Pediatric Anesthesia Exposure: Decoding Its Neurodevelopmental Implications and Navigating the Nuances.

General anesthesia is fundamental in pediatric medical interventions, but its potential neurodevelopmental impact on children has raised concerns, necessitating a thorough investigation. This systematic review aimed to assess the association between pediatric anesthesia exposure and neurodevelopmental outcomes, focusing on dosage effects and identifying high-risk groups. The study involved an extensive literature search across PubMed, Medline, and Google Scholar, selecting 40 relevant studies from an initial pool of 2,000, based on inclusion criteria that focused on children under 18 years exposed to anesthesia, excluding those with major comorbidities or perioperative physiological insults. It was observed that while a single exposure to anesthesia had minimal impact on general neurodevelopment, repeated or prolonged exposures posed greater concerns. Despite these findings, the study identified gaps in certain areas like adaptive behavior and sensory cognition due to limited data. The conclusion drawn is that although the evidence on anesthesia-induced neurotoxicity in children remains inconclusive, the implications of pediatric anesthesia exposure are significant enough to warrant careful consideration by healthcare professionals, who should balance the procedural benefits against the risks. This study also calls for future research to standardize methodologies and employ consistent, validated neurodevelopmental measurement tools.

The Use of Facial Fillers in Clinical Practice: The Level of Patient Satisfaction and an Overview of Common Clinical Complications. / [Artículo traducido] Uso de rellenos faciales en la práctica clínica: nivel de satisfacción del paciente y visión general de las complicaciones clínicas comunes.

BACKGROUND: Patient esthetic satisfaction following facial fillers is an essential topic that should be studied as the number of individuals seeking treatment increases. The face is an essential component of the human body that is frequently associated with beauty, youthfulness, and health. Individuals may seek facial augmentation with fillers for a variety of reasons, such as congenital, acquired by means of aging or disease, or current aesthetic trends. OBJECTIVE: The aim is to assess patient's aesthetic satisfaction and description of common clinical complications in relation to the facial filler injections. METHOD: A cross sectional survey using a questionnaire derived from the global aesthetic improvement scale and WHO quality of life scale, convenience sampling was used to recruit patients attending cosmetic clinics, descriptive analysis and Chi-square methods were used to analyze the data. RESULTS: In the study, 500 female participants, with an average age of 28.48 years, were included. Over 90% reported improvement after filler treatment, ranging from improved to very much improved. A statistically significant correlation was observed between patient satisfaction and the number of filler treatments and the anatomical injection site. However, no statistically significant correlation was found when considering age groups. Local side effects, such as swelling and redness at the injection site, were common but generally mild and of short duration. CONCLUSION: Although the satisfaction level is currently high, practitioners in the field need to pay more attention to this important outcome, since understanding the patient's motivation and expectation before proceeding with the procedure is very important and can contribute significantly in determining patient satisfaction with the result.

The Use of Facial Fillers in Clinical Practice: The Level of Patient Satisfaction and an Overview of Common Clinical Complications.

BACKGROUND: Patient esthetic satisfaction following facial fillers is an essential topic that should be studied as the number of individuals seeking treatment increases. The face is an essential component of the human body that is frequently associated with beauty, youthfulness, and health. Individuals may seek facial augmentation with fillers for a variety of reasons, such as congenital, acquired by means of aging or disease, or current aesthetic trends. OBJECTIVE: The aim is to assess patient's aesthetic satisfaction and description of common clinical complications in relation to the facial filler injections. METHOD: A cross sectional survey using a questionnaire derived from the global aesthetic improvement scale and WHO quality of life scale, convenience sampling was used to recruit patients attending cosmetic clinics, descriptive analysis and Chi-square methods were used to analyze the data. RESULTS: In the study, 500 female participants, with an average age of 28.48 years, were included. Over 90% reported improvement after filler treatment, ranging from improved to very much improved. A statistically significant correlation was observed between patient satisfaction and the number of filler treatments and the anatomical injection site. However, no statistically significant correlation was found when considering age groups. Local side effects, such as swelling and redness at the injection site, were common but generally mild and of short duration. CONCLUSION: Although the satisfaction level is currently high, practitioners in the field need to pay more attention to this important outcome, since understanding the patient's motivation and expectation before proceeding with the procedure is very important and can contribute significantly in determining patient satisfaction with the result.

