Ca2+-induced redistribution of Ca2+/calmodulin-dependent protein kinase II associated with an endoplasmic reticulum stress response in vascular smooth muscle.

The relation between CaM kinase II activity and high Ca2+-mediated stress responses was studied in cultured vascular smooth muscle cells. Treatment with ionomycin (1 microM) for 5 min caused a significant loss of CaM kinase II activity in whole cell homegenates and prominent vesiculation of the endoplasmic reticulum (ER). Similar losses of CaM kinase II activity were observed in the soluble lysate as assessed by activity measurements and Western blotting. Examination of the post-lysate particulate fraction showed that the loss of CaM kinase II from the soluble lysate was accompanied by a redistribution of CaM kinase II to this fraction. The ionomycin-mediated response was limited to this concentration (1 microM); lower concentrations of ionomycin as well as stimulation with angiotensin II (1 microM) orATP (100 microM) did not cause a shift in CaM kinase II distribution. Treatment with neither the CaM kinase II inhibitor KN-93 nor the phosphatase inhibitor okadaic acid altered the ionomycin-induced redistribution indicating that CaM kinase II activation and/or phosphorylation was not part of the mechanism. The response, however, was eliminated when the cells were treated in Ca2+-free medium. Washout of ionomycin led to only a partial restoration of the kinase activity in the soluble fraction after 10 min. Immunofluorescence microscopy of resting cells indicated colocalization of antibodies to CaM kinase II and an ER protein marker. ER vesiculation induced by ionomycin coincided with a parallel redistribution of CaM kinase II and ER marker proteins. These data link ionomycin-induced ER restructuring to a progressive redistribution of CaM kinase II protein to an insoluble particulate fraction and loss of cellular CaM kinase II activity. We propose that redistribution of CaM kinase II and loss of cellular activity are components of a common Ca2+-overload induced cellular stress response in cells.

Difficult or impossible ventilation after sufentanil-induced anesthesia is caused primarily by vocal cord closure.

INTRODUCTION: Opioid-induced rigidity often makes bag-mask ventilation difficult or impossible during induction of anesthesia. Difficult ventilation may result from chest wall rigidity, upper airway closure, or both. This study further defines the contribution of vocal cord closure to this phenomenon. METHODS: With institutional review board approval, 30 patients undergoing elective cardiac surgery participated in the study. Morphine (0.1 mg/kg) and scopolamine (6 microg/kg) given intramuscularly provided sedation along with intravenous midazolam as needed. Lidocaine 10% spray provided topical anesthesia of the oropharynx. A fiberoptic bronchoscope positioned in the airway photographed the glottis before induction of anesthesia A second photograph was obtained after induction with 3 microg/kg sufentanil administered during a period of 2 min. A mechanical ventilator provided 10 ml/kg breaths at 10/min via mask and oral airway with jaw thrust. A side-stream spirometer captured objective pulmonary compliance data. Subjective airway compliance was scored. Pancuronium (0.1 mg/kg) provided muscle relaxation. One minute after the muscle relaxant was given, a third photograph was taken and compliance measurements and scores were repeated. Photographs were scored in a random, blinded manner by one investigator. Wilcoxon signed rank tests compared groups, with Bonferroni correction. Differences were considered significant at P < 0.05. RESULTS: Twenty-eight of 30 patients exhibited decreased pulmonary compliance and closed vocal cords after opioid induction. Two patients with neither objective nor subjective changes in pulmonary compliance had open vocal cords after opioid administration. Both subjective and objective compliances increased from severely compromised values after narcotic-induced anesthesia to normal values (P = 0.000002) after patients received a relaxant. Photo scores document open cords before induction, progressing to closed cords after the opioid (P = 0.00002), and opening again after a relaxant was administered (P = 0.00005). CONCLUSION: Closure of vocal cords is the major cause of difficult ventilation after opioid-induced anesthesia.

Myosin light chain kinase phosphorylation in nitrovasodilator induced swine carotid artery relaxation.

