Effects of surface charge and palladium on hepatic and kidney injury induced by polystyrene nanoparticles co-administered to mice with paraquat and cisplatin.

Recently, with the advancement of nanotechnology, various nanoparticles have been developed and used in fields such as electronics, cosmetics, and foods. However, the toxicity of nanoparticles has yet to be fully investigated. In particular, the interactions between nanoparticles and therapeutic drugs require further study. We previously reported that unmodified polystyrene nanoparticles with a particle size of 50 nm (NPP50) co-administered with paraquat (PQ) or cisplatin (CDDP) induce hepatic and kidney injury. Here, we determined if NPP50 modified with the amino group (NPP50-NH2), carboxyl group (NPP50-COOH), or palladium (Pd-NPP50) caused liver or kidney injury when co-administered with PQ or CDDP. The results showed that when NPP50-NH2, NPP50-COOH, or Pd-NPP50 was administered alone via the mouse tail vein, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) did not increase or cause injury. When NPP50, NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with PQ, serum levels of ALT and AST increased in the NPP50 group but did not increase in the NPP50-NH2, NPP50-COOH, or Pd-NPP50 groups. When NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with CDDP, ALT, AST, and BUN values did not increase. These data suggest that injury due to the interaction of polystyrene nanoparticles with CDDP or PQ can be suppressed by changes in the surface charge of nanoparticles or by Pd modification.

Prevalent emm types and superantigen gene patterns of group A Streptococcus in Thailand.

Group A Streptococcus (GAS) are globally distributed bacterial pathogens. We examined the emm genotypes, which are important indicators of virulence, of 349 clinical GAS isolates collected using two surveillance systems, i.e. Invasive Bacterial Infection Surveillance (IBIS) from 2010 to 2011 (234 isolates) and routine surveillance of clinically isolated bacteria from various hospitals during 1996-2011 (115 isolates) in Thailand. The major emm genotypes in IBIS samples were emm44 (12·0%), emm104 (6·8%), emm22 (5·6%), and emm81 (5·6%), whereas only one isolate (0·4%) had the emm1 genotype, which is significantly more common in invasive cases in the Western world. In samples collected during routine surveillance, emm238 (10·4%), emm44 (8·7%), and emm165 (7·0%) were dominant. The major superantigen gene profiles were similar between the groups, and 30·1% of isolates did not possess the phage-encoded superantigens (speA, speC, speH, speI, speK, speL, speM, ssa). Although most isolates exhibited limited gene profiles, emm44 isolates had highly variable gene profiles (15 patterns). We conclude that emm44 is the predominant GAS genotype in Thailand, and isolates varied in superantigen gene profiles.

Toxicity of 50-nm polystyrene particles co-administered to mice with acetaminophen, 5-aminosalicylic acid or tetracycline.

We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were acetaminophen (APAP), 5-aminosalicylic acid (5-ASA), tetracycline (TC), and sodium valproate (VPA). All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with APAP, 5-ASA or TC together with polystyrene particles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. On the other hand, co-administration of VPA and NPP50, NPP200 or NPP1000 did not elevate toxicity. The results show that NPP50 differs in hepatotoxicity depending on the drug co-administered. These findings suggest that further evaluation of the interactions between polystyrene nanoparticles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology.

Differential diagnosis of cerebral infarction using an algorithm combining atrial fibrillation and D-dimer level.

We created an algorithm for diagnosing subtypes of cerebral infarction (CI) during the acute stage by combining atrial fibrillation (AF) and D-dimer levels. One-hundred and eight patients hospitalized for acute CI were retrospectively analyzed. CI was classified into cardioembolic, atherothrombotic, lacunar infarction or others. Patients were classified in AF group if they had AF on admission or a prior history of AF. This group was diagnosed to suffer cardioembolic infarction. In non-AF group, cardioembolic infarction was diagnosed when D-dimer level exceeded the cutoff point determined using a receiver operating curve. Then, usefulness of the algorithm was validated prospectively in 259 consecutive patients with acute CI. For the retrospective group, cardioembolic infarction was found in 82% of the AF group. In non-AF group, cardioembolic infarction was found in only 2%, when D-dimer level was <1.6 microg/ml. However, 41% of non-AF group with atherothrombotic infarction had elevated D-dimer level (> or =1.6 microg/ml). Results for the validation group were similar to those for the retrospective group (sensitivity, 89%; specificity, 66%; positive predictive value, 50%; and negative predictive value, 94%). D-dimer level in combination with AF can be useful for distinguishing CI subtypes during the acute stage.

