The target of vasovagal syncope is hemostasis and not heart protection

Severe bleeding is the original context of vasovagal reflex (VVR). As pointed out by the authors, the only way to induce the VVR in all mammals is controlled bleeding. A blood loss of about 30% is sufficient to induce bradycardia and hypotension in all species studied. This is a strong clue that progressive hemorrhage probably has been the context in the common past of all mammals in which the VVR evolved. The response of an organism to smaller amounts of blood loss is centralization of circulation. Vasoconstriction in the splanchnic organs and in the muscles elevates central venous pressure, keeps blood pressure constant and concentrates the perfusion to the heart and brain. During this initial phase, one can speak of a “heart defense mechanism”. However, this strategy is no longer life-saving if the hemorrhage progresses. After a critical blood loss of 30%, switching over the autonomic response to vasodilation and cardiac inhibition is the organism’s last chance to stop the bleeding as pointed out in the CPT [3]. In this way, a larger portion of the cardiac output is now distributed back to the splanchnic organs and the muscles and away from the heart and the brain. Thus, what happens now is just the opposite of a heart defense mechanism. There is no more need for heart protection in an animal bleeding to death. However, if hemostasis succeeds within a few minutes of hypotension, the VVR is terminated, and, after reperfusion, the heart and brain have a good chance of survival without permanent damage.

It is correct that this process is characterized by a change between sympathetic activation and inhibition also seen in VVS induced by orthostatic stress or by lower body negative pressure (LBNP). However, this temporal sequence does not imply causality. The common denominator of blood loss, standing and LBNP is central hypovolemia, which the brain interprets as a signal of hemorrhage. Thus, we see a diphasic circulatory response to orthostasis and LBNP as in the case of bleeding.

The factors of so-called emotional syncopes are blood, injury and medical instrumentation. Nearly all textbooks on syncope mention strong emotions as a possible trigger of vasovagal syncope (VVS). However, it is remarkable that there is no systematic study on VVS in emotional situations independent of a blood, injury or medical instrumentation context. Case reports unequivocally demonstrating reflex hypotension and bradycardia after experiencing pleasure, anger, thirst for revenge, etc., are rare too. There are a few case reports about patients fainting during laughing (gelastic syncope) [5, 12]. However clear vasovagal mechanisms have not been demonstrated in these patients. Moreover, it is not clear in these cases whether the emotion itself or rather afferent signals associated with laughing (e.g., from the diaphragm) triggered fainting. In some studies involving healthy subjects or patients with blood-injury-injection (BII) phobia, the occurrence of vasovagal presyncopes or syncopes when presenting surgery or blood-drawing videos was compared to responses to disgust or fear-related or neutral videos [6‐8, 11]. Vasovagal responses were evoked by blood-injury-related stimuli, but not by other emotional stimuli. Thus, a BII context seems to be the typical background of the so-called emotional syncope, which is in accordance with the CPT [3].

The autonomic response pattern in BII-related fainting is not necessarily diphasic. In 1998, I published the circulatory response during and after a venipuncture in a man with a long history of fainting in BII settings [4]. He had normal blood pressure (BP) and heart rate (HR) values before venipuncture. No significant circulatory changes occurred within the following 2 min. Subsequently, the patient reported discomfort, but he did not lose consciousness for 2 min further. BP and HR declined continuously before full syncope appeared followed by 30 s of asystole. In contrast to the prediction of the HDT, there was clearly no diphasic response.

No diphasic responses in a group of fainters (blood donors) were also demonstrated in the study of Gilchrist and Ditto [6] using impedance cardiography and HR variability analysis. Subsequent fainters already showed lower sympathetic activity than non-fainters in the waiting phase for blood donation instead of a diphasic autonomic response. In a study of Ritz et al. [11] using videos about surgery as a stimulus for VVR, only 20% of BII-phobic patients showed a diphasic circulatory response pattern.

Activation of the coagulation system during blood loss and lower body negative pressure. In an editorial to the first publication of the CPT [3] in Clinical Autonomic Research, Levi [10] added evidence to this theory by reporting a paper about two patients who fainted during venipuncture [2]. In both cases, the blood levels of von Willebrand factor and factor VIII increased dramatically after fainting. These findings could be replicated in two experimental studies [9, 14] in normal subjects who suffered vasovagal pre-syncope during LBNP. Moreover, Zaar et al. [14] demonstrated platelet activation and a significant acceleration of coagulation after LBNP-induced pre-syncope. A reduction in coagulation time is even present during lower levels of LBNP-induced decreases of central venous pressure (CVP) insufficient to induce pre-syncope. This response is comparable to coagulation changes after CVP reductions caused by blood removal (up to 1000 ml total) [13].