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New synthetic routes to 1,2,3-dithiazolo-1,2,3-dithiazolylium salts, based on double Herz condensations of N-alkylated 2,6-diaminopyridinium salts with sulfur monochloride, have been developed. The two prototypal 1,2,3-dithiazolo-1,2,3-dithiazolyl radicals HBPMe and HBPEt have been prepared and characterized in solution by cyclic voltammetry and EPR spectroscopy. Measured electrochemical cell potentials and computed (B3LYP/6-31G) gas-phase disproportionation enthalpies favor a low on-site Coulombic repulsion energy U in the solid state. The crystal structures of HBPR (R = Me, Et) have been determined by X-ray crystallography (at 293 K). Both consist of slipped pi-stacks of undimerized radicals, with many close intermolecular S- - -S contacts. Magnetic, conductivity, and optical measurements have been performed and the results interpreted in light of extended Hückel band calculations. The crystalline materials are paramagnetic above 100 K, with room-temperature conductivities sigma(RT) of 10(-5)-10(-6) S cm(-1); the slightly greater conductivity of the R = Et compound can be associated with a more well developed band structure. We suggest a Mott-Hubbard insulator ground state for these materials, with an on-site Coulomb repulsion energy U of about 1.0 eV.

Selection of phenotypically distinct bacterial colonies on a Petri dish is typically performed by one of two methods: chemical or mechanical. Chemical methods (e.g., antibiotic selection) rely on inherent growth advantages of the unique phenotypes desired and thus have limited applicability. Mechanical methods are generally slow and require relatively large colonies (typically hundreds of colonies per plate). Here the use of imaged light to select bacterial colonies is explored, employing either photodynamic therapy agents or a ferrochelatase mutation in combination with porphyrin precursors to sensitize the bacteria to light and a computer-controlled light projection system to illuminate some bacterial colonies while leaving others in the dark. A CCD camera was used to distinguish between bacteria expressing green fluorescent protein (GFP) from nonfluorescent colonies. The fluorescence image from the camera was then used to create a virtual masking image for photoselection. Using a simple commercial projector it was possible to confer a 56-fold selective advantage to colonies expressing GFP. This represents a potentially powerful tool in directed evolution experiments using large libraries., (Copyright 2003 Wiley Periodicals, Inc.)

Background: The Myocor Myosplint is a transcavitary tensioning device designed to change left ventricular (LV) shape and reduce wall stress. Regional wall stress cannot be measured in the intact heart and LV function after surgical remodeling is often confounded by inotropic agents and mitral repair. We used a realistic mathematical (finite element) model of the dilated human LV to test the hypothesis that Myosplint decreased regional ventricular fiber stress and improved LV function., Methods: A finite element model was used to simulate the effects of Myosplint on the LV stroke volume/end-diastolic pressure (Starling) relationship and regional distributions of stress in the local muscle fiber direction (fiber stress) for a wide range of diastolic and end-systolic material properties. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction. An elastance model for active fiber stress was incorporated in an axisymmetric geometric model of the globally dilated LV wall., Results: Both diastolic compliance and end-systolic elastance shifted to the left on the pressure-volume diagram. LV end-diastolic volume and end-systolic volumes were reduced by 7.6% and 8.6%, respectively. Mean end-diastolic and end-systolic fiber stress was decreased by 24% and 16%, respectively. Although the effect of Myosplint on the Starling relationship was not significant, there were trends toward an improvement in this relationship at low diastolic stiffness, C, high peak intracellular calcium concentration, Ca(0), and high arterial elastance, E(A). Of note, the effect of C was twice that of Ca(0) and E(A). Diastolic function would, therefore, be expected to be the prime determinant of success with Myosplint., Conclusions: Myosplint reduces fiber stress without a decrement in the Starling relationship. Myosplint should be much more effective than partial ventriculectomy as a surgical therapy for patients with dilated cardiomyopathy and end-stage congestive heart failure.

Patients with Parkinson's disease (PD) can experience cognitive impairment. There are currently no medications indicated for the treatment of cognitive impairment in PD. Clinicians are faced with the dilemma as to whether or not to treat patients with PD with the acetylcholinesterase inhibitors that are currently approved for use in Alzheimer's disease (AD) and that have shown promise in clinical trials of Dementia with Lewy bodies (DLB). Although these medications may help cognition, there is a theoretical concern that by increasing acetylcholine relative to dopamine, they might worsen motor function. We report the case of a patient with PD and cognitive impairment who developed a marked worsening of motor function, mood, and anxiety in the setting of a pharmacologic challenge study using a 3-mg oral dose of the acetylcholinesterase inhibitor, rivastigmine. We believe that the mechanism of the motor and perhaps psychiatric worsening was increased central cholinergic tone. We conclude that further studies should be done to evaluate the efficacy and tolerability of these agents in this illness but that caution should be exercised when using acetylcholinesterase inhibitors in patients with PD.

