Protection from atherosclerotic lesion formation by reduction of artery wall motion

We have studied mechanical factors that could determine how stenosis protects against distal atherosclerosis in cynomolgus monkeys fed an atherogenic diet. Critical aortic stenosis was produced by coarctation of the thoracic aorta. After 3 months, coarcted monkeys had a mean aortic pressure gradient of 25 +/- 1 mm Hg and a 76% +/- 2% lumen stenosis. Aortic wall motion was measured by means of in vivo ultrasonic sonomicrometry. Dynamic tracings of aortic pressure and diameter were recorded simultaneously at standard locations proximal and distal to the stenosis and at comparable sites in noncoarcted control animals. In the proximal aorta, mean blood pressure and pulse pressure were increased (p less than 0.05), but wall motion and intimal lesion area were not different from those determined in control monkeys. In the aorta distal to the coarct, mean blood pressure was no different from that in control animals but pulse pressure was diminished; in addition, there was marked reduction of arterial wall motion (p less than 0.001). This was accompanied by a significant reduction of intimal plaque area (p less than 0.05) and acid lipase activity (p less than 0.001). Thus, inhibition of plaque formation in the distal aorta coincided with reduction of pulse pressure and aortic wall motion rather than with blood pressure or hypercholesterolemia. Inhibition of arterial wall motion may account for the sparing effect often encountered in human arteries distal to stenosing atherosclerotic plaques.     

Aortoplasty compared with resection for coarctation of the aorta in young children

We repaired coarctation of the aorta in a group of 18 children less than 3 years old, using either resection with end-to-end anastomosis (8 patients, Group 1) or patch graft aortoplasty (10 patients, Group 2). The two groups were similar preoperatively in age, pressure difference between proximal and distal aorta (delta PA0), and severity of aortic arch hypoplasia. Three patients, all less than 2 months old, died early postoperatively. Among the survivors, the right brachial artery systolic pressure was significantly higher in Group 1 (133.1 +/- 7.0 mm Hg) (mean +/- standard error of the mean) than in Group 2 (102.5 +/- 7.2 mm Hg) (p less than 0.05). The delta PA0 was significantly higher in Group 1 (33.0 +/- 7.5 mm Hg) than in Group 2 (5.1 +/- 2.3 mm Hg) (p less than 0.01). Three patients in Group 1 required reoperation and were treated with patch graft aortoplasty; relief of delta PO0 was complete in 2. Patch graft aortoplasty is more effective than resection in reducing proximal aortic systolic pressure and in relieving delta PA0 in infants and small children with coarctation of the aorta.     

Daytime ambulatory blood pressure correlates strongly with the echocardiographic diameter of aortic coarctation.

OBJECTIVE: To relate the echocardiographic aortic arch-diameter to ambulatory and clinic blood pressure (BP) in patients with aortic coarctation. DESIGN: Eighteen adult patients (50% men) were recruited from the coarctation registry of the Linkoping Heart Centre. Biplane-trans-oesophageal echocardiography (TEE) was performed with Acuson XP 128/10, ambulatory BP was recorded with Spacelab models 90202/90205. RESULTS: Systolic clinic and ambulatory BP levels were higher in patients than in the 36 controls (clinic BP: 146 +/- 25 mmHg vs 119 +/- 10 mmHg, p = 0.0009, ambulatory BP: 140 +/- 18 mmHg vs 124 +/- 11 mmHg, p = 0.009). The differences in diastolic BP levels were less obvious (clinic BP: 87 +/- 16 mmHg vs 76 +/- 8 mmHg, p = 0.02, ambulatory BP: 84 +/- 13 mmHg vs 77 +/- 9 mmHg, p = 0.052). Daytime ambulatory BP was more strongly related than clinic BP to the coarctation diameter (AD) (systolic BP r= -0.73, p = 0.0006 and r = -0.61, p = 0.007, respectively). In surgically corrected patients (n = 14) only the correlations between ambulatory systolic daytime (r = -0.61, p = 0.02) and night-time (r = -0.58, p = 0.03) BP to AD was statistically significant. CONCLUSION: Ambulatory BP correlates strongly with aortic coarctation measured by TEE and would thus be the preferred technique for evaluating BP in this patient category.     

