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The Valsalva manoeuvre ( VM), a forced expiratory effort against a closed airway, has a wide range of applications in several medical disciplines, including diagnosing heart problems or autonomic nervous system deficiencies. The changes of the intrathoracic and intra-abdominal pressure associated with the manoeuvre result in a complex cardiovascular response with a concomitant action of several regulatory mechanisms. As the main aim of the reflex mechanisms is to control the arterial blood pressure ( BP), their action is based primarily on signals from baroreceptors, although they also reflect the activity of pulmonary stretch receptors and, to a lower degree, chemoreceptors, with different mechanisms acting either in synergism or in antagonism depending on the phase of the manoeuvre. A variety of abnormal responses to the VM can be seen in patients with different conditions. Based on the arterial BP and heart rate changes during and after the manoeuvre several dysfunctions can be hence diagnosed or confirmed. The nature of the cardiovascular response to the manoeuvre depends, however, not only on the shape of the cardiovascular system and the autonomic function of the given patient, but also on a number of technical factors related to the execution of the manoeuvre including the duration and level of strain, the body position or breathing pattern. This review of the literature provides a comprehensive analysis of the physiology and pathophysiology of the VM and an overview of its applications. A number of clinical examples of normal and abnormal haemodynamic response to the manoeuvre have been also provided. [ABSTRACT FROM AUTHOR]

Background Pioglitazone is a thiazolidinedione ( TZD) insulin sensitizer approved for use in human type 2 diabetes mellitus. Therapeutic options for diabetes in cats are limited. Objective To evaluate the effects of pioglitazone in obese cats, which are predisposed to insulin resistance, to assess its potential for future use in feline diabetes mellitus. Animals A total of 12 obese purpose-bred research cats (6 neutered males and 6 spayed females, 5-7 years of age, weighing 5.4-9.8 kg). Methods Randomized, placebo-controlled 3-way crossover study. Oral placebo or pioglitazone (Actos™; 1 or 3 mg/kg) was administered daily for 7-week periods, with IV glucose tolerance testing before and after each period. Results Three mg/kg pioglitazone significantly improved insulin sensitivity (geometric mean [95% CI] 0.90 [0.64-1.28] to 2.03 [1.49-2.78] min −1pmol−1L; P = .0014 versus change with placebo), reduced insulin area under the curve during IVGTT (geometric mean [range] 27 [9-64] to 18 [6-54] min∙nmol/L; P = .0031 versus change with placebo), and lowered serum triglyceride (geometric mean [range] 71 [29-271] to 48 [27-75] mg/dL; P = .047 versus change with placebo) and cholesterol (geometric mean [range] 187 [133-294] to 162 [107-249] mg/dL; P = .0042 versus change with placebo) concentrations in the obese cats. No adverse effects attributable to pioglitazone were evident in the otherwise healthy obese cats at this dosage and duration. Conclusions and Clinical Importance Results of this study support a positive effect of pioglitazone on insulin sensitivity and lipid metabolism in obese cats, and suggest that further evaluation of the drug in cats with diabetes mellitus or other metabolic disorders might be warranted. [ABSTRACT FROM AUTHOR]

Clark, M., Thomaseth, K., Heit, M., Hoenig, M. Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs. J. vet. Pharmacol. Therap. 35, 342-350. Protamine zinc insulins are generally considered to be long acting, with slow absorption from subcutaneous tissue. Protamine zinc recombinant human insulin (PZIR) may be useful to treat diabetic dogs. The purpose of this study was to describe the pharmacokinetics and pharmacodynamics of PZIR in dogs. PZIR was administered subcutaneously to 10 healthy Beagles using an incomplete crossover design, at doses of 0.3 or 0.5 U/kg (each n = 5), 0.8 U/kg ( n = 10), or 0.8 U/kg at three separate sites ( n = 6). Insulin and glucose concentrations were measured over 24 h. The shapes of insulin and glucose curves were variable among dogs, and the relationship between insulin dose, concentration, and glucose-lowering effect was nonlinear. For single-site 0.8 U/kg, median (range) onset of action was 3.5 h (0.5-10 h), time to glucose nadir was 14 h (5 to >24 h), and duration of action was >24 h (16 to >24 h). Mathematical model predictions of times to 50% and 90% insulin absorption, and fraction of insulin absorbed in 24 h, were not significantly different among protocols. Results confirm the tendency toward a late onset and long duration of action for PZIR in dogs. This insulin may be an alternative treatment option for diabetic dogs. [ABSTRACT FROM AUTHOR]

