Regulation of Phytosiderophore Release and Antioxidant Defense in Roots Driven by Shoot-Based Auxin Signaling Confers Tolerance to Excess Iron in Wheat.

Iron (Fe) is essential but harmful for plants at toxic level. However, how wheat plants tolerate excess Fe remains vague. This study aims at elucidating the mechanisms underlying tolerance to excess Fe in wheat. Higher Fe concentration caused morpho-physiological retardation in BR 26 (sensitive) but not in BR 27 (tolerant). Phytosiderophore and 2-deoxymugineic acid showed no changes in BR 27 but significantly increased in BR 26 due to excess Fe. Further, expression of TaSAMS. TaDMAS1, and TaYSL15 significantly downregulated in BR 27 roots, while these were upregulated in BR 26 under excess Fe. It confirms that inhibition of phytosiderophore directs less Fe accumulation in BR 27. However, phytochelatin and expression of TaPCS1 and TaMT1 showed no significant induction in response to excess Fe. Furthermore, excess Fe showed increased catalase, peroxidase, and glutathione reductase activities along with glutathione, cysteine, and proline accumulation in roots in BR 27. Interestingly, BR 27 self-grafts and plants having BR 26 rootstock attached to BR 27 scion had no Fe-toxicity induced adverse effect on morphology but showed BR 27 type expressions, confirming that shoot-derived signal triggering Fe-toxicity tolerance in roots. Finally, auxin inhibitor applied with higher Fe concentration caused a significant decline in morpho-physiological parameters along with increased TaSAMS and TaDMAS1 expression in roots of BR 27, revealing the involvement of auxin signaling in response to excess Fe. These findings propose that tolerance to excess Fe in wheat is attributed to the regulation of phytosiderophore limiting Fe acquisition along with increased antioxidant defense in roots driven by shoot-derived auxin signaling.

Role of Silicon Counteracting Cadmium Toxicity in Alfalfa (Medicago sativa L.).

Cadmium (Cd) is one of the most phytotoxic elements causing an agricultural problem and human health hazards. This work investigates whether and how silicon (Si) ameliorates Cd toxicity in Alfalfa. The addition of Si in Cd-stressed plants caused significant improvement in morpho-physiological features as well as total protein and membrane stability, indicating that Si does have critical roles in Cd detoxification in Alfalfa. Furthermore, Si supplementation in Cd-stressed plants showed a significant decrease in Cd and Fe concentrations in both roots and shoots compared with Cd-stressed plants, revealing that Si-mediated tolerance to Cd stress is associated with Cd inhibition in Alfalfa. Results also showed no significant changes in the expression of two metal chelators [MsPCS1 (phytochelatin synthase) and MsMT2 (metallothionein)] and PC (phytochelatin) accumulation, indicating that there may be no metal sequestration or change in metal sequestration following Si application under Cd stress in Alfalfa. We further performed a targeted study on the effect of Si on Fe uptake mechanisms. We observed the consistent reduction in Fe reductase activity, expression of Fe-related genes [MsIRT1 (Fe transporter), MsNramp1 (metal transporter) and OsFRO1 (ferric chelate reductase] and Fe chelators (citrate and malate) by Si application to Cd stress in roots of Alfalfa. These results support that limiting Fe uptake through the down-regulation of Fe acquisition mechanisms confers Si-mediated alleviation of Cd toxicity in Alfalfa. Finally, an increase of catalase, ascorbate peroxidase, and superoxide dismutase activities along with elevated methionine and proline subjected to Si application might play roles, at least in part, to reduce H2O2 and to provide antioxidant defense against Cd stress in Alfalfa. The study shows evidence of the effect of Si on alleviating Cd toxicity in Alfalfa and can be further extended for phytoremediation of Cd toxicity in plants.

Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity.

