Defective phosphatidylinositol 3-kinase signaling in central control of cardiovascular effects in the nucleus tractus solitarii of spontaneously hypertensive rats.

Recently we have shown functional involvement of the phosphatidylinositol 3-kinase (PI3K)-Akt-nitric oxide synthase (NOS) signaling pathway in central control of cardiovascular effects in the nucleus tractus solitarii (NTS) of normotensive Wistar-Kyoto (WKY) rats. In this study we determined whether PI3K/Akt signaling was defective in spontaneously hypertensive rats (SHR). WKY rats and SHR were anesthetized with urethane. Mean blood pressure (MBP) and heart rate (HR) were monitored intra-arterially. Unilateral microinjection (60 nL) of insulin (100 IU/mL) into the NTS produced prominent depressor and bradycardic effects in 8- and 16-week-old normotensive WKY and 8-week-old SHR. However, no significant cardiovascular effects were found in 16-week-old SHR after insulin injection. Furthermore, pretreatment with PI3K inhibitor LY294002 and NOS inhibitor L-NAME into the NTS attenuated the cardiovascular response evoked by insulin in WKY and 8-week-old SHR but not in 16-week-old SHR. Unilateral microinjection of 1 mmol/L of PI(3,4,5)P(3) (phosphatidylinositol 3,4,5-triphosphate), a phospholipids second messenger produced by PI3K, into the NTS produced prominent depressor and bradycardic effects in 8- or 16-week-old WKY rats as well as 8-week-old SHR but not in 16-week-old SHR. Western blot analysis showed no significant increase in Akt phosphorylation in 8-week-old pre-hypertensive SHR after insulin injection. Similar results were also found in hypertensive 16-week-old SHR. Our results indicate that the Akt-independent signaling pathway is involved in NOS activation to regulate cardiovascular effects in the NTS of 8-week-old pre-hypertensive SHR. Both Akt-dependent and Akt-independent signaling pathways are defective in hypertensive 16-week-old SHR.

Efficacy and safety of slow-release fluvastatin 80 mg daily in Chinese patients with hypercholesterolemia.

BACKGROUND: Before this study, the efficacy and safety of doubling the dosage of fluvastatin from 40 mg/day to 80 mg/day in Chinese patients with primary hypercholesterolemia remained to be determined. METHODS: In this open-label, active-controlled randomized 2-center study, patients with primary hypercholesterolemia were randomized to treatment with immediate-release fluvastatin 40 mg/day (n = 30) or slow-release fluvastatin 80 mg/day (n = 31) for 12 weeks. The primary efficacy variable was percent change in low-density lipoprotein (LDL) cholesterol level from baseline. Secondary efficacy variables were percent changes in total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol levels, and the percent of patients achieving LDL cholesterol goals of the US National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) II. RESULTS: Both fluvastatin dosages (40 mg/day vs 80 mg/day) effectively reduced LDL cholesterol (-22.5% vs -29.9%; p = 0.087), total cholesterol (-17.3% vs -22.5%; p = 0.140), and triglyceride levels (-14.0% vs -12.3%; p = 0.813) (all p < 0.0001 for comparison with baseline), and slightly increased HDL cholesterol levels (+5.2% vs +5.6%; p = 0.917), after 12 weeks of treatment. The percent of patients achieving LDL cholesterol goals of the NCEP ATP II was 37% versus 65% (p < 0.05). The adverse event profiles for the 2 fluvastatin dosages were similar. CONCLUSION: In Chinese patients with primary hypercholesterolemia, doubling the dosage of fluvastatin from 40 to 80 mg once daily was effective and safe regarding reduction of LDL cholesterol level, and allowed more patients to achieve LDL cholesterol goals of the NCEP ATP II.

Novel effect of carvedilol on Ca2+ movement in renal tubular cells.

