Catherine Moorehead

The Effect of Weight Loss on the Sensitivity of Blood Pressure to Sodium in Obese Adolescents

To clarify the role of sodium intake in the regulation of blood pressure in obese subjects, we measured blood pressure in 60 obese and 18 nonobese adolescents after successive two-week periods of a high-salt diet (greater than 250 mmol of sodium per day) and a low-salt diet (less than 30 mmol per day). When they were changed from a high-salt to a low-salt diet, the obese group had a significantly larger mean change (+/- SE) in mean arterial pressure (-12 +/- 1 mm Hg) than did the nonobese group (+1 +/- 2 mm Hg; P less than 0.001). The variables that best predicted the degree of sodium sensitivity were the fasting plasma insulin level, the plasma aldosterone level while the low-salt diet was being given, the plasma norepinephrine level while the high-salt diet was being given, and the percentage of body weight made up by fat. Fifty-one of the obese adolescents were also studied before and after a 20-week weight-loss program. After the weight-loss program, the 36 subjects who lost more than 1 kg of body weight had a reduced sensitivity of blood pressure to sodium (difference from value during high-salt diet to that during low-salt diet, -1 +/- 1 mm Hg). The blood pressure of the remaining 15 adolescents was still sensitive to sodium intake (-11 +/- 3 mm Hg). These results support the hypothesis that the blood pressure of obese adolescents is sensitive to dietary sodium intake and that this sensitivity may be due to the combined effects of the hyperinsulinemia, hyperaldosteronism, and increased activity of the sympathetic nervous system that are characteristic of obesity.

Insulin and Renal Sodium Retention in Obese Adolescents

The effect of insulin on the renal handling of sodium was studied in obese and nonobese subjects by using euglycemic hyperinsulinemia. Seven water-loaded obese (14–19 years old) and five nonobese young adults (18–21 years old) had insulin given intravenously at a rate of 40 munits/m2/min. Blood glucose and creatinine clearance were not altered by euglycemic hyperinsulinemia in either the obese or the nonobese group. Hyperinsulinemia resulted in a significant decrease in urinary sodium excretion in both groups of subjects (by 54.2±3% [mean±SEM] in the obese and by 50.9±3.1% in the nonobese group). However, the amount of glucose required to maintain euglycemia was significantly less in the obese versus nonobese group, 89.5±6.2 versus 329.2±16 mg glucose/m2/min (p < 0.001). There was no relation in either group between the amount of glucose required to maintain euglycemia and the change in urinary sodium excretion. On a separate day, all of the obese subjects underwent 3 hours of water diuresis but without insulin. There was no change in urinary sodium excretion with sustained water diuresis alone. However, when compared with the nonobese group, the obese group of subjects had a significantly higher resting mean arterial pressure, heart rate, and plasma norepinephrine concentration; during the insulin clamp, neither group experienced a significant change in mean arterial pressure or heart rate, and only the nonobese group experienced an increase in plasma norepinephrine. In obese subjects, we have found, despite the presence of insulin resistance to carbohydrate metabolism, that euglycemic hyperinsulinemia was associated with a normal decrease in urinary sodium excretion. Therefore, the data support the hypothesis that insulin resistance with respect to glucose metabolism leads to hyperinsulinemia, which in turn could lead to chronic sodium retention.

Increased forearm vascular reactivity in patients with hypertension after repair of coarctation.

To determine whether altered vascular reactivity could contribute to hypertension after repair of coarctation, the change in forearm and calf vascular resistances to small intra-arterial infusions of norepinephrine were measured in six patients who had undergone surgical correction of coarctation of the aorta but still had upper extremity hypertension and compared with similar measurements made in five normotensive patients with mild heart disease. Only the mean upper extremity pressure was significantly greater in the group that underwent repair of coarctation (102 +/- 11 vs 83 +/- 5 mm Hg, p less than .05, for mean arm pressures and 96 +/- 13 vs 83 +/- 7 mm Hg for mean leg pressures in patients who had coarctation vs normotensive patients, respectively). Forearm and calf blood flows were measured in the right arm and leg with a mercury-in-plastic strain-gauge plethysmograph. Forearm and calf vascular resistances were calculated by dividing mean arterial pressure of the appropriate extremity by the blood flow of that extremity. Norepinephrine was infused into the right brachial and femoral arteries of the patients at doses of 0.02, 0.05, 0.1, 0.2, 0.3, 0.5, and 0.7 microgram/min. Resting forearm and calf vascular resistances were similar in both groups of patients. The norepinephrine dose-response curves showed that control patients required more than three times the norepinephrine to produce the same percent increase in forearm vascular resistance (after 0.2 microgram/min forearm vascular resistance increased by 55% in the coarctation group, while the resistance in the control group increased by only 3%, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperinsulinemia and the aldosterone and pressor responses to angiotensin II.