Chronic inflammation contributes to multiple ageing-related musculoskeletal and neurodegenerative diseases, cardiovascular diseases, asthma, rheumatoid arthritis, and inflammatory bowel disease. More recently, chronic neuroinflammation has been attributed to Parkinson's and Alzheimer's disease and autism-spectrum and obsessive-compulsive disorders. To date, pharmacotherapy of inflammatory conditions is based mainly on nonsteroidal anti-inflammatory drugs which in contrast to cytokine-suppressive anti-inflammatory drugs do not influence the production of cytokines such as tumour necrosis factor-α or nitric oxide. However, their prolonged use can cause gastrointestinal toxicity and promote adverse events such as high blood pressure, congestive heart failure, and thrombosis. Hence, there is a critical need to develop novel and safer nonsteroidal anti-inflammatory drugs possessing alternate mechanism of action. In this study, plants used by the Dharawal Aboriginal people in Australia for the treatment of inflammatory conditions, for example, asthma, arthritis, rheumatism, fever, oedema, eye inflammation, and inflammation of bladder and related inflammatory diseases, were evaluated for their anti-inflammatory activity in vitro. Ethanolic extracts from 17 Eucalyptus spp. (Myrtaceae) were assessed for their capacity to inhibit nitric oxide and tumor necrosis factor-α production in RAW 264.7 macrophages. Eucalyptus benthamii showed the most potent nitric oxide inhibitory effect (IC50 5.57 ± 1.4 µg/mL), whilst E. bosistoana, E. botryoides, E. saligna, E. smithii, E. umbra, and E. viminalis exhibited nitric oxide inhibition values between 7.58 and 19.77 µg/mL.

Apigenin-induced nitric oxide production involves calcium-activated potassium channels and is responsible for antiangiogenic effects.

BACKGROUND: The dietary flavonoid apigenin (Api) has been demonstrated to exert multiple beneficial effects upon the vascular endothelium. The aim of this study was to examine whether Ca(2+)-activated K(+) channels (K(Ca)) are involved in endothelial nitric oxide (NO) production and antiangiogenic effects. METHODS: Endothelial NO generation was monitored using a cyclic guanosine monophosphate radioimmunoassay. K(Ca) activity and changes of the intracellular Ca(2+) concentration [Ca(2+)](i) were analyzed using the fluorescent dyes bis-barbituric acid oxonol, potassium-binding benzofuran isophthalate, and fluo-3. The endothelial angiogenic parameters measured were cell proliferation, [(3)H]-thymidine incorporation, and cell migration (scratch assay). Akt phosphorylation was examined using immunohistochemistry. RESULTS: Api caused a concentration-dependent increase in cyclic guanosine monophosphate levels, with a maximum effect at a concentration of 1 mum. Api-induced hyperpolarization was blocked by the small and large conductance K(Ca) inhibitors apamin and iberiotoxin, respectively. Furthermore, apamin and iberiotoxin blocked the late, long-lasting plateau phase of the Api-induced biphasic increase of [Ca(2+)](i). Inhibition of Ca(2+) signaling and the K(Ca) blockade both blocked NO production. Prevention of all three (NO, Ca(2+), and K(Ca) signaling) reversed the antiangiogenic effects of Api under both basal and basic fibroblast growth factor-induced culture conditions. Basic fibroblast growth factor-induced Akt phosphorylation was also reduced by Api. CONCLUSIONS: Based on our experimental results we propose the following signaling cascade for the effects of Api on endothelial cell signaling. Api activates small and large conductance K(Ca), leading to a hyperpolarization that is followed by a Ca(2+) influx. The increase of [Ca(2+)](i) is responsible for an increased NO production that mediates the antiangiogenic effects of Api via Akt dephosphorylation.

A new signaling mechanism of hepatocyte growth factor-induced endothelial proliferation.

BACKGROUND: The hepatocyte growth factor (HGF) has been shown to promote endothelial cell proliferation. In this study, the signaling cascade responsible for the HGF-induced proliferation was examined. METHODS: The proliferation of human umbilical cord vein endothelial cells (HUCVEC) was determined using cell counts. Changes of the membrane potential were analyzed using the fluorescence dye DiBAC. Intracellular cGMP-levels were measured by means of [3H]-cGMP-radioimmunoassay. Phosphorylation of the p42/p44 MAP-kinase (MAPK) and the endothelial nitric oxide synthase (eNOS) was analyzed by immunocytochemistry. RESULTS: A dose-dependent (1-30 ng mL(-1)) increase of HUCVEC proliferation with a maximum at a concentration of 15 ng mL(-1) was induced by HGF. This effect was significantly reduced by the addition of the K+ channel blocker iberiotoxin (100 nmol L(-1)), eNOS inhibitor L-NMMA (300 micromol L(-1)), or the MEK inhibitor PD 98059 (20 micromol L(-1)). A HGF-induced hyperpolarization that was blocked by iberiotoxin was observed. In addition, HGF-induced activation of the eNOS was blocked by the K+ channel inhibitor. An increase of +101% MAPK phosphorylation was induced by HGF, which was blocked, if the cells were treated with L-NMMA (n = 20; P < 0.05), whereas HGF-induced phosphorylation of the eNOS was not affected by MEK inhibition. CONCLUSIONS: Hepatocyte growth factor modulates endothelial K+ channels causing an activation of the eNOS; the increase of nitric oxide is necessary for the phosphorylation of the MAPK inducing the proliferation of HUCVEC.