Crystals of (Cl2C3NS)(ClC2NS2), an isothiazolyl-substituted 1,2,3-dithiazolyl radical, consist of evenly spaced, slipped pi-stacks; magnetic and conductivity measurements indicate the material is a Mott insulator with sigma RT = 2 x 10(-7) S cm-1.

Study Objective: To evaluate the accuracy of four once-daily aminoglycoside dosing nomograms in producing the desired gentamicin peak concentration (Cmax) target of 20 microg/ml in patients with varying degrees of renal function., Design: Retrospective analysis using prospectively collected pharmacokinetic data., Setting: Rural teaching hospital., Patients: Ninety patients receiving intravenous gentamicin divided into three groups (30 patients each) determined by estimated renal function: group 1, creatinine clearance (Cl(cr),) 60 ml/minute or greater; group 2, Cl(cr) 40-59 ml/minute; group 3, Cl(cr) 20-39 ml/minute. Intervention. Serum gentamicin concentrations were collected for a 2-point (two consecutive infusions and one predose and one postdose concentration sampled during steady state) or 3-point (single infusion and one predose and two postdose concentrations at least 1.5 estimated half-lives apart) pharmacokinetic study for determination of patient-specific pharmacokinetic parameters (elimination rate constant, volume of distribution at steady state, and clearance) after 30-minute infusions of gentamicin 2.8 +/- 1.6 mg/kg., Measurements and Results: The four nomograms evaluated were from Hartford Hospital, Barnes-Jewish Hospital, University of Rochester, and the Sanford Guide. With a pharmacokinetic analysis program and the patient-specific pharmacokinetic parameters, Cmax and minimum concentration (Cmin) were determined with use of the recommended doses and dosing intervals of the four nomograms. Also, the gentamicin dose and interval needed to achieve a Cmax and Cmin of 20 microg/ml and 0.2 microg/ml, respectively, were determined. Dosing was based on total body weight unless that weight was more than 25% of ideal body weight, in which case, an adjusted body weight was used. In general, the recommended dosages and resultant Cmax produced by the nomograms were significantly less (p < 0.05) than the dosage and Cmax actually needed to achieve a Cmax:minimum inhibitory concentration (MIC) ratio of 10 or greater for bacteria with an MIC of 2 microg/ml., Conclusion: Once-daily aminoglycoside dosing using the four nomograms resulted in inaccurate dosing, and because of the large variability in human pharmacokinetics, dosing nomograms such as these should be abandoned in favor of individualizing dosages with therapeutic drug monitoring.

Surgical therapies for heart failure that reduce left ventricular (LV) size have failed to improve LV function. Recent reports describe the direct injection of myocytes into the LV wall and suggest that myocyte transplantation improves regional contractile ability and improves LV function. Using a previously described finite element model, we simulated myocyte transplantation in the failing LV and tested the hypothesis that myocyte transplantation improves LV function (Starling relationship). An elastance model for active fiber stress was incorporated in an axisymmetric geometric model of the dilated, poorly contractile LV (dilated cardiomyopathy [DCM]). The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction. Systolic material properties were depressed by assigning a peak intracellular calcium concentration (Ca2+) of 1.8 micromoL (normal value: 4.2 micromoL). Six different simulations of myocyte transplantation were performed in which transplanted areas were assigned a peak intracellular calcium concentration (Ca2+) of 4.2 micromoL. The pattern of myocyte engraftment was varied (transmural versus subepicardial; confluent versus heterogeneous), as was the amount of the LV free wall that was transplanted (17% vs 33%). Models were created and loaded with a range of physiologic LV pressures. Simulated myocyte transplantation increased the slope of the end-systolic elastance curve, improved the Starling relationship, and improved stroke volume and ejection fraction compared with DCM. This study demonstrated an improvement in LV function after myocyte transplantation.

