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Anesth Analg 2000;91:76-81
© 2000 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Dilation by Isoflurane of Preconstricted, Very Small Arterioles from Human Right Atrium Is Mediated in Part by K+-ATP Channel Opening

Kyung W. Park, MD*, Hai B. Dai, MD{dagger}, Mark E. Comunale, MD*, Alok Gopal, MD*, and Frank W. Sellke, MD{dagger}

Departments of *Anesthesia and Critical Care and {dagger}Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Address correspondence and reprint requests to Kyung W. Park, MD, Department of Anesthesia & Critical Care, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Address e-mail to kpark{at}caregroup.harvard.edu


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The adenosine triphosphate (ATP)-sensitive potassium channels (K+-ATP channels) are activated by decreases in intracellular ATP and help to match blood flow to tissue needs. Such metabolism-flow coupling occurs predominantly in the smallest arterioles measuring 50 µm or less in diameter. Previous studies demonstrated that isoflurane may activate the K+-ATP channels in larger arteries. We examined whether isoflurane also activates the channels in the smallest arterioles of ~50 µm. Microvessels of ~50 µm were dissected from right atrial appendages from patients undergoing coronary artery bypass surgery and were monitored in vitro for diameter changes by videomicroscopy. With or without preconstriction with the thromboxane analog U46619 1 µM, vessels were exposed to isoflurane 0%–3% either in the presence or absence of the K+-ATP channel blocker glibenclamide 1 µM. Without preconstriction, isoflurane neither dilated nor constricted the vessels significantly. After preconstriction, isoflurane had a concentration-dependent dilation of the small arterioles (39 ± 13% [mean ± SD] dilation at 3% isoflurane) (P < 0.001), and this effect was significantly attenuated by glibenclamide (18 ± 5% dilation at 3% isoflurane) (P < 0.01). In comparison, nitroprusside 10-4 M produced 79 ± 6% dilation, and adenosine diphosphate 10-4 M produced 29 ± 7% dilation. We conclude that isoflurane-mediated dilation of the smallest resistance arterioles may be in part based on activation of the K+-ATP channels when the arterioles are relatively constricted.

Implications: Vasodilation of very small coronary arterioles by isoflurane depends on preexisting tone and may in part be mediated by the K+-ATP channels.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Adenosine 5'-triphosphate (ATP)-sensitive potassium channels (K+-ATP channels) were first described in cardiac myocytes (1) and have since been described in other tissue types, including vascular smooth muscle (2). These channels are activated by decreases in intracellular ATP, such as from ischemia or inhibitors of cell metabolism (e.g., cyanide, dinitrophenol) (3) and selectively blocked by the antidiabetic sulfonylureas (4). In addition, vasodilators that release endothelium-dependent hyperpolarizing factor may work by opening K+-ATP channels (2). Because these channels produce vasodilation in regions of ischemia and ATP depletion, they may help to match blood flow to tissue needs (5).

In the coronary circulation, blood flow is matched to tissue needs by several mechanisms, including myogenic constriction, flow-induced endothelium-dependent dilation, neurohumoral vasomotor factors, and, most importantly, metabolism-flow coupling (6). Metabolism-flow coupling occurs predominantly in the smallest arterioles measuring 50 µm or less in diameter (7).

Cason et al. (8) demonstrated that isoflurane-induced increases in coronary blood flow were blocked by the K+-ATP channel antagonist glibenclamide, suggesting that the isoflurane-mediated effect may be via the K+-ATP channels. Zhou et al. (9) isolated relatively large porcine coronary arteries measuring ~170 µm and showed that, after preconstriction of these vessels with acetylcholine, isoflurane produced dilation blocked by glibenclamide. Because the beneficial effect of the K+-ATP channels in metabolism-flow coupling is expected in the smallest arterioles, in this study we examined whether isoflurane produces K+-ATP channel-dependent dilation in human coronary arterioles measuring ~50 µm.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
In accordance with institutional investigational review board standards, right atrial appendage specimens, which are routinely discarded during venous cannulation for coronary artery bypass surgery, were collected in cold (4°C), modified Krebs buffer solution (NaCl 120 mM, KCl 5.9 mM, dextrose 11.1 mM, NaHCO3 25 mM, NaH2PO4 1.2 mM, MgSO4 1.2 mM, CaCl2 2.5 mM). Anesthesia for the surgery consisted of 10–15 µg/kg of fentanyl IV, variable concentrations of isoflurane in oxygen titrated to effect, neuromuscular blockade with pancuronium, and phenylephrine IV as needed for blood pressure control. Comorbidity profile of the patients was as shown in Table 1.


