The study subjects included 6 dogs (20-25 kg), regardless of the gender. After an intramuscular injection of 25 mg/kg ketamine sulfate, endotracheal intubation was performed and anesthesia was maintained with 2% enflurane. Each anesthetized dog was fixed on a stand, and its respiration was maintained using an artificial ventilator. Fig. 1A shows the positions of the direct blood pressure sensor for IBP, electrocardiogram (ECG) electrodes, and PPG sensors. IBP was monitored by inserting a microtipped catheter into the right femoral artery, and the PPG signal was measured at the dog's tail because the tail is one of easiest areas to set a PPG sensor and one of best areas to acquire precious vascular information. The overall experimental procedure is shown in Fig. 1C. The experimental animals were stabilized for 15 min after the experimental preparation was completed. To induce a hemodynamic change, 16 mg/mL of diluted dopamine was injected into a vein for 2 min at the rate of 20 µg/kg · min^-1 by using an infusion pump. Thereafter, the infusion pump was ceased, and 1 mg of epinephrine was intravenously injected in order to induce a stronger hemodynamic change.

Considering the pharmacological properties of dopamine and epinephrine, these two drugs are established as important frequently used cardiac stimulants.11-13 Dopamine (3, 4-dihydroxyphenylethylamine) is a precursor of norepinephrine and is produced by the decarboxylation of dihydroxyphenylalanine (dopa) during the biosynthesis of catecholamines.14 It is metabolized by monoamine oxidase (MAO) and catechol O-methyl transferase (COMT), and it becomes inactive after destruction in the digestive tract. During dopamine medication, depending on the concentration, it exhibits different hemodynamic effects on dopaminergic, β1-adrenergic, and α1-adrenergic receptors. In most cases, 160 mg dopamine is diluted in 100 mL of glucose solution to obtain a concentration of 16 mg/mL for i.v. administration. Different hemodynamic effects are exhibited depending on the dose.15,16 At a low dose (0.5-3.0 µg/kg · min^-1), it mainly activates the dopaminergic receptor. At an intermediate dose (3.0-7.0 µg/kg · min^-1), dopamine activates the β1-adrenergic receptors to increase the heart rate (HR) and cardiac output. At a high dose (> 10 µg/kg·min^-1), it mostly activates the α1-adrenergic receptors in the vessels, and vascular constriction raises the blood pressure.15,17,18

Epinephrine is a hormone secreted from the adrenal medulla and is also known as adrenaline. Epinephrine is accepted as a stimulation transmitter in the sympathetic nerve, and epinephrine injection excites the β1-adrenergic receptors in the heart to enhance myocardial contraction via positive inotropic effects. Epinephrine increases the HR via positive chronotropic action and enhances the irritability of the cardiac muscle via positive bathmotropic action. Its positive dromotropic action reduces stimulus conduction.19,20 Thus, cardiac output increases; however, cardiac efficiency is reduced because of the remarkable increase in oxygen consumption in the cardiac muscle.13 A significant reduction in systole than in diastole is observed in the heart activated by epinephrine. Conclusively, the total number of diastoles per minute increases with the cardiac output.12,18 However, if the HR is increased beyond the physiological range, sufficient relaxation will not occur; therefore, cardiac output will be reduced. Epinephrine in the vessels simultaneously activates the α-receptor and β-receptors, but the activation of the α-receptors is dominant and manifested as vasoconstriction. Epinephrine is the strongest agent for increasing blood pressure, and an abrupt increase in blood pressure is noticed depending on the i.v. injection dose.19 This rise in blood pressure results from increased cardiac output due to enhanced myocardial contraction and the HR. Moreover, SBP increases abruptly to a value more than DBP, i.e., pulse pressure increases.11,13,20

The PPG signal is influenced by external factors such as the distance between the light source and photodetector, contact force, and temperature.5 In our experiment, a band type PPG sensor (MAX-N, Nellcor, Pleasanton, CA, USA) was used to monitor the change in the waveforms obtained from the cardiovascular system and minimize the effect of contact force.10 To minimize the effect of temperature,21 ambient temperature was maintained at 24 ± 0.7℃. To measure the PPG signal, an infrared light-emitting diode (LED) with a center wavelength of 890 nm and a photodetector with a center wavelength of 900 nm were used. The signal was measured in the transmission mode. The DC component of the PPG signal detected by the photodetector, using an analog low-pass filter with a cut-off frequency of 20 Hz. Then the AC component of the PPG signal was extracted using a high-pass filter with a cut-off frequency of 0.15 Hz. Power Lab (ML880, ADInstruments, Bella Vista, NSW, Australia) with a 12-bit A/D converter was used to acquire signals at a sampling rate of 200 Hz per channel and digitize them. A constant current source circuit was used to drive the LED, and the amplification ratio was kept constant.

