Elizabeth Davis

Lymphocyte and monocyte subset changes during cardiopulmonary bypass : effects of aging and gender

Complications of cardiopulmonary bypass (CPB) may be associated with either immune suppression or immune activation, but the specific effects of CPB on many lymphocyte and monocyte subsets are unclear. In addition, the increasing age of patients undergoing cardiac surgery raises the possibility of even greater effects on the immune system in elderly patients. We measured immunophenotypic alterations of circulating lymphocytes and monocytes after CPB in male and female cardiac surgery patients who were either younger than 60 or older than 75 years of age. The total lymphocyte counts in all patients decreased postoperatively; older patients had significantly lower counts at all time points. The absolute decline was greatest among T cells and particularly CD4+ T cells, which reached an average nadir of 251 cells/microl on postoperative day 1 in the older patients. The percentages of CD8+, CD4+CD45RA+, and CD4+CD45RO+ T cells did not change significantly, whereas the percentages of B cells and natural killer cells increased. Both T and B lymphocytes and monocytes showed evidence of activation, with increased percentages of CD3+HLADr+, CD3+IL2R+, and CD19+CD23+ lymphocytes and increased expression of CD11b on monocytes. By contrast, expression of class II major histocompatibility antigen (HLADr) monocytes decreased significantly. We conclude that CPB produces a profound alteration in the pool of circulating lymphocytes and monocytes, evidenced by decreased numbers of lymphocyte subsets including CD4+ cells and decreased expression of monocyte surface membrane proteins important for antigen presentation; CPB also activates a variety of specific circulating mononuclear cell subsets. Older patients showed patterns of lymphocyte and monocyte activation comparable to those of younger patients; however, they had consistently lower lymphocyte numbers and a trend toward decreased monocyte HLADr expression, potentially placing them at greater risk for infectious complications. Gender had no effect.

Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial.

In this prospective, randomized, placebo-controlled, double-blinded study, we determined the effects of two commonly used adjuncts, mannitol and dopamine, on &bgr;2-microglobulin (&bgr;2M) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). &bgr;2M excretion rate has been described as a sensitive marker of proximal renal tubular function. One-hundred patients with a preoperative serum creatinine level ≤1.5 mg/dL were prospectively randomized into 4 groups: 1) placebo, 2) mannitol 1 g/kg added to the CPB prime, 3) dopamine 2 &mgr;g · kg−1 · min−1 from the induction of anesthesia to 1 h post-CPB, or 4) mannitol plus dopamine. The primary outcome measure was &bgr;2M excretion rate at 1 h post-CPB. Secondary outcome measures included &bgr;2M excretion rate at 6 and 24 h post-CPB; urinary flow rate and creatinine clearance at 1, 6, and 24 h post-CPB; and the highest postoperative serum creatinine level. Length of intensive care stay and hospitalization, as well as adverse events, were also considered secondary outcomes. Dopamine significantly increased &bgr;2M excretion rate at 1 h post-CPB (2.48 ± 3.61 &mgr;g/min) compared with placebo (0.59 ± 1.04 &mgr;g/min; P = 0.001). This effect was not ameliorated by the addition of mannitol (&bgr;2M excretion rate, 2.05 ± 2.77 &mgr;g/min; P = 0.007 compared with placebo). &bgr;2M excretion rate was similar in patients given placebo or mannitol alone (P = 0.831). Rather than being a protective drug in the setting of CPB, dopamine alone or in combination with mannitol increases &bgr;2M excretion rate, which may be a measure of renal tubular dysfunction. The clinical implications of this increase and whether it is also seen in patients with established renal dysfunction undergoing CPB require additional investigation.

Acadesine inhibits neutrophil CD11b up-regulation in vitro and during in vivo cardiopulmonary bypass ☆ ☆☆ ★ ★★ ♢

Granulocyte adhesion to ischemic tissue, mediated in large part by beta 2 integrin receptors, is important in the pathophysiology of reperfusion injury. Acadesine, a drug that modulates adenosine levels in ischemic tissue, has been shown to reduce reperfusion injury in animal models of ischemia. The purpose of this study was to measure changes in granulocyte CD11b/CD18 in an in vitro assay and in an in vivo trial of acadesine administered during cardiopulmonary bypass to determine whether this agent might modulate up-regulation of this adhesion receptor. In vitro, whole blood was incubated with acadesine or control diluent, stimulated with N-formyl-methionyl-leucyl-phenylalanine, and granulocyte CD11b measured. Acadesine significantly (p < 0.01) inhibited N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61%. In similar experiments, adenosine also inhibited N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation (p < 0.01). In vivo, 34 patients at our institution participating in a multicenter trial of acadesine during cardiopulmonary bypass were randomized to placebo, low-dose, or high-dose acadesine infusion perioperatively. Combining low- and high-dose treatment groups, there was significant (p = 0.05) inhibition of granulocyte CD11b up-regulation in patients receiving acadesine; granulocyte CD11b expression in the acadesine group peaked at 2.8 times baseline versus 4.3 for placebo. By contrast, monocyte CD11b up-regulation (peaking after cardiopulmonary bypass at 3 times baseline) was not affected by acadesine. Acadesine and adenosine inhibit up-regulation of granulocyte CD11b in vitro, and acadesine is capable of a similar inhibition during in vivo cardiopulmonary bypass. This inhibition may contribute to the ability of these agents to decrease in vivo reperfusion injury.

