Search

Despite the popularity of single-dose cardioplegic techniques, the time window and targeted population for successful reperfusion remain unclear. We tested currently available techniques based on cell viability and integrity to demonstrate long-term cardioprotection and clarify whether these solutions were performed on neonatal/adult endothelium and myocardium by examining different cell lines. Cell viability with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test proliferation assay and membrane integrity with the lactic dehydrogenase (LDH) cytotoxicity test were documented in a cell culture/microscopy setting on adult (human umbilical vein endothelium [HUVEC]), neonatal (H9C2-cardiomyocytes), and myofibroblast (L929) cell lines. Apoptotic cell activity and necrosis were evaluated by acridine orange/propidium iodide (AO/PI) staining. Twenty-four hours after seeding, cells were incubated in control (Dulbecco’s modified Eagle), St. Thomas and blood cardioplegia (4:1), histidine–tryptophan–ketoglutarate (HTK), and del Nido solutions at 32°C followed by an additional 6, 24, and 48 hours in standard conditions (37°C, 5% CO2). Experiments were repeated eight times. In MTT cell viability analysis, HTK protection was significantly better than the control medium in L929 cell lines at 48th hours follow-up and acted markedly better on the HUVEC cell line at 24th and 48th hours. del Nido and HTK provided significantly better protection on H9C2 (at 24th and 48th hours). Apoptotic and necrotic cell scoring as a result of AO/PI staining was found consistent with MTT results. The LDH test demonstrated that the level of cell disruption was significantly higher for St. Thomas and blood cardioplegia in H9c2 cells. Experimental studies on cardioplegia aimed at assessing myocardial protection use time-consuming and often expensive approaches that are unrealistic in clinical practice. We have focused on identifying the most effective cell types and the direct consequences of different cardioplegia solutions to document long-term effects that we believe are the most underestimated ones in the cardioplegia literature.

We present our multidisciplinary and multistep strategy in patients undergoing minimally invasive aortic valve replacement (mAVR) on minimally invasive extracorporeal circulation (MiECC) compared with control groups of a single strategy and conventional techniques. This cohort study included high-risk patients (Society of Thoracic Surgeons [STS] risk score >8%) undergoing aortic valve surgery under different strategies during the period from January 2017 until March 2019. Patients were matched for age, gender, body mass index, and STS score: group 1 (MiAVR) based on a minimally invasive technique with J-mini-sternotomy, rapid deployment valve (RDV), and type IV customized MiECC; group 2 (control-mAVR) consisted of minimally invasive technique with only J mini-sternotomy and RDV on a conventional extracorporeal system; group 3 (control-MiECC): full sternotomy and type IV customized MiECC; and group 4 (control): full sternotomy on a conventional extracorporeal system. The MiAVR group had significantly less duration of x-clamp time (35.4 ± 11 minutes), postoperative respiratory support (4.1 ± 1 hour), postoperative hemorrhage (250 ± 50 mL), and intensive care unit stay (1 ± .5 days) than the control-conventional (group 4) group. Seventy-six percent of patients did not receive any blood products in MiAVR (p= .025 vs. group 4). Incidence of atrial fibrillation (8%) and low cardiac output (14%) in MiAVR were significantly better than control. Critics of minimally invasive techniques sustain that potential advantages are offset by a longer cross-clamp and cardiopulmonary bypass duration, which may translate into inferior clinical outcomes. We advocate that our multidisciplinary approach supported by multiple technologies may be associated with faster recovery and superior outcomes than conventional minimally/conventional techniques.

