THE CREATION OF ARTIFICIAL SUBCUTANEOUS ARTERIOVENOUS FISTULAS IN PATIENTS WITH MALIGNANT HEMATOLOGICAL DISEASE

Creation of an artificial subcutaneous arteriovenous fistula was attempted in five patients with malignant hæmatological disorders (two with Hodgkin's disease, two with acute lymphatic leukæmia, and one with acute myeloid leukæmia). The average time from the start of treatment to attempted creation of the fistulæ was four years. Neither direct arteriovenous anastomosis nor an interposition mandril graft was successful in any patient. Failure was attributed to impaired venous run-off secondary to previous episodes of thrombophlebitis induced by the intravenous administration of cytotoxic drugs. The use of an arteriovenous fistula early in the course of the disease might minimize these later problems.     

RENAL ANGIOGRAPHY AND THE MANAGEMENT OF SEVERE CLOSED RENAL TRAUMA1

The purpose of this study was to determine the place of selective renal angiography in the assessment of major renal trauma. Thirty-one cases of renal injury assessed by urography and angiography were reviewed, and the radiological features correlated with the subsequent clinical course. Based on the angiographic findings, a classification of these more severe injuries is proposed, and the prognostic significance of renal ischæmia demonstrated. Because conservative treatment in those cases with significant ischæmia is likely to fail, early elective surgery is recommended. In this selected group, viable renal tissue can be preserved, and the necessity for subsequent nephrectomy due to secondary hæmorrhage, or continuing urine leakage, is avoided.     

ACUTE MESENTERIC ISCHÆMIA

The experience of acute mesenteric ischæmia at St Vincent's Hospital, Melbourne, has been reviewed over 17 years. The mortality remains appallingly high. This applies particularly to those patients who had thrombosis of the superior mesenteric artery, amongst whom the mortality in this series was 97%. The mortality was slightly less in the group suffering from embolic occlusion of the superior mesenteric artery (66%), and in those suffering from thrombosis of the superior mesenteric vein (60%). A mortality of 66% was also found in patients suffering from non-occlusive gut ischæmia. Delay in diagnosis accounted for this high mortality. Early diagnosis is all-important, and this depends on the performance of mesenteric angiography in any patient suspected of having mesenteric ischæmia. Appropriate surgery may then be carried out in the occlusive group and supportive treatment, including intraarterial papaverine infusion, given to those with non-occlusive ischæmia. There is a pressing need for simple non-invasive tests to segregate those patients suffering from acute mesenteric ischæmia from those whose acute abdomen is due to some other cause.     

CLAUDICATION OF THE CAUDA EQUINA

The term “claudication of the cauda equina” is examined. It has arisen from semantic errors, and a belief in ischæmia for which there is no scientific evidence. Its use tends to hamper rather than assist the investigation of patients with obscure pain in the lower limb. A preferable alternative term, “atypical sciatica”, is suggested.     

An Assessment of the Xenon- 133 Method of Measuring Muscle Blood Flow1

The ¹¹³Xe method for measuring muscle blood flow is discussed, and has been evaluated in both normal and ischæmic limbs, a standard amount of ischæmic exercise being employed as the stimulus to hyperæmia. This is considered to be a reliable technique with a high degree of reproducibility, which may be applied to advantage in the clinical assessment of patients with peripheral vascular disease.     

RECONSTRUCTION OF VERTEBRAL ARTERY STENOSIS1

Eight patients with transient attacks of cerebrovascular insufficiency were treated by reconstruction of an atheromatous stenosis at the origin of a vertebral artery. The technique was relatively simple and safe, and was effective in relieving symptoms. Previous reviews suggest that the symptoms of vertebrobasilar insufficiency tend to be persistent, frequent and distressing, and that they can be a prelude to brain stem infarction. The collateral circulation to the vertebrobasilar system may be restricted by anatomical variations and by disease, particularly affecting the circle of Willis. Bilateral vertebral artery disease can cause appreciable ischæmia even without associated carotid artery disease. Carotid endarterectomy is not particularly effective in relieving vertebrobasilar symptoms. Vertebral artery reconstruction appears to be the appropriate treatment for vertebrobasilar insufficiency.     