Magnetic circular dichroism of myoglobin-thiolate complexes.

Various complexes of myoglobin (Mb) with thiolate were studied by use of magnetic circular dichroism (MCD) spectroscopy. 1. MetMb-ethyl, n-propyl and isopropylmercaptan complexes offered MCD spectra similar to that of cytochrome P-450 (P-450) with respect to shape and intensity ratio of Soret MCD to Q0-0 MCD. The MCD spectra did not show any pH dependence. The complexes reduced by sodium dithionite exhibited the MCD spectrum of deoxyMb, indicative of release of thiolate anion from the heme iron. 2. Cysteine and cysteine methyl ester coordinated to the heme iron at pH 9.18 but not at pH 6.86 and 11.45. The complex formed at pH 9.18 gave an MCD spectrum similar to that of P-450, and an MCD spectrum of deoxy Mb on reduction with sodium dithionite. 3. The 2-mercaptoethanol complex exhibited three A terms associated with the Q0-0-1, and Soret transitions at pH 6.86 similar to those of Fe(II) cytochrome c, which indicates that Mb was reduced by this reagent at pH 6.86. At pH 9.18 2-mercaptoethanol gave an MCD spectrum similar to that of alkyl mercaptan just after the addition. With the time changed into deoxy Mb through some intermediate of reduced Mb-thiolate complex. At pH 11.45 2-mercaptoethanol formed complex which exhibited an MCD spectrum similar to those of other alkylmercaptans. 4. Sodium sulfide gave an MCD spectrum which resembled that of the normal thiol Mb complex just after addition at pH 6.86. The complex was gradually reduced to give 610 nm trough in addition to the MCD of deoxy Mb. The Mb-sulfur complex formed at pH 9.18 was gradually reduced to give an MCD spectrum which was fairly different from that of deoxy Mb. A similar MCD spectrum was observed at pH 11.45 just after the addition of Na2S. These results were considered to suggest the saturation of one of the conjugated double bonds of the porphyrin by sulfur.

Magnetic circular dichroism studies on horseradish peroxidase.

Magnetic circular dichroism (MCD) spectra were observed for native (Fe(III)) horseradish peroxidase (peroxidase, EC 1.11.1.7), its alkaline form and fluoro- and cyano-derivatives, and also for reduced (Fe(II)) horseradish peroxidase and its carbonmonoxy-- and cyano- derivatives. MCD spectra were obtained for the cyano derivative of Fe(III) horseradish peroxidase, and reduced horseradish peroxidase and its carbonmonoxy- derivative nearly identical with those for the respective myoglobin derivatives. The alkaline form of horseradish peroxidase exhibits a completely different MCD spectrum from that of myoglobin hydroxide. Thus it shows an MCD spectrum which falls into the ferric low-spin heme grouping. Native horseradish peroxidase and its fluoro derivatives show almost identical MCD spectra with those for the respective myoglobin derivatives in the visible region, though some changes were detected in the Soret region. Therefore it is concluded that the MCD spectra on the whole are sensitive to the spin state of the heme iron rather than to the porphyrin structures. The cyanide derivative of reduced horseradish peroxidase exhibited a characteristic MCD spectrum of the low-spin ferrous derivative like oxy-myoglobin.

Magnetic circular dichroism studies on acid and alkaline forms of horseradish peroxidase.

