Drug‐induced vasodilation: In vitro and in vivo study on the effects of lidocaine and papaverine on rabbit carotid artery

Abstract

Flap ischemia is often encountered during pedicled and free tissue transfer. In this study, the vascular effects of varying doses of lidocaine, papaverine, and a combination of the two agents were evaluated and compared in an in vitro and in vivo model in the rabbit carotid artery. In the in vitro study, 14 rings from the rabbit carotid artery were bathed in KrebsRingers solution and stretched progressively to an optimal tension of 3.7-4.2 grams. Their isometric contractile activity was measured. The specimens were precontracted with norepinephrine (1 µM), and a dose response curve was established by adding cumulatively either lidocaine (to 7 arterial rings) or papaverine (to 7 arterial rings) at increasing concentrations. In the in vivo study, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 30 animals using 9-0 nylon suture and standard microsurgical techniques. In each animal, one side was treated with heparinized sodium chloride and served as the control. The other side was treated blindly, during and after the anastomoses, with a topical application of 1 ml of either lidocaine 2% (n = 5), lidocaine 20% (n = 5), papaverine (30 mg/ml, n = 5), lidocaine 2% combined with papaverine (30 mg/ml, n = 5), or lidocaine 20% combined with papaverine (30 mg/ml, n = 5). For 30-60 minutes after the procedure, blood flow changes in the vessels were continuously monitored with a transonic doppler applied to both carotid arteries. The 20% lidocaine group was flushed with saline at the end of the first hour and monitored for an additional 60 minutes. Papaverine elicited a concentration-dependent relaxation of norepinephrine precontracted carotid artery rings in vitro. Lidocaine elicited a biphasic response, with low concentrations (10 −6 -10 −4 M) increasing the norepinephrine-induced contraction and high concentrations (10 −4 -10 −2 M) relieving this contraction. Microsurgical anastomosis produced a significant decrease of blood flow through the rabbit carotid artery as measured by the transonic doppler. Drug application did not alter the systemic blood pressure of the animals. Topical application of lidocaine 2% did not significantly change the blood flow after microvascular anastomosis. Topical application of lidocaine 20%, papaverine (30 mg/ml), or lidocaine (2% or 20%) combined with papaverine significantly increased the blood flow in the rabbit carotid artery. In the lidocaine 20% group, the blood flow remained significantly increased after the drug was flushed with heparinized saline solution. These results demonstrate that topical lidocaine 20%, papaverine, and lidocaine 2% or 20% combined with papaverine significantly increase blood flow in the rabbit carotid artery after microvascular anastomosis. The data confirm the use of papaverine and lidocaine 20%, alone or in combination, as spasmolytics during clinical microsurgery. This suggests that lidocaine 2% alone is not the ideal drug to relieve vascular constriction, and further studies on the clinical use of low concentrations of t...

The Efficacy of Hydrodilatation for the Prevention of Vasospasm following Microsurgical Anastomosis

“…In previous studies papaverine has been shown to result in a significant increase in the diameter of the vessels and prevent vasospasm. 11,20 In our study, we do confirm these results regarding the increase in the vessel diameter following topical application of papaverine following anastomosis. Another advantage of papaverine is its quick onset which is crucial in microsurgery settings.…”

“…Previous studies have shown that papaverine is more effective than lidocaine at low concentrations for inducing vasodilatation. 10,11 In a previous study by Saçak and Sirinoğlu, postoperative saline irrigation of the pedicle was proposed as a new method for preventing vasospasm following microsurgical reconstruction. 12 Saline solution was also used in this current study for hydrodilatation.…”

Vasodilation by Verapamil‐Nitroglycerin Solution in Microvascular Surgery

“…Vessel contraction was induced with lidocaine 2% when applied topically to a rabbit carotid artery 10 . In a subsequent report, the same authors reported that higher concentrations of lidocaine (20%) produced vasodilation similar to that of papaverine in rabbit carotid arteries 19 . Other groups have similarly reported dose‐dependent vasoconstriction caused by lidocaine 20 , 21 .…”

“…10 In a subsequent report, the same authors reported that higher concentrations of lidocaine (20%) produced vasodilation similar to that of papaverine in rabbit carotid arteries. 19 Other groups have similarly reported dosedependent vasoconstriction caused by lidocaine. 20,21 Lidocaine doses of 20% may lead to unwanted systemic toxicity, while lidocaine 2% may lead to vasoconstriction.…”

Topical nitroglycerin for the treatment of intraoperative microsurgical vasospasm

“…With regard to efficacy, papaverine has been shown to cause vasodilation in normal vessels, cause a significant increase in vessel diameter, improve arterial microanastomosis patency relative to saline, provide effective relief of vasospasm (blood flow 116% compared to controls), and some degree of prevention of vasospasm (Evans et al, ; Gherardini et al, ; Hou, Seaber, & Urbaniak, ; Swartz et al, ). Several studies have shown that time to effect with papaverine was less between 1 and 5 minutes following topical application (Evans et al, ; Gherardini et al, ; Hou, Seaber, & Urbaniak, ; Kerschner & Futran, ). Overall, it is easy to see why papaverine is the agent of choice for most microsurgeons; not only is it one of the most studied drugs to treat microvascular vasospasm, but it is an effective spasmolytic agent with a quick onset and a reasonable duration of effect.…”