Mycotic Aneurysms of the Aortic Root1

The clinical details of six patients presenting with mycotic aneurysms as complications of aortic valve endocarditis are presented. A distinction is made between this little-described condition and congenital sinuces and fistulæ. The lesion was demonstrated in all of the patients by cineangiography, and this investigation is strongly recommended. The mortality in the series was high, due to a combination of preoperative toxæmia and resistant heart failure. It is suggested that early investigation of patients presenting with unresponsive aortic endocarditis may reduce the mortality of surgery and will commonly demonstrate the presence of sinuses and fistulæ, facilitating both the planning and performance of the operation.     

ACTIVATION OF THE KALLIKREIN KININ SYSTEM IN INTERSTITIAL CYSTITIS

PURPOSE: We investigated whether the kallikrein kinin system is activated in interstitial cystitis by measuring urinary excretion rates of kinin peptides, active and total kallikrein, and the kininase neutral endopeptidase in women with interstitial cystitis. We compared these excretion rates to a control group of women with stress incontinence and normal bladder function. MATERIALS AND METHODS: Catheter urine was collected from subjects during a water diuresis (approximately 10 ml. per minute) before and after distention of the bladder with 100 ml. water. The contribution of the bladder wall to urinary kinins was assessed by measuring the change in kinin levels after 2 minutes of bladder stasis before and after distention. RESULTS: Absolute bradykinin and kallidin excretion rates were similar in women with interstitial cystitis and control subjects. Two minutes of bladder stasis after bladder distention increased urinary bradykinin (p = 0.02) but not kallidin excretion rates. Active and total kallikrein excretion rates were similar in patients with interstitial cystitis and control subjects. Neutral endopeptidase excretion rates were reduced in the initial urine collection from subjects with interstitial cystitis but were similar in both groups during later collection periods. CONCLUSIONS: These data provide evidence for increased bradykinin levels in the bladder wall of subjects with interstitial cystitis, which may be due in part to reduced neutral endopeptidase levels. These increased bradykinin levels may participate in the pathogenesis and symptomatology of interstitial cystitis.     

Vasorelaxation in isolated bone arteries: Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide bradykinin studied in pigs

We assessed the effects of vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP), and bradykinin in arteries (diameter = 230 μm) isolated from cancellous bone from pigs. Arterial segments (2 mm long) were mounted on a myograph for measurement of isometric force development. After submaximal pre-contraction with norepinephrine, VIP (10^-10-10^-7 M), CGRP (10^-11-10^-7 M), SP (10^-6 M), and bradykinin (10^-11-10^-6 M) were added. 44 arterial segments (23 pigs) were investigated. VIP-, CGRP-, and bradykinin induced a concentration-dependent vasorelaxation, while SP mediated a transient relaxation. After mechanical removal of the endothelium, the effects of SP and bradykinin were completely abolished, while the relaxation to CGRP was still pronounced. This indicates that the effects of SP and bradykinin are mediated by the endothelium, while CGRP mainly mediates relaxation by a direct effect on vascular smooth muscle cells. The relaxations to CGRP and bradykinin were still significant after inhibition of nitric oxide synthase with 10^-4 M N -nitro-L-arginine (L-NNA) and inhibition of prostaglandin synthesis with 10^-5 M indomethacin, indicating the existence of an alternative vasorelaxing pathway. Our findings support the theory of a vaso-regulatory role of neuropeptides in bone.     

The role of bradykinin in endotoxic shock of intestinal origin.

A relationship was looked for between blood levels of bradykinin and endotoxaemia produced by superior mesenteric artery occlusion in the rabbit. The levels of bradykinin were unrelated to and unaltered by the degree of endotoxaemia observed in the systemic and portal circulations. These findings suggest that bradykinin is not responsible for the release of endotoxin from the gut, or the circulatory collapse which follows.     

Effect of Nafamostat Mesilate on Bradykinin Generation and Hemodynamics During LDL Apheresis

Abstract: Dextran-sulfate (DS) cellulose used for low-density lipoprotein (LDL) apheresis seems to be a weak activator of the contact phase of the intrinsic coagulation pathway because the surface of this substance has negative charges. Heparin, a commonly used anticoagulant, has no effect on this process whereas the process is inhibited by a newly developed anticoagulant, nafamostat mesilate (NM). The effects on bradykinin generation were compared between heparin and NM. Five patients with severe hypercholesterolemia were treated with LDL apheresis using either heparin or NM on a different day. During apheresis with heparin, factor XII, high molecular weight kininogen, and prekallikrein were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing plasma through the DS column, and this led to the rise of bradykinin levels from 12 ± 5 (mean ± SE) to 72 ± 14 pg/ml after treatment of 1,000 ml of plasma. NM suppressed almost completely the rise of bradykinin levels. Although blood pressure was apt to decrease during apheresis with heparin, there was no significant difference in blood pressure between heparin and NM. Since an angiotensin-converting enzyme inhibitor may lead to a marked rise in blood levels of bradykinin by suppressing its degradation, the use of NM is recommended for apheresis in patients taking this drug.     

