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. 2023 Oct 25;13(1):18269.
doi: 10.1038/s41598-023-45568-4.

Effect of AT1 receptor blockade on cardiovascular outcome after cardiac arrest: an experimental study in rats

E A F Araújo Filho  1 , M J C Carmona  2 , D A Otsuki  3 , D R R Maia  3 , L G C A Lima  4 , M F Vane  3
Affiliations

Effect of AT1 receptor blockade on cardiovascular outcome after cardiac arrest: an experimental study in rats

E A F Araújo Filho et al. Sci Rep. .

Abstract

Angiotensin II receptor 1(AT1) antagonists are beneficial in focal ischemia/reperfusion (I/R). However, in cases of global I/R, such as cardiac arrest (CA), AT1 blocker's potential benefits are still unknown. Wistar male rats were allocated into four groups: Control group (CG)-animals submitted to CA by ventricular fibrillation induced by direct electrical stimulation for 3 min, and anoxia for 5 min; Group AT1 (GAT1)-animals subjected to CA and treated with 0.2 mg/kg of candesartan diluted in dimethylsulfoxide (DMSO) (0.1%); Vehicle Group (VG): animals subjected to CA and treated with 0.2 ml/kg of DMSO and Sham group (SG)-animals submitted to surgical interventions, without CA. Cardiopulmonary resuscitation consisted of group medications, chest compressions, ventilation, epinephrine (20 mcg/kg) and defibrillation. The animals were observed up to 4 h after spontaneous circulation (ROSC) return, and survival rates, hemodynamic variables, histopathology, and markers of tissue injury were analyzed. GAT1 group had a higher rate of ROSC (62.5% vs. 42.1%, p < 0.0001), survival (100% vs. 62.5%, p = 0.027), lower incidence of arrhythmia after 10 min of ROSC (10% vs. 62.5%, p = 0.000), and lower neuronal and cardiac injury scores on histology evaluation (p = 0.025 and p = 0.0052, respectively) than GC group. The groups did not differ regarding CA duration, number of adrenaline doses, or number of defibrillations. AT1 receptor blockade with candesartan yielded higher rates of ROSC and survival, in addition to neuronal and myocardial protection.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Study protocol. CPR: cardiopulmonary resuscitation. Surgical instrumentation: invasive arterial pressure, venous central access.
Figure 2
Figure 2
Study flow diagram. CG: Control group; GAT1: Candesartan group; VG: Vehicle group; CPR: Cardiopulmonary resuscitation; ROSC: Return of Spontaneous Circulation.
Figure 3
Figure 3
Cumulative survival curve of rats subjected to cardiac arrest and treated with adrenaline (GC, n = 16) or candesartan (GAT1, n = 10) and sham-operated rats (Sham, n = 4).
Figure 4
Figure 4
Mean arterial pressure (A) and Heart rate (B) of rats subjected to cardiac arrest and treated with adrenaline (GC, n = 10) or candesartan (GAT1, n = 10) and sham-operated rats (Sham, n = 4). *p < 0.05 vs GC and Sham.
Figure 5
Figure 5
(A) and (B) Histological analysis of cerebral tissue samples collected from rats subjected to cardiac arrest and treated with adrenaline (GC, n = 10) or candesartan (GAT1, n = 10) and sham-operated rats (Sham, n = 4). (A) Cerebral tissue sections stained with H&E, showing neuronal injury at 4 h after sepsis induction. Magnification 50 μm × 100. The black arrow represents red neurons. (B) Neuronal injury score measured in the brain cortex.
Figure 6
Figure 6
(A) and (B). Histological analysis of myocardial tissue samples collected from rats subjected to cardiac arrest and treated with adrenaline (GC, n = 10) or candesartan (GAT1, n = 10) and sham-operated rats (Sham, n = 4). (A) Heart tissue sections stained with H&E, showing myocardial injury at 4 h after cardiac arrest induction. Magnification 50 μm × 100. The black arrow represents lymphocytic infiltrate. (B) Myocardial injury score measured in the subendocardial layer in the left and right ventricle.
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