The heme vicinities of the acid and alkaline forms of native (Fd(III)) horseradish peroxidase were investigated in terms of the magnetic circular dichroism (MCD) spectroscopy. The MCD spectrum of the acid form of native horseradish peroxidase was characteristic of a ferric high spin heme group. The resemblance in the MCD spectrum between the acid form and acetato-iron (III)protoporphyrin IX dimethyl ester suggests that the heme iron of the acid form has the electronic structure similar to that in a pentocoordinated heme complex. The MCD spectra of native horseradish peroxidase did not shown any substantial pH dependence in the pH range from 5.20 to 9.00. The MCD spectral change indicated the pK value for the equilibrium between the acid and alkaline forms to be 11.0 which agrees with the results from other methods. The alkaline form of native horseradish peroxidase at pH 12.01 exhibited the MCD spectrum of a low spin complex. The near infrared MCD spectrum suggests that the alkaline form of native horseradish peroxidase has a 6th ligand somehow different from a normal nitrogen ligand such as histidine or lysine. It implicates that the alkaline form has an overall ligand field strength of between the low spin component of metmyoglobin hydroxide and metmyoglobin azide.

Infrared magnetic circular dichroism of myoglobin derivatives.

By use of a newly constructed CD instrument, infrared magnetic circular dichroism (MCD) spectra were observed for various myoglobin derivatives. The ferric high spin myoglobin derivatives such as fluoride, water and hydroxide complexes, commonly exhibited the MCD spectra consisting of positive A terms. Therefore, the results reinforced the assignment that the infrared band is the charge transfer transition to the degenerate excited state (eg (dpi)). Since the fraction of A term estimated was approximately 80% for myoglobin fluoride and approximately 35% for myoglobin water, the effective symmetry for myoglobin fluoride is determined to be as close as D4h, while that for myoglobin water seems to have lower symmetry components. The ferric low spin derivatives such as myoglobin cyanide, myoglobin imidazole and myoglobin azide showed positive MCD spectra which are very similar to the electronic absorption spectra. These MCD spectra were assigned to the charge transfer transitions from porphyrin pi to iron d orbitals on the ground that they were observed only for the ferric low spin groups and insensitive to the axial ligands. The lack of temperature dependence in the MCD magnitude indicated that the MCD spectra are attributable to the Faraday B terms. Deoxymyoglobin, the ferrous high spin derivative, had fairly strong positive MCD around 760 nm with an anisotropy factor (delta epsilon/epsilon) of 1.4-10(-4). It shows some small MCD bands from 800 to 1800 nm. Among the ferrous low spin derivatives, carbonmonoxymyoglobin did not give any observable MCD in the infrared region while oxymyoglobin seemed to have significant MCD in the range from 700 to 1000 nm.

Studies on the charge transfer band in high spin state of ferric myoglobin and hemoglobin by low temperature optical and magnetic circular dichroism spectroscopy.

The behavior of charge transfer band, appearing at 600-650 nm in ferric high spin derivatives of myoglobin and hemoglobin, was studied under various conditions by low temperature optical and magnetic circular dichroism spectroscopy. Optical absorption spectra have demonstrated that: (1) The charge transfer band at 630 nm of myoglobin (Fe3+)-H2O (pH 7.0) at room temperature split into three bands, 627 nm, 645 nm and 664 nm (shoulder) at 77 degrees K, whereas that of hemoglobin (Fe3+)-H2O showed no splitting. (2) By lowering the pH value from 7.5 to 4.3 this splitting in myoglobin was observed to disappear only in the presence of a small amount of phosphate ion, accompanying a midpoint at pH 6.7 +/- 0.1. This does not originate from the released hemin. (3) Hemin (pH 7.55) showed no splitting of the charge transfer band at 77 degrees K. (4) This splitting depended on the species of 6th ligand. For myoglobin-F- the splitting could scarcely be observed, whereas the proton-donating ligands such as HCOOH and CH3OH exhibit the splitting as well as H2O. Magnetic circular dichroism spectra have demonstrated that: (5) The charge transfer band at 600-500 nm indicated Faraday A term and B term. (6) A negative B term band was observed at 650 nm for myoglobin-H2O in the glassic solvent of potassium glycerophosphate-glycerol, whereas it was not observed for hemoglobin-H2O. Several discussions were performed on the origin of splitting of the charge transfer band in myoglobin-H2O. It is now concluded that the hydrogen bond between the 6th ligand and the distal histidine contributes to the splitting of the charge transfer band around 630 nm for myoglobin Fe3+)-H2O at low temperature and that disappearance of the splitting at low pH is originated from the presence of phosphate ion.

