Naphazoline intoxication managed with minimally invasive cardiac output monitoring.

Naphazoline, a nonspecific alpha-adrenoceptor stimulant, is a potent vasoconstrictor used in nasal sprays, eye drops, and over-the-counter antiseptics. Naphazoline intoxication increases afterload by constricting the peripheral arteries, which can lead to complications including multiple organ failure. Although phentolamine, a nonselective alpha-adrenoceptor antagonist, and nicardipine, a calcium channel blocker, are used for the treatment of naphazoline intoxication, no established administration protocols currently exist. We present the case of a 32-year-old male with depression who ingested 150 mL of an antiseptic containing 0.1% naphazoline (equivalent to 150 mg of naphazoline). Five hours after ingestion, the patient was admitted to hospital exhibiting signs of naphazoline intoxication, such as bradycardia (46 beats/min), blood pressure of 166/122 mmHg, and peripheral cyanosis. We used the FloTrac™/EV1000™ system (Edwards Lifesciences, Irvine, CA, USA), a minimally invasive cardiac output monitoring system, to monitor systemic vascular resistance. The systemic vascular resistance index (SVRI) was elevated (4457 dyne.s/cm5/m2; nomal range: 1970-2390 dyne.s/cm5/m2) upon admission and initial treatment with continuous intravenous infusion of phentolamine led to SVRI normalization within 2 h. With the goal of maintaining SVRI normalization, continuous infusion with nicardipine was then started. At 10 h after treatment initiation, the nicardipine dose peaked at 9 mg/h (1.9 µg/kg/min). Treatment was discontinued 8 h later, and the patient was discharged on the fourth day without sequelae. In conclusion, the use of a minimally invasive cardiac output monitoring system to track vascular resistance can effectively guide the dosing of phentolamine or nicardipine in the treatment of naphazoline intoxication.

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.

Regulation of cerebrovascular compliance compared with forearm vascular compliance in humans: a pharmacological study.

Increasing evidence indicates that cerebrovascular compliance contributes to the dynamic regulation of cerebral blood flow but the mechanisms regulating cerebrovascular compliance in humans are unknown. This retrospective study investigated the impact of neural, endothelial, and myogenic mechanisms on the regulation of vascular compliance in the cerebral vascular bed compared with the forearm vascular bed. An index of vascular compliance (Ci) was assessed using a Windkessel model applied to blood pressure waveforms (finger photoplethysmography) and corresponding middle cerebral artery blood velocity or brachial artery blood velocity waveforms (Doppler ultrasound). Data were analyzed during a 5-min baseline period (10 waveforms) under control conditions and during distinct sympathetic blockade (experiment 1, phentolamine; 10 adults), cholinergic blockade (experiment 2, glycopyrrolate; 9 adults), and myogenic blockade (experiment 3, nicardipine; 14 adults). In experiment 1, phentolamine increased Ci similarly in the cerebral vascular bed (131 ± 135%) and forearm vascular bed (93 ± 75%; P = 0.45). In experiment 2, glycopyrrolate increased cerebrovascular Ci (72 ± 61%) and forearm vascular Ci (74 ± 64%) to a similar extent (P = 0.88). In experiment 3, nicardipine increased Ci but to a greater extent in the cerebral vascular bed (88 ± 88%) than forearm vascular bed (20 ± 45%; P = 0.01). Therefore, adrenergic, cholinergic, and myogenic mechanisms contribute to the regulation of cerebrovascular and forearm vascular compliance. However, myogenic mechanisms appear to exert more specific control over vascular compliance in the brain relative to the forearm.NEW & NOTEWORTHY Vascular compliance represents an important determinant in the dynamics and regulation of blood flow through a vascular bed. However, the mechanisms that regulate vascular compliance remain poorly understood. This study examined the impact of neural, endothelial, and myogenic mechanisms on cerebrovascular compliance compared with forearm vascular compliance. Distinct pharmacological blockade of α-adrenergic, endothelial muscarinic, and myogenic inputs altered cerebrovascular and forearm vascular compliance. These results further our understanding of vascular control and blood flow regulation in the brain.

