Respiratory Responses to Intravenous Infusion of Sodium Lactate in Male and Female Wistar Rats

Abstract

In patients with panic disorder or premenstrual dysphoria, anxiety attacks can be triggered by intravenous administration of sodium lactate. Since respiratory symptoms, such as hyperventilation and shortness of breath, are characteristic features of spontaneous as well as lactate-induced panic, an involvement of central or peripheral chemoreceptors in this reactionIn patients with panic disorder (Liebowitz et al. , 1985Pitts and McClure 1967) or premenstrual dysphoria (Facchinetti et al. 1992;Sandberg et al. 1993), but not in healthy controls, intravenous (i.v.) administration of sodium lactate elicits an anxiety reaction strongly resembling spontaneous panic attacks. The anxiogenic effect of sodium lactate has been attributed to changes in calcium concentrations (Pitts and McClure 1967), pH (Grosz andFarmer 1972), redox activity (Carr et al. 1986), pCO 2 (Gorman et al. 1988a), and osmolarity (Jensen et al. 1991;Peskind et al. 1998). However, all these theories and findings have also been questioned, and the mechanism by which sodium lactate elicits panic attacks hence is as yet unexplained.Likewise, the reason why patients with panic disorder or premenstrual dysphoria differ from controls with respect to sensitivity to lactate is a matter of controversy. Notably, a more rapid and substantial rise in brain lactate has been observed in panic patients as compared with control subjects (Dager et al. 1999), but the difference between patients and controls may also be due to different responsiveness to a given concentration (Pohl et al. 1994;Rifkin et al. 1981).Panic attacks are almost always associated with hyperventilation and respiratory discomfort, such as shortness of breath; it has thus been suggested that lactate-induced as well as spontaneous panic attacks may be due to an activation of a hyperresponsive suffocation alarm system involving activation of central or peripheral chemoreceptors (Klein 1993). Supporting this concept, an anxiety-provoking effect similar to that of lactate has been observed after inhalation of CO 2 in panic disorder subjects and in women with premenstrual dysphoria (Gorman et al. , 1988aGriez et al. 1987;Harrison et al. 1989;Kent et al. 2001;Papp et al. 1997;Perna et al. 1994;Woods et al. 1986).We have previously reported that intravenous administration of sodium lactate to Wistar rats, but not to rats of the Sprague-Dawley strain, elicits an increase in blood pressure and variable effects on heart rate (Wikander et al. 1995). Such cardiovascular response is in line with the assumption that lactate induces a stimulation of central or peripheral chemoreceptors. In the present study, the effect of sodium lactate on respiratory rate and tidal volume in freely moving, unrestrained male and female rats of the Wistar strain was explored. Given the previous reports suggesting that spontaneous panic attacks are menstrual cycle-dependent (Basoglu et al. 2000;Breier et al. 1986;Cameron et al. 1988;Cook et al. 1990;Klein 1993), that panic disorder may improve during pregnancy (Hertzberg and Wa...

Modeling Cerebral Arteriovenous Lactate Kinetics after Intravenous Lactate Infusion in the Rat

“…Lactate (1 mol/L, sodium-L-lactate) was infused at a rate of 100 L/min (equivalent to 100 mol/min) for 5 to 33 minutes (n ‫ס‬ 7). Similar protocols have been used in humans as well as in rats (e.g., Peskind et al, 1998;Wikander et al, 1995;Olsson et al, 2002). In the present and the previously published experiments with rats (Wikander et al, 1995;Olsson et al, 2002), the amount of infused Na salt ranges between 0.5 and 3 mmol (or 2 mmol to 12 mmol per kilogram body weight).…”

Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study

“…45 A disturbance of cerebrovascular regulation could contribute to elevated brain lactate responses in PD. 32,33 Lactate is a respiratory stimulant in humans 9 and animals, 26,27 and is a panicogen in PD patients, although the mechanism(s) of these effects are not yet known. Chemosensitive cells in both brainstem and suprapontine regions, including the ventral medulla, locus ceruleus, raphe nuclei, periaqueductal gray, hypothalamus and amygdala, strongly influence the regulation of arousal, as well as respiration and cardiovascular function.…”

“…9 The latter reflects lactate's action as a respiratory stimulant. 26,27 Thus, sodium lactate infusion, like hyperventilation, leads to increased production of endogenous lactic acid as a homeostatic response to alkalosis. Of the many published lactate infusion studies, only two examined patient versus control subject comparisons of serum lactate levels matched for total volume of exogenous lactate infused.…”

Control of Breathing During Exercise

“…For example, Brack et al (52) found that injection of a panicogenic agonist into the PAG of anesthetized rats elicited a hyperpnea, and a hyperpnea is a common feature of a panic attack (12,256,257).…”