Activity and transport of antithrombin during acute limb ischemia.

Antithrombin (AT III), a major circulating anticoagulant, may be influenced by ischemia-induced changes in microvascular integrity and contribute to localized hypercoagulability. In a nonheparinized intact canine hindlimb model we determined AT III activity by chromogenic substrate assay (S-2238); coagulation changes with fibrinogen, activated partial thromboplastin time (aPTT), and prothrombin time (PT); and transvascular exchange by lymph-to-plasma total protein concentration ratio. Femoral venous plasma and lymph samples were assayed during 1 hour of steady state (C), 6 or 8 hours of aortoiliac occlusion (I), and 1 or 3 hours of reperfusion (R). Four groups were studied: GI, sham operated (n = 5); GII, moderate ischemia (n = 7), arterial pressure 30% to 45% C, GIII, 6 hours of severe ischemia (n = 7), arterial pressure 5% to 20% C; and GIV, 8 hours of severe ischemia (n = 5), arterial pressure 5% to 20% C. All parameters varied near baseline in the control group and the group with moderate ischemia. Fibrinogen decreased after 3 hours of ischemia in GIII from 218 +/- 38 to 175 +/- 46 mg/dl (mean +/- SEM) and in GIV from 254 +/- 39 to 201 +/- 44 mg/dl (p less than 0.005) as aPTT and PT increased. All parameters returned to baseline on R in GIII only. Plasma AT III decreased in GIV from 89% +/- 4.6% to 53.6% +/- 16.2% (p less than 0.005) after 3 hours and remained low during late I and R.(ABSTRACT TRUNCATED AT 250 WORDS)

Capnographic waveforms in esophageal intubation: effect of carbonated beverages.

Capnography is a useful tool in differentiating tracheal from esophageal intubation. It may be an especially useful tool in emergency airway management by rescue squads or in the emergency department. However, in clinical practice the question has arisen as to whether prior ingestion of carbonated beverages can generate false-positive capnographic evidence of endotracheal intubation when in fact esophageal intubation has occurred. To answer this question, we compared the difference between tracheal and esophageal capnographic waveforms in dogs in the setting of recent ingestion of carbonated beverages. Esophageal capnographic recordings from three of five dogs undergoing esophageal ventilation were strikingly positive for exhaled carbon dioxide; however, the waveforms were significantly different from waveforms of tracheal ventilation. We conclude that esophageal intubation, after recent ingestion of carbonated beverages, may give false-positive waveforms suggestive of tracheal intubation. Rapidly diminishing CO2 concentrations, however, help differentiate esophageal from tracheal ventilation in this setting.

Transvascular protein movement in the intact ischemic hindlimb.

Postischemic limb swelling following reperfusion may be related to microvascular changes associated with ischemia. We used lymph-to-plasma total protein concentration ratios (L/P) and lymph flow (QL) as an index of transvascular exchange in the intact dog hindlimb during steady state (C) (1 hr), ischemia (I) (6 hr), and reperfusion (R) (3 hr). Central pressures, femoral arterial and venous pressures (PA, PV) and QL were recorded every 15 min. Lymph was collected from a femoral lymphatic in the passively flexed leg (50 cycles/min). Three groups of animals were studied: GI, sham-operated (N = 5); GII, moderate ischemia (N = 7, PA = 30-45% C); and GIII, severe ischemia (N = 7, PA = 5-20% C). In GI, QL gradually increased over 10 hr without change in L/P. Moderate ischemia produced a decrease in QL, 3.55 +/- 2.02 mg/hr to 0.92 +/- 0.53 mg/hr (P less than 0.0001), and QL remained below baseline during R with no change in L/P over the 10 hr. Severe ischemia produced a similar decrease in QL, 1.91 +/- 2.05 mg/hr to 0.15 +/- 0.1 mg/hr (P less than 0.01); however, an increase to 2.56 +/- 2.14 mg/hr occurred during R. Severe ischemia increased L/P 0.42 +/- 0.08 to 0.64 +/- 0.23 (P less than 0.001) and remained elevated during R at 0.63 +/- 0.18 (P less than 0.001). An increase in the wet-to-dry weight ratio of ischemic to nonischemic muscle after reperfusion was noted only in GIII, 3.82 +/- 1.17 vs 2.60 +/- 0.45 (P less than 0.04). Severe ischemia produces changes in vascular integrity which augment protein flow. Prevention of these vascular changes may help to minimize the muscle swelling of reperfusion.

Coagulation responses to heparin in the ischemic limb: assessment of thrombin and platelet activation during vascular surgery.

