Defining uremic arterial functional abnormalities in patients recently started on haemodialysis: combined in vivo and ex vivo assessment.

Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD patients. Abdominal fat biopsies were obtained from 11 HD patients and 26 non-uremic controls. Subcutaneous arteries were dissected and mounted on a wire myograph, and cumulative concentration-response curves to noradrenalin, endothelin-1, a thromboxane A2 agonist (U46619), angiotensin II, vasopressin, bradykinin (BK), acetylcholine (ACh) and sodium nitroprusside (SNP) were constructed. Pulse wave velocity and blood pressure were measured in HD patients. Enhanced (P<0.05-0.0001) maximal contractile responses (Rmax) to all spasmogens (particularly vasopressin) were observed in arteries from HD patients compared to controls, and this effect was more pronounced in arteries with an internal diameter>600 µm. The potency (pEC50) of U46619 (P<0.01) and vasopressin (P<0.001) was also increased in arteries>600 µm of HD patients. The maximal relaxant response to the endothelium-dependent dilators ACh and BK were lower in HD patients (P<0.01-P<0.0001) (worse for ACh than BK); however the endothelium-independent dilator SNP was similar in both groups. PWV was significantly correlated with the vasoconstrictor response to vasopressin (P = 0.042) in HD patients. HD patients are primed for hypertension and end organ demand ischaemia by a highly sensitised pressor response. The failure of arterial relaxation is mediated by endothelial dysfunction. Intrinsic vascular abnormalities may be important in sensitising HD patients to recurrent cumulative ischaemic end organ injury.

The safety and efficacy of the use of vasopressin in sepsis and septic shock.

Sepsis remains a significant problem and cause of morbidity and mortality in intensive care. Vasopressin infusions are currently used as rescue therapy for the treatment of vasodilatory, catecholamine-resistant septic shock. At present, there are no large randomised, controlled trials in the literature investigating vasopressin in this role, although two such studies are currently ongoing in Canada. This review outlines the pathophysiology of sepsis and that of vasopressin in sepsis and reviews the available evidence for the use of vasopressin in sepsis and septic shock. A review of the safety data for vasopressin in this indication is included. Recommendations for the use of vasopressin in septic shock, along with suggestions for the direction of further work in the field are presented.

Octreotide decreases canine gastric mucosal blood flow: a controlled assessment by endoscopic reflectance spectrophotometry.

The aim of this study was to evaluate the effects of octreotide, a long-acting somatostatin analogue, on canine gastric mucosal blood flow and hemodynamics. We hypothesized that octreotide might decrease gastric mucosal blood flow without causing adverse hemodynamic effects. Two groups of dogs were anesthetized (six normal dogs and six dogs with prehepatic portal hypertension), and each dog was administered intravenous octreotide, normal saline solution, and vasopressin for 30 minutes on separate days in a blinded, randomized fashion. Vasopressin was included as treatment for a positive control. Gastric mucosal blood flow was assessed at the fundus, corpus, and antrum by endoscopic reflectance spectrophotometry. A femoral arterial catheter monitored systemic blood pressure and heart rate. Treatment responses for all observations were calculated for each dog as a percentage of baseline values. For mucosal blood flow, treatment responses did not differ significantly over time or between animal group or gastric location. Octreotide significantly decreased indices of hemoglobin concentration (-19%, p = 0.01) and oxygen saturation (-17%, p = 0.0002) compared to saline (-9% and -7%, respectively). The mean arterial pressure was increased after octreotide compared to saline (+23% versus +7%, p = 0.01), but octrotide had no effect on heart rate (+2% versus +1%). Vasopressin also decreased the indices of hemoglobin concentration (-34%) and oxygen saturation (-82%) significantly more than saline (p = 0.001). Vasopressin increased mean arterial pressure (+55%), but also caused reflex bradycardia (-22%) significantly more than saline (p = 0.001). We conclude that octreotide decreases canine gastric mucosal blood flow and appears to cause minimal hemodynamic changes.

Experimental assessment of drug-induced changes in cognitive function: vasopressin as a case study.

Two important forms of cognition are knowledge about internal states and social cognition. Knowledge about internal states is dependent on the ability to discriminate between different classes of visceral sensations and to associate them specifically to distinctive cues. The phenomenon of conditioned taste aversion (CTA) is the best example of this type of knowledge. Many chemicals induce interoceptive changes that can be perceived by animals and give rise not only to subjective sensations but also to causal attributions. However, the possibility that animals are able to discriminate different forms of interoceptive changes in a CTA paradigm has received little attention. Studies of the mechanisms of vasopressin-induced CTA provide evidence that it is the case and that animals are able to classify in different categories sensations related to the vasopressor activity of vasopressin and sensation induced by a prototypical aversive drug, apomorphine. Social cognition involves what individuals know about each other. One of the requirements for social cognition is social recognition, i.e., the ability to identify other individuals and classify them in different categories. Social recognition can be assessed by changes in duration of investigation of another animal when the stimulus animal is presented at different intervals. This form of memory is based on olfactory characteristics of the stimulus animal in rats and it can be enhanced or attenuated by memory-modulating drugs, as demonstrated by experiments with vasopressin.