Public knowledge, attitude and practice towards antibiotics use and antimicrobial resistance in Saudi Arabia: A web-based cross-sectional survey.

BACKGROUND: Antimicrobial resistance is a global issue that causes significant morbidity and mortality. Therefore, this study aims to assess knowledge, attitudes, and practices (KAP) of the general Saudi populations toward antibiotics use. DESIGN AND METHODS: A cross-sectional, anonymous online survey was conducted from January 1 to May 11, 2020, across five major regions of Saudi Arabia. Participants (aged ≥18 years) were invited through social media to complete an online self-structured questionnaire. All data were analyzed by Statistical Package (SPSS v.25). Descriptive statistics, Pearson's Chi-squared, t-tests, one-way analysis of variance (ANOVA), and Pearson correlation analyses were conducted. RESULTS: Out of 443 participants, the majority (n=309, 69.8%) were females, 294 (64.4%) were married, 176 (39.7%) were 25-34 years of age, 338 (76.3%) were living in the Eastern Province, 313 (70.7%) had college or higher education, 139 (31.4%) were not working, and 163 (36.8%) had a monthly income of USD 800-1330. Overall, most participants demonstrated good knowledge and practice (88% and 85.6%, respectively).  However, 76.8%had inadequate attitude score levels towards antibiotics use. Of all the respondents, 74.9% knew that not completing a full course of antibiotics may cause antibiotics resistance, 91.33% did not agree that antibiotics should be accessed without a prescription, and 94.04% will not hand over leftover antibiotics to family members. Factors associated with adequate knowledge were female, medical jobs, and higher income (p<0.05). CONCLUSIONS: Our findings revealed that while most participants were aware of antibiotics use and demonstrated good knowledge, good practices, they had negative attitudes towards antibiotics use.

Public Knowledge, Attitudes, and Practice towards COVID-19 Pandemic in Saudi Arabia: A Web-Based Cross-Sectional Survey.

(1) Background: COVID-19 has become a worldwide public health problem. No previous study has investigated factors associated with COVID-19 knowledge, attitude, and practice (KAP) after completely lifting the curfew in all Saudi Arabia regions and cities. Therefore, adequate knowledge, a positive attitude, and correct control of COVID-19 are essential to eradicate the disease. Hence, this study aims to assess factors associated with KAP of COVID-19; (2) Methods: This cross-sectional web-based survey was performed with the participation of 4305 individuals aged over 15 years living in Saudi Arabia from 11 to 19 August 2020. They were included using the snowball sampling method; (3) Results: Of the 4305 participants, 94.9% were Saudis, 60% females, and 45.4% were in the age group of 20-34 years, 61.7% married, and 49.3% from the Eastern Province of Saudi Arabia. Most of the participants demonstrated good KAP levels (89.6%, 87.2%, and 87.2%) towards the COVID-19 pandemic, respectively. In addition, most of the participants (85.8%) used the internet and social media as a source for COVID-19 information (4) Conclusions: The finding showed that most of the participants demonstrated good knowledge of COVID-19, positive attitudes, and demonstrated good practices for preventing the spread of disease infection.

Prophylactic antibiotics for percutaneous endovascular procedures.

