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Ann Thorac Surg 2001;71:138-141
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

Comparison of systemic vasodilators: effects on flow in internal mammary and radial arteries

^a Department of Anesthesia, E. Wolfson Medical Center, Holon, Israel
^b Department of Cardiothoracic Surgery, E. Wolfson Medical Center, Holon, Israel

Accepted for publication July 15, 2000.

Address reprint requests to Dr Cohen, Department of Cardiothoracic Surgery, E. Wolfson Medical Center, Holon, 58001 Israel
e-mail: sally{at}wolfson.health.gov.il

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. Spasm is a major concern with the use of arterial conduits in coronary artery bypass surgery (CABG). We evaluated the effect of systemic vasodilators on in vivo radial artery flow compared with internal mammary artery (IMA) flow.

Methods. Fifty patients undergoing primary CABG with a mean age of 69 ± 5 years enrolled in this study and were randomized to 1 of 5 groups based on the vasodilating agent administered (nitroglycerin, nitroprusside, dobutamine, milrinone, and normal saline as control group). Radial artery and IMA flows, blood pressure, central venous pressure, and heart rate were measured before and 10 minutes after drug administration.

Results. Mean arterial pressure decreased significantly after drug administration in both the nitroglycerin (p = 0.007) and nitroprusside (p < 0.001) groups and increased in the dobutamine group (p < 0.001). There were no significant differences between IMA flow or radial flow among the groups before drug administration. A multivariate general linear model was created and revealed drug (specifically nitroglycerin) as the only predictor to increase flow in the IMA (p < 0.001) or the radial artery (p = 0.009).

Conclusions. We conclude that intravenous nitroglycerin causes in vivo vasodilatation of both the IMA and radial artery and is a good systemic vasodilator to be given when harvesting these two conduits.

	Introduction

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The increased patency rate of the internal mammary artery (IMA) graft and its association with improved survival has induced surgeons to use other arterial grafts [1–4]. As such, the use of the radial artery as an alternative conduit for coronary artery bypass grafting (CABG) has increased [4, 5–7]. A major concern with the use of this conduit is spasm, which can lead to acute ischemia and may contribute to reduced late patency [8–10]. The effect of topical and systemic vasodilators on IMA flow in vivo have been well investigated [11–14]. The effect of systemic vasodilators on in vivo radial artery flow has not been studied. The purpose of this study was to evaluate the effect of systemic vasodilators on the radial artery compared with left IMA.

	Material and methods

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Fifty patients undergoing primary CABG were enrolled in the study. Patients were included in the study if they met the following criteria: (1) age less than 75 years, (2) ejection fraction (EF) more than 45%, (3) no clinical evidence of congestive heart failure (CHF), (4) creatinine less than 2.0 mg/100 mL, (5) no evidence of significant chronic obstructive lung disease, and (6) normal liver function. Patients who met these criteria were randomized into 1 of 5 groups of 10 patients each based on the vasodilating agent administered. Each patient’s physiologic monitoring included blood pressure (BP), heart rate (HR), and central venous pressure (CVP).

Anesthesia was induced with fentenyl 0.015 to 0.01 mg/kg, midazolam 0.05 to 0.1 mg/kg, and nurcuron 0.1 mg/kg. Anesthesia was maintained with fentenyl, isoflorane, and nurcuron as needed. All patients were explored through a median sternotomy. The mammary artery was harvested with a 2-cm pedicle using diathermy and hemoclips (Ligaclip; Ethicon, Cincinnati, OH) to control side branches. The radial artery was dissected as a pedicle from the brachial fossa to the wrist. The artery was dissected with diathermy and hemoclips were used to control side branches. Each patient was heparinized with 3 mg/kg and both arteries were transected. The IMA was transected proximal to the bifurcation. Each artery was allowed to bleed freely for 30 seconds, and this was defined as preoperative flow. Simultaneously, BP, HR, and CVP were measured and recorded as preoperative measurement.

After these measurements, depending upon the assigned group, the patient received either nitroglycerin 0.5 to 3 mic/kg^-1/min^-1 for 10 minutes (Nitrocine; Schwarz Pharma, Mannheim, Germany), dobutamine 1 to 3 mic/ kg^-1/min^-1 for 10 minutes (Butamine; Taro, Haifa Israel), nitroprusside 0.2 to 2 mic/kg^-1/min^-1 for 10 minutes (Niprus; Schwarz Pharma, Mannheim, Germany), milrinone 50 mic/kg over 2 minutes, and nothing for 8 minutes (Primacor; Sanofi, New York, NY), or normal saline solution (0.9%) NaCl 10 mL/h for 10 minutes (0.9% sodium chloride solution; Travenol Laboratories, Ashdod, Israel). Each drug was introduced at the minimal dose and raised to the maximal dose within its range that did not cause an adverse hemodynamic effect. A hemodynamic effect was defined as a change in HR or pulse pressure more than 10%. The drugs reached maximal doses in all but the nitroprusside patients. Ten minutes after starting the drug, including milirone, the flows in the IMA and radial artery were measured again (postoperative flow). Hemodynamic measurements taken at the time were defined as postoperative measurement.