Influence of a jejunal fistula on gastric emptying

The aim was to determine whether a proximal jejunal fistula would speed gastric emptying after truncal vagotomy and Roux distal gastrectomy. Eight vagotomy-gastrectomy dogs were studied; 4 had a jejunal fistula, and 4 other dogs without a fistula served as controls. The rate of gastric emptying of 100 ml 25% dextrose in the fistula dogs with the fistula open (95 +/- 3 ml/20 min) was faster than in the same dogs with the fistula closed (62 +/- 10 ml/20 min; p less than 0.05) and faster than in dogs without a fistula (77 +/- 5 ml/20 min; p less than 0.05). The rate of emptying in dogs with the fistula closed, however, was similar to the rate in dogs without a fistula (p greater than 0.05). We concluded that diversion of the enteric content to the exterior through a proximal jejunal fistula increases the rate of gastric emptying of 25% dextrose solutions in dogs with truncal vagotomy and Roux gastrectomy.     

Effects of exsanguination and sodium nitroprusside on compliance of the spinal canal during aortic occlusion.

To evaluate the effects of sodium nitroprusside (SNP) and partial exsanguination (EXS) on systemic hemodynamics and cerebrospinal fluid dynamics, we monitored proximal and distal blood pressure (BP), cerebrospinal fluid pressure (CSFP), spinal cord perfusion pressure (SCPP), and compliance of the spinal canal (CSC) in 10 mongrel dogs during aortic cross-clamping of the descending thoracic aorta. CSC was measured by serial injections of 2 ml of saline solution into the cisterna cerebellomedullaris via a percutaneously placed catheter with simultaneous measurements of CSFP. Data were acquired at baseline (BL), during aortic cross-clamping with proximal hypertension (AXC), and after control of proximal hypertension with EXS and SNP. During the cross-clamp interval, mean proximal aortic pressure (PxBP) rose from 114 +/- 6 to 150 +/- 3 mm Hg (P less than 0.001), whereas mean blood pressure decreased to 88 +/- 5 and 82 +/- 4 mm Hg during the SNP and EXS intervals, respectively (P less than 0.05 vs BL). EXS and SNP were equally effective in controlling PxBP (82 +/- 4 vs 88 +/- 5 mm Hg, P greater than 0.05). Mean distal aortic pressure (DsBP) decreased from systemic values to 21.5 +/- 1.9 mm Hg during AXC, and to 12.4 +/- 1.0 and to 8 +/- 0.8 mm Hg during EXS and SNP, respectively (P less than 0.05 AXC vs EXS and SNP). SNP lowered DsBP significantly more than EXS, 8 +/- 0.8 vs 12.4 +/- 1.0 mm Hg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of alternative cardioplegic techniques

Cold potassium cardioplegia provides adequate protection for coronary bypass operations, but severe coronary stenoses limit cardioplegic delivery to ischemic regions. The traditional technique delivers cardioplegic solution into the aortic root during the performance of distal anastomoses. The proposed alternative technique constructs proximal as well as distal anastomoses during a prolonged cross-clamp period, but permits more uniform cooling. The two techniques were compared in a prospective concurrent trial of 45 patients undergoing elective coronary bypass grafting. The traditional technique was employed in 26 patients (Group A) and the alternative technique in 19 patients (Group B). In both groups, 700 to 1,000 ml of a crystalloid cardioplegic solution was infused into the aortic root after application of the aortic cross-clamp. In Group A (traditional technique), 500 ml was infused into the aortic root after each distal anastomosis. In Group B (alternative technique), cardioplegic solution was administered through the vein graft after each distal anastomosis, and a proximal anastomosis was constructed after distal anastomoses to the most ischemic regions to permit continued cardioplegic delivery to these regions. The cross-clamp period was shorter in Group A than in Group B (44 +/- 15 versus 60 +/- 18 minutes, p less than 0.01), but the mean temperature in the most ischemic region was warmer (Group A, 19 degrees +/- 3 degrees C; Group B, 15 degrees +/- 3 degrees C, p less than 0.05). The postoperative CK-MB was higher in Group A (Group A, 47 +/- 36; Group B, 21 +/- 9 IU/L, p less than 0.01). Cardiac lactate production persisted longer in Group A (Group A, 4 +/- 1; Group B, 1 +/- 1 hours postoperatively, p less than 0.05). Volume loading 4 hours postoperatively produced a similar increase in left atrial pressure and cardiac index in both groups. In response to volume loading, Group A patients produced lactate, but Group B patients extracted lactate (change in cardiac lactate extraction: Group A, -1.7 +/- 2.3; Group B, +2.5 +/- 5.1 mg/dl, p less than 0.05). The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cooling and immediate reperfusion. This alternative technique resulted in less injury (CK-MB release) and more rapid recovery of myocardial metabolism.     

