Background/Objectives: Kienböck disease (idiopathic avascular necrosis of the lunate) is treated almost exclusively surgically; its pharmacological evidence base comprises fewer than five primary publications and ~20 patient-level observations. Femoral-head, jaw, and knee osteonecrosis have decades of evidence, including randomised trials. We ask whether extra-carpal evidence can be translated to Kienböck disease and the wider Carpal Avascular Necrosis Family (lunate, scaphoid/Preiser, capitate, hamate, triquetrum). Methods: We conducted a narrative review reported per SANRA, searching PubMed, CrossRef, Google Scholar and three specialty registries from inception to 2026 across eleven drug classes and eleven skeletal sites. All references were independently verified against primary sources (PubMed/CrossRef). No Kienböck-specific randomised or controlled data exist; all conclusions therefore rest on indirect, extra-carpal evidence. Results: Three pathways (subchondral insufficiency fracture, microvascular ischaemia, hypercoagulability) predict drug-class plausibility differently by site. Iloprost is the candidate most consistently aligned across the translation axes, though no direct lunate data exist; teriparatide provides the only randomised evidence suggesting reversal of established osteonecrosis at any site (medication-related osteonecrosis of the jaw). The lunate sits within a coherent carpal AVN family sharing end-arterial supply, Lichtman-grade trajectories, and a near-identical evidence vacuum. Conclusions: A Four-Axis Translation Framework (mechanistic alignment, anatomic concordance, Lichtman-stage applicability, lunate-specific risk-benefit geometry) is proposed to evaluate which extra-carpal evidence is admissible at the lunate; with the carpal AVN family construct, these are the review's two novel contributions.

6-Cyanodopamine (6-CYD) and 6-nitrodopamine (6-ND) are newly described endogenous catecholamines. However, their presence and vascular actions in rat aorta remain unclear. Thoracic aortas from male Wistar rats were analyzed for basal catecholamine release by LC-MS/MS. Vascular reactivity was assessed in U-46619-precontracted rings with intact or removed endothelium and after pharmacological inhibition with N[ω]-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), indomethacin, SQ-22536, SCH-23390, and haloperidol. Tyrosine hydroxylase (TH) expression was examined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Rat aorta basally released both 6-CYD and 6-ND, with 6-ND levels exceeding 6-CYD. Both catecholamines produced concentration-dependent relaxation, with 6-ND showing greater potency than 6-CYD (pEC50: 8.9 ± 0.5 and 8.5 ± 0.6, respectively). Endothelium removal abolished 6-CYD relaxation and significantly reduced 6-ND relaxation. L-NAME, ODQ, indomethacin, and SQ-22536 significantly inhibited responses to 6-CYD, but not to 6-ND, indicating different mechanisms of action. SQ-22536 also attenuated forskolin- and iloprost-induced relaxation, supporting involvement of adenylyl cyclase/cAMP signaling in 6-CYD responses. SCH-23390 had no effect on 6-CYD- and 6-ND-induced relaxation. Haloperidol reduced the effect of sumanirole- and 6-CYD-induced relaxation but had no effect on 6-ND-induced relaxation, suggesting involvement of D2-like receptor in 6-CYD signaling. Tyrosine hydroxylase protein and mRNA were detected by immunohistochemistry and fluorescent in situ hybridization respectively, in endothelial cells and adventitial neural structures. Rat thoracic aorta basally releases 6-CYD and 6-ND, and although both act as potent vasodilators, they have distinct mechanisms of action. These findings shed new light on mechanisms by which the vascular endothelium regulates vascular tone.

