thromboxane-a2 and Aortic-Aneurysm

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-oxygenase 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-PGF1 alpha, the hydrolysis product of prostacyclin (PGI2) rose from 20 +/- 10 to 1170 +/- 80 pg/ml (p less than 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 less than 0.05). A pulmonary source for PGI2 and TxA2 was indicated by the observation that arterial 6-keto-PGF1 alpha and TxB2 levels exceeded those in pulmonary arterial blood by 180 +/- 50 and 110 +/- 30 pg/ml, respectively (p less than 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 X m2 (p less than 0.05) in placebo treated patients, and there was a 6% decline in plasma contractility as bioassayed with a rat papillary muscle (p less than 0.05). Placebo patients entered surgery with a PAWP greater than or equal to 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 less than 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 +/- 0.1 1/min X m2. This was in contrast to the CI decrease in six other ibuprofen treated patients of 0.9 +/- 0.2 1/min X m2 whose PAWP at the start of surgery was less than 10 mmHg (mean 6 mmHg) (p less than 0.05), and to placebo patients whose initial PAWP was greater than or equal to 10 (p less than 0.05). Platelet counts fell from 185,000 to 121,000/mm3 in placebo patients (p less than 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.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm; Blood Platelets; Epoprostenol; Female; Heart; Hematologic Tests; Hemodynamics; Humans; Ibuprofen; Ligation; Male; Middle Aged; Myocardial Contraction; Myocardial Infarction; Papillary Muscles; Pulmonary Wedge Pressure; Serotonin; Thromboxane A2; Thromboxanes

Contact between blood and foreign surfaces, e.g. vascular grafts, causes activation and release of platelets. One consequence of platelet activation is production of thromboxane A2 (TxA2). The physiological effects of TxA2, i.e. platelet aggregation and vaso-constriction are counteracted by another prostanoid, prostacyclin (PGI2). Acetylsalicylic acid (ASA) causes a longlasting inhibition of platelet TxA2 production and a more shortlasting inhibition of PGI2 production. The present study examines TxA2 and PGI2 synthesis in patients receiving synthetic arterial grafts, some of which were treated with ASA. The prostanoid synthesis was evaluated by measurement of their main urinary metabolites with gas chromatography-mass spectrometry. Platelet release was evaluated by measurements of beta-thromboglobulin (beta-TG) and the plasma coagulation by measurements of fibrinopeptide A (FPA). These compounds were also measured in urine in order to avoid artifacts caused by activation of platelets and plasma coagulation during blood sampling. Following replacement of the abdominal aorta with a synthetic vascular graft there was a marked increase in the synthesis of TxA2 and PGI2. Increased levels of beta-TG and FPA were also demonstrated. Administration of ASA on the first and second postoperative days significantly reduced the synthesis of TxA2 but caused no significant effects on the other parameters measured. It is concluded that ASA may be beneficial in the postoperative period since it counteracts TxA2 with vasoconstricting and platelet aggregating properties but leaves PGI2 with vasodilating and antiaggregating properties relatively uneffected.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm; Aortic Diseases; Arterial Occlusive Diseases; Aspirin; Blood Vessel Prosthesis; Epoprostenol; Female; Humans; Male; Thromboxane A2

Limb ischemia in experimental animals leads to white blood cell (WBC) and thromboxane (Tx)A2 dependent pulmonary dysfunction. This study examines the pulmonary sequelae of lower torso ischemia in 20 consecutive patients aged 63 +/- 5 years (mean +/- SEM) who underwent elective abdominal aortic aneurysm surgery. After 30 minutes of aortic cross-clamping, plasma TxB2 levels had risen from 77 +/- 26 pg/ml to 359 +/- 165 pg/ml (p less than 0.01) and was temporally related to increases in mean pulmonary artery pressure (MPAP) from 18 +/- 1 to 23 +/- 3 mmHg (p less than 0.01), as well as to increases in pulmonary vascular resistance (PVR) from 0.07 +/- 0.02 to 0.12 +/- 0.02 mmHg sec/ml (p less than 0.01). Each time that the aortic clamp was repositioned and with final declamping, after 83 +/- 10 minutes, there were further increases in MPAP to a peak of 32 +/- 2 mmHg (p less than 0.01) and in PVR to 0.26 +/- 0.030 mmHg sec/ml (p less than 0.01), corresponding to a plasma TxB2 level of 406 +/- 177 pg/ml (p less than 0.01). MPAP and PVR returned to baseline values within 30 minutes of declamping. Ten minutes after removal of the aortic clamp, platelet levels had fallen from 180 +/- 41 to 97 +/- 17 X 10(3)/mm3 (p less than 0.01) and WBC levels from 8900 +/- 1100 to 4700 +/- 400/mm3 (p less than 0.01). Both platelets and WBC returned towards normal levels, but at 24 hours, while WBC was elevated at 13000 +/- 900/mm3 (p less than 0.01), platelets were 44% of baseline at 135 +/- 14 X 10(3)/mm3 (p less than 0.01). Four to 8 hours after surgery, pulmonary dysfunction was manifest by increases in physiologic shunt from 9 +/- 2% to 16 +/- 2% (p less than 0.01), and peak inspiratory pressure (PIP) from 23 +/- 2 to 33 +/- 2 cmH2O (p less than 0.01). Chest radiography demonstrated interstitial pulmonary edema in all patients, whereas pulmonary artery wedge pressure was 12 +/- 2 mmHg, excluding the possibility of left ventricular failure. After 24 hours, pulmonary edema had resolved, and the PIP and PaO2 had both returned to baseline. These data indicate that reperfusion of the ischemic lower torso leads to the synthesis of TxA2, an event temporally related to pulmonary hypertension and transient leukopenia with subsequent pulmonary microvascular injury manifest by interstitial edema.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm; Blood Pressure; Cardiac Output; Female; Humans; Hypertension, Pulmonary; Ischemia; Leg; Leukocyte Count; Male; Middle Aged; Platelet Count; Postoperative Complications; Pulmonary Edema; Reperfusion; Respiratory Function Tests; Thromboxane A2; Time Factors

To evaluate the in vivo production of thromboxane A2 and prostacyclin their major urinary metabolites were measured in patients following graft replacement of the abdominal aorta. Specific methods based on gas chromatography-mass spectrometry were used to measure the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha. The excretion of these metabolites increased tenfold and almost fortyfold during post-operative Day 1 and remained elevated 6-10 days p.o. In a group undergoing cholecystectomy smaller changes of shorter duration were seen. It is concluded from this study that synthetic grafts cause prolonged increase in the in vivo formation of thromboxane A2 and prostacyclin. The reason for the increased TxA2 formation is probably platelet interaction with the foreign surface, whereas the increase of PGI2 could be part of a vascular defense against induced thrombotic activity. Those increases may have pathophysiologic implications.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aorta, Abdominal; Aortic Aneurysm; Blood Vessel Prosthesis; Cholecystectomy; Epoprostenol; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Postoperative Period; Smoking; Thromboxane A2; Thromboxane B2