Percutaneous endovascular techniques are used increasingly in the vascular armamentarium. Commonly performed as day case procedures under local anaesthetic, they are suited to the highly co-morbid vascular patient population. Furthermore, technological advances have resulted in ever improving outcomes for aneurysmal and occlusive disease. Endovascular procedures such as endovascular aneurysm repair or iliac artery stenting are traditionally associated with reduced infectious complications compared to equivalent open techniques. However, when they do occur, they are equally devastating and often associated with limb loss or death since the only effective treatment is removal of all infected material. The use of prophylactic antibiotics to reduce infectious complications in open surgery has a strong evidence base, but there is no equivalent data for percutaneous endovascular procedures. The Society of Interventional Radiology published formal guidelines for adult antibiotic prophylaxis in 2010. Based on relatively poor quality studies, they nevertheless represent the first official guidance in the field and stress the need for large randomised controlled trials to further guide the debate. Broadly, the benefits of reduced infectious complications must be balanced against the fiscal cost of increased antimicrobial usage, promotion of multi-drug resistant organisms and patient side-effect profiles. The number needed to treat to prevent one infection is high yet without it a small but significant number of patients will suffer serious adverse outcomes secondary to infection of endovascular prostheses. This review article aims to summarise the evidence around the use of prophylactic antibiotics in percutaneous endovascular procedures.

Phase IIa randomized, placebo-controlled study of antimicrobial photodynamic therapy in bacterially colonized, chronic leg ulcers and diabetic foot ulcers: a new approach to antimicrobial therapy.

BACKGROUND: With increasing problems of antibiotic resistance, photodynamic therapy (PDT) is being developed as a novel antimicrobial treatment. Following light activation, cationic photosensitizer PPA904 [3,7-bis(N,N-dibutylamino) phenothiazin-5-ium bromide] kills a broad spectrum of bacteria in vitro and this has a variety of potential clinical applications. OBJECTIVES: To determine if PDT in bacterially colonized chronic leg ulcers and chronic diabetic foot ulcers can reduce bacterial load, and potentially lead to accelerated wound healing. METHODS: Sixteen patients with chronic leg ulcers and 16 patients with diabetic foot ulcers (each eight active treatment/eight placebo) were recruited into a blinded, randomized, placebo-controlled, single-treatment, Phase IIa trial. All patients had ulcer duration > 3 months, bacterially colonized with > 10 colony-forming units cm . After quantitatively assessing pretreatment bacterial load via swabbing, PPA904 or placebo was applied topically to wounds for 15 min, followed immediately by 50 J cm of red light and the wound again sampled for quantitative microbiology. The wound area was measured for up to 3 months following treatment. RESULTS: Treatment was well tolerated with no reports of pain or other safety issues. In contrast to placebo, patients on active treatment showed a reduction in bacterial load immediately post-treatment (P < 0·001). After 3 months, 50% (four of eight) of patients with actively treated chronic leg ulcer showed complete healing, compared with 12% (one of eight) of patients on placebo. CONCLUSIONS: This first controlled study of PDT in chronic wounds demonstrated significant reduction in bacterial load. An apparent trend towards wound healing was observed; further study of this aspect with larger patient numbers is indicated.

Hydroxymethyl lysine is a source of bioavailable lysine for ruminants.

Experiments were conducted to evaluate the availability to ruminants of lysine from hydroxymethyl lysine, a product potentially resistant to ruminal degradation yet able to release free lysine when subjected to the acidic environment of the abomasum. An in vitro ruminal fermentation assay that led to ammonia production from free lysine was used for initial assessments, but the hydroxymethyl lysine was inhibitory to lysine degradation at the concentrations tested in vitro; therefore, an in vivo assay with sheep, using plasma lysine concentrations as the response criterion, was used for assessment. twelve mature sheep were fed graded amounts of lysine from either a commercially available ruminally protected lysine product with known availability or from hydroxymethyl lysine. the protected lysine product provided 3 or 6 g/d of metabolizable lysine, whereas the hydroxymethyl lysine provided 3 or 6 g/d of total lysine. Plasma lysine concentrations increased linearly in response to both the ruminally protected lysine product and hydroxymethyl lysine. by slope ratio analysis, the bioavailability of lysine in hydroxymethyl lysine was estimated to be 94% of that for the commercially available product. We concluded that hydroxymethyl lysine may be used as an effective means of supplementing lysine to ruminants.

Review of medical and surgical management of Clostridium difficile infection.