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  		Table 1. Comparison of Comorbidities of Patients Contributing Vessels to Different Experimental Groups
 
From the most muscular section of the specimen, small arterioles measuring ~50 µm in diameter and 150–250 µm in length at baseline were dissected free of the surrounding tissues. Each vessel was placed in a vessel chamber, cannulated with dual micropipettes (20–30 µm in diameter), and secured with 10-0 sutures. The vessel was continuously bathed with modified Krebs buffer, gassed with a 95% O2/5% CO2 mixture, maintained at 37°C with a pH of 7.4, and studied in a no-flow state. The pressure in the micropipettes was maintained at 40 mm Hg to provide vessel distension. The vessel was visualized with an inverted phase-contrast microscope connected to a videocamera. The vessel image was projected onto a television screen. Changes in vessel internal lumen diameter were monitored with an optical density video detection system, as previously described (10).

To establish the stability of our human vessel preparation, seven vessels were monitored for changes in internal diameter in a preliminary study. The vessel diameter equilibrated within 10 min and remained stable thereafter for at least 2 h. By using additional vessels, vessel responses to the thromboxane analog U46619 1 µM and the endothelium-independent dilator nitroprusside 1 µM were measured after 30 min of equilibration in the chamber. After rinsing with fresh Krebs solution and reequilibration, the vessel responses to the same agents were measured at 90 min. Vessel responses at 30 min and at 90 min were compared to confirm stability of our vessel preparation.

In the main part of the study, each vessel was mounted in the vessel chamber and equilibrated at 37°C for 30 min. The diameter measured at the end of equilibration was taken as the baseline diameter in all groups. To examine the K+-ATP channel-dependent effect of isoflurane, four groups of vessels were examined (Table 2). Group 1 vessels were equilibrated in the vessel chamber for 30 min without the K+-ATP channel blocker glibenclamide 1 µM and, without preconstriction, were then exposed to isoflurane 0%–3%. Group 2 vessels were equilibrated with glibenclamide 1 µM and, without preconstriction, were then exposed to isoflurane. Group 3 vessels were equilibrated without glibenclamide 1 µM and, after preconstriction with the thromboxane analog U46619 1 µM, were then exposed to isoflurane. Group 4 vessels were equilibrated with glibenclamide 1 µM and, after preconstriction with U46619 1 µM, were then exposed to isoflurane. Preconstriction by U46619 produced a 25%–30% reduction in diameter from the baseline in all groups and was not affected by glibenclamide. Vessels were subjected to isoflurane 0%–3% by adding the anesthetic to the 95% O2/5% CO2 mixture bubbling the Krebs buffer solution, using an in-line vaporizer. In a preliminary experiment using gas chromatography, we determined that, in our experimental preparation, isoflurane reached steady-state concentrations after introduction in the vessel chamber in <10 min and that the millimolar concentration and partial pressure of isoflurane in the chamber reflected its concentration in the gas mixture bubbled into the buffer solution (11). The anesthetic content in the gas mixture was monitored continuously by using a Rascal II Gas Analyzer (Ohmeda, Salt Lake City, UT) that was previously calibrated to industrial standards.


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  		Table 2. Experimental Groups to Examine the K+-ATP Channel Dependence of the Vasomotor Effect of Isoflurane
 
At the end of each experiment, the anesthetic was discontinued, and the vessel chamber was rinsed with fresh Krebs solution. The vessel was reequilibrated at 37°C, and its viability was tested by its response to KCl 100 mM. Only data from vessels that constricted to KCl by 20% or more were retained for further analysis. Viable vessels constricted to KCl by 35%–40%.

