Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides.

Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Over years, many attempts have been made to modify this hormone and find AVP analogues with different pharmacological profiles that could overcome its limitations. Non-peptide AVP analogues with low molecular weight presented good affinity to AVP receptors. Natural peptide counterparts, found in animals, are successfully applied as therapeutics; for instance, lypressin used in treatment of diabetes insipidus. Synthetic peptide analogues compensate for the shortcomings of AVP. Desmopressin is more resistant to proteolysis and presents mainly antidiuretic effects, while terlipressin is a long-acting AVP analogue and a drug recommended in the treatment of varicose bleeding in patients with liver cirrhosis. Recently published results on diverse applications of AVP analogues in medicinal practice, including potential lypressin, terlipressin and ornipressin in the treatment of SARS-CoV-2, are discussed.

Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study.

BACKGROUND: Pretransplant renal function is the major determinant of survival after liver transplantation (LTx). Patients with hepatorenal syndrome (HRS) have a poor outcome after LTx compared with patients transplanted without HRS. AIM: To analyze the impact of treatment of HRS before LTx on outcome after transplantation. METHODS: The outcome of patients with HRS (n=9) treated with vasopressin analogues before LTx was compared with that of a contemporary control group of patients without HRS (n=27) matched by age, severity of liver failure, and type of immunosuppression. RESULTS: Cases and controls were similar with respect to pretransplantation characteristics. Three-year survival probability was similar between the two groups (HRS-treated: 100% vs control: 83%, P=0.15). No significant differences were found between the two groups with respect to the incidence of impairment of renal function after LTx (HRS-treated: 22% vs control: 30%), severe infections (22 vs 33%), acute rejection (33 vs 41%), days in Intensive Care Unit (6+/-1 vs 8+/-1), days in hospital (27+/-4 vs 31+/-4), and transfusion requirements (11+/-3 vs 10+/-2 units). CONCLUSIONS: Patients with HRS treated with vasopressin analogues before LTx have a posttransplantation outcome similar to that of patients transplanted with normal renal function. These results suggest that HRS should be treated before LTx.

Ornipressin (Por 8): An efficient alternative to counteract hypotension during combined general/epidural anesthesia.

UNLABELLED: We sought to evaluate the efficacy and side effect profile of a small dose of ornipressin, a vasopressin agonist specific for the V1 receptor, administered to reverse the hypotension associated with combined general/epidural anesthesia. A total of 60 patients undergoing intestinal surgery were studied. After the induction of anesthesia, 7-8 mL of bupivacaine 0.5% with 2 microg/kg clonidine and 0.05 microg/kg sufentanil after an infusion of 5 mL of bupivacaine 0.06% with 0.5 microg x kg(-1) x h(-1) clonidine and 0.1 microg/h of sufentanil were administered by an epidural catheter placed at T7-8 vertebral interspace. When 20% reduction of baseline arterial blood pressure developed, patients were randomly assigned to receive, in a double-blinded design, dopamine started at 2 microg x kg(-1) x min(-1), norepinephrine started at 0.04 microg x kg(-1) x min(-1), or ornipressin started at 1 IU/h. Fifteen patients presenting without hypotension were used as control subjects. Beside routine monitoring, S-T segment analysis, arterial lactacidemia, and gastric tonometry were performed. Ornipressin restored arterial blood pressure after 8 +/- 2 vs 7 +/- 3 min in the norepinephrine group and 11 +/- 3 min in the dopamine group (P < 0.05). This effect was achieved with 2 IU/h of ornipressin in most of the patients (11 of 15). Ornipressin did not induce any modification of the S-T segment; however, it significantly increased intracellular gastric PCO(2) (P < 0.05), indicating splanchnic vasoconstriction. IMPLICATIONS: In the population studied, small-dose ornipressin was effective to restore arterial blood pressure without causing major ischemic side effects.

Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine.