Aims The purpose of the study was to determine long-term cardiovascular autonomic adaptation to moderate endurance aerobic exercise in people with Type 2 diabetes in order to test the hypothesis of an enhanced vagal drive. Methods We analysed the power spectral density of heart rate cyclic variations at rest, while lying, and while standing in 12 sedentary, non-smoking, Type 2 diabetic individuals. Testing was performed before and after a 6-month, supervised, progressive, aerobic training programme, twice weekly. Heart rate variability was assessed by autoregressive power spectral analysis (PSA); this method allows reliable quantification of low-frequency (LF) and high-frequency (HF) components, which are considered to be under mainly sympathetic and purely parasympathetic control, respectively. Results In 10-min electrocardiogram recordings, mean RR intervals values lying and standing were similar before and after physical exercise. Likewise, total heart rate variability, expressed as total power spectral density (PSD), was not altered by exercise. In contrast, on standing, the HF component, expressed in normalized units, was significantly higher (20.1 ± 4 vs. 30.4 ± 5, P < 0.01), whereas the LF component was significantly lower (68.1 ± 7 vs. 49.8 ± 8, P < 0.01) after exercise; hence, on standing, the LF/HF ratio, reflecting the sympathetic vs. parasympathetic balance, was markedly lower (16.2 ± 11 vs. 5.2 ± 3.2, P = 0.003). No significant exercise-related changes in these PSA components were observed on lying. Conclusions A twice-weekly, 6-month, moderate, aerobic exercise programme, without a concomitant weight loss diet, is associated with significant improvements in cardiovascular autonomic function in overweight, non-smoking, Type 2 diabetic individuals. [ABSTRACT FROM AUTHOR]

Abstract Background The role of amylin, which is cosecreted together with insulin by the pancreatic B-cells, in the pathogenesis of type-2 diabetes is still unclear. To elucidate a possible relation between amylin and glucagon we directly evaluated the respective prehepatic secretions following administration of a 75-g oral glucose load (OGL) in humans. Materials and methods We studied six healthy controls (C), six obese, insulin resistant subjects (O) and six patients with type 2 diabetes (D). Catheters were placed in the femoral artery and hepatic vein according to the hepatic vein catheterization technique. Splanchnic blood flow was assessed by infusion of indocyanine-green dye. The measured variables were analyzed by a general circulatory model for calculation of prehepatic secretion. Results The total amount of released glucagon was not different between the respective groups (20·5 ± 2·3 in C, 27·7 ± 5·1 in O and 27·9 ± 5·4 µg/4 h in D). When considered as the difference from the fasting profile, however, glucagon secretion was reduced by 3·5 ± 14% in C, 25 ± 12% in O and increased by 36 ± 21% in D (P = 0·051, D vs. C). Amylin secretion was increased in O (1·10 ± 0·15) vs. C (0·63 ± 0·05, P < 0·05) and D (0·24 ± 0·10 nmol, P < 0·01). Following glucose administration, glucagon secretion significantly inversely correlated with secretion of amylin ( r = -0·6, P < 0·01), but not with that of insulin ( r =-0·23, P = 0·36). Conclusions The inverse correlation between amylin and glucagon secretion suggests that amylin modulates glucagon secretion following oral glucose administration. This study proves for the first time a role of endogenous amylin in the regulation of glucose homeostasis. [ABSTRACT FROM AUTHOR]