Renal hemodynamic and tubular response to furosemide in man during normal and restricted sodium intake

To investigate the factors determining the natriuretic response to furosemide (F) during Na restriction, we performed clearance studies in 7 healthy humans on a daily Na intake of 200 and 20 mmol. The maximum urine flow during water loading (Vmax) and simultaneous F administration was used as index of tubular fluid output from the proximal tubules. The F-induced natriuresis was only moderately reduced during Na restriction (Na excretion on low vs. normal Na intake: 4.28 +/- 0.25 vs. 4.94 +/- 0.25 mmol/min; p less than 0.05). The diminished natriuresis was mainly due to a significant fall in Na delivery to Henle's loop of 0.51 +/- 0.10 mmol/min which was either caused by a decrease in filtered Na load or a rise in fractional proximal reabsorption. Fractional distal Na reabsorption was less suppressible by F during Na restriction, but this contributed relatively little (0.15 +/- 0.11 mmol/min) to the total reduction in Na excretion (0.66 +/- 0.10 mmol/min). The F-induced increases in uric acid, phosphate, and bicarbonate excretion suggest an additional proximal site of action of F. This was confirmed by a rise in lithium clearance (CLi), another alleged index of tubular fluid delivery from the proximal tubules. However, the magnitude of the rise in CLi to values markedly exceeding Vmax suggest that CLi overestimates tubular fluid delivery to Henle's loop during F administration.     

Dietary marine oil supplements fail to affect cholesterol metabolism or inhibit atherosclerosis in rabbits with diet-induced hypercholesterolemia

Dietary marine oil supplements may protect against atherosclerosis, although their influence on plasma lipids, in vivo cholesterol metabolism, and aortic cholesterol accumulation remains uncertain. The effects of daily administration of marine oil--delivering 100 mg of eicosapentaenoic acid, 59 mg of docosahexaenoic acid, and 221 mg of omega-3 fatty acids per kilogram--were assessed in 33 New Zealand white rabbits. Six animals (group I) were immediately killed. In the remaining animals stable hypercholesterolemia was induced with a 0.25% cholesterol-enriched diet. After 7 weeks on this diet, six animals were killed (group II). Total plasma cholesterol had increased significantly (982 +/- 119 mg/dl vs. 55.6 +/- 7.1 mg/dl, mean +/- SEM, p less than 0.001). The remaining animals randomly received a tap-water placebo (group III, n = 12) or marine oil (group IV, n = 9) daily. After 3 months, total plasma cholesterol was similar (p = NS) among group II (982 +/- 119 mg/dl), group III (965 +/- 54 mg/dl), and group IV (913 +/- 46 mg/dl). No significant differences in HDL cholesterol, LDL cholesterol, VLDL cholesterol, or triglyceride levels developed between the placebo and marine oil groups. Two-hour, hepatic total lipid, neutral steroid, fatty acid, bile acid, and cholesterol synthesis rates were not significantly affected by marine oil treatment. Thoracic aortic cholesterol content increased during cholesterol feeding (5.7 +/- 0.9 mg/gm vs. 1.1 +/- 0.05 mg/gm, group II vs. group I, p less than 0.05). Marine oil supplementation had no effect on the progressive accumulation of cholesterol in the thoracic aorta (28.8 +/- 2.5 mg/gm vs. 29.4 +/- 1.8 mg/gm, group IV vs. group III, p = 0.84). The abdominal aortic cholesterol contents were also similar. These results do not support the use of dietary marine oil supplements for the amelioration of lipid metabolism or the prevention of atherosclerosis.     