Quality assurance for intraoperative transesophageal echocardiography monitoring: A report of 846 procedures

We evaluated our experience with 846 consecutive transesophageal echocardiography (TEE) intraoperative monitoring procedures performed between November 1989 and July 1991. TEE frequency was 36 +/- 11 per month (range 16-55) and represented 69.8% of cardiac valve surgery cases, 40.2% of coronary artery bypass graft cases, and 2.2% of total operative caseload. Major patient complications consisted of transient vocal cord paresis and ingestion of glutaraldehyde-disinfectant solution. Minor complications consisted of a chipped tooth (one case) and pharyngeal abrasions (three cases). The Quality Assurance (Q/A) Program evaluated both record keeping and quality of imaging, as judged by cardiologist echocardiographer reviewers. The percentage of completion for each Q/A indicator was as follows: medical record documentation, 88%; database form annotation, 94%; and provision of videotape recording, 91%. TEE database forms were analyzed further in terms of the percentage of fields completed. Completion scores were 73%. The following scoring system was utilized for videotape evaluation by the cardiologists: 1 = excellent; 2 = good; 3 = poor. The median grade for both two-dimensional echocardiography and color flow Doppler (CFD) examinations was 2. Poor quality images (grade 3) were present in 15.2% of two-dimensional echocardiography and 20.3% of color flow Doppler examinations, and disproportionately associated with 4/26 attendings. Supplemental audit of the cardiology reviewers performance demonstrated 569/846 videotapes showed no objective evidence of review. The cardiology reviewer forms of the remaining 277 videotapes were evaluated in terms of the percentage of fields completed. The completion score was 56%. These data suggest the need for formal Q/A for intraoperative TEE, both for anesthesiologists and reviewing cardiologists.

A clinical computer database entry form for an intraoperative anesthesiology-based transesophageal echocardiography monitoring service

Transesophageal echocardiography (TEE) has been increasingly applied to supplement and, in instances, to supplant conventional intraoperative cardiac monitoring. Our body of experience (>1600 intraoperative TEE procedures), combined with insights gleaned from an intramural quality assurance study, and clinical implications of certain recent advances in the field, led us to develop the following TEE computer database entry form. The form, completed intraoperatively, consists of a patient and surgical procedure demographics section, followed by fields based on the TEE examination. The scans encompass transverse plane basal short axis, long axis, and transgastric views of the heart and great vessels. The two-dimensional echocardiographic, saline-contrast, color flow and pulsed Doppler data represent both right and left ventricular performance, valvular function and specific lesions. This database entry form is intended to serve as a guide for performance of a nominally complete intraoperative study and facilitate maintenance of a TEE archive consistent with current advances.

Quantitative echocardiographic assessment of regional wall motion and left ventricular asynchrony with color kinesis in cardiac surgery patients

Conventional echocardiographic interpretation of regional wall motion abnormalities is subjective and experience dependent. Delayed contraction in the ejection phase (tardokinesis) and regional systolic asynchrony, sensitive markers of myocardial ischemia, cannot be accurately assessed visually. We used color kinesis (CK), a technique that evaluates spatiotemporal patterns of endocardial motion, to objectively detect regional wall motion abnormalities in patients undergoing coronary bypass surgery, and we compared it with conventional assessment of grayscale images by less experienced reviewers; we used expert grading as the gold standard for comparisons. Quantitative CK analysis agreed more closely with expert grading than less experienced reviewers (&kgr; coefficients, 0.74 versus 0.52 and 0.5). Global tardokinesis, identified in 9 of 26 patients (2 with normal fractional area change), was associated with an increased index of systolic asynchrony. Regional tardokinesis was identified in 48 of 150 segments: 27 segments had a normal magnitude of wall motion, 18 were hypokinetic, and 3 were severely hypokinetic/akinetic. Mildly hypokinetic segments showed delayed systolic motion, whereas residual motion of severely hypokinetic/akinetic segments occurred in early systole, reflecting passive effects produced by adjacent myocardial contraction. Quantitative CK may be a useful supplement to visual assessment, particularly for less experienced readers. By diagnosing tardokinesis, common among cardiac surgical patients even with normal standard ejection phase indices, quantitative CK may improve the intraoperative detection of regional ischemic changes.