Valoración de la función del túbulo renal por la estimación de la excreción de agua y solutos / Measurement of kidney tubules function by water and solutes excretion

Se estudiaron 106 personas adultas de ambos sexos; 21 normales, 33 diabéticos sin evidencias de nefropatía y 52 portadores de nefropatía. Los pacientes con nefropatía se dividieron en tres grupos según el tipo: I) Nefropatía glomerular vascular, 15 observaciones: II) Nefropatía túbulo intersticial (NTI) o nefropatía obstructiva, 17 observaciones; III) Nefropatía diabética; 20 observaciones. Se determinó: osmolaridad urinaria (Uosm), clearence osmolar (Cosm), reabsorción tubular de agua (Fe H2O), fracción excretada osmolar (Fe osm), fracción excretada de sodio (Fe Na), fracción excretada de potasio (Fe K) y clearence de creatinina (Ccr). Las determinaciones se realizaron luego de ayuno de ocho horas y en 31 observaciones luego de administrar vasopresina por vía subcutánea. En los pacientes con Ccr disminuido de los grupos I y II se comprobó: disminución de Uosm, Cosm, TeH2O y aumento de Fe H2O, Fe K. Se encontraron netas diferencias entre los grupos. La Fe Na se encontró normal en las glomerulopatías y aumentada en las nefrotías túbulointersticiales. La variación de las FeK Fe H2O y Fe osm fueron significativamente mayores en las nefropatías túbulointersticiales. La administración de vasopresina no determinó diferencias en los resultados

Assessment of myocardial perfusion by videodensitometry in the canine model.

Assessment of the functional severity of coronary stenoses has become increasingly important as the intrinsic limitations of coronary angiography have been documented. Videodensitometric coronary flow reserve has been proposed as a means to assess the physiologic significance of a coronary stenosis in humans. This study compared videodensitometric assessment of coronary flow with microsphere quantitation in the closed chest canine model. In five dogs, flow rates were assessed at baseline, after vasodilation with adenosine, after vasoconstriction with vasopressin and during rapid cardiac pacing. The videodensitometric peak density, time to one-half peak density and washout time (time from peak to one-half peak density) were compared at each flow state with flow assessed by microsphere injection. Reproducibility of videodensitometric measurements from two different coronary injections during the same flow state was best with peak density (r = 0.94). Videodensitometric flow ratios (flow state under study to flow at rest) using peak density demonstrated a fair correlation with flow ratios by microsphere (r = 0.81). There was poor correlation between flow ratios when time to one-half peak or washout time was used. Videodensitometric flow measurements used in vivo to assess a wide range of drug-induced coronary flows may not accurately reflect coronary flow measured by microsphere.

A scintigraphic method for the assessment of intraluminal volume and motility of isolated intestinal segments.

The isolated in vivo intestinal segment is a popular experimental preparation for the investigation of intestinal function, but its value has been limited because no method has been available for measuring changes in intraluminal volume under experimental conditions. We report a scintigraphic technique for measuring intraluminal volume and assessing intestinal motility. Between 30 and 180 ml, the volume of a 75-cm segment of canine jejunum, perfused with Tc-99m-labeled tin colloid, was found to be proportional to the recorded count rate. This method has been used to monitor the effects of the hormone vasopressin on intestinal function.

Assessment of urine-concentrating ability in man: effect of fludrocortisone and urea in enhancing response to vasopressin.

1. Healthy subjects, given a long-acting preparation of vasopressin intramuscularly, excreted a significantly less concentrated urine than when subjected to fluid deprivation for 28 h. 2. When fludrocortisone, a potent mineralocorticoid, was given in addition to vasopressin the urine was not significantly less concentrated than after fluid deprivation. 3. Oral urea-loading also enhanced the urine-concentrating power of vasopressin but its effect was less marked than that of fludrocortisone. Oral urea did not increase further the urine concentration achieved by combined fludrocortisone and vasopressin. 4. Renal concentrating power was assessed in fourteen patients with renal disease and impaired concentrating ability. Fludrocortisone significantly enhanced the urine concentration achieved by vasopressin alone and the resultant urine was not significantly less concentrated than that achieved by fluid deprivation. 5. The action of fludrocortisone in enhancing the urine-concentrating effect of vasopressin is similar to that of aldosterone and is probably due to the increased sequestration of solute in the renal medulla, caused by increased reabsorption of sodium chloride in the ascending limb of the loop of Henle. 6. In the clinical assessment of renal concentrating power, the combined use of fludrocortisone and vasopressin has potential advantages over established methods.