Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

Ruptured functioning adrenal tumour, atypical presentation with renal colic and hypertension.

Pheochromocytomas are uncommon tumours that originate in chromaffin cells. They are a representation of 0.1%-1% of all cases of secondary hypertension. Most pheochromocytomas are unilateral and benign, featuring catecholamine production, as well as the production of other neuropeptides. Pheochromocytomas are mostly located in the adrenal gland; the frequency of occurrence is highest between 30 and 50 years of age; however, up to 25% of cases may be linked to multiple endocrine neoplasia type 2, Von-Hippel-Landau disease and type 1 neurofibromatosis in the young.We present a case of ruptured left adrenal pheochromocytoma with an atypical presentation. A 30-year-old male patient presented with severe left flank pain and hypertension. The CT scan of the abdomen showed bleeding from the left adrenal mass, where resuscitation and angioembolisation were done. Embolisation of the inferior and superior arteries was done, but the middle failed. The patient experienced a significant drop in haemoglobin and a haemorrhagic shock post angioembolisation, which called for emergency laparotomy. The patient is currently doing well with an uneventful postoperative course.

Thromboxane A2 in the paraventricular hypothalamic nucleus mediates glucoprivation-induced adrenomedullary outflow.

Glucoprivation stimulates a rapid sympathetic response to release and/or secrete catecholamines into the bloodstream. However, the central regulatory mechanisms involving adrenoceptors and prostanoids production in the paraventricular hypothalamic nucleus (PVN) that are responsible for the glucoprivation-induced elevation of plasma catecholamines are still unresolved. In this study, we aimed to clarify whether glucoprivation-induced activation of noradrenergic neurons projecting to the PVN can induce α- and/or ß-adrenergic receptor activation and prostanoids production in the PVN to elevate plasma catecholamine levels. We examined the effects of α- and ß-adrenergic receptor antagonists, a cyclooxygenase inhibitor, a thromboxane A synthase inhibitor, and a PGE2 subtype EP3 receptor antagonist on intravenously administered 2-deoxy-D-glucose (2-DG)-induced elevation of noradrenaline in the PVN and plasma levels of catecholamine in freely moving rats. In addition, we examined whether intravenously administered 2-DG can increase prostanoids levels in the PVN microdialysates. Intracerebroventricular (i.c.v.) pretreatment with phentolamine (a non-selective α-adrenergic receptor antagonist) suppressed the 2-DG-induced increase in the plasma level of adrenaline, whereas i.c.v. pretreatment with propranolol (a non-selective ß-adrenergic receptor antagonist) suppressed the 2-DG-induced elevation of the plasma level of noradrenaline. I.c.v. pretreatment with indomethacin (a cyclooxygenase inhibitor) and furegrelate (a thromboxane synthase inhibitor) attenuated the 2-DG-induced elevations of both noradrenaline and adrenaline levels. Furthermore, 2-DG administration elevated the thromboxane B2 level, a metabolite of thromboxane A2 in PVN microdialysates. Our results suggest that glucoprivation-induced activation of α- and ß-adrenergic receptor in the brain including the PVN and then thromboxane A2 production in the PVN, which are essential for the 2-DG-induced elevations of both plasma adrenaline and noradrenaline levels.

Erectile dysfunction: a global review of intracavernosal injectables.

PURPOSE: Data assessing the effectiveness of intracavernosal injections (ICIs) for the treatment of erectile dysfunction (ED) are limited. This study evaluates intracavernosal injectable therapies for ED and reviews available guidelines that inform clinical practice. METHODS: A systematic search using electronic databases (Medline, Pubmed) was performed for studies investigating injectable management strategies for ED published after 1990. Primary outcome measures were to comparatively evaluate clinical efficacy, continuation rates and adverse event profiles of each injectable agent as monotherapy or in combination. The secondary outcome measurement was to discuss available guidelines that inform clinical practice for injectable agents. RESULTS: ICIs demonstrate clinical efficacy in 54-100% of patients, early discontinuation rates of ≤ 38% and adverse events in ≤ 26%. Discontinuation rates are typically greatest within 3-6 months of commencement. Anxiety related to the initial injection occurs in approximately 65% and anxiety levels can remain high for 4 months. Approval of intracavernosal injection agents is mainly limited to alprostadil with the recent addition of aviptadil/phentolamine combination therapy in a select few geographical regions. Although combination therapies are attractive alternative options, their formulations are variable and should be standardised before widespread acceptance is achieved. CONCLUSIONS: ICIs are associated with good clinical efficacy rates, high discontinuation rates and a moderate side-effect profile. They represent an important tool in the urological armamentarium for treating ED in patients that cannot tolerate or are refractory to oral therapies.