The Influence of Technical Factors upon Renal Homograft Function1

Though immunological rejection is the chief obstacle to the prolonged survival of renal homografts, a significant number of graft failures can be attributed to complications of surgical technique. The purpose of this paper is to analyse the influence of vascular anomalies in the donor kidney upon graft function. Factors considered include the duration of “warm” and “cold” ischæmia, the technical improvisation of the vascular anastomoses, and the utilization of both kidneys from any cadaver. During the past three and a half years, 43 renal homografts have been transplanted into 40 patients at the Prince Henry Hospital, Sydney. Although there has been a high incidence of vascular anomaly in this series, no donor kidney has been discarded for this reason, and satisfactory graft function has been obtained in 31 of the transplanted kidneys.     

Effects of antihypertensive therapy on intrarenal angiotensin and bradykinin levels in experimental renal insufficiency

BACKGROUND: Whereas angiotensin converting enzyme inhibitors and angiotensin type 1 receptor antagonists have beneficial effects in the remnant model of renal failure, calcium channel blockers do not consistently improve renal disease in this model. This study examined whether these different means of blood pressure reduction have different effects on renal levels of angiotensin (Ang) and bradykinin peptides. METHODS: Rats subjected to five-sixths nephrectomy were divided into groups with similar hypertension and proteinuria at 4 to 5 weeks. They then received either no treatment, or enalapril, losartan or nifedipine for 2 weeks. Following repeat measurements of proteinuria and blood pressure, Ang II and bradykinin peptides were measured in the remnant kidney and renin, Ang II, and aldosterone were measured in the plasma. RESULTS: All three drugs had equivalent blood pressure-lowering effects. Enalapril and losartan reduced proteinuria but nifedipine did not. Reduction of proteinuria in rats treated with enalapril and losartan was associated with a reduction in Ang II levels in both the peri-infarct and intact portions of the remnant kidney. By contrast, nifedipine increased Ang II levels in the intact portion of the remnant kidney. Losartan reduced bradykinin levels in the peri-infarct portion of the remnant kidney while enalapril reduced bradykinin levels in the intact portion of the remnant kidney. Nifedipine had no effect on intrarenal bradykinin levels. CONCLUSIONS: The differential effects of enalapril, losartan and nifedipine on proteinuria and intrarenal Ang II and bradykinin levels suggest that the ability of an antihypertensive to decrease proteinuria may depend on its ability to decrease kidney Ang II and bradykinin levels.     

Kinin kinetics during different dialysis protocols with AN69 dialyser in ACEI-treated patients

The effect of different dialysis modes on kinin kinetics wasstudied in seven stable haemodialysis patients treated withAN69 dialysers and ACE inhibitors (ACEI). AN69 haemodiafiltrationwith calcium-enriched substitution (HDF), AN69 haemodialysiswith 1.75 (HD 1.75) and 1.50 (HD 1.50)mmol/l dialysate calcium,AN69 haemodialysis with 1.25mmol/l dialysate calcium and substitutionof 2.25 mmol/h calcium (HD +Ca), and cellulose acetate haemodiafiltration(CA HDF) were compared. Dialysis was uneventful in all patients.During dialysis, serum calcium, sodium, pH, albumin, and bradykininwere measured at the start and after 5 min at arterial, venous,and postinfusion side of the extracorporeal circuit. Serum predialysisbradykinin was 107±18fmol/ml (mean±SEM) in patientson HDF, 61±9 fmol/ml in patients on HD 1.50, 49±13fmol/ml in patients on HD 1.75, 35±3 fmol/1 in patientson HD±Ca, and 75±27 fmol/ml in CA HDF. No significantchange of mean bradykinin levels occurred after 5 min at thearterial and venous side of the dialyser or postinfusion. Individualhigh bradykinin levels, up to 2672 fmol/ml, were observed butwithout clinical consequences, suggesting that the thresholdvalue is difficult to determine. No significant correlationswere evidenced between bradykinin levels and any of the biochemicalmeasurements. The present data show an intraindividual variabilityof the bradykinin levels with variation coefficients rangingfrom 0.386 to 2.783. The present study illustrates that haemodialysisand haemodiafiltration with AN69 in ACEI-treated patients, underthe present conditions, does not result in anaphy-lactoid reactionsor in a clinically significant release of bradykinin. The occurrenceof anaphylactoid reactions with high bradykinin levels is probablythe result of several concurrent bioincompatible factors insensitized patients.     

