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

Pingarrón-Martín, Lorena; Arias-Gallo, L.J.

doi:10.1007/s10006-012-0387-9

Cited by 8 publications

(5 citation statements)

References 16 publications

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“… 90 , 91 , 92 , 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 Moreover, a retrospective analysis of clinical studies assessing the potential effect of PDE5i in ED suggests that use of sildenafil improves the outcome of CVD patients 96 and that there should be no safety concerns in the use of this drug in CVD patients.…”

Section: The Therapeutic Potential Of Pde5 Inhibit...mentioning

confidence: 74%

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 Inhibit...mentioning

confidence: 74%

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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“…Local blood supply is essential for the entire healing process. Considering the mechanism of action presented by this class of drugs [ 8 , 14 , 16 , 17 , 48 ], a positive effect was expected at some stage of the scarring process. Blood inflow is not only necessary to supply the recovering wound but also responsible for carrying the first repair and defense cells to the repair site [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…Considering its vasodilatory effect, its current characteristic indications, include sexual dysfunction and pulmonary hypertension. Other benefits from sildenafil-induced vasodilation have been investigated, including studies on the improvement of flap viability, colonic anastomosis, pressure ulcers, fractures, microvascular anastomoses, musculoskeletal injury, and scarring [12][13][14][15][16][17][18][19][20][21][22]. Despite the number of studies on sildenafil application (most studied drug of all drugs of this class) to increase flap viability, some pharmacological features indicate that tadalafil has the highest applicability in random skin flaps [23].…”

Section: Introductionmentioning

confidence: 99%

Effects of sildenafil and tadalafil on skin flap viability

et al. 2021

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Vascular complication is one of the causes of skin flap healing failure. Sildenafil and tadalafil, a type-5 phosphodiesterase inhibitor, can improve flap viability, however, the action mechanisms involved in this process are still unclear. To assess the effects of orally administered sildenafil and tadalafil on the healing kinetics and skin flap viability, sixty-two Wistar rats were divided into three groups: control (n = 22), sildenafil (n = 20), and tadalafil (n = 20). The solutions were administered orally (dose: 10 mg/kg) immediately after the surgical procedure and then every 24 h. At postoperative days 7 and 14, the skin flap samples were collected, submitted to histological processing and evaluated under optical microscopy. In experimental groups (sildenafil and tadalafil), we found an increased vascularization (p < 0.05) on the 7th and 14th day associated with the ulcer size decrease on the 14th day, although it was not significant. There was a higher influx of neutrophils and a decrease of mononuclear population on the 7th day (p < 0.05). On the 14th day, these differences were observed only in the tadalafil group (p < 0.05). This study suggested positive results with the use of sildenafil and tadalafil as adjuvant drugs in skin flap viability.

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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: Discussionmentioning

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

Cited by 8 publications

References 16 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

Effects of sildenafil and tadalafil on skin flap viability

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

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