The effect of carvedilol on intracellular free Ca(2+) levels ([Ca(2+)](i)) has not been explored previously. This study was aimed to examine the effect of carvedilol on Ca(2+) handling in renal tubular cells. Madin-Darby canine kidney cells were used as a model for renal tubular cells and fura-2 was used as a fluorescent Ca(2+) probe. Carvedilol increased [Ca(2+)](i) in a concentration-dependent manner with an EC(50) value of 5 microM. Extracellular Ca(2+) removal partly inhibited the [Ca(2+)](i) signals. Carvedilol-induced Ca(2+) influx was verified by measuring Mn(2+)-induced quench of fura-2 fluorescence. Carvedilol-induced store Ca(2+) release was reduced by pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) but not with 5 microM ryanodine or 2 microM carbonylcyanide m-chlorophenylhydrazone (a mitochondrial uncoupler). Carvedilol (30 microM)-induced Ca(2+) release was not affected by inhibiting phospholipase C with 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-l)amino)hexyl)-1H-pyrrole-2,5-dione (U73122; 2 microM), but was potentiated by increasing cAMP levels or inhibiting protein kinase C. The carvedilol-induced Ca(2+) mobilization was not significantly sequestered by the endoplasmic reticulum or mitochondria. This study shows that carvedilol increased [Ca(2+)](i) in renal tubular cells by causing Ca(2+) release from the endoplasmic reticulum and other unknown stores in an inositol-1,4,5-trisphosphate-independent manner, and by inducing Ca(2+) influx. The Ca(2+) release was modulated by cAMP and protein kinase C.

Effect of arvanil (N-arachidonoyl-vanillyl-amine), a nonpungent anandamide-capsaicin hybrid, on ion currents in NG108-15 neuronal cells.

The effects of arvanil (N-arachidonoyl-vanillyl-amine), a structural hybrid between capsaicin and anandamide, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. Arvanil (0.2-50 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Arvanil produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of arvanil-induced inhibition of I(Ca,L) was 2 microM. Arvanil (5 microM) could shift the steady-state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. No effect of arvanil (20 microM) on delayed rectifier K(+) current (I(K(DR))) was observed; however, capsaicin (20 microM), glyceryl nonivamide (20 microM) and capsinolol (20 microM) suppressed it significantly. Arvanil (20 microM) caused a slight reduction in the amplitude of erg (ether-à-go-go-related)-mediated K(+) current (I(K(erg))) without modifying the activation curve of this current, while capsaicin and glyceryl nonivamide were more effective in suppressing I(K(erg)). Under current-clamp configuration, arvanil decreased the firing frequency of action potentials. Arvanil-mediated inhibition of I(Ca,L) appeared to be independent of its binding to either vanilloid or cannabinoid receptors. The channel-blocking properties of arvanil may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

Inhibitory effect of the plant-extract osthole on L-type calcium current in NG108-15 neuronal cells.

The effects of osthole, a coumarin isolated from Cnidium monnieri (L.) Cusson, on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were investigated with the aid of the whole-cell voltage-clamp technique. Osthole (0.3-100 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Osthole produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of the osthole-induced inhibition of I(Ca,L) was 4 microM. The presence of osthole (3 microM) shifted the steady state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. Osthole (3 microM) also produced a prolongation in the recovery of I(Ca,L) inactivation. Although osthole might suppress phosophodiesterases to increase intracellular adenosine-3',5'-cyclic monophosphate (cyclic AMP) or guanosine-3',5'-cyclic monophosphate (cyclic GMP), sp-cAMPS did not affect I(Ca,L) and 8-bromo-cyclic GMP slightly suppressed it. Thus, osthole-mediated inhibition of I(Ca,L) was not associated with intracellular cyclic AMP or GMP. However, no effect of osthole on voltage-dependent K(+) outward current was observed. Under a current-clamp mode, osthole could decrease the firing frequency of action potentials. Therefore, the channel-blocking properties of osthole may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

Real-time dobutamine stress myocardial contrast echocardiography for detecting coronary artery disease: correlating abnormal wall motion and disturbed perfusion.