Renal concentration defect induced by cisplatin. The role of thick ascending limb and papillary collecting duct

The effects of cisplatin (5 mg/kg BW given intraperitoneally) on renal concentration mechanism were evaluated initially by clearance studies in rats 5-7 days after cisplatin administration and compared to normal rats. During hypotonic saline infusion, cisplatin rats showed a lower inulin clearance (0.56 +/- 0.07 vs. 1.12 +/- 0.09 ml/min/100 g BW, p less than 0.01), a higher fractional distal delivery (CNa + CH2O/Cin) (36.3 +/- 4.4 vs. 22.8 +/- 4.5%, p less than 0.05), and lower CH2O/CNa + CH2O (33.6 +/- 5.8 vs. 56.5 +/- 5.0%, p less than 0.01). During hypertonic saline infusion the TcH2O/Cosm was lower in cisplatin (18.3 +/- 1.1%) than in normal rats (33.4 +/- 3.5%, p less than 0.01). These results suggest a defect in NaCl transport in the thick ascending limb of Henle and proximal tubule. In order to characterize these tubular defects, we measured Na-K-ATPase activity (microM Pi/mg protein/h). In the renal cortex of cisplatin rats the ATPase activity was lower (18.1 +/- 3.2) than in normal rats (33.4 +/- 6.4, p less than 0.05), also in the inner strip of the outer medulla of cisplatin rats Na-K-ATPase was reduced (26.0 +/- 5.7) when compared with normal rats (67.3 +/- 9.2, p less than 0.01), presumably representing a decrease in enzyme activity in the thick ascending limb.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated dietary protein intake impairs the renal hemodynamic response to hyperaminoacidemia in patients with primary glomerular diseases

We have evaluated the renal hemodynamic response to a mixed amino acid infusion in 7 control subjects and in 8 patients with primary glomerulonephritis (GN). In order to evaluate the role of dietary protein intake in this response, GN patients were maintained for 3 weeks on two separate dietary regimens providing 130 +/- 5 g of protein/day (study 1) and 60 +/- 3 g of protein/day (study 2), respectively. Normal subjects were studied while consuming a free diet. In GN patients, following the reduction in dietary protein intake basal RPF and GFR decreased from 589 +/- 109 to 422 +/- 81 ml/1.73 m2/min (p less than 0.01, vs. study 1) and from 75 +/- 7 to 70 +/- 8 ml/1.73 m2/min (p = NS). Filtration fraction rose from 0.14 +/- 0.02 to 0.19 +/- 0.03 (p less than 0.05). In study 1, during amino acid infusion GFR and RPF did not change significantly from baseline (75 +/- 7 vs. 66 +/- 8 ml/1.73 m2/min at 180 min and 589 +/- 109 vs. 567 +/- 102 ml/1.73 m2/min, respectively). These results are at variance with data obtained in normal controls in whom both GFR and RPF rose significantly following hyperaminoacidemia. In contrast, when dietary protein intake was reduced, a normal renal hemodynamic response to amino acid infusion was restored (GFR went from 70 +/- 8 to 90 +/- 18 ml/1.73 m2/min and RPF from 422 +/- 81 to 517 +/- 90 ml/1.73 m2/min, both p less than 0.05 vs. basal), both absolute and percentage increases were similar to what was observed in controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin(GIK) improves myocardial metabolism in patients during blood cardioplegia

