Lelcuk S

Endoscopic decompression of acute colonic obstruction. Avoiding staged surgery.

Colostomy is the traditional treatment for acute obstruction of the sigmoid colon. This entails two or three surgical procedures in a high-risk group of patients. Presented is a nonsurgical approach used in three patients with acute colonic obstruction. Decompression of the bowel was achieved with a tube introduced proximal to the obstruction with the aid of a flexible sigmoidoscope. In a fourth patient, in whom the obstruction was next to the splenic flecture, the procedure failed. In all instances where decompression was successful, a one-stage procedure--primary resection and anastomosis--was performed.

Determinants of cardiovascular stability during abdominal aortic aneurysmectomy (AAA).

Patients undergoing abdominal aortic aneurysmectomy (AAA) develop depressed cardiac function during aortic clamping. The importance of volume status and thromboxane (Tx) mediated declines in cardiac contractility in determining this event was studied. In a blinded fashion, patients received the cyclo-oxy-genase inhibitor ibuprofen 12 mg/kg by mouth (n = 11) or a placebo (n = 15), 1.5 hours prior to surgery. In the placebo group levels of 6-keto-PGF]a, the hydrolysis product of pros-tacyclin (PGI2) rose from 20 ± 10 to 1170 + 80 pg/ml (p < 0.05) soon after incision. Concentrations of TxB2, the stable hydrolysis product of TxA2, were unchanged until 30 minutes after the aorta was clamped when arterial TxB2 concentrations rose from 90 ± 20 to 230 ± 30 pg/ml (mean ± SEM) (p < 0,05). A pulmonary source for PGI2 and TxA2 was indicated by the observation that arterial 6-keto-PGF1(, and TxB2 levels exceeded those in pulmonary arterial blood by 180 ± 50 and 110 + 30 pg/ml, respectively (p < 0.05). Levels of TxB2 in circulating platelets remained unchanged from baseline in the placebo group. During aortic clamping, cardiac index (CI) fell 0.7 ± 0.2 1/min m2 (p < 0.05) in placebo treated patients, and there was a 6% decline in plasma contractility as bioassayed with a rat papillary muscle (p < 0.05). Placebo patients entered surgery with a PAWP ≥10 mmHg (mean 13 mm). Ibuprofen suppressed production of TxB2, such that 30 minutes after aortic clamping TxB2 was 70 ± 30 pg/ml, a value lower than control patients (p < 0.05). Further, plasma no longer depressed contractility of the papillary muscle. Five patients given ibuprofen had an initial pulmonary arterial wedge pressure (PAWP) of 10 mmHg or greater (mean 12 mmHg). During aortic clamping there was an insignificant decrease in CI of 0.2 ± 0.11/min m2. This was in contrast to the CI decrease in six other ibuprofen treated patients of 0.9 ± 0.2 1/min m2 whose PAWP at the start of surgery was <10 mmHg (mean 6 mmHg) (p < 0.05), and to placebo patients whose initial PAWP was ≥10 (p < 0.05). Platelet counts fell from 185,000 to 121,000/mm3 in placebo patients (p < 0.05), but did not fall when ibuprofen was given. Creatinine concentrations were unaffected by ibuprofen. Blood replacement in placebo and ibuprofen patients was similar, 1.90 ± 0.20 and 0.65 ± 0.15 1, respectively. Results indicate that CI

Arachidonic acid metabolites mediate early burn edema.

Standard burns were sequentially produced on the backs of Sprague-Dawley rats at 0, 1, 2, and 2 1/2 hr, followed by the IV injection of Evans blue dye. All animals were killed at 3 hr, and burns evaluated by wet/dry weight ratios, and Evans blue extravasation scored 1-4 by two observers. Five groups of rats were compared to controls. Rats made neutropenic by exposure to 137cesium showed no significant difference in wet/dry weight ratio or Evans blue extravasation compared to controls. At 1 1/2 hr four other groups were treated with various inhibitors of arachidonic acid metabolism including ibuprofen, a cyclo-oxygenase inhibitor; FPL 55712, a leukotriene (LT) receptor antagonist; ketoconazole, an inhibitor of thromboxane (Tx) synthetase; and lodoxamide, a calcium channel inhibitor. All treated groups showed significant reduction of Evans blue dye extravasation. Wet/dry weight ratios were significantly reduced in rats treated with FPL 55712 and ketoconazole before or after burning. These data support the postulate that oxygenation products of arachidonic acid, particularly Tx and LT, are important mediators in early burn edema.