A pressure transducer (SPC-350, Millar Instruments, Houston, TX, USA) was used to measure the IBP, and the signals were acquired at a sampling rate of 200 Hz using Power Lab. The acquired data was additionally analyzed with LabVIEW 8.2 (National Instruments). The HR was detected from the ECG signal using a set of automatic programming routines involving the zero-crossing-Based QRS detection algorithm.22 SBP, DBP, and PPG components were detected using a set of automatic programming routines involving low-pass filtering, zero-phase filtering, differentiation, and threshold peak/foot detection algorithm.

Fig. 2 shows that the PPG signal has the following components: transmission current (I_T), absorption current (I_A), pulsation current (I_S), and cycle (R), which are related to the total current (I₀). I_T is inversely related to tissue blood volume, while I_S is proportional to increase in blood volume during contraction periods. R is the actual cardiac cycle. Transmission and pulsation currents (I_T and I_S) usually fluctuate in a low-frequency range such as the respiration rate. Low-frequency fluctuation in the cardiac cycle is mainly controlled by the sympathetic nerve.23 Variation in blood flow (I_A and I_S) is generated due to vasoconstriction and vasodilation, both of which are significantly affected by the sympathetic nervous system.24 Therefore, PPG signal specifically provides information regarding blood volume as well as that on blood pumping and its transportation status.5 The I_T component is used in studies that measure blood volume, while the I_S component validates the existence of resistance in studies on the vascular compliance with the cardiovascular system, such as hypertension.25

Low-frequency fluctuation of I_T and I_S originates from automatic variations in the sympathetic nerve activity. Activation of the sympathetic nerve leads to vasoconstriction. This is the result of low compliance (high resistance) in the arterial system and reduction in blood flow in tissue, which results in the increase of I_T and reduction of I_S.9,26-28

To monitor the hemodynamic change induced after the drug injection, the HR, SBP, and DBP were measured every 30 sec for 15 min. For normalization, these parameters were also measured for 30 sec before the drug injection.

The absolute values for the DC and AC signals in the PPG were in different ranges because of the anatomical differences in the measured area for each subject. To compare the results of all the subjects under the same conditions, the average value for 30 sec before the injection was set at 1 and the average value for every 30 sec was normalized to analyze the 15-min data. These were used for comparing the changes in the PPG signal components with IBP pressure changes. With regard to the values of the PPG components, transmission current during systole (I_Tsys) and transmission current during diastole (I_Tdia) were detected from the foot and peak of the DC signal, respectively. Pulsation current (I_S) was analyzed by the amplitude of the AC signal.

The statistical program used in this study was SPSS 12.0 (SPSS Inc, Chicago, IL, USA) for Windows. Statistical analyses were performed to evaluate the difference in response of data between two points of drug administration time for IBP, HR and PPG components by the Student t-test. The changes in the IBP, HR, and PPG components were expressed as means with standard deviations. Pearson's correlation coefficients were evaluated via the correlation analyses of the PPG components and IBP. For all statistical analyses, p < 0.05 was considered significant.

During the first 2 min of dopamine injection at the rate of 20 µg/kg · min^-1, SBP increased from 92.3 ± 12.69 mmHg to 108.7 ± 20.23 mmHg, while DBP increased from 66.1 ± 10.75 mmHg to 81.8 ± 18.22 mmHg. After cessation of dopamine administration, blood pressure slightly reduced. After the intravenous (i.v.) injection of epinephrine, SBP, and DBP significantly increased from 102.6 ± 18.44 mmHg to 214.5 ± 23.82 mmHg and from 76.7 ± 18.28 mmHg to 153.0 ± 15.17 mmHg, respectively. Blood pressure was observed to be a maximum 2-3 min after the injection of epinephrine. In addition, the pulse pressure, i.e., the difference between SBP and DBP, also increased.

The HR before drug injection was 91.4 ± 12.69 bit/min, and the maximum HR was 122.9 ± 13.75 bit/min at 4 min after drug injection. During the injection of dopamine, the HR tended to show a consistent elevation. After the i.v. injection of epinephrine, the HR increased for 1 min and then reduced slightly (Fig. 3).

Before injection, the average values for 30 sec of DC and AC components of PPG were set at 1. After the injection, the average values for every 30 sec were normalized. After the drug injection, the changes in I_Tsys (foot of the DC component of PPG) and I_Tdia (peak of the DC component of PPG), which reflect changes in blood volume, were minimal with values of 0.70 ± 0.035 and 0.71 ± 0.035, respectively, at 5-6 min. The variations in I_S (amplitude of the AC component of PPG), which reflect changes in vascular compliance and resistance, were maximized with the value of 1.024 ± 0.273 at 11-13 min (Fig. 4).

In regards to the variation in I_T (the DC component of PPG) according to change in IBP in all the subjects, an increase in IBP indicated a significant reduction in I_Tsys and ITdia. In addition, the correlation coefficient between I_Tsys and SBP as shown in Table 1 was 0.939 (p < 0.01). It was 0.942 (p < 0.01) for DBP and I_Tdia. From these findings, a high correlation could be determined between IBP change and variation in the DC component of PPG (Fig. 5, Table 1).