen in the aerobic control (2.24 +/- 0.52 and 0.78 +/- 0.10 respectively, P < 0.05 in both instances). PC fully reversed the effect of ischemia (CK = 2.97 +/- 0.31 and MTT = 0.61 +/- 0.05; P < 0.05 vs. ischemia alone group but P = NS vs. aerobic control group). Both Glibenclamide and 5-HD abolished the protection induced by PC (CK = 6.23 +/- 0.5 and 7.84 +/- 0.64; MTT = 0.18 +/- 0.03 and 0.13 +/- 0.02, respectively, P < 0.05 vs. PC), but interestingly, the protective effect of PC was not abolished by HMR 1883 (CK = 2.85 +/- 0.24 and MTT = 0.58 +/- 0.05, P = NS vs. PC). Diazoxide mimicked the protective effect of PC (CK = 3.56 +/- 0.32 and MTT = 0.58 +/- 0.02, P = NS vs. PC), however pinacidil exhibited less protection than PC (CK = 4.02 +/- 0.16 and MTT = 0.30 +/- 0.02, P < 0.05 vs. PC). CONCLUSIONS: These studies demonstrate that KATP channels are the end-effectors of ischemic preconditioning and that protection is mediated by mitochondrial KATP channels in human right atrial myocardium.