Sevoflurane but not isoflurane can reduce prostacyclin production of endothelial cells.

BACKGROUND AND OBJECTIVE: Little is known about the interaction of newer volatile anaesthetics with endothelial eicosanoid production. Sevoflurane may possibly reduce prostacyclin formation. Thus, we compared the influences of sevoflurane and isoflurane on endothelial prostacyclin production. METHODS: Production of prostacyclin of human umbilical vein endothelial cells was measured by the ELISA technique under basal conditions and after stimulation with calcium ionophore A 23187 10 micromol or histamine 0.1 micromol in the absence and presence of 1 and 2 minimal alveolar concentrations (MAC) of sevoflurane or isoflurane. RESULTS: The basal production of prostacyclin was unaffected by the volatile anaesthetics. Stimulation of endothelial cells increased prostacyclin formation 3-5-fold. Sevoflurane at 2 MAC, but not at 1 MAC, could reduce stimulated prostacyclin production by about half (P < 0.05). Isoflurane had no inhibitory effect. Inhibition of cyclo-oxygenase function by acetylsalicylic acid abolished the induced burst of prostacyclin formation completely. CONCLUSIONS: Sevoflurane, but not isoflurane, can reduce stimulated endothelial prostacyclin production in a concentration-dependent manner. Because at least 2 MAC of sevoflurane were required, this effect should be of minor importance under clinical conditions of balanced anaesthesia.

[Low alkali-hydroxide content in soda limes does not lead to reduction of compound A formation from sevoflurane during low-flow anesthesia]. / Einfluss von niedrigem Alkalimetallgehalt im Atemkalk auf Compound-A-Bildung während Low-flow-Narkosen mit Sevofluran.

The alkali hydroxide content in soda lime induces Compound A formation from Sevoflurane (Sevo). This study was designed to answer the question if the use of potassium hydroxide-free Soda Lime (SL) would lead to lower Compound A levels as compared to Sodasorb (SO). A total of 30 patients scheduled for elective laparoscopic cholecystectomy received Sevo anaesthesia under low-flow conditions (0.8 l/min fresh gas flow). Each absorbent was used in 15 patients, but 3 patients of the SO group were excluded due to technical problems with Compound A analysis. Hemodynamic parameters, parameters of ventilation and gas concentrations were documented. Compound A concentrations were measured by gas chromatography from gas samples before Sevo application and 20, 40, 60, 90 and 120 min after low-flow start. Mean endtidal Sevo concentrations were 1.94 +/- 0.17 (SO) and 1.97 +/- 0.15 (SL) vol %, the total anaesthetic exposition was 1.52 +/- 0.36 (SO) and 1.64 +/- 0.47 (SL) MAC-h (n.s). The maximum Compound A concentration was significantly higher in SL group (19.6 +/- 2.8 vs. 11.7 +/- 4.1 ppm, p < 0.001). Therefore, elimination of potassium hydroxide from carbon dioxide absorbents alone did not lead to a reduction of Compound A formation during low-flow anaesthesia.

Sevoflurane and isoflurane protect the reperfused guinea pig heart by reducing postischemic adhesion of polymorphonuclear neutrophils.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) contribute to reperfusion injury. Because volatile anesthetics can reduce PMN adhesion in the reperfused, nonworking heart, the authors analyzed whether this action of volatile anesthetics affects cardiac performance after ischemia and reperfusion and further clarified the underlying mechanism. METHODS: Isolated guinea pig hearts perfused with crystalloid buffer and performing pressure-volume work were used. Hearts were subjected to 15 min global ischemia and 20 min reperfusion. In the intervention groups an intracoronary bolus of 3 x 10(6) PMNs was applied in the second min of reperfusion, either in the absence or presence of 0.5 or 1 minimum alveolar concentration sevoflurane or isoflurane. The number of sequestered PMNs was calculated from the difference between coronary input and output (coronary effluent) of PMNs. Performance of external heart work, determined pre- and postischemically, served as criterion for recovery of myocardial function. Additionally, the expression of the integrin CD11b on the cell surface of PMN was measured before and after coronary passage. RESULTS: Injection of PMN in the reperfusion phase, but not under nonischemic conditions, reduced recovery of external heart work significantly (from 55+/-7% to 19+/-11%). Addition of sevoflurane or isoflurane in concentrations of 0.5 and 1 minimum alveolar concentration to the perfusate reduced postischemic PMN adhesion from 36+/-8% to basal values (20+/-7%) and prevented decline of cardiac function. CD11b expression on PMNs increased significantly during postischemic coronary passage under control conditions. Again, both anesthetics in both concentrations inhibited that activation. CONCLUSIONS: Volatile anesthetics reduce PMN adhesion in the reperfused coronary system and thereby preserve cardiac function. Reduced expression of the adhesion molecule CD11b on PMNs in the presence of sevoflurane or isoflurane is, at least in part, responsible for the cardioprotective effect.