Background Despite the increasing popularity of single-dose cardioplegia techniques in coronary artery bypass grafting, the time window for successful reperfusion remains unclear. This study aimed to compare different cardioplegic techniques based on early and 30-day clinical outcomes via thorough monitoring.Methods This prospective cohort study included high-risk patients undergoing coronary artery bypass grafting and receiving 3 different types of cardioplegia between January 2017 and June 2019. Group 1 (n= 101) had a single dose of del Nido cardioplegia, group 2 (n= 92) had a single dose of histidine-tryptophane-ketoglutarate, and group 3 (n= 119) had cold blood cardioplegia. Patients were examined perioperatively by memory loop recording and auto-triggered memory loop recording for 30 days, with documentation of predefined events.Results Interleukin-6 and cardiac troponin levels in group 1 were significantly higher than those in groups 2 and 3. The incidence of predefined events as markers of inadequate myocardial protection was significantly higher group 1, with more frequent atrial fibrillation attacks and more hospital readmissions. The readmission rate was 17.6% in group 1, 9% in group 2, and 8% in group 3.Conclusions Our data demonstrate the long-term efficacy of cardioplegic techniques, which may become more crucial in high-risk patients who genuinely have a chance to benefit from adjunct myocardial protection. Patients given del Nido cardioplegia had a significantly more prominent inflammatory response and higher troponin levels after cardiopulmonary bypass. This group had issues in the longer term with significantly more cardiac events and a higher rehospitalization rate.

Objective This study aims to compare del Nido cardioplegia (DNC) and histidine–tryptophan–ketoglutarate (HTK) cardioplegic solutions in minimally invasive aortic valve replacement (mini-AVR) surgery to discuss the safety level of myocardial protection and rationale for redosing intervals.Methods During the period from January 2017 to June 2019, 200 patients undergoing mini-AVR (solely or with concomitant procedures) were prospectively randomized to DNC (n= 100) and HTK (n= 100), both up to 90 minutes ischemic time. Patients with ischemic time over 90 minutes, needing a redosing, were further analyzed in 2 subgroups with DNC-R (n= 30) and HTK-R (n= 36). Sensitive biomarkers, in addition to routine biochemistry, were also documented at baseline (T1), after cessation of cardiopulmonary bypass (T2), and on the first postoperative day (T3). Transmural myocardial biopsies were sampled for staining.Results No statistical differences could be demonstrated in DNC and HTK groups with up to 90 minutes cross-clamp times in routine biochemical measurements and basic perioperative clinical outcomes. DNC-R showed significantly more arrhythmia/AV block incidence resulting in more extended intensive care unit (ICU) stay. Interleukin-6 and syndecan-1 in DNC and DNC-R groups were substantially higher at T2. Aquaporin-4 levels were significantly lower in the DNC-R group, demonstrating unsatisfactory response of cells to an excessive volume at T2.Conclusions DNC and HTK provided acceptable myocardial protection as single-dose applications. DNC-R had significantly unbalanced levels of biomarkers, and more arrhythmia/AV block incidence resulting in more extended ICU stay. For patients who may need redosing HTK may be preferable to DNC.

This prospective randomized study compares the inflammatory response and fibrinolytic activation of fully coated/uncoated and open/closed extracorporeal circuits (ECC) in high risk patients. Over a 2-month period, 48 patients with EuroSCOREs 6 or greater undergoing coronary revascularization were pro spectively randomized to one of the four perfusion protocols: Group 1: Closed and totally hyaluronan based heparin free coated (Vision HFO-GBS-HF™, Gish Biomedical, Rancho Santa Margarita, CA) ECC with a soft-shell coated venous reservoir (SVR11S2-HFC™, Gish Biomedical) and a hard-shell cardiotomy (CAPVRF44, Gish Biomedical) (n= 12); Group 2: Closed and totally uncoated identical ECC with soft-shell uncoated venous reservoir and a hard-shell cardiotomy (n= 12); Group 3: Open, totally hyaluronan based heparin free coated ECC (n= 12); and Group 4: Control-open, uncoated ECC (n= 12). Blood samples were collected at T1: Baseline; T2: 15 minutes after cardiopulmonary bypass (CPB) initiation; T3: before cessation of CPB; T4: 15 minutes after protamine reversal, and T5: in the intensive care unit. Serum IL-6 levels were significantly lower at T2 in all study groups, at T3 for coated groups, and T4 for closed+coated group (p< .05 versus control). Creatine kinase M-band (MB) levels in coronary sinus blood demonstrated well preserved myocardium after CPB in both coated groups versus Control (p< .05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups versus control at T2, for both coated groups at T3 and only for closed+coated group at T4 (p< .05). Postoperative hemorrhage (mL) was 510 ± 40 in closed+coated and 536 ± 40 in open+coated groups (control: 784 ± 48, p≤ .05). No significant differences in thrombin-antithrombin complex and free plasma hemoglobin were observed. Desorbed protein amount on ECC (mg/dL) was 1.7 ± .01 in closed+coated, 2.01 ± .01 in open+coated, and 3.3 ± .015 in control groups (p≤ .05). Use of a closed and completely heparin free coated ECC may reduce neutrophil degradation, cytokine release characterized by improved clinical outcomes including reduced blood loss, reduced requirement for inotropes, and reduced atrial fibrillation.