?Angiotensin-converting-enzyme��-Hemmer induziertes Angio?dem

Angiotensin-converting enzyme (ACE) inhibitors block the catalysis of angiotensin I to angiotensin II and also the breakdown of bradykinin. ACE inhibitor-induced angioedema is mediated by inhibited bradykinin degradation leading to enhanced bradykinin plasma levels. The efficacy of currently used standard treatments with antiallergic drugs is questionable. A patient with acute ACE inhibitor-induced angioedema was treated with icatibant, a specific bradykinin B2 receptor antagonist approved for the treatment of hereditary angioedema. A single subcutaneous injection of 30?mg icatibant resulted in a rapid onset of symptom relief and a remarkable shortening of duration of the attack.     

Comparative nasal effects of bradykinin and histamine: influence on nasal airways resistance and plasma protein exudation.

BACKGROUND--Bradykinin may contribute to the pathogenesis of allergic rhinitis. Like histamine, nasal challenge with bradykinin induces rhinorrhoea, nasal blockage, and plasma protein leakage. Their comparative nasal potencies have not, however, been fully elucidated. METHODS--Three double blind, randomised, placebo controlled and cross-over studies were undertaken to compare objectively the nasal effects of bradykinin, histamine, and vehicle. RESULTS--Both bradykinin and histamine produced dose dependent increases in nasal airways resistance (NAR). There was no significant difference in the effects of bradykinin and histamine on NAR at any dose level. On a molar basis, however, bradykinin was 6.98 times more potent than histamine in inducing a 50% increase in NAR. Nasal challenge with bradykinin and histamine also induced significant rhinorrhoea compared with vehicle. The amount of rhinorrhoea induced by histamine was significantly greater than that induced by bradykinin at any dose level. Bradykinin and histamine induced dose dependent nasal pain and nasal itch respectively. When administered as single doses both bradykinin (1.9 mumol) and histamine (1.9 mumol) induced significant rhinorrhoea compared with the vehicle. The volume of rhinorrhoea secretions induced by histamine was 29% greater than that induced by bradykinin. In contrast, although NAR was increased significantly more by histamine than by the vehicle, the effect of bradykinin on NAR was significantly greater than histamine and vehicle in both magnitude and duration of effect. The incremental effect of bradykinin on lavage albumin levels was also significantly greater than both histamine and vehicle. CONCLUSIONS--This study shows that the nasal vascular effects of histamine are less prominent than its actions on rhinorrhoea, and that the greater obstructive effect of bradykinin than histamine on NAR may contribute to the relative lack of efficacy of H1 antihistamines on nasal blockage in clinical disease.     

Volatile Anesthetics Affect Calcium Mobilization in Bovine Endothelial Cells

Background: The site where volatile anesthetics inhibit endothelium-dependent, nitric oxide-mediated vasodilation is unclear. To determine whether anesthetics could limit endothelium-dependent nitric oxide production by inhibiting receptor-mediated increases in cytosolic Calcium2+, experiments were performed to see if the inhalational anesthetics halothane, isoflurane, and enflurane affect intracellular Calcium2+ ([Ca2+]i) transients induced by the agonists bradykinin and adenosine triphosphate in cultured bovine aortic endothelial cells.

Methods: Bovine aortic endothelial cells, which had been loaded with the fluorescent Calcium2+ indicator Fura-2, were added to medium preequilibrated with volatile anesthetic (1.25% and 2.5% for isoflurane, 1.755 and 3.5% for enflurane, and 0.75% and 1.5% for halothane). In Calcium2+ -containing medium, intracellular Calcium sup 2+ transients were elicited in response to bradykinin (10 nM and 1 micro Meter) or adenosine triphosphate (1 micro Meter and 100 micro Meter).