Endothelin-1-induced proliferation of human endothelial cells depends on activation of K+ channels and Ca+ influx.

AIMS: Endothelin-1 (ET-1) promotes endothelial cell growth. Endothelial cell proliferation involves the activation of Ca2+-activated K+ channels. In this study, we investigated whether Ca2+-activated K+ channels with big conductance (BK(Ca)) contribute to endothelial cell proliferation induced by ET-1. METHODS: The patch-clamp technique was used to analyse BK(Ca) activity in endothelial cells derived from human umbilical cord veins (HUVEC). Endothelial proliferation was examined using cell counts and measuring [3H]-thymidine incorporation. Changes of intracellular Ca2+ levels were examined using fura-2 fluorescence imaging. RESULTS: Characteristic BK(Ca) were identified in cultured HUVEC. Continuous perfusion of HUVEC with 10 nmol L(-1) ET-1 caused a significant increase of BK(Ca) open-state probability (n = 14; P < 0.05; cell-attached patches). The ET(B)-receptor antagonist (BQ-788, 1 micromol L(-1)) blocked this effect. Stimulation with Et-1 (10 nmol L(-1)) significantly increased cell growth by 69% (n = 12; P < 0.05). In contrast, the combination of ET-1 (10 nmol L(-1)) and the highly specific BK(Ca) blocker iberiotoxin (IBX; 100 nmol L(-1)) did not cause a significant increase in endothelial cell growth. Ca2+ dependency of ET-1-induced proliferation was tested using the intracellular Ca2+-chelator BAPTA (10 micromol L(-1)). BAPTA abolished ET-1 induced proliferation (n = 12; P < 0.01). In addition, ET-1-induced HUVEC growth was significantly reduced, if cells were kept in a Ca2+-reduced solution (0.3 mmol L(-1)), or by the application of 2 aminoethoxdiphenyl borate (100 micromol L(-1)) which blocks hyperpolarization-induced Ca2+ entry (n = 12; P < 0.05). CONCLUSION: Activation of BK(Ca) by ET-1 requires ET(B)-receptor activation and induces a capacitative Ca2+ influx which plays an important role in ET-1-mediated endothelial cell proliferation.

Measurement of the spin asymmetry in the photoproduction of pairs of high- p(T) hadrons at HERMES

We present a measurement of the longitudinal spin asymmetry A(||) in photoproduction of pairs of hadrons with high transverse momentum p(T). Data were accumulated by the HERMES experiment using a 27.5 GeV polarized positron beam and a polarized hydrogen target internal to the HERA storage ring. For h(+)h(-) pairs with p(h(1))(T)>1.5 GeV/c and p(h(2))(T)>1.0 GeV/c, the measured asymmetry is A(||) = -0. 28+/-0.12(stat)+/-0.02(syst). This negative value is in contrast to the positive asymmetries typically measured in deep inelastic scattering from protons, and is interpreted to arise from a positive gluon polarization.

Preconditioning myocardium with demand ischemia in the presence of a critical coronary artery stenosis.