The aim of this study was to test the hypothesis that abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion are attenuated further by insulin(GIK) than by alpha-ketoglutarate enrichment of blood cardioplegia alone. Twenty-eight males (47 to 78 years) undergoing coronary artery bypass grafting (CABG) participated in a prospective, controlled, randomized study. All patients had alpha-ketoglutarate-enriched blood cardioplegia. Insulin(GIK) was infused in 13 patients during aortic cross-clamping. Insulin(GIK) prevented lactate release during cardioplegia (1.5+/-15 vs -44+/-14 micromol/min, p = 0.04), and a significant extraction of lactate was induced shortly after declamping the aorta (15+/-3 vs 2+/-1%, p = 0.001). Free fatty acid uptake was reduced after cardioplegic cross-clamping (5.7+/-1.6 vs 16.0+/-3.8 micromol/min, p = 0.02). More positive/less negative levels of alanine, aspartate, glutamine, glycine, ornithine, taurine and tyrosine were found in all the insulin-treated patients. We conclude that insulin(GIK) attenuates abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion further than is obtained with alpha-ketoglutarate enrichment of blood cardioplegia alone.     

Clinical significance of the fractional excretion of anions in metabolic acidosis.

The fractional excretion of anions has been proposed as a new index for the differential diagnosis of metabolic acidosis, identifying the properties of the conjugate base by examining the renal handling of the anion. Here, we investigated clinical significance of the fractional excretion of anions in pathophysiologic diagnosis of metabolic acidosis by measuring urine ammonium (NH4+) excretion, the ratio of A plasma anion gap/delta plasma HCO3- concentration (deltaAG/deltaHCO3-), and fractional excretion of anions in three different groups of metabolic acidosis: acid overproduction (8 patients with lactic acidosis, 8 with diabetic ketoacidosis, 3 with hippuric acidosis following glue sniffing), acid underexcretion (10 patients with chronic renal failure) and normal controls (10 normal volunteers who underwent 3-day NH4Cl loading). As expected, urine NH4+ excretion was higher in overproduction acidosis than in acid-loaded normal controls (88.1 +/- 12.3 vs. 54.0 +/- 3.7 mmol/day, p < 0.05), and it was lower in chronic renal failure than in acid-loaded normal controls (12.8 +/- 1.7 vs. 54.0 +/- 3.7 mmol/day, p < 0.05). The fractional excretion of anions had no difference between overproduction acidosis and chronic renal failure (41.2 +/- 42.8% vs. 41.0 +/- 8.1%). However, the fractional excretion of anions showed significant differences between the subgroups in acid overproduction (lactic acidosis, 4.7 +/- 0.3%; diabetic ketoacidosis, 45.8 +/- 3.1%; hippuric acidosis, 126.0 +/- 14.4%; p < 0.05). The ratio of plasma deltaAG/deltaHCO3- also exhibited significant differences between the subgroups in acid overproduction (lactic acidosis, 1.5 +/- 0.1; diabetic ketoacidosis, 1.0 +/- 0.1; hippuric acidosis, 0.3 +/- 0.1; p < 0.05). There was an inverse linear correlation between the fractional excretion of anions and the ratio of plasma deltaAG/deltaHCO3- (r2 =-0.89, p < 0.05). In conclusion, determination of the fractional excretion of anions may provide a useful clue to the differential diagnosis of metabolic acidosis caused by acid overproduction.     

Effects of the site of distal anastomosis on the branch flow of coronary arteries in an A-C bypass grafting

Hemodynamics of coronary branch with retrograde blood flow of the host artery was examined in seven mongrel dogs, when the distal side of the graft was anastomosed at distal site to branching point in A-C bypass grafting. A Y-shaped tube was interposed to reconstruct coronary blood flow between the right carotid artery and the left anterior descending coronary artery (LAD), its one arm of Y was connected to proximal site of the branching point of the first diagonal artery (proximal anastomosis), and the other arm was connected to distal site of the branching point (distal anastomosis). After the LAD was ligated just distal to the bifurcation from the left main coronary artery, each arm was clamped in turn, and blood flow of the first diagonal branch was evaluated. Heart rate, left ventricular pressure and cardiac output (cardiac function), and blood pressure, flow and resistance of the interposed tube (bypass function) were not changed significantly in each arm clamped. The diagonal branch flow decreased from 11.2 +/- 2.7 ml/min (mean +/- S.D.) in proximal anastomosis to 10.3 +/- 3.1 ml/min in distal anastomosis with significant difference (P less than 0.05). The diagonal branch/bypass graft flow ratio decreased from 0.422 +/- 0.159 in proximal anastomosis to 0.395 +/- 0.160 in distal anastomosis with significant difference (p less than 0.05). The blood flow in systolic phase of the diagonal branch tended to increase in distal anastomosis as compared with proximal anastomosis. However, diastolic flow of the branch significantly decreased from 8.3 +/- 2.1 ml/min in proximal anastomosis to 7.1 +/- 2.2 ml/min in distal anastomosis (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Minor role of ketone bodies in energy metabolism by skeletal muscle tissue during the postoperative course.