Alkylation of the zwitterionic heterocycle 8-chloro-bis[1,2,3]dithiazolo[4,5-b:5',4'-e]pyridine (ClBP) with alkyl triflates affords 8-chloro-4-alkyl-4H-bis[1,2,3]dithiazolo[4,5-b:5',4'-e]pyridin-2-ium triflates [ClBPR][OTf] (R = Me, Et, Pr). Reduction of these salts with decamethylferrocene affords the corresponding ClBPR radicals as thermally stable crystalline solids. The radicals have been characterized in solution by cyclic voltammetry and EPR spectroscopy. Measured electrochemical cell potentials and computed (B3LYP/6-31G) gas-phase disproportionation enthalpies are consistent with a low on-site Coulombic barrier U to charge transfer in the solid state. The crystal structures of ClBPR (R = Me, Et, Pr) have been determined by X-ray crystallography (at 293 K). All three structures consist of slipped pi-stacks of undimerized radicals, with many close intermolecular S.S contacts. ClBPMe undergoes a phase transition at 93 K to a slightly modified slipped pi-stack arrangement, the structure of which has also been established crystallographically (at 25 K). Variable-temperature magnetic and conductivity measurements have been performed, and the results interpreted in light of extended Hückel band calculations. The room-temperature conductivities of ClBPR systems (sigma(RT) approximately 10(-)(5) to 10(-)(6) S cm(-)(1)), as well as the weak 1D ferromagnetism exhibited by ClBPMe, are interpreted in terms of weak intermolecular overlap along the pi-stacks. The latter is caused by slippage of the molecular plates, a feature necessitated by the steric size of the R and Cl groups on the pyridine ring.

Reduced neuronal NOS (nNOS) expression and biochemical activity was found in the striatum (P<0.05) and cerebellum P<0.05) of late-stage R6/1 Huntington's disease (HD) mice. The changes in NOS biochemical activity correlated with body weight (P<0.001), abnormal clasping (P<0.05) and motor functioning (P<0.05) scores. HD transgenic mice missing both copies of the nNOS gene showed accelerated disease progression relative to HD transgenic mice wildtype or heterozygous for the nNOS gene. On the other hand, mice with one copy of the nNOS gene had delayed onset of their HD-related symptoms relative to HD transgenic mice wildtype for nNOS. Administration of an iNOS inhibitor had no effect on behavioral progression. The effects of nNOS genotype on behavior may be related to abnormal expression of nNOS during development, which was increased relative to controls in R6/2 mice 3 weeks of age (presymptomatic), but decreased in R6/2 mice relative to controls at 6 (around the time of symptom onset) and 11 (late-stage disease) weeks of age. Finally, protein expression of calmodulin kinase II and IV, both of which are regulators of nNOS transcription and activation, had a pattern of increased expression early in development, and decreased expression late in development, similar to that seen for nNOS. These findings indicate that nNOS activity is altered in a complex manner in HD transgenic mice and suggest that these abnormalities occur in the setting of a more global disturbance of calcium-regulated proteins.

Widespread disturbances in calcium-dependent proteins are reported both in humans with advanced Huntington's disease (HD) and in symptomatic HD transgenic mice. Using a HD mouse model transgenic for exon 1 of the abnormal gene (e.g. the Bates R6/2 mouse), we found increased expression of calmodulin kinase IV and neuronal nitric oxide synthase (NOS) in 3-week-old presymptomatic HD mice striatum and cortex. Conversely, reduced expression was found at 6 weeks (early symptom onset) and 11 weeks (advanced disease) of age. The changes in protein expression may have a broad impact on the HD striatum. Calmodulin kinase IV directly regulates the activation of the transcription factors CREB (cyclic AMP response element binding protein) and CREM (cyclic AMP response element modulator) and, as well, modulates the activity of neuronal NOS. In homeostasis, nitric oxide is involved in long-term potentiation, neurotransmission, endocrine regulation and cerebral blood flow regulation, among others, while under pathological conditions nitric oxide combines with superoxide to produce the potent neurotoxin peroxynitrite. The current findings suggest that mutant HD protein may alter these processes by disturbing the regulation of calmodulin kinase IV and neuronal NOS expression across the lifespan of the HD mouse.

This study examined the effects of Huntington's disease (HD) on neural activity during performance of the Porteus maze task. fMRI data were acquired from three HD patients and three controls. Reduced fMRI signal was observed in the patients relative to the controls in occipital, parietal and somato-motor cortex and in the caudate, while increased signal was found in HD in the left postcentral and right middle frontal gyri. The altered fMRI responses in HD patients may result from neural, metabolic, neurovascular coupling and/or hemodynamic differences associated with this disorder.

