Abstract 3316: Low Flow Reperfusion in the Ischemic Blood-Perfused Isolated Heart
The standard Langendorff isolated buffer-perfused heart model has significant physiologic limitations in the study of ischemia and reperfusion primarily due to its limited oxygen carrying capacity and the absence of neutrophils. We utilized a small volume autologous whole blood-perfused isolated rat heart model to test the hypothesis that, low flow reperfusion following ischemia but prior to full flow reperfusion improves recovery of left ventricular (LV) function.
Methods: In anesthetized Sprague Dawley rats (400–450g), the femoral artery and jugular vein were cannulated and 40 ml/kg of autologous blood was withdrawn and replaced concurrently with saline. The blood was added to a recirculating circuit, which included water-jacketed tubing warmed to 37.0° C, a silicone membrane oxygenator and a reservoir. Hearts were immediately excised and perfused on the circuit. Hearts were divided into three groups; 25 min of ischemia before full reperfusion (CTRL group) or 15 min of ischemia followed by low flow at 1% (1% group) or 10% (10% group) of baseline coronary flow for 10 min and then full flow reperfusion. All hearts received full flow reperfusion for 60 min. LV function was continuously monitored. In a subgroup, blood was collected at various time points during baseline and reperfusion for measures of hydrogen peroxide production.
Results: In 3-hour non-ischemic perfusion experiments (n=3), LV functional decline was 5% per hour. The 10% low flow group (n=6) had significantly higher recovery of developed pressure and rate pressure product (p <0.001 with ANOVA) during reperfusion than the CTRL group (n=7). The very low flow (1%) group (n=6) was no different from the CTRL group (no low flow) in recovery of LV function. Hydrogen peroxide production during reperfusion in the CTRL group was similar to that previously observed in the buffer-perfused heart, with production peaking during early reperfusion in the range of 150 nM.
Conclusions: The autologous, whole blood-perfused isolated heart is a viable, more physiologic, model for studies of ischemia/reperfusion and low flow in the isolated heart. These data emphasize the important role of low flow reperfusion to improve functional recovery of the heart and support earlier work done in the buffer perfused heart.
This research has received full or partial funding support from the American Heart Association, Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).