Clostridium difficile infection (CDI) has become an important area in our daily clinical practice. C. difficile is known to cause a broad spectrum of conditions ranging from asymptomatic carriage, through mild or moderately severe disease with watery diarrhoea, to the life-threatening pseudomembranous colitis (PMC), with toxic megacolon and ileus. Peoples who have been treated with broad-spectrum antibiotics, patients with serious underlying co-morbidities and the elderly are at greatest risk. Over 80% of CDIs reported are in people aged over 65. Due to the alarming increase in its frequency, appearance of more virulent strains and occasional need for life-saving surgical intervention, a more coherent multidisciplinary approach is needed. Combination of rapid turn round time and accurate diagnosis will result in a better management of CDI and a timely implementation of infection control measure. Discontinuation of causative agents such as antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. Relapses of CDI have been reported in about 20-25% of cases, this may increase to 45-60% after the first recurrence. Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis is made to avoid sepsis or bowel perforation. Colectomy may improve the outcome of the patient with systemic or complicated Clostridium difficile colitis. This article reviews the changing epidemiological picture, microbiology, histopathology and both medical and surgical managements.

Possibilities for fertility restoration: a new surgical technique.

Previously published work concluded that uterine artery microvascular anastomosis in the porcine model was feasible with subsequent normal vascular function in pregnancy. of the anastomosed vessels. The objective of this study was to assess the feasibility of uterine autotransplantation in a porcine model using microvascular anastomoses. Eight large white/landrace sows of proven fertility were used. A supracervical hysterectomy with or without bilateral salpingo-oophorectomy (BSO) was performed. After 1 hour of cold storage in a transplant solution, the specimen was reintroduced and followed by stepwise vascular reanastomosis. Objective perfusion index measurements suggested adequate uterine perfusion after transplantation. Postoperatively, sow 1 survived to 3 months with no signs of oestrus, and sows 2, 6, and 8 were killed on days 6, 33, and 54, respectively, for pelvic infection. Histopathology of the uterine grafts revealed gradual vessel thromboses. Microvascular reanastomosis is feasible, however, unsuccessful in uterine autotransplantation because of gradual vessel thromboses. The porcine model is highly susceptible to postoperative infection.

Induction and maintenance therapy of cytomegalovirus central nervous system infection in HIV-infected patients.

OBJECTIVE: To evaluate the efficacy and safety of the foscarnet-ganciclovir combination in induction therapy (IT) and maintenance therapy (MT) for cytomegalovirus (CMV) central neurological disorders in HIV-infected patients. DESIGN: An open pilot non-comparative multicentre study. METHODS: Thirty-one patients with acute CMV encephalitis (CMVe) (n = 17) or CMV myelitis (CMVm) (n = 14) during the era before highly active antiretroviral therapy (HAART) received intravenous IT with foscarnet 90 mg/kg plus ganciclovir 5 mg/kg twice a day followed by MT. The primary endpoint was clinical efficacy, assessed at the end of the induction phase. RESULTS: The foscarnet-ganciclovir combination in IT resulted in a 74% (23 out of 31 patients) clinical improvement or stabilization. Eight patients did not respond clinically. Side-effects leading to drug discontinuation occurred in 10 patients during IT. Among the 23 patients who qualified for the maintenance phase, CMV disease progressed in 10, with a median time to the first relapse of 126 days (range 64-264 days). Overall, the median survival time was 3 months [95% confidence interval (CI), 2-4 months]. CONCLUSION: The combination of foscarnet and ganciclovir can safely be used for CMV central nervous system (CNS) infection, with an improvement or stabilization in 74% of patients. Life-long MT with this combination is recommended as long as the immune system is profoundly impaired.

Candida parapsilosis: an unusual organism causing prosthetic heart valve infective endocarditis.

We report a case of Candida parapsilosis prosthetic heart valve infective endocarditis in a 67-year-old man. The infection was successfully treated with liposomal amphotericin B (AmBisome) and flucytosine. Surgical replacement of the infected valve was necessary. Recurrence was prevented with oral fluconazole 400mg daily as maintenance therapy. The patient remained well after 2 years of follow-up.

