Discussion

By continuously monitoring systemic haemodynamics of children during cardiopulmonary bypass and the subsequent 48 postoperative hours, we found the novel and consistent arterial pressure waves with a period of ∼ 90 s (∼0.01 Hz) that occurred most frequently in patients with aortic arch abnormalities (42%), secondarily in those with ventricular septal defect (24%) and rarely in other CHD types. In both Aorta and Ventricular Septal Defect Groups, the waves were mostly found immediately after surgical repair with or without the use of cardiopulmonary bypass and lasted 3 to 48 h after CICU admission.

To our knowledge, such waves have not been reported in children with CHD following cardiac surgery. The arterial pressure waves have drawn much attention in the past century. ^{Reference Guyton and Statterfield1–Reference Carroll4} They could be categorised into four types with distinctive frequencies. ^{Reference Carroll4} The first type, with a period of ∼ 1 s, is largely caused by heartbeats; the second (∼5 s, i.e., Traube-Hering waves,) is largely affected by respiration; and the third (∼10 s in humans, i.e., Mayer waves) may occur in healthy humans ^{Reference Taylor, Williams, Seals and Davy16} as well as in various pathological states including cerebral ischaemia ^{Reference Guyton and Statterfield1} and sudden circulatory changes. ^{Reference Guyton and Harris2} Of interest, the frequency of Mayer waves is consistent within species (e.g., 0.3 Hz in rabbits, 0.4 Hz in rats). ^{Reference Julien5} The fourth (∼60 s) has been found in animals like cats, dogs, and rabbits, not yet in humans. ^{Reference Barcroft and Nisimaru17,Reference Roy18} It was named the “spleen wave” because it was caused by the rhythmic spleen volume change. ^{Reference Barcroft and Nisimaru3} Therefore, the waves identified in our patients with a period of ∼ 90 s are the slowest and have not been reported in humans or animals. Besides the period, the wave morphology was also distinctive: the blood pressure increased sharply but decreased in a slower and more intermittent way in the waves we identified (Figure 1), while it fluctuated smoothly in the previous ones. ^{Reference Guyton and Harris2,Reference Barcroft and Nisimaru17,Reference Barcroft, Nisimaru and Steggerda19}

Importantly, such arterial pressure waves had clear clinical implications. Integrating two patient groups’ results, we found that the occurrence of the waves, when compared between the subgroups with or without the waves and particularly within the subgroup with the waves, was significantly associated with poorer systemic haemodynamics (lower blood pressures), myocardial mechanics and efficiency (lower dP/dTmax and cardiac cycle efficiency), worse cerebral oxygenation (lower Vm and ScO₂), and brain injury (worse electroencephalogram background abnormalities and higher number of electroencephalogram sharp waves) as well as renal oxygenation (lower SrO₂).

Both Aorta and Ventricular Septal Defect Groups are characterised by a volume increase in systemic circulation after repair, and specifically in the lower body in the case of aortic arch abnormalities, particularly relative to the smaller systemic arterial vascular bed before repair. Previous studies have identified the “spleen wave” early in 1882, ^{Reference Roy18} that is, a sudden rise in blood pressure or recovery of spleen circulation after a temporary stoppage could elicit rhythmic spleen volume changes in cats, dogs, and rabbits, all with a period of ∼ 60 s, as a potential adaptative mechanism, ^{Reference Barcroft and Nisimaru17} and this volume change could further induce synchronous arterial pressure waves. ^{Reference Barcroft and Nisimaru3} Later experiments showed that similar volume changes in intestine ^{Reference Barcroft, Nisimaru and Steggerda19} and kidney ^{Reference Roy18} could also induce similar arterial pressure waves. This hypothesis may be supported by the relatively higher incidence of wave presence in the left to right shunt CHD types (Table 1) in contrast to the low incidence in tetralogy of Fallot. Of note, synchronised fluctuations in SrO₂ were also found in about 70% of patients with the waves.