Testicular torsion is a urological emergency that causes ischemia-reperfusion (I/R) injury and may result in irreversible germ cell loss and impaired fertility. Oxidative stress, inflammation, and apoptotic pathways play central roles in its pathogenesis. Transient Receptor Potential Melastatin-7 (TRPM7), a bifunctional ion channel/kinase, has recently been implicated in I/R-related cellular injury. Iloprost, a prostacyclin analogue with vasodilatory and antioxidant properties, may offer protective effects; however, its impact on TRPM7-mediated pathways in testicular I/R injury remains unclear. This study aimed to investigate the effects of iloprost on oxidative stress, apoptosis, and TRPM7 expression in an experimental testicular torsion-detorsion model. Thirty-five male Sprague Dawley rats were randomized into five groups: control, sham, iloprost, torsion-detorsion (T/D), and T/D + iloprost. After 60 min of torsion and subsequent detorsion, iloprost (2 µg/kg, intraperitoneal) was administered in the treatment group. Testicular tissues and serum samples were analyzed after 48 h. Histopathology (H&E), apoptosis (TUNEL assay), TRPM7 immunohistochemistry and mRNA expression (RT-qPCR), and serum total antioxidant status (TAS) and total oxidant status (TOS) were evaluated. Torsion-detorsion significantly increased TOS levels, apoptotic cell ratio (ACR), TRPM7 expression, and Bax mRNA expression, while reducing TAS levels (p < 0.05). Iloprost administration significantly improved oxidative stress parameters, restoring TAS and reducing TOS compared with the untreated T/D group. However, it did not significantly reduce histopathological damage, ACR, TRPM7 expression, or Bax mRNA expression. Bcl-2 expression remained largely unchanged across groups. Iloprost improved systemic oxidative status in testicular I/R injury but did not significantly attenuate TRPM7 expression, apoptotic changes, or structural damage under the experimental conditions used. The concurrent increase in TRPM7 expression and apoptotic indices following torsion-detorsion suggests an association between these alterations; however, the present study does not establish a causal relationship between TRPM7 and apoptosis. As TRPM7 activity was not directly assessed or experimentally manipulated, further studies involving TRPM7 inhibition or genetic silencing are required to determine its mechanistic role in testicular I/R-induced apoptosis.

Background and Objectives: Ischemia-reperfusion (IR) injury to skeletal muscle induces both structural and functional impairments, primarily attributed to increased production of reactive oxygen species and subsequent inflammation following reperfusion. Iloprost (ILO), a stable prostacyclin analog, exerts cytoprotective effects through reduction in oxidative stress as well as by improvement of microvascular function. The purpose of the present study was to investigate the influence of iloprost on Isthmin-1 (ISM-1), adropin and transient receptor potential canonical 6 (TRPC6) immunoreactivity in rat lower extremity muscles in an experimental IR model. Materials and Methods: Thirty male Wistar albino rats, were divided into five groups, each with an equal number of rats; Control, Sham, ILO, IR, and IR + ILO. The ILO group received an intravenous infusion of 2 ng/kg/min ILO. After intracardiac blood was collected, muscle tissue samples were rapidly removed. Serum total oxidant status (TOS) and total antioxidant status (TAS) levels were measured. Histopathological examination of the collected muscle tissue samples was performed using hematoxylin-eosin staining, and immunohistochemical staining was used to assess the immunoreactivity of ISM-1, adropin, and TRPC6. Results: The IR group showed increased serum total oxidant status levels and immunoreactivity for ISM-1, adropin, and TRPC6, while total antioxidant status levels decreased. Compared with the IR group, the IR + ILO group showed decreased serum TOS levels and immunoreactivity for ISM-1, adropin, and TRPC6, while TAS levels increased. Conclusions: Treatment with ILO may have a protective effect on the skeletal muscle of lower extremities exposed to ischemia-reperfusion injury. This effect may be due to a reduction in oxidative stress and the regulation of immunoreactivity of ISM-1, adropin, and TRPC6.

Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition associated with increased perioperative morbidity and mortality, particularly in patients undergoing cardiac or high-risk non-cardiac surgery. Inhaled pulmonary vasodilators (iPVs) offer a targeted strategy to reduce pulmonary vascular resistance (PVR) and improve right ventricular (RV) function while minimizing systemic hypotension. Traditional vasodilators such as nitroglycerin and sodium nitroprusside lack pulmonary specificity and can exacerbate systemic hypotension. Inhaled agents including nitric oxide (NO), epoprostenol (iEPO), iloprost, milrinone (iMIL) and levosimendan provide selective pulmonary vasodilation with more favorable hemodynamic profiles. This narrative review summarizes current evidence and clinical considerations for the use of iPVs in the perioperative management of PH and discusses pharmacokinetics, delivery mechanisms, adverse effects, and logistical considerations for these agents. New emerging PH therapies are included based on early clinical trial data as they have the potential to impact perioperative care in the future. Overall, iPVs represent a valuable tool in the perioperative care of patients with PH. Continued research is needed to refine clinical protocols, evaluate emerging agents, and establish outcome-based evidence for their routine use.

