Renal Hypoxanthine Balance in Cardiac Surgery: Effects of Felodipine Anders Jeppsson, MD, PhD, Lars-G6ran Andersson, MD, PhD, Rolf Ekroth, MD, PhD, and Per-Olof Joachimsson, MD, PhD Objective: To test the hypothesis that felodipine, a renal vasodilator, can prevent a release of hypoxanthine during rewarming after moderate hypothermic cardiopuimonary bypass and that this is related to improved renal oxygen supply. Design: A prospective, randomized, and controlled study. Setting: Operating room in the cardiothoracic surgery department of a university hospital. Participants: Twenty-two patients submitted to elective first-time coronary bypass surgery. Interventions: A catheter was placed in the left renal vein for thermodilution renal blood flow (RBF) measurement and blood sampling. In 11 patients, felodipine was infused during the hypothermic period of cardiopulmonary bypass. Measurements and Main Results: Renal uptake (renal arte- riovenous concentration difference x RBF) of hypoxanthine was maintained during rewarming in felodipine-treated patients but not in control patients (55 _+ 28 v -39-+ 1 nmol/min, p < 0.05). Oxygen consumption was higher after felodipine infusion despite unchanged total RBF. A positive correlation between renal oxygen consumption and hypoxan- thine uptake and release (r = 0.74, p < 0.01) was observed. Conclusions: Felodipine maintained renal uptake of hypo- xanthine during rewarming after hypothermic cardiopulmo- nary bypass. This maintenance is the effect of improved renal oxygen supply secondary to improved nutritive blood flow at the expense of nonnutritive renal blood flow, Copyright © 1999 by W.B. Saunders Company KEY WORDS: cardiac surgery, cardiopulmonary bypass, re- nal function, felodipine, hypoxanthine A CUTE RENAL FAILURE remains an important complica- tion in cardiac surgery.. ~The main cause is believed to be renal hypoperfusion and ischemia. 1,2 It was previously demon- strated that renal vascular resistance (RVR) is increased (in relation to systemic vascular resistance [SVR]) during cardiac surgery. 3 This increase leads to a smaller fraction of cardiac output perfusing the kidneys. In addition, blood pressure and renal blood flow (RBF) autoregulation is not operative during cardiopulmonary bypass (CPB). 3 These factors conceivably predispose for the development of renal hypoperfusion and ischemia. Furthermore, it was reported that the normally occurring renal uptake of hypoxanthine was transformed into a release during rewarming in most patients undergoing cardiac surgery. 4 A release of hypoxanthine generally represents the breakdown of energy-rich purine nucleotides and signifies impaired energy supply and demand balance. 5 This observation suggests that the rewarming period may be at particular risk for the development of perioperative renal ischemia. Based on these considerations it was hypothesized that the perioperative use of a vasodilating agent, such as the calcium channel hlocker felodipine, could prevent the release of hypoxanthine during rewarming and that this prevention was related to improved renal perfusion and oxygen supply. PATIENTS AND METHODS Twenty-two men fulfilling the inclusion criteria (preoperative. serum creatinine <130 omol/L, no renal or other disorder apart from atherosclerosis, 50 to 69 years of age, body weight of 60 to 99 kg, and undergoing elective first-time coronary bypass surgery) participated in the study. The patients were randomly allocated to one of two groups. One group (n = 11) received infusion of felodipine during the second half of the hypothermic CPB period. The other group (n = 11) received vehicle only and served as controls. Patient characteristics are l:istedin Table 1. The study protocol was approved by the Research Ethics Connnittee of the Medical Faculty, University of Uppsala, and informed consent was given by all patients. The patients were premedicated with morphine and scopolamine. Anesthesia was induced with fentanyl (5 to 10 ~tg/kg), thiopental (2 to 4 mg/kg), and pancuronium (0.1 mg/kg) and maintained with enflurane in oxygen and air (with an oxygen fraction of 40% to 50% before and 100% after CPB). Additional fentanyl doses were given when needed (1 to 20 lag&g). In five cases (two in control patients and three in the group later receiving felodipine), nitrous oxide was used before CPB. During CPB, isoflurane was used instead of enflurane. The operations were performed with a standard nonpulsatile CPB, with moderate hypothermia (nasopharyngeal temperature 28°C) and hemodilution (hematocrit 20% to 30%). Acid-base management was in accordance with the alpha-stat principle. 6 Heparin was used for anticoagulation (300 U/kg plus 7,500 U in CPB prime solution). Cardioprotection was achieved with St Thomas' crystalloid cardiople- gia. Cardioplegia, 1,000 mL, was infused after aortic cross-clamping followed by additional doses of 300 to 400 mL every 20 minutes or when the myocardial temperature exceeded 20°C. Weaning from CPB was performed after rewarming to a rectal temperature of at least 35°C. Renal function measurements were made at five preset periods, each of 8 to 10 minutes' duration: Period 1--after induction of anesthesia Period 2--CPB with flow rate 2.20 L/min/m 2 at 28 °C Period 3---CPB with flow rate 2.20 L/mirdm 2 at 28°C Period 4---CPB during rewarming at a nasopharyngeal temperature of 37°C Period 5--immediately after CPB Each period started with measurement of RBF followed by simulta- neous arterial and renal venous blood sampling. After the second measurement period, the patients were randomized into groups that received either intravenous infusion of felodipine or vehicle only during the third measurement period. The infusion rate of felodipine was 0.1 rag/rain during the first 3 minutes and thereafter 0.01 mg/min, which is the recommended dose in the treatment of hypertension. The desired serum concentration is greater than 6 nmol/L.7 The third measurement From the Department of Thoracic and Cardiovascular Surgery, Sahlgrenska University Hospital, GOteborg; and Departments of Clini- cal Physiology and Anesthesiology, Uppsala University Hospital, Uppsala, Sweden. Supported by grants from Uppsala University Hospital, Sahlgrenska University Hospital, Gtteborg Medical Society, and Hdssle Ltd, Mb'ln- dal, Sweden. Address reprint requests to Anders Jeppsson, MD, PhD, Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden, Copyright © 1999 by W.B. Saunders Company 1053-0770/99/1306-0012510.00/0 Journal of Cardiothoracic and Vascular Anesthesia, Vo113, No 6 (December), 1999: pp 715-719 715