Characterization of the Cardiovascular Autonomic Dysfunction in an Experimental Model of Intermittent Acute Porphyria
Authors: Sanches Iris Callado , Freitas Sarah Cristina , Barros Rodrigo Fernandes , Irigoyen Maria‐Cláudia , De Angelis Kátia , Penatti Carlos 
Published: November 2023

Introduction

Delta‐aminolevulinic acid (ALA) is an important endogenous prooxidant in the pathophysiology of porphyria. The ALA treatment may allow the elaboration of an experimental model for the study of neuroautonomic manifestations of porphyria. Porphyrias are enzymatic derangements congenital or acquired in the biochemical formation of the heme group. Individuals affected may manifest serious dysautonomic disorders such as cardiac arrhythmia, arterial blood pressure variation and neurogenic pain.

Objective

To characterize the effects of ALA inoculation on cardiovascular autonomic modulation in male Wistar rats.

Methods

16 male Wistar rats (100–115g) were divided into 2 groups (n=8): controls (C) and treated with ALA (ALA). The animals were inoculated with ALA (40mg/kg; ip) on alternate days. At the end of the 30‐day protocol, the carotid artery was catheterized for direct recording of arterial pressure (AP) and heart rate (HR) (CODAS, 2kHz), and subsequent spectral analysis of the basal AP record for the evaluation of cardiovascular autonomic modulation, in time and frequency domains. Statistical analysis was performed using the unpaired t‐test, p<0.05.

Results

Treatment with ALA induced a reduction in mean AP (C:107±3; ALA:92±2mmHg) in relation to C group, which probably compromised tissue perfusion. No differences in HR was observed between groups (C:388±10; ALA:391±9bpm).In the HR variability analysis, no difference was observed for the pulse interval (PI) between groups (C:188.5±3.15, ALA:169.4±8.18ms). However, there was a decrease in both PI variance (C:140.59±31.04, ALA: 59.98±16.40ms) and PI standard deviation (C:13.23±2.05, ALA:6.94±1.01ms) in the ALA group. Autonomic dysfunction was observed in ALA group with a decrease in high frequency (HF) band of PI (C: 29.12±5.26, ALA:11.80±3.05ms2) and low frequency (LF) band of PI (C:8.73±1.44, ALA:2.99±0.93ms2), but without difference in sympathovagal (LF/HF) balance. In addition, RMSSD, another indicator of parasympathetic modulation, was also reduced in ALA group (C:11.83±1.22, ALA:5.81±1.08ms). Regarding the parameters of systolic AP variability (SAP), SAP decrease was observed in ALA group (C:128.16±4.38, ALA:108.01±2.98mmHg), associated with a decrease in vascular sympathetic modulation (LF‐SAP band ‐ C:5.92±1.77, ALA:1.85±0.39mmHg2).

Conclusion

The results of this study allow to improve the characterization of the clinical manifestations of porphyria. The autonomic dysfunction model was characterized by a dysfunction of both sympathetic and parasympathetic cardiovascular modulation. This type of dysautonomy is also observed in streptozotocin‐diabetic rats, suggesting that the oxidant activity of ALA has an effect similar to that produced by the chronic hyperglycemic state. The porphyria model will allow to advance the understanding of its pathophysiology and to aid the clinical management of the autonomic dysfunctions of the affected individuals.