Disadvantages of Prostacyclin Infusion During Cardiopulmonary Bypass: A Double-Blind Study of 50 Patients Having Coronary Revascularization

Prostacyclin (PGI2) has been suggested for use in cardiopulmonary bypass (CPB) because of its positive effects on platelet number and function. Fifty patients who underwent coronary artery bypass grafting using a bubble oxygenator received heparin, 3 mg per kilogram of body weight, and then were randomly assigned to receive PGI2, 25 ng/kg/min, beginning 5 minutes before and until the end of CPB (26 patients) or a placebo (24 patients). Both groups were similar in sex, age, heparin dose, protamine dose, and CPB time. During CPB, mean arterial pressure fell significantly with PGI2 (76 +/- 2 mm Hg to 53 +/- 2 mm Hg; p less than 0.05) and necessitated pressor substances. Platelet counts fell significantly in both groups with the start of CPB, but after 60 minutes were similar in both groups (118 +/- 9 X 10(3) versus 130 +/- 8 X 10(3); not significant [NS]) and were unchanged 3 hours after CPB. Total chest tube output was 647 +/- 51 ml (placebo group) versus 576 +/- 34 ml (PGI2 group) (NS); 18 of the patients given PGI2 required 26 transfusions compared with 16 transfusions in 8 of the patients given a placebo (p less than 0.05). In PGI2 patients, arterial oxygen tension on 100% oxygen fell from 281 +/- 18 mm Hg before CPB to 223 +/- 17 mm Hg immediately after CPB (p less than 0.05). The placebo patients did not show a change in this variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of ischemia-induced thromboxane synthesis in man.

The ability of the imidazole derivative, ketoconazole, to inhibit thromboxane (Tx)A2 synthesis in response to ischemia was tested in ten volunteers. Two hours after taking placebo or ketoconazole 400 mg by mouth, plasma levels of the stable degradation product of TxA2, TxB2, were 300 +/- 129 pg/ml (mean +/- SEM) and 297 +/- 80 pg/ml, respectively. Arm ischemia for 10 min induced by inflation of a cuff to 220 mm Hg led to a rise in TxB2 levels to 657 +/- 157 pg/ml after placebo (p less than 0.05) and 337 +/- 81 pg/ml after ketoconazole. One hour after cuff deflation, TxB2 returned to pre-ischemia levels in both groups. Platelet TxB2 concentrations were 27 +/- 6 ng in the placebo and 35 +/- 6 ng/10(9) platelets in the ketoconazole group, and were unchanged by cuff inflation. The fact that plasma and platelet TxB2 values were not lower 2 hr after ketoconazole treatment was explored in another group of four nonstressed volunteers who received 400 mg of drug. After 2 hr, TxB2 values had fallen from 170 +/- 30 pg to 120 +/- 10 pg; at 4 hr, 6 hr, and 8 hr they were 30 +/- 20 pg, 5 +/- 5 pg, and 5 +/- 5 pg/ml, respectively. These results indicate that tourniquet ischemia provokes TxA2 synthesis, and that the source of this prostanoid is likely to be ischemic tissue and not platelets. Finally, ketoconazole can profoundly inhibit both background and stimulated TxA2 synthesis.

Thromboxane A2 moderates permeability after limb ischemia.

Reperfusion after limb ischemia results in muscle edema as well as excess secretion of thromboxane A2 (TxA2), an agent associated with permeability increase in other settings. This study tests whether TxA2 moderates the permeability following limb ischemia. A tourniquet inflated to 300 mmHg was applied for 2 hours around the hind limb of four groups of dogs. In untreated animals (N = 25), 2 hours following tourniquet release, plasma TxB2 values rose from 320 pg/ml to 2416 pg/ml (p less than 0.001), and popliteal lymph values rose from 378 pg/ml to 1046 pg/ml (p less than 0.001). Platelet TxB2 was unaltered and plasma 6-keto-PGF1 alpha levels did not vary. Following ischemia, lymph flow (QL) increased from 0.07 to 0.37 ml/h (p less than 0.05), while the lymph/plasma (L/P) protein ratio was unchanged at 0.41. These measurements indicate increased permeability since increase in hydrostatic pressure in a second group by tourniquet inflation to 50 mmHg (N = 7) led to a rise in QL from 0.07 to 0.22 ml/h, but a fall in the L/P ratio to 0.32, a value lower than the ischemic group (p less than 0.05). Pretreatment with the imidazole derivative ketoconazole (N = 11) reduced platelet Tx synthesis from 42 ng to 2 ng/10(9) platelets, but lymph TxB2 levels rose to 1703 pg/ml after ischemia, indicating an extravascular or vessel wall site of synthesis not inhibited by ketoconazole. Pretreatment with a lower molecular weight imidazole derivative OKY 046 (N = 9) inhibited all Tx synthesis after ischemia. Prior to tourniquet inflation, both OKY 046 and ketoconazole lowered plasma TxB2 levels as well as the L/P ratio (p less than 0.05). After ischemia, OKY 046, but not ketoconazole, maintained the L/P ratio at 0.33, a value below that of untreated animals (p less than 0.05). These results indicate that nonplatelet-derived TxA2 modulates both baseline and ischemia-induced increases in microvascular permeability in the dog hind limb.

