Norah Milne

Analysis of nutrient hepatic blood flow after 8-mm versus 16-mm portacaval H-grafts in a prospective randomized trial

BACKGROUND In previous unrandomized studies, we demonstrated that patients undergoing 8-mm diameter portacaval H-grafts with collateral ablation (partial shunts) have lower rates of portasystemic encephalopathy (PSE) postoperatively than patients undergoing total portacaval shunts. We postulated that nutrient hepatic blood flow was greater after partial shunts because 8-mm grafts preserved some portal flow. METHODS To test this hypothesis, we analyzed hepatic hemodynamics in 18 of 30 randomized patients who consented to be studied after complete operative recovery, grouped according to shunt size. We measured nutrient hepatic blood flow using 99m-Tc-Mebrofenin tracer elimination kinetics, and fractionated it into its portal venous and hepatic arterial components. PSE was assessed by blinded observers. Stepwise logistic regression was used to select the variable that best predicted encephalopathy. From 1989 to 1993, we conducted a randomized, prospective trial of partial (8 mm) versus total (16 mm) portacaval H-grafts. Group differences were compared using one-way analysis of variance (ANOVA). RESULTS Hepatic encephalopathy occurred in 2 of 10 patients with partial shunts versus 5 of 8 patients with total shunts. Nutrient hepatic blood flow was significantly higher for partial shunts compared with total shunts (403 +/- 601 versus 243 +/- 17mL/min). Three variables--nutrient hepatic blood flow, portal blood flow, and hepatic arterial flow--were analyzed by stepwise logistic regression. Nutrient hepatic blood flow was selected as the best predictor of hepatic encephalopathy. In this series, PSE did not occur in any patient with more than 325 mL/min of nutrient hepatic blood flow. CONCLUSION These findings provide a physiologic basis for clinical observations demonstrating a lower incidence of PSE with partial shunts and indicates the superiority of partial over total shunts. Partial shunts, by preserving portal flow, maintain higher nutrient hepatic blood flow than total shunts and thus minimize PSE rates.

18F-Fallypride PET of Pancreatic Islets: In Vitro and In Vivo Rodent Studies

Islet cell loss in the pancreas results in diabetes. A noninvasive method that measures islet cell loss and also tracks the fate of transplanted islets would facilitate the development of novel therapeutics and improve the management of diabetes. We describe a novel dopamine D2/D3 receptor (D2/D3R)–based PET method to study islet cells in the rat pancreas and in islet cell transplantation. Methods: 18F-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D2/D3R inhibitor haloperidol. After intravenous 18F-fallypride (28–37 MBq) administration, normal rats and rats pretreated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for 18F-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of 18F-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using 18F-fallypride PET. Results: 18F-fallypride bound to isolated islet cells and pancreatic sections with an endocrine or exocrine selectivity of approximately 4; selectivity was reduced by haloperidol, suggesting that binding was D2/D3R-specific. Chemical destruction of islets by streptozotocin decreased 18F-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of 18F-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm3 as measured by PET/CT. The ratio of 18F-fallypride uptake in the pancreas to reference tissue (erector spinae muscle) was 5.5. Rat islets transplanted into the spleen were visualized in vivo by 18F-fallypride and confirmed by immunostaining. The ratio of spleen-transplanted islets to erector spinae muscle was greater than 5, compared with a ratio of 2.8 in untransplanted rats. Conclusion: These studies demonstrate the potential utility of 18F-fallypride as a PET agent for islet cells.

Exercise Performance of Polycythemic Chronic Obstructive Pulmonary Disease Patients: Effect of Phlebotomies

The purpose of this study was to determine the effects of phlebotomy on the exercise tolerance and right and left ventricular ejection fraction of polycythemic patients with chronic obstructive pulmonary disease. Ten patients with COPD (mean FEV1 = 1.32 +/- 0.55 L) and polycythemia (mean Hct = 62 +/- 3 percent) were studied before and after their hematocrits had been reduced to approximately 50 percent. Post-phlebotomy the maximal oxygen consumption increased from 1.09 +/- 0.34 L/min to 1.26 +/- 0.43 L/min (p less than 0.05) and the maximum workload increased from 56.5 +/- 32.6 watts to 74.5 +/- 23.4 watts (p less than 0.05). The increase in the exercise tolerance appeared to be primarily due to an increased cardiac output at Emax. There was no relationship between the increases in the upright exercise capacity and changes in the supine ejection fractions of the right or left ventricular either at rest or during exercise.