BACKGROUND: Real-time myocardial contrast echocardiography (MCE) makes possible the simultaneous visualization of changes in perfusion imaging and wall motion. OBJECTIVES: To assess the accuracy of real-time MCE for detecting the presence and extent of coronary artery disease (CAD), and to evaluate the correlation between wall motion and myocardial perfusion by visual examination. METHODS: A total of 140 consecutive patients without resting wall motion abnormalities were screened to undergo dobutamine stress MCE with power modulation and coronary angiography. Significant coronary disease was defined by the quantification of over 50% stenosis in a major epicardial vessel. The visual identification of wall motion and myocardial perfusion abnormalities was determined by blind review. RESULTS: Eight patients were excluded due to suboptimal images (feasibility 94.3%). Myocardial contrast enhancement analysis and wall motion analysis were similar in terms of sensitivity (81.2% versus 83.5%, respectively) and specificity (76.5% versus 80.9%, respectively) in detecting the presence of CAD. Myocardial contrast enhancement analysis tended to have a greater sensitivity than wall motion analysis in detecting the ischemic extent over multiple vascular territories among patients with multiple-vessel disease (sensitivity 83.8% versus 71.4% [P=0.09], and abnormal segment length 54.7+/-21.1% versus 48.9+/-24.7% [P=0.03] for myocardial contrast enhancement and wall motion analysis, respectively). There was good concordance between the presence of myocardial ischemia and wall motion abnormality for the segment-by-segment analysis (89.7% agreement, kappa = 0.745). The correlation of the wall motion score and perfusion score at peak stress was also good (r=0.793, P=0.015). CONCLUSIONS: Dobutamine stress MCE with power modulation is similar in sensitivity and specificity to wall motion analysis for detecting the presence of CAD. However, it provides greater sensitivity in evaluating the extent of ischemia in patients with multiple-vessel disease.

Cardiac manifestations of relapsing polychondritis--a case report.

Relapsing polychondritis is a systemic autoimmune disease that may be associated with inflammatory arthritis, vasculitis, aortitis, and inflammation of the aortic valve and ring. Information describing the cardiac manifestations of relapsing polychondritis is limited. The authors encountered a patient with relapsing polychondritis who had pericardial effusion and aortic valve regurgitation. The patient's history is reported and relevant literatures are reviewed.

Block of L-type Ca2+ current by beauvericin, a toxic cyclopeptide, in the NG108-15 neuronal cell line.

The effects of beauverficin, a cyclodepsipeptide compound, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were investigated with the aid of the whole-cell voltage-clamp technique. Beauvericin (0.3-100 microM) reversibly produced an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Beauvericin caused no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of beauvericin-induced inhibition of I(Ca,L) was 4 microM. Neither gabapentin (30 microM) nor omega-conotoxin GVIA (3 microM) had effects on I(Ca,L). Beauvericin (30 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -15 mV. The inhibitory effects of beauvericin on I(Ca,L) exhibited tonic and use-dependent characteristics. Beauvericin also suppressed I(Ca,L) evoked by repetitive action potential waveforms effectively. However, beauvericin (30 microM) had no effect on delayed rectifier K+ current in NG105-18 cells. Under current-clamp configuration, beauvericin reduced the firing frequency of action potentials. Therefore, this study indicates that beauvericin is a relatively specific inhibitor of L-type Ca2+ current in NG108-15 cells.

Differential effects of quercetin, a natural polyphenolic flavonoid, on L-type calcium current in pituitary tumor (GH3) cells and neuronal NG108-15 cells.

The effects of quercetin, a natural polyphenolic compound, on voltage-dependent L-type Ca(2+) current (I(Ca,L)) in rat pituitary GH(3) cells were investigated with the aid of the whole-cell voltage-camp technique. Quercetin (0.5-200 microM) stimulated I(Ca,L) in a concentration-dependent manner. The current-voltage (I-V) relationship of I(Ca,L) was slightly shifted to more negative potentials in the presence of quercetin. The EC(50) value of the quercetin-induced stimulation of I(Ca,L) was about 7 microM. The presence of quercetin (5 microM) shifted the steady state inactivation curve of I(Ca,L) to a more negative potential by approximately -10 mV. Although quercetin might increase intracellular cyclic AMP, sp-cAMPS did not affect I(Ca,L). In addition, neither flavone nor wortmannin had any effect on the amplitude of I(Ca,L), while epicatechin and genistein slightly suppressed it. Quercetin (50 microM) decreased the amplitude of tetrodotoxin-sensitive Na(+) current in GH(3) cells. Under current-clamp configuration, quercetin could increase the firing frequency of actions potentials. Conversely, in NG108-15 neuronal cells, quercetin suppressed the amplitude of I(Ca,L). The quercetin-induced inhibition of I(Ca,L) was abolished in NG108-15 cells preincubated with t-butyl hydroperoxide (1 mM). Quercetin-mediated stimulation of I(Ca,L) in GH(3) cells was presumably not associated with the level of intracellular cyclic AMP, or with the activity of tyrosine or phosphoinositide 3-kinases. Therefore, the effects of quercetin on ion currents may, at least in part, contribute to the underlying mechanisms through which it affects neuronal or neuroendocrine function.