Nitrovasodilators are hypothesized to induce smooth muscle relaxation by their metabolism to nitric oxide, which then activates soluble guanylyl cyclase, increases [cGMP], and activates cGMP-dependent protein kinase. cGMP-dependent phosphorylation is then proposed to decrease intracellular [Ca2+] ([Ca2+]i) and to reduce the Ca(2+)-sensitivity of contraction. We hypothesized that one component of decreased Ca(2+)-sensitivity, reduced Ca(2+)-sensitivity of MLC phosphorylation, was due to phosphorylation of myosin light chain kinase (MLCK) on the peptide site A. In the swine carotid artery, histamine (10 microM) stimulation increased aequorin-estimated [Ca2+]i, MLCK site A phosphorylation, MLC phosphorylation, and force. Subsequent addition of 100 microM nitroglycerin (NTG) or 100 microM sodium nitroprusside (NP) to histamine-stimulated tissues increased [cGMP], decreased both MLC phosphorylation and force, but did not significantly alter [cAMP], [Ca2+]i, or MLCK site A phosphorylation. Addition of NTG and NP alone to unstimulated tissues increased MLCK site A phosphorylation, but did not alter [Ca2+]i. In tissues preincubated with NP, subsequent histamine contraction was slowed compared with controls, however, this slowed rate of contraction appeared to result from an attenuation of histamine-dependent increases in [Ca2+]i. These data suggest that, in swine carotid artery, nitrovasodilators can decrease the Ca(2+)-sensitivity of MLC phosphorylation without increasing MLCK site A phosphorylation. Nitrovasodilators, per se, can induce site A MLCK phosphorylation, potentially by cGMP dependent activation of cAMP-dependent protein kinase.

Upper airway closure: a primary source of difficult ventilation with sufentanil induction of anesthesia.

Large-dose opioid induction of anesthesia can lead to difficult ventilation via a mask. Poor ventilatory compliance (VC) may be secondary to "rigid" chest and abdominal wall musculature, glottic closure, or upper airway obstruction. This double-blind study assessed the contribution of the upper airway to poor VC by inducing sufentanil anesthesia in patients undergoing cardiac surgery who are ventilated via a mask (Group M) or endotracheal tube fiberoptically inserted (Group E). After induction of anesthesia with sufentanil 3 microgram/kg from time (T) = 0 min to T = 2 in Group M (n = 17) or Group E(n = 23), VC and adductor pollicis (AP) twitch tension was measured continuously. Immediately prior to muscle relaxant (pipecuronium or doxacurium) administration at T = 3, Group E demonstrated significantly better VC (46 mL/cm H2O [39-55 interquartile range (IQR)]) than Group M (19 mL/cm H2O [7-24 IQR]). The effect of muscle relaxant administration on VC preceded its effect at the AP. After complete relaxation of the AP at T = 9, both groups had similar VC. Difficult ventilation during sufentanil induction of anesthesia lies at the level of the glottis or above. Bypassing these structures with an endotracheal tube overcomes the usual decreased VC.

Focal increases in [Ca2+]i may account for apparent low Ca2+ sensitivity in swine carotid artery.

Estimates of [Ca2+]i sensitivity in intact smooth muscle are frequently obtained by measuring [Ca2+]i with indicators such as aequorin or Fura-2. We investigated whether focal increases in [Ca2+]i could impair such measures of [Ca2+]i sensitivity. Stimulation of swine carotid artery with 10 microM histamine increased aequorin estimated [Ca2+]i, Fura-2 estimated [Ca2+]i and Ca2+ sensitivity without significantly altering the aequorin/Fura-2 ratio (an estimate of [Ca2+]i homogeneity). Subsequent inhibition of Na+/Ca2+ exchange by replacement of Na+ in the PSS with choline+ significantly increased aequorin-estimated [Ca2+]i but only minimally increased Fura-2 estimated [Ca2+]i, myosin light chain (MLC) phosphorylation and force. This resulted in a large increase in the aequorin/Fura-2 ratio, suggesting an increase in [Ca2+] inhomogeneity. Addition of 100 microM histamine to tissues in the choline+ buffer initially increased both aequorin and Fura-2 estimated [Ca2+]i, but after 10 min exposure both of the [Ca2+]i estimates declined to pre-histamine levels. Histamine addition significantly increased MLC phosphorylation and force, indicating increased Ca2+ sensitivity, but the aequorin/Fura-2 ratio remained elevated and unchanged from pre-histamine values. These data show that under certain conditions, aequorin and Fura-2 can yield widely differing estimates of [Ca2+]i and thus can cause misleading assessments of Ca2+ sensitization mechanisms. These discrepancies may arise from inhomogeneous or focal increases in [Ca2+]i which can be evaluated with the aequorin/Fura-2 ratio.

Focal [Ca2+]i increases detected by aequorin but not by fura-2 in histamine- and caffeine-stimulated swine carotid artery.