Comparative effect of deliberate hypotensive anesthesia using nitroglycerine vs. phentolamine on event related potentials and cognitive functions in patients undergoing septoplasty: a randomized controlled trial.

BACKGROUND: Postoperative cognitive dysfunction is a noteworthy complication of deliberate hypotensive anesthesia. The aim of this work was to compare the effect of deliberate hypotensive anesthesia using nitroglycerine versus phentolamine on event-related potentials and cognitive function in patients undergoing septoplasty surgery. METHODS: This prospective randomized controlled trial was conducted on 80 patients indicated for septoplasty under general anesthesia; 40 patients received intra-operative Nitroglycerine and 40 patients received intra-operative Phentolamine. Cognitive assessment (using Paired Associate Learning test (PALT) and Benton Visual Retention test (BVRT)) and P300 recording were done for all included patients pre-operatively and one week postoperatively. RESULTS: The scores of PALT and Benton BVRT significantly declined one week following surgery in both Nitroglycerine and Phentolamine groups. There was no statistically significant difference between Nitroglycerine and Phentolamine groups in the postoperative decline in either PALT or BVRT (P-value = 0.342, 0.662 respectively). The values of P300 latency showed a significant delay one week following surgery in both Nitroglycerine and Phentolamine groups (P-value ≤ 0.001, 0.001), but in Nitroglycerine group, the delay is significantly higher than in Phentolamine group (P-value = 0.003). The values of P300 amplitude significantly decreased one week following surgery in both Nitroglycerine and Phentolamine groups (P-value ≤ 0.001, 0.001), but there was no statistically significant difference between Nitroglycerine and Phentolamine groups (P-value = 0.099). CONCLUSION: Phentolamine is preferred over nitroglycerin in deliberate hypotensive anesthesia because it has less harmful effect on cognitive function than nitroglycerin.

EFFECTIVENESS OF PHENTOLAMINE MESYLATE IN REVERSAL OF LOCAL ANESTHESIA: SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: The aim of the present paper is to summarize the effectiveness of Phentolamine mesylate on the reversal of local anesthesia (LA). METHODOLOGY: Seven electronic databases were searched for randomized clinical trials in patients who received LA (population) and either received a Phentolamine injection (intervention) after LA compared to placebo or sham (control) to cause a return of normal sensation (outcome). Risk of bias assessment was performed using Cochrane risk of bias assessment tool 2.0. The hazard ratio (HR) was calculated as the event (time to return to the normal sensation) was a time-dependent event, as well as the weighted mean difference (WMD), was computed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of the evidence. RESULTS: Ten studies met our inclusion criteria and were included in this review. After pooling the results quantitatively, the value of the HR in the tongue was 0.56 (95% CI: 0.41-0.75, P<.001); in lower lip, the value was 0.56 (95% CI: 0.38-0.83, P = .004) and for upper lip, the value was 0.50 (95% CI: 0.31-0.80, P = .004). The WMD for the time to return for normal sensation was -47.71 min for the tongue (95% CI: -73.63 to -21.80 min, P<.001), -73.29 min for lower lip (95% CI: -88.41 to -58.16 min, P<.001) and -86.86 min for upper lip (95% CI: -101.16 to -72.57 min, P<.001). There is a high certainty of evidence that patients who have been administered local anesthesia may achieve faster recovery of normal sensation in tongue, and moderate certainty of evidence for return of normal sensation in lower lip and upper lip, if Phentolamine was administered after the local anesthesia. The adverse effects were reported in a few studies and were minor, not necessitating any medical intervention. CONCLUSIONS: Phentolamine might be a useful adjunct in patients who desire an earlier return of normal sensation and function after local anesthesia. Future research should be directed to study the cost-effectiveness or dental patient-reported outcomes of Phentolamine after local anesthetic injections.