Interaction of photosynthetic pigments with various organic solvents 2. Application of magnetic circular dichroism to bacteriochlorophyll a and light-harvesting complex 1.

Magnetic circular dichroism (MCD) and absorption spectra of metal bacteriochlorin complexes have been measured on bacteriochlorophyll (BChl) a in various solvents and different forms of light-harvesting complexes 1 (LH1 complexes). In hydrophilic organic solvents, the MCD intensity of the Q(y)(0-0) transition of BChl a was sensitive to the wavelength of absorption maximum of Q(x)(0-0), and the ratio of MCD Q(y)(0-0) intensity to the dipole strength (B/D) was inversely proportional to the difference in energy between the Q(x)(0-0) and Q(y)(0-0). The similar correlation has been observed in metal chlorin derivatives as previously reported. The correlation depends on the coordination number of the Mg atom in BChl a and the molecules ligating to it. In a hydrophobic solvent such as carbon tetrachloride (CCl(4)), however, the correlation did not hold because of the existence of aggregates. Hence, the correlation between the values of B/D and the energy difference can be used to estimate the type and number of the molecules ligated to the Mg atom and to disclose the existence of aggregated pigments. We further apply the correlation to the LH 1 complex treated with n-octyl beta-D-glucopyranoside.

Magnetic circular dichroism on oxygen complexes of hemoproteins: correlation between magnetic circular dichroism magnitude and electronic structures of oxygen complexes.

Magnetic circular dichroism (MCD) and natural circular dichroism (CD) spectra are reported for horseradish peroxidase Compounds II and III, and kangaroo myoglobin Compound II at pH values of 8.5 and 4.9. These compounds exhibited MCD spectra of apparent Faraday A term both in the Soret and Q regions, except for myoglobin compounds in the Soret region where intrinsic temperature dependence showed large contribution from Faraday C terms. Comparison of these data with the MCD spectra of the dioxygen complexes of hemoglobin (myoglobin) and cytochrome P-450 revealed that the magnitude of the apparent Faraday A term trough at the Q0-0 bands decreased in the order of O2 complexes of hemoglobin (myoglobin) ([theta]M not equal to 16) greater than horseradish peroxidase Compound III ([theta]M not equal to 8) greater than O2 complex of cytochrome P-450 ([theta]M not equal to 4). The [theta]M values of the oxygen complex of cytochrome P-450 is similar to those observed for the compounds II of horseradish peroxidase and kangaroo myoglobin. From these observations it was concluded that the magnitude of MCD, especially the trough depth of the Q0-0 band, has direct correlation to the electronic states of the oxygen complexes of the hemoproteins. The implication of the findings was discussed in terms of the iron electronic structures perturbed by the axial ligation.

Magnetic and natural circular dichroism spectra of cytochgromes P-450(11) beta and P-450scc purified from bovine adrenal cortex.

Magnetic (MCD) and natural circular dichroism (CD) spectra various complexes of cytochrome P-450(11) beta (P-450(11) beta) and cytochrome P-450scc (P-450scc) from bovine adrenal cortex were measured from 250 nm to 700 nm. MCD and CD spectral contours of cytochromes P-450(11) beta and P-450scc in the Soret and visible regions were, as a whole, analogous to those of cytochromes P-450 from rabbit liver microsomes and also from Pseudomonas putida in their high-spin ferric, high-spin ferrous and ferrous-CO complexes. MCD spectrum of the low-spin ferric P-450scc free from the substrate, cholesterol, was very similar to that caused by addition of 20 alpha-hydroxycholesterol, a reaction intermediate. However, it was distinct from those of the low-spin ferric P-450(11) beta and P-450scc complexes caused by addition of external nitrogenous ligands. The electronic states of the heme in the low-spin ferric P-450 free from substrates seemed to be subtly different from those of low-spin complexes coordinated with external nitrogenous ligands. Soret CD spectra of ferric low-spin complexes were not so different from each other. Upon reduction of high-spin ferric P-450(11) beta or P-450scc, the Soret CD magnitudes increased significantly in contrast with those of other P-450s, the Soret CD magnitudes of which decrease upon reduction. This may reflect an increased proximity of the neighbouring aromatic groups upon reduction of high-spin P-450(11) beta or P-450scc. High substrate specificity of adrenal P-450s compared with liver P-450s can be explained in view of the above findings. THe CD spectra in the near ultraviolet region (250-350 nm) were found to be quite sensitive to the spin change for ferric P-450scc, while the MCD spectra in this region did not reflect substantially the spin state of the enzyme. MCD parameters of cytochrome P-450s were compared to those of other hemoproteins in diagrams describing selected MCD spectral values of hemoproteins so far available and were discussed in connection with the structures of the heme environment of P-450.

