M.Sc Thesis

M.Sc StudentKovalevsky Maya
SubjectMonitoring Cardiac Function Based on the Work Pressure Time
Integral Relationship in Rats with
Volume-Overload Induced Heart Failure
DepartmentDepartment of Biomedical Engineering
Supervisors ASSOCIATE PROF. Amir Landesberg
PROF. Zaid A. Abassi


           Quantification of cardiac performance is critical for the management of patients with cardiac diseases. Evaluation of cardiac function using the available hemodynamic and geometrical indices falls short in identifying the turnover point from reversible compensatory response to decompensation. The most widely used index of cardiac contractility in pre-clinical study is the maximal elastance. However, measurements of the elastance are not feasible in most clinical studies. According to the elastance model cardiac mechanical energy is comprised of the external work and the potential energy. Our previous investigations of the sarcomeric control of contraction have suggested that the stress-time integral is a surrogate measure of the potential energy.

           The current study tests the hypothesis that exploring the relationship between unitary external-work (uEW) and the stress-time integral (sTI), can assist in identifying the transition from adaptive compensation to decompensation and development of chronic heart failure. The uEW is defined as the external work per myocardial mass.

            We have utilized a model of volume overload in order to monitor the adaptive compensatory response and the development of decompensation. Volume overload was induced by creating aortocaval fistula (ACF) between the abdominal aorta and the inferior vena cava in Sprague-Dawley rats. We have analyzed the data of 59 rats with ACF and 3 2 Sham operated rats, at various time intervals (up to 21 weeks) after the creation of the fistula. The data were recorded with the Millar Pressure-Volume Loop System.

            ACF caused cardiac hypertrophy that deteriorated to heart failure. There was no significant change in heart rate and interestingly the ACF rats were able to maintain peak systolic pressure. The max dp/dt was similar in sham and ACF rats. Cardiac-output immediately increased in the first week and reached maximal value at the second week. Thereafter it declined close to the normal level. A decrease in total peripheral resistance (TPR) was observed in the first four weeks. Thereafter there was a “pseudo-normalization” of the TPR.

            The sham group fell within the same range on the uEW-sTI plane, denoted as the normal reference region. The ACF group presented maximal increase in both the uEW and the ϭT on the second week. Additional index was derived from EW-PTI plane: the efficacy. The efficacy describes the ratio of the uEW to sTI. The unitary mechanical energy and efficacy characterize four phases of myocardial response: 1- an immediate acute failure in the first week, 2- a maximal compensatory response in the second week, 3- a pseudo-normalization (return to the normal performances) after 4 weeks, and 4- deterioration to chronic heart failure from the eighth week. The calculated elastance using various methods of single beat approximation yielded inconsistent results.

  The suggested novel method has scientific and clinical merits. The uEW-sTI plane provides a framework for quantifying cardiac function that can be used for identifying the transition point from compensation to decompensation. The suggested method utilizes a single pressure volume loop. The suggested mechanical energy and efficacy should be tested in patients as indices of cardiac contractility, for continuous monitoring and optimization of treatment.