A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances.

PURPOSE: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD. METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed. RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia. CONCLUSION: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD. TRIAL REGISTRATION: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

Association of periprocedural phentolamine infusion with favorable outcome in patients with chronic kidney disease and chronic coronary syndrome undergoing coronary catheterization: a prospective randomized controlled pilot study.

BACKGROUND: Chronic kidney disease (CKD) is a major risk factor for contrast induced acute kidney injury (CI-AKI) in chronic coronary syndrome (CCS) patients undergoing coronary catheterization. We aimed to evaluate the efficacy of phentolamine in prevention of CI-AKI in CKD and CCS patients undergoing percutaneous coronary catheterization for diagnostic angiography ± stenting. METHODS: Participants with CKD and CCS planned for percutaneous coronary catheterization were included, while participants with normal kidney functions were excluded. A consecutive sample of 107 participants (mean age 58.62 ± 8.96 years, 64.5% males) was selected, underwent diagnostic coronary angiography or percutaneous coronary intervention, and received either conventional CI-AKI prevention strategy (group 1) or periprocedural phentolamine and conventional CI-AKI prevention strategy (group 2). RESULTS: The percentages of study participants who had CI-AKI were 82.9% for group 1 and 17.1% for group 2, respectively. The incidence rate of CI-AKI was significantly lower in group 2 versus group 1 (p <  0.001). The urine output (ml/kg) and the urine output (ml/hour) within 72 hours post procedure was significantly higher in group 2 versus group 1 (t(105) = - 0.69, p <  0.001, t(105) = - 52.46, p < 0.001, respectively), the peak change in serum creatinine and the percentage of change relative to the baseline serum creatinine at 72 hours post procedure was significantly lower in group 2 versus group 1 (t(102) = 0.2, p 0.018, t(102) = 23.54, p < 0.001, respectively), and the incidence rate of major adverse cardiac and cerebrovascular events within 90 days post procedure was significantly lower in group 2 versus group 1 (t(102) = 1.168, P < 0.001), respectively. There was a statistically significant association of periprocedural phentolamine infusion with prevention of CI-AKI (OR = 0.041, 95% CI 0.0149-0.1128, P < 0.0001). CONCLUSION: Our study highlights the potential role of phentolamine for protection of the kidney in CKD patients planned for coronary catheterization. TRIAL REGISTRATION: Pan African Clinical Trial Registry Number: PACTR202209493847741. Date of Trial Registration: 22/09/2022.

Alpha-blockade during congenital heart surgery admissions: analysis from national database.

INTRODUCTION: The effects of alpha-blockade on haemodynamics during and following congenital heart surgery are well documented, but data on patient outcomes, mortality, and hospital charges are limited. The purpose of this study was to characterise the use of alpha-blockade during congenital heart surgery admissions and to determine its association with common clinical outcomes. MATERIALS AND METHODS: A cross-sectional study was conducted using the Pediatric Health Information System database. De-identified data for patients under 18 years of age with a cardiac diagnosis who underwent congenital heart surgery were obtained from 2004 to 2015. Patients were subdivided on the basis of receiving alpha-blockade with either phenoxybenzamine or phentolamine during admission or not. Continuous and categorical variables were analysed using Mann−Whitney U-tests and Fisher exact tests, respectively. Characteristics between subgroups were compared using univariate analysis. Regression analyses were conducted to determine the impact of alpha-blockade on ICU length of stay, hospital length of stay, billed charges, and mortality. RESULTS: Of the 81,313 admissions, 4309 (5.3%) utilised alpha-blockade. Phentolamine was utilised in 4290 admissions. In univariate analysis, ICU length of stay, total length of stay, inpatient mortality, and billed charges were all significantly higher in the alpha-blockade admissions. However, regression analyses demonstrated that other factors were behind these increased. Alpha-blockade was significantly, independently associated with a 1.5 days reduction in ICU length of stay (p < 0.01) and a 3.5 days reduction in total length of stay (p < 0.01). Alpha-blockade was significantly, independently associated with a reduction in mortality (odds ratio 0.8, 95% confidence interval 0.7−0.9). Alpha-blockade was not independently associated with any significant change in billed charges. CONCLUSIONS: Alpha-blockade is used in a subset of paediatric cardiac surgeries and is independently associated with significant reductions in ICU length of stay, hospital length of stay, and mortality without significantly altering billed charges.