Role of serotonin in patients with acute respiratory failure.

An early event in the evolution of acute respiratory failure (ARF) is thought to be the activation of platelets, their pulmonary entrapment and subsequent release of the smooth muscle constrictor serotonin (5HT). This study tests the thesis that inhibition of 5HT will improve lung function. The etiology of ARF in the 18 study patients was sepsis (N = 10), aspiration (N = 3), pancreatitis (N = 1), embolism (N = 2), and abdominal aortic aneurysm surgery (N = 2). Patients were divided into two groups determined by whether their period of endotracheal intubation was less than or equal to 4 days (early ARF, N = 12) or greater than 4 days (late ARF, N = 6). Transpulmonary platelet counts in the early group showed entrapment of 26,300 +/- 5900 platelets/mm3 in contrast to the late group where there was no entrapment (p less than 0.05). The platelet 5HT levels in the early group were 55 +/- 5 ng/10(9) platelets, values lower than 95 +/- 15 ng/10(9) platelets in the late ARF group (p less than 0.05), and 290 +/- 70 ng/10(9) platelets in normals. The selective 5HT receptor antagonist, ketanserin was given as an intravenous bolus over 3 minutes in a dose of 0.1 mg/kg, followed by a 30-minute infusion of 0.08 mg/kg. During this period mean arterial pressure (MAP) fell from 87 +/- 5 to 74 +/- 6 mmHg (mean +/- SEM) (p less than 0.05). One and one-half hours following the start of therapy, MAP returned to baseline. At this time, patients with early ARF showed decreases in: physiologic shunt (Qs/QT) from 26 +/- 3 to 19 +/- 3 (p less than 0.05); peak inspiratory pressure from 35 +/- 2 to 32 +/- 2 cmH2O (p less than 0.05) and in mean pulmonary arterial pressure from 32 +/- 2 to 29 +/- 1 mmHg (p less than 0.05). At 4 hours all changes returned to baseline levels. In early ARF ketanserin did not alter pretreatment values of: pulmonary arterial wedge pressure, 17 +/- 3 mmHg; cardiac index, 2.8 +/- 0.3 L/min X m2; platelet count, 219,000 +/- 45,000/mm3; platelet 5HT, 55 +/- 5 ng/10(9) platelets; plasma 5HT, 142 +/- 21 ng/ml; plasma thromboxane B2, 190 +/- 30 pg/ml; or plasma 6-keto-PGF1 alpha, 40 +/- 10 pg/ml. Ketanserin infusion in patients with late ARF yielded no benefit. In both ARF groups the decreases in QS/QT were inversely related to the duration of intubation (r = 0.70; p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclo-oxygenase products mediate hypoxic pulmonary hypertension

High-risk infants with a fetal pattern of circulation demonstrate hyperactivity of the pulmonary vascular bed in response to stimuli including mucous plugging, atelectasis, and endotrachial tube suctioning. The resultant increase in pulmonary vascular resistance (PVR) leads to pulmonary hypertension, severe right-to-left shunting, and hypoxemia. Stimuli that trigger pulmonary hypertension cause hypoxia, suggesting the importance of hypoxic pulmonary vasoconstriction (HPV). Although many humoral mediators of HPV have been hypothesized, none have been proven. This study investigates the possible role of the cyclo-oxygenase derivatives thromboxane A2 and prostacyclin as determinants of hypoxic pulmonary hypertension. Open-chested lambs were ventilated with 13% O2 prior to and following treatment with OKY 046, a selective thromboxane inhibitor. In untreated lambs, the partial pressure of arterial oxygen fell from 80 +/- 27 (mean +/- SD) to 35 +/- 13 mm HG (P less than .01). The mean arterial pressure (MAP) remained at 50 +/- 7 mm HG, and the cardiac output (CO) was unchanged at 0.8 +/- 0.2 L/min. The mean pulmonary arterial pressure (MPAP) rose from 11 +/- 4 to 20 +/- 4 mm HG (P less than .01) whereas the PVR increased 70% (P less than .01). TxB2 rose from 147 +/- 85 to 271 +/- 154 pg/mL (P less than .05), and 6-keto-PGF1 alpha rose from 105 +/- 96 to 142 +/- 110 pg/mL. These substances are the hydrolysis products of TxA2 and prostacyclin respectively. In animals treated with OKY 046 prior to ventilation with 13% O2, values for MAP, CO, and PVR were similar to those of the nontreatment period.(ABSTRACT TRUNCATED AT 250 WORDS)