Incidence, timing of pre-syncope, and the influence of climbing
Twelve (30%) out of the 40 tests were prematurely interrupted due to signs and symptoms of a pre-syncope, i.e., dizziness, light-headedness, pallor, warmth, blurred vision, and nausea (Fig. 2). The mean suspension time until the occurrence of the pre-syncope was 44.7 ± 13.3 min (minimum 13.4, maximum 59.7). Seven of the 12 (58.3%) pre-syncopal episodes occurred in participants who climbed before the suspension phase with a mean time to pre-syncope of 47.0 ± 10.5 min. The remaining five (41.7%) pre-syncopal episodes were observed without climbing prior to the suspension phase and occurred after a mean time of 41.5 ± 17.2 min. Four participants experienced pre-syncope during both tests (i.e., with and without prior climbing). The time until pre-syncope of these four participants was 40.4 ± 8.5 min with and 48.5 ± 8.1 min without climbing (P = 0.068).
The 28 tests without a pre-syncopal episode were interrupted because the predefined maximal duration of the suspension phase (60 min) was reached (43%) or due to pain (36%) or numbness/palsy (21%) in the lower extremities. The mean duration of the suspension phase in tests without a pre-syncope was 47.1 ± 13.5 min.
Pain, numbness, and palsy in the lower extremities
During 24 tests (60%), participants reported pain in the lower extremities ≥ 3/10 on a 10-step NRS (Breivik et al. 2008). Among participants who experienced a pre-syncope, 75% (9 out of 12) reported a pain level ≥ 3 on the NRS. Although pain level did not differ between participants with and without a pre-syncope neither in the climbing session (5.1 ± 2.9 vs. 4.0 ± 2.8 on the NRS, P = 0.430) nor without previous climbing (3.5 ± 2.7 vs. 5.1 ± 2.9, P = 0.310), pre-syncope had an effect on pain level (P = 0.003, estimated marginal means for pain 2.9 without pre-syncope and 8.0 with pre-syncope) in a general linear model with climbing, pre-syncope and its interaction term as fixed factors and subject as random factor. Numbness was reported in 18 (45%) and palsy of the lower legs in 12 (30%) cases. Clinically, marked cyanosis of the lower legs was observed during the suspension phase.
Results of the linear mixed models (LMM)
The analysis of the factors (i.e., time, climbing, pre-syncope, pain and interactions of time with climbing, time with pre-syncope and time with pain) that influenced the progresses of the diameter of the SFV, StO2, HR, systolic BP, SV, LVEDD, LVESD and ScO2 during the suspension and post-suspension phases is presented in Table 2.
Table 2 P values for fixed effects considered in the linear mixed model
Time had an effect on all the parameters, while climbing (considering also its interaction with time) only on HR, systolic BP and StO2. For ScO2 the interaction of climbing with time did not reach statistical significance but was very close to it (P = 0.052). Interaction of pre-syncope with time had an effect on HR and SBP, indicating that participants with and without pre-syncope showed different progresses. Pre-syncope alone had an effect on SFV, LVEDD, and LVESD, indicating that participants with and without pre-syncope had a steady difference during the tests, i.e., participants who experienced a pre-syncope had a smaller diameter of the SFV (1.1 mm) and slightly larger ventricular diameters (1.2 mm for LVEDD and 1.9 mm for LVESD).
In the following paragraphs, for each parameter the results of the pairwise comparisons of the time points are described.
Venous pooling
Diameter of the superficial femoral vein
The mean baseline diameter of the right SFV in the supine position was 6.4 ± 1.6 mm and increased to 9.9 ± 1.8 mm while standing (P < 0.001). The mean diameter of the SFV at the beginning of the suspension phase was 10.2 ± 2.1 mm. During the suspension phase, the diameter did not change significantly, neither in the pre-syncope cases nor in the cases without pre-syncope. Likewise, no influence of climbing on the SFV diameter was found. At 5 min of the post-suspension phase (in the supine position), a decrease in the diameter of the SFV was observed (10.6 ± 2 mm at the last measurement during suspension vs. 6.2 ± 1.6 mm at 5 min in the post-suspension phase, P < 0.001). SFV diameter changes during the tests are depicted in Fig. 3.
Tissue oxygen saturation (StO2) of the calf muscle
Baseline StO2 decreased from supine to the standing position (70.1 ± 6.6 vs. 56.4 ± 5.6%, P < 0.001). During the first 5 min of the suspension phase, a decrease in StO2 was detected in participants who did not climb (57.3 ± 5.5 vs. 52.4 ± 6.1%, P = 0.001), while StO2 did not change when participants had climbed before suspension (53.2 ± 4.4 vs. 52.8 ± 4.6%, P = 1.000). From minute 5 of the suspension phase to 3 min before end of the suspension phase, StO2 decreased further in both groups (52.6 ± 5.3 vs. 48.7 ± 5.6%, P = 0.002). During the first 5 min of the post-suspension phase, an increase in StO2 was observed (49.4 ± 6.5 vs. 63.6 ± 5.1%, P < 0.001). StO2 changes during the tests are depicted in Fig. 3.
Localized bioelectrical-impedance analysis
The resistance (R) (200.2 ± 18.6 vs. 193.6 ± 17.9, P < 0.001) and reactance (Xc) (27.7 ± 4.2 vs. 26.6 ± 3.7, P = 0.001) changed from supine to standing position. Xc further decreased from the start to the last measure during the suspension phase (26.4 ± 3.6 vs. 22.9 ± 3.1, P < 0.001) while R (192.3 ± 18.3 vs. 190.7 ± 17.6, P = 0.201) did not change. The general linear model showed no effect of climbing (P = 0.514 and P = 0.253 for R and Xc, respectively) or pre-syncope (P = 0.981 and P = 0.701 for R and Xc, respectively) from the start to the last measure during the suspension phase.