The vasopressor action of angiotensin II (ANG II) in ball pythons (Python regius).

Angiotensin II (ANG II) is part of the renin-angiotensin system (RAS) in vertebrates and exert vasoconstriction in all species studied. The present study examines the vasopressor effect of ANG II in the ball python (Python regius), and examines whether ANG II exert its effect through direct angiotensin receptors or through an activation of α-adrenergic receptors. The studies were conducted in snakes with chronic arterial catheters that had recovered from anesthesia. In addition to demonstrating a clear and pronounced dose-dependent rise in arterial blood pressure upon repeated injections of boluses with ANG II (0.001-1 µg/kg), we demonstrate that the pressor response persisted following α-adrenergic blockade using the α-adrenergic antagonist phentolamine (2.5 mg/kg). Unfortunately, it proved impossible to block the ANG receptors using losartan (1, 3 or even 10 mg/kg). The pressor response to ANG II was associated with a significant rise in heart rate at the higher dosages, pointing to a resetting of the barostatic mechanism for heart rate regulation. The responses were similar in fasting and digesting pythons despite the expected rise in baseline values for blood pressure and heart rate of the digesting snakes.

Ganoderic acid A protects neural cells against NO stress injury in vitro via stimulating ß adrenergic receptors.

Excessive nitric oxide (NO) causes extensive damage to the nervous system, and the adrenergic system is disordered in many neuropsychiatric diseases. However, the role of the adrenergic system in protection of the nervous system against sodium nitroprusside (SNP) injury remains unclear. In this study, we investigated the effect of ganoderic acid A (GA A) against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection. We found that SNP (0.125-2 mM) dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents. Pretreatment with GA A (10 µM) significantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells, but not in PC12 cells. Furthermore, pretreatment with GA A caused significantly higher adrenaline content in SH-SY5Y cells than in PC12 cells. In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells, we added adrenaline, phentolamine, metoprolol, or ICI 118551 1 h before GA A was added to the culture medium. We found that addition of adrenaline (10 µM) significantly improved GA A protection in PC12 cells. The addition of ß1-adrenergic receptor antagonist metoprolol (10 µM) or ß2-adrenergic receptor antagonist ICI 118551 (0.1 µM) blocked the protective effect of GA A, whereas the addition of α-adrenergic receptor antagonist phentolamine (0.1 µM) did not affect GA A protection in SH-SY5Y cells. These results suggest that ß-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries, and excessive adrenaline system activation caused great damage to the nervous system.

Adrenaline Auto-injector injuries to digits; a systematic review and recommendations for emergency management.

AIMS: Accidental injury to digits with Adrenaline Auto-injectors (AAIs) is becoming increasingly common. Digital AAI injury causes painful ischaemia that can lead to necrosis and patient anxiety. There is a lack of understanding amongst surgeons regarding how to manage these injuries. We aimed to determine an optimal treatment algorithm for their management. METHODS: We conducted a systematic review using the search engines MEDLINE, PubMed, EMBASE, CINAHL, BNI, AMED, Google Scholar. Search items included ("epinephrine OR adrenaline") AND ("Digit" OR "Finger" OR "Thumb") AND ("Injury" OR "Accidental"). RESULTS: A total of 49 articles were identified describing 111 cases. In 58 cases; 52% of cases were managed with phentolamine, 24% were managed with nitroglycerine and 7% were treated with warm soaks. The remaining 17% of cases were managed with a variety of alternative treatments. Mean recovery time following treatment with phentolamine infiltration was 33 min, whilst symptoms persisted for several hours in some cases with observation/warm soaks and nitroglycerine. Phentolamine was more effective when injected into the AAI puncture site (mean resolution time: 17 min) in comparison to injection as a digital block (74 min). CONCLUSION: Phentolamine is the most effective method of reversing symptoms and treating ischaemic digits when compared to alternative therapies. Symptoms resolved much quicker when phentolamine was infiltrated into the site of injury compared to being infiltrated as a digital block. We propose a treatment algorithm for management of these injuries. Hand surgeons should be aware of AAI injuries and be able to advise on their management.