The ratios between postoperative measurement to preoperative measurement and postoperative flow to preoperative flow were calculated for each set of variables.

Statistical analysis
Data are presented as mean ± SD for continuous variables and as the number of occurrences for noncontinuous variables. Two-tailed Student’s t test was used to compare differences between variables at time 1 and time 2 within each drug group. One way analysis of variance (ANOVA) or ² were used as appropriate to compare differences between groups. The influence of different potential variables on flow ratios were studied by a multivariate general linear model. A value of p less than 0.05 was used to indicate significance.

	Results

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There was a significantly higher preoperative mean arterial pressure (MAP) in the group receiving nitroglycerin, and there was a significant drop in MAP in this group from preoperative measurement to postoperative measurement (p = 0.007). All other groups had similar preoperative MAPs. An increase in postoperative MAP was measured in the dobutamine group (p < 0.001) and a decrease in the nitroprusside group (p < 0.0001). There was no difference among the groups for preoperative HR or postoperative HR (Table 1). Dobutamine caused an increase in HR from preoperative to preoperative measurements (p < 0.0001). There were no significant differences among the groups for preoperative CVP. Milrinone caused a significant decrease in CVP from the preoperative to the postoperative measurements (p < 0.0001; Table 1).

View larger version (30K): [in this window] [in a new window]   Fig 1. Pretreatment and posttreatment left internal mammary artery (LIMA) flow (A) and radial flow (B) according to treatment group. The p values of each pretreatment and posttreatment pair are based on a paired t test.

	Comment

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Both the IMA and radial arteries are midsize musculoskeletal arteries with the potential for vasoconstriction [15, 16]. Histologically, the radial artery has a wider lumen but thicker media with many leiomyocytes [17] and deficiencies of the internal elastic lamina [4]. Pharmacologically, the response to vasoconstriction in vitro is greater in the radial artery than the mammary artery [15, 16]. The maximal vasoconstrictive response of the radial artery to noradrenalin is twice that of the IMA [4].

Vasodilators are thought to prevent vasospasm in the radial artery [4]. The use of verapamil and nitroglycerin solutions on the harvested radial artery has been shown to cause vasodilation [18]. In vitro studies have shown milrinone able to inhibit radial artery contraction by pretreatment and to relax a precontracted radial artery [15]. When using the radial artery during CABG, systemic vasodilators during surgery are considered to be important by most surgeons [4, 15]. There are strong recommendations for administering calcium-channel blockers postoperatively when using the radial artery as a conduit for coronary grafts [5].

Our study is the first to simultaneously compare in vivo flow of the IMA and radial artery. It is also the first to evaluate the in vivo effect of systemic vasodilators on radial artery flow. Our study shows that the flow before vasodilating drug administration is higher in the radial artery compared with the IMA. This could be explained by the physical properties of the radial artery with its wider lumen. This fact will not relate to flow through the coronary grafts, as the flow is more dependent upon distal run-off [19].

Both the IMA and radial artery respond to systemic nitroglycerin with an increase in flow. We have previously shown this effect with nitroglycerin in a study [11] involving the IMA only, and the current findings reinforce the previous study’s findings. We had previously postulated that only nitroglycerin, as opposed to other vasodilators, had an in vivo effect on the IMA flow because we resected the distal muscular part of the IMA [11]. Therefore, it was surprising to us to find that nitroglycerin was the only vasodilator to increase flow in the relatively muscular radial artery. We were particularly surprised that milrinone had no effect, since it has been shown to vasodilate the radial artery in vitro [4]. It is noteworthy that nitroprusside increased the flow of both arteries at very low doses. A larger dose of nitroprusside probably would have shown a statistical increase of flow in the radial artery in the multivariate analysis. However, the systemic hypotension caused by increased doses of nitroprusside make this finding clinically insignificant.

This study has some significant limitations. First, the flow through the IMA and radial arteries can vary significantly from moment to moment. As such, a single measurement of each of these flows may have a wide margin of error. Second, the cardiac index was not measured in this study, and hence we do not have a calculated systemic vascular resistance as well. That is partially negated by the fact that it has been previously shown that mammary flow is related more to MAP and midsize vessel spasm [11] than to measurements of cardiac index and systemic resistance. Third, the preoperative MAP of the nitroglycerin group was significantly higher than the other groups despite randomization. That is negated by the fact that this factor was not significant in the multivariate analysis. In addition, the high preoperative MAP should have improved the preoperative flow, which would have blunted our positive findings, if it affected the results at all.

With these limitations in mind, we conclude that intravenous nitroglycerin causes in vivo vasodilation of both the IMA and radial arteries and is a good systemic vasodilator to be given when harvesting these two conduits for CABG.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
The authors thank Sally Esakov for editorial assistance.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) 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 Author home page(s): Benjamin Medalion Amram J. Cohen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zabeeda, D. Articles by Cohen, A. J. Search for Related Content PubMed PubMed Citation Articles by Zabeeda, D. Articles by Cohen, A. J. Related Collections Cardiac - pharmacology Coronary disease