Using a regional cardiopulmonary bypass (CPB) registry, we compared the practice of CPB at eight northern New England institutions to recently published recommendations. We examined CPB practice among 3597 adult patients undergoing isolated coronary artery bypass grafting surgery from January 2004 to June 2005. Registry variables were used to compare regional CPB practice to recommendations on topics of neurologic protection (pH management, avoidance of hyperthermia, minimizing return of pericardial suction blood, aortic assessment, arterial line filtration), maintenance of euglycemia, reduction of hemodilution, and attenuation of the inflammatory response. We report overall regional practice (regional minimum, maximum). All centers used alpha-stat pH management and arterial line filters. Avoidance of hyperthermia (temperature <37°C) was achieved during 23.4% of procedures (regional minimum, 1.5%; maximum, 83.2%). Minimizing return of pericardial suction blood was achieved in 23.7% of cases (0.7%, 93.6%). Aortic assessment was performed during 45.7% of procedures (1.3%, 98.9%). Maintenance of euglycemia (<200 mg/dL) was accomplished in 82.7% (57.1%, 97.9%) of cases. Hemodilution (hematocrit <23% on CPB) was lower for men 32.4% (20.6%, 52.3%) than women 77.9% (64.7% 88.9%). Men were less likely to receive red blood cell transfusions in the operating room (11.0%; 1.8%, 20.9%) than women (54.6%; 30.1%, 70.6%). In an effort to attenuate the inflammatory response, surface coated circuits were used in 83.3% of procedures (8.8%, 100%). During this time, gaps existed between regional CPB practice and recently published recommendations. We continue to prospectively measure CPB practice relating to these recommendations to monitor and improve the care provided to our patients.

We tested documented in vitro and ex vivo advantages of novel hyaluronan based heparin bonded extracorporeal circuits in a prospective randomized study. During the period from June until September 2005, 40 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n= 20): Group 1 was treated with hyaluronan-based heparin-bonded circuits and group 2 was treated with uncoated control circuits. Complete blood count, fibrinogen, albumin, C3a, interleukin-2 levels, and thromboelastographic data were documented after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 minutes after initiation of CPB (T3), before cessation of CPB (T4), 15 minutes after reversal with protamine (T5), and the first postoperative day at 8:00 a.m. (T6). Hollow fibers were collected for consecutive biomaterial analysis by optical and scanning electron microscopy (SEM). Desorbed protein deposition on fibers was compared by spectrophotometry. Leukocyte counts were lower in T4-T6 in group 1 (p< .05). Platelet counts demonstrated significant differences at T4 and T5 in coated group (p< .05). Albumin and fibrinogen levels were better preserved in Group 1 at T4, T5 and T4, T6, consecutively (p< .05). C3a and IL-2 levels were lower at T3-T5 and T4-T5 in intervention group (p< .05). Postoperative hemorrhage was 412 ± 50 mL in group 1 and 684 ± 50 ml in group 2 (p< .05). Respiratory support time was shorter in group 1 versus control (p< .05). Platelet adhesion was significantly lower in intervention group. Amount of desorbed protein was 1.44 ± 0.01 mg/dL in group 1 and 1.94 ± 0.01 mg/dL in control (p< .05). SEM and spectrophotometry demonstrated better surface preservation in the hyaluronan coated group. Novel hyaluronan-based heparin-bonded circuits reduce platelet adhesion-aggregation and protein adsorption and provide better perioperative clinical parameters through platelet, albumin, and fibrinogen-sparing effects.