The relative importance of adrenergic stimulation and demand ischemia as important preconditioning stimuli remains unclarified. The purpose of this investigation was to use a partial coronary stenosis to define the preconditioning role of demand ischemia. Dobutamine was infused intravenously before coronary occlusion in closed-chest swine with and without an artificial coronary stenosis in the mid-left anterior descending coronary artery. Control animals had no stenosis and did not receive dobutamine before occlusion. All three groups underwent 45 minutes of occlusion followed by 120 minutes of reperfusion. At baseline, regional myocardial blood flow in the area at risk was reduced in animals with a stenosis, but global left ventricular systolic function, measured by gated blood pool scan, was equivalent in all three groups. Animals with and without a stenosis received equivalent catecholamine stress with dobutamine, but only animals with a stenosis manifested ischemia during the infusion. At 2 hours after reperfusion, infarct size as a percentage of the area at risk was smaller in animals with a stenosis given dobutamine. Demand ischemia preconditions myocardium in closed-chest swine. Increased demand alone without ischemia had marginal preconditioning effects. This may have clinical relevance to patients with severe stenoses exposed to stressful stimuli before the development of myocardial infarction.

Economic effects of community versus hospital-based faculty pneumonia care.

To compare the length of stay and charges for patients with pneumonia admitted in 1995 to the teaching and nonteaching services of a Northeastern teaching hospital, we reviewed the charts of 237 patients. Patients cared for by hospital-based generalists working with housestaff (teaching service) were discharged more quickly and with lower or equivalent charges than patients cared for by community-based attending physicians working either with housestaff (private teaching service) or alone (nonteaching service). Academic teaching services staffed by general medicine faculty may provide efficient inpatient pneumonia care.

Presence of a critical coronary artery stenosis does not abolish the protective effect of ischemic preconditioning.

BACKGROUND: Episodic, severe coronary artery flow restriction preconditions the myocardium much like brief occlusions. The necessity for full reperfusion after a preconditioning intervention to elicit the preconditioning response is unclear. This study investigated in closed-chest swine the effect of a persistent critical coronary stenosis with moderate flow reduction on ischemic preconditioning. METHODS AND RESULTS: Farm pigs (n = 23) assigned to one of four groups--(1) control, (2) stenosis, (3) preconditioned (PC), or (4) preconditioned plus stenosis (PC/S)--underwent percutaneous instrumentation with a percutaneous transluminal coronary angioplasty catheter advanced to the mid-left anterior descending coronary artery. An artificial coronary stenosis (82% diameter reduction) was mounted on the catheter just proximal to the balloon in the two stenosis groups. Preconditioning stimulus consisted of two 10-minute balloon occlusions followed by 15 minutes of reperfusion. All groups subsequently underwent 45 minutes of occlusion followed by 120 minutes of reperfusion. Baseline regional myocardial blood flow in the area at risk (AAR), measured with colored microspheres, was lowest in the stenosis groups, with flow expressed as a percentage of normal zone flow. Infarct size (percent of AAR), determined by staining slices of the heart with triphenyltetrazolium, was significantly reduced in PC compared with control pigs (15.1 +/- 5.9% versus 66.8 +/- 6.4%, respectively; P < .001). Infarct size in PC/S pigs was also significantly reduced (29.7 +/- 7.1%, P = .004 versus control) but was not different in degree from PC pigs (P = .6). The stenosis by itself conferred no preconditioning benefit (percent of AAR = 69.0 +/- 5.4%). CONCLUSIONS: A moderate flow-limiting stenosis did not prevent preconditioning but may have attenuated the effect. This may be analogous to the clinical scenario in which intermittent coronary occlusion and reperfusion superimposed on a critical stenosis precede a prolonged occlusion treated with thrombolysis.

Unsuccessful emergency medical resuscitation--are continued efforts in the emergency department justified?

BACKGROUND: The majority of attempts to resuscitate victims of prehospital cardiopulmonary arrest are unsuccessful, and patients are frequently transported to the emergency department for further resuscitation efforts. We evaluated the efficacy and costs of continued hospital resuscitation for patients in whom resuscitation efforts outside the hospital have failed. METHODS: We reviewed the records of 185 patients presenting to our emergency department after an initially unsuccessful, but ongoing, resuscitation for a prehospital arrest (cardiac, respiratory, or both) by an emergency medical team. Prehospital and hospital characteristics of treatment for the arrest were identified, and the patients' outcomes in the emergency room were ascertained. The hospital course and the hospital costs for the patients who were revived were determined. RESULTS: Over a 19-month period, only 16 of the 185 patients (9 percent) were successfully resuscitated in the emergency department and admitted to the hospital. A shorter duration of prehospital resuscitation was the only characteristic of the resuscitation associated with an improved outcome in the emergency department. No patient survived until hospital discharge, and all but one were comatose throughout hospitalization. The mean stay in the hospital was 12.6 days (range, 1 to 132), with an average of 2.3 days (range, 1 to 11) in an intensive care unit. The total hospital cost for the 16 patients admitted was $180,908 (range per patient, $1,984 to $95,144). CONCLUSIONS: In general, continued resuscitation efforts in the emergency department for victims of cardiopulmonary arrest in whom prehospital resuscitation has failed are not worthwhile, and they consume precious institutional and economic resources without gain.