Dobutamine stress echocardiography for noninvasive diagnosis of cardiac allograft vasculopathy: a comparison with angiography and intravascular ultrasound.

This study was performed to assess the value of dobutamine stress echocardiography for noninvasive diagnosis of cardiac allograft vasculopathy (CAV) compared with coronary angiography and intravascular ultrasound (IVUS) in 50 consecutive orthotopic heart transplant recipients. In 46 of 50 patients, a technically adequate echocardiogram could be obtained. Using a 16-segment model, a total of 675 segments were analyzed. At rest, wall motion abnormalities were found in 61 of 675 (9.0%) left ventricular segments in 15 of 46 patients. At maximal dobutamine stress, 103 of 675 segments (15.3%) had wall motion abnormalities (25 of 46 patients). Based on IVUS and angiographic findings, patients were allocated to 2 groups. Group I (n=18) had absent or only mild intimal hyperplasia (mean IVUS grade < or = 3.0 on a 6-grade scale). Group II (n=28) had moderate to severe intimal hyperplasia (mean grade > 3.0 with or without angiographic evidence of CAV. The prevalence of wall motion abnormalities was significantly higher in group II than in group I, both at rest (50 of 415 vs 11 of 270 coronary segments in 13 of 28 vs 2 of 18 patients) and during maximal stress (88 of 415 vs 15 of 270 coronary segments in 22 of 28 vs 3 of 18 patients). Quantitative M-mode echocardiography demonstrated decreased wall thickening in group II versus group I patients at maximal dobutamine dosage in the septum (48 +/- 18% vs 61 +/- 17%; p < 0.01) as well as in the left ventricular posterior wall (77 +/- 21% vs 96 +/- 21%; p <0.005). Regional myocardial dysfunction as assessed by dobutamine stress echocardiography was associated with IVUS evidence of moderate to severe intimal hyperplasia. Dobutamine stress echocardiography appears to be a feasible noninvasive method for detection of CAV in heart transplant recipients, which may reduce the need for routine coronary angiography.

Altered low density lipoproteins in peripheral vascular disease patients.

Several studies have shown that peripheral vascular disease (PVD) patients have abnormal lipoproteins. The mechanism whereby this abnormal lipid metabolism influences arterial occlusive disease in these PVD patients is not known. In the present study we found that low density lipoproteins (LDL) obtained from PVD patients have lower affinity to B receptor of normal fibroblasts compared to LDL obtained from control subjects. The nanograms of 125I LDL bound per milligram of B receptor was 254 +/- 19 for LDL from control subjects, 152 +/- 12 for LDL from PVD without diabetes, and 108 +/- 8 for PVD with diabetes (P less than 0.01). Further, the preincubation of LDL obtained from PVD patients with pentoxifylline (xanthine derivative used for PVD) increased the binding affinity of the LDL to B receptor sites from 107 +/- 9 to 210 +/- 34 (P less than 0.01). There was no significant difference in the binding properties of LDL with fibroblasts either from PVD patients (254 +/- 19) or control subjects (267 +/- 22) (P greater than 0.5), thereby suggesting that the number of receptor sites may be the same in both types of fibroblasts. From these results it can be concluded that defect in the metabolism of LDL may promote arterial occlusive disease seen in the PVD patients.

Hepatic and renal metabolism before and after portasystemic shunts in patients with cirrhosis.

