The present study examined whether the forearm oxygenation response correlated with MAP recovery during PSVT and VT. The major findings of this study are that (1) both PSVT and VT resulted in a decrease in forearm oxygenation irrespective of MAP changes; (2) MAP recovery during PSVT was correlated with the decrease in oxygenation; (3) MAP recovery during VT was not correlated with the decrease in oxygenation, irrespective of the presence or absence of α1– and β1-AR blockers or the drugs infused during EPS; (4) the recovery of PP was related to MAP recovery during both PSVT and VT. These novel findings suggest that the decrease in forearm oxygenation, presumably caused by vasoconstriction, contributes to MAP recovery during PSVT, but is insufficient to recover MAP during VT. In contrast, PP recovery may reflect partial recovery of SV and sympathetic arterial stiffening, which subsequently assists in MAP recovery during PSVT and VT.
We observed a gradual decrease in forearm oxygenation during both PSVT and VT (Fig. 1), which indicates a reduction in peripheral tissue blood flow16,17,18,19. Moreover, it was likely caused by vasoconstriction rather than a decrease in perfusion pressure (i.e., MAP; Fig. 2), which is consistent with a previous study whereby ventricular pacing resulted in a decrease in forearm blood flow and an increase in vascular resistance21. Vasoconstriction during tachyarrhythmia is caused primarily by the arterial baroreflex to recover MAP1,2,3. Notably, the decrease in forearm oxygenation was maintained even when the MAP returned to the baseline level during PSVT (Fig. 1). This phenomenon may be due to the decrease in PP, which is another stimulus to the arterial baroreceptors22. Indeed, increased muscle sympathetic nerve activity appears to be maintained throughout ventricular pacing, irrespective of the recovery of MAP to pre-pacing levels3,4.
Decreased peripheral blood flow caused by vasoconstriction is believed to contribute to MAP recovery during tachyarrhythmia. We confirmed that the decrease in forearm oxygenation correlated negatively with the recovery of MAP throughout PSVT (Fig. 3), which indicates that as the forearm oxygenation decreased, the MAP increased. Interestingly, the effectiveness of forearm oxygenation reduction lessened with MAP restoration over time because MAPrecovery reached a plateau (Fig. 1), and the slope of the correlation appeared to reduce as time passed from the onset of PSVT (Fig. 3). In contrast, we found that the decrease in forearm oxygenation during VT increased with time, but was unrelated to MAP recovery (Figs. 2 and 3), suggesting that peripheral vasoconstriction did occur (preventing further hypotension), but it lacked efficacy in terms of MAP recovery. Therefore, we inferred that the reduction in peripheral blood flow caused by vasoconstriction was useful in the recovery of MAP during PSVT, but not during VT.
The differential effects of forearm oxygenation reduction on MAP recovery between the PSVT and VT groups were attributed to the variations in CO and/or the ability to evoke vasoconstriction. Previous studies have demonstrated lower SV and CO during ventricular pacing than those during atrial pacing and dual-chamber cardiac pacing at the same rate5,6,7,8. The same applies to the comparison between VT and PSVT. Additionally, the heart dysfunction observed in patients with VT (Table 1) may have also contributed to a decrease in CO during tachyarrhythmia, resulting in less blood delivered to the peripheral vasculature during VT. When the blood supply is lowered beyond a certain threshold, peripheral vasoconstriction cannot effectively increase peripheral vascular resistance, resulting in the failure of AP recovery. Although we were unable to measure CO in this study, our results indicate that CO during tachyarrhythmia may be a determinant of the effectiveness of peripheral vasoconstriction in MAP recovery.
Interestingly, MAP recovery correlated with PP recovery during both PSVT and VT (Fig. 4), while MAP recovery correlated with only the TOI response in PSVT (Fig. 3). Partial recovery of SV during PSVT and VT may contribute to PP and MAP recovery. In a previous study5, CO transiently decreased and then returned to its control level during constant atrial or ventricular pacing, presumably due to the increase in venous pressure (i.e., higher filling pressure) that resulted from the accumulation of blood in the large veins and atria. Another contributor to PP and MAP recovery is an increase in the sympathetic vasomotor outflow to the central and peripheral arteries during PSVT and VT. The augmented sympathetic vasomotor drive causes not only peripheral vasoconstriction but also arterial stiffening23, which lead to a larger forward wave amplitude, earlier reflected wave arrival, and greater PP24.