Results: Both bradykinin and adenosine triphosphate triggered a rapid rise to peak [Ca2+]i followed by a gradual decline to a plateau above the resting level. Although basal [Ca2+]i was unaltered by the anesthetics, both halothane and enflurane, in a dose-dependent manner, depressed the peak and plateau of the [Ca2+] sub i transient elicited by 10 nM bradykinin, whereas isoflurane had no effect. When [Ca2+]i transients were elicited by 1 micro Meter bradykinin, halothane (1% and 5%) did not alter peak and plateau levels. Halothane and enflurane also decreased [Ca2+]i transients evoked by 1 micro Meter and 100 micro Meter adenosine triphosphate, whereas isoflurane also had no effect in this setting.     

Bradykinin preconditioning in coronary artery bypass grafting

Background

Experimental studies have shown that activation of bradykinin B₂ receptor is one of the most important triggers of ischemic preconditioning. However, the effect of exogenous administration of bradykinin in cardiac surgery is not yet known. The present prospective randomized study was designed to investigate the effect of bradykinin pretreatment in patients undergoing elective coronary artery bypass surgery.

Methods

Forty-one patients with multiple-vessel coronary artery disease and stable angina, admitted for the first time for elective coronary artery bypass surgery, were randomized into control or bradykinin (BK) groups. Patients in the BK group received bradykinin infusion for 7 minutes (total dose 25 μg) before the initiation of cardiopulmonary bypass. Perioperative cardiac specific troponin I (cTnI) and creatine kinase cardiac isoenzyme (CKMB) release and hemodynamics were recorded.

Results

Bradykinin infusion caused acute decrease of blood pressure in most of the cases and the mean minimum mean blood pressure during bradykinin infusion was 72.7% of the original mean blood pressure (MBP) level (74.7 ± 7.9 vs 54.4 ± 12.1 mm Hg, p < 0.01). There were no differences in baseline levels of cTnI and CKMB between the groups. The postoperative cTnI levels were lower than 10 ng/mL in most patients in both groups (18 in the BK group and 15 in the control group). There was no difference in cTnI between the groups. However, patients who received bradykinin released significantly less CKMB than did the controls postoperatively (6 hours, BK, 22.1 ± 9.5 vs control, 23.6 ± 12.7 U/L; 12 hours, BK, 19.4 ± 12.4 vs control, 28.7 ± 23.8 U/L; 24 hours, BK, 21.5 ± 14.7 vs control, 35.5 ± 28.9 U/L; 48 hours, BK, 14.4 ± 7.5 vs control, 23.5 ± 13.6 U/L; analysis of variance [ANOVA] for repeated measurement, p = 0.036). Maximum CKMB was also lower in the BK group (22.4 ± 14.4 vs 37.7 ± 27.5 U/L, p = 0.044). There was no significant difference between the groups in any of the hemodynamic variables.

Conclusions

Exogenous bradykinin infusion showed weak cardioprotective effect in the low-risk patients undergoing coronary artery bypass surgery but the dose used in the study caused acute decrease of systemic blood pressure.     