Details of coronary stenosis morphology influence its hemodynamic severity and distal flow reserve.

Differences in coronary flow reserve with anatomically similar coronary artery stenoses have been attributed to 1) nonstandard physiologic conditions, 2) inadequacies of measurements of coronary artery stenosis dimension and/or coronary blood flow, and 3) inadequate hyperemic stimulus. Our study tested the hypothesis that details of coronary artery stenosis geometry, which may or may not be apparent on coronary angiograms, also may contribute importantly to such differences. A simple and complex coronary artery stenosis, each of which reduced vessel cross-sectional area by 84%, was introduced in random order into the left anterior descending coronary artery of nine closed-chest, sedated swine. The simple stenosis had a single lumen while the complex stenosis had five small lumena whose combined area equaled that of the single lumen stenosis. Measurements of hemodynamics and regional myocardial blood flow (microspheres) were made at control and after 10 minutes of adenosine infused at 400 micrograms/min and then at 800 micrograms/min distal to each stenosis. Both heart rate and aortic mean pressure were controlled and thus did not change versus initial baseline (129 +/- 4 minutes and 120 +/- 10 mm Hg, mean +/- SD, respectively) during the study. Baseline total flow (ml/sec) distal to the stenosis was similar at each control (1.05 +/- 0.35 vs. 0.92 +/- 0.34, simple versus complex, respectively; p = NS). At maximal adenosine, total flow with the simple stenosis was 3.44 +/- 0.92 versus 2.77 +/- 0.51 for complex (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue acidosis: role in sustained arteriolar dilatation distal to a coronary stenosis.

This study tested the hypothesis that myocardial tissue acidosis is responsible for maintenance of reduced arteriolar tone distal to a severe coronary arterial stenosis. Domestic swine (n = 10) were instrumented with a coronary arterial stenosis that reduced vessel diameter 80%. Measurements of hemodynamic indexes were made 1) before stenosis, 2) at 5, 20, and 60 minutes after stenosis placement, and 3) after each of three, 20-minute NaOH infusions (0.05 M, 0.1 M, and 0.5 M) distal to the stenosis (group 1). Intracellular pH at the end of 30 minutes of 0.5 M NaOH infusion distal to the stenosis was measured in a second group (n = 6) of swine (group 2). After stenosis placement in group 1, endocardial blood flow declined significantly, and evidence of regional acidosis (increased coronary venous Pco2 and decreased coronary venous pH) and ischemia (lactate production) developed. One hour later, evidence of acidosis persisted, though to a lesser extent. Myocardial oxygen and lactate metabolism exhibited similar patterns. Infusion of 0.5 M NaOH (0.38 ml/min) reduced (p less than 0.01) distal zone epicardial blood flow but did not change endocardial flow. Regional myocardial oxygen extraction (75 +/- 8%, mean +/- SD) and consumption (8.2 +/- 2.3 ml/min/100 g) also declined significantly (p less than 0.01) in response to 0.5 M NaOH infusion compared with 60 minutes after stenosis (86 +/- 4 and 12.4 +/- 2.8 ml/min/100 g respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic response to prolonged reduction of myocardial blood flow distal to a severe coronary artery stenosis.