Background: Myocardial infarct expansion and left ventricular (LV) remodeling are integral components in the evolution of chronic heart failure and predict morbidity and mortality. Radiofrequency (RF) heating and patch placement of chronic LV aneurysms caused a sustained reduction in LV infarct area and volume in an ovine infarct model. This study evaluated the effect of RF heating and epicardial patch as an adjunct to coronary artery bypass graft on LV volumes in patients with prior myocardial infarction, evidence of akinetic/dyskinetic scar, and LV ejection fraction < or =40%., Methods and Results: Ten patients (3 female; mean age, 64+/-11 years) scheduled for coronary artery bypass graft were enrolled (Canadian Cardiovascular Society angina class 2.1+/-1.1; New York Heart Association class 3.1+/-0.5). Intraoperative digital photography demonstrated an acute 39% reduction in infarct area (n=5; P=0.01), and transesophageal ECGs demonstrated a 16% acute reduction in LV end-diastolic volumes (n=9; P=0.002) after RF treatment. There were no intraoperative or procedure-related postoperative complications, and during an average follow-up of >180 days, there have been no safety issues. All patients had complete relief of their angina and improvement in exercise tolerance. Serial transthoracic ECGs over the 6 months of follow-up after RF treatment demonstrated persistent reductions in LV end-diastolic volume (29%; P<0.0001) and LV end-systolic volume (37%; P<0.0001) with improved ejection fraction (P<0.02)., Conclusions: RF heating and patch placement in these 10 patients resulted in acute reduction in infarct area and ventricular volumes that were maintained 180 days after procedure. This technique may reduce the incidence of congestive heart failure and mortality in these patients and warrants investigation in larger clinical trials.

Objectives: Residual stress is the stress (force per unit area) that remains when all external loads (eg, left ventricular chamber and pericardial pressures) are removed. It has been suggested that ventricular volume reduction surgery can reconstitute the residual stress-strain state of the left ventricle. To determine the extent to which residual stress is involved, we used a mathematical (finite element) model to simulate the effect of volume reduction operations on left ventricular stroke volume/end-diastolic pressure (Starling) relationships, as well as on regional distributions of stress in the local muscle fiber direction (fiber stress)., Methods: The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction. An elastance model for active fiber stress was incorporated in an axisymmetric geometric model of the dilated, poorly contractile left ventricular wall., Results: When residual stress is implemented in the model simulation of volume reduction operations, the additional decrease in stroke volume at fixed left ventricular end-diastolic pressure is small (10% volume reduction: 2.0% at 1 mm Hg and 2.0% at 20 mm Hg; 20% volume reduction: 2.2% at 1 mm Hg and 3.1% at 20 mm Hg). Furthermore, there is little change in the mean fiber stress throughout the left ventricular wall (10% volume reduction: +1.0% at end-diastole and -0.3% at end-systole; 20% volume reduction: +2.1% at end-diastole and -1.0% at end-systole)., Conclusions: These results suggest that residual stress produced by volume reduction operations has little effect on left ventricular function and the mean fiber stresses at end-diastole and end-systole.

Background: This study tested the hypothesis that induction and reperfusion with warm substrate-enriched (IRWSE) blood cardioplegia improves postoperative left ventricular (LV) function in patients undergoing elective coronary bypass surgery (CABG)., Methods: After giving informed consent, 67 patients scheduled for CABG surgery were randomized to either IRWSE + cold blood (CB) or CB alone. IRWSE cardioplegia consisted of 37 degrees C substrate-enriched (glutamate, aspartate, hyperkalemic) anterograde and retrograde blood cardioplegic solution followed by non-substrate-enriched cardioplegic solution given at 4 degrees C to 8 degrees C. LV function was measured with ventriculograms, volume conductance catheters, echocardiography, and multiple gated (image) acquisition., Results: The end-systolic pressure-volume relationship was improved postbypass in the IRWSE + CB group (CB, 1.5 +/- 0.74 mm Hg/mL vs IRWSE + CB, 2.1 +/- 1.2 mm Hg/mL; p = 0.042). The postoperative ejection fraction (EF%) was better preserved in the CB group (CB, 65 +/- 11.53% vs IRWSE + CB, 58.62 +/- 11.75%; p < 0.04)., Conclusions: Our results demonstrate a transient improvement in LV systolic function in the immediate postbypass period in CABG patients in the IRWSE + CB group. The intraoperative benefits of the IRWSE + CB technique did not persist in the postoperative period.