Prothrombotic response to norepinephrine infusion, mimicking norepinephrine stress-reactivity effects, is partly mediated by α-adrenergic mechanisms.

BACKGROUND: Stress-induced prothrombotic changes are mediated by the sympathetic nervous system and critically involved in mental triggering of acute coronary syndromes, but the underlying psychobiology is not fully understood. We tested the hypothesis that a norepinephrine (NE) infusion to mimic effects of stress-induced NE release on blood coagulation elicits prothrombotic changes and examined to what extent these would be mediated by an alpha-adrenergic mechanism. METHODS AND RESULTS: In a single-blind placebo-controlled within-subjects design, 24 middle-aged, non-smoking, non-obese and normotensive men participated in three experimental trials with an interval between one and two weeks. Each trial applied two sequential infusions of 1 and 15 min duration with varying substances [i.e., saline as placebo, the non-specific α-blocker phentolamine (2.5 mg/min), and NE (5 µg/min)]: trial 1=saline + saline; trial 2=saline + NE, and trial 3=phentolamine + NE. Plasma levels of clotting factor VIII activity (FVIII:C), fibrinogen, and D-dimer were assessed from blood samples collected immediately before and 1 min and 20 min after infusion procedures. Compared to saline + saline, saline + NE induced increases over time in FVIII:C, fibrinogen, and D-dimer levels. With phentolamine + NE, fibrinogen levels remained increased compared to saline + saline, but changes in FVIII:C and D-dimer levels were no more different. Coagulation changes did not differ between saline + NE and phentolamine + NE. CONCLUSIONS: NE infusion activates blood coagulation. The resulting prothrombotic state could be one psychobiological mechanism underlying mental triggering of acute coronary syndromes. Blockade of α-adrenergic receptors partly attenuated NE effects on coagulation and could be implied to have preventive potential in susceptible individuals.

Hormonal modulation of cannibalistic behaviors in mosquito (Culex pipiens) larvae.

Cannibalism has been observed occasionally in a limited number of different animal species, but the underlying mechanisms that foster this behavior are mostly unknown. Here we show that mosquito (Culex pipiens) larvae show this behavior towards conspecifics under certain conditions. Cannibalism was only observed in 4th instar larvae and only in response to starvation. Well fed animals never showed any cannibalistic behavior. Starvation induced cannibalism of Culex 4th instar was predominantly directed towards 3rd instars rather than to 1st or 2nd instar larvae. Specific mandibular structures of these larvae enable this cannibalistic behavior. We could show that treatment with the biogenic amine octopamine, which is known to be involved in the control of starvation and aggression, increased the rate of cannibalism of food-deprived 4th instar larvae significantly. Incubation with the octopamine receptor antagonist phentolamine suppressed this cannibalistic behavior. Moreover, octopamine not only increased the rate of cannibalism, it also induced a shift towards smaller prey. A role of octopamine in this starvation induced behavior was further supported by direct measurements of the total content of this important neuroactive compound. Taken together, we could show that 4th instar mosquito larvae showed cannibalistic behavior after starvation and that this behavior apparently depends on octopamine.

Reversing the effects of 2% Lidocaine: A randomized controlled clinical trial.