To determine whether hyperinsulinemia alters angiotensin II-medlated aldosterone secretion, the increase in plasma aldosterone after intravenous angiotensin II (5, 10, and 20 ng/kg/min for 15 minutes each) was measured before and after euglycemic hyperinsulinemia in seven chronically instrumented dogs. In a random sequence on 4 successive days, dogs received either 0, 2, 4, or 8 milllunits/kg/min insulin. Euglycemic hyperinsulinemia, at all insulin doses, resulted in a significantly greater (p < 0.01) change in the angiotensin U-stimulated increments of plasma aldosterone than was observed when angiotensin II was administered alone. However, there was no dose-dependence of insulins effect on angiotensin H-stimulated aldosterone. The effect of weight gain on the angiotensin II response was also evaluated in five dogs. After weight gain, euglycemic hyperinsulinemia augmented angiotensin H-stimulated aldosterone to the same magnitude that was observed before weight gain. Possible mechanisms whereby insulin could increase angiotensin II-stimulated aldosterone production include: increased intracellular potassium, reduced plasma free fatty acids, and a direct action of insulin to induce increased adrenal steroidogenesis. In addition to altering the angiotensin II-aldosterone dose-response curve, hyperinsulinemia also increased the pressor action of angiotensin II. In contrast to the angiotensin II-aldosterone response, progressive hyperinsulinemia resulted in a progressive increase in the pressor response to angiotensin II. The increased pressor response is probably due to an increased activation of the sympathetic nervous system by insulin.

Pathogenesis of weight-related changes in blood pressure in dogs

We have previously shown that weight gain in the dog results in an increase in blood pressure. To study the pathogenesis of the rise in blood pressure associated with weight gain, we compared the serial changes in blood pressure, body weight, sodium balance, plasma volume, and three hormones known to affect sodium balance (norepinephrine, insulin, and aldosterone) in seven dogs fed a high fat diet for 6 weeks and seven dogs fed a control diet. The sodium content of both diets was equal. During a 2-week control period, no differences were noted between the two groups. Weight gain was associated with a progressive increase in blood pressure (mean pressure increased by 18.5±2.1 mm Hg in the high fat group) and plasma volume (plasma volume increased from 1,426±202 to 2,053±250 ml in the high fat group). Sodium retention occurred after 1 week of the high fat diet and persisted. Over the 6-week period, the dogs on the high fat diet increased their cumulative sodium balance by 2,024±462 meq versus an increase of only 289±97 meq for the dogs on the control diet. In the high fat diet group of dogs, there was a significant relation between change in cumulative sodium balance and the change in blood pressure and plasma volume. After 1 week of the high fat diet, norepinephrine was the only hormone that significantly increased from baseline. Over the next 5 weeks norepinephrine increased no further, whereas fasting insulin and aldosterone progressively increased. Over the entire study period, fasting insulin was the hormone that best correlated with the change in blood pressure observed in the high fat diet dogs. Thus, the change in blood pressure associated with weight gain in the dog is directly related to sodium retention. The observed change in sodium balance also appears to relate initially to a change in plasma norepinephrine concentration and later to a change in fasting insulin and aldosterone concentrations.

Role for aldosterone in blood pressure regulation of obese adolescents.

To determine the role of aldosterone in the regulation of blood pressure (BP) in obese adolescents, supine and 2-hour upright plasma renin activity (PRA), and aldosterone and cortisol were measured in 10 nonobese and 30 obese adolescents before and after a 20-week weight loss program. The obese adolescents had significantly higher supine and 2-hour upright plasma aldosterone concentrations (17 +/- 8 vs 6 +/- 2 ng/dl [p less than 0.01 supine obese vs nonobese] and 30 +/- 11 vs 14 +/- 8 ng/dl [p less than 0.01 2-hour upright]). Although PRA was not significantly different between the 2 groups of children, a given increment in PRA produced a greater increment in aldosterone in the obese adolescents. In addition, obese subjects had a significantly increased mean BP (93 +/- 12 vs 74 +/- 8, p less than 0.005) and a weak correlation between BP and plasma aldosterone concentration. Compared with an obese control group, weight loss resulted in a significant decrease in plasma aldosterone (p less than 0.01) without an associated decrease in PRA. After weight loss there was also a significant decrease in the slope of the posture-induced relation between PRA and aldosterone. In addition to weight loss being associated with a significant decrease in BP (p less than 0.01), there was a significant correlation between the change in plasma aldosterone and the change in mean BP (r = 0.538; p less than 0.002 change in upright aldosterone vs change in mean BP). Obese adolescents have an increased plasma aldosterone concentration that may be important in the regulation of their BP.

Transhepatic Cardiac Catheterization in Children: Evaluation of Efficacy and Safety

