Cardiac effects of renal ischemia

Abstract

Mortality in acute kidney injury (AKI) remains unacceptably high, yet the cause of death is commonly related to dysfunction of extra-renal organs. We and others have observed remote organ abnormalities after renal ischemia. The term cardiorenal syndrome was first applied to the "crosstalk" between the organs by the National Heart, Lung and Blood Institute of the National Institutes of Health and the clinical importance is increasingly appreciated. Nevertheless, more information is needed to effectively address the effect of renal injury on the heart. Since AKI often occurs in patients with co-morbidities, we have investigated the effect of renal ischemia in the setting of cardiac failure. We hypothesized that the cardiac effects of renal ischemia would be significantly amplified in experimental cardiomyopathy due to doxorubicin. Male Sprague-Dawley rats with preexisting cardiac and renal injury due to low dose doxorubicin were subjected to bilateral renal artery occlusion. Cardiac structure and function were examined 48 hours after reperfusion. Loss of functional myocardial tissue with decreases in left ventricular pressure, increases in apoptotic cell death, inflammation and collagen and greater disruption in ultrastructure were seen in the doxorubicin/ischemia group as compared to those animals treated with doxorubicin alone. These results suggest that preexisting co-morbidities can result in much more severe distant organ effect of acute renal injury. The results of these studies are relevant to human AKI.

Impaired microvascular circulation in distant organs following renal ischemia

“…Many factors can alter microvascular flow, including inflammation, erythrocyte aggregation and impaired deformability as well as hematocrit. We [33,41,44,45] and others [46][47][48][49][50][51] have documented inflammation following renal ischemic injury. Although we did observe decreases in microvascular flow in proximity to obstructing leukocytes, our data indicate that inflammation was not the major factor in decreased microvascular plasma velocity in remote organs following renal ischemia in this model, since significant improvements in microvascular flow, but not adherent leukocytes, were observed with the platelet inhibitor dipyridamole.…”

“…All quantification was performed without knowledge of experimental group. Additional measures of inflammation included myeloperoxidase activity [38,41] and polymerase chain reaction for complement component C3 and intercellular adhesion molecule-1 (ICAM) [30] measured in tissue.…”

“…Cardiac abnormalities have been demonstrated following renal ischemia [41,42], yet the heart is not amenable to intravital microscopy to assess plasma flow as it would require cardioplegia and thus not be physiological. In hematoxylin and eosin stained sections (Fig 8B ), rare leukocytes were seen in the postischemia hearts.…”

Cardiac damage following renal ischemia reperfusion injury increased with excessive consumption of high fat diet but enhanced the cardiac resistance to reperfusion stress in rat

“…Many reports in the literature show the negative effect of cardiac surgery on kidney function that eventually leads to the development of AKI [ 31 , 32 ]. However, very few literature is available in support of the negative impact of renal surgery on cardiac function [ 33 ]. This effect of surgery on the distant organs also depends on co-existing morbidities and risk factors [ 34 ].…”

Does cardiac impairment develop in ischemic renal surgery in rats depending on the reperfusion time?

“…Understanding the temporal patterns of distant cardiac effects of renal IRI is of utmost clinical importance, to managing post-renal surgical patients from postoperative complications, rehospitalization and effective rehabilitation procedures [ 19 ]. Monitoring the heart of renal surgical patients enables to implementation of various strategies to reduce cardiac-associated mortality and morbidity.…”