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Biomedical subjects

R Sutton

Publications and source records attributed to R Sutton.

At least 199 records · Page 11Linked to original sources

Atrial natriuretic peptide response to rapid atrial pacing in cardiac-denervated dogs.

The effects of rapid atrial pacing on central hemodynamics, plasma hormones, and renal function were investigated in eight control and nine cardiac-denervated dogs under chloralose anesthesia. Pacing at approximately 250 ppm for 60 min caused similar increases in pulmonary wedge and right atrial pressures, systemic vascular resistance, and plasma atrial natriuretic peptide (ANP) in both groups. In control dogs, pacing produced a fall in both plasma vasopressin (AVP) and plasma renin activity (PRA) and a rise in urine flow rate associated with an increase in free water but not sodium clearance. In contrast, in cardiac-denervated dogs, both plasma AVP and PRA increased during pacing; urine flow rate did not change, and marked sodium retention occurred. This study supports the concept that the increase in urine flow during rapid atrial pacing is mediated by inhibition of renin and AVP secretion through intact cardiac nerves. The secretion of ANP is unaffected by cardiac denervation. The natriuretic and vasodilator actions of high plasma ANP concentrations during rapid atrial pacing can be inhibited either by neurally mediated cardiorenal effects in normal animals or by stimulation of the renin-angiotensin system after cardiac denervation.

Animals↗

Protease activity in pancreatic islet isolation by enzymatic digestion.

Commercial Collagenase* prepared from Clostridium histolyticum is widely used in isolation of pancreatic islets. It is known that the enzyme is very impure and that there are substantial variations in effectiveness between batches. Our studies suggest that one of the impurities of importance in islet isolation is a protease that has not been very well characterized. Comparison of two batches of enzyme, one of which was known to give good yields of islets and the other poor yields, showed that they had very similar activity against collagen (measured by digestion of insoluble collagen followed by assay of soluble products with ninhydrin) but substantially different activities against azocasein as measured by optical density increase (measured by release of dye). Eighteen batches of Collagenase were examined for efficiency in islet isolation, and the yields obtained correlated with manufacturer's data of activity against casein. The data show that low caseinase activity is associated with performance in islet isolation (r = .5 after adjusting for collagenase activity). The effect of supplementing a batch of collagenase, known to be poor in isolating islets, with proteolytic enzymes was investigated. Trypsin and papain had apparently no effect, but dispase significantly increased yield. Dispase alone failed to digest pancreas. Size-exclusion high-performance liquid chromatography identified a peak associated with high protease activity and efficiency in islet isolation, having an Mr of approximately 30,000, compared to 78,000 for collagenase. The protease, like collagenase, is inhibited by EDTA. Increased Ca2+ and Mg2+ (up to 10 mM) did not affect activity. Both the protease and collagenase are stable under normal use but are inactivated by heating at 56 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Metabolic function of intraportal and intrasplenic islet autografts in cynomolgus monkeys.

Intraportal islet autografting can restore near-normal glucose homeostasis in large diabetic animals, but the long-term failure rate of such grafts remains high. To assess the effect of the site of transplantation, we compared the hormonal responses to glucose (500 mg/kg i.v.) of intraportal (IP) and intrasplenic (IS) islet autografts in the cynomolgus monkey previously rendered diabetic by total pancreatectomy. Intravenous glucose tolerance tests (IVGTTs) 6 wk after IP grafting (n = 10) demonstrated nearly normal plasma glucose changes, with qualitatively normal but quantitatively reduced insulin and glucagon responses; only two animals have maintained these responses for greater than 2 yr. IVGTTs 6 wk after IS grafting (n = 4) demonstrated more abnormal plasma glucose changes, with qualitatively normal but weak insulin responses and glucagon levels that did not fall in response to hyperglycemia; only one animal has maintained fasting normoglycemia for greater than 9 mo. These results suggest that IS transplantation confers no benefit over IP transplantation in this model.

Animals↗

Pacemaker policy.

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Bradycardia↗

Rebound increase in plasma renin and vasopressin following graded infusions of atrial natriuretic peptide in man.

The effects of graded infusions of atrial natriuretic peptide (ANP) on hemodynamics, renal function, plasma renin activity (PRA) and plasma arginine vasopressin (AVP) were investigated in a two part study in 6 volunteers. Three 30-min iv infusions of either saline control or ANP at graded rates of 4, 10 and 40 pmol kg-1 min-1 were given. ANP infusions were associated with a significant increase in sodium clearance from 1.08 +/- 0.21 to 2.83 +/- 0.50 ml/min, an increase in hematocrit and a net fluid loss. Plasma AVP remained constant during ANP infusions but increased significantly afterwards when plasma ANP concentrations were falling rapidly, and this was accompanied by marked antidiuresis. PRA fell by 23% during the saline control infusions and by 50% during ANP infusions. Following cessation of ANP infusions there was a significant rebound increase in PRA. No changes were observed in blood pressure, heart rate, glomerular filtration rate or renal plasma flow. These results suggest an interaction in man between ANP and the hormones renin and AVP.

