Jon Offstad

Endothelin is released from the porcine coronary circulation after short-term ischemia

Endothelin (ET) is increased in plasma after myocardial infarction. Whether brief periods of myocardial ischemia not leading to myocardial infarction also increase plasma ET is not known. The purpose of the present study was to examine cardiac ET balance in association with a 10-min LAD occlusion followed by reperfusion. Venous blood was selectively sampled from the transiently ischemic myocardium using a shunt between the anterior interventricular vein and the right atrium in eight pentobarbital-anesthetized pigs. Flow in the shunt was measured with a Doppler flow probe. Arterial blood was drawn from the aortic arch. Plasma ET was measured using an ET [1-21]-specific 125I assay system. This assay system has no cross-reactivity with big ET. A net cardiac ET uptake of 0.7 (0.3-1.4) fmol min-1 g-1 (median, 95% confidence interval) in the control period shifted to a net release during the first 10 min of reperfusion. The release reached a maximum of 2.8 (0.4-6.0) fmol min-1 g-1 after 1.5 min of reperfusion. Cardiac venous ET concentration increased from 3.4 (2.5-4.8) to 4.4 (3.6-6.9) and 4.4 (3.6-6.6) fmol ml-1 at 1.5 and 5 min of reperfusion, respectively (p < 0.001 for both). Arterial ET concentration decreased from 4.8 (3.9-6.1) to 2.7 (2.4-4.3) fmol ml-1 at 10 min of reperfusion (p < 0.001). ET is released from the porcine heart for several minutes during reperfusion after a brief coronary artery occlusion.

Importance of Endogenous Adenosine During Ischemia and Reperfusion in Neonatal Porcine Hearts

BACKGROUND Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. METHODS AND RESULTS Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P<.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P<.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P<.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P<.05). CONCLUSIONS In neonatal porcine hearts, endogenous adenosine produced during ischemia does not influence ischemic injury or functional recovery. Elevating endogenous adenosine by draflazine elicits cardioprotection in both low-flow and zero-flow conditions.