1. We hypothesized that the homogeneity of intracellular [Ca2+] ([Ca2+]i) varies and is regulated in arterial smooth muscle. 2. We evaluated this hypothesis by exploiting the different characteristics of several [Ca2+]i indicators: (1) aequorin, which theoretically can measure focal increases in [Ca2+]i, (2) fura-2, which is predominantly a measure of mean cytoplasmic [Ca2+], and (3) myosin light chain phosphorylation and force, which reflect increases in [Ca2+] near the contractile apparatus. 3. From the differences in the observed aequorin and fura-2 signals, we developed an index of the relative degree of [Ca2+]i homogeneity as the ratio of the aequorin signal and fura-2 signal. 4. Stimulation with intermediate concentrations of histamine (1 and 10 microM) or high [K+]o (25 and 40 mM) increased [Ca2+]i and contractile stress. Relative [Ca2+]i homogeneity, estimated from the aequorin/fura-2 ratio, remained similar to levels observed in unstimulated tissues. 5. Higher concentrations of histamine (100 microM) also increased [Ca2+]i and stress, but the aequorin/fura 2 ratio declined , indicating increased [Ca2+]i homogeneity. Similarly, the aequorin/fura-2 ratio decreased when extracellular Ca2+ was removed. 6. Stimulation with histamine in low extracellular [Ca2+] transiently increased [Ca2+]i and the aequorin/fura-2 ratio. Similarly, in tissues treated with low extracellular [Ca2+], restoration of extracellular Ca2+ transiently increased both [Ca2+]i and the aequorin/fura-2 ratio. Although both of these experiments demonstrated a transient decrease in [Ca2+]i homogeneity, only histamine stimulation led to increased myosin light chain phosphorylation and force. These results indicate that the focal increases in [Ca2+]i observed with histamine stimulation and Ca2+ restoration occurred in different cellular regions. 7. Addition of caffeine (20 mM) increased [Ca2+]i and [cAMP], but this was not accompanied by sustained increased myosin light chain phosphorylation or contraction. Phosphorylation of myosin light chain kinase did not appear to underlie the lack of increase in myosin light chain phosphorylation. Rather, caffeine induced a sustained increase in the aequorin/fura-2 ratio, suggesting that caffeine inhibits smooth muscle contraction by localizing increases in [Ca2+]i to a region distant from the contractile apparatus. 8. These data suggest that there can be transient and sustained focal increases in [Ca2+]i. Aequorin detected increased [Ca2+]i in small regions of the cytoplasm during release from and refilling of the intracellular Ca2+ store and with caffeine stimulation. Dual use of aequorin and fura-2 permits determination of relative [Ca2+]i homogeneity in smooth muscle.

Myosin light chain kinase phosphorylation in swine carotid artery contraction and relaxation.

We investigated the role of myosin light chain kinase (MLCK) phosphorylation in regulating the sensitivity of vascular smooth muscle myosin light chain (MLC) phosphorylation to intracellular Ca2+ concentration ([Ca2+]i). 32PO4-loaded swine carotid arteries were stimulated with histamine or high K+, MLCK was isolated, and the relative phosphorylation of tryptic peptides was measured. In nonlabeled tissues, we measured [Ca2+]i with aequorin, MLCK activity ratio, MLC phosphorylation, and force. A comparison of MLCK phosphorylation on peptide A (mol P in site A/mol MLCK) and MLCK activity ratio showed an inverse relation, suggesting that MLCK site A phosphorylation can regulate the Ca2+ sensitivity of MLCK. MLCK site A phosphorylation and MLCK activity ratio depended on [Ca2+]i. Histamine stimulation yielded greater MLC phosphorylation than high K+ stimulation over a range of [Ca2+]i; however, there were no apparent stimulus-dependent differences in MLCK phosphorylation, suggesting that stimulus-dependent differences in the Ca2+ sensitivity of MLC phosphorylation are not based on differences in MLCK phosphorylation. We also determined whether MLCK phosphorylation was involved in adenosine 3',5'-cyclic monophosphate-mediated relaxation. In histamine-contracted tissues, forskolin decreased [Ca2+]i, MLC phosphorylation, and force. MLCK phosphorylation decreased to an extent consistent with the decrease in [Ca2+]i. In KCl-stimulated tissues, forskolin did not alter [Ca2+]i or increase MLCK phosphorylation but forskolin did decrease MLC phosphorylation. Thus, in swine carotid artery, MLCK phosphorylation appears to be regulated exclusively by Ca2+ and plays little role in stimulus-dependent differences in Ca2+ sensitivity of MLC phosphorylation or in mediating forskolin-induced relaxation.

