Acute and Critical Care

Original Articles

Basic science and research
Impact of tadalafil on cardiovascular and organ dysfunction induced by experimental sepsis: Marcelo Almeida Nakashima, Gabrielle Delfrate, Lucas Braga Albino, Gustavo Ferreira Alves, Junior Garcia Oliveira, Daniel Fernandes; Acute Crit Care. 2025;40(1):46-58. Published online February 12, 2025; DOI: https://doi.org/10.4266/acc.002904

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Background
Sepsis is a life-threatening condition that affects the cardiovascular and renal systems. Severe hypotension during sepsis compromises tissue perfusion, which can lead to multiple organ dysfunction and death. Phosphodiesterase 5 (PDE5) degrades intracellular cyclic guanosine monophosphate (cGMP) levels which promotes vasodilatation in specific sites. Our previous studies show that inhibiting cGMP production in early sepsis increases mortality, implying a protective role for cGMP production. Then, we hypothesized that cGMP increased by tadalafil (PDE5 inhibitor) could improve microcirculation and prevent sepsis-induced organ dysfunction.
Methods
Rats were submitted to cecal ligation and puncture (CLP) sepsis model and treated with tadalafil (2 mg/kg, s.c.) 8 hours after the procedure. Hemodynamic, inflammatory and biochemical assessments were performed 24 hours after sepsis induction. Moreover, the effect of tadalafil on the survival of septic rats was evaluated for 5 days.
Results
Tadalafil treatment improves basal renal blood flow during sepsis and preserves it during noradrenaline infusion. Sepsis induces hypotension, impaired response to noradrenaline, and increased cardiac and renal neutrophil infiltration, in addition to increased levels of plasma nitric oxide and lactate. None of these dysfunctions were changed by tadalafil. Additionally, tadalafil treatment did not increase the survival rate of septic rats.
Conclusions
Tadalafil improved microcirculation of septic animals; however, no beneficial effects were observed on macrocirculation and inflammation parameters. Then, the potential benefit of tadalafil in the prognosis of sepsis should be evaluated within a therapeutic strategy covering all sepsis injury mechanisms.

Citations

Citations to this article as recorded by

Endothelial miR-7052 Safeguards Blood–Brain Barrier Integrity During Endotoxemia by Co-repressing ANGPT2 and PDE5A
Wenyuan Yang, Haigang Wu
Molecular Neurobiology.2026;[Epub] CrossRef
Role of vascular smooth muscle cell pathobiology in sepsis‑induced vasoplegia (Review)
Hang Ruan, Xiao-Yan Shen, Shi-Yan Liu, Shu-Sheng Li
International Journal of Molecular Medicine.2026; 57(4): 1. CrossRef
Protective Effects of Pentoxifylline on Peripheral Microcirculatory Dysfunction and Renal Cortical Oxygen Deficiency in a Rat Model of LPS‐Induced Sepsis
Bülent Ergin, H. Rob Taal, Deniz Erol Kutucu, Wijnie van Dam, Aysegul Kapucu, Sinno S. H. P. Simons, Can Ince, Irwin K. M. Reiss
Microcirculation.2026;[Epub] CrossRef

The Effect of Low-dose Dopamine on Splanchnic and Renal Blood Flow in Patients with Septic Shock under the Treatment of Norepinephrine: Jong Joon Ahn, Tae Hyung Kim, Ki Man Lee, Tae Sun Shim, Chae Man Lim, Sang Do Lee, Woo Sung Kim, Dong Soon Kim, Won Dong Kim, Younsuck Koh; Korean J Crit Care Med. 2001;16(1):36-41.

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Abstract PDF: BACKGROUND
Norepinephrine, which is frequently administered as a vasopressor to the patients with septic shock, can decrease splanchnic and renal blood flows and aggravate splanchnic and renal ischemia. The low-dose dopamine (LDD) has been frequently combined with norepinephrine to ameliorate renal and splanchnic hypoperfusion in patients with septic shock. However, the effect of the LDD on the splanchnic and renal blood flow has not been fully elucidated. This investigation was carried out to determine the effect of the LDD on the splanchnic and renal blood flow in the patients with septic shock under the treatment of norepinephrine.
METHODS
Eleven patients with septic shock were included in this study. All of them were under the norepinephrine treatment as the mean arterial pressure (MAP) was less than 70 mm Hg in spite of the adequate fluid resuscitation. With stabilization of MAP, the LDD (2 g/kg/min) was administered for two hours in each patients. Hemodynamics, gastric intramucosal pH (pHi), gastric regional PCO2 (rPCO2), rPCO2 - PaCO2, urine volume, urine sodium excretion and creatinine clearance were compared between with and without the LDD infusion. Diuretics was not used during the study period.
RESULTS
Age of patients (n=11) was 64 12 and the APACHE III score was 84 17. The mortality rate of the subjects was 64%. Dosage of norepinephrine was 0.55 0.63 g/kg/min during the study period. There were no significant differences in hemodynamics (central venous pressure, cardiac output, pulmonary artery occlusion pressure, mixed venous gas), pHi, rPCO2, rPCO2 - PaCO2 depending on the concomitant infusion of the LDD. The volume of urine tended to increase (P=0.074) after concomitant LDD, but the changes in urine sodium excretion and creatinine clearance were not significantly different.
CONCLUSIONS
The combined infusion of the LDD with norepinephrine did not improve splanchnic and renal blood flow in the patients with septic shock.

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