For comparison of magnitudes of vasomotor effects, additional vessels were used to generate concentration-response curves to adenosine diphosphate (ADP) 10-9–10-4 M and to the endothelium-independent dilator nitroprusside 10-9–10-4 M, after preconstriction of each vessel with U46619 1 µM.

Vasomotor responses of the vessels after 30 min of equilibration versus 90 min of equilibration were compared by using Student’s t-test (two-tailed). Whether isoflurane had any concentration-dependent effect on vessel diameter was determined by a one-way analysis of variance (ANOVA) (Sheffé’s linear contrast), with post-hoc t-tests for multiple comparison with the response at the smallest concentration when the initial one-way ANOVA yielded a significant P value. The concentration response curves to isoflurane with or without glibenclamide were compared by two-way ANOVA with a repeated measures factor, with post-hoc Neuman-Keuls test and stratified z-tests to identify the concentrations at which the differences in responses were significant. The Monte Carlo randomization test (two-tailed) was used to compare proportions. This nonparametric test is considered superior to the {chi}2 test when the sample size is small for one or more of the boxes in the contingency tables. All data are presented as the means ± SD. P < 0.05 was considered significant. All statistics were calculated by using True Epistat software (Epistat Services, Richardson, TX).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Vessel responses to the thromboxane analog U46619 and the endothelium-independent dilator nitroprusside at 30 min of equilibration were not significantly different from those at 90 min of equilibration, demonstrating stability of our vessel preparation (Fig. 1).



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  		Figure 1. Response of human right atrial arterioles to the thromboxane analog U46619 1 µM and the endothelium-independent dilator nitroprusside 1 µM after 30 min of equilibration vs after 90 min of equilibration. Vasomotor responses to the drugs tested remained stable over the time period, and there was no significant difference between 30 min and 90 min.

 
Comorbidity profiles of the patients in the four experimental groups were not significantly different from one another (Table 1).

Without preconstriction with U46619, isoflurane produced neither significant dilation nor constriction (Fig. 2) (P = 0.64) (Group 1: n = 7, baseline vessel size 64 ± 3 µm [range 58–68 µm]). With previous exposure to glibenclamide and without preconstriction with U46619, isoflurane tended to have a modest concentration-dependent constrictive effect, but this effect did not reach significance (Fig. 2) (P = 0.09) (Group 2: n = 9, baseline vessel size 59 ± 5 µm [range 53–68 µm]).



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  		Figure 2. Response of human right atrial arterioles to isoflurane without preconstriction. Without preconstriction with U46619 nor the presence of glibenclamide (Group 1), isoflurane produced neither significant dilation nor constriction (P = 0.64). In the presence of the K+-ATP channel blockade with glibenclamide (Group 2), isoflurane tended to produce mild constriction of the arterioles, but this effect did not reach significance (P = 0.09).

 
After preconstriction with U46619, human right atrial appendage arterioles demonstrated concentration-dependent dilation to isoflurane (Fig. 3) (P < 0.001) (Group 3: n = 9, baseline vessel size 55 ± 5 µm [range 47–63 µm]). This dilatory effect of isoflurane was significantly attenuated by prior equilibration of the vessels with glibenclamide (Fig. 3) (P < 0.01) (Group 4: n = 8, baseline vessel size 56 ± 6 µm [range 48–63 µm]).



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  		Figure 3. Response of human right atrial arterioles to isoflurane after preconstriction with U46619 1 µM. In the absence of glibenclamide, isoflurane produced concentration-dependent dilation of the arterioles (Group 3) (P < 0.001). This effect was attenuated by glibenclamide (Group 4) (P < 0.01). *P < 0.05 vs control. #P < 0.05 vs isoflurane 0% within the same group.

 
After preconstriction with U46619, right atrial appendage arterioles demonstrated significant concentration-dependent dilation to nitroprusside (P < 0.001) (n = 8, baseline vessel size 53 ± 3 µm [range 50–58 µm]), and relatively modest dilation to ADP (P < 0.01) (n = 8, baseline vessel size 59 ± 6 µm [range 47–68 µm]) (Fig. 4).



