Clinical benefits of continuous leukocyte filtration during cardiopulmonary bypass in patients undergoing valvular repair or replacement.

Valve operations in the form of repair or replacement make up a significant population of patients undergoing surgical procedures in the USA annually with the use of cardiopulmonary bypass. These patients experience a wide range of complications that are considered to be mediated by activation of complement and leukocytes. The extracorporeal perfusion circuit consists of multiple synthetic artificial surfaces. The biocompatibility of the blood contact surfaces is a variable that predisposes patients to an increased risk of complement mediation and activation. This can result in an inflammatory process, causing leukocytes to proliferate and sequester in the major organ systems. The purpose of this study was to determine whether filtration of activated leukocytes improved clinical outcomes following surgical intervention for valve repair or replacement. In this paper, we report a retrospective matched cohort study of 700 patients who underwent valve procedures from June 1999 to December 2002. The control group (CG) consisted of patients who had a conventional arterial line filter. In the study group (SG), patients had a conventional arterial line filter and a leukocyte arterial line filter (Pall Medical, NY). In the SG, blood diverted to the cardioplegia system was also leukocyte depleted to enhance myocardial preservation by adapting this device to the outflow port on the filter. Patient characteristics were similar for the SG and the CG, including 228 males and 122 females, mean age (62.4 versus 64.2 years), cardiopulmonary bypass time (127+/-64 versus 116+/-53 min), and aortic crossclamp time (84+/-23 versus 81+/-23 min). Our results demonstrate that the SG achieved statistically significant reduction in the time to extubation (p =0.03) and the number of patients with prolonged intubation in excess of 24 hours (p <0.04), in addition to improved postoperative oxygenation (p=0.01), and decreased length of hospital stay (p =0.03). We believe that leukocyte filters are clinically beneficial, as demonstrated by the results presented in this study.

Intraoperative modality of treatment for peritoneal carcinomatosis: use of hyperthermic interperitoneal chemoperfusion.

The use of hyperthermia as an adjunct to chemotherapy in the treatment of peritoneal carcinomatosis is a promising technique for patients who otherwise have a poor prognosis for survival. We, herein, report an overview and description of our technique for the safe conduct of this treatment. Included in these data are a total of 71 patients who underwent an intraoperative treatment with Mitomycin C at temperatures of 41-42 degrees C for a 90- to 120-min time period. The treatment protocol, perfusion system description, technical considerations, and potential complications are also included. The prognosis for intraabdominal carcinomatosis is poor with conventional treatments and modalities. We believe that the use of this technique offers a very positive clinical alternative for patients undergoing treatment for laparoscopic palliation of malignant ascites and/or surgical debulking for intraoperative treatment and prevention of metastasis.

Alternatives to estrogen replacement therapy for preventing osteoporosis.

Osteoporosis is a leading cause of disability and death in older Americans; women are at higher risk than men. Bone is a living tissue that undergoes continuous remodeling throughout life. Several drugs-including sex hormones, bisphosphonates, calcitonin, and sodium fluoride-can arrest the progression of osteoporosis and prevent fractures. Calcium and vitamin D supplementation may prevent the development of osteoporosis in high-risk individuals and are useful adjuncts when used with other treatments.

Dilation of cerebral arterioles by cytochrome P-450 metabolites of arachidonic acid.

We have recently shown that brain tissue can synthesize cytochrome P-450 monooxygenase metabolites of arachidonic acid (AA), including 5,6-epoxyeicosatrienoic acid (5,6-EET), and 14,15-EET. The purpose of this investigation was to determine the vasoactivity of EETs and AA on the cerebral microcirculation. Pial arteriolar diameter was measured in rabbits and cats using in vivo microscopy and the closed cranial window technique. Prostaglandin (PG) E2 and 6-keto-PGF1 alpha formed by the brain cortex during application of these fatty acids was measured in cerebrospinal fluid by use of radioimmunoassay. A transient dose-dependent dilation was produced by 5,6-EET (1-15 micrograms/ml), with the maximum being 23% of control in both species. Other EETs had little or no activity, and AA-induced dilation was greater in rabbits than in cats. Indomethacin or superoxide dismutase plus catalase prevented dilation by 5,6-EET and AA, indicating that both produce dilation via cyclooxygenase-dependent oxygen radicals. PGE2 and 6-keto-PGF1 alpha levels were increased by AA but not by EETs, implying that EETs do not directly activate AA metabolism. Since 5,6-EET, but not other EETs, is known to be a substrate for cyclooxygenase, our data are consistent with brain cyclooxygenase metabolism of 5,6-EET with concomitant generation of dilator oxygen radicals. An implication of these results is that many previous studies of the cerebral circulation which based conclusions on results with cyclooxygenase inhibitors may need to be additionally interpreted.

Effect of fish oil n-3 fatty acids on cerebral microcirculation.

Dietary fish oil containing the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) is being consumed by many individuals in an effort to reduce thrombosis and heart disease. However, little is known about how these fatty acids can affect cerebrovascular function. The purpose of the present study was to begin to examine the effects of these fatty acids on cerebral arteriolar diameter and to compare their effects with that of arachidonic acid (AA). Pial arteriolar diameter responses to the topically applied fatty acids [0.2-200 micrograms/ml cerebrospinal fluid (CSF)] were measured in rabbits using in vivo microscopy and the acute cranial window technique. Prostaglandin E2 (PGE2) formed by the brain in response to AA, EPA, and DHA was measured in CSF using radioimmunoassay. EPA induced a dose-dependent dilation response of which the maximum was 29%, whereas the maximal dilation produced by AA was 100%. The arteriolar effect of EPA was reduced by indomethacin or superoxide dismutase plus catalase, indicating vasoactivity due to oxygen radicals formed by cyclooxygenase metabolism of EPA. DHA itself had no effect on diameter or adenosine-induced dilation but reduced dilation by AA when coapplied with AA. AA induced a 65-fold maximal increase in PGE2, whereas EPA and DHA had comparatively little effect. These results imply that substitution of n-3 fatty acids for AA in brain phospholipids may result in less cyclooxygenase-dependent cerebrovascular reactivity. This alteration in reactivity may produce important effects with respect to the brain's blood flow response to a number of physiological and pathological challenges.