The dose-response relationship of tranexamic acid.

BACKGROUND: Prophylactic administration of the antifibrinolytic drug tranexamic acid decreases bleeding and transfusions after cardiac operations. However, the best dose of tranexamic acid for this purpose remains unknown. This study explored the dose-response relationship of tranexamic acid for hemostatic efficacy after cardiac operation. METHODS: In prospective, randomized, double-blinded fashion, 148 patients undergoing cardiac operation with extracorporeal circulation were divided into six groups: a placebo group and five groups receiving tranexamic acid in loading doses before incision (range 2.5 to 40 mg.kg-1) and one-tenth the loading dose hourly for 12 h. The mass of blood collected by chest tubes over 12 h represented blood loss. Allogeneic transfusions within 12 h and within 5 d of surgery were tallied. RESULTS: The six groups presented similar demographics. Patients receiving placebo had increased postoperative D-dimer concentration compared to groups receiving tranexamic acid. Patients receiving at least 10 mg.kg-1 tranexamic acid followed by 1 mg.kg-1.h-1 bled significantly less (365, 344, and 369 g.12 h-1, respectively, for those three groups) compared with patients who received placebo (552 g, P < 0.05). Tranexamic dose did not affect transfusions. Only initial hematocrit affected whether a patient received an allogeneic transfusion within 5 days of operation (odds ratio 2.08 for each 3% absolute decrease in hematocrit). CONCLUSIONS: Prophylactic tranexamic acid, 10 mg.kg-1 followed by 1 mg.kg-1.h-1, decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit.

Steady-state dependence of stress on cross-bridge phosphorylation in the swine carotid media.

Tonic contractions of the swine carotid media are typically characterized by initial transients in myoplasmic [Ca2+] and cross-bridge phosphorylation followed by force maintenance with reduced intracellular [Ca2+] and cross-bridge phosphorylation ("latch"). The presence of effective mechanisms in the carotid media to limit steady-state myoplasmic [Ca2+] and cross-bridge phosphorylation to modest increases over resting values has limited experimental attempts to determine the dependence of active stress (force/tissue cross-sectional area) on cross-bridge phosphorylation. In this study, we employed stimulation protocols that combined effective contractile agonists with inhibitors of Ca2+ extrusion or sequestration to achieve high steady-state levels of cross-bridge phosphorylation (up to 60%). Increases in cross-bridge phosphorylation from 30 to 60% were not associated with significant increases in stress in agreement with the predictions of Hai and Murphy [Am. J. Physiol. 254 (Cell Physiol. 23): C99-C106, 1988] four-state cross-bridge model for the carotid media. Thus cross-bridge phosphorylation may suffice to determine force generation in vascular smooth muscle if both phosphorylated and dephosphorylated attached cross bridges (or latch bridges) contribute to active stress.

Electrical field stimulation-mediated relaxation of rabbit middle cerebral artery. Evidence of a cholinergic endothelium-dependent component.

The effects of electrical field stimulation (EFS) of rabbit middle cerebral arteries were examined using wire-mounted arterial segments. EFS of segments maintained at rest tension caused a tetrodotoxin-sensitive sympathetic contraction. In agonist-contracted segments maintained at approximately 60% of tissue maximum force, EFS caused a relaxation in two thirds of the preparations. Maximum response (mean +/- SEM) was 33 +/- 3.5% of maximal relaxation. The EFS relaxation was tetrodotoxin-sensitive but was not blocked by either chronic surgical sympathectomy or exposure to guanethidine (5 microM). Electron microscopy of chromaffin-fixed arterial sections showed the presence of chromaffin-positive large and small vesicles. Within the same sheath of Schwann were also a smaller number of nerve profiles containing many small clear vesicles. Removal of the vascular endothelium or treatment with atropine (10 nM) eliminated the EFS relaxation in approximately 50% of the segments and reduced the response in another 35-40%; in the remainder, relaxation was unaffected. Combined data for endothelium removal and atropine treatment showed that each caused a significant (p less than 0.01) reduction in the EFS relaxation. Atropine also significantly reduced EFS relaxation in guanethidine-treated segments. There was no reduction in EFS relaxation after procedures that antagonized ATP- or substance P-mediated relaxations. These results indicate that EFS of precontracted rabbit middle cerebral artery causes a neurogenic nonadrenergic relaxation. The neuroeffector mechanism mediating this response has a predominantly cholinergic endothelium-dependent component as well as a noncholinergic endothelium-independent component.

