Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

McIntyre, CW

Abstract

Patients with chronic kidney disease requiring hemodialysis to sustain life have extremely high rates of cardiovascular morbidity/mortality. This is both a consequence of the disease process and treatment. Hemodialysis induces systemic circulatory stress is largely due to the extracorporeal circuit and volume removal. The stress induced by intermitted hemodialysis is repetitive with cumulative cardiovascular effect and is the principal driver of heart failure and sudden death in this vulnerable population. The insults imposed by hemodialysis result in left ventricular regional wall motion abnormalities and lead to myocardial stunning with permanent damage to the vasculature and myocardium. Currently, the adversity caused by hemodialysis remains under appreciated and largely ignored. The aim of this thesis is to explore intradialytic methods to detect and ameliorate hemodialysis-induced circulatory stress (myocardial stunning).

The utility of a non-invasive intradialytic hemodynamic monitoring system using photoplethysmography to detect hemodialysis-induced circulatory stress through the skin was explored. In this first thesis project, we determined that pulse strength, an output generated by PPG technology was associated with the development of myocardial stunning.

Building on this initial finding, the second thesis project supported the significance of the pulse strength variable as a signal to the development of regional wall motion abnormalities/myocardial stunning during hemodialysis. Additionally, we determined that intradialytic changes in cutaneous perfusion were detected earlier in treatment and were directly associated with direct measures of global cardiac perfusion using intravenous contract/computerized tomography imaging. Both findings were associated with rates of ultrafiltration/fluid removal during dialysis (previously identified as principal drivers of hemodialysis-induced acute cardiac injury).

Exercise pre-conditioning, a phenomenon that is cardio-protective against ischemic-reperfusion injury was explored, in the form of intradialytic exercise. In the third project, we found there to be a reduction in the number of treatment-induced regional wall motion abnormalities at the peak of hemodialysis stress when intradialytic exercise was incorporated into treatment. Moreover, any amount of exercise had an immediate influence with no detrimental effect on treatment tolerability.

This work describes the utility and benefit of non-invasive microcirculatory monitoring for the early detection of hemodialysis-induced circulatory stress and demonstrates the pre-conditioning benefit that intradialytic exercise has on the reduction of myocardial stunning in the hemodialysis population

Summary for Lay Audience

Patients with kidney disease have a higher risk of cardiovascular problems than people without kidney disease. When about 90% of their kidney function is lost, they need dialysis to live. Hemodialysis cleans the blood and also removes large amounts of fluid (because of low urination) with each hemodialysis treatment (four hours, three times weekly). Hemodialysis puts stress on the blood vessels and hinders the ability of the heart to pump blood throughout the body (circulatory stress). This causes long term damage and can lead to sudden death. The goals of this thesis were to see if a monitoring system that is placed on the skin during dialysis could detect circulatory stress (myocardial stunning) and to test whether or not exercise (cycling) during dialysis could prevent or reduce circulatory stress (myocardial stunning).

The blood vessels in the body, more specifically the very small vessels of the microcirculation are affected by low blood flow during dialysis. In the first project we found that changes in blood flow in the skin during dialysis was predictive of myocardial stunning.

The second project, in addition to the findings above, we found that the changes in blood flow in the skin represented changes in blood flow in the heart and that the rate of fluid removal contributed to these changes.

Previous research has shown that small repeated amounts of exercise protected the heart from harm during a heart attack (pre-conditioning effect). The third thesis chapter tested exercise during dialysis, using a stationary bike to see if it provided the same protection. We found that when patients cycled during dialysis, they had less myocardial stunning than when they did not exercise.

These results help us to understand what type of monitoring would help detect the stress caused by dialysis and what activities may reduce or prevent stress on the heart.

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