BACKGROUND: Hypothermic circulatory arrest (HCA) is used during surgical treatment of certain congenital heart defects. The possibility of ischemic neurologic injury associated with HCA has led some surgeons to use low-flow cardiopulmonary bypass (CPB) during the hypothermic interval (hypothermic low flow [HLF]). This study investigates the inflammatory response to HCA and HLF, and reports the consequences of this response on pulmonary and right ventricular function. METHODS: Piglets (3.1 to 6.6 kg) were cooled to 16 degrees to 18 degrees C using CPB, and randomized: HCA for 60 minutes (n = 7), or HLF (50 cc.kg(-1).min(-1)) for 60 minutes (n = 6). The piglets were rewarmed to 36 degrees C and weaned from CPB. Serum tumor necrosis factor-alpha (TNF-alpha) concentration, percent lung water, and pulmonary and cardiac function were measured before and after CPB. RESULTS: Tumor necrosis factor-alpha was higher after HLF (2,990.5 +/- 884.5 pg/mL), compared with HCA (347.6 +/- 89.2 pg/mL; p = 0.03). The percent lung water was higher after HLF (84.8% +/- 0.3%) than HCA (82.0% +/- 0.4%; p < 0.001). The alveolar to arterial oxygen gradient was worse after HLF (457 +/- 42 mm Hg) than HCA (285.8 +/- 45 mm Hg; p = 0.02). Pulmonary vascular resistance was greater after HLF (36.08 +/- 8.28 mm Hg.mL(-1).m(-2).min(-1)) than HCA (14.55 +/- 3.46 mm Hg. mL(-1).m(-2).min(-1); p = 0.049). The right ventricular pressure waveform peak derivative, corrected for systolic pulmonary artery pressure, was lower after HLF (14.1 +/- 1.4 sec(-1)), than HCA (23.8 +/- 2.7 sec(-1); p = 0.01). CONCLUSIONS: Hypothermic low flow extends exposure to CPB, and is associated with an increased inflammatory response compared with HCA. The greater inflammatory response after HLF may result in substantial nonneurologic morbidity in the postoperative period, demonstrated by pulmonary and right ventricular dysfunction. Interventions that attenuate the inflammatory response to CPB may prevent pulmonary and right ventricular dysfunction after HLF.