Limited data are available concerning the effects of mild-to-moderate, sustained reductions of coronary blood flow on myocardial aerobic metabolism. This study tested the hypothesis that a sustained flow reduction distal to a severe coronary artery stenosis may be well tolerated (after the initial insult is passed) because of gradual improvement in the balance between myocardial oxygen supply and demand. Studies were performed in eight sedated, closed-chest domestic swine that were instrumented with an artificial coronary arterial stenosis (80% diameter reduction). Hemodynamics, regional myocardial blood flow and oxygen, lactate, acid, and base metabolism were measured before stenosis and at 5, 20, 60, 120, and 180 minutes after stenosis insertion. Regional myocardial function (ultrasonic length sensors) was measured serially during 2 hours in three additional swine. After stenosis placement, endocardial and transmural flows declined (p less than 0.05) compared with flows before stenosis (from 1.54 +/- 0.37 to 0.73 +/- 0.24 ml/min/g [mean +/- SD] and from 1.44 +/- 0.31 to 1.19 +/- 0.25 ml/min/g, respectively). Thereafter, flows remained unchanged for the duration of the study. Similarly, prestenosis heart rate (135 +/- 7 beats/min), aortic mean pressure (113 +/- 17 mm Hg), and tension time index (27.1 +/- 3.6 mm Hg.sec) remained constant for the duration of the study. In contrast, regional coronary venous pH declined (p less than 0.05) compared with prestenosis levels (7.35 +/- 0.02) 5 minutes after stenosis (7.28 +/- 0.04), but it returned to prestenosis levels during the next hour. Regional coronary venous PCO2 exhibited a similar pattern (i.e., acute increase during poststenosis with gradual return to prestenosis levels).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of endogenous prostacyclin in myocardial blood flow regulation distal to a severe coronary stenosis.

To test the hypothesis that endogenous prostacyclin is required to maintain reduced arteriolar tone distal to a severe coronary arterial stenosis under basal conditions and during challenge with a vasoconstrictor eicosanoid such as thromboxane A2 10 closed chest, domestic swine were prepared with an artificial stenosis, which reduced the luminal diameter of the left anterior descending coronary artery by 80%. Haemodynamic variables, regional myocardial blood flow (microsphere method), and lactate metabolism were measured at control (1); after infusion of U46619 (thromboxane A2 mimetic) distal to the stenosis at 1 microgram.min-1 for 10 min and 5 micrograms.min-1 for 10 min; at control (2); after indomethacin infusion distal to the stenosis; and after repeat infusion of U46619. At the end of the study the animal hearts were removed and their coronary vessels harvested for in vitro determination of prostacyclin (PGI2) production. Regional myocardial blood flow in all layers of the heart distal to the stenosis did not change compared with control during the initial 1 microgram.min-1 dose of U46619 but was reduced significantly after the 5 micrograms.min-1 dose (approximately 20% vs control). Distal zone flow (all layers) returned to baseline at control (2) and remained unchanged after indomethacin infusion. Although distal zone flows were reduced significantly in response to the second 5 micrograms.min-1 dose, the reduction in each layer after indomethacin was comparable to that observed with the 5 micrograms.min-1 dose before indomethacin infusion. Finally, the in vitro production of PGI2 by coronary vessels was considerably impaired by indomethacin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pressure-controlled intermittent coronary sinus occlusion on pacing-induced myocardial ischemia in domestic swine.

This study tested the hypothesis that pressure-controlled intermittent coronary sinus occlusion (PICSO) would be useful in ameliorating myocardial ischemia under conditions characterized by preserved, but reduced (relative to demand), myocardial blood flow. Studies were conducted in closed-chest, sedated domestic swine prepared with an artificial stenosis that reduced luminal diameter of the animal's left anterior descending coronary artery by 80%. Measurements of hemodynamics, regional myocardial blood flow, and oxygen, lactate, and nucleoside metabolism were obtained in 10 animals (1) before placement of stenosis, (2) 30 min after insertion of stenosis, (3) after 30 and 60 min of PICSO, and (4) 30 min after discontinuation of PICSO. Two groups of control animals were studied to observe the natural history of metabolic markers of ischemia. Control group I consisted of four animals studied concurrently and subjected to the same protocol except for the fact that PICSO was not applied. Control group II consisted of eight additional animals studied as a group. A specially designed balloon-tipped catheter positioned in the proximal portion of the animal's great cardiac vein was used to provide PICSO. Heart rate was controlled by atrial pacing (rate, 145 beats/min) through the study. After placement of the stenosis, flow in endocardial and transmural layers distal to the stenosis declined significantly (p less than .01) vs control. Application of PICSO failed to increase arterial inflow distal to the stenosis in any myocardial layer. Myocardial aerobic metabolism was adversely affected by stenosis and changed from consumption of lactate, inosine, and hypoxanthine before stenosis to production at 30 min after stenosis. Although PICSO was associated with reduced production and a return toward consumption of lactate, inosine, and hypoxanthine, a similar pattern of changes in lactate, inosine, and hypoxanthine metabolism was observed in control animals over a comparable period of time. In addition, regional myocardial oxygen extraction and consumption were not changed vs poststenosis levels by PICSO. However, in comparison with controls, PICSO did accelerate the rate of resolution of myocardial ischemia as assessed by lactate metabolism. At 30 min of PICSO (or sham) the change vs poststenosis was +33.6 +/- 25.0 mumol/min/100 g in the PICSO but only +6.7 +/- 29.7 in the control group (p = .05). We conclude, therefore, that even though PICSO did not alter the final level of myocardial ischemia under conditions modeled in this study it did accelerate its rate of resolution, an effect that may be beneficial clinically.