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  		Figure 4. Response of human right atrial arterioles to the endothelium-independent dilator nitroprusside and the endothelium-dependent dilator adenosine diphosphate (ADP). Both drugs produced concentration-dependent dilation of human right atrial arterioles. However, adenosine diphosphate had a relatively weak effect. #P < 0.05 vs the lowest concentration of each dilator.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Our most significant findings are as follows. (A) As have been previously noted in animals (10,11), the vasomotor effect of isoflurane on very small arterioles from right atrial appendages of patients undergoing coronary artery bypass surgery depends on the preexisting tone of the vessels. After preconstriction, isoflurane produces significant concentration-dependent dilation of the vessels; with no added tone, it does not produce either significant dilation or constriction. (B) The dilatory effect of isoflurane evident after preconstriction is significantly attenuated by the K+-ATP channel blocker glibenclamide, suggesting that the effect may in part be mediated by opening the K+-ATP channels.

The activity of the K+-ATP channels is directly linked to intracellular concentrations of ATP. The ATP concentrations in normal cardiac myocytes have been reported to be 3–4 mM (12), somewhat larger than the concentration needed to suppress the K+-ATP channel activity, which is on the order of 1 mM (1). Under ischemic conditions or in the presence of inhibitors of mitochondrial metabolism, the ATP content may decrease as low as 10% of control, and the channels are activated (13). In addition to small intracellular concentrations of ATP, the channels may be activated by G proteins coupled to adenosine receptors (14). Furthermore, ADP displaces ATP from its inhibitory binding site to the channel and, in small concentrations, increases channel activity (3).

The activation of the K+-ATP channel leads to an outward K+ current and shortening of the plateau phase of the action potential, accompanied by a reduced contraction. This may be one mechanism for preventing the intracellular ATP concentration from decreasing to irreversibly small levels (1). Furthermore, K+, released from the myocytes, is a potent vasodilator in small concentrations and contributes to vasodilation of nearby arterioles (15), thus tending to restore myocyte ATP concentrations. Finally, the K+-ATP channels are present in vascular smooth muscle as well (2), and ischemia would lead to activation of the channels in the vessels and those in the surrounding myocytes. As a result, the vascular smooth muscle relaxes and the vessel dilates. Thereby, the K+-ATP channels mediate matching of blood flow to tissue metabolism. Indeed, the K+-ATP channels have been implicated in hypoxic dilation of coronary arterioles (5), ischemic preconditioning of the myocardium (16), and protection of the myocardium after acute coronary occlusion (4).

Therefore, anesthetic effects on the K+-ATP channels may have implications on how the anesthetics affect myocardial protection. Previous studies have been performed in relatively large coronary artery isolations or whole heart preparations. Larach and Schuler (17) reported that halothane attenuated prostaglandin F2{alpha}-induced constriction of porcine epicardial coronary artery rings and that this attenuating effect was blocked by glibenclamide if the endothelium was intact, but not if the endothelium was denuded. This suggested that halothane had K+-ATP channel-mediated, endothelium-dependent vasorelaxant effect on these conductance arteries. They also found that, in tetrodotoxin-arrested rat hearts, halothane-mediated increase in blood flow was attenuated by glibenclamide. Similarly, Cason et al. (8) demonstrated in vivo that isoflurane-mediated increase in regional myocardial blood flow was blocked by glibenclamide. In isolated porcine coronary arteries measuring ~170 µm preconstricted with acetylcholine, Zhou et al. (9) demonstrated that isoflurane had a concentration-dependent dilatory effect, which was blunted by glibenclamide. However, Kersten et al. (18) showed that, in dogs with chronic coronary occlusion, a sevoflurane-mediated increase in collateral blood flow was independent of the K+-ATP channels. Propofol-mediated dilation of rat coronary arterioles was also independent of the K+-ATP channels (19).

In comparison with previous studies, ours is significant in that we examined the effect of isoflurane in very small coronary arterioles of ~50–60 µm, which are thought to be mainly involved in metabolism-flow coupling (7). In addition, we used coronary arteries from patients with known coronary artery disease and were thus able to examine the behavior of diseased vessels to isoflurane. Although our literature review did not demonstrate definitive evidence that atrial and ventricular vessels behave similarly, in the literature right atria have served as acceptable sources of coronary vessels (20).