In 11 men undergoing infrainguinal bypass surgery, simultaneous blood samples were analyzed by use of sensitive markers of thrombin activity (fibrinopeptide A, FPA) and platelet behavior (beta-thromboglobulin, beta-TG), as well as conventional clotting times. FPA levels were consistently higher in the venous outflow from the ischemic limb compared with the arterial inflow (p less than .01), while no venoarterial difference was noted for beta-TG. This suggests that there is increased thrombin generation, but not platelet activation localized to the ischemic limb. After a mean dose of 6800 units of heparin given during surgery, FPA levels fell significantly (p less than .03), and the activated clotting time (ACT) was prolonged to 230 to 260 sec, but beta-TG levels did not change. Anticoagulation during lower extremity vascular surgery may be usefully monitored by the activated clotting time because an ACT longer than 250 sec is correlated with lower FPA levels (less than 10 ng/ml), reflecting significant inhibition of coagulation.

Problems in the measurement of zinc using heparin as an anticoagulant.

Although several reports imply that anticoagulants and preservatives contain zinc, the quantity of zinc in heparin, if any, has not been documented. Zinc concentration was determined by flame atomic absorption spectroscopy in varying dilutions of multiple commercially obtained samples of purified sodium heparin N = 15 (microgram Zn/1000 Units heparin). Rubber stoppers of sterile heparin vials and of blood evacuation tubes were incubated in pre-analyzed water or saline on a mechanical shaker with fluid aliquots obtained up to 27 hours and analyzed for zinc content (microgram Zn/0.1 ml). Heparin, with contact or without contact with rubber stoppers, recorded identical zinc concentrations. Zinc concentrations varied from 0.222 +/- 0.01 (mean +/- SE) to 3.49 +/- 0.005 microgram Zn/1000 Units heparin. Leaching of zinc from rubber stoppers of vacutainer tubes (N = 9) was noted only with those containing known chelators of zinc. These results indicate that zinc is present in certain lots of sodium heparin and that caution must be exercised when reporting zinc concentrations of blood samples that contain sodium heparin as the anticoagulant.

Zinc transport by the heart lymphatic system after acute myocardial infarction.

Open-chest dog preparations were used to determine divalent cation transport following acute myocardial infarction. Cardiac lymph flow, lymph and plasma protein, zinc, calcium, and magnesium content and hemodynamic measurements were recorded every 20 min before and after coronary artery occlusion in sham operated (N = 4), infarcted (N = 6), and lymph-ablated animals (N = 4). During the 4-hr occlusion period, with constant blood pressure, lymph flow increased from 1.53 +/- 0.25 to 2.15 +/- 0.44 mg/hr (SEM), P less than 0.01. Zinc decreased in plasma from 0.69 +/- 0.10 to 0.41 +/- 0.08 micrograms/ml, P less than 0.01, and in lymph from 0.69 +/- 0.08 to 0.40 +/- 0.02 micrograms/ml, P less than 0.01. Zinc to protein ratio decreased similarly to total zinc in plasma and lymph. Changes in calcium and magnesium were insignificant. Lymph to plasma concentration ratios increased for protein from 0.57 +/- 0.05 to 0.62 +/- 0.02, P less than 0.05, and for zinc from 1.10 +/- 0.26 to 1.21 +/- 0.14, P less than 0.05. Heart lymph clearance (lymph:plasma ratio X lymph flow) steadily rose for protein from 0.31 to 0.06 to 0.50 +/- 0.08, P less than 0.05, and for zinc from 0.59 +/- 0.18 to 0.92 +/- 0.15, P less than 0.05. Lymph and plasma measurements did not change significantly in sham-operated animals. Plasma zinc remained unchanged from baseline after coronary occlusion in all lymph-ablated animals. The increased clearance of protein and zinc suggests that plasma proteins are zinc carriers after acute myocardial infarction and that the reduction of plasma zinc is dependent upon an intact cardiac lymphatic circulation.

Effects of coronary flow reduction on capillary-myocardial exchange in dogs.

The effects of coronary flow reduction on tracer capillary permeability surface area (PS) and distribution volumes were studied in open-chest dog preparations. A mixture of 51Cr-labeled red blood cells, 125I-labeled albumin, [14C]sucrose, and tritiated water (3H2O) was introduced into a shunt connecting the carotid and left anterior descending coronary arteries. Sampling from the coronary sinus produced a multiple indicator curve from which [14C]sucrose PS and 3H2O volumes were computed. Curves were observed in control situations and after the cannula was partially clamped. In six dogs, cardiac lymph was collected and analyzed for total protein. Paired comparison of control and flow-restricted indicator curves showed that flow reduction decreased the absolute values of PS and tracer volumes. The ratio of sucrose volume to weight of perfused tissue increased with flow reduction. The ratio of sucrose PS to weight of perfused tissue increased with moderate flow reduction and decreased with severe flow reduction. The results suggest that flow reduction has two effects which competively affect exchange: 1) flow restriction reduces surface area by capillary derecruitment, and 2) the remaining functional capillaries appear to undergo an increase in permeability to small molecules.