To evaluate changes of peripheral ketone body (KB) metabolism after operation, muscle metabolism in postsurgical patients was studied at 3 hours (SI) and 24 hours (SII) after surgery by the forearm catheter technique. Data were compared to those of equivalent fasted controls (CI, CII). In a manner consistent with enhanced mobilization of endogenous substrate stores, arterial concentrations of free fatty acids (FFA), 3-hydroxybutyrate (3-HOB), and acetoacetate (AcAc) were markedly elevated immediately after surgery. This increase was accompanied by a rise in muscular utilization of AcAc (SI: 0.21 +/- 0.05 mumol/100 g/min; CI: 0.08 +/- 0.05, p less than 0.05) and 3-HOB (SI: 0.24 +/- 0.06 mumol/100 g/min; CI: 0.11 +/- 0.01, p less than 0.05). Surprisingly, on the first postoperative day, concentrations of AcAc and 3-HOB fell below those of fasting controls. Concomitantly, the utilization rate of AcAc by muscle (SII: 0.07 +/- 0.03 mumol/100 g/min; CII: 0.27 +/- 0.04, p less than 0.05) was significantly lower in patients than in controls. Reduction of the fractional extraction rate of AcAc (SI: 38.4 +/- 3.8%; SII: 24.0 +/- 6.1%, p less than 0.05), as well as a net production of 3-HOB by muscle (SII: -0.08 +/- 0.05 mumol/100 g/min; CII: 0.49 +/- 0.13, p less than 0.05) 24 hours after surgery indicated a reduced peripheral capacity for KB removal. Since this finding was related to a significantly higher rate of muscular glycerol production (SII: -0.13 +/- 0.03 mumol/100 g/min; CII: -0.06 +/- 0.02, p less than 0.05), one may suggest that increased intramuscular availability of FFA from triglyceride hydrolysis was responsible for the impairment of peripheral KB utilization. These results indicate that KBs contribute little to energy metabolism in skeletal muscle tissue in the late postoperative phase.     

Cardiotomy suction versus red cell spinning during repair of descending thoracic aortic aneurysms

Two consecutive series of patients undergoing repair of descending thoracic and thoracoabdominal aortic aneurysms with partial cardiopulmonary bypass and low systemic heparinization (activated coagulation time: ACT greater than 180 sec) for proximal unloading and distal protection were analyzed. During the surgical procedures, thoracic shed blood was recovered either with a red cell spinning autotransfusion device (n=10) or two pump suckers and Duraflo II heparin surface coated cardiotomy reservoirs (n=10). There were 5/10 acute lesions and 1/10 ruptures for the autotransfusion group versus 5/10 acute lesions and 2/10 ruptures for the cardiotomy group (NS). Extension of aortic resection (range 1-8) was 3.6+/-1.2 for autotransfusion versus 3.5+/-1.4 for cardiotomy suction (NS). Mean number of reimplanted patches for intercostal and visceral reperfusion was 0.3+/-0.6 for autotransfusion versus 0.6+/-1.0 for cardiotomy (NS). Perfusion time was 41+/-17 min for autotransfusion versus 60+/-19 min for cardiotomy (p less than 0.05) and cross clamp time was 33+/-14 min for autotransfusion versus 43+/-17 min for cardiotomy (p less than 0.01). Total heparin dose was for 9500+/-2100 IU for autotransfusion versus 9800+/-1300 IU for cardiotomy (NS). The mean of the lowest ACTs measured during perfusion was 281+/-121 sec for autotransfusion versus 258+/-58 sec for cardiotomy (NS). The total protamine dose given was 7800+/-2100 IU for autotransfusion versus 9700+/-1900 IU for cardiotomy (p less than 0.05). The volume of washed red cells prepared was 3186+/-1318 ml for autotransfusion versus 0 for cardiotomy (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of a neurotoxin (benzalkonium chloride) on the lower esophagus

