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Ann Thorac Surg 1996;62:769-771
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Effect of Normothermic Papaverine to Relieve Intraoperative Spasm of the Internal Thoracic Artery

Fuat Bilgen, MD, M. Fikri Yapici, MD, Aykut erbetçiolu, MD, I. Arif Tarhan, MD, Türkan Çoruh, MD, Azmi Özler, MD

Departments of Cardiovascular Surgery and Anesthesiology, Siyami Ersek Thoracic and Cardiovascular Surgery Center, Istanbul, Turkey

Accepted for publication April 30, 1996.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Background. After mobilization, vasospasm often reduces flow through the internal thoracic artery. An established method of relaxing the artery and increasing flow is to use papaverine at ambient temperature (20° to 22°C) as a topical vasodilator. However, the pharmacologic actions of papaverine generally have been assessed at 37°C.

Methods. In 60 patients in whom the left internal thoracic artery was used for myocardial revascularization, we investigated the effects of normal saline solution at 20°C (group I), papaverine at 20°C (group II), and papaverine at 37°C (group III). Under controlled hemodynamic conditions, free flow was measured before any pharmacologic intervention and a median of 16 minutes after the pedicle had been sprayed with one of the agents.

Results. Normal saline solution at 20°C produced a small increase in flow from 37.5 ± 8.1 mL/min to 50 ± 10.2 mL/min. A significant increase occurred with papaverine at 20°C, from 38.05 ± 6.5 mL/min to 78.75 ± 21.2 mL/min (p< 0.0001). Papaverine at 37°C, however, produced an increase in flow from 36.9 ± 12.6 mL/min to 103.3 ± 44.6 mL/min (p < 0.0001) and proved to be more effective than papaverine at room temperature (p = 0.0174).

Conclusions. We recommend topical use of papaverine at 37°C to relieve intraoperative spasm of the internal thoracic artery.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
The internal thoracic artery (ITA) is the conduit of choice for coronary artery operations because it has a better long-term patency rate than saphenous vein grafts [1–3]. Numerous references have suggested that survival is superior when the left ITA rather than a saphenous vein is used to graft the left anterior descending coronary artery [1, 3, 4]. Operative preparation of the ITA often results in vasospasm with reduction in early graft flow, which could cause perioperative morbidity and even death in high-risk patients [5]. An established method of dealing with this problem is to spray papaverine solution on the ITA graft and to wrap the artery in a papaverine-soaked swab before grafting.

Papaverine is frequently used during surgical procedures at ambient temperature (20° to 22°C), whereas the pharmacologic actions of papaverine generally have been assessed at 37°C [6–10]. In this study, therefore, we compared the effects on ITA free flow of normal saline solution at room temperature, papaverine at room temperature, and papaverine at 37°C to identify the best method for the treatment of ITA spasm.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
We studied 60 patients whose left ITA was mobilized and who were undergoing elective coronary artery bypass operation (Table 1). All patients received calcium antagonists, ß blockers, and nitrates until the date of operation. Each patient was randomly allocated to one of three equal-sized groups. The ITA was dissected on a pedicle, from the subclavian vein to just beyond the bifurcation into the superior epigastric and muscular phrenic arteries, with the aid of diathermy and metal ligature clips. Five minutes after systemic heparin treatment, the artery was divided distally and the first flow was determined by measuring the volume of blood expelled from the end of the bleeding artery in a 30-second period. Time of measurement, heart rate, and mean arterial and central venous pressures were also recorded. The tip of the artery was occluded with a bulldog clamp, and the artery, with the nonfascial surface anterior, was laid on a moist swab beneath the left sternal edge.

The topical solutions consisted of the following: (1) normal saline solution at room temperature (20°C), 4 mL of 0.9% sodium chloride solution; (2) papaverine at room temperature (20°C), 6 mg in 4 mL of 0.9% sodium chloride solution; and (3) papaverine at 37°C, 6 mg in 4 mL of 0.9% sodium chloride solution.

This study was approved by the ethics and scientific committee on February 8, 1994.