[Coronary surgery on the beating heart under extracorporeal circulation in high-risk patients. An acceptable compromise?]. / La chirurgie coronaire à coeur battant sous circulation extracorporelle chez les patients à haut risque. Un compromis acceptable?

Coronary artery surgery with cardioplegia in high risk patients carries a risk of myocardial ischaemia and, without cardiopulmonary bypass, is not always technically feasible. The authors assessed an alternative, surgery on the beating heart with haemodynamic assist by cardiopulmonary bypass in 43 consecutive patients with poor left ventricular function (mean ejection fraction: 0.26), evolving myocardial ischaemia or acute myocardial infarction, old age (mean: 79.5 years) and comorbid conditions. Results were assessed mainly on clinical criteria. In addition, 9 patients had pre- and post-cardiopulmonary bypass measurements of markers of myocardial ischaemia (troponine Ic) and systemic inflammation (interleukines 6 and 10, elastase). In 6 cases, right atrial biopsy was analysed for expression of messenger ribonucleic acid coding for heat shock protein (HSP) 70; the data were compared with those of patients operated under warm blood cardioplegia. There was one cardiac death and one myocardial infarction. Myocardial conservation was confirmed by the minimal increase in troponine Ic levels and the significant increase in HSP 70 in RNA suggesting myocardial adaptation to stress. On the other hand, the minimal concentrations of mediators of inflammation were not significantly changed. In selected high risk patients, coronary revascularisation on the beating heart under cardiopulmonary bypass could be a valuable alternative. It conserves the potentially deleterious effects of cardiopulmonary bypass but peroperative global myocardial ischaemia, an important factor in the aggressivity of cardiac surgery, is eliminated.

Inhibition of the pacemaker current: a bradycardic therapy for off-pump coronary operations.

BACKGROUND: The accurate performance of coronary anastomoses on the beating heart requires some form of myocardial immobilization that can be achieved pharmacologically. Different classes of drugs can be used to induce bradycardia, but the most effective in this setting of off-pump operation has not yet been determined. METHODS: Fifty-six isolated buffer-perfused rabbit hearts were divided into seven equal groups. Control hearts were continuously perfused throughout the experimental time course. A second group of hearts underwent 60 minutes of potassium arrest (at 37 degrees C) followed by 1 hour of reperfusion. The following pharmacologic approaches were tested in the remaining five groups: short-acting beta-blockade (esmolol, 6 x 10(-3) mol/L and 3 x 10(-4) mol/L), opening of adenosine triphosphate-dependent potassium channels (nicorandil, 10(-3) mol/L and 10(-5) mol/L), and inhibition of the pacemaker current, which largely accounts for the diastolic depolarization of sinoatrial node cells (S 16257-2, 3 x 10(-6) mol/L). Each drug was infused at a constant rate for 60 minutes, after which hearts were perfused for 1 additional hour with drug-free buffer. Heart rate and isovolumic measurements of function and coronary flow were serially taken during and after drug infusion. RESULTS: The worst recovery of systolic and, moreover, diastolic function was yielded by potassium arrest. Neither esmolol nor nicorandil was able to induce a significant bradycardia. However, nicorandil did not impair function which, conversely, was markedly depressed after esmolol therapy. Significant bradycardia (p < 0.0001 versus corresponding baseline values and versus all other groups) was only achieved with pacemaker current inhibition, which was otherwise associated with an excellent preservation of contractility, diastolic function, and coronary flow. CONCLUSIONS: Inhibition of the pacemaker current seems to be an effective approach for inducing intraoperative bradycardia without compromising left ventricular function or flow.

On-pump, beating-heart coronary artery operations in high-risk patients: an acceptable trade-off?

