Kline J A, Raymond R M, Schroeder J D, Watts J A
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina 28232, USA.
Toxicol Appl Pharmacol. 1997 Aug;145(2):357-62. doi: 10.1006/taap.1997.8195.
Verapamil poisoning is known to produce hyperglycemia and metabolic acidosis in humans. The purpose of this study was to elucidate mechanisms of verapamil-induced hyperglycemia in awake dogs. Mongrel canines were chronically instrumented to permit studies in the conscious state. In six healthy dogs, steady-state glucose infusion requirement after 1 hr of insulin infusion at 1000 mU/min was 19 +/- 1 mg/kg/min. In six separate dogs, verapamil toxicity was induced via verapamil infusion in the portal vein; during verapamil toxicity, the glucose infusion requirement with an insulin infusion rate of 1000 mU/min was significantly decreased (3 +/- 1 mg/kg/min; p < 0.05, unpaired t test). Eleven other verapamil-toxic dogs were also treated with either saline (n = 6, 3.0 ml/kg/hr) or glucagon (n = 5, 10 microg/kg/min). Insulin concentrations were not changed vs basal concentrations in either group. Catecholamine concentrations increased at least 15-fold in all groups (from 458 +/- 169 to 6973 +/- 480 pg/L in the saline-treated group). Glucose concentrations increased in saline-treated animals from 3.7 +/- 0.3 to 11.2 +/- 1.0 micromol/L, and with glucagon treatment, increased from 3.3 +/- 0.3 to 16.1 +/- 1.6 micromol/L (p < 0.05 vs saline, ANOVA). Verapamil poisoning appears to produce hyperglycemia by inducing systemic insulin resistance, blocking insulin release, together with an intact stress hormone response and glucogenic capacity.
已知维拉帕米中毒会导致人体出现高血糖和代谢性酸中毒。本研究的目的是阐明清醒犬中维拉帕米诱导高血糖的机制。对杂种犬进行长期仪器植入，以便在清醒状态下进行研究。在6只健康犬中，以1000 mU/min的速率输注胰岛素1小时后，稳态葡萄糖输注需求量为19±1 mg/kg/min。在另外6只犬中，通过门静脉输注维拉帕米诱导维拉帕米中毒；在维拉帕米中毒期间，胰岛素输注速率为1000 mU/min时的葡萄糖输注需求量显著降低（3±1 mg/kg/min；p<0.05，非配对t检验）。另外11只维拉帕米中毒犬也分别接受了生理盐水（n = 6，3.0 ml/kg/hr）或胰高血糖素（n = 5，10 μg/kg/min）治疗。两组的胰岛素浓度与基础浓度相比均未改变。所有组的儿茶酚胺浓度至少增加了15倍（生理盐水治疗组从458±169 pg/L增至6973±480 pg/L）。生理盐水治疗的动物血糖浓度从3.7±0.3 μmol/L增至11.2±1.0 μmol/L，胰高血糖素治疗的动物血糖浓度从3.3±0.3 μmol/L增至16.1±1.6 μmol/L（方差分析，与生理盐水组相比p<0.05）。维拉帕米中毒似乎通过诱导全身胰岛素抵抗、阻断胰岛素释放，同时伴有完整的应激激素反应和生糖能力而导致高血糖。