Other mechanisms, related to the anatomical and haemodynamic features of aortic arch abnormalities, may uniquely contribute to the higher incidence of the waves in Aorta Group. Before surgery, Aorta Group had adapted to a high upper-body blood pressure and perfusion status. The abrupt decrease in upper-body blood pressure and perfusion after repair may have triggered the brainstem ischaemic response. Central nervous system ischaemia could stimulate the respiratory and cardiac control nuclei in the brain-stem to increase blood pressure as compensative mechanisms to improve brain perfusion and relieve the ischaemic stimulation, and such ischaemia has been used to induce Mayer waves in dogs. ^{Reference Guyton and Statterfield1}

Another potential mechanism for the waves in Aorta Group may lie in the bluntness of the pressoreceptor-autonomic system, which regulates blood pressure via a negative reflex mechanism, and the system delay would result in arterial pressure waves. ^{Reference Guyton and Harris2} This bluntness has contributed to the genesis of Mayer waves. ^{Reference Julien5} Patients with aortic arch abnormalities have been found to have blunted baroreceptor sensitivity due to vascular abnormalities like an increase in collagen and a decrease in smooth muscle content in the pre-coarctation vascular beds, which diminish vascular elasticity even before operation ^{Reference Polson, McCallion and Waki21–Reference Sehested, Baandrup and Mikkelsen23} and are not completely reversible after repair. ^{Reference Celermajer and Greaves24} Besides, the elevated renin and angiotensin II after repair ^{Reference Streeten and Blackman25} may further contribute to this bluntness via acting upon areas of postrema and nucleus tractus solitarii. ^{Reference Polson, McCallion and Waki21} This lack of cerebral vascular elasticity may make the brain more difficult to adapt to the haemodynamics stress caused by the waves, as indicated by the substantially higher electroencephalogram sharp wave number and worse background abnormalities in Aorta Group. ^{Reference Vrselja, Brkic, Mrdenovic, Radic and Curic26,Reference O’Rourke and Safar27} Attention has been increasingly paid to cerebral vascular changes, like intracranial aneurysm, ^{Reference Curtis, Bradley and Wilde28} and brain injuries, like stroke, ^{Reference Trenk, Lammers and Radke29} from the early perioperative period into adulthood in patients with aortic arch abnormalities. ^{Reference Trenk, Lammers and Radke29,Reference Ryan and Richard30}

When the arterial pressure waves occurred, synchronised fluctuations in ScO₂ were also observed in most of patients, reflecting a loss of cerebral autoregulation. ^{Reference Steiner, Pfister, Strebel, Radolovich, Smielewski and Czosnyka7} The loss of cerebral autoregulation has been well documented in children undergoing cardiopulmonary bypass ^{Reference Brady, Mytar and Lee8,Reference Votava-Smith, Statile and Taylor31,Reference Bassan, Gauvreau and Newburger32} and other critically ill patients like sepsis. ^{Reference Crippa, Subirà and Vincent33} It usually applies to what occurs under hypotension (e.g., MBP < 40 mmHg during cardiopulmonary bypass). ^{Reference Brady, Mytar and Lee8,Reference Crippa, Subirà and Vincent33} However, this is not the case in our present study. The synchronised ScO₂ fluctuations did not specifically occur under hypotension, rather they have a clear time window, i.e., the early postoperative period. Such loss of cerebral autoregulation may be more similar to that observed in severe head injury patients with Mayer waves. ^{Reference Lemaire, Khalil and Cervenansky34} However, the waves identified in our study are unique and have the slowest frequency compared to other waves ever reported. The loss of cerebral autoregulation, in either way, would render the brain vulnerable to injuries. For example, an abrupt increase in blood pressure would be particularly dangerous for causing haemorrhagic complications. ^{Reference Neil, Volpe, Volpe, Inder, Darras, de Vries, du Plessis, Neil and Perlman35} This might also contribute to the worse brain injury in our patients with the waves, particularly in Aorta Group.

Some studies have reported the positive implications of the arterial pressure waves. ^{Reference Julien5,Reference Aalkjær, Boedtkjer and Matchkov36} For example, Mayer waves could trigger the liberation of endothelium-derived nitric oxide and benefit the end-organ function. ^{Reference Julien5} Likewise, rhythmic vasomotion, leading to a blood flow motion, could improve tissue oxygen delivery and metabolism. ^{Reference Aalkjær, Boedtkjer and Matchkov36} Thus, although these waves were associated with poorer haemodynamics and compromised brain perfusion and function, they might not contribute to them. Rather they might serve as an adaptive mechanism responding to them, like pacemaker for example. ^{Reference Julien5} Clearly, these above-discussed mechanisms are purely speculative, based on previous studies on other types of arterial pressure waves. Note that 46 patients with different CHD types and different age and gender had the same unique wave frequency (∼0.01 Hz), so there may be other mechanisms underlying the wave genesis in children with CHD following surgical repair that need explorations and expectedly complex. Mayer waves found more than 70 years ago remain an enigma. ^{Reference Julien5}