BACKGROUND: Current cardioplegic techniques do not consistently avoid myocardial ischemic damage in high-risk patients undergoing coronary artery bypass grafting. Alternatively, revascularization without cardiopulmonary bypass is not always technically feasible. We investigated whether an intermediary approach based on maintenance of a beating heart with cardiopulmonary bypass support but without aortic cross-clamping might be an acceptable trade-off. METHODS: Thirty-seven consecutive patients underwent coronary artery bypass grafting (with an average of two grafts per patient) in a pump-supported, non-cross-clamped beating heart. Inclusion criteria were poor left ventricular function (18 patients; mean ejection fraction, 0.25), evolving myocardial ischemia or infarction (11 patients, 5 of whom were in cardiogenic shock), and advanced age (3 patients; mean age 79.5 years) with comorbidities. Results were assessed primarily on the basis of clinical outcome. In addition, measurements of plasma levels of markers of myocardial damage (troponin Ic) and systemic inflammation (interleukin-6, interleukin-10, elastase) were done in 9 patients before and after bypass. In 6 patients, right atrial biopsy specimens were taken before and after bypass and processed by Northern blotting for the expression of messenger ribonucleic acid coding for the cardioprotective heat-shock protein 70. These biologic data were compared with those from control patients who underwent warm cardioplegic arrest within the same time span. RESULTS: There was one cardiac-related death (2.7%), one Q-wave myocardial infarction, and no strokes. Four other deaths occurred from noncardiac causes, yielding an overall mortality rate of 13.5%. Limitation of myocardial injury was demonstrated by the minimal increase in postoperative troponin Ic levels (3.3 +/- 1.0 micrograms/L versus 6.6 +/- 1.5 micrograms/L in controls; p < 0.05) and the finding that heat-shock protein 70 messenger ribonucleic acid levels (expressed as a percentage of an internal standard) were significantly increased after bypass compared with pre-bypass values (279% +/- 80% versus 97% +/- 21%; p < 0.05). In the control group (cardioplegia), end-arrest values of heat-shock protein 70 messenger ribonucleic acid were not significantly changed from baseline (148% +/- 49% versus 91% +/- 29%), a finding suggesting a defective adaptive response to surgical stress. Conversely, peak levels of inflammatory mediators were not significantly different between the two groups. The eight grafts to the left anterior descending coronary artery that were assessed angiographically, by transthoracic Doppler echocardiography, or both methods were patent with satisfactory anastomoses. CONCLUSIONS: In select high-risk patients, on-pump, beating-heart coronary artery bypass grafting may be an acceptable trade-off between conventional cardioplegia and off-pump operations. It is still associated with the potentially detrimental effects of cardiopulmonary bypass but eliminates intraoperative global myocardial ischemia.

Warm blood cardioplegia in high risk patients.

OBJECTIVE: Despite overall good clinical results, cardiac surgery in high risk patients, such as those with poor left ventricular function or heavily hypertrophied myocardium, is still challenging. This study was designed to assess the efficacy of warm blood cardioplegia (WBC) in these two subgroups of patients. METHODS: Fifty-two patients, with an ejection fraction less than 50%, who underwent surgical revascularization, and 36 patients, with marked left ventricular hypertrophy (LVH), who were operated on for aortic valve replacement (AVR), were consecutively studied. All of them received continuous retrograde 'warm' blood cardioplegia. Results were assessed on clinical outcomes and compared with those predicted from a risk-stratifying index which has been previously validated in a large multicenter population-based study (Ontario score). RESULTS: For cardiac revascularization, the rates of overall hospital mortality, Q-wave infarctions and inotropic use were respectively 5.8%, 9.6% and 21.1%, comparing favorably with those of the Ontario Group. For aortic valve replacement, the incidence of hospital mortality and Q-wave infarction was 2.8%. CONCLUSIONS: By virtue of the study design, these data cannot conclusively establish the superiority of warm blood cardioplegia over other methods of myocardial protection. However, they support the safety of this technique, and suggest that these subgroups of high risk patients might represent the elective indication for aerobic arrest.

[Valvular homografts]. / Les homogreffes valvulaires.

Renewed interest in heart valve homografts is related to recent advances in viability. Increased viability is achieved by collecting explanted hearts from multi-organ donors and cryopreservation. Right access is usually used in case of hereditary cardiopathy to resect or repair the aortic, mitral and tricuspid valves. Life-long anticoagulant treatment can thus be avoided. Current mid-term and long-term results are very promising.

