The dose of NO had been selected on the basis of findings from previous reports that 10 to 20 ppm allows the maximum possible pulmonary vasodilation in PAH patients. NO was supplied from a pure NO source tank (Oxhydrique; Machelen, Belgium) and was delivered through a tight facemask. The inspired fraction of NO was monitored by chemiluminescence after calibration against a standard NO concentration (42 chemi-luminescence NO-NO2-Nox analyser; Thermo Environmental Instruments Inc; Franklin, MA). The dose of epoprostenol conformed to standard practice at the initiation of long-term continuous IV epoprostenol therapy. The dose of dobutamine was selected on the basis of experimental data showing that this inotropic drug is without flow-independent pulmonary vascular effects at doses of up to 10 ^g/kg/min. natural breast enlargement cream
Results are presented as the mean ± SE. Paired t tests were used to compare the hemodynamic values after different pharmacologic interventions to baseline levels. A p value of < 0.05 was defined as being statistically significant.
Results Effects of Pulmonary Hypertension
As shown in Table 1, the patients had increased levels of Ppa, Pra, and PVR, a normal Ppao level, and decreased cardiac output, with a PVZ spectrum showing marked increases in Z0, Z1, and Zc, a shift of Fmin to higher frequencies, and a negative first harmonic phase angle, with Z0 cross-shifted to higher frequencies (Table 1). Representative PVZ spectra with source pressure and flow signals are shown in Figures 1 to 3.
Compared to previously reported primary pulmonary hypertension (PPH) patients, our patients had higher Ppa and PVR values, and lower cardiac output, suggesting a more advanced stage of the disease. The differences were quantitatively similar when only the subgroup of our 14 PPH patients was considered. There were more important increases in Z1 and Zc, amounting up to seven times normal, but Fmin and RF were not different (Table 1).
Figure 1. PVZ spectra in a 51-year-old patient in NYHA functional class III with PPH before and during the inhalation of 20 ppm NO. Mean Ppa and PVR decreased from 53 mm Hg and 13.5 Wood units, respectively, to 49 mm Hg and 10.8 Wood units, respectively, during NO inhalation. Left, A: shows a magnification of the PVZ modulus between 2 and 15 Hz, which are used for the calculation of Zc. Right, B: shows Ppa and Doppler velocity tracings before and during the inhalation of NO. Inhaled NO therapy shifted the PVZ spectrum to lower ratios of pressure and flow moduli and to lower frequencies, which were related mainly to the NO-induced decrease in pressure and the improved flow in later systole.
Figure 2. Same data as shown in Figure 1, with similar effects of IV prostacyclin seen in the same patient. PGI2 = prostaglandin-I2.
Figure 3. Pulmonary vascular impedance spectra with source pressure and flow waves before and during the administration of 8 ^g/kg/min dobutamine, in a 55-year-old patient with PPH who was in NYHA class III. The mean Ppa was 64 mm Hg and remained unchanged during dobutamine infusion. PVR decreased from 17.3 to 11.2 Wood units because of an increase in cardiac output from 2.9 to 4.3 L/min. Left, A: dobutamine therapy had no significant effect on the PVZ spectrum. Right, B: shows that the predominant effect of dobutamine is a global increase in flow.
Table 1—Hemodynamic Measurements in 22 Patients With PAH Compared to Previously Reported Measurements in PPH Patients and Healthy Control Subjects
|Variables||Laskey et al||Present Study|
Healthy Control Subjects (n = 10)
(n = 8)
|PAH Patients (n = 22)||PPH Patients (n = 14)|
|PVR, dyne*s*cm||73 ± 10||880 ± 158||1,282 ± 160||1,457 ± 170|
|Ppa, mm Hg||14 ± 2||50 ± 3||63 ± 3||62 ± 2|
|Pra, mm Hg||11 ± 1||13 ± 1|
|Ppao, mm Hg||9 ± 3||8 ± 4||12 ± 1||12 ± 1|
|Q, L/min||7.4 ± 0.5||4.5 ± 0.6||3.5 ± 0.3||3.1 ± 0.2|
|Z0, dyne*s*cm||1,506 ± 138||1,687 ± 195|
|Z1, dyne*s*cm||38 ± 4||385 ± 75||289 ± 23||319 ± 31|
|Z1 phase, rad||– 0.98 ± 0.06||– 1 ± 0.06|
|Zc, dyne*s*cm||22 ± 4||55 ± 9||124 ± 11||143 ± 15|
|Fmin, Hz||3.6 ± 0.3||5.3 ± 0.3||6.6 ± 0.4||6.3 ± 0.5|
|F0 cross, Hz||7 ± 0.7||6.4 ± 0.8|
|R0F||0.33 ± 0.04||0.88 ± 0.06||0.84 ± 0.01||0.83 ± 0.02|