Peripheral vasodilation is considered an important factor in the pathophysiology of the hepatorenal syndrome (HRS). Therefore, the aim of this study was to evaluate the therapeutic potential of the vasoconstrictor ornipressin plus dopamine in the treatment of the most severe form of HRS, namely HRS type 1. Seven cirrhotic patients (creatinine clearance 15 +/- 1 mL/min, UNaV 7 +/- 2 mmol/24 h) with HRS type 1 were included in the study after normalization of central venous pressure with intravenous albumin and low-dose dopamine had failed to prevent further deterioration of renal function. Ornipressin was given continuously (intravenous 6 IU/h) in combination with dopamine (2-3 microgram/kg/min) until creatinine clearance had increased to above 40 mL/min or adverse events prevented further treatment. HRS was reverted in 4 of 7 patients after 5 to 27 days (creatinine clearance 51 +/- 4 mL/min, UNaV 47 +/- 11 mmol/24 h) of treatment. Withdrawal was necessary in 1 patient after 15 days because of intestinal ischemia. Treatment failure was observed in 2 of 7 patients (creatinine clearance 19 +/- 10 mL/min, UNaV 8 +/- 3 mmol/24 h). Two of 4 responders had recidivant HRS 2 and 8 months after initial therapy, respectively. HRS in 1 of these patients was reverted with 18 days of ornipressin retreatment. The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia. Altogether, 3 of 7 patients survived HRS type 1, 1 after successful ornipressin therapy and liver transplantation, 1 with 2 successful courses of ornipressin, and 1 with liver transplantation after ornipressin treatment had failed. Thus, ornipressin plus dopamine can be a useful therapeutic option in patients with HRS type 1, especially as bridge to liver transplantation.

Preliminary study of microsurgical repairs of the inferior alveolar nerve in rats using primary suturing and laser weld techniques.

A comparison of primary suturing and a new laser weld technique is described for the microsurgical repair of the inferior alveolar nerve in Wistar rats. A reliable method of exposure of the inferior alveolar nerve has been developed in order to allow intraosseous repairs of the nerve involving suturing with 10:0 nylon and a laser weld technique using an albumin-based solder, containing indocynine cardiogreen, plus an infrared (810 nm wavelength) diode laser. Seven cases of microsuture and laser weld repairs were performed with a 29.4% reduction in total operating time in the laser weld group. Histochemical analysis showed comparable mean neuron counts and mean tracer uptake by neurons for the microsuture and laser weld groups. Giant cell reactions were identified in two of the primary suture cases and axon deflection in three cases demonstrating possible advantages of the laser weld technique which showed no adverse reactions by axons or epineurium to the coagulative repair with the solder. The technique of laser weld repair, on initial analysis, therefore appears comparable with traditional suture repairs and indeed may possess several advantages. Further studies are recommended.

Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion.

Hepatorenal syndrome is caused by a marked vasoconstriction of the renal circulation. It is suggested that the renal vasoconstriction is related to an overactivity of vasoconstrictor systems secondary to a vasodilation of the arterial circulation that causes a reduction in effective arterial blood volume. To test this hypothesis, 16 cirrhotic patients with hepatorenal syndrome were treated with a combination of ornipressin, a potent vasoconstrictor agent, and plasma volume expansion with albumin to improve effective arterial blood volume. The combined treatment was administered either for 3 or 15 days (8 patients each), and the effects on renal function, vasoactive systems, and systemic hemodynamics were assessed. The 3-day treatment with ornipressin and albumin was associated with a normalization of the overactivity of renin-angiotensin and sympathetic nervous systems, a marked increase in atrial-natriuretic peptide levels, and only a slight improvement in renal function. However, when ornipressin and albumin were administered for 15 days, a remarkable improvement in renal function was observed, with normalization of serum-creatinine concentration, a marked increase in renal plasma flow and glomerular filtration rate, and a persistent suppression in the activity of vasoconstrictor systems. However, 3 of 8 patients on 15-day therapy treatment had to be discontinued because of ischemic complications. In conclusion, the decrease in effective arterial blood volume and the activation of vasoconstrictor systems play a crucial role in the pathogenesis of hepatorenal syndrome. Although the prolonged administration of ornipressin combined with plasma volume expansion reverses hepatorenal syndrome, this treatment should be used with great caution in clinical practice because of the risk of ischemic complications.

An analysis of fluid loss during transcervical resection of submucous myomas.

OBJECTIVE: To determine the contribution of several variables to fluid loss during transcervical resection of submucous myomas. DESIGN: An observational study using multiple linear regression analyses. SETTING: A university-affiliated training hospital and a university department of clinical epidemiology and biostatistics. PATIENT(S): Patients with submucous myomas. INTERVENTION(S): Transcervical resection of submucous myomas and monitoring of fluid loss. MAIN OUTCOME MEASURE(S): Patient age, uterine enlargement, treatment with GnRH analogues or 8-ornithine-vasopressin, type of anesthesia, number of myomas, intramural extension of the myoma (type of myoma), and operating time were tested as variables. RESULT(S): Only intramural extension of the myoma and operating time were obviously related to fluid loss. For the other variables, such a relation was weak at best. The relation between fluid loss and operating time was not modified by any of the other variables. CONCLUSION(S): Because fluid loss is an important limiting factor in the transcervical resection of submucous myomas, special attention should be paid to reduction of the operating time and preoperative assessment of the intramural extension of the myoma to guide appropriate patient selection.

