Evaluation of the effects of gabapentin on the physiologic and echocardiographic variables of healthy cats: a prospective, randomized and blinded study

Veronezi, Tayná Mayer; Lopes, Daniela Jardim; Zardo, Izadora L; Ferronatto, João Vb; Trojan, Marcelo Marchetti; Franck, Kirian R; Azevedo, A.; Spiering, Adriana G; Nunes, Luciana Neves; Fadel, Leandro; Costa, Fernanda Vieira Amorim da

doi:10.1177/1098612x221131270

Cited by 7 publications

(11 citation statements)

References 23 publications

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“…Although GBP has long been used in a neurosetting, its cardiovascular side effects have recently attracted attention in human medicine, veterinary medicine, and basic medical science areas [8,18]. However, the exact actions and underlying mechanisms of GBP on the heart, blood vessels, and autonomic regulation remain to be completely elucidated.…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats

Pendyala,

Pribil,

Schaal

et al. 2023

Cells

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Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant for the treatment of partial seizures and neuropathic pain. Whereas a majority of the side effects are associated with the nervous system, emerging evidence suggests there is a high risk of heart diseases in patients taking GBP. In the present study, we first used a preclinical model of rats to investigate, firstly, the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and secondly the effects of chronic GBP treatment (i.p. 100 mg/kg/day × 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In the first experiment, we found that i.v. GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (* p < 0.05 and ** p < 0.01 vs. baseline; n = 4). In the second experiment, we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Notably, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.

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Section: Discussionmentioning

confidence: 99%

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats

Pendyala,

Pribil,

Schaal

et al. 2023

Cells

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“…2 Gabapentin has been shown to decrease visit-associated stress in feline patients in a variety of clinical scenarios, including the measurement of BP, and in general is considered to be a relatively safe medication with minimal clinically significant effects on physiologic parameters. [4][5][6][7][8][9][10][11][12][13] However, special consideration should be given when using gabapentin in patients with compromised kidney function. Gabapentin is eliminated almost entirely through renal excretion, and decreased renal function significantly influences the pharmacokinetics of gabapentin in humans.…”

Section: Introductionmentioning

confidence: 99%

“…15 In addition, dose-normalized serum gabapentin concentrations were positively correlated with serum creatinine, indicating that greater caution is needed in more advanced kidney disease. 15 Previous studies evaluating the effect of gabapentin on BP have been performed in normal feline patients, 11,12 but the effect of gabapentin on BP in cats with CKD has not been assessed. Anecdotal incidents of hypotension associated with higher doses of gabapentin (particularly in cats with CKD) have been reported.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease

Quimby,

Jones,

Saffire

et al. 2024

Journal of Feline Medicine and Surgery

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Objectives The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). Methods A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2–4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. Results After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82–170) than after administration of the placebo (median 150 mmHg, range 102–191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96–170) than after administration of the placebo (median 155 mmHg, range 102–191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82–139) than after administration of the placebo (median 137 mmHg, range 102–177; P = 0.002). The median change in BP was −12 mmHg (range −95 to 10) for healthy cats and −12 mmHg (range −43 to 21) for cats with CKD (no significant difference between subgroups). Conclusions and relevance Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.

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“… 9 A more recent randomized, masked study compared hemodynamic and echocardiographic variables in gabapentin- vs placebo-treated young cats and found no significant difference in Doppler-derived SBP between groups. 12 However, no studies are available using direct measurement of BP, which is particularly important in this species to overcome the known inaccuracy and imprecision of indirect BP measurement methods.…”

Section: Introductionmentioning

confidence: 99%

Effect of gabapentin on ambulatory, direct, systemic arterial blood pressure in apparently healthy cats in the at-home and in-clinic environments

De Lombaert,

Lourenço,

Coleman

et al. 2023

Journal of Feline Medicine and Surgery

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Objectives Situational increases in blood pressure (BP) frequently confound the accurate diagnosis of pathological systemic hypertension in cats. The objective of this study was to investigate the effect of gabapentin on direct, ambulatory systolic arterial BP (SBP) in cats in at-home and in-clinic environments. Methods Six adult purpose-bred cats with surgically implanted femoral artery telemetric BP-sensing catheters were administered 100 mg of gabapentin or a placebo orally in two randomized, masked, crossover study phases. In the first, direct BP was measured continuously in undisturbed cats for 24 h before (at-home baseline) and 4 h after administration of study drug. The mean SBP after administration of the drug was compared between treatments. In the second study period, cats were administered gabapentin or placebo 90 mins before transport to a clinic, where direct BP was measured continuously during a simulated veterinary visit that included an indirect BP measurement session. Changes in mean direct SBP relative to the 24-h at-home pre-treatment period were calculated for each of one waiting room and two examination-room periods, and compared between treatments. Concurrent in-clinic direct and indirect SBP measurements were compared within-cat. Data were compared using linear mixed models. Results Direct SBP data from one cat were excluded due to implant failure. There were no differences in at-home or in-clinic SBP between treatment groups, with large inter-individual variability. Cats in both treatment groups experienced in-clinic increases in direct SBP relative to at-home baseline (range 11–50 and 10–52 mmHg in placebo- and gabapentin-treated cats, respectively). Across all visits, direct SBP was 15.6 mmHg higher than indirect SBP ( P <0.001). No effects of treatment on difference between direct and indirect SBP were identified. Conclusions and relevance Significant effects of gabapentin on direct SBP were not identified, though a type II error is possible. Situational increases cannot be excluded in gabapentin-treated cats with high SBP.

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Evaluation of the effects of gabapentin on the physiologic and echocardiographic variables of healthy cats: a prospective, randomized and blinded study

Cited by 7 publications

References 23 publications

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats

Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease

Effect of gabapentin on ambulatory, direct, systemic arterial blood pressure in apparently healthy cats in the at-home and in-clinic environments

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