Hepatic cirrhosis with portal hypertension and gastroesophageal hemorrhage is a disease complex that continues to be treated by surgical portasystemic shunts. Whether or not a reduction or diversion of portal blood flow to the liver adversely affects the ability of the liver to maintain fuel homeostasis via gluconeogenesis, glycogenolysis, and ketogenesis is unknown. 11 patients with biopsy-proven severe hepatic cirrhosis were studied before and after distal splenorenal or mesocaval shunts. Hepatic, portal, and renal blood flow rates and glucose, lactate, pyruvate, glycerol, amino acids, ketone bodies, free fatty acids, and triglyceride arteriovenous concentration differences were determined to calculate net precursor-product exchange rates across the liver, gut, and kidney. The study showed that hepatic contribution of glucose and ketone bodies and the caloric equivalents of these fuels delivered to the blood was not adversely affected by either a distal splenorenal or mesocaval shunt. In addition to these general observations, isolated findings emerged. Mesocaval shunts reversed portal venous blood and functionally converted this venous avenue into hepatic venous blood. The ability of the kidney to make a substantial net contribution of ketone bodies to the blood was also observed.

Pentoxifylline in the treatment of intermittent claudication of the lower limbs.

Pentoxifylline, a methyl xanthine analogue was evaluated for treatment of intermittent claudication in a double-blind placebo controlled parallel group study in seven centers in the United States. Tests were performed on 128 cases, including 42 who took pentoxifylline (600 mg by mouth daily, increased stepwise to 1200 mg daily at the end of one month) and 40 who took placebo for 24 weeks. Twenty-five patients on pentoxifylline and 21 on placebo were dropped from the study for reasons unrelated to the drug. Walking ability on a treadmill was increased significantly after 2 weeks and remained so throughout the study in the pentoxifylline vs. the placebo group. Ability to walk until first experiencing intermittent claudication was a more sensitive index than the maximum ability to walk. The drug did not cause changes in blood pressure or in heart rate. Other than mild nausea, there were no significant side effects.

Effects of catechol estrogen methyl ethers on lipid metabolism in prepubertal rats.

Thirty-five day old ovariectomised rats were given daily subcutaneous injections (0.05-5.0 micrograms/100 gm body weight) of estradiol (E2) 2-methoxyestradiol (2-ME2) or 4-methoxyestradiol (4-ME2) for six days. At the end of the last injection, the animals were sacrificed and serum lipoproteins were analysed. It was observed that cholesterol decreased significantly in normal fed animals who received E2 and 4-ME2, while no effect was seen in cholesterol fed animals. In the E2 treated group there was a decrease in esterified and free cholesterol, while in the 4-ME2 group only esterified cholesterol decreased. High density lipoproteins were significantly elevated in the E2 treated group. However, there was an increase in very low density lipoproteins and a decrease in low density lipoproteins in 2-ME2 and 4-ME2 treated groups. These results suggest that catechol estrogens may play an important role in the lipoprotein metabolism and atherosclerotic diseases, and the mechanism of action may differ from that of estradiol.

Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients.

The efficacy, safety, and tolerance of pentoxifylline (Trental, Hoechst-Roussel Pharmaceuticals, Inc.) in the treatment of intermittent claudication associated with chronic occlusive arterial disease (COAD) were evaluated in a double-blind, placebo-controlled, parallel-group, multicenter clinical trial involving a total of 128 outpatients. The response to treatment was ascertained at regular intervals during the trial by measuring the distance walked prior to the onset of claudication when patients were subjected to a standardized treadmill test. Pentoxifylline given orally in doses up to 1200 mg/day was significantly more effective than placebo in increasing both the initial and absolute claudication distances in patients with COAD. Reduction of lower limb paresthesias also suggested greater clinical improvement in the pentoxifylline treated patients. These results support the hypothesis that pentoxifylline reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD. White the precise mode of therapeutic action requires clarification, pentoxifylline was well tolerated with minimal unwanted effects.

Comparative review of early and intermediate patency rates of polytetrafluoroethylene and autogenous saphenous vein grafts for lower extremity ischemia.