Adult↗

Exocrine contamination impairs implantation of pancreatic islets transplanted beneath the kidney capsule.

The effect of exocrine contamination on islets implanted under the kidney capsule has been studied by histological examination of pure or exocrine-contamination human, monkey, or rat islets transplanted to the kidney capsule of the nude rat, monkey, or rat, respectively. Exocrine contamination resulted in an appearance suggestive of impaired islet implantation, due to tissue necrosis and subsequent fibrosis. The effect of exocrine contamination was examined quantitatively in a rat islet isograft model in which handpicked DA rat islets were transplanted under the kidney capsule of normal DA rats. The islets were either pure or deliberately recontaminated with exocrine tissue (50 or 90% contamination). Four hundred pure islets were placed under one kidney capsule and 400 islets (of similar size and from the same islet preparation) were contaminated and then placed under the contralateral kidney capsule. After 2 weeks the kidneys were removed and extracted for insulin content. The insulin content of kidneys bearing islets contaminated by either 50 or 90% exocrine tissue was significantly reduced when compared to the contralateral kidney bearing pure islets. These findings support the view that exocrine contamination of islets resulted in impaired islet implantation when transplanted to a confined site such as the kidney subcapsule.

Animals↗

Decline of atrial natriuretic peptide release in dogs during sustained rapid cardiac pacing.

1. To assess the ability of the atria to maintain elevated plasma concentrations of atrial natriuretic peptide (ANP), the temporal changes in plasma ANP concentrations were studied in seven chloralose-anaesthetized dogs during 4 h of sustained rapid cardiac pacing. 2. Heart rate increased from 124 +/- 26 (mean +/- SEM) to 278 +/- 28 beats/min for the 4 h duration of rapid cardiac pacing. Mean pulmonary wedge pressure increased from 3.6 +/- 1.8 to 17.4 +/- 7.1 mmHg at 30 min (P less than 0.01) and mean right atrial pressure rose from -1.7 +/- 1.9 to 2.0 +/- 2.8 mmHg at 30 min (P less than 0.01). Both remained constant at these elevated pressures for the entire 240 min of rapid pacing. 3. Arterial ANP concentrations increased in all dogs from 87 +/- 11 to a maximum of 1263 +/- 592 pmol/l at 30 min (P less than 0.01), falling to 411 +/- 42 pmol/l after 60 min and to 146 +/- 70 pmol/l after 240 min of rapid continuous pacing (P less than 0.01 compared with 30 min). Coronary sinus ANP concentrations showed a similar pattern, rising from 241 +/- 79 to a maximum of 1837 +/- 203 pmol/l after 30 min (P less than 0.01). These peak values likewise were not sustained, falling to 962 +/- 198 pmol/l after 60 min and 297 +/- 41 pmol/l after 240 min of rapid pacing (P less than 0.01 compared with 30 min). 4. It is concluded that atria are unable to maintain the peak concentrations of ANP reached after 30 min of rapid pacing despite persistently elevated atrial pressures.

Animals↗

Atrial natriuretic peptide released by rapid ventricular pacing in dogs does not cause a natriuresis.

1. The relationships between the haemodynamic, renal and endocrine changes induced by rapid ventricular pacing were studied in ten chloralose-anaesthetized dogs paced from the right ventricular apex for 60 min at 250 beats/min. 2. Pacing increased mean right atrial and mean pulmonary wedge pressure (P less than 0.05), and decreased cardiac output and mean arterial pressure (P less than 0.05). 3. Coronary sinus atrial natriuretic peptide (ANP) concentrations were approximately fourfold greater than arterial concentrations; both increased markedly during pacing (P less than 0.01). Plasma concentrations of arginine vasopressin and plasma renin activity did not change significantly. 4. Urine flow and free water clearance increased during the latter 30 min of pacing (P less than 0.05). There was no significant change in sodium clearance despite high sustained concentrations of ANP. 5. Without the availability of specific inhibitors of ANP release or action, we are unable to exclude the possibility that ANP may have prevented sodium clearance from otherwise decreasing during rapid ventricular pacing. Nevertheless, the dissociation between elevated ANP concentrations and natriuresis in this study indicates that a rise in ANP concentrations per se is not sufficient to produce a natriuresis.

Animals↗

Benefits of dual chamber pacing in sick sinus syndrome.