Prospective and randomized study of the antihypertensive effect and tolerability of three antihypertensive agents, losartan, amlodipine, and lisinopril, in hypertensive patients.

We prospectively evaluated the antihypertensive effect and tolerability of three different antihypertensive agents, losartan (angiotensin II receptor blocker), amlodipine (calcium channel blocker), and lisinopril (angiotensin-coverting enzyme inhibitor), in patients with mild-to-moderate hypertension. After a 2-week washout period, 121 patients were randomly allocated to three different groups for 12 weeks. Medications were titrated upward as necessary to achieve the goal office-recorded sitting diastolic blood pressure (SiDBP) (defined as SiDBP <90 mmHg or SiDBP > or = 900 mmHg but with a > or = 10 mmHg drop from baseline). Efficacy and tolerability were assessed after 4, 8, and 12 weeks of therapy with each regimen. At 12 weeks, significant differences in SiDBP compared with data of baseline were noted in all three groups ( P < 0.001 in all comparisons). Similarly, significant differences in the sitting systolic blood pressure compared with baseline data were also seen for all three groups ( P < 0.001 in all comparisons). The number of patients reaching goal SiDBP were comparable for the three groups: 25 patients (62.5%) in the losartan group, 27 patients (67.5%) in the amlodipine group, and 22 patients (59.5%) in the lisinopril group (not significant). Amlodipine produced a more pronounced reduction in SiDBP than the other two medications, although without statistical significance. Patients receiving lisinopril showed a high incidence of coughing (31.7%). Low leg edema was noted only in the amlodipine group (7.5%). Compared with the amlodipine and lisinopril groups, the losartan group seemed to have relatively fewer episodes (7.5%), and fewer patients (three cases) experienced adverse effects. In conclusion, this study demonstrates that losartan has the same antihypertensive effect, but has superior tolerability compared with the other two drugs. Coughing was a common side effect of lisinopril therapy in our population.

Stimulatory effects of squamocin, an Annonaceous acetogenin, on Ca(2+)-activated K+ current in cultured smooth muscle cells of human coronary artery.

The patch-clamp recording technique was used to investigate the effect of squamocin, an Annonaceous acetogenin, on ion currents in cultured smooth muscle cells of human coronary artery. In whole-cell configuration, squamocin (0.3-100 microM) induced Ca(2+)-activated K+ current [IK(Ca)] in a concentration-dependent manner with an EC50 value of 4 microM. Squamocin-stimulated IK(Ca) was suppressed by iberiotoxin (200 nM), paxilline (1 microM), or tetraethylammonium chloride (5 mM), yet not by apamin (200 nM) or glibenclamide (10 microM). In cells dialyzed with 10 mM EGTA, this compound had little effect on IK(Ca). When cells were exposed to Ca(2+)-free solution, squamocin (3 microM) induced a transient increase in IK(Ca). In continued presence of squamocin, an additional increase in extracellular Ca2+ (1 mM) caused a significant increase in IK(Ca). Pretreatment with carbonyl cyanide m-chlorophenyl hydrazone (CCCP; 3 microM) for 5 h did not alter the magnitude of squamocin-induced IK(Ca). However, squamocin (30 microM) suppressed the amplitude of voltage-dependent L-type Ca2+ current. In cell-attached configuration of single-channel recordings, squamocin applied to the bath increased the activity of large-conductance Ca(2+)-activated K+ (BKCa) channels without altering single-channel conductance. Conversely, in inside-out patches, squamocin applied to the intracellular surface had no effect on BKCa channel activity, whereas niflumic acid increased it effectively. These findings provide the evidence that squamocin can activate IK(Ca) in coronary arterial smooth muscle cells. Initial transient activation of IK(Ca) may reflect the squamocin-induced Ca2+ release from intracellular Ca2+ stores, whereas the sustained activation of IK(Ca) may arise from the squamocin-induced Ca2+ influx across the cell membrane. The stimulatory effect of squamocin on these channels should affect the functional activity of vascular smooth muscle cells.

Behavior of nonselective cation channels and large-conductance Ca2+-activated K+ channels induced by dynamic changes in membrane stretch in cultured smooth muscle cells of human coronary artery.