One hundred nine primary bypass operations were performed on 97 patients who had limb ischemia caused by arteriosclerosis obliterans, over a 32-month period starting in January, 1978. The majority of those procedures were done for rest pain or gangrenous changes. The greater saphenous vein was used whenever possible (44 of 109 procedures), and a polytetrafluoroethylene (Gore-Tex) prosthesis was used in 65 of 109 procedures. Average follow-up was 9.3 months. The cumulative patency rate in all vein grafts was 93.1% at 1 month and 73.4% after 31 months, whereas the cumulative patency rate for polytetrafluoroethylene was 83.3% at 1 month and 51% at 31 months. The difference is not statistically significant (0.10 less than P less than 0.25). In above-knee procedures for claudication, polytetrafluoroethylene performed identically to vein (P greater than 0.50), although vein appeared to perform better in above-knee procedures done for rest pain or necrosis. A limited number of below-knee revascularizations were performed, and although no conclusions of statistical significance can be drawn, cumulative patency of vein appeared to be better than polytetrafluoroethylene. For additional comparative analysis, this study was compared to a previous study in which Dacron was used in femoropopliteal arterial reconstructions. Patency rates in above-knee revascularizations appeared to be comparable in Dacron and polytetrafluoroethylene. Diabetes did not appear to alter age of onset of disease or patency rates, although smokers became symptomatic 10 years earlier than nonsmokers. Although the early and long-term results of arterial reconstructions in the ischemic extremity are known, the availability of new alternate arterial prostheses raises the question of the optimum material depending on the specific clinical circumstances.

Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

The roles of liver, kidney, and gut in maintaining fuel homeostasis were studied in 28 patients with severe hepatic cirrhosis, 25 of whom had alcohol-induced cirrhosis. Hepatic, portal, and renal blood flow rates were measured and combined with substrate concentration differences across liver, gut, and kidney to calculate the net flux of free fatty acids, ketone bodies, triglycerides, and glucose with selected glucose precursors, including glycerol, lactate, pyruvate, and amino acids. Data from the catheterization studies were related to hepatic histology, glycogen content, and activities of gluconeogenic enzymes and compared with data obtained from control patients. The effects of food deprivation on net flux of fuels across the liver, gut, and kidney were assessed after overnight and after 3d of fasting. Activities of gluconeogenic enzymes were normal, but hepatic glycogen content was diminished in cirrhotic livers, probably as a consequence of extensive hepatic fibrosis. Extrahepatic splanchnic tissues (gut) had only a small influence on total splanchnic flux rates of carbohydrates, lipids and, amino acids. In cirrhotic patients, there was no mean renal glucose contribution to the bloodstream after an overnight or after a 3-d fast. After an overnight fast hepatic glucose production in patients with cirrhosis was diminished as a result of low-rate glycogenolysis. Hepatic gluconeogenesis and ketogenesis were increased. This pattern of hepatic metabolism mimics that seen in "normal" patients after more advanced stages of starvation. After 3 d of starvation, patients with hepatic cirrhosis have hepatic gluconeogenic and ketogenic profiles comparable to those of normal patients undergoing starvation of similar duration. Nevertheless, the total number of caloric equivalents derived from ketone bodies plus glucose corrected for recycled lactate and pyruvate added to the bloodstream by the cirrhotic livers that could be terminally oxidized by peripheral tissues was less than the contributions made by the normal livers, both after and overnight and after a 3-d fast.

Diagnosis and management of penetrating arterial and venous injuries in the extremities.

Physical examination of a patient in whom a significant vascular injury of the extremity is suspected will almost always provide a prompt and accurate diagnosis of arterial injury. Prompt operation based on the clinical assessment, without specialized diagnostic studies, results in limb salvage and minimal morbidity.

Infrapopliteal arterial reconstruction in the severely ischemic lower extremity. A comparison of long-term results of peroneal and tibial bypasses.