OBJECTIVES: Prolonged soft tissue anesthesia following a dental appointment is a complaint that is frequently reported by patients. Soft tissue anesthesia generally exceeds the duration of pulpal anesthesia by a few hours. This can lead to difficulties with smiling, drinking, speaking and lip/cheek biting following dental appointments. Phentolamine Mesylate (PM) is a pharmacological agent capable of reducing the duration of soft tissue anesthesia following dental treatments. Many clinical trials supporting its efficacy have used sham injections compared to injections with PM. The present study aims to evaluate the effect of PM on the duration of soft tissue anesthesia compared to a control injection of saline water. METHODS: This randomized controlled trial recruited 40 participants above 18 years of age. Following an inferior alveolar nerve block using 1.8 ml of Lidocaine 2%, 1:100 000 epinephrine, participants were randomized into one of 2 groups. The test group received an injection of 0.4 mg PM (OraVerse). Participants in the control group received an injection of sterile saline water. Participants were trained in self-assessing their anesthesia, which they did until return to normal sensation. RESULTS: Thirty-six participants completed the study. PM significantly reduced the duration of soft tissue anesthesia in the lower lip (104 vs 170 min, p = .001), and tongue (83 vs 134 min, p = .004) compared to the control injection. No serious adverse events were encountered. The only adverse events observed were post-operative pain and discomfort. CONCLUSIONS: Phentolamine Mesylate hastens the return to normal soft tissue sensation and function by approximately one hour compared to a control injection of water. CLINICAL SIGNIFICANCE: Phentolamine Mesylate can be considered a safe and effective way of reducing the duration of soft tissue anesthesia following a dental appointment. This controlled clinical trial is registered at the National Institutes of Health (ClinicalTrials.gov) #NCT02861378.

Phentolamine inhibits angiogenesis in vitro: Suppression of proliferation migration and differentiation of human endothelial cells.

It is widely known that the ß-adrenergic receptor (AR) blocker (propranolol) inhibits human endothelial cell (EC) angiogenesis in vitro, but how the α-AR antagonist (phentolamine) affects human EC angiogenesis has not yet been studied. Here, we show for the first time that both human dermal microvascular ECs (HDMECs) and human brain microvascular ECs (HBMECs) express α-ARs. Moreover, our results indicate that phentolamine inhibits the proliferation, migration, and tubulogenesis of HDMECs and HBMECs. Finally, VEGFR-2 and Ang1/2 expression of HDMECs was suppressed by phentolamine. Together, these results indicate that phentolamine impairs several critical events of neovascularization, and α-ARs, as well as the VEGF/VEGFR-2 and Ang/Tie-2 signaling pathways, may be involved in these processes. Our results suggest a novel therapeutic strategy for the use of α-blockers in the treatment of human angiogenesis-dependent diseases.

[Application value of Toshiba 320-row dynamic volumetric CT angiography in the diagnosis of venous erectile dysfunction].

Objective: To investigate the application value of Toshiba 320-row dynamic volumetric CT angiography in the diagnosis of venous erectile dysfunction (VED). METHODS: We enrolled in this study 33 patients diagnosed with ED by audiovisual sexual stimulation screening in the outpatient department. Penile erection was induced in the patients by injection of 2 mg phentolamine plus 30 mg papaverine into the corpus cavernosum, followed by that of contrast agent of iobitridol through the vein and corpus cavernosum successively. Then 320-row dynamic volumetric CT angiography was performed and the images of the corpus cavernosum in the arterial and venous phases were collected and processed. RESULTS: Different degrees of abnormal venous drainage were observed in 29 of the patients, including 7 cases (24.1%) of back deep venous leakage, 6 cases (20.7%) of foot venous leakage, 3 cases (10.3%) of dorsal superficial venous leakage, 1 case (3.5%) of intervertebral venous leakage, 2 cases (6.9%) of cavernous venous leakage, and 10 cases (34.5%) of mixed venous leakage. Ten of the patients underwent surgery, dorsal deep penile vein ligation in 2 cases, dorsal deep vein embedding plus foot vein ligation in 4, and foot vein ligation in the other 4. Eight of the patients were followed up for 3－12 months post-operatively, during which 2 achieved obvious erectile improvement, while the other 6 gained normal penile erection. CONCLUSIONS: Toshiba 320-row dynamic volumetric CT angiography is a reliable method for the diagnosis of VED, which displays the precise location of venous leakage for clinical treatment, with the advantages of clearer images, lower doses of contrast agent and radiation, and faster examination than X-ray penile angiography.