Achalasia of the esophagus may be associated with abnormalities of the myenteric plexus (hypo- and anganglionosis). This report evaluates this relationship by studying the effect of benzalkonium chloride (BK, a topical neurotoxin) on the lower esophagus. Following midline laparotomy, topical BK (0.5%) was applied to the muscularis of the lower 1.0 cm of the esophagus for 30 min in 38 Sprague-Dawley rats (200 g). Thirty-eight additional rats acted as controls (unoperated, n = 19; sham laparotomy, n = 19). At 1 and 3 months animals were evaluated for weight gain, daily food intake (g/100 gm body wt), lower esophageal sphincter (LES) manometry, and contrast esophagram. At 3 months, the esophagus was evaluated for histologic study and acetylcholinesterase staining. Esophagram showed distal narrowing with proximal dilatation in BK rats (inner diameter 4.71 +/- 0.61 vs 6.17 +/- 0.58 in controls, P less than 0.001). Daily food intake was significantly less in BK rats (5.57 +/- 0.41 g vs controls 7.69 +/- 0.33 g P less than 0.001). Daily weight gain was also less in BK rats (1.13 +/- 0.34 vs controls 1.83 +/- 0.25, P less than 0.001). An increased LES pressure was noted in BK rats (5.45 +/- 0.89 mmHg vs controls 4.04 +/- 1.04 mmHg; P less than 0.1). A histologic study showed aganglionosis in BK rats with positive cholinesterase staining fibers compared to controls. Topical BK results in distal esophageal aganglionosis characterized by distal narrowing, proximal dilatation, decreased food intake, and limited weight gain when compared to controls. These findings are similar to those observed in achalasia and support a primary neurogenic cause for its etiology.     

Flowmetric evaluation of internal mammary artery flap during repair of aortic coarctation.

Resection of the internal shelf through a longitudinal aortotomy and widening with the free end of the left in situ internal mammary artery (IMA) were steps in correction of aortic coarctation with isthmus hypoplasia in nine patients aged 9-14 (mean 10.5) years. Electromagnetic flowmetry was performed on the left IMA before and after the repair. The essential finding was considerably increased mean blood flow in the IMA flap during cross-clamping proximal to the completed repair, from 53 +/- 48 to 430 +/- 74 ml/min (378 +/- 78%). The IMA thus is a powerful conduit with extraordinary flow capacity when runoff is appropriate. Integration of IMA as a viable flap in the repair of aortic coarctation implies that this artery increases its collateral flow contribution to the distal aorta.     

Glutamine metabolism by the endotoxin-injured lung.

The alterations in lung glutamine (GLN) metabolism that occurs in the endotoxin-injured lung were studied in rats and subsequently correlated with flux changes that occur in patients with the adult respiratory distress syndrome (ARDS). Measurements in animals were made at various time-points following the administration of endotoxin, while studies in surgical patients were done in a group of healthy controls, in patients with "early" sepsis who had normal chest x-ray films, and in patients with radiographic and physiologic evidence of ARDS. In healthy control rats, net amounts of GLN are released by the lungs into the systemic circulation. This release rate doubled 30 minutes after intravenous endotoxin (1,580 +/- 320 nmol GLN/100 g BW/min vs. 736 +/- 179 in controls, p less than 0.01) but glutamine synthetase activity was unchanged, suggesting an outpouring of cellular glutamine stores. Two hours after endotoxin treatment, this accelerated fractional release of glutamine by the lungs was no longer detected. By the 12-hour time-point, the lungs reversed to an organ of net glutamine balance (234 +/- 248 nmol/100 g BW/min, p less than 0.05 vs. controls and ENDO30 min) despite a more than two-fold increase in glutamine synthetase activity (p less than 0.01). Simultaneously, lung weights were increased by 21% (p less than 0.01) and histologic examination showed an interstitial infiltrate and pulmonary edema. Similar observations were made in humans; patients with "early" sepsis exhibited a marked increase in lung glutamine release, while patients with ARDS demonstrated glutamine balance across the lungs (4,030 +/- 910 nmol GLN/kg BW/min vs. 637 +/- 496 in ARDS, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenergic modulation of extrarenal potassium disposal in men with end-stage renal disease.