Ventilatory compliance after three sufentanil-pancuronium induction sequences.

Poor ventilatory compliance, a predictable side effect of high-dose opioid induction techniques, is purportedly blunted by pretreatment with nondepolarizing muscle relaxant. This study used both total compliance and a subjective compliance score to compare three different sequences of opioid induction using a 2-min infusion of sufentanil 3 micrograms.kg-1. Nineteen patients in each of three groups received a total of 100 micrograms.kg-1 of pancuronium, in the following randomized double-blinded fashion: control, all pancuronium 1 min after sufentanil; pretreated, 1 mg pancuronium 1 min before sufentanil and the balance of pancuronium 1 min after sufentanil; and mixed, all pancuronium mixed with sufentanil. Topical lidocaine prior to induction permitted early oral airway insertion midway through the sufentanil infusion. Immediately at the conclusion of sufentanil infusion, a tightly fitted mask, anterior jaw thrust, and mechanical ventilator permitted measurement of plateau airway pressure and exhaled volume in five replicates. Pressure and volume measurements were repeated 5 min later. Total compliance was calculated as the median plateau airway pressure divided into its associated exhaled volume. Groups did not differ in demographics. In one control patient and two pretreated patients hemoglobin oxygen saturation as measured by pulse oximetry decreased below 90%. Immediately after sufentanil infusion, the total compliance for control patients of 4.1 ml.cmH2O-1 (mean [2.6-6.5, 95% confidence interval] ) did not differ from that of the pretreated group (6.3 [3.5-11.4] ml.cmH2O-1), but the mixed group exhibited higher compliance (40.3 [33.8-47.9] ml.cmH2O-1) than the other groups (P less than 10(-8]. All groups achieved similar total compliances several minutes after a total of 100 micrograms.kg-1 pancuronium had been administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery.

BACKGROUND: Desmopressin-induced release of tissue plasminogen activator from endothelial cells may explain the absence of its hemostatic effect in patients undergoing cardiac surgery. Prior administration of the antifibrinolytic drug tranexamic acid might unmask such an effect, and combination therapy might thereby improve postoperative hemostasis. METHODS AND RESULTS: A double-blinded design randomly allocated 163 adult patients undergoing coronary revascularization, valve replacement, both procedures, or repair of atrial septal defect to four treatment groups: placebo, tranexamic acid given as 10 mg/kg over 30 minutes followed by 1 mg.kg-1.hr-1 for 12 hours initiated before skin incision, desmopressin given as 0.3 micrograms/kg over 20 minutes after protamine infusion, and both drugs. One surgeon performed all operations. Blood loss consisted of mediastinal tube drainage over 12 hours. Follow-up visits sought evidence of myocardial infarction and stroke. Desmopressin decreased neither the 12-hour blood loss nor the amount of homologous red cells transfused. Tranexamic acid alone significantly reduced 12-hour blood loss, by 30% (mean, 318 versus 453 ml; p less than 0.0001), without enhancement by desmopressin. Tranexamic acid also decreased the proportion of patients receiving homologous blood within 12 hours of operation (8% versus 21%, p = 0.024) and within 5 days of operation (22% versus 41%, p = 0.011). CONCLUSIONS: Desmopressin exerts no hemostatic effect, with or without prior administration of antifibrinolytic drug. Prophylactic tranexamic acid alone appears economical and safe in decreasing blood loss and transfusion requirement after cardiac surgery.

Selective variation of agonist and neurally mediated vasoconstriction with rabbit middle cerebral artery branch order.