Functional Elements Associated with Hepatic Regeneration in Living Donors after Right Hepatic Lobectomy

We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre‐donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single‐photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg−1 of body weight day−1) by CT were 0.60±0.22 mL from the baseline to T1, 0.05±0.02 mL from T1 to T2, and 0.01±0.01 from T2 to T3; by SPECT they were 0.54±0.20, 0.04±0.01, and 0.01±0.02, respectively. At T3, the liver volumes were 84%±7% of the baseline according to CT and 92%±13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75±0.07 for intravenous cholate (P<0.001), 0.88±0.15 for galactose (P=0.07), 0.84±0.08 for PHM (P=0.002), and 0.83±0.19 for the estimated HBF (P=0.06). At T1, these ratios adjusted per liter of liver were up to 50% greater than the baseline values, suggesting recruitment of HBF by the regenerating liver. Increased cholate shunt, increased spleen volume, and decreased platelet count, were consistent with an altered portal circulation. In conclusion, initial hepatic regeneration is rapid, accounts for nearly two‐thirds of total regeneration, and is associated with increases in HBF and cholate uptake. Right lobe donation alters the portal circulation of living donors, but the long‐term clinical consequences, if there are any, are unknown. Liver Transpl 19:292–304, 2013.

Computer analysis of portal hemodynamics after small-diameter portacaval H-grafts: the theoretical basis for partial shunting

We have previously reported on the clinical results of partial shunting using small-diameter portacaval H-grafts. In this study, we defined the theoretical basis for partial shunting using the Wheatstone bridge model of the splanchnic circulation. The model was modified to include a variable resistance for a portacaval shunt and was programmed as a computer simulation. We calculated portal flow as a function of shunt resistance to determine the resistance necessary to maintain prograde portal flow in patients with portal hypertension. The resistance of 8- and 10-mm portacaval H-grafts, as positioned clinically, was determined using a laboratory apparatus. The experimentally derived values for resistance were inserted into the graph of portal flow predicted by the computer program. Portacaval H-grafts 8 mm in diameter should produce prograde portal flow, 10-mm H-grafts should be borderline, and shunts larger than 10 mm should routinely result in reversed flow. These predictions were confirmed by clinical observations in 29 patients undergoing portacaval H-grafts.

Clinical InvestigationsExercise Performance of Polycythemic Chronic Obstructive Pulmonary Disease Patients: Effect of Phlebotomies

The purpose of this study was to determine the effects of phlebotomy on the exercise tolerance and right and left ventricular ejection fraction of polycythemic patients with chronic obstructive pulmonary disease. Ten patients with COPD (mean FEV1 = 1.32 +/- 0.55 L) and polycythemia (mean Hct = 62 +/- 3 percent) were studied before and after their hematocrits had been reduced to approximately 50 percent. Post-phlebotomy the maximal oxygen consumption increased from 1.09 +/- 0.34 L/min to 1.26 +/- 0.43 L/min (p less than 0.05) and the maximum workload increased from 56.5 +/- 32.6 watts to 74.5 +/- 23.4 watts (p less than 0.05). The increase in the exercise tolerance appeared to be primarily due to an increased cardiac output at Emax. There was no relationship between the increases in the upright exercise capacity and changes in the supine ejection fractions of the right or left ventricular either at rest or during exercise.

Factors affecting the quantitative liver-spleen scan in normal individuals.