Failure of preconditioning to improve postcardioplegia stunning of minimally infarcted hearts.

BACKGROUND: Ischemic preconditioning is an effective means of reducing myocardial infarct size, but its ability to attenuate stunning after an episode of surgically relevant global ischemia remains elusive. Likewise, the role played by adenosine in this setting has not been established conclusively. This study was designed to address these two issues. METHODS: Thirty isolated, crystalloid-perfused rabbit hearts were subjected to 60 minutes of normothermic potassium arrest and 60 minutes of reperfusion. They were divided into three equal groups. The first group had no prearrest intervention and served as a control. In the second group, ischemic preconditioning was achieved with 5 minutes of zero-flow ischemia followed by 5 minutes of buffer reperfusion before arrest. In the third group, the hearts were first infused for 5 minutes with the nucleoside transport inhibitor draflazine (10(-6) mol/L), the efficacy of which was demonstrated by reversal of the normally high inosine to adenosine ratio in the coronary effluent. These hearts subsequently were given 2 additional minutes of ischemic (zero-flow) preconditioning followed by 5 minutes of reperfusion before arrest. During reperfusion, function was measured serially under isovolumic conditions. Myocardial necrosis was estimated from the release of creatine kinase after the initial 5 minutes of reflow, and the planimetrically determined extent of infarction was determined by triphenyltetrazolium chloride staining. RESULTS: Baseline hemodynamic data were comparable among the three groups. Neither ischemic preconditioning alone nor ischemic preconditioning with draflazine-induced enhancement of endogenous adenosine levels improved postischemic recovery of function over that seen in control, untreated hearts. These results correlated with a minimal amount of infarction in the control group (on average, <10% of the left ventricle), which was not reduced further by either preconditioning regimen. CONCLUSIONS: These data support the idea that, in the absence of substantial necrosis, ischemic preconditioning does not ameliorate postischemic stunning, which leads to the question of its usefulness in clinical cardiac operations. Although, in this model, protection was not potentiated by increasing endogenous concentrations of adenosine, it remains a worthwhile goal to identify the final effectors of the signaling pathway accounting for the otherwise demonstrated cardioprotective effects of preconditioning because of the potential for these mediators to act as effective antiischemic agents.

Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass.

BACKGROUND: The adhesion of neutrophils to endothelial cells and their subsequent transendothelial migration play a major role in inflammatory damage elicited by cardiopulmonary bypass (CPB) because these events are linked to the release of cytotoxic proteases and oxidants. However, the patterns of neutrophil trafficking in relation to systemic temperature during clinical CPB have not yet been characterized. METHODS AND RESULTS: Twenty case-matched patients undergoing warm (31.8 +/- 0.4 degrees C) or cold (26.3 +/- 0.5 degrees C, P < .0001 versus warm) bypass were studied. Blood samples were simultaneously collected from the right and left atria before, at the end of, and 30 minutes after CPB. Plasma levels of C3a, P- and E-selectins, elastase, and interleukin-8 were determined by immunoassays. The results demonstrate: (1) a rise in C3a, reflecting complement activation, (2) a fall in soluble E-selectin consistent with an increased adhesiveness of activated neutrophils, (3) a rise in soluble P-selectin expected to enhance endothelial adhesion of these neutrophils, (4) a rise in elastase, suggesting an adhesion-triggered neutrophil degranulation, and finally (5) a rise in interleukin-8 that is likely to promote transendothelial migration of adherent neutrophils. All of these changes occurred in the two groups of patients and were significant compared with prebypass values. However, in none of the groups was there a significant difference between right and left atrial values for any of the markers. The single difference between cold and warm bypass patients was a significant reduction of elastase release in the cold group (P < .001 versus the warm group). CONCLUSIONS: Clinical CPB is associated with biological changes suggesting the occurrence of neutrophil trafficking. Hypothermia provides only partial protection through a reduced release of elastase. Overall, these results reinforce the rationale for the development of therapeutic strategies targeted at blunting the neutrophil-mediated component of bypass-induced inflammatory damage.