Magnetic circular dichroism studies of cytochrome P-450cam. Characterization of axial ligands of ferric and ferrous low-spin complexes.

MCD was applied to ferric and ferrous low-spin complexes of cytochrome P-450 cam to elucidate the electronic states and the nature of the axial ligands of the heme in cytochrome P-450cam. (1) Low-spin complexes of ferric cytochrome P-450cam, produced either by ligation of external ligands such as pyridine and imidazole derivatives or by being freed of (-)-camphor, showed sinusoidal Soret and alpha-MCD bands. The magnitude ratio of the Soret vs. alpha-MCD bands was quite sensitive to the nature of axial ligands of the ferric low-spin complexes. The ratio (2.7) for the camphor-free form of cytochrome P-450cam, thus, was the smallest among those (2.7-9.0) for low-spin forms of cytochrome P-450cam and other corresponding low-spin hemoproteins (ratio 7.8-13.9). The ratio (4.2) for the alpha-picoline-bound form of cytochrome P-450cam, however, was the closest to that (2.7) for the camphor-free form of cytochrome P-450cam among those (4.2-9.0) for the external ligand-bound form of cytochrome P-450cam. The ratio for the 2-methylimidazole-bound form of cytochrome P-450cam was the smallest among those of cytochrome P-450cam bound with imidizole derivatives. Thus, among the nitrogen-bound low-spin forms, the low-spin form with a sterically hindered nitrogen ligand trans to the thiolate anion (-S-) most reproduced spectral characteristics of the native low-spin ferric form. Low-temperature absorption studies offered the same results. (2) It was found that MCD magnitudes of alpha-bands of ferrous low-spin complexes are intimately related to the electronic character of axial ligands. Thus, the CO, O2 and NO-bound forms of cytochrome P-450cam, which have two pi-type axial ligands, showed the smallest alpha-MCD bands ([theta]M = 5.2-7.5) among complexes, while ferrous cytochrome b5 and cytochrome c, which have two sigma-electron-donating axial ligands, showed the largest magnitude ([theta]M = 120-176). The data for the ferrous low-spin complexes of other hemoproteins so far available were well rationalized in consideration of the property of the axial ligands.

Magnetic circular dichroism of Pseudomonas putida cytochrome P-450 in near infrared region.

Magnetic circular dichroism spectra of oxidized, reduced and carbonmonoxy reduced forms of cytochrome P-450 from D-camphor grown Pseudomonas putida (P-450cam) were studied in the near infrared region (650 to 1200 nm) at various temperatures in the presence of D-camphor. Oxidized P-450cam with camphor exhibited positive (+) and negative (-) magnetic CD bands at 825 and 970 nm, respectively, and both of them were assigned to Faraday B terms. The magnetic CD spectrum of reduced P-450cam in the presence of D-camphor exhibited at least five components in the region between 650 to 1175 nm and one of them at 760 nm showed considerably smaller magnitude than that of the corresponding band of deoxymyoglobin. These results were interpreted to mean that the heme-iron in both oxidized and reduced P-450cam has a ligand field symmetry lower than C4v, i.e. a strong rhombic character of the heme in cytochrome P-450. Carbonmonoxide complex of reduced P-450cam exhibited no detectable magnitude of magnetic CD in the near infrared region but showed CD bands at 710 (-) and 850 (+) nm. The results were compared and discussed with those of carbonmonoxy hemoglobin and myoglobin. In addition, temperature dependent changes in the spin state of oxidized P-450cam from high to low by decrease of temperature were observed by measuring both magnetic CD and absorption spectra in the near ultraviolet and visible regions (300 to 650 nm), provided that the temperature of the sample was varied slowly (approximately 3 degrees C/min) between room and liquid nitrogen temperature in a 0.03 M phosphate buffer (pH 7.2) containing a saturated amount of D-camphor and 70% (v/v) glycerol. The significance of this phenomenon is also discussed.