INTRODUCTION: The effects of membrane stretch on ion channels were investigated in cultured smooth muscle cells of human coronary artery. METHODS AND RESULTS: In the cell-attached configuration, membrane stretch with negative pressure induced two types of stretch-activated (SA) ion channels: a nonselective cation channel and a large-conductance Ca2+-activated K+ (BK(Ca)) channel. The single-channel conductances of SA cation and BK(Ca) channels were 26 and 203 pS, respectively. To elucidate the mechanism of activation of these SA channels and to minimize mechanical disruption, a sinusoidal change in pipette pressure was applied to the on-cell membrane patch. During dynamic changes in pipette pressure, increases in SA cation channel activity was found to coincide with increases in BK(Ca) channel activity. In the continued presence of cyclic stretch, the activity of SA cation channels gradually diminished. However, after termination of cyclic stretch, BK(Ca) channel activity was greatly enhanced, but the activity of SA cation channels disappeared. CONCLUSION: This study is the first to demonstrate that the behavior of SA cation and BK(Ca) channels in coronary smooth muscle cells is differentially susceptible to dynamic changes in membrane tension.

An outbreak of food-borne illness due to methomyl contamination.

BACKGROUND: On December 26, 2002, 124 dinners took ill while eating lunch at a seafood restaurant in the town of Chiching in Kaohsiung municipality of Taiwan. Sixty-nine people were sent to the emergency departments of the Municipal Chiching Hospital and Yuan's General Hospital. METHODS: We analyzed the clinical symptoms, detailed food history, and ingested amount of each food from 59 hospitalized adult patients and identified the source of the outbreak. RESULTS: The median latency period from beginning eating to first symptoms was 5 min. Twenty-six symptoms and signs were recorded. The most commonly reported clinical effects were general weakness (84%), ataxia (82%), dizziness (82%), vomiting (80%), sweating (75%), floating sensation (71%), headache (69%), dyspnea (69%), and blurred vision (67%). Thirty-one patients had residual symptoms 7 days after ingestion. Of the six residual symptoms reported, the most frequent ones were dizziness (40%), poor appetite and dry mouth (11%), and gastrointestinal disturbance (11%). The presence of residual symptoms correlated with the severity of the initial complaints (p < 0.01). Almost all patients ate cooked rice (93%) and leaf vegetable stir-fried with crab claw (93%). The amount of each food eaten by the patients was not associated with the severity of symptoms (p > 0.05). High levels of methomyl in leaf vegetables of "leaf vegetables stir-fried with crab claws" (380 ppm) and fried mussels (1113 ppm) were found by the Food Inspection Center at the Department of Health. The food history and chemical analysis of the poison indicated methomyl was the cause of this outbreak. Twenty-four patients recovered completely within 7 days. CONCLUSION: Food-related methomyl intoxication produced a rapid onset of significant clinical toxicity in 124 individuals. Based on the analysis of 55 adult patients, the most common effects were gait ataxia, dizziness, generalized weakness, and vomiting.

Echocardiographic features of primary cardiac sarcoma.

Primary cardiac sarcoma is extremely rare and seldom causes symptoms until late in its course. Discomfort may occur only when the mass causes obstruction to the intracardiac flow. Early diagnosis is vital because it allows prompt and relevant management. We describe the history and echocardiographic features in four patients with primary cardiac sarcoma and review the current literature.

Initial experience of using color kinesis in the diagnosis of coronary artery disease.

BACKGROUND: Color kinesis (CK) is a recently developed echocardiographic technique. This report describes our initial effort in the validation of the use of CK for the diagnosis of coronary artery disease (CAD). METHODS: Two-dimensional (2-D) echocardiography and CK were studied in 30 normal subjects and 24 CAD patients. Coronary angiography was performed in the 24 patients. Significant (> 70% luminal diameter stenosis) CAD was present in 18 patients (79%), all of whom had history of myocardial infarction. Regional fractional area change in each segment was displayed as a stacked color histogram. The histograms derived from these 30 normal subjects were averaged to obtain the normal pattern of left ventricular contraction; the mean value +/- 1 SD was considered the reference histogram. When the regional fractional area change deviated from this normal reference, this segment was considered as having regional wall motion abnormality. The detection of wall motion abnormalities by visual interpretation of 2-D echocardiography, reviewing the CK loop recording, and CK stacked histograms were compared. To assess the relationship of measurement of endocardial excursion of CK images, the width of the color band was measured at the midpoint of each segment along a line perpendicular to the cardiac border. The endocardial excursion measured by 2 independent observers was compared using linear regression analysis and calculation of intraclass correlation coefficient. RESULTS: The sensitivity and specificity for detection of CAD were 77.8% and 66.6%, respectively, for CK loop reviewing, 83.3% and 66.7% for CK stacked histogram analysis, and 77.8% and 83.3% for 2-D echocardiography. The overall accuracies for CAD detection were 75% for CK loop reviewing, 79.2% for CK stacked histogram analysis, and 79.2% for the 2-D echocardiography (not significant in all comparisons). The correlation of measurement of endocardial excursion from the CK images by 2-observers was good (r = 0.85, p < 0.01), and intraclass correlation coefficient was 0.99 (p < 0.0001). CONCLUSIONS: Our data demonstrate that both the CK loop reviewing and stacked histogram analysis were comparable to 2-D echocardiography for detecting CAD.

