Abstract 5123: Assessment of Myocardial Microvascular Abnormalities in Chronic Kidney Disease
Recent data has shown that chronic kidney disease (CKD) has been linked to the development of cardiovascular disease and been associated with an adverse prognosis. It has been hypothesized that effects on the coronary microcirculation play a critical role in the exacerbation of disease. Thus, we assessed the myocardial microvasculature in CKD, using fluorescent microangiography (FMA) and myocardial contrast echocardiography (MCE).
Methods: 8 week old male Fischer 344 rats underwent subtotal nephrectomy (n=10) (SNX), or sham surgery (n=10). Systolic blood pressure (SBP), proteinuria, left ventricular (LV) ejection fraction (EF), end-diastolic pressure volume relationship (EDPVR) and Tau were assessed at baseline and 8 weeks following surgery. MCE was performed to assess regional myocardial perfusion, and rats were subjected to FMA (10% solution of 0.02μm fluorescent microspheres). Thick (200 μm) sections of fixed tissue can then be visualized under confocal microscopy. Stacks of images are collected and 3D reconstruction and visualization carried out in order to quantify the density, size and shape of blood vessels. An automated tracing algorithm was used to create a solid 3D model.
Results: SNX animals showed increased in SBP and urinary protein confirming CKD. LVEF was preserved (68±16 versus 53±14 % in controls), while diastolic function was impaired in both the energy-dependent early (Tau) (16.7±3.1 versus 11.0±1.2 msec; p<0.05) and late passive EDPVR, a measure of LV compliance (0.052±0.026 versus 0.018±0.009 mmHg/ul in controls; p<0.01). FMA analysis illustrated a reduction in average vessel diameter (3.84±0.08 versus 4.68±0.16 μM in controls; p < 0.05), and a reduction in vascular density (2.81E-03±1.72E-04 versus 3.63E-03±1.56E-04 μM in controls; p < 0.01). MCE-derived endocardial-epicardial blood flow ratio was reduced in CKD as compared to sham controls (0.67±0.14 versus 1.12±0.35 in controls; p<0.05).
Conclusion: Myocardial microvascular loss occurs in CKD, and is associated with a reduction in endocardial blood flow and impaired diastolic function, with preserved LV systolic function.