當心臟出現心跳強弱交替的現象(cardiac alternans)會導致心臟中電訊號的傳導阻礙(conduction block)而導致心律不整，傳統上是利用成比例放大的控制方法來控制這種現象。在此篇論文中我們提出一種非線性控制方法來抑制離體心臟中心跳強弱交替的現象。在這個方法中，我們利用兩種電刺激的週期來取代原本固定的刺激週期(T0)；這兩種週期分別為T1 = T0+ΔT/2與T2 = T0-ΔT/2，而當中ΔT是在週期T0中加入的微擾。我們利用相鄰兩次心跳的壓力差(Pn、Pn+1)判定電刺激週期為T1或是T2；當Pn > Pn+1時則使用T1為電刺激週期，反之則使用T2。我們的結果顯示，這種T1T2的控制方法可以成功地抑制在離體心臟中心跳強弱交替的現象。此篇論文另外一個實驗是關於心律變異性的研究(heart rate variability, HRV)。心律的變異性在離體心臟中是來自於位於右心房的竇房結(SA node)，而心臟細胞培養系統可以用來模擬竇房結。我們利用兩種方式來瞭解心律變異性的機制，第一種方法是利用藥物來減少離體心臟收縮的力，而我們的結果顯示當心臟收縮的力變小時則心律變快且心律變異性變小；此外，我們比較利用加藥與升溫兩種方式所造成心律變異性的變化，發現利用藥物改變心臟收縮的力的方式的效果比升溫較為顯著。第二種方式是利用改變在心臟細胞的溫度來觀察心律變異性的變化，而實驗結果顯示，當溫度越高時心律會加快，而心律變異性變小。Alternan responses in heart can cause conduction blocks and lead to fatal conditions such as ventricular fibrillation (VF). It would be important to know how to suppress the alternan response in hearts. In this thesis, we report a nonlinear control method to suppress the alternan responses in isolated heart experiments. In this method, the pacing period T0 is replaced by two periods; namely T1 = T0+ΔT/2 and T2 = T0-ΔT/2 where ΔT =T1-T2 is a small perturbation of the original period T0. Measured pressures of the isolated heart from the previous beat (Pn-1) and the current beat (Pn) are used to determine whether T1 or T2 should be used. In our control scheme, T1 is used when Pn > Pn-1 ; otherwise T2 is used. This method is different from the traditional proportional gain method. Results from experiments show that this T1T2 method can successfully suppress alternan response from isolated hearts.Another experiment in this thesis is to understand the variability of the interbeat interval which is controlled by SA node in an isolated whole heart. Primary cardiac co-cultures are also used to model the SA node in the heart. To understand the mechanism of the heart rate variability, we add a drug to suppress the contraction of the isolated whole heart, and also control the temperature of the cardiac cultures to see the effects of mechanical and temperature. The result shows that when we reduce the contraction of the isolated whole heart, the heart rate increases and the heart rate variability decreases. However, the decrement of heart rate variability is larger than the temperature effect on the isolated whole heart. For the experiment of temperature effect in cell cultures, the heart rate increases and the heart rate variability decreases when we increase the temperature.