Long-term clinical follow-up after successful direct coronary stenting without predilatation.

BACKGROUND: Direct stent implantation without predilatation is considered a promising new technique that may reduce procedural time, radiation exposure, ischemic time and cost, but little information is available concerning the long-term outcome. The aim of this study was to investigate the long-term clinical outcome of successful direct stenting without predilatation. METHODS: We prospectively undertook a clinical follow-up program (minimum 8 months) in a consecutive series of 101 patients (113 lesions) who were successfully treated with direct stenting without predilatation. RESULTS: Clinical follow-up was obtained in all 101 patients at a mean period of 12.8 months (range 8 to 18.9). Stress test results were available in 94 patients (94%). During the follow-up period, 23 patients (23%) had one or more events, which included death in 2 patients (2%), target vessel revascularization in 14 (14%), myocardial infarction in 1 (1%) and positive stress test results or recurrence of symptoms (Canadian Cardiovascular Society I to II) treated medically in 6 (6%). Cumulative event-free survival at 8 and 18 months were 80% and 72%, respectively. Long-term clinical event rate was not significantly different among the clinical presentations, lesion types, or stent types. Angiographic follow-up was performed in 43 (43%) patients with 45 lesions. Restenosis (defined as 50% diameter stenosis) was observed in 14 of the lesions (31%). CONCLUSIONS: Direct stenting without predilatation is an effective method of coronary intervention in terms of low long-term clinical event rate.

Prone-position ventilation induces sustained improvement in oxygenation in patients with acute respiratory distress syndrome who have a large shunt.

OBJECTIVES: Prone-position ventilation (PPV) induces acute improvement in oxygenation in many patients with acute respiratory distress syndrome (ARDS), with some maintaining their oxygenation even after they were returned to the supine position, but it is unclear what clinical factors determine the sustained oxygenation benefit. We hypothesized that patients with ARDS who have a larger shunt would have a better acute and sustained oxygenation response to PPV. DESIGN: Prospective, nonrandomized interventional study. SETTING: Medical and surgical intensive care units, university tertiary care center. PATIENTS: Twenty-two consecutive patients, with ARDS with an average PaO2/FiO2 of 94, were administered PPV for 12 hrs followed by supine-position ventilation for 2 hrs. MEASUREMENTS: Hemodynamic and gas exchange variables were monitored. The shunt was measured as venous admixture at an FiO2 of 1.0, and compliances of the respiratory system, lung, and chest wall were measured by the esophageal balloon technique before PPV, during PPV, and during subsequent supine-position ventilation. MAIN RESULTS: Fourteen patients (64%) responded to PPV, with PaO2/FiO2 increasing by > or =20. These changes were associated with a decrease in chest wall compliance. Responders had significantly shorter time from ARDS to PPV, a lower baseline PaO2/FiO2, and a higher venous admixture. All responders maintained the improvement in oxygenation and had a greater respiratory system compliance after returning to the supine position. Time from ARDS to PPV and baseline lung injury score were negatively associated, whereas chest wall compliance, heart rate, and PaCO2 were positively associated with sustained improvement in oxygenation. CONCLUSIONS: PPV induced acute and sustained improvement in oxygenation in many patients with ARDS. The sustained improvement is more significant if PPV is administered early to patients with a larger shunt and a more compliant chest wall. Measuring venous admixture and chest wall compliance before PPV may help select a subgroup of patients with ARDS who may benefit the most from PPV.