Portal venous infusion of oleate solution has pressor effects. We have examined efferent mechanisms, measured the response to sustained infusion, and determined the effect of linoleate. Eight conscious animals received concurrent infusions of prazosin or vehicle with portal venous infusion of oleate. Oleate alone increased mean arterial pressure from 109.0 +/- 4.1 to 123.0 +/- 5.8 mmHg (P = 0.02), whereas no increase in blood pressure occurred when oleate was infused with prazosin. In 10 rats, concurrent infusion of losartan had no effect on the pressor activity of portal oleate infusion. Twenty-two animals received portal oleate or vehicle as a continuous infusion for 7 days. Mean arterial pressure (126.1 +/- 2.0 vs. 107.8 +/- 2.6 mmHg, P < 0.001) and heart rate (383 +/- 5 vs. 366 +/- 5, P = 0.0257) were increased in oleate-infused animals. No differences in plasma fatty acids, glucose, insulin, pressor hormones, liver enzymes, or in vitro arterial pressor responsiveness were observed. Portal venous infusion of linoleate increased arterial pressure by 12.2 +/- 3.2 mmHg (P = 0.033). These results indicate that alpha-adrenergic activity is necessary for the acute pressor effects of portal oleate, that sustained portal oleate infusion results in persistent blood pressure elevation, and that other long-chain fatty acids besides oleate have pressor effects.

Our aims were (1) to determine the effect of six commercially available aspirin (ASA) preparations on in vitro platelet aggregation, and (2) to relate changes in platelet function to ASA kinetics. Each of six subjects took a single dose of one of the following preparations--600 mg Asproclear, 600 mg Bufferin, 600 mg Bi-prin, 600 mg compressed ASA, 650 mg Ecotrin, or 650 mg S.R.A.--in random order every 3 wk. Venous blood was drawn before and at 2, 4, 6, and 24 hr after ASA dosage to measure platelet aggregation in response to collagen and adenosine diphosphate and, at more frequent intervals, to characterize ASA kinetics. Asproclear, Bufferin, Bi-prin, and compressed ASA yielded peak plasma ASA levels of 28 to 56 mumol/l (5 to 10 mg/l) within 15 to 60 min and peak salicylic acid (SA) levels of 72 to 290 mumol/l (10 to 40 mg/l) within 2 hr. Ecotrin and S.R.A. yielded plasma SA levels of 14 to 87 mumol/l (2-12 mg/l) within 4 to 24 hr and no measurable ASA at any time after dosing. Platelet aggregation was inhibited to an equal extent by all preparations. The time course for this inhibition was the same for all preparations but Ecotrin (which led to a more delayed effect). There was significant recovery of collagen-induced platelet aggregation at 24 hr with all preparations but Ecotrin. With Ecotrin and S.R.A. there was inhibition of platelet aggregation in the absence of measurable circulating ASA. We postulate that this was due to acetylation of cyclooxygenase in the portal circulation and that inhibition of peripheral cyclooxygenase may be spared.

Introduction: The prevalence of acromegaly in the general population ranges 4-14/100,000. 45-80% of acromegaly patients have obstructive sleep apnoea (OSA). The OSA population might represent a target group for earlier detection of acromegaly, thereby reducing associated long-term morbidity. Methods: Patients attending the sleep service (11/2014-04/2018) were recruited in a prospective multicentre cohort study. All had serum IGF-1 measurement and completed a screening questionnaire for five key symptoms associated with acromegaly. Those with raised age-specific IGF-1 underwent further biochemical assessment to investigate for acromegaly. Results: 1080 participants (73% male, mean age 55.6±12.0yrs) with confirmed OSA were recruited across two sites. Forty-three patients (4%) reported at least 4/5 acromegaly-related symptoms. There was no correlation between serum IGF-1 and symptom score. Sixty-one patients (5.7%) had elevated IGF-1 level on initial assessment. Fifty-one had repeat IGF-1 testing, while one had growth hormone measurement of &lt;1µg/L. Nine patients were lost to follow-up, including one death. Of the repeat IGF-1 tests, results were normal in 24 cases and no further investigation was undertaken. Repeat IGF-1 results were unavailable in 3 cases. In the remaining 24 patients with persistently raised IGF-1, 11 had GH &lt;1µg/L, suggesting that acromegaly was unlikely. The remainder (n=13), as well as the 3 individuals with unavailable IGF-1 results, had an oral glucose tolerance test. One patient (BMI of 23.7kg/m2) was diagnosed with acromegaly, was diagnosed with severe OSA and reported 4/5 acromegaly-related symptoms during screening. Conclusion: Our study identified a single case of acromegaly within the OSA population that may represent a higher prevalence than in the background population, however is based on a single case. As a consequence of the significant number of patients with elevated serum IGF-1 measurements requiring further investigation, IGF-I is not currently a cost-effective screening tool for early detection of acromegaly in OSA patients. Funding: Ipsen UK

Objective Obstructive sleep apnoea (OSA) is reported to have effects on a number of hormone systems including the hypothalamo‐pituitary axis. We aimed to determine the impact of OSA severity on insulin‐like growth factor‐I (IGF‐I) levels. Design and Methods This is a prospective cohort study performed between November 2014 and May 2017. IGF‐I was measured on serum samples, and data were collected on demographics, BMI and parameters of OSA. Results 611 participants were recruited (202 female, 53.5 ± 12.5 years; mean BMI 36.2 ± 8.0 kg/m2). 26.2% had mild OSA; 27.3%, moderate OSA; and 44.5%, severe OSA. 15.2% of IGF‐I values were below the age‐related reference range. Increasing BMI correlated with greater AHI (r = .28, p < .001), ODI (r = .30, p < .001), severity of OSA (r = .17, p < .001), duration with oxygen saturation (SaO2) <90% (r = .29, p = .001) and reduced median SaO2 levels (r = .19, p < .001). IGF‐I levels correlated negatively with age (r = −.13, p = .001), BMI (r = −.16, p < .001), diabetes (r = −.108, p = .009), AHI (r = ‐0.10, p = .043) and severity of OSA (r = −.10, p = .013). No association of IGF‐I was observed with ODI, median SaO2 levels or duration of SaO2 < 90%. Regression analyses were used to examine determinants of IGF‐I, all of which contained the independent variables of age, gender and BMI. All models showed IGF‐I to be predicted by age and BMI (p < .05); however, none of the parameters of OSA were significant within these models. Conclusion Insulin‐like growth factor‐I levels in OSA are dependent on age and BMI; however, no additional effect of any OSA parameter was observed, supporting the hypothesis that OSA effects on IGF‐I are indirect through concomitant body composition and metabolic parameters.