The effects of DDD (fully automatic) and VVI (ventricular demand) pacing modes on exercise tolerance, symptom diary cards, and Holter monitoring were investigated in a randomised double blind crossover study of 16 patients who had had DDD pacemakers implanted because of frequent syncope. Eight patients presented with sick sinus syndrome and, with one exception, retrograde atrioventricular conduction and eight age and sex matched patients presented with 2:1 or complete atrioventricular block. Maximal symptom limited exercise in those with atrioventricular block was significantly higher after one month of DDD pacing than after VVI pacing. In those with sick sinus syndrome, however, maximal effort tolerance was not significantly different for the two pacing modes. In all but one patient with sick sinus syndrome sinus rhythm developed during exercise in VVI pacing. For both VVI and DDD modes maximal atrial rates were significantly lower in those with sick sinus syndrome. Palpitation and general wellbeing were significantly improved during DDD pacing in the eight patients with sick sinus syndrome. Shortness of breath was improved by DDD pacing in the eight patients with atrioventricular block but not in those with sick sinus syndrome. Holter monitoring showed that sick sinus syndrome patients remained in paced rhythm, either DDD or VVI, for most of the 24 hour period. DDD pacing was better than VVI pacing in sick sinus syndrome with retrograde atrioventricular conduction. Despite their ability to show sinus rhythm and inhibit their pacemakers on exercise patients with sick sinus syndrome are just as likely to have symptomatic benefit from DDD pacing as patients with atrioventricular block.

Adult↗

Bilateral inguinal hernias: simultaneous or sequential repair?

Two hundred and forty four patients underwent either simultaneous bilateral inguinal hernia repair (n = 122) or unilateral inguinal hernia (n = 122) repair at a general hospital between January 1971 and December 1981. The two groups of patients were matched for age and sex. Both groups had a similar overall incidence of post-operative complications and in both groups the duration of post-operative stay and duration of operating time were similar. Chest infections developed in 12 patients after bilateral repair and in 3 patients after unilateral repair (P less than 0.02). All patients were assessed prospectively from 4 to 15 years after operation, when no significant difference in the number of recurrent hernias was found. Our results suggest that simultaneous bilateral inguinal herniorrhaphy is economical in terms of both operating time and duration of hospital stay, and that this economy is not bought at a cost of increased short term morbidity or long-term recurrence rate.

Adult↗

Role of atrial pressure and rate in release of atrial natriuretic peptide.

To investigate whether atrial natriuretic peptide (ANP) release during paroxysmal tachycardia is due to increased atrial rate or increased atrial pressure, plasma ANP concentrations were measured during atrial pacing at increasing rates in six alpha-chloralose-anesthetized dogs whose atrial pressures were maintained artificially low by balloon occlusion of the inferior vena cava (IVC). These ANP concentrations were compared with those seen during identical increasing atrial rates in the same dogs without IVC occlusion. During incremental pacing without IVC occlusion, pulmonary wedge pressure (PWP; mean +/- SE) rose progressively from 5.3 +/- 1.6 at 200 to 20.2 +/- 2.3 mmHg at 350 beats/min (P less than 0.01), and right atrial pressure (RAP) rose progressively from 2.5 +/- 0.9 at 200 to 6.7 +/- 2.1 mmHg at 350 beats/min (P less than 0.05). At the same time, arterial and coronary sinus ANP concentrations rose from 116 +/- 55 and 339 +/- 91 to 1,126 +/- 226 and 1,960 +/- 456 pmol/l, respectively (P less than 0.01). In contrast, incremental pacing with IVC occlusion produced no significant increase in PWP and RAP. Arterial and coronary sinus ANP concentrations during IVC occlusion were, respectively, 208 +/- 126 and 388 +/- 159 at 200 and 261 +/- 83 and 345 +/- 80 pmol/l at 350 beats/min (NS). This study demonstrates that the release of ANP during tachycardia is primarily dependent on increased atrial pressure and not atrial rate.

Animals↗

Atrial natriuretic peptide inhibits postural release of renin and vasopressin in humans.

The effects of infusions of atrial natriuretic peptide (ANP) on the hormonal and hemodynamic responses to head-up tilt were investigated in six healthy adults. Head-up tilt at 45 degrees for 2 h during placebo saline infusion caused a 7% fall in blood volume accompanied by increases in plasma renin activity (PRA) and plasma arginine vasopressin (AVP) of 112 and 175%, respectively. Head-up tilt was repeated during an infusion of ANP producing a four- to sixfold increase in plasma ANP concentrations. This resulted in an 18% fall in plasma volume, yet despite this greater fall in plasma volume, PRA did not change. Two subjects experienced vasovagal symptoms toward the end of the ANP infusions accompanied by large increases in plasma AVP. In the other four subjects, plasma AVP remained unchanged during ANP infusions. Both procedures resulted in similar increases in plasma norepinephrine levels and in heart rate. Infusion of ANP prevents the posturally stimulated release of renin and AVP.

Adult↗

Anaphylaxis following "Hexabrix" during routine coronary angiography.

A case is described of an anaphylactic reaction to "Hexabrix 320" radiographic contrast medium in a patient undergoing routine coronary angiography. The case is reported because such reactions to "Hexabrix" are considered rare, because the patient was pretreated with hydrocortisone and chlorpheniramine, and because of the continuous monitoring that occurred during the procedure.

Aged↗