BACKGROUND In some children with congenital heart disease, conventional venous access is unavailable for cardiac catheterization. This study investigates a novel transhepatic venous approach to cardiac catheterization in children and evaluates its efficacy and safety. METHODS AND RESULTS Percutaneous transhepatic puncture was performed using a 22-gauge Chiba needle under fluoroscopic guidance. After wire exchanges were performed, a 5F to 8F sheath was positioned in the low right atrium and cardiac catheterization was performed. On completion of the catheterization, the sheath was withdrawn and a 3-mm steel coil was placed in the parenchymal tract between the hepatic vein and liver capsule. Liver enzyme studies were obtained before and after transhepatic catheterization, and an abdominal ultrasound was performed to evaluate the liver 24 hours after the procedure. Percutaneous transhepatic cardiac catheterization was performed successfully in 17 of 18 children in whom it was attempted. Patient age was 30 +/- 8 months (mean +/- SEM; range, 1 day to 9 years), weight was 10.5 +/- 1.5 kg (3.1 to 27.5 kg), and mean right atrial pressure was 10 +/- 1 mm Hg (5 to 19 mm Hg). Time from initial needle puncture to right atrial entry was 6.2 +/- 1.2 minutes. Diagnostic catheterization was performed successfully in all 17 children, and additional interventional procedures were performed in 5 children. The total catheterization time was 2.0 +/- 0.2 hours. Serum aspartate aminotransferase increased from 57 +/- 15 to 78 +/- 8 IU/L (P = .06), but alanine aminotransferase and gamma-glutamyl transpeptidase did not change. Ultrasound was performed 24 hours after transhepatic catheterization, and no evidence was found in any patient of hemorrhage or subcapsular hematoma. CONCLUSIONS These data suggest that this novel transhepatic approach provides an effective and safe route for diagnostic and interventional cardiac catheterization in children.

Therapeutic Effect of Propranolol on Paradoxical Hypertension after Repair of Coarctation of the Aorta

Patients undergoing repair of coarctation of the aorta often have self-limited but severe hypertension in the first week after surgery (paradoxical hypertension). We conducted a controlled trial of treatment with propranolol before repair of coarctation of the aorta in 14 children to determine whether the drug would prevent paradoxical hypertension. Seven patients were randomly assigned to receive propranolol for two weeks before surgery and throughout the first postoperative week, and seven patients were assigned to receive standard postoperative care. Both groups had a similar significant (P less than 0.05) increase in the plasma norepinephrine level in response to surgery; however, when compared with no treatment, treatment with propranolol reduced not only the rise in systolic (P = 0.004) and diastolic (P = 0.003) blood pressure but also the postoperative increase in plasma renin activity (P less than 0.01). We conclude that prophylactic propranolol can prevent paradoxical hypertension and should therefore become a routine part of the operative care of patients with coarctation of the aorta.

Stent redilation in canine models of congenital heart disease: Pulmonary artery stenosis and coarctation of the aorta

In a canine puppy model, pulmonary artery stenosis was created by banding the left pulmonary artery to 30-40% of its original diameter. Animals underwent right heart catheterization and angiography 1-2 mo later, and Palmaz P308 stents were implanted. Stent redilation was performed 3-5 mo later. One mo postredilation, the animals were restudied and sacrificed. Coarctations of the aorta were created by transverse aortic incision and longitudinal repair. P308 stent implantation was performed 2-3 mo later. Stent redilation was performed after 6-10 mo, and the animals were restudied and sacrificed 1-2 mo later. Stent implantation was performed in 6 puppies with pulmonary artery stenosis, as 2 animals developed postoperative pulmonary arterial hypoplasia, precluding stenting. The stenosis diameter increased from 4.8 +/- 0.5 mm to 7.4 +/- 0.6 mm (mean +/- SE) following stenting (P = 0.005), and increased further to 9.2 +/- 0.7 mm following redilation (P < 0.001). There were no significant vessel tears or ruptures. Coarctation stenting was performed in 8 animals. The coarctation was dilated from 5.8 +/- 0.9 mm to 9.8 +/- 0.6 mm (P < 0.001), and to 13.5 +/- 0.5 mm at redilation (P = 0.002). Redilation could not be performed in 1 animal. Aortic rupture and death occurred in 2 of 7 animals at redilation. Stent implantation and redilation in experimental pulmonary artery stenosis appears safe and effective. Though stent implantation for coarctation of the aorta appears safe, there was a 28% aortic rupture rate at stent redilation in this model.

Use of Balloon-expandable stents to treat experimental peripheral pulmonary artery and superior vena caval stenosis: Preliminary experience

SummaryCurrent therapy of congenital or acquired stenoses of the peripheral pulmonary arteries and superior vena cava are frequently ineffective. This report describes our initial experience with the use of a balloon-expandable stainless steel stent to treat experimentally created branch pulmonary artery and superior vena cava stenosis. Fifteen adult mongrel dogs had surgically created stenoses of either a branch pulmonary artery and/or superior vena cava. A balloon-expandable stainless steel (0.076 mm), 3 cm long, intravascular stent was used in all animals. Stents were successfully placed in 13 of 15 dogs (nine with branch pulmonary stenosis and four with superior vena caval stenosis) with hemodynamic and angiographic relief of the stenoses in all. In three animals, successful stent placement was not accomplished because the distal right pulmonary artery was found to be totally obstructed in two and in one dog with combined vena cava and pulmonary stenosis the distal right pulmonary artery was so severely stenotic that the stenosis could not be crossed. Repeat catheterization performed 6 months following stent placement documented persistent gradient relief and angiographic evidence of unobstructed flow through the stent without thrombus formation and with patent side branch vessels. Our preliminary results suggests that balloon-expandable stents are a potential therapy for the treatment of branch pulmonary artery and superior vena cava stenoses.