Anti-inflammatory and anti-resorptive efficacy of adrenergic blockers on late replanted rat incisors.

BACKGROUND/AIM: In addition to their anti-inflammatory and anti-osteoclastogenesis properties, adrenergic blockers may also have promising anti-resorptive effects that can prevent root resorption when teeth are replanted because of avulsion. The aim of this study was to investigate the effects of phentolamine (Ph) and propranolol (Pr) in gels on the repair process of late replanted rat incisors. A further aim was to evaluate the biocompatibility of both drugs to human periodontal ligament fibroblasts (HPDLFs). MATERIALS AND METHODS: Forty-eight maxillary right incisors were extracted from male Wistar rats, stored in paper napkins for 60 minutes, and randomly allocated to one of eight groups (n = 6). The root canal, root surface, and alveolus were treated with 0.75 µg/mL Ph gel (Ph0.75), 10 µg/mL Ph gel (Ph10), 100 µg/mL Ph gel (Ph100), 2.5 µg/mL Pr gel (Pr2.5), 10 µg/mL Pr gel (Pr10), 100 µg/mL Pr gel (Pr100), or sodium carboxymethylcellulose gel (CMC) before replantation. In the control group (CH), only the root canal was treated with calcium hydroxide paste. Thirty days following surgery, the animals were euthanized, and the right hemimaxilla was removed to perform micro-CT and histomorphometric analysis to determine osteoclastic activity. Ethanolic solutions of Ph10 and Pr10 were selected based on the in vivo study, and the viability of HPDLFs stimulated with lipopolysaccharide was determined by MTT assays. RESULTS: The micro-CT and histomorphometric analysis revealed no significant differences among the treatments (P > .05). The presence of active osteoclasts was significantly decreased in the Ph10 and Pr10 groups (P < .05). Ph10 and Pr10 produced statistically similar cell survival rates compared to the control group (P > .05). CONCLUSIONS: Ph10 and Pr10 significantly decreased osteoclastogenesis in delayed replanted rat teeth and were not cytotoxic toward HPDLFs.

Effect of phentolamine mesylate on regression of lidocaine-epinephrine epidural anaesthesia in sheep.

OBJECTIVE: To determine the impact of epidural phentolamine on the duration of anaesthesia following epidural injection of lidocaine-epinephrine. STUDY DESIGN: Blinded randomized experimental study. ANIMALS: A group of 12 adult ewes weighing 25.7 ± 2.3 kg and aged 8-9 months. METHODS: All sheep were administered epidural lidocaine (approximately 4 mg kg-1) and epinephrine (5 µg mL-1). Of these, six sheep were randomized into three epidural treatments, separated by 1 week, administered 30 minutes after lidocaine-epinephrine: SAL: normal saline, PHE1: phentolamine (1 mg) and PHE2: phentolamine (2 mg). The other six sheep were administered only epidural lidocaine-epinephrine: treatment LIDEP. Each injection was corrected to 5 mL using 0.9% saline. Noxious stimuli were pinpricks with a hypodermic needle and skin pinch with haemostatic forceps to determine the onset and duration of sensory and motor block. Heart rate, noninvasive mean arterial pressure (MAP), respiratory rate and rectal temperature were recorded. RESULTS: The onset times were not different among treatments. Duration of sensory block was significantly shorter in SAL (57.5 ± 6.2 minutes), PHE1 (60.7 ± 9.0 minutes) and PHE2 (62.0 ± 6.7 minutes) than in LIDEP (81.7 ± 13.4 minutes) (p < 0.05). Duration of motor blockade was significantly shorter in PHE1 (59.4 ± 5.4 minutes) and PHE2 (54.3 ± 4.0 minutes) than in SAL (84.8 ± 7.0 minutes) and LIDEP (91.5 ± 18.2 minutes) (p < 0.01). MAP in PHE2 was decreased at 10 minutes after administration of phentolamine (p < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Epidural administration of 5 mL normal saline after epidural injection of lidocaine-epinephrine reduced the duration of sensory but not motor block in sheep. Epidural administration of phentolamine diluted to the final volume of 5 mL diminished both the duration of sensory and motor block in sheep administered epidural lidocaine-epinephrine.