Phentolamine mesylate: It's role as a reversal agent for unwarranted prolonged local analgesia.

Administration of local anesthesia is an integral procedure prior to dental treatments to minimize the associated pain. It is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA) can be detrimental, inconvenient, and unnecessary. Phentolamine mesylate, a Food and Drug Administration-approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This article reviews the development of the drug phentolamine mesylate and its indication as a local anesthetic reversal agent. A literature search for phentolamine mesylate as a STA reversal agent was conducted in PubMed using the terms "dental local anesthesia reversal, phentolamine mesylate" up to March 2014. The search was limited to articles published in English. The search revealed 13 PubMed indexed articles stating the development and application of phentolamine mesylate. Phentolamine mesylate is an important step in the progress of developing patient care as well as an aid to the dental clinician.

[Successful anesthetic management of a patient with giant pheochromocytoma using high-dose landiolol hydrochloride].

We report successful anesthetic management of a patient with pheochromocytoma using high-dose landiolol hydrochloride. A 55-year-old man was scheduled to undergo resection of giant pheochromocytoma. Epidural anesthesia was not performed due to anticoagulant therapy for lower limb thrombus. Tracheal intubation was performed with the Pentax-AWS Airwayscope. Preoperative screening revealed urine adrenaline 2.567.0 microg x day(-1) urine noradrenaline 1,734.0 microg x day(-1), and a tumor diameter of 96 x 60 mm. Catecholamine surge was controlled with 50 microg x kg(-1) x min(-1) continuous infusion of landiolol hydrochloride and IV bolus phentolamine. On tumor resection, although systemic blood pressure increased to 294 mmHg and was unresponsive to repeated phentolamine administration, the heart rate remained at 70-105 beats x min(-1) and there were no significant ST changes.

Differential effect of beta-adrenergic receptor antagonism in basolateral amygdala on reconsolidation of aversive and appetitive memories associated with morphine in rats.

Positive and negative emotional experiences induced by addictive drugs play an important role in the development of dysfunctional drug-related memory, which becomes resistant to extinction and contributes to high rate of relapse. Those memories may undergo a process called reconsolidation that in some cases can be disrupted by pharmacological treatment. The basolateral amygdala (BLA) has been shown to mediate the reconsolidation of drug-related appetitive memory, but its role in withdrawal-related aversive memory remains elusive. The present study used conditioned place preference (CPP) and conditioned place aversion (CPA) paradigms to investigate the role of BLA and its noradrenergic receptors in reconsolidation of morphine-associated emotional memory in rats. We found that inhibition of protein synthesis in BLA disrupted the reconsolidation of morphine CPP (m-CPP) and CPA related to morphine withdrawal (m-CPA). A high dose of the ß-noradrenergic receptor antagonist propranolol (3 µg) in BLA-impaired reconsolidation of m-CPA but not m-CPP, whereas a low dose (0.3 µg) was ineffective. In contrast, neither low nor high doses of the α-noradrenergic receptor antagonist phentolamine (1 or 10 µg) blocked the reconsolidation of m-CPP and m-CPA. In addition, infusion of propranolol (3 µg) into nucleus accumbens after retrieval of either m-CPP or m-CPA did not affect its reconsolidation. The findings indicate that appetitive and aversive addictive memories share common neural substrates in BLA, but the specific neurotransmitter mechanism on reconsolidation of morphine-associated negative and positive memories can be dissociable.

Intravenous phentolamine abolishes coronary vasoconstriction in response to mild central hypovolemia.