Influence of serotonin on myocardial blood flow in the presence and absence of a coronary arterial stenosis: observations in domestic swine.

This study tested the hypothesis that 5-HT may impair coronary flow regulation by inappropriately increasing arteriolar tone in the coronary circulation. Ten closed chest, domestic swine were studied both in the presence and in the absence of a severe artificial intraluminal coronary stenosis. A 5-French micromanometer catheter with fluid lumen was placed in the left anterior descending coronary artery and used to record pressure and infuse 5-HT (40 and 100 micrograms/min) into the coronary circulation. For the stenosis phase of the protocol the catheter was embedded in the artificial stenosis. Hemodynamics, regional myocardial blood flow (microsphere technique), coronary vascular resistance, lactate consumption, and oxygen metabolism were measured at control and at 5 min of each 5-HT dose. In the absence of coronary artery stenosis (i.e., full vasodilatory reserve), there was no change in regional myocardial blood flow or coronary vascular resistance during 5-HT infusion. In the presence of a severe coronary stenosis (i.e., limited vasodilator reserve) 5-HT produced a significant (P less than 0.05) decrease versus control in the distal left anterior descending: circumflex zone endocardial blood flow ratio (0.63 +/- 0.19, mean +/- 1 SD, to 0.55 +/- 0.15) and a significant (P less than 0.05) increase versus control in endocardial (50.6 +/- 16.6 to 61.2 +/- 19.8 mm Hg/ml/min/g) and transmural (49.9 +/- 9.5 to 57.2 +/- 12.8) coronary vascular resistance. Thus, 5-HT does not impair coronary flow regulation when full vasodilatory reserve is present. When coronary vasodilatory reserve is impaired by the presence of a severe proximal stenosis, 5-HT causes modest impairment of endocardial flow regulation.

Objective assessment of coronary angioplasty for multivessel disease: results of exercise stress testing.

The efficacy of coronary angioplasty in multivessel coronary artery disease was evaluated in a series of 145 consecutive patients in whom angioplasty had been successful and in whom a follow-up exercise stress test was performed within 2 months. Exercise stress test results of these patients with multivessel disease were compared with those of 177 patients with single vessel disease after successful coronary angioplasty. The postangioplasty exercise test showed ischemia in 13% of patients with single vessel and 29% of those with multivessel disease, although only 7 and 13%, respectively, experienced angina. The mean exercise duration was comparable for patients with multivessel disease (453 +/- 174 s) and single vessel disease (476 +/- 166 s). To assess the impact of the degree of revascularization in patients with multivessel disease on the results of exercise testing, 48 patients with completely revascularized vessels and 97 with incompletely revascularized vessels were evaluated. The mean exercise duration (459 +/- 178 versus 450 +/- 173 s), mean maximal heart rate (132 +/- 31 versus 136 +/- 25 beats/min) and mean systolic blood pressure (174 +/- 25 versus 170 +/- 26 mm Hg) were similar in completely and incompletely revascularized groups. Exercise-induced angina occurred in 13% of both groups. Ischemic ST segments were more common in the incompletely revascularized group (34 versus 19%, p = 0.06). Thus, exercise stress testing provides evidence that successful angioplasty can relieve electrocardiographic manifestations of ischemia as well as anginal symptoms in the majority of patients with either single or multivessel coronary artery disease who are suitable candidates for the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)