[Efficacy and prognosis of phentolamine in the treatment of patients with myocardial injury due to sepsis].

Objective: To explore the effect of phenolamine on the outcome and prognosis of patients with myocardial injury due to sepsis. Methods: From January 2015 to December 2017, 62 septic patients with myocardial injury were randomly divided into study group (n=32) and control group (n=30). Two groups were given conventional treatment, while the study group was treated with phentolamine. The NT-pro brain natriuretic pepitide (NT-proBNP), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), creatine kinase isoenzymes (CK-MB) and tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1ß, IL-6 were detected at 0,12, 24, 48, 72 h and 7 d after hospitalization. And left ventricular ejection fraction (LVEF), e', E and A in each time period were observed. The 28 d survival rate and length of ICU stay were observed in both groups. The data were compared with single sample t test between the two groups. Results: After 12, 24, 48, 72 h and 7 d, NT-proBNP, cTnI, LDH, CK-MB, TNF-α, hs-CRP, IL-1ß, IL-6 in the study group were all significantly lower than those in the control group (all P<0.05). The cardiac function indexes of LVEF, E/A and E/e' in the study group were all significantly improved when compared with those in the control group (all P<0.05). The length of ICU stay and 28-day mortality in the study group were significantly lower than those in the control group ((9.8±3.6) d vs (13.0±4.1) d, t=3.152, P=0.004; 21.9% vs 36.7%, χ(2)=5.078, P=0.021). Conclusion: Combined application of phentolamine can significantly improve the outcome of sepsis patients with myocardial injury and improve the survival rate.

Clinical efficacy of phentolamine in the treatment of feeding intolerance in premature infants with low birth weight.

OBJECTIVE: To discuss the clinical efficacy of phentolamine in the treatment of feeding intolerance in premature infants with low birth weight. METHODS: Seventy-one low-birth-weight infants with feeding intolerance were randomly divided into the phentolamine group and the erythromycin group (38 patients and 33 patients, respectively). The infants were given basic treatment, such as gastric lavage, temporary fasting, nutritional support and abdominal massage. The phentolamine group was intravenously pumped with phentolamine as the basis of basic treatment, while the erythromycin group was given erythromycin as the basis of basic treatment. The time for gastrointestinal symptoms to disappear, the time the basic standard was reached, the time parenteral nutrition was used, the total time enteral feeding was implemented, the length of stay, and the increase in physical indexes according to the corrected gestational age of 40 weeks of the two groups were compared. RESULTS: There was no significant difference between the phentolamine group and the erythromycin group in vomiting disappearance time or the increase in physical indicators at the corrected gestational age of 40 weeks (P>0.05), while the abdominal distension disappearance time, the time of restoration to birth weight, the time to reach the basic standard, the total time of parenteral nutrition, the total time of enteral feeding, and the length of stay in the phentolamine group were shorter than those in the erythromycin group, with significant differences (P<0.05). CONCLUSION: Phentolamine has a significant effect on alleviating symptoms and shortening the treatment time while treating feeding intolerance in premature infants with low birth weight, without adverse events, so it is worthy of clinical promotion.

