A totally implantable drug infusion defice: laboratory and clinical experience using a model with single flow rate and new design for modulated insulin infusion.

The Infusaid implantable infusion pump with a single delivery rate has maintained chronic intravenous heparin infusion in man for greater than 35 mo and for greater than 5 yr in the dog. Intra-arterial infuson of fluorodeoxyuridine has been maintained for greater than 8 mo in man. In a pilot study using a commercially available, transcutaneously controllable, magnetically activated valve for baseline superimposed bolus insulin infusion, the feasibility of maintaining near normal serum glucose in diabetic dogs was demonstrated. The effect of long-term intravenous cannulation was investigated; it was found that the intimal tissues of the vena cava surrounding the cannulae were largely unaltered and microemboli could not be detected in the lungs of the animals studied. Cannula plugging, which occurred on several occasions due to thrombus formation in the final centimeter of the cannula, has been solved by changes in pump design and refilling procedures. The problem of insulin precipitation in flow passages of the pump remains unsolved, but there are indications that substances entering the cannula from the blood may be involved. A new pump design for modulated insulin infusion is described.

Effect of early propranolol treatment in an animal model of congestive cardiomyopathy. II. beta-adrenergic receptors and left ventricular function.

Young turkeys inbred for congestive cardiomyopathy (CCM) were treated with propranolol prior to the development of cardiac enlargement. One-day-old inbred CCM and commercial turkeys received 2 mg X kg-1 X day-1 of propranolol for 1 month and were compared with untreated age matched inbred CCM and commercial turkeys. Heart weight, body weight, and binding characteristics of cardiac beta-adrenergic receptors, using (-)3H-dihydroalprenolol as a ligand, were determined at 10 and 28 days. Left ventricular shortening fraction was determined at 28 days and at 32 days, 4 days after propranolol was discontinued, in treated and untreated inbred CCM and commercial turkeys. Propranolol did not prevent the development of cardiac hypertrophy in inbred CCM turkeys at 28 days of age and did not effect body weight or heart weight in either inbred CCM or commercial turkeys at 10 or 28 days of age. In the inbred CCM turkeys, the maximum number of binding sites (Bmax) and the binding affinity (Kd) of beta-adrenergic receptors were not changed by propranolol treatment. In the propranolol-treated commercial turkeys, Bmax the of beta-receptors was increased at 28 days of age compared with untreated age matched controls, 382 vs 194 fmol X mg-1 (p less than 0.05). Untreated inbred CCM turkeys when compared with untreated age matched commercial turkeys show a significant reduction of binding affinity of beta-receptors at both 10 and 28 days of age, Kd = 10.4 vs 6.2 nmol X litre-1 at 10 days and 11.3 vs 5.2 nmol X litre-1 at 28 days (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of early propranolol treatment in an animal model of congestive cardiomyopathy: I Mortality and Ca2+ transport in sarcoplasmic reticulum.

Young turkeys inbred for congestive cardiomyopathy were treated with propranolol prior to the development of cardiac enlargement. One-day-old inbred and commercial turkeys received propranolol, 2 mg X kg-1 X day-1 for 1 month. Propranolol treated inbred birds showed a significantly reduced mortality from 5 to 15 days of age when compared with untreated inbred birds. However, by 28 days of age, cumulative mortality in the treated inbred birds was equal to that in the untreated inbred birds, 29 and 32%, respectively. Propranolol-treated and untreated commercial birds have a 28-day cumulative mortality of 5%. Ca2+ transport in isolated cardiac sarcoplasmic reticulum was studied at 10 and 28 days of age. At 10 days of age Ca2+ uptake and Ca2+ binding in propranolol-treated birds was reduced to 56% and 83%, respectively, of values in untreated inbred birds. By 28 days of age Ca2+ uptake and Ca2+ binding in treated and untreated inbred birds were similar. Ca2+-stimulated ATPase activity was significantly elevated in treated inbred birds compared with age-matched untreated inbred birds at 10 and 28 days of age. Ca2+ transport in isolated cardiac SR from propranolol-treated commercial control birds was not significantly different from the values in untreated commercial birds at 10 or 28 days of age. Improvement in early mortality may be due to the prevention of arrhythmias. Propranolol alters Ca2+ transport in isolated cardiac SR from inbred birds by uncoupling Ca2+-stimulated ATPase. Whether this is due to a direct effect of propranolol on the SR membrane or occurs from its beta-adrenergic blocking action is unclear.

The use of an implantable insulin pump in the treatment of type II diabetes.

We treated five patients with Type II diabetes by means of a subcutaneously implanted intravenous insulin pump and compared their metabolic response with that observed during conventional insulin therapy. The use of the pump improved control of glycemia, as manifested by reductions in mean plasma glucose (from 188 +/- 46 to 106 +/- 12 mg per deciliter [mean +/- S.D.]), fasting glucose (from 187 +/- 42 to 80 +/- 13 mg per deciliter), and postprandial glucose (from 287 +/- 74 to 182 +/- 29 mg per deciliter), together with a diminution of glycemic excursion and normalization of glycosylated hemoglobin A1 (from 12.1 +/- 2 to 8.0 +/- 1 per cent). At the end of the study the pumps had been in place for a mean of 7.0 months (range, 5.5 to 9.7 months) without mishap and with good patient acceptance. Our data suggest that improved blood glucose control can be achieved by means of a permanently implanted continuous insulin-infusion device in ambulatory patients with Type II diabetes who require insulin, and that the need for daily insulin injections can thereby be eliminated.