|Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Geriatric, hypertensive, and diabetic patients are at increased risk for cardiovascular instability during general anesthesia with volatile anesthetics. We have recently shown that in systemic resistance arteries, volatile anesthetic actions on vascular reactivity are greatly influenced by the presence of endothelium (Anesthesiology 2000;92:1426-40,2001;95:990-8). Since aging, hypertension, and diabetes mellitus are all associated with alterations in endothelial function, volatile anesthetics may influence vascular reactivity differently in those populations. This study was designed to investigate possible changes in vascular responsiveness to volatile anesthetics in the presence of aging, hypertension, and diabetes mellitus.
Isometric force was recorded in small mesenteric arteries from young (7-8 weeks), middle-aged (24-27 weeks), geriatric (81-84 weeks), streptozotocin-induced diabetic (24-27 weeks), and spontaneously hypertensive (24-27 weeks) rats. The experiments were performed in
either presence of endothelium or in its absence.
The concentration-response curve to norepinephrine, the sympathetic neurotransmitter, in the presence of endothelium was shifted to the left in the hypertensive, diabetic, and geriatric rats compared with healthy young or middle-aged rats. The concentration-response (i.e.endothelium-dependent vasorelaxation) curve to acethylcholine was shifted to the right in the hypertensive, diabetic, and geriatric rats compared with healthy young rats. Isoflurane and sevoflurane, in clinical concentrations, enhanced both submaximal and maximal responses to norepinephrine in an endothelium-dependent manner in healthy young and middle-aged rats, but not in the hypertensive, diabetic, and geriatric rats. No significant differences were observed in the concentration-response curve to norepinephrine or the anesthetic action on norepinephrine response in the absence of endothelium.
In mesenteric resistance arteries from the hypertensive, diabetic, and geriatric rats, endothelial function appears to be impaired, leading to enhanced contractile response to norepinephrine, attenuated vasodilator response to acethylcholine, and altered vascular response to volatile anesthetics. The enhancing action of isoflurane or sevoflurane on contractile response to norepinephrine, which has been shown to be mediated by endothelium in small mesenteric arteries, is inhibited in the presence of hypertension, diabetics, and aging, possibly contributing to the cardiovascular instability often observed in the hypertensive, diabetic, and aged subjects during anesthesia with isoflurane or sevoflurane. Less