Renal injury, as indicated by apoptosis in the kidney, results from the production and release of cytokines due to cardiac ischemia

Scope and method of study. Renal dysfunction has been observed by clinicians in a small percentage of their patients after cardiopulmonary bypass surgery. It is thought by these same clinicians, the release of cytokines due to cardiac ischemia are the culprits to the harming of the kidney. The purpose of these studies was to obtain a better understanding in the mechanism causing renal injury after cardiac ischemia. We looked at the cytokine tumor necrosis factor alpha (TNF). The cardiac ischemic modeled used for these studies was accomplished by occluding the left coronary artery of anesthetized adult male rats for a time frame of 15 minutes. After the 15 minutes the kidneys were harvested for the various studies. Our lab first measured serum TNF pre and post 15 minutes of induced cardiac ischemia using ultrasensitive TNF ELISA. Secondly, after 15 minutes of coronary occlusion we took the rat kidneys and prepared them for Western blot analysis looking for the early marker of apoptotis---cleaved poly ADP-ribose polymerase (PARP). Thirdly, post cardiac ischemic rat kidneys were prepared for immunohistochemistry and probed for cleaved PARP and active caspase 3. Finally, these studies examined the function of TNF in renal injury after cardiac ischemia by measuring the pro-apoptotic proteins of caspases 2, 3, 9 as well as cleaved PARP in rat kidneys after sham control, cardiac ischemia, TNF inhibition, and TNF infusion with out coronary occlusion.; Findings and conclusions. We found serum TNF consistently increased after cardiac ischemia. In looking at renal tissue, our lab found increased levels apoptotic activity (caspases 2, 3, 9, and cleaved PARP) over that of control in our ischemic studies. For the first time our studies revealed the renal cells most affected by myocardial infarction, these cells are the cortical proximal tubules. In looking at the role of TNF in renal injury, we discovered there is increased apoptotic signaling (caspases 2, 3, 9, and cleaved PARP) in the TNF inhibition and TNF infusion studies, but not to the degree as seen with coronary ischemia. This indicates there are other influences causing renal injury other than TNF after cardiac ischemia without reperfusion. Further studies need to be done creating a time course of renal injury after coronary occlusion, looking at the kidney after reperfusion of the myocardium, and looking at the other cytokines that might be adding to the renal damage.