Antiinflammatory effects of Tacrolimus in a mouse model of pleurisy

INTRODUCTION: Tacrolimus is an antibiotic macrolide with immunosuppressant properties isolated from Streptomyces tsukubaensis. OBJECTIVES: This study evaluated whether the acute and systemic administration of Tacrolimus significantly interfered in leukocyte migration, exudation, myeloperoxidase and adenosine-deaminase and nitric oxide levels, as well as Interleukin-1 (IL-1beta) and tumor necrosis factor alpha (TNFalpha) levels in a mouse model of pleurisy in comparison to those obtained with dexamethasone. MATERIALS AND METHODS: Pleurisy was induced by carrageenan (Cg, 1%), bradykinin (BK, 10 nmol), histamine (HIS, 1 micromol) or substance P (PS, 20 nmol) administered by intrapleural route (ipl.) and the inflammatory parameters (cell migration and exudation) were analyzed 4 h after. In the model of pleurisy induced by carrageenan, other markers in the pleural fluid, such as cytokines (TNFalpha and Il-1beta), nitrite/nitrate (NOx), myeloperoxidase (MPO) and adenosine-deaminase (ADA) levels, were also studied. Dexamethaseone (0.5 mg/kg, i.p., 0.5 h before) was also analyzed in all protocols. RESULTS: In the pleurisy induced by carrageenan, Tacrolimus (1 mg/kg, i.p.) and dexamethasone (0.5 mg/kg, i.p.) administered 0.5 h before caused a significant decrease in leukocytes, neutrophils and exudation (P < 0.01). Under the same conditions, Tacrolimus and dexamethasone did not modify the blood's white or red cells (P > 0.05). Tacrolimus showed a long lasting antiinflammatory effect, inhibiting leukocytes and neutrophils for up to 24 h (P < 0.01), whereas the inhibition of exudation was less marked (up to 2 h) (P < 0.01). These drugs caused a marked reduction in MPO activity, as well as IL-1beta and TNFalpha levels (P < 0.01), but only Tacrolimus inhibited ADA activity (P < 0.01). On the other hand, dexamethasone, but not Tacrolimus, inhibited NOx levels (P < 0.01). In the same conditions, Tacrolimus significantly inhibited cell migration induced by either bradykinin, histamine or substance P (P < 0.05). In a similar manner, dexamethasone inhibited leukocyte influx induced by bradykinin and histamine (P < 0.05). Regarding exudation effects, dexamethasone markedly inhibited this parameter induced by BK, HIS or SP, whereas Tacrolimus only inhibited exudation caused by HIS (P < 0.05). CONCLUSIONS: The results of the present work indicate that Tacrolimus showed important antiinflammatory properties against pleurisy in mice that are different from those caused by dexamethasone. The inhibition of proinflammatory cytokine (TNFalpha, IL-1beta), enzyme (myeloperoxidase, adenosine-deaminase) and mediator (bradykinin, histamine, substance P) release and/or action appears to account for Tacrolimus's actions.     

Sevoflurane mimics ischemic preconditioning effects on coronary flow and nitric oxide release in isolated hearts.

BACKGROUND: Like ischemic preconditioning, certain volatile anesthetics have been shown to reduce the magnitude of ischemia/ reperfusion injury via activation of K+ adenosine triphosphate (ATP)-sensitive (K(ATP)) channels. The purpose of this study was (1) to determine if ischemic preconditioning (IPC) and sevoflurane preconditioning (SPC) increase nitric oxide release and improve coronary vascular function, as well as mechanical and electrical function, if given for only brief intervals before global ischemia of isolated hearts; and (2) to determine if K(ATP) channel antagonism by glibenclamide (GLB) blunts the cardioprotective effects of IPC and SPC. METHODS: Guinea pig hearts were isolated and perfused with Krebs-Ringer's solution at 55 mm Hg and randomly assigned to one of seven groups: (1) two 2-min total coronary occlusions (preconditioning, IPC) interspersed with 5 min of normal perfusion; (2) two 2-min occlusions interspersed with 5 min of perfusion while perfusing with GLB (IPC+GLB); (3) SPC (3.5%) for two 2-min periods; (4) SPC+GLB for two 2-min periods; (5) no treatment before ischemia (control [CON]); (6) CON+GLB; and (7) no ischemia (time control). Six minutes after ending IPC or SPC, hearts of ischemic groups were subjected to 30 min of global ischemia and 75 min of reperfusion. Left-ventricular pressure, coronary flow, and effluent NO concentration ([NO]) were measured. Flow and NO responses to bradykinin, and nitroprusside were tested 20-30 min before ischemia or drug treatment and 30-40 min after reperfusion. RESULTS: After ischemia, compared with before (percentage change), left-ventricular pressure and coronary flow, respectively, recovered to a greater extent (P<0.05) after IPC (42%, 77%), and treatment with SPC (45%, 76%) than after CON (30%, 65%), IPC+GLB (24%, 64%), SPC+GLB (20%, 65%), and CON+GLB (28%, 64%). Bradykinin and nitroprusside increased [NO] by 30+/-5 (means +/- SEM) and 29+/-4 nM, respectively, averaged for all groups before ischemia. [NO] increased by 26+/-6 and 27+/-7 nM, respectively, in SPC and IPC groups after ischemia, compared with an average [NO] increase of 8+/-5 nM (P<0.01) after ischemia in CON and each of the three GLB groups. Flow increases to bradykinin and nitroprusside were also greater after SPC and IPC. CONCLUSIONS: Preconditioning with sevoflurane, like IPC, improves not only postischemic contractility, but also basal flow, bradykinin and nitroprusside-induced increases in flow, and effluent [NO] in isolated hearts. The protective effects of both SPC and IPC are reversed by K(ATP) channel antagonism.