In concordance with the previous studies, our findings demonstrate that, in coronary arteries with significant preexisting tone (such as by preconstriction in vitro), isoflurane produces K+-ATP channel-dependent vasodilation, not only in large vessels (9) but also in very small vessels. This effect is present not only in the normal coronary circulation (8,9), but also in patients with coronary artery disease. It is notable, however, that demonstration of K+-ATP channel dependence of isoflurane-mediated vasodilation was possible only in microvessels with significant preexisting tone. Arterioles in an ischemic region are likely to be (nearly) maximally dilated because of ischemia itself, and isoflurane may not contribute to any further dilation of such vessels with low tone in vivo. Therefore, although isoflurane may certainly have an agonistic effect on opening the K+-ATP channels of arterioles, our data do not support the conclusion that K+-ATP channel-dependent vasodilation is likely to be an important mechanism whereby isoflurane protects the myocardium from ischemia.

Nevertheless, isoflurane and other volatile anesthetics have been demonstrated to confer myocardial protection against ischemia-reperfusion injury when the anesthetic is administered either before or during ischemia (21–26). As with ischemic preconditioning, whereby brief period(s) ischemia before a longer period of ischemic insult protects the myocardium from ischemic injury, volatile anesthetics confer myocardial protection against ischemic insult by mechanisms involving the adenosine receptors, protein kinase C activation, and opening of the K+-ATP channels in the myocytes (22–26).

Does activation of the K+-ATP channels in the vascular smooth muscle have no role in protection from ischemia? In a recent study, Novalija et al. (27) demonstrated, in isolated guinea pig hearts, that sevoflurane tended to preserve coronary blood flow response to bradykinin and nitroprusside after a period of coronary occlusion, and that this effect was abolished by glibenclamide. Although vascular activation of K+-ATP channels by isoflurane may not contribute to myocardial protection against ischemia, it may be a mechanism of coronary vasomotor protection against it.

In summary, we found that, in very small arterioles of patients with coronary artery disease, isoflurane produces vasodilation that is dependent on the preexisting tone, and may in part be mediated by opening of the K+-ATP channels. We discuss the reason why this effect of isoflurane is probably not a mechanism of myocardial protection, but possibly one of coronary vasomotor protection observed by other investigators.


   Acknowledgments
 
This study was supported, in part, by United States Public Health Service Grant HL46716 and by a grant from the Beth Israel Anesthesia Foundation.


