Search

We used spectral analysis of heart rate (HR), blood pressure (BP), and respiration to examine the effects of lactate on cholinergic and adrenergic influences on HR and BP variability, a technique found to be very useful in cardiovascular research. We specifically used high frequency (0.2-0.5 Hz) and midfrequency (0.07-0.15 Hz) powers to study cholinergic and adrenergic activity in nine normal control subjects before and after lactate and placebo infusions. Our results demonstrate a marked decrease in cholinergic activity and a significant increase in sympathovagal ratios of HR modulation after lactate infusions. This altered sympathovagal balance may contribute to the panicogenic effects of lactate in panic disorder patients.

Using spectral analysis of the continuous time series signal before and during lactate and placebo infusions, the authors studied heart rate variability in six patients with panic disorder and nine normal comparison subjects. The decrease in high-frequency (0.20-0.50 Hz) power and the increase in sympathovagal ratios (mid-frequency [0.07-0.15 Hz] to high-frequency powers) after the administration of intravenous sodium lactate were significantly greater in the patients than in the normal subjects after correction of the values for the amount of lactate infused. This result suggests an exaggerated cardiac vagal withdrawal in patients with panic disorder during lactate infusions.

Gamma aminobutyric acid (GABA), an inhibitory neurotransmitter, may play an important role in anxiety. We studied changes in plasma GABA levels in nine healthy subjects before and after infusions of sodium lactate and dextrose. Plasma GABA significantly decreased during infusions of sodium lactate (109.3 +/- 4.4 versus 91.6 +/- 5.1 pmol/ml; P = 0.0001) but not during infusions of dextrose.

In a double-blind study using sodium lactate and isoproterenol infusions to provoke panic attacks, 73 of 86 panic disorder patients and 10 of 45 controls panicked with lactate, and 58 of 86 patients and 4 of 45 controls panicked with isoproterenol. We measured baseline and peak anxiety ratings in 10 controls with lactate-induced panic attacks, 31 controls who did not panic during lactate infusions, and 63 panic disorder patients who did panic during lactate infusions. The controls who panicked with lactate had robust increases in their anxiety ratings very similar to the increases experienced by patients who panicked with lactate.

Preinfusion anxiety, heart rate, and blood pressure were measured in 31 normal subjects who received sodium lactate infusions. Eight subjects developed symptoms of panic anxiety during these infusions. Preinfusion anxiety as measured by psychologic symptoms of anxiety on the Panic Description Scale was significantly higher in the panickers while heart rate and blood pressure were not.

Seventy panic disorder patients participated in a double-blind, placebo-controlled, randomized infusion study in which sodium lactate and isoproterenol were used to induce panic anxiety. Patients who panicked during lactate, isoproterenol, and placebo infusions generally had higher preinfusion anxiety scores. These findings held true irrespective of the order the infusions were given. Stepwise multiple regression analyses comparing panickers with nonpanickers as the criterion variable revealed that the items "afraid of going crazy," "feeling unsteady," and "feeling paralyzed" on the Panic Description Scale had the highest predicting values.

We compared the responses of bulimic subjects to those of panic disorder patients and normal controls during infusions of sodium lactate and isoproterenol in a double-blind, placebo-controlled study. Four of 8 bulimics infused with lactate had panic attacks. Three of 9 bulimics infused with isoproterenol panicked, and 1 bulimic panicked with a placebo infusion. Although bulimics were less likely than panic disorder patients to panic during provocative infusions, their anxiety levels as measured by a panic description scale were as great. A large portion of the anxiety response in bulimics occurred in those who had concurrent panic attacks.

Eleven of 45 normal control subjects experienced panic attacks during lactate and/or isoproterenol infusions. Ten of the 11 subjects were followed up for a mean period of 32.5 months. Two subjects reported the development of spontaneous panic attacks during the follow-up period; one related the development of these attacks to the infusion experience. Neither subject met DSM-III criteria for panic disorder either before or after the infusions. Twenty-six healthy control subjects who did not experience panic attacks during the infusion experience did not report any attacks during a follow-up period of 31.1 months.

To investigate the relationship between naturally occurring and drug-induced panic attacks, we compared the phenomenology of panic attacks in 12 panic disorder patients who panicked during both placebo and lactate infusion and in 9 panic disorder patients who panicked during both placebo and isoproterenol infusions. Panic attacks during lactate and isoproterenol infusions were similar to the panic attacks during placebo infusions.

The authors infused 45 control subjects with sodium lactate. Eight of 10 subjects with lactate-induced panic attacks and 26 of 35 without panic attacks were interviewed. An investigator, blind to the outcome of the infusion study, obtained family histories of 160 relatives. There was a high prevalence of anxiety disorders among first-degree relatives of subjects with panic attacks. There was no significant difference in the prevalence of mood disorders and substance abuse between first-degree relatives of subjects with (N = 45) and without (N = 115) panic attacks. The results suggest that individuals with a family history of anxiety disorders may be vulnerable to lactate-induced panic attacks.

Fourteen patients with panic disorder were infused with sodium lactate both before and after treatment with tricyclic antidepressants. All patients had panic attacks before treatment, and only five after treatment. There was a significant decrease in measures of anxiety prior to and during infusions after treatment. The patients were able to tolerate more lactate during reinfusions. The comparison of reinfusion panickers and nonpanickers revealed that the reinfusion panickers had higher levels of anxiety, as measured by psychological symptoms on the Panic Description Scale, during both their pretreatment and posttreatment infusions. Tricyclic antidepressants appear to increase the threshold for lactate-induced panic attacks.

Resting and pre-infusion heart rates recorded in 66 panic disorder patients revealed no significant differences between panickers and nonpanickers. There was also no significant difference in pre-fusion heart rates between either lactate or isoproterenol panickers and placebo nonpanickers. There was neither a sensitizing nor a desensitizing effect of laboratory-induced panic attacks on subsequent pre-infusion heart rates.

The effects of infusion-induced panic-anxiety on subsequent pre-infusion anxiety ratings and infusion-induced panic attacks were studied in 64 panic disorder patients, in a double-blind randomized study using sodium lactate, isoproterenol, and placebo infusions. While there was a decrease of preinfusion anxiety from one infusion to the next infusion both for panickers and nonpanickers, there was no evidence of either a significant decrease or an increase in the frequency of subsequent panic attacks. These results suggest that there is neither a desensitizing nor a sensitizing effect of pharmacologically induced panic attacks on subsequent infusions in a serial three-infusion design.