Effect of Hepatic Artery Spasm on a Rat Model of Hepatic Ischemia-Reperfusion Injury.

OBJECTIVES: To investigate hemodynamic changes in the hepatic artery after hepatic ischemia-reperfusion injury (IRI) in rats via ultrasound (US) imaging and to discuss the protective effect of phentolamine (PHT) pretreatment on hepatic IRI. METHODS: Fifty rats were randomly divided into 3 groups: a sham operation group (n = 10), a control ischemia-reperfusion group (n = 20), and a PHT pretreatment group (n = 20). Color Doppler flow imaging and contrast-enhanced US examinations were performed in each group at 30 minutes (n = 10) and 90 minutes (n = 10) after reperfusion. Blood samples were obtained to analyze serum alanine aminotransferase and aspartate aminotransferase levels, and liver tissue specimens were collected for pathologic analysis. RESULTS: Using US, we found that hepatic artery resistance at 30 minutes after reperfusion in the control group was higher than that in the sham group (mean resistive index [RI] ± SD, 0.65 ± 0.09 versus 0.50 ± 0.09; P < .01), which was higher at 30 than 90 minutes (RI, 0.65 ± 0.09 versus 0.50 ± 0.08; P < .01) after reperfusion in the control group. However, the hepatic artery resistance and liver microcirculation in the PHT group were better than those in the control group at 30 minutes after reperfusion (RI, 0.54 ± 0.09 versus 0.65 ± 0.09; P < .05; time to peak, 31.94 ± 2.02 versus 48.34 ± 4.74 seconds; P < .01). Compared to the control group, the aspartate aminotransferase and alanine aminotransferase levels were significantly lower at 30 minutes after reperfusion in the PHT group (P < .05). A pathologic examination revealed a smaller hepatic artery diameter and a depressed vessel wall in the control group. CONCLUSIONS: The hepatic artery can undergo a transient spasm during the hepatic IRI process, which can exacerbate liver damage. Phentolamine treatment can alleviate hepatic artery spasms, improve liver perfusion, and reduce liver injury by ameliorating the hepatic microcirculation.

[Pharmacokinetics Study of Phentolamine Mesylate Injection in Healthy Volunteers].

OBJECTIVE: To study the pharmacokinetic profile of phentolamine mesylate injection in healthy Chinese volunteers. METHODS: A total of 16 healthy volunteers were randomly divided into two groups, each receiving anterior teeth submucosal infiltration anesthesia and inferior alveolar nerve block anesthesia, respectively. The participants were injected with 0.9 mL, 1.8 mL, and 3.6 mL of 2% lidocaine HCl with 1∶100 000 epinephrine over three periods sequentially, followed by corresponding sequential injection of 0.2 mg, 0.4 mg, 0.8 mg of phentolamine mesylate at the same sites 30 min later.Blood samples were drawn from 5 min before injection to 15 h post the injection of phentolamine mesylate (16 time points). Adverse events were closely observed all the time. Plasma phentolamine mesylate was detected using UPLC-MS/MS with isotope as internal standard. WinNolin 6.1 software was used to calculate the pharmacokinetic parameters. RESULTS: Time to peak concerntration (Tmax) ranged from 12 to 13 min. Half-time of elimination (t1/2) ranged from 3.84 to 4.07 h, with a clearance (CL) of 190 L/h. Peak concentration (Cmax), area under concentration-time curves from 0 to t hour and from 0 to infinite time (AUC0-t and AUC0-∞) increased proportionally in the dose range of 0.2 mg to 0.8 mg. The results of confidence interval analysis showed nearly linear dynamic characteristics for the injection of phentolamine mesylate. All participants experienced mild adverse events, including pain at the injection point, dizziness, and palpitations. These adverse events disappeared without treatments. CONCLUSIONS: Phentolamine mesylate injection is effective for reversing oral local anesthetic effects.