Animal studies indicate alpha-adrenergic coronary vasoconstriction helps maintain left ventricular function during physiological stress. Whether this process occurs in humans is unknown. In the current study, we used transthoracic Doppler echocardiography to test the effect of lower body negative pressure (LBNP) on coronary blood flow velocity (CBV, left anterior descending coronary artery) and myocardial function in eight young healthy subjects before and after systemic infusion of phentolamine, a nonselective alpha blocker. Heart rate (HR) and blood pressure (BP) were monitored on a beat-by-beat basis. Peak diastolic CBV and myocardial systolic and diastolic tissue velocities (Sm and Em), were quantified at baseline, and at -5 mmHg, -10 mmHg, and -15 mmHg LBNP. Coronary vascular resistance index (CVRI) was calculated as the quotient of diastolic BP and CBV. Phentolamine reduced baseline diastolic BP and increased HR but did not affect the reflex adjustments to LBNP. The reduction in CBV due to LBNP was blunted by phentolamine at -10 mmHg and -15 mmHg. Importantly, the increase in CVRI (i.e., coronary vasoconstriction) was abolished by phentolamine at -5 mmHg (0.21 ± 0.06 vs. 0.83 ± 0.13), -10 mmHg (0.24 ± 0.03 vs. 1.68 ± 0.31), and -15 mmHg (0.27 ± 0.10 vs. 2.34 ± 0.43). These data indicate that alpha-adrenergic coronary vasoconstriction is present during low levels of LBNP. With alpha blockade, more coronary flow is needed to maintain cardiac function. Our data suggest that alpha-adrenergic tone enhances coronary flow efficiency, presumably by redistributing flow from the epicardium to the endocardium.

Milnacipran inhibits itch-related responses in mice through the enhancement of noradrenergic transmission in the spinal cord.

We investigated whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, exhibits an antipruritic effect through the spinal action in mice. Intrathecal injections of milnacipran (0.1 - 10 µg/site) significantly suppressed serotonin-induced biting, which is an itch-related response. However, such an effect was not observed with fluvoxamine (10 µg/site), which is a selective serotonin reuptake inhibitor. Furthermore, an intraperitoneal injection of milnacipran (10 mg/kg) inhibited serotonin-induced biting. When phentolamine (1.0 µg/site), a non-selective α-adrenoceptor antagonist, was intrathecally injected, it inhibited the above response of milnacipran. These results suggest that milnacipran suppresses itching through the inhibition of noradrenaline reuptake in the spinal cord.

Effects of phentolamine infusion during selective cerebral perfusion in neonatal piglets.

BACKGROUND: An optimal selective cerebral perfusion protocol in pediatric cardiac surgery is unknown. Phentolamine is frequently used in pediatric cardiopulmonary bypass. We sought to determine the effects of continuous phentolamine infusion during selective cerebral perfusion. METHODS: Twenty-seven neonatal piglets (3.38 ± 0.32 kg) were randomly assigned to 3 groups; sham (n = 7, anesthesia alone, no surgery or bypass), control (n = 10, saline infusion), or experimental (n = 10, phentolamine infusion 0.1 mg/kg per hour). Animals underwent 90 minutes of selective cerebral perfusion. Cerebral vascular resistance index (CVRI) and metabolic rate of oxygen (CMRO2) were determined every 15 minutes. Standardized sections of hippocampus, basal ganglia, and neo-cortex were obtained. Tissue samples were stained for caspase-3 and analyzed for positive apoptotic cell count. Data were analyzed with repeated measures and one-way analysis of variance. RESULTS: The CVRI tended to increase over time in the control group and decrease over time in the experimental group, but difference was not statically significant (0.46 ± 0.24 vs 0.39 ± 0.10 mm Hg × min × kg(2/3)/mL, p = 0.15). Mean CMRO2 was higher in the control group compared with the experimental group (0.90 ± 0.27 vs 0.59 ± 0.12 mLO2/min × kg(2/3), p = 0.005) and decreased over time in both groups. The percentage of caspase-3 positive cells was significantly different among regions (hippocampus = 16.9 ± 8.8; basal ganglia = 14.6 ± 7.5; neocortex = 10.8 ± 6.3; p < 0.0001) but not significantly different among sham (11.8% ± 2.68%), control (14.4% ± 2.24%), and experimental (15.5% ± 2.24%) groups. CONCLUSIONS: A continuous infusion of phentolamine during selective cerebral perfusion significantly decreases CMRO2 and tends to decrease CVRI when compared with control. At the dose studied and at the time of tissue sampling, phentolamine does not appear to decrease apoptosis during or early after selective cerebral perfusion.