Impaired vasoconstriction may also explain the lack of relationship between decreased forearm oxygenation and MAP recovery during VT. However, the present study revealed that the reduction in forearm oxygenation during VT was independent of changes in MAP and appeared to be greater than that during PSVT (Figs. 1 and 2). These results suggest that the decrease in blood flow during VT was not simply secondary to hypotension, but was influenced by similar or greater vasoconstriction compared to that during PSVT. This inference is supported by previous findings25,26,27 that large AP changes (> 30 mmHg) evoked similar arterial baroreflex responses of sympathetic nerve activity between patients with and without left ventricular dysfunction and/or heart failure, which are common in patients with VT (Table 1)9. Similarly, in the present study, the change in AP (> 30 mmHg) and average depressor response during VT were equal (Fig. 2). These results suggest that sympathetic vasomotor outflow may increase to a similar or greater degree during VT than PSVT, irrespective of heart dysfunction. Such a rise in sympathetic vasomotor outflow would cause vasoconstriction at least in the forearm muscles because intraarterial (radial artery) administration of α1– or α2-adrenergic receptor (AR) agonist produced equivalent forearm vasoconstriction in normal volunteers and patients with heart failure28. However, caution is needed because the findings for α1-AR responsiveness in congestive heart failure are not unanimous29. Even if the α1-AR responsiveness was impaired by ~ 50% as shown in the common femoral artery30, the weak vasoconstriction would restore MAP somewhat, which might result in “gentle” slope of the relationship between decreased forearm oxygenation and MAP recovery during VT. The above background implies a low possibility that impaired vasoconstriction in patients with VT results in a lack of correlation between forearm oxygenation reduction and AP recovery; however, this should be verified by future studies.
Other possible confounders could explain the lack of a relationship between the TOI response and MAPrecovery during VT. First, vasoactive drugs taken before EPS, especially α1-AR blocker, may have reduced the ability to evoke peripheral vasoconstriction. However, excluding the data of (1) patients receiving α1– and β1-AR blockers and (2) the drugs infused during EPS had no effect on the ΔTOI-MAPrecovery relationship as shown in Table 3. Second, patients with VT had a higher prevalence of chronic kidney disease than those with PSVT (Table 1). However, previous studies31,32 have found similar baroreflex control of sympathetic activity between control participants and patients with chronic renal failure. We confirmed the lack of relationship during VT by excluding data of chronic kidney disease (Table 3). Finally, the initial decrease in MAP tended to be greater during VT than PSVT; however, the degree of initial hypotension was unrelated to the lack of the ΔTOI-MAPrecovery relationship (Table 3). Although we attempted to account for the confounders in the present study, other possible confounders (e.g., structural heart disease and heart dysfunction) may explain the lack of ΔTOI-MAPrecovery relationship during VT. Thus, our results can be considered pilot data.
The AP response and tachyarrhythmia symptoms vary greatly among patients33. Our findings suggest that AP recovery during tachyarrhythmia is dependent on the type of tachyarrhythmia. Patients with VT and smaller CO, as well as an impaired ability for peripheral vasoconstriction, are encouraged to receive therapy (e.g., ablation) due to poor tachyarrhythmia tolerance. Likewise, the same may be true in patients with PSVT as syncope can occur during PSVT34,35. If VT/PSVT patients have an impaired ability for peripheral vasoconstriction as observed in heart failure patients, chronic use of carvediol (mixed β and α1-AR antagonist) may improve the vascular α1-AR signal transduction and hence the vasoconstrictor ability with a decrease in resting AP36.
The present study had several limitations. First, peripheral blood flow was not directly measured, but was instead estimated according to the forearm oxygenation response. Second, the rate, duration, and AP responses during tachyarrhythmia were not artificially regulated because this study was conducted during actual tachyarrhythmias and not during cardiac pacing, to understand the clinical status of the patients. Third, it was difficult to measure CO, SV, and intraventricular pressure during tachyarrhythmia in patients because of the nature of the observational study design as well as the spontaneous nature of tachyarrhythmias, their immediate termination, and the limited time for evaluation.
In conclusion, the present study demonstrated for the first time a differential relationship between forearm oxygenation reduction, presumably caused by vasoconstriction, and MAP recovery during PSVT and VT after the exclusion of some confounders. Therefore, in clinical and daily situations, restricting peripheral blood flow is likely associated with MAP recovery during PSVT, but not during VT. This discrepancy may be the result of a difference in CO and/or the vasoconstriction ability during PSVT and VT. Predicting CO and vasoconstriction ability during tachyarrhythmia could be valuable for preventing syncope onset in clinical and everyday settings and selecting therapy.