Table 1. Summary of studies evaluating the effects of anesthesia on hemodynamics in rats with experimental cirrhosis and/or portal hypertension.
| 1st author Year, Ref | Species/strain/sex/BW | Anesthetics doses/route of administration | Main end-points | PP measured | Main results |
|---|---|---|---|---|---|
| Belghiti J, 1981 16 | Male SD rats | • Control: Awake rats | Anesthetic influence on CO and PP in normal and PPVL rats. | YES | • PP was measured four consecutive times in normal and PPVL rats, as follows: anesthetized, awake, re-anesthetized, and re-awakened. |
| BW: 200–250 gr | • Halothane vol % NS | ||||
| • Halothane anesthesia decreased PP, MAP, and CO compared to awake rats in normal and PPVL rats. | |||||
| Lee S.S, 1985 17 | Male SD rats | • Control: Awake rats | Pentobarbital influence on hemodynamics and blood flow distribution in PPVL and sham-operated rats. | YES | In both Sham-operated and PPVL rats, pentobarbital anesthesia: |
| • Pentobarbital sodium: 5 mg/100 mg BW ip | • Decreased CO and HABF, and increased TPR. | ||||
| BW: NS | • Did not change absolute blood flow values of splanchnic organs or PBF in either group, but the fractions of CO perfusing splanchnic organs were significantly increased in both groups. | ||||
| • PP, HR, and MAP were not influenced by anesthesia in any group. | |||||
| Lee S.S, 1986 18 | Male SD rats | • Control: Awake rats | Pentobarbital influence on hemodynamics and blood flow in BDL and sham-operated rats. | YES | Pentobarbital anesthesia: |
| • Pentobarbital sodium: 5 mg/100 mg BW ip. | • Decreased CO and increased TPR in both BDL and sham-operated rats. | ||||
| BW: NS | • Decreased PBF and HABF, and increased HR and portal resistance in BDL rats. | ||||
| • Did not influence PP or MAP in BDL or sham-operated rats. | |||||
| Conclusion: Pentobarbital anesthesia is not suitable for hemodynamic studies. | |||||
| Debaene B, 1990 15 | Male SD rats | • Controls: Awake cirrhotic rats | Anesthetic influence on systemic hemodynamics and splanchnic blood flow in BDL rats that were normo-or hypo-volemic. | NO | Before hemorrhage: |
| • CI was higher in conscious rats and rats receiving isoflurane. | |||||
| BE: 308 ± 5 gr | • Ketamine: 30 mg/kg iv bolus followed by a continuous iv infusion of 1.5 mg/kg/min | • No differences in MAP, PBF, or HR between anesthetics. | |||
| • Splanchnic blood flow was lower in enflurane and similar among the rest of anesthetics; but HABF was similar in conscious rats, isoflurane and halothane groups, and lower with ketamine. | |||||
| • Halothane 1% | After hemorrhage: | ||||
| • Enflurane 2.2% | • CI and PBF decreased similarly in all groups. | ||||
| • Isoflurane 1.3% | • MAP was significantly higher in the ketamine and isoflurane compared with the enflurane and halothane groups. HABF was similar in conscious rats and isoflurane group. | ||||
| All anesthetic agents had the same effect on PBF, but they acted differently on HABF. | |||||
| Conclusion: Isoflurane seemed the most efficient anesthetic for preserving the splanchnic circulation in hypovolemic cirrhotic rats. | |||||
| Sikuler E, 1991 19 | Male SD rats | • Controls: Awake sham and BDL rats | Influence of ketamine anesthesia on systemic hemodynamics and blood flow distribution in BDL rats. | NOT in awake rats. | Compared with awake sham animals, anesthesia with ketamine: |
| • Increased PBF in sham-operated rats, but it did not change MAP, HR, CO, or HABF. | |||||
| BW: 220–240 gr | • Ketamine: 100–150 mg/kg im | • Increased MAP in BDL rats, but it did not affect HR, CO, HABF, or PBF. | |||
| • TPR was lower in awake rats compared with anesthetized BDL and sham rats. | |||||
| Van Roey G, 1997 13 | Male Wistar rats | • Ether. | Anesthetic influence on systemic and splanchnic hemodynamics compared with the awake state in normal and cirrhotic rats that were either normo or hypovolemic. | YES | Hemodynamics studies in awake rats were performed 3 hours after recovery from ether narcosis for placement of catheters. |
| • Pentobarbital: 60 and 30 mg/kg ip for normal and cirrhotic rats. | |||||
| BW: 150 gr | • Ether: Dose adjusted to the depth of narcosis. Few hemodynamic effects, but continuous observation of the animal was essential. | ||||
| • Ketamine: 150 and 75 mg/kg ip for normal and cirrhotic rats. | |||||
| • Pentobarbital: Markedly suppressed the sympathetic nervous system and produced profound hypotension in cirrhotic rats. No influence on PP. | |||||
| • Diacepam-fluanisone: 2.5–1 mg/kg ip and 2–0.6 mg/kg im for normal-cirrhotic rats. | • Ketamine: Unpredictable individual sensitivity to Ketamine, especially in cirrhotic rats, with a total mortality > 30%. Ketamine did not influence MAP or PP and decreased RR in normal and cirrhotic normovolemic rats. | ||||
| Cirrhosis was induced by CCl4 administration. | |||||
| • Diazepam-fluanisone: Produced profound hypotension. | |||||
| Conclusion: Hemodynamic experiments in cirrhotic rats should be preferably performed in awake rats. |
Abbreviations: BDL: common bile duct ligation, BW: body weight, CCl4: carbon tetrachloride, CI: cardiac index, CO: cardiac output, HABF: hepatic arterial blood flow, im: intramuscular, ip: intraperitoneal, iv: intravenous, MAP: mean arterial pressure, NS: not specified, PBF: portal blood flow, PP: portal pressure, PPVL: partial portal vein ligation, RR: respiratory rate, SD: Sprague-Dawley, TPR: total peripheral resistance.
Based on the previous information, the present study aimed to compare the performance of the combination of ketamine+diazepam (KD) given i.m. versus inhalational anesthesia with sevoflurane, which has minimal (< 3%) hepatic metabolism, as the anesthetic regime for measuring hepatic and systemic hemodynamics in rats with non-cirrhotic portal hypertension induced by partial portal vein ligation (PPVL).