All values are expressed as mean ± standard deviation. Differences between the groups in the flow measurements were determined by Student's t test and analysis of variance. A p value < 0.05 was considered statistically significant.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Sex ratios and ages of the three groups are shown in Table 1.

The differences among groups in body surface area and time between flow measurements were not significant (p > 0.05). Heart rates, mean arterial pressures, and central venous pressures at the time of the first and second flow measurements were not significantly different (p > 0.05), either within or between groups (see Table 1).

Medians of the first and second flow measurements for each method are shown in Table 2. There was no significant difference among the first flow rates of the three groups. Normal saline solution at 20°C produced a small increase in flow from a median of 37.5 ± 8.1 mL/min to 50 ± 10.2 mL/min (p < 0.05).

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
The ITA is frequently in spasm with reduced flow immediately after mobilization. Spontaneous relaxation does not occur in the time between the end of mobilization and the start of cardiopulmonary bypass. To solve this problem, papaverine is frequently used at ambient temperature (20° to 22°C). Papaverine causes relaxation by blocking the intracellular enzyme phosphodiesterase in vascular smooth muscle cells. This prevents the breakdown of cyclic 3`,5` adenosine monophosphate, which promotes vascular smooth muscle relaxation. Because enzyme activity is progressively reduced at lower temperatures, blocking of phosphodiesterase by papaverine may result in less relaxation at ambient temperature than at 37°C. Studies have shown papaverine to be an effective dilator of isolated animal blood vessels at 37°C [6–10]. Rusch and colleagues [11] have shown that papaverine is a slower and less potent dilator of canine saphenous veins at 25°C than at 37°C. That study did not examine the effect of papaverine at 37°C to relieve intraoperative spasm of the ITA.

The concentration of papaverine used in this study was that proposed by Mills and Bringaze [12]. A volume of 4 mL was adequate to cover the ITA pedicle. He and co-workers [13], in an in vitro study, found that glyceryl trinitrate was more potent than papaverine in relaxing preconstricted segments of human ITA. Nifedipine also produced maximal relaxation, but took longer than glyceryl trinitrate to achieve this. Cooper and co-workers [14] compared the effects on ITA free flow of normal saline, papaverine, nifedipine, glyceryl trinitrate, and sodium nitroprusside. They found that the most effective vasodilator was sodium nitroprusside. In this study, all topical vasodilators were used at room temperature (18° to 20°C). In another study, the ability of various vasodilators to inhibit ITA contraction was investigated using discarded segments of human ITA that were not used in coronary artery bypass grafting [15]. This study concluded that papaverine should be used for the treatment of vasospasm seen during isolation of the ITA intraoperatively, whereas nifedipine may be a better drug for the treatment or prevention of perioperative ITA spasm.

Several other means to improve flow through the ITA have been suggested. Among these are gentle massage of the pedicle or the use of an appropriate-sized probe or a balloon catheter to dilate the entire length of the artery. More recently, intraluminal dilation with papaverine has been shown to produce a dramatic increase in ITA free flow to a mean value of 229 mL/min [12]. However, van Son and co-workers [16] have shown that hydrostatic dilation of the internal mammary, musculophrenic, and superior epigastric arteries may have detrimental effects on the histologic characteristics of the intima and the internal elastic lamina. They advocated wrapping the ITA with a papaverine-soaked sponge as an appropriate technique to increase ITA flow.

In conclusion, papaverine is frequently used as a topical vasodilator for treatment of ITA spasm intraoperatively at ambient temperature (20° to 22°C). The mechanism of papaverine-induced relaxation involves inhibition of enzyme activity, which is a temperature-dependent process. Our findings show that papaverine at 37°C is a more effective topical vasodilator for ITA free flow than is papaverine at 20°C.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Address reprint requests to Dr Bilgen, Ataehir 65 ADA, Mimoza Apt. 3-6 Da, 14 81120, Küçükbakkalköy, Istanbul, Turkey.

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bilgen, F. Articles by Özler, A. Search for Related Content PubMed PubMed Citation Articles by Bilgen, F. Articles by Özler, A.