Hemodynamic changes
Heart rate
Baseline HR increased from supine to the standing position (63.1 ± 7.9 vs. 72.4 ± 9.4 bpm, P < 0.001). During suspension, HR decreased from the start to 3 min before the end of the suspension phase in participants who had climbed before (113.3 ± 15.9 vs. 96.0 ± 18.5 bpm, P < 0.001) but did not change in participants who had not climbed (79.8 ± 14.4 vs. 84.4 ± 15.2 bpm, respectively, P = 0.098). In participants with pre-syncope, HR decreased in the last 3 min before the pre-syncopal event (96.3 ± 22.4 vs. 82.2 ± 19.4 bpm, P = 0.043) and decreased further during the first 5 min of the post-suspension phase (82.2 ± 19.4 vs. 62.9 ± 13.5 bpm, P = 0.033). In participants who did not manifest a pre-syncope, HR remained stable until the end of the suspension phase and decreased only in the first 5 min of the post-suspension phase (86.4 ± 15.8 vs. 60.3 ± 10.1 bpm, P < 0.001). HR changes are depicted in Fig. 4.
Systolic blood pressure
Systolic BP increased at baseline from supine to standing (121.1 ± 13.2 vs. 138.7 ± 14.7 mmHg, P < 0.001). In participants who had not climbed before the test, systolic BP did not change from the start of the suspension phase until 3 min before end of the suspension phase (143.8 ± 12.8 vs. 148.0 ± 15.3 mmHg, P = 0.272) but increased in participants who had climbed before (123.6 ± 17.1 vs. 139.2 ± 21.8 mmHg, P = 0.034). In participants with pre-syncope, systolic BP decreased significantly in the last 3 min before the pre-syncopal event (142.5 ± 18.6 vs. 101.6 ± 17.4 mmHg, P = 0.001) while it did not change in participants without a pre-syncope (144.1 ± 19.6 vs. 141.7 ± 20.4 mmHg, P = n.s.). During the first 5 min of the post-suspension phase, systolic BP decreased in participants without a pre-syncope (141.7 ± 20.4 vs. 128.9 ± 17.8 mmHg, P = 0.038) and increased in participants who had a pre-syncope (though not reaching statistical significance; 101.6 ± 17.4 vs. 124.9 ± 18.2 mmHg, P = n.s.). Systolic BP changes are depicted in Fig. 4.
Stroke volume
In both participants with and without climbing before the suspension phase, stroke volume decreased from the beginning of the suspension phase to 3 min before the end of the suspension (80.1 ± 14.7 vs. 69.7 ± 15.9 ml, P = 0.007). No statistically significant reduction of stroke volume in participants with a pre-syncope was detected before the occurrence of signs and symptoms of pre-syncope. In the first 5 min of the post-suspension phase, SV increased (73.5 ± 16.5 vs. 98.9 ± 14.9 ml, P < 0.001). SV changes are depicted in Fig. 4.
Left ventricular diameters
LVEDD
Baseline LVEDD decreased from supine to standing (44.0 ± 4.2 vs. 40.7 ± 3.8 mm, P < 0.001). During the suspension phase, no significant change in LVEDD was observed. LVEDD increased from the last measure taken before the end of suspension to the start of post-suspension phase (39.3 ± 3.6 mm vs. 41.9 ± 4.2 mm, P = 0.001). LVEDD changes are depicted in Fig. 4.
LVESD
LVESD did not change at baseline from supine to standing (27.6 ± 3.9 mm vs. 26.5 ± 3.6 mm, P = 0.098). No pairwise comparison of the time points was significant.
Cerebral oxygen saturation (ScO2)
ScO2 did not change from supine to standing at baseline (67.9 ± 4.7 vs. 67.2 ± 4.3%, P = 0.199). Between the start and 3 min before the end of suspension phase, a statistically significant increase in ScO2 was observed in participants who did not climb before suspension (66.3 ± 4.5 vs. 69.9 ± 5.6%, P = 0.001; relative change from start + 5.4% ± 5.2%), whereas in those with prior climbing, ScO2 remained constant (70.3 ± 5.8 vs. 69.8 ± 5.9%, P = n.s.; relative change from start − 0.5% ± 7.1%). In the participants with pre-syncope, ScO2 did not change significantly in the 3 min preceding the pre-syncope (73.0 ± 6.2 vs. 69.1 ± 6.2%, P = n.s.; relative changes from start + 3.8% ± 8.6% vs. − 1.8% ± 7.1%). Also during the first 5 min of the post-suspension phase, ScO2 did not change (68.4 ± 5.5 vs. 69.5 ± 5.2%, P = 0.194; relative changes from start + 0.4% ± 6.8% vs. + 2.0% ± 7.1%).
Baroreceptor-sensitivity
39 out of 40 tests were included in the baroreceptor-sensitivity analysis (one with missing data was excluded). Overall, no time effect of pre-syncope on baroreceptor-sensitivity was found (P = 0.308). Nonetheless, in the first minutes during suspension in the tests without prior climbing, baroreceptor-sensitivity was higher in participants without syncope compared to the ones with pre-syncope (12.6 ± 3.6 vs. 7.7 ± 3.8, P = 0.026). In the tests with prior climbing, no such differences were found (7.2 ± 3.3 vs. 6.7 ± 3.5, P = 0.782).