Circular dichroism spectra of purified cytochromes P-450 from rabbit liver microsomes.

Circular dichroism (CD) spectra were measured for cytochromes P-450 (P-450) purified from phenobarbital- and 3-methylcholanthrene-induced rabbit liver microsomes. No striking difference in alpha-helix content was seen between phenobarbital-induced P-450 (PB P-450) (50%), phenobarbital-induced P-448 (PB P-448) (40%) and 3-methylcholanthrene-induced P-448 (MC P-448) (45--50%) in terms of ultraviolet CD spectra. Strong negative CD spectra associated with 3-methylcholanthrene transitions for MC P-448 in the near-ultraviolet region (250--310 nm) and weaker negative CD spectra associated with Soret transitions for PBP-448 ([theta] = 50 000) and MCP-448 ([theta] = 160 000), indicated that structures of these preparations are strikingly different from each other. Reduction of P-450 and P-448 led to a remarkable decrease of the Soret CD trough, suggesting that reduction was accompanied by a striking conformational change in the vicinity of the heme. Since CO complexes of reduced P-450 and P-448 showed a CD trough and an S-shaped CD, respectively, associated with the absorption peak at 450 nm, the heme vicinities are remarkably different from each other. The CD spectra in the visible region are also discussed. It was noticed that P-420, the denatured form of P-450, exhibited no CD spectra in the Soret and visible regions.

Properties of the reaction center of the thermophilic purple photosynthetic bacterium Chromatium tepidum.

Reaction centers were purified from the thermophilic purple sulfur photosynthetic bacterium Chromatium tepidum. The reaction center consists of four polypeptides L, M, H and C, whose apparent molecular masses were determined to be 25, 30, 34 and 44 kDa, respectively, by polyacrylamide gel electrophoresis. The heaviest peptide corresponds to tightly bound cytochrome. The tightly bound cytochrome c contains two types of heme, high-potential c-556 and low-potential c-553. The low-potential heme is able to be photooxidized at 77 K. The reaction center exhibits laser-flash-induced absorption changes and circular dichroism spectra similar to those observed in other purple photosynthetic bacteria. Whole cells contain both ubiquinone and menaquinone. Reaction centers contain only a single active quinone; chemical analysis showed this to be menaquinone. Reaction center complexes without the tightly bound cytochrome were also prepared. The near-infrared pigment absorption bands are red-shifted in reaction centers with cytochrome compared to those without cytochrome.

Interaction of photosynthetic pigments with various organic solvents. Magnetic circular dichroism approach and application to chlorosomes

Magnetic circular dichroism (MCD) and absorption spectra have been measured on three intact photosynthetic pigments with the chlorin ring as macrocycle: chlorophyll a, bacteriochlorophyll c and d, in various hydrophilic organic solvents. The MCD intensity of a Qy(0-0) transition for the Mg chlorin derivative was sensitive to the coordination state of the central Mg atom by the solvent molecules. The coordination number has been characterized in terms of the relationship between the ratio of Qy(0-0) MCD intensity to its dipole strength (B/D) and the difference in energies of Qx(0-0) and Qy(0-0) transitions. This relationship depends not only on the coordination number of the magnesium (Mg) atom but also on the coordination interaction of the solvent molecules to the Mg atom, and can clarify the spectroscopic change of chlorosomes by alcohol treatment. We propose that the correlation between the MCD intensity of Qy(0-0) transition and the energy difference can be used as a new measure for determining the coordination number of the Mg atom and for estimating the interaction strength of the Mg atom with solvent molecules.

Respiratory modulation of muscle sympathetic nerve activity in patients with chronic heart failure.