The feasibility of limb salvage with bypasses to the infrapopliteal arterial tree has been established. In this review, our experience with bypasses to the peroneal artery is compared with that to the tibial arteries. Autogenous saphenous veins were employed in 164 limb salvage arterial revascularizations because of gangrene, ischemic ulceration, or rest pain. These were retrospectively analyzed by the life-table method. Femorotibial (137) or femoroperoneal (27) bypasses were performed on the basis of adequate preoperative arteriograms demonstrating the distal arterial tree, but with no popliteal runoff. Overall operative mortality was 6.1%. Initial limb salvage was 71.2 +/- 3.9% following femorotibial bypass and 51.9 +/- 9.6% after femoroperoneal bypass. Five and seven year cumulative limb salvage rates for femorotibial bypass were 48.5 +/5.2% and 43.4 +/- 6.7%; those for femoroperoneal were equivalent at 38.2 +/- 9.9%. Since long-term limb salvage can be realized in a large number of patients by revascularization of the distal arterial tree, primary amputation is seldom indicated. Operative approach to the ischemic limb must be based on a thorough preoperative arteriogram which demonstrates contrast within vessels down to the distal foot. This is almost always seen and arterial reconstruction is usually feasible. Therefore, limb salvage should be attempted in lieu of primary amputation whether tibial or peroneal arteries are visualized on preoperative arteriogram.

Hemodynamic patterns in human hepatic cirrhosis: a prospective randomized study of the hemodynamic sequelae of distal splenorenal (Warren) and mesocaval shunts.

Increasingly successful operative management of gastroesophageal variceal hemorrhage has been achieved by newer techniques of portal venous reconstruction. Although it is postulated that the clinical success may be due to more selectivity in portal venous shunting, direct determination of the effect of portasystemic shunt on portal vein blood flow has not been possible. Direct determinations of portal vein blood flow were performed preoperative on unanesthetized, hemodynamically stable cirrhotic patients by observation of radiopaque water-insoluble droplets. Patients were then randomized into elective distal splenorenal (Warren) or mesocaval shunt and determinations were performed postoperatively under similar conditions when clinically possible. Although portal vein blood flow was not significantly different before (929 +/- 147 ml/min) or after 899 +/- 271 ml/min) distal splenorenal shunt, there was a large change in portal vein blood flow after mesocaval shunt, decreasing from 772 +/- 177 ml/min (hepatopetal) to -1021 +/- 310 ml/min (hepatofugal) p < 0.01). After either procedure total hepatic blood flow (as determined by cardiac green clearance) was not significantly changed, nor was renal blood flow; however, cardiac output was significantly increased after mesocaval shunt. Thus the theoretical hemodynamic goals of the selective distal splenorenal shunt, i.e., preservation of the hepatopetal flow within the portal vein, is achieved as determined in the early postoperative period. The correlation between these changes and the eventual clinical outcome remains to be determined.

Salvage of extremities with ischemic necrosis in diabetic patients by infrapopliteal arterial bypass.

Initial and long-term limb salvage can be achieved by infrapopliteal bypass in diabetic patients with ischemic necrosis of the distal extremity. Mortality is low in all groups, and mortality of subsequent amputation apparently is not affected by the previous bypass. An adequate arteriogram and consideration of distal bypass are frequently indicated in the diabetic patients in whom ischemic necrosis is present. Limb salvage may be feasible even in those diabetic patients in whom popliteal artery is not patent on preoperative arteriogram by bypasses to anterior tibial, posterior tibial, or peroneal artery.

The elderly patient with severe arterial insufficiency of the lower extremity: limb salvage by femoro-popliteal reconstruction.

To determine the feasibility of limb salvage in elderly patients in whom severe ischemia of the lower extremity is present, the results of femoro-popliteal reconstruction done primarily for limb salvage were reviewed. Of 310 femoro-popliteal bypasses, 72 were performed on patients 70 years of age or older. In the over-70 group, ischemic necrosis was present in 70.8% rest pain in 22.2%, and claudication in 7.0%. Initial limb salvage patients 70 years of age or older was 71.4%. Cumulative limb salvage at 5 years was 51.1% and at 10 years was 44.8%. Operative mortality, including mortality of subsequent amputation, when required, was 8.3%. Appreciable limb salvage can be achieved by femoro-popliteal arterial reconstruction in lieu of primary amputation in elderly patients in whom severe arterial insufficiency of the lower extremity is present.

Long-term results of femoroinfrapopliteal bypass in diabetic patients with severe ischemia of the lower extremity.

In patients with severe lower extremity ischemia (ischemic necrosis or pain at rest associated with physical findings of peripheral arterial insufficiency), diabetes mellitus should not deter thorough arteriography and consideration of arterial reconstruction. Infrapopliteal bypass can produce prolonged limb salvage in diabetic patients in lieu of primary amputation.