Efficacy of Intravenous Granisetron in Suppressing the Bradycardia and Hypotension Associated with a Rabbit Model of the Bezold‐Jarisch Reflex

Abstract

This study investigated whether granisetron, a 5-HT3 receptor antagonist, can alter the Bezold-Jarisch reflex (i.e., hypotension and inappropriate heart rate slowing). A hemorrhagic rabbit model that has been shown to induce the Bezold-Jarisch reflex was used. In 11 rabbits (3.8 kg), catheters were placed in the carotid arteries one day before experimental hemorrhage. On the day of the study, the rabbits were given intravenous granisetron (50 micrograms/kg) or an equal volume of saline. Five minutes after administration of granisetron or saline, hemorrhage was induced by continuous blood withdrawal at 5 mL/min and blood pressure (BP) and heart rates were obtained at frequent intervals until systolic BP declined to 80 mmHg. Six rabbits received saline and five granisetron. An average of 77.6 mL +/- 16.4 mL of blood was removed in the group receiving granisetron (compared with 56.5 mL +/- 13.1 mL for the saline group) before achieving the target systolic BP of 80 mmHg. The group receiving granisetron demonstrated the same ability to increase their heart rate from baseline as the saline group. However, the granisetron group had a final heart rate that was closer to their maximal heart rate than the saline group. In this animal model, granisetron was significantly more effective at preventing inappropriate heart rate slowing and allowed significantly more blood to be removed before reaching the target blood pressure. This implies that granisetron may be effective in preventing vasovagal syncope, although further study should be carried out to verify these potentially interesting findings.

Use of Granisetron for prevention of hypotension and bradycardia due to spinal anesthesia: A double blind randomised control trial

“…2,5,6 Second, Tsikouris et al found the role of Granisetron for the prevention of neurally mediated hypotension upon head upright tilt testing associated with systemic vasodilatation. 7 Third, Radoslaw et al found that 8 mg intravenous Ondansetron, another 5-HT3 antagonist, attenuates the SBP and MAP drop in spinal anesthesia and emphasized the need for further studies.…”

“…3,4 Few other studies have shown the role of Ondansetron and Granisetron in the prevention of the Bezold-Jarisch reflex. 5,6,7 The rationale of conducting this study was to explore whether Granisetron alone can prevent hypotension and bradycardia due to spinal anaesthesia.…”

Witnessed asystole during spinal anesthesia treated with atropine and ondansetron: a case report

“…[1][2][3][4][5][6][7][8] In some animals the BJR can be abolished with 5-HT 3 antagonists. [9][10][11] Current recommendations to treat asystole during spinal block include immediate restoration of volume by gravity or fluid bolus, early use of atropine, ephedrine, epinephrine, vasopressin, and thump pacing. The early use of epinephrine and volume restoration (and the relative inefficacy of atropine) have been emphasized previously.…”

“…10,[16][17][18]21,22 Direct stimulation of the cardiac 5-HT 3 chemoreceptors located on cardiac vagal afferents with 5-HT or with 5-HT 3 agonists will elicit the BJR in several mammals. 9,11 Conversely, in rats, epicardial injection of the 5-HT 3 antagonist MDL 72222 has been shown to completely abolish the reflex.…”

“…21 Furthermore, in a hemorrhagic rabbit model, granisetron was effective at preventing inappropriate HR slowing and allowed significantly more blood to be removed before reaching the target BP compared to the saline control. 10 Interestingly, non-cardiac 5-HT 3 receptors have been demonstrated also in the rat lung, 23 gastrointestinal mucosa 24 and rabbit carotid sinus. 25 All could be blocked with 5-HT 3 antagonists to prevent bradycardia and hypotension induced by 5-HT or phenyl biguanide (a 5-HT 3 agonist).…”