Sildenafil effect on prevention of thrombosis after microsurgical anastomosis: experimental rat model of thrombotic suture

Pingarrón-Martín, Lorena; Arias-Gallo, L.J.; Chamorro-Pons, Manuel

doi:10.1016/j.ijom.2013.07.409

Cited by 3 publications

(4 citation statements)

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“…Its ameliorating outcomes in patients with ED depend on its vasodilating properties, which are beneficial also in other clinical settings including cardiovascular disease (CVD) 90–93 . In preclinical studies, PDE5 inhibitors’ effects on thrombosis have been examined in an experimental rat model of thrombotic suture suggesting a benefit in applying sildenafil in the anastomosis with already present thrombogenic disease 94 . The same effect is shown in clinical studies in which sildenafil reduced thrombosis, thromboembolic events, and the risk of thrombotic strokes in patients during low‐level hemolysis (LLH) on HeartMate II support 95 .…”

Section: The Therapeutic Potential Of Pde5 Inhibitors In Platelet Dis...mentioning

confidence: 99%

The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders

Degjoni

Campolo

Stefanini

et al. 2022

Journal of Thrombosis and Haemostasis

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Platelets are the “guardians” of the blood circulatory system. At sites of vessel injury, they ensure hemostasis and promote immunity and vessel repair. However, their uncontrolled activation is one of the main drivers of thrombosis. To keep circulating platelets in a quiescent state, the endothelium releases platelet antagonists including nitric oxide (NO) that acts by stimulating the intracellular receptor guanylyl cyclase (GC). The latter produces the second messenger cyclic guanosine‐3′,5′‐monophosphate (cGMP) that inhibits platelet activation by stimulating protein kinase G, which phosphorylates hundreds of intracellular targets. Intracellular cGMP pools are tightly regulated by a fine balance between GC and phosphodiesterases (PDEs) that are responsible for the hydrolysis of cyclic nucleotides. Phosphodiesterase type 5 (PDE5) is a cGMP‐specific PDE, broadly expressed in most tissues in humans and rodents. In clinical practice, PDE5 inhibitors (PDE5i) are used as first‐line therapy for erectile dysfunction, pulmonary artery hypertension, and lower urinary tract symptoms. However, several studies have shown that PDE5i may ameliorate the outcome of various other conditions, like heart failure and stroke. Interestingly, NO donors and cGMP analogs increase the capacity of anti‐platelet drugs targeting the purinergic receptor type Y, subtype 12 (P2Y12) receptor to block platelet aggregation, and preclinical studies have shown that PDE5i inhibits platelet functions. This review summarizes the molecular mechanisms underlying the effect of PDE5i on platelet activation and aggregation focusing on the therapeutic potential of PDE5i in platelet disorders, and the outcomes of a combined therapy with PDE5i and NO donors to inhibit platelet activation.

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Section: The Therapeutic Potential Of Pde5 Inhibitors In Platelet Dis...mentioning

confidence: 99%

The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders

Degjoni

Campolo

Stefanini

et al. 2022

Journal of Thrombosis and Haemostasis

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“…In addition to surgical and technical factors, the success of microsurgery is closely related to patients' health status, health problems, and medications. Several studies have examined the effects of various substances, including low-molecular-weight heparin, steroids, sildenafil, and vinblastine, on enhancing microvascular anastomosis patency [1][2][3][4][5][6]. However, the benefits of these substances have not been proven.…”

Section: Fig 1 Organized Thrombusmentioning

confidence: 99%

“…Dextran, heparin, low-molecular-weight heparin, and steroids are commonly administered in clinical practice to prevent thrombus formation. Several drugs, including vinblastine, sildenafil, and botulinum toxin, have been used to increase anastomosis patency in experimental studies; however, the clinical applications of these drugs are currently limited [1,2,5,6].…”

Section: Introductionmentioning

confidence: 99%

Antithrombotic effect of epigallocatechin gallate on the patency of arterial microvascular anastomoses

et al. 2019

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Background Microvascular anastomosis patency is adversely affected by local and systemic factors. Impaired intimal recovery and endothelial mechanisms promoting thrombus formation at the anastomotic site are common etiological factors of reduced anastomosis patency. Epigallocatechin gallate (EGCG) is a catechin derivative belonging to the flavonoid subgroup and is present in green tea ( Camellia sinensis ). This study investigated the effects of EGCG on the structure of vessel tips used in microvascular anastomoses and evaluated its effects on thrombus formation at an anastomotic site. Methods Thirty-six adult male Wistar albino rats were used in the study. The right femoral artery was cut and reanastomosed. The rats were divided into two groups (18 per group) and were systemically administered either EGCG or saline. Each group were then subdivided into three groups, each with six rats. Axial histological sections were taken from segments 1 cm proximal and 1 cm distal to the microvascular anastomosis site on days 5, 10, and 14. Results Thrombus formation was significantly different between the EGCG and control groups on day 5 (P=0.015) but not on days 10 or 14. The mean luminal diameter was significantly greater in the EGCG group on days 5 (P=0.002), 10 (P=0.026), and 14 (P=0.002). Intimal thickening was significantly higher on days 5 (P=0.041) and 10 (P=0.02). Conclusions EGCG showed vasodilatory effects and led to reduced early thrombus formation after microvascular repair. Similar studies on venous anastomoses and random or axial pedunculated skin flaps would also contribute valuable findings relevant to this topic.

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“…Sildenafil citrate is being used for different indications as erectile dysfunction and pulmonary hypertension. There have been studies investigating the effect of sildenafil on flap survival, colon anastomosis, pressure ulcers, fracture, microvascular anastomoses, skeletal muscle injury and incisional wound healing [3,[12][13][14][15][16][17][18]. Effect of sildenafil on wound healing by secondary intention has not been researched before.…”

Section: Introductionmentioning

confidence: 99%

Effect of topically applied sildenafil citrate on wound healing: experimental study

Gürsoy

Oruç²,

Kankaya³

et al. 2014

Biomol Biomed

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Wound healing is a complex process that necessitates organization of different cell types and several signalling molecules. The aim of this study is to evaluate the effect of different concentrations of sildenafil citrate, which decreases cGMP degradation, on wound healing by secondary intention.This study was performed using 25 Sprague Dawley rats weighing 200-250 grams. 4 dorsal defects were created. Four different treatment modalities which were 1% and 5% sildenafil citrate gel prepared with carbopol, pure carbopol gel without any drug in it and 0,9% NaCl solution; were applied to each lesion of the same rat. Randomly selected five rats (25 rats in total) were sacrificed on 3rd, 5th, 7th, 10th, and 14th days; and the effect of each modality was evaluated by means of defect area measurement, histopathological examination and measurement of tissue hydroxyproline levels.Sildenafil citrate gel application decreased the defect areas in a dose independent manner starting from 3rd day and dose dependent manner after 7th day. By means of vascularization, sildenafil citrate increased vascularity starting from 3rd day. The strength of acute inflammation was superior in sildenafil groups starting from 5th day; and the amount and maturation of granulation in the wound bed, as well as the strength of chronic inflammation were superior in defects treated with sildenafil citrate as early as 7th day.

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Sildenafil effect on prevention of thrombosis after microsurgical anastomosis: experimental rat model of thrombotic suture

Cited by 3 publications

References 0 publications

The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders

The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders

Antithrombotic effect of epigallocatechin gallate on the patency of arterial microvascular anastomoses

Effect of topically applied sildenafil citrate on wound healing: experimental study

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