Prostacyclin (PGI2, epoprostenol) and its more stable analogues iloprost and cicaprost are used in the treatment of pulmonary arterial hypertension (PAH) and other related diseases. Currently, PGI2 therapy is the most effective treatment for PAH, but is administered intravenously due to its instability under physiological conditions. We considered creating more chemically stable hybrids of PGI2 by merging essential features of iloprost/cicaprost with a more stable C-7 fluorinated PGI2, which maintained the cyclic enol ether. The synthesis employed our key bicyclic enal and furnished the required PGI2 analogues in just 7-8 steps, providing the most expedient route to this class of molecules. This led to the discovery of compound 9, a picomolar-potent, IP receptor-selective, and chemically stable PGI2 analogue that combined the ω-side chain of cicaprost with the C-7 difluorinated enol ether of PGI2. This compound provides the most potent PGI2 analogue tested to date.

Severe frostbite is a dynamic microvascular injury that can progress to delayed tissue loss despite appropriate initial care. Contemporary management emphasizes rapid rewarming, antithromboxane therapy, clinical grading, selective thrombolysis, and prostacyclin-based treatment. Iloprost is the prostacyclin analogue most often described, but access may be delayed in some Canadian settings. We developed and implemented a monitored intravenous epoprostenol pathway for Cauchy grade 2-4 frostbite and retrospectively evaluated 23 patients treated between December 2017 and November 2025. The pathway incorporated rapid rewarming, grading, topical and systemic antithromboxane therapy, eligibility criteria, dose titration, physiologic monitoring, dose modification, multidisciplinary care, and follow-up. Overall, 153 of 216 affected digits were preserved. Preservation varied by severity: 62 of 65 grade 2 digits, 74 of 100 grade 3 digits, and 7 of 41 grade 4 digits were preserved. Twelve patients avoided amputation altogether. Mean treatment duration was 3.8 days, and most patients reached 8 ng/kg/min at least once. Documented adverse effects or dose-limiting symptoms occurred in 9 patients and were managed with dose reduction or temporary interruption. Available records did not identify thrombolytic therapy, permanent discontinuation for adverse reaction or grade 2 reassessment, or serious drug-attributed adverse events. Protocol-guided intravenous epoprostenol was feasible and generally well tolerated. Findings should be interpreted as descriptive and hypothesis-generating rather than evidence of treatment efficacy.

Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostacyclin and their analogues are widely used in clinical practice for their potent biological effects. PGE1/PGE2 analogues, including misoprostol and sulprostone, are primarily used in obstetrics for labour induction, abortion, and postpartum haemorrhage management, whereas PGI2 analogues such as iloprost and treprostinil are key drugs in pulmonary arterial hypertension treatment. Despite structural similarities, these compounds produce contrasting vascular effects due to differences in receptor selectivity, signalling pathways, and tissue distribution. PGE1/PGE2 analogues activate EP receptors, particularly EP1 and EP3 with varying selectivity profile, promoting vasoconstriction and have been associated with cardiovascular complications such as coronary vasospasm. In contrast, PGI2 analogues act mainly on IP receptors, promoting vasodilation, inhibition of platelet aggregation, and beneficial vascular remodelling, with a generally favourable cardiovascular safety profile. Although cardiovascular effects have been reported with both classes of analogues, the underlying mechanisms, and especially their direct effects on human coronary arteries (HCA) remain insufficiently explored. In this context, we combined a review of the clinical and experimental literature that integrates clinical reports with original ex vivo pharmacological investigations on isolated HCA. Both PGE2 and misoprostol induce concentration-dependent vasoconstriction, primarily via EP3 receptors, which is significantly reduced by a TP receptor antagonist, suggesting a potential EP3-TP pathway interaction. All tested PGI2 analogues consistently induced relaxation in our HCA preparations, a finding that aligns with their general improvement of cardiovascular clinical parameters, with only rare exceptions. Together, these findings summarize the cardiovascular effects of clinically-used prostanoids and provide mechanistic insights to optimize their therapeutic use while minimizing cardiovascular risk.