In normal subjects, beta-adrenergic stimulation lowers the serum potassium, whereas alpha-stimulation raises it. Epinephrine, a mixed alpha and beta agonist, acutely lowers the blood potassium in normal subjects, but not in patients with end-stage renal disease. This study was designed to determine whether the resistance to the hypokalemic effect of epinephrine in dialysis patients is due to a blunted beta-adrenergic response, or to an augmented alpha-adrenergic response. The infusion of epinephrine at low doses (0.01 microgram/kg/min) produced a significant increase in serum potassium in hemodialysis patients (+0.21 +/- 0.07 mmol/liter, P less than 0.05), as compared to a nonsignificant decrease (-0.06 +/- 0.04 mmol/liter) in normal subjects. Epinephrine at high physiologic doses (0.04 microgram/kg/min) failed to significantly change the serum potassium in the dialysis patients (-0.10 +/- 0.14 mmol/liter), but substantially lowered serum potassium in the controls (-0.64 +/- 0.10 mmol/liter, P less than 0.001). There was no significant correlation (r = 0.03) between the baseline serum potassium concentration and the magnitude of change during epinephrine infusion. Epinephrine infusion (0.04 microgram/kg/min) during beta-blockade with propranolol produced a greater rise in serum potassium in the dialysis patients as compared to the controls (+0.69 +/- 0.11 vs. +0.32 +/- 0.11 mmol/liter, P less than 0.05). Epinephrine infusion (0.01 microgram/kg/min) during alpha-blockade with phentolamine resulted in similar changes in serum potassium in dialysis patients and in normal control (-0.10 +/- 0.12 vs. -0.10 +/- 0.06 mmol/liter). Moreover, phentolamine reversed the increase in serum potassium observed in dialysis patients during the infusion of epinephrine following beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of sodium nitroprusside on spinal cord perfusion and paraplegia during aortic cross-clamping

To evaluate the effects of sodium nitroprusside (SNP) on hemodynamics, cerebrospinal fluid dynamics, and neurological outcome after 30 minutes of thoracic aortic occlusion, we monitored proximal and distal blood pressure, cerebrospinal fluid pressure, spinal cord blood flow, and somatosensory evoked potentials. In group 1 (n = 6), no attempts were made to control proximal hypertension, whereas in group 2 (n = 6), proximal blood pressure was controlled with intravenous infusion of SNP. There was no significant difference in proximal or distal blood pressure or cerebrospinal fluid pressure between the two groups at baseline. During the crossclamp interval, the mean proximal aortic pressure rose from 108 +/- 21 to 146 +/- 14 mm Hg (p less than 0.001) in the control group, whereas the mean blood pressure in the SNP group was maintained at 99.8 +/- 12 mm Hg (p = not significant compared with baseline blood pressure). Mean distal aortic pressure decreased from systemic values to 23 +/- 7 mm Hg in control animals and to 11 +/- 5 mm Hg in the SNP group (p less than 0.005). In the latter group, cerebrospinal fluid pressure increased significantly from 10.6 +/- 1.9 to 20.1 +/- 5.5 mm Hg (p less than 0.005). In animals receiving SNP, spinal cord blood flow was decreased in the lower spinal cord segments and increased in the upper cord segments. When compared with controls, this difference did not reach significance.(ABSTRACT TRUNCATED AT 250 WORDS)