High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.

Intracellular distributions of essential elements in cardiomyocytes.

We describe the intracellular distributions of nine essential elements (P, S, Cl, K, Ca, Mn, Fe, Cu, and Zn) found in cardiomyocytes imaged using synchrotron X-ray induced fluorescence. Cardiomyocytes were isolated from rat hearts, flash frozen on Si(3)N(4) windows, freeze-dried, and imaged with approximately 300 nm spatial resolution. Distinct longitudinal patterns in cardiomyocytes were most apparent for the elements Fe and Cu, which clearly colocalized. Transverse striations were apparent for P, S, Fe, and Zn, while those for Zn were consistently the most prominent ( approximately 10(-3)M) and appeared with a periodicity in the range 1.63-1.75 microm, the expected length of a sarcomere. Transverse striations for high concentrations of P, Fe, and Zn and low concentrations of S colocalized and coincided with the I-band of the intact cardiomyocyte. Fluorescence microscopy using FluoZin-3 in intact cardiomyocytes suggests that Zn(2+) influx is through sarcolemmal calcium channels and that significant stores of intracellular Zn(2+) may be released quickly (<1s) into the cytosol. These data collectively suggest that Zn(2+) is buffered by structures associated near the T-tubules and/or in the sarcoplasmic reticulum and is found in relative abundance sufficient to act as a modifier of Ca(2+) regulation or as a possible signaling messenger for gene expression.