BACKGROUND: Sympathoexcitation and respiratory instability are closely related to worsening of chronic heart failure. To elucidate the dynamic nature of respiratory modulation of sympathetic activity in patients with heart failure, we studied within-breath variation of muscle sympathetic nerve activity (MSNA) under various ventilatory volumes. METHODS AND RESULTS: MSNA, blood pressure, and respiratory flow were recorded in 23 patients with left ventricular ejection fraction

Modulation of left ventricular diastolic distensibility by collateral flow recruitment during balloon coronary occlusion.

OBJECTIVES: The goals of this study were to elucidate the scaffolding effect of blood-filled coronary vasculature and to determine the functional role of recruited collateral flow in modulating left ventricular (LV) distensibility during balloon coronary occlusion (BCO). BACKGROUND: Although LV distensibility is an important factor affecting acute dilation after myocardial infarction, the response of LV diastolic pressure-volume (P-V) relations to coronary occlusion is inconsistent in humans. METHODS: Micromanometer and conductance derived LV P-V loops were serially obtained from 16 patients undergoing percutaneous transluminal coronary angioplasty. Coronary collateral flow recruitment was angiographically evaluated by contralateral and ipsilateral contrast injection during BCO. RESULTS: In the group with poor collateral flow (grades 0-I; n = 8), BCO resulted in a downward and rightward shift of the diastolic P-V relations, where end-diastolic volume (EDV) increased by 13% (p < 0.05) without appreciable change in end-diastolic pressure (EDP; 18 +/- 6 to 18 +/- 8 mm Hg). In contrast, BCO in the group with good collateral flow (grades II-III; n = 8) shifted the diastolic P-V relations upward to the right with a concomitant increase in minimal pressure (min-P; 6 +/- 4 to 10 +/- 5 mm Hg, p < 0.05), EDP (15 +/- 7 to 21 +/- 9 mm Hg, p < 0.05) and EDV (+/- 10%, p < 0.05). Reactive hyperemia after balloon deflation caused a rapid and parallel upward shift of the diastolic P-V relations with a marked increase in min-P and EDP, especially in the group with poor collateral flow, before any improvement in LV contraction or relaxation abnormalities. CONCLUSIONS: Grades of coronary filling, either retrograde or anterograde, abruptly modulate LV distensibility through the rapid scaffolding effect of coronary vascular turgor.

Time-varying spectral analysis of heart rate and left ventricular pressure variability during balloon coronary occlusion in humans: a sympathoexicitatory response to myocardial ischemia.

OBJECTIVES: We assessed time-varying spectral components of heart rate and left ventricular (LV) pressure variability during coronary angioplasty to elucidate dynamic autonomic responses to transient myocardial ischemia. BACKGROUND: Sympathoexcitatory reflexes elicited by acute coronary occlusion are rarely addressed in the clinical settings because of a lack of technique to monitor transient changes in sympathetic activation. METHODS: RR interval and LV pressure and volume were serially recorded in 14 patients with effort angina during balloon coronary angioplasty. Wavelet analysis was applied for determination of nonstationary spectral components of RR interval and LV peak pressure variability. RESULTS: The wavelet analysis revealed that coronary occlusion provoked low-frequency (LF) fluctuations of RR interval (seven patients) and LV peak pressure (six patients) at 0.06 +/- 0.01 Hz, but not in the remaining patients. Following the balloon inflation, the LF component of RR interval began to increase after the onset of myocardial ischemia, peaked at about 80 s, and then declined in the late phase of inflation. Consequently, the ratio of low to high frequency component rose to be significantly greater in the LF augmentation group than in the no LF augmentation group in the middle phase of coronary occlusion. The patients with no LF augmentation had little evidence of myocardial ischemia as reflected by changes in ST segment and LV systolic function during coronary occlusion. CONCLUSIONS: The wavelet analysis of RR interval and LV pressure variability clearly showed a dynamic profile of spectral components in response to transient coronary artery occlusion. The resultant regional myocardial ischemia elicited a profound sympathoexcitatory response followed by a gradual suppression. This method provides a useful tool to gain a new insight into the nonstationary autonomic influence on the cardiovascular system.