Photons have proven to be excellent carriers of quantum information and play essential roles in numerous quantum information processing (QIP) applications. In particular, heralded single-photon sources via spontaneous parametric-down conversion (SPDC) have been a key technology for demonstrating small-scale QIP, yet their low generation efficiency is a critical limitation to furthering the scale-up of optical QIP technology. In order to efficiently overcome the probabilistic nature of SPDC, here we demonstrate time multiplexing for up to 30 time slots of a periodically pumped heralded single-photon source using a switchable low-loss optical storage cavity. We observe a maximum single-photon probability of 38.6±0.4% in periodic output time windows, corresponding to ∼6 times enhancement over a nonmultiplexed source but with no increase in the contribution of unwanted multiphoton events. Combining this time-multiplexing technique with a heralded source producing pure single-photon states should enable larger-scale optical QIP systems than previously realized.

Cardiac surgery requiring cardiopulmonary bypass (CPB) has increased in both number and safety over the past four decades. Postoperative bleeding continues to be a major cause of perioperative morbidity. The reported incidence varies from 4-32%.

The continued ability to treat bacterial infections requires effective antibiotics. The development of new therapeutics is guided by knowledge of the mechanisms of action of and resistance to these antibiotics. Continued efforts to understand and counteract antibiotic resistance mechanisms at a molecular level have the potential to direct development of new therapeutic strategies in addition to providing insight into the underlying biochemical functions impacted by antibiotics. The interaction of antibiotics with the peptidyltransferase center and adjacent exit tunnel within the bacterial ribosome is the predominant mechanism by which antibiotics impede translation, thus stalling growth. Resistance enzymes catalyze the chemical modification of the RNA that composes these functional regions, leading to diminished binding of antibiotics. This review discusses recent advances in the elucidation of chemical mechanisms underlying resistance and driving the development of new antibiotics.

This prospective randomized study compares novel hyaluronan-based heparin-bonded circuits vs. uncoated controls across EuroSCORE patient risk strata including biomaterial evaluation. Over a two-year period, 90 patients undergoing coronary artery bypass grafting were prospectively randomized to one of the two perfusion protocols: Group 1 was treated with hyaluronan-based heparin-bonded preconnected circuits (Vision HFO-GBS, Gish, CA, USA) and Group 2 with identical uncoated controls. Each group was composed of three subgroups (n=15) with respect to preoperative evaluation of low (EuroSCORE 0-2), medium (3-5) and high (6+) risk patients. Blood samples were collected after induction (T1) and heparinization (T2), 15 min after cardiopulmonary bypass start (T3), before cessation of CPB (T4), 15 min after reversal (T5), and the first postoperative day (T6). In high-risk patients, platelet counts demonstrated significant preservation at T4, T5 and leukocyte counts were lower at T5 in hyaluronan group (P

Purpose This prospective, randomized study compared the clinical performance of three types of circuits: a newly introduced, fully-coated, interchangeable open-closed circuit with a dual configuration (hard shell with a bypass shunt), reduced length, and reduced prime of less than 800 cc (CondECC); a completely coated circuit (ECC); and a similar uncoated, open circuit with standard length and prime (CONT).Methods 75 patients undergoing reoperation for coronary revascularization were randomly allocated into three groups (N=25): Group 1: CondECC with shortened tubing, components and an open-closed configuration of low priming volume with a centrifugal pump and a shunt which bypassed the reservoir for closed configuration; Group 2: ECC with a roller pump and hard-shell reservoir; Group 3: CONT. Blood samples for CBC, inflammatory mediators [Interleukin-2 (IL-2), Complement-3a (C3a)] and flow cytometry (CD11 b/CD18) were collected after induction (T1) and heparin administration (T2), 15 min after cardiopulmonary bypass (CPB) (T3), before cessation of CPB (T4), 15 min after reversal (T5), and the first postoperative day (T6).Results Leukocyte counts demonstrated significant increases at T4, T5 in CONT but remained stable in ECC and CondECC (p<0.05). Platelets were preserved better at T4, T5 in both ECC and CondECC study groups (p<0.05). IL-2 and C3a levels were significantly lower at T3, T4, T5 in CondECC and T4, T5 in ECC (p<0.05). Blood protein adsorption analysis demonstrated increased amount of microalbumin on CONT fibers (p<0.05).Conclusions The CondECC is a flexible, dual-function, open/closed configuration system that was easy to use, safe and achieved better biocompatibility when compared to coated and uncoated conventional circuits.