   Footnotes
 
Presented, in part, at the American Society of Anesthesiologists Annual Meeting, Dallas, TX, October 1999.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature 1983;305:147–8.[Medline]
  2. Standen JB, Quayle JM, Davies NW, et al. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science 1989;245:177–80.[Abstract/Free Full Text]
  3. Ashcroft FM. Adenosine 5'-triphosphate-sensitive potassium channels. Ann Rev Neurosci 1988;11:97–118.[Web of Science][Medline]
  4. Robertson DW, Steinberg MI. Potassium channel modulators: scientific applications and therapeutic promise. J Med Chem 1990;33:1529–41.[Web of Science][Medline]
  5. Daut J, Maier-Rudolph W, von Beckerath N, et al. Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science 1990;247:1341–4.[Abstract/Free Full Text]
  6. Jones CJH, Kuo L, Davis MJ, Chilian WM. Distribution and control of coronary microvascular resistance. Adv Exp Med Biol 1993;346:181–8.[Medline]
  7. Jones CJ, Kuo L, Davis MJ, Chilian WM. Regulation of coronary blood flow: coordination of heterogeneous control mechanisms in vascular microdomains. Cardiovasc Res 1995;29:585–96.[Web of Science][Medline]
  8. Cason BA, Shubayev I, Hickey RF. Blockade of adenosine triphosphate-sensitive potassium channels eliminates isoflurane-induced coronary artery vasodilation. Anesthesiology 1994;81:1245–55.[Web of Science][Medline]
  9. Zhou X, Abboud W, Manabat NC, et al. Isoflurane-induced dilation of porcine coronary arterioles is mediated by ATP-sensitive potassium channels. Anesthesiology 1998;89:182–9.[Web of Science][Medline]
  10. Park KW, Dai HB, Lowenstein E, et al. Heterogeneous vasomotor responses of rabbit coronary microvessels to isoflurane. Anesthesiology 1994;81:1190–7.[Web of Science][Medline]
  11. Park KW, Dai HB, Lowenstein E, Sellke FW. Vasomotor responses of rat coronary arteries to isoflurane and halothane depend on pre-exposure tone and vessel size. Anesthesiology 1995;83:1323–30.[Web of Science][Medline]
  12. Khairallah PA, Mommaerts WFHM. Nucleotide metabolism in cardiac activity. Circ Res 1953;1:8–11.[Abstract/Free Full Text]
  13. Grinwald PM, Hearse DJ, Segal MB. A possible mechanism of glycolytic impairment after adenosine triphosphate depletion in the perfused rat heart. J Physiol 1980;301:337–47.[Abstract/Free Full Text]
  14. Kirsch GE, Codina J, Birnbaumer L, Brown AM. Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes. Am J Physiol 1990;259:H820–6.[Abstract/Free Full Text]
  15. Spruce AE, Standen NB, Stanfield PR. Studies on the unitary properties of adenosine-5'-triphosphate-regulated potassium channels of frog skeletal muscle. J Physiol 1987;382:213–37.[Abstract/Free Full Text]
  16. Grover GJ, Sleph PG, Dzwonczyk S. Role of myocardial ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A1-receptors. Circulation 1992;86:1310–6.[Abstract/Free Full Text]
  17. Larach DR, Schuler HG. Potassium channel blockade and halothane vasodilation in conducting and resistance coronary arteries. J Pharmacol Exp Ther 1993;267:72–81.[Abstract/Free Full Text]
  18. Kersten JR, Schmeling T, Tessmer J, et al. Sevoflurane selectively increases coronary collateral blood flow independent of KATP channels in vivo. Anesthesiology 1999;90:246–56.[Web of Science][Medline]
  19. Park KW, Dai HB, Lowenstein E, Sellke FW. Propofol-associated dilation of rat distal coronary arteries is mediated by multiple substances, including endothelium-derived nitric oxide. Anesth Analg 1995;81:1191–6.[Abstract]
  20. Metais C, Li J, Simons M, Sellke FW. Effects of coronary artery disease on expression and microvascular response to VEGF. Am J Physiol 1998;275:H1411–8.[Abstract/Free Full Text]
  21. Warltier DC, Al-Wathiqui MH, Kampine JP, Schmeling WT. Recovery of contractile function of stunned myocardium in chronically instrumented dogs is enhanced by halothane or isoflurane. Anesthesiology 1988;69:552–65.[Web of Science][Medline]
  22. Kersten JR, Schmeling TJ, Hettrick DA, et al. Mechanism of myocardial protection by isoflurane: role of adenosine triphosphate-regulated potassium channels. Anesthesiology 1996;85:794–807.[Web of Science][Medline]
  23. Cope DK, Impastato K, Cohen MV, Downey JM. Volatile anesthetics protect the ischemic rabbit myocardium from infarction. Anesthesiology 1997;86:699–709.[Web of Science][Medline]
  24. Cason BA, Gamperl AK, Slocum RE, Hickey RF. Anesthetic-induced preconditioning: previous administration of isoflurane decreases myocardial infarct size in rabbits. Anesthesiology 1997;87:1182–90.[Web of Science][Medline]
  25. Ismaeil MS, Tkachenko I, Gamperl AK, et al. Mechanisms of isoflurane-induced myocardial preconditioning in rabbits. Anesthesiology 1999;90:812–21.[Web of Science][Medline]
  26. Toller WG, Kersten JR, Pagel PS, et al. Sevoflurane reduces myocardial infarct size and decreases the time threshold for ischemic preconditioning in dogs. Anesthesiology 1999;91:1437–46.[Web of Science][Medline]
  27. Novalija E, Fujita S, Kampine JP, Stowe DF. Sevoflurane mimics ischemic preconditioning effects of coronary flow and nitric oxide release in isolated hearts. Anesthesiology 1999;91:701–12.[Web of Science][Medline]
Accepted for publication February 23, 2000.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press