Marvin A. McMillen

Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion

Massive transfusion may cause abnormalities of electrolytes, clotting factors, pH, and temperature and may occur in a scenario of refractory coagulopathy and irreversible shock. Identification of correctable variables to improve survival is complicated by the interplay of this pathophysiology. Temperature may be an under-appreciated problem in the genesis of coagulopathy. In vitro studies have demonstrated that platelet function and vascular response are critically temperature-dependent. We reviewed the records of 45 trauma patients without head injury or co-morbid medical illness who required massive transfusions. The mean Injury Severity Score was 55±6, a mean of 22.5±5 units of blood was transfused, and mortality was 33%. Nonsurvivors were more likely to have had penetrating injury (88% versus 55%), received more transfusions (26.5±9 versus 18.6±1, p

Nonoperative management of adult blunt splenic trauma. Criteria for successful outcome.

Nonoperative management of blunt splenic trauma in adults is controversial despite numerous reports advocating this mode of therapy. Blunt splenic trauma is frequently managed without operation at our institution and, to define criteria that may predict a successful outcome, a retrospective review (1980 to 1988) of all adult splenic injuries was undertaken. Splenic injuries were documented by scintillation studies, CAT scanning, or at laparotomy. Sixty of 252 (24%) splenic injuries were initially treated without operation, which included bed rest, ICU monitoring, frequent physical exams, nasogastric tube, serial hematocrits, and follow-up splenic imaging. Five patients (5 of 60) failed nonoperative management and required interval laparotomy. Reasons for failure included blood loss greater than four units, enlarging splenic defect, or increasing peritoneal signs. Parameters predicting a successful outcome were localized trauma to the left flank or abdomen, hemodynamic stability, transfusion requirements less than four units, rapid return of GI function, age less than 60 years, and early resolution of splenic defects on imaging studies. No morbidity or deaths resulted from delayed operative intervention. In carefully selected adult patients, blunt splenic trauma may be successfully managed without operation.

Effect of cholecystokinin receptor blockade on human lymphocyte proliferation

Cholecystokinin is a peptide produced by neuroendocrine cells in gut and neurons in brain and gut. Proliferating human peripheral blood mononuclear cells (H-PBMC) also make small amounts of cholecystokinin. Cholecystokinin increases intracellular calcium (Ca2+) in H-PBMC. This can be blocked with L 364, 718, a non-toxic specific cholecystokinin antagonist. Cholecystokinin is a comitogen for H-PBMC and activates H-PBMC in a cyclosporine-resistant fashion. If cholecystokinin is a critical lymphokine, then L 364, 718 should block H-PBMC mitogenesis. H-PBMC from healthy donors were stimulated in vitro with either phytohemagglutinin or anti-CD3 monoclonal antibody. L 364, 718 was not toxic for H-PBMC, yet inhibited mitogenesis at 10(-7), 10(-6), and 10(-5) M. The small amount of cholecystokinin made by H-PBMC may play a critical role in H-PBMC mitogenesis.

The straight radial-antecubital PTFE angio-access graft in an era of high-flux dialysis

Straight radial-antecubital polytetrafluoroethylene (PTFE) grafts were placed in 10 older (greater than 55 years) male patients with significant intercurrent diseases who were considered candidates for high-flux dialysis. Graft patency was 90% at 6 months, and suitable flow for high-flux dialysis (greater than 400 mL/minute) could be achieved with all grafts. Shorter dialysis times with no major cardiovascular, hemodynamic, or extremity complications were achieved with this mode of therapy. The principles and practicalities of high-flux dialysis are reviewed. This small series of patients demonstrates that the relatively low resting flow of the straight radial-antecubital PTFE graft should not be a major consideration in the choice of this vascular access procedure in patients being considered for high-flux dialysis. Straight radial-antecubital PTFE grafts preserved both the ulnar collateral to the hand and the brachial artery for later access, yet provided adequate flow in all patients in whom they remained patent.

Role of Endothelin in Ischemia‐Reperfusion Injury

Resumption of blood flow to organs and tissue after shock or ischemia is associated with a leukocyte-mediated “repehsion injury” that further exacerbates the underlying ischemic damage. While monocytes and neutrophils cause the injury, the mediators and mechanism of this activation are still unknown. Endothelin-1 (ET-1) is produced by endothelial cells and increases in production/ secretion during ischemia, shock, and sepsis. Endothelin is a potent constrictor of vascular smooth muscle cells by increasing intracellular calcium ([Ca2+]i) by an inositol triphosphate (IP3) mechanism. Endothelin has also been shown to release IP3 and increase [Ca2+]i in mesangial and anterior pituitary cells. Previous work from our laboratory has shown that endothelin also causes increased [Ca2+], selectively in human peripheral blood monocytes.1 We therefore asked whether endothelin has any effect on activation of human monocytes and production of interleukin-6,8 and prostaglandin E2.

Cyclosporine inhibits protein kinase C-dependent signals in human peripheral blood lymphocytes

T helper lymphocyte activation is thought to occur when the T3T1 receptor is activated by antigen, and a calcium signal and stimulus to protein kinase C appear to be essential for interleukin-2 production and lymphocyte proliferation. Previous work from our lab has demonstrated that the calcium signal is unaffected by cyclosporine. In this report, a macrophage and T suppressor/cytotoxic-depleted population of human peripheral blood mononuclear cells is stimulated with Sepharose beads bound to OKT3 monoclonal antibody and Sepharose-OKT3 plus a phorbol ester (a stimulus to protein kinase C). Cyclosporine inhibits both the Sepharose/OKT3-mediated and Sepharose/OKT3/phorbol myristic acetate-mediated mitogenesis. Cyclosporine inhibits either protein kinase C or protein kinase C-dependent intracellular signals necessary for T helper activation and proliferation.

Decrease in cyclosporin-mediated prostacyclin production in renal versus carotid arteries: A mechanism for cyclosporin-induced hypertension☆

Although the mechanism of cyclosporin (CsA)-induced hypertension is unknown, it has been shown to inhibit prostacyclin (PGI2) production directly, which may be a factor. We determined whether CsA had a differential effect on PGI2 production from the carotid artery (CA) and internal jugular vein (JV) compared to that from the renal artery (RA) and vein (RV) as a possible contributing factor to renovascular hypertension based upon the ability of organs to regulate their own blood flow according to local circumstances. The neck and renal vessels were removed from anesthetized adult female dogs (N = 8) and placed in a stimulation chamber, with Cell I being control (Hepes buffer), Cell II containing 0.3 mg/ml CsA, and Cell III containing CsA and 25 microM arachidonic acid (AA). Following serial stimulation periods, the supernatant was evaluated for PGI2 production by radioimmunoassay. PGI2 production from CA was significantly higher than that from RA following control and AA stimulation, 1474 +/- 382 pg/cm2-min vs 733 +/- 173 pg/cm2-min (P less than 0.05) and 2236 +/- 347 vs 1090 +/- 217 (P less than 0.01), respectively. CsA-induced PGI2 production from the carotid arteries was significantly greater than that from the renal arteries, 2944 +/- 586 vs 1003 +/- 235 (P less than 0.005). However, stimulation with AA following CsA resulted in sustained PGI2 production in both arteries that was similar to stimulation with CsA alone, 3014 +/- 600 vs 2944 +/- 586 for the carotids and 1278 +/- 280 vs 1003 +/- 235 for the renal arteries.(ABSTRACT TRUNCATED AT 250 WORDS)