The quantitative liver–spleen scan (QLSS) can estimate the functional hepatic mass and the organ volumes by precise measurement of sulfur colloid (SC) distribution. The normal range determined in prior studies was estimated from patients with absence of chronic liver disease in which intense fasting appeared to produce slightly abnormal values. This study was to determine the effect of fasting or fed status and colloid particle size on quantitative measurements from the QLSS in a small cohort of normal individuals. Twelve persons without any medical problems had QLSS taken twice, 2 weeks apart, one fasting and one postprandial. Patients were scanned after injection of 5–6 mCi of SC; six patients were given solution A (5- to 12-μm particle size) and six patients solution B (2- to 12-μm particle size). SPECT and planar analysis were performed. SC distribution of total counts between the liver and the spleen {[L/(L + S)]t ratio}, liver–spleen index (LSI), and liver–bone marrow index (LBI) were calculated. The perfused hepatic mass (PHM) is the average of the LSI and LBI. Spleen and liver volumes are expressed as milliliters per pound ideal body weight (IBW). Results showed that the liver and spleen volumes (solution B postprandial, 9.27 ± 2.48 and 1.47 ± 0.57 ml/lb IBW, respectively) and LBI were not affected by the type of SC solution or by ingestion status. L/(L + S) total and pixel count ratios were significantly higher for solution B and postprandial studies. [L/(L + S)]t, LSI, and PHM increased significantly (P < 0.05) from fasting to postprandial for solution A (0.71 ± 0.13 vs 0.79 ± 0.08, 80 ± 14 vs 91 ± 8, and 102 ± 10 vs 106 ± 8, respectively) and for solution B (0.81 ± 0.05 vs 0.90 ± 0.02, 86 ± 4 vs 95 ± 3, and 101 ± 5 vs 110 ± 3). Neither fasting nor postprandial LSI and PHM were significantly different between solution A and solution B. We conclude the following. (1) The QLSS functional indices in “true” normal patients fall within the previously reported normal range. (2) Calculated liver and spleen volumes are not altered by fasting or sulfur colloid particle size. (3) Fasting significantly decreased the [L/(L + S)]t, LSI, and PHM. (4) A postprandial scan may be preferable since the normal values for [L/(L + S)]t, LSI, and PHM are greater, with a narrower range, than fasting values.

Relative sensitivity of Tc-99m WBC versus In-111 WBC in a patient with Crohn disease and steroid use

Numerous studies have shown that chemotaxis is affected by certain antibiotics and steroids. The authors present the case of a patient with Crohn disease relapse with multiple small-bowel fistulae and mesenteric abscesses. Whereas the Tc-99m WBC scan failed to show the intra-abdominal inflammatory foci, an In-111 WBC scan performed within a week delineated the abscesses very well, and these were later confirmed at surgery. This case is presented not only to illustrate the relative sensitivities of a Tc-99m WBC versus an In-111 WBC scan, but also to discuss the impediment to polymorphonuclear chemotaxis by steroids, which may be a contributory factor to the sensitivities of the different radiopharmaceuticals selected for detection of intra-abdominal septic foci.

Exercise-induced changes in left ventricular function after phlebotomy in patients with polycythemic COPD.

The exercise capacity of polycythemic COPD patients has been shown to improve after phlebotomy, possibly because of reduction of ventricular afterload by decreased blood viscosity, resulting in increased cardiac output. Ten patients with polycythemic COPD and mean hematocrit 62% were studied at rest and during exercise before and after reduction of mean hematocrit to 50% by repeated phlebotomy. Pulmonary function was evaluated by physiologic exercise testing on a bicycle ergometer. Cardiac function was evaluated by rest and exercise RNVG. Significant increase in exercise tolerance and maximal oxygen uptake at peak exercise, with significant reduction in mean systemic BP, were demonstrated. Ejection fractions did not change, but dV/dt for ejection from the left ventricle at peak exercise improved significantly. Mean SV counts, ESV counts, and EDV counts were measured and the fractional increase with exercise compared for prephlebotomy and postphlebotomy, assuming that resting volumes would not change. ESV counts and EDV counts were both proportionately, though not significantly, reduced postphlebotomy. The data tend to support the hypothesis that the afterload on the left ventricle is reduced, with resulting improved myocardial contractility and left ventricular function. Improved peripheral oxygen uptake may also be a factor.

Pancreatitis secondary to endoscopic retrograde cholangiopancreatography on a whole-body Ga-67 scan.

A 65-year-old man who had fever, nausea, vomiting, and elevated liver enzymes for 2 weeks had an abdominal CT and an endoscopic retrograde cholangiopancreatography (ERCP), both of which were normal. Fever and a persistent leukocytosis followed the ERCP. Two days later, a whole-body Ga-67 scan to rule out an intraabdominal abscess showed intense gallium concentration within the pancreas, suggesting pancreatitis secondary to the ERCP. The serum amylase and lipase also were high at this time. A repeated CT of the abdomen showed peripancreatic stranding and an edematous swollen pancreas, confirming the diagnosis of pancreatitis.