Haemodynamic measures

Standardised (Van Bortel et al., 2002, Laurent et al., 2006), non-invasive

haemodynamic measures were made in duplicate between 1 to 4 minutes apart at each time point, and averaged for analyses.

3.3.4.1. Brachial blood pressure

For both Healthy and T2DM studies, brachial BPs were taken with a semi-automated oscillometric device (Omron T915, Omron Healthcare, Kyoto, Japan) usually on the left arm. However, the right arm was occasionally used for BPs if there were contraindications for constriction of the left arm, such as previously vascular surgery, or if the right arm was not able to be cannulated. BPs were taken on the same arm throughout a single test session and the BP arm did not change between baseline measures and measures inside the climate chamber. Moreover, BPs were always measured on the same arm throughout subsequent test sessions.

3.3.4.2. Pulse wave analysis

The PWA and PWV results for both studies were recorded using applanation tonometry (Figure 3.1, A and B). PWA was performed on radial artery waveform, usually captured from the left radial pulse, using brachial BP as the calibrating value. For Healthy and T2DM studies, all artery waveforms were collected for a minimum of 12 seconds each with a Millar tonometer (SPC-301, Millar Instruments, TX, USA) and processed with dedicated PWA software.

Chapter 3 – General Methods

BONE

SENSOR TONOMETER

Figure 3.1. A) SphygmoCor apparatus, tonometer and laptop showing an aortic pulse wave synthesised from the measured radial pulse used in both studies, and B) the principle of applanation tonometry.

In applanation tonometry, an artery is compressed against an underlying structure (bone or muscle) and the force of the blood pressure against the artery wall is detected by the sensor.

SphygmoCor software version 8.2 (AtCor Medical, Sydney, Australia) was used for the Healthy Group study, while the subsequent software update, version 9.0 was used for the T2DM Group study. The inbuilt algorithms in the software that calculate central

haemodynamic parameters did not change between versions, however, there were some changes to waveform capture methods, i.e. a change from manual to automated capture. These changes did not affect the waveform properties, or values obtained. PWA synthesises the aortic artery pressure from the measured radial artery pressure waveform, and uses a generalised transfer function that has been validated by comparing synthesised results to those measured by direct aortic catheterisation during rest and haemodynamic

perturbations including the Valsalva manoeuvre, nitroglycerin, and exercise (Gallagher et al.,

B

ARTERY

Tonometer

SphygmoCor PWA report

ECG leads A

2004, Sharman et al., 2006, Chen et al., 1997). Same-day within-participant measures of AIx can be variable and often have a greater range than aortic PWV or aortic systolic BP

(Wilkinson et al., 1998). Despite this, aortic BP, AIx and PWV as measured by the

SphymoCor system have previously been shown to be highly reproducible and in accord with measures made by different technology (Wilkinson et al., 1998). Moreover, aortic BP, AIx and PWV data measured by PWA have been shown to have similar reproducibility to that of traditional cuff-measured brachial BPs (Fillipovsky et al., 2000). AIx has previously shown good-to-excellent reproducibility on same-day repeated measures [interclass

correlation coefficient (ICC) 0.86] (Papaioannou et al., 2007). The test-retest reproducibility between same-day PWA measures, taken ~3-5 minutes apart, in a subsample of seven healthy participants in the current studies was found to be excellent and comparable to those reported by Papaioannou et al., (2007). The ICC for AIx was 0.94; technical error of the mean (TEM) was 3.16%; 95% confidence interval (CI) of the difference between the first and second measure was -1.5 to 1.4. For aortic systolic BP, ICC was 0.96; TEM was 1.36mm Hg (95% CI: -0.2 to 1.1) and for aortic PWV, ICC was 0.70; TEM was 0.32 m.s-1 _{(95% CI: -0.3}

to 0.1).

Besides aortic BP, PWA provides several other estimates of central haemodynamic function including AP. AP is the difference between the first and second systolic pressure peaks. Aortic PP (systolic pressure minus diastolic pressure), mean BP (MBP; the true mean pressure of the integrated averaged radial arterial waveforms), AIx (AP divided by PP

expressed as a percentage), time to reflected wave (Tr), systolic (SPTI) and diastolic (DPTI) pressure-time integrals and subendocardial viability ratio (SEVR). SPTI reflects the work of the heart and oxygen consumption, DPTI represents the pressure-time for coronary

perfusion and the energy demands of the heart, and SEVR, which is the ratio of SPTI and DPTI, reflects myocardial oxygen supply and demand.

Chapter 3 – General Methods 3.3.4.3. Pulse wave velocity

In this thesis, PWV was recorded and calculated by the SphygmoCor system. Aortic PWV was measured by simultaneously recording electrocardiogram (ECG)-gated carotid and femoral artery waveforms, while brachial PWV was calculated from the carotid and radial artery pulse waveforms and simultaneous ECG (O'Rourke et al., 2002, Wilkinson et al., 1998). Similar to PWA, artery waveforms for PWV were collected for a minimum of 12 seconds via applanation tonometry. PWV was calculated as the pulse travel time divided by the artery path length (AtCor Medical, 2009). The pulse travel time was calculated by the foot-to-foot method with the foot of each pulse waveform identified by intersecting

tangential algorithms (AtCor Medical, 2009). The aortic artery path length was calculated by deducting the distance between the carotid pulse site and the sternal notch (in mm), from the distance of the sternal notch to the femoral artery pulse; taking a direct path to the femoral pulse site in the upper leg. Similarly, the brachial artery path length was calculated by deducting the distance between the carotid pulse site and the sternal notch from the path length of the sternal notch to the radial pulse, estimating the artery path to the point of the shoulder and directly down to the radial pulse site (AtCor Medical, 2009). The strongest palpated pulse for each arterial site was identified with permanent marker and distances were measured with a non-stretch, flexible tape measure.