Renal and neurohormonal changes following simultaneous administration of systemic vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with hepatorenal syndrome.

BACKGROUND/AIMS: Intravenous ornipressin in cirrhotic patients with hepatorenal syndrome causes marked improvement of systemic hemodynamics and suppression of plasma renin and norepinephrine but only moderate improvement of renal function. This study was designed to investigate whether these beneficial effects could be enhanced by the simultaneous administration of dopamine. The renal effects of the i.v. infusion of norepinephrine plus prostacyclin in patients with hepatorenal syndrome were also assessed. METHODS: Renal plasma flow, glomerular filtration rate, free water clearance, sodium excretion and the plasma levels of renin and norepinephrine were measured in baseline conditions and during the administration of ornipressin (6 i.u./h) and ornipressin (6 i.u./h) plus dopamine (2 micrograms/kg.min) in nine patients with hepatorenal syndrome. Five additional patients with hepatorenal syndrome were studied prior to and following the administration of norepinephrine (0.45 +/- 0.1 microgram/kg.min) and norepinephrine (0.85 +/- 0.2 microgram/kg.min) plus prostacyclin (5 ng/kg.min). RESULTS: Despite a significant increase in arterial pressure and marked suppression of plasma renin activity during ornipressin and ornipressin plus dopamine administration, no significant improvement in renal function was observed. Norepinephrine and norepinephrine plus prostacyclin also failed to increase renal perfusion and glomerular filtration rate. CONCLUSIONS: The combined administration of systemic vasoconstrictors (ornipressin or norepinephrine) and vasodilators (dopamine or prostacyclin), at the doses used in the current study and for a short period of time, does not improve renal function in cirrhotic patients with hepatorenal syndrome. The current study does not confirm a potential role for ornipressin in the treatment of hepatorenal syndrome.

Embarazo ectópico intersticial: tratamiento laparoscópico, informe sobre 5 casos / Interstitial pregnancy: laparoscopic treatment, report of 5 cases

Se analiza la experiencia de un servicio de cirugía translaparoscópica (CTL) en embarazos intersticiales. Se trata de 5 casos resueltos totalmente por laparoscopia. Se describen los estudios prequirúrgicos necesarios. Su técnica quirúrgica y las maniobras necesarias para evitar un complicante sangrado. Destaca un abordaje conservador del mismo. Se informan datos sobre evolución reproductiva

[Clinico-pharmacological case (2). Bradycardia and ventricular tachycardia of the torsades de pointes type as a side effect of vasopressin: 3 case reports]. / Der klinisch-pharmakologische Fall (2).Bradykardie und ventrikuläre Tachykardia vom Typ Torsade de pointes als Nebenwirkung von Vasopressin: drei Fallberichte.

We present three patients with ornipressin-induced bradycardia, one of which developed also ventricular tachycardia of the torsade de pointes type. All three patients were treated with this vasopressin derivative because of bleeding esophageal varices due to portal hypertension in liver cirrhosis. Bradycardia ceased after discontinuing ornipressin therapy. One patient was treated successfully with atropine, one with isoprenalin and magnesium (he had to be defibrillated); the third patient recovered after cessation of ornipressin administration. Bradycardia is a known but rarely reported side effect of vasopressin and its derivatives. Animal studies suggest that this effect is due to its cardiodepressive action and also to a vagus-mediated reflex following vasopressin-induced increase in blood pressure. When injected directly into the ventricles of the brain, vesopressin leads to a decrease of the heart rate without affecting blood pressure; however, it remains unclear whether this mechanism is responsible for bradycardia after intravenous administration. Careful monitoring is essential during the treatment with vasopressin and its derivatives.

Effect of L-ornithine 8-vasopressin on blood loss during liposuction.

In this comparative study, we carried out liposuction on 20 patients randomly divided in two groups to find an alternative medication to epinephrine that would not result in secondary effects at the cardiovascular level but would offer a similar vasoconstricting capacity. Also, a variation of the wet technique is described that decreases blood loss secondary to liposuction. The area to undergo liposuction is infiltrated with a cannula of our own design. Epinephrine is not used as a vasoconstrictor but rather L-ornithine 8-vasopressin at a concentration of 0.01 IU/ml chilled saline. With this new technique, the amount of blood removed is minimal, even in the case of extraction of large volumes of fat.