Phentolamine Mesylate May be a Safe and Effective Option to Reduce Discomfort and Time to Recovery After Dental Care With Local Anesthesia.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Effectiveness and safety of phentolamine mesylate in routine dental care. Daubländer M, Liebaug F, Niedeggen G, Theobald K, Kürzinger M-L. J Am Dent Assoc 2017; 148(3):149-56. SOURCE OF FUNDING: The study was funded by Sanofi-Aventis Deutschland, Berlin, Germany TYPE OF STUDY/DESIGN: Two study designs were used: a prospective noninterventional, postauthorization efficacy (controlled observational) study, and a prospective noninterventional uncontrolled observational study.

Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae.

The goal of this in vitro study was to examine the effect of the alpha-2 adrenoceptor agonist dexmedetomidine on phenylephrine (alpha-1 adrenoceptor agonist)-induced contraction in isolated rat aortae and to elucidate the associated cellular mechanisms, with a particular focus on alpha-1 adrenoceptor antagonism. Dexmedetomidine dose-response curves were generated in isolated endothelium-intact and endothelium-denuded rat aortae precontracted with phenylephrine or 5-hydroxytryptamine. Endothelium-denuded aortic rings were pretreated with either dexmedetomidine or the reversible alpha-1 adrenoceptor antagonist phentolamine, followed by post-treatment with the irreversible alpha-1 adrenoceptor blocker phenoxybenzamine. Control rings were treated with phenoxybenzamine alone. All rings were repeatedly washed with Krebs solution to remove all pretreatment drugs, including phenoxybenzamine, phentolamine and dexmedetomidine. Phenylephrine dose-response curves were then generated. The effect of rauwolscine on the dexmedetomidine-mediated change in phenylephrine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined using western blotting. The magnitude of the dexmedetomidine-mediated inhibition of phenylephrine-induced contraction was higher in endothelium-intact aortae than in endothelium-denuded aortae or endothelium-intact aortae treated with Nω-nitro-L-arginine methyl ester. However, dexmedetomidine did not significantly alter 5-hydroxytryptamine-induced contraction. In further experiments, prazosin attenuated dexmedetomidine-induced contraction. Additionally, pretreatment with either dexmedetomidine plus phenoxybenzamine or phentolamine plus phenoxybenzamine produced greater phenylephrine-induced contraction than phenoxybenzamine alone, suggesting that dexmedetomidine protects aortae from the alpha-1 adrenoceptor blockade induced by phenoxybenzamine. Rauwolscine attenuated the dexmedetomidine-mediated enhancement of phenylephrine-induced eNOS phosphorylation. Taken together, these results suggest that dexmedetomidine attenuates phenylephrine-induced contractions via alpha-1 adrenoceptor blockade and endothelial nitric oxide release in the isolated rat aorta.

Amitraz and its metabolite modulate honey bee cardiac function and tolerance to viral infection.

The health and survival of managed honey bee (Apis mellifera) colonies are affected by multiple factors, one of the most important being the interaction between viral pathogens and infestations of the ectoparasitic mite Varroa destructor. Currently, the only effective strategy available for mitigating the impact of viral infections is the chemical control of mite populations. Unfortunately, the use of in-hive acaricides comes at a price, as they can produce sublethal effects that are difficult to quantify, but may ultimately be as damaging as the mites they are used to treat. The goal of this study was to investigate the physiological and immunological effects of the formamidine acaricide amitraz and its primary metabolite in honey bees. Using flock house virus as a model for viral infection, this study found that exposure to a formamidine acaricide may have a negative impact on the ability of honey bees to tolerate viral infection. Furthermore, this work has demonstrated that amitraz and its metabolite significantly alter honey bee cardiac function, most likely through interaction with octopamine receptors. The results suggest a potential drawback to the in-hive use of amitraz and raise intriguing questions about the relationship between insect cardiac function and disease tolerance.