The in vitro contractions of four successive branches of the rabbit middle cerebral artery to norepinephrine (NE), serotonin (5HT), histamine, and electrical field stimulation (EFS) were examined. Internal lumen diameters of the four branches (designated MCA, M1, M2, M3, proximal to distal) ranged from a mean of 270 microns in the MCA to 160 microns in the M3 segments. NE produced a small alpha adrenoceptor-mediated response in the MCA (12% of tissue maximum); this was diminished in the M1 segment and there was no evidence of alpha adrenoceptor-mediated responses in the M2 and M3 branches. NE contractions, mediated through low affinity sites (extraceptors), did not change with branch order. Maximal responses to 5HT (1 microM) were small and also diminished with branch order; the MCA and M1 contracted to 24 and 18% of tissue maximum, respectively. Negligible responses were obtained in M2 and M3. EFS resulted in contractions that were tetrodotoxin- and guanethidine-sensitive. Maximum EFS responses were 21% tissue maximum in the MCA, 13% in the M1, and less than 5% in the M2 and M3. In contrast, maximal contractile responses to histamine (100 microM) were at or near tissue maximum in all segments. Removal of the endothelium did not influence the size of the contraction to NE, 5HT or histamine in the MCA and M1 segments. Neither NE, 5HT, nor histamine caused relaxation responses in agonist or KCl-contracted segments. The results indicate a differential variation in responsiveness with increasing branch order in the rabbit cerebrovascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that neuropeptide Y and norepinephrine mediate electrical field-stimulated vasoconstriction of rabbit middle cerebral artery.

We investigated the contractile response of isolated rabbit middle cerebral artery (MCA) segments to electrical field stimulation (EFS). The dynamics of the EFS contraction were compared with a similar-sized branch of rabbit ear artery. In comparison with the ear artery, the EFS contractions of the MCA displayed a longer latency and a higher stimulus frequency threshold. Greater stimulation train lengths were required to attain equilibrium, and the time course of EFS response--including force development, plateau, and return to rest tension--was significantly slower than in the ear artery. Morphological and pharmacological studies of the MCA showed that it receives sympathetic adrenergic innervation: whole-mount preparations displayed catecholamine histofluorescence; electron micrographs of MCA sections revealed a population of varicosities containing chromaffin positive large and small vesicles; and EFS contractions were blocked by tetrodotoxin (30 nM) and guanethidine (5 microM) and by chronic surgical sympathectomy. Exposure to prazosin (10 microM) or phenoxybenzamine (1 microM) blocked norepinephrine contractions but did not significantly influence the EFS contraction. Procedures and drugs that antagonized the responses to neuropeptide Y, serotonin, or histamine were also ineffective in blocking the EFS contraction. The involvement of ATP could not be assessed, since the purinergic P2 agonist alpha,beta-methylene ATP was ineffective in blocking ATP-mediated contractions. The EFS contraction, however, could be blocked by a combination of neuropeptide Y desensitization and phenoxybenzamine (30 nM) or prazosin (0.1 microM). These results suggest that norepinephrine and neuropeptide Y are released from sympathetic nerves and mediate EFS contraction by occupation of postjunctional alpha-adrenoceptor and neuropeptide Y receptors. Since the blockade of only one of these components does not diminish the response to EFS, the adrenergic neuroeffector system in this artery may involve complex prejunctional regulatory mechanisms.

Mixed venous oximetry during automatic implantable cardioverter-defibrillator placement.

Mixed venous oxygen saturation (SvO2) monitoring was used to assess tissue and circulatory recovery following induced ventricular tachycardia or fibrillation in 17 patients undergoing surgery for automatic implantable cardioverter-defibrillator (AICD) placement. Return of systemic arterial pressure conventionally determines adequate recovery. The duration of circulatory arrest during defibrillator threshold (DFT) testing, measured from the moment of absent phasic pressure at the radial artery until its return, was 18 +/- 8 seconds (mean +/- SD, n = 118 episodes). The absolute decrease in SvO2 from baseline to nadir for these 118 episodes was 14% +/- 6% absolute, and correlated well with the duration of circulatory arrest (r = 0.757, P = 0.0001). The time from onset of phasic arterial blood pressure to the nadir of SvO2, available for 46 episodes, was 28 +/- 14 seconds, and did not correlate with the duration of arrest. The time from onset of phasic pressure to the return of SvO2 to within 1% (absolute) of baseline saturation, available for 84 episodes, was 52 +/- 32 seconds and, in the aggregate, correlated poorly (r = 0.401) with duration of arrest. Simultaneous recording of arterial pressure and SvO2 (n = 41) showed that arterial recovery (6 +/- 3 seconds) occurred long before SvO2 recovery (48 +/- 16 seconds, P = 0.0001). The authors interpret these data as showing that mixed venous oximetry, compared to arterial blood pressure, provides a more sensitive indicator of tissue recovery following periods of circulatory arrest during DFT testing of AICDs.