Nicotine chewing gum is designed to maintain plasma nicotine levels during a smoking cessation effort while the individual copes with the loss of the repetitive behavioral components of smoking. The plasma nicotine levels obtained with hourly gum chewing were compared with levels obtained with cigarette smoking in nine patients with lung disease. Chewing 2- and 4-mg nicotine gum hourly produced mean steady-state plasma nicotine levels of 11.8 and 23.2 ng/mL, respectively. This compares with a mean plasma nicotine trough level during usual smoking of 15.7 ng/mL and a mean trough level of 18.3 ng/mL with hourly smoking of a cigarette with a nicotine yield of 1.1 mg. Few side effects were seen with the use of either the 2- or 4-mg gum. In a short-term study, nicotine gum proved an acceptable source of nicotine for aiding smoking cessation.(JAMA 1982;248:865-868)

We characterized scavenger receptor pathways of human alveolar macrophages and cultured monocytes using radiolabeled maleylated bovine serum albumin (MAL-BSA) and acetylated low-density lipoprotein (Ac-LDL) as ligands. Human alveolar macrophages and cultured human monocytes degraded both MAL-BSA and Ac-LDL. Both ligands were bound and degraded in a specific and saturable fashion. Specificity of degradation was tested using excess MAL-BSA and Ac-LDL, polyanionic compounds, and alpha-casein as inhibitors. Alveolar macrophages utilized the classical scavenger receptor pathway to degrade MAL-BSA and Ac-LDL. In contrast, cultured monocytes utilized two receptor pathways to degrade MAL-BSA: the classical scavenger receptor pathway and a secondary alpha-casein-inhibitable pathway. These results demonstrate differences in the activities of receptor systems in cultured monocytes compared to alveolar macrophages.

In 76 smokers, correlations between plasma nicotine and alveolar carbon monoxide levels of the individual smoker and the nicotine and CO yields of his cigarette were very poor. In 24 smokers of low-nicotine, low-tar cigarettes, mean alveolar CO levels did not differ from those of smokers of regular cigarettes. Mean plasma nicotine levels were lower in smokers of low-nicotine cigarettes, but a wide overlap of individual values occurred. The implication that an individual shifting to ultra-low-tar cigarettes reduces risks of cardiopulmonary disease is unwarranted.(JAMA 1983;250:2840-2842)

The lower morbidity and mortality of pipe smokers compared with cigarette smokers may be due to different inhaling patterns of pipe smokers. Plasma nicotine levels were determined in three groups of pipe smokers: (1) primary pipe smokers, (2) persons who smoke both pipes and cigarettes, and (3) secondary pipe smokers, ie, former cigarette smokers who now smoke pipes only. Primary pipe smokers inhaled minimally, as evidenced by low plasma nicotine concentrations after pipe smoking. In contrast, persons who smoke cigarettes and also pipes had high plasma nicotine levels after pipe smoking (mean, 22 ng/mL) and, hence, must have inhaled. Secondary pipe smokers (former cigarette smokers) had mostly low levels of plasma nicotine (mean, 6 ng/mL), suggesting that not all cigarette smokers continue to inhale when converting to pipe smoking. Pipe smoking may be safer than cigarette smoking in certain individuals.(JAMA 1982;248:577-578)