Objective: Myocardial infarct expansion and subsequent left ventricular remodeling are associated with increased incidence of congestive failure and mortality. Collagen is known to denature and contract when heated above 65 degrees C. We therefore tested the hypothesis that radio frequency heating of myocardial infarct tissue with application of a restraining patch causes a sustained reduction in myocardial infarct area and left ventricular volume., Methods: Thirteen male Dorset sheep underwent surgical coronary artery ligation. At least 14 weeks later, animals were randomized to either radio frequency infarct heating (95 degrees C) with application of a restraining patch or a sham operation. Before treatment, after treatment, and 10 weeks later, left ventricular volume was measured with transdiaphragmatic echocardiography and myocardial infarct area was measured with an array of sonomicrometry crystals., Results: Radio frequency infarct heating causes an acute decrease of 34% (-215 +/- 82 mm(2); P =.0002) in infarct area at end-diastole that is maintained at 10 weeks (-144 +/- 79 mm(2); P =.0002). Radio frequency infarct heating causes a downward trend in end-diastolic left ventricular volume measured by echocardiography of 20% (-15.7 +/- 6.3 mL; P = no significant difference) and end-systolic left ventricular volume of 32% (-17.1 +/- 9.8 mL; P =.09), which are significantly decreased at 10 weeks (-13.6 +/- 22.3 mL; P =.007 and -15.3 +/- 21.9 mL; P =.008, respectively). Radio frequency infarct heating causes an acute improvement in systolic function (P <.001), a sustained increase in left ventricular ejection fraction (+0.11%; P =.06), and preserved stroke volume., Conclusion: Radio frequency heating of chronic left ventricular myocardial infarct causes a sustained reduction in infarct area and left ventricular volume. This technique may beneficially reverse infarct expansion and left ventricular remodeling after myocardial infarction.

Unlabelled: We tested the hypothesis that L-arginine (the substrate for nitric oxide production)-combined with amrinone, milrinone (Type III phosphodiesterase [PDE] inhibitors), zaprinast, or sildenafil (Type V PDE inhibitors)-would vasodilate synergistically. Internal mammary artery segments were excised from anesthetized swine, divided into rings, and suspended in a tissue bath at 37 degrees C. Force of contraction was measured during dose-response testing of combinations of L-arginine and amrinone, milrinone, zaprinast, or sildenafil. Amrinone and milrinone were additive to L-arginine. N(G)-methyl-L-arginine (L-NMA) inhibited the effects of milrinone but not amrinone. The effective concentration of amrinone eliciting 50% relaxation (EC(50)) was 3.8E-05M (n = 6) when given alone and 4. 4E-05M (n = 6) with L-NMA. Milrinone had EC(50) = 6.0E-06M alone (n = 6) and 2.8E-05M (n = 6) with L-NMA. Zaprinast (EC(50) = 6.5E-05M, n = 6) and sildenafil (EC(30) = 1.8E-05M, n = 6) were synergistic with L-arginine. L-NMA blocked their effects, increasing the EC(50) for zaprinast to 9.9E-03M and the EC(30) for sildenafil to 6.1E+02M. In conclusion, L-arginine is additive to the vasodilation of the type III PDE inhibitors, amrinone and milrinone, but synergistic with the type V PDE inhibitors, zaprinast and sildenafil., Implications: Amrinone and milrinone, Type III cAMP-dependent phosphodiesterase inhibitors, are additive to L-arginine-dependent vasodilation. Zaprinast and sildenafil, Type V cGMP-dependent phosphodiesterase inhibitors, are synergistic with L-arginine.

Background: The endotracheal cardiac output monitor (ECOM) is a new device that uses an endotracheal tube with multiple electrodes to measure cardiac output (CO). It measures the changes in electrical impedance caused by pulsatile blood flow in the aorta. The system was tested for safety and efficacy in 10 swine., Methods: Swine (60-80 kg) were chronically instrumented with a transit time flow probe on the ascending aorta and vascular occluders on the vena cava and pulmonary artery. After a minimum recovery of 4 days, the animals were anesthetized and intubated with an ECOM endotracheal tube. CO measurements from the ECOM system were compared to transit time flow probe measurements using linear regression and Bland-Altman analysis. Three different inotropic states were studied: (1) baseline; (2) increased (dobutamine); and (3) decreased (esmolol). CO was changed at each inotropic state by impeding left ventricular filling with the vena cava or pulmonary artery occluders. CO values between 0 and 15 l/min were studied. Pigs were studied for 24 h consecutively., Results: There was no deterioration of the impedance signal with time and no tracheal injury from the ECOM electrodes. There is a linear relationship between the ECOM and transit time flow probe CO between 0 and 15 l/min (slope = 0.94; intercept = 0.15 l/min; R2= 0.77). The mean difference between the two measures (bias) is 0.15 l/min and the SD is 1.34 l/min. The limits of agreement are -2.53 to 2.82 l/min., Conclusion: Endotracheal CO monitor is a promising technology that needs further evaluation in clinical trials.

Partial ventriculectomy (PV) has been proposed by Batista and colleagues to improve cardiac function in patients with dilated cardiomyopathy (DCM); however, results have been mixed. We tested the hypothesis that preoperative diastolic function affects the stroke volume/end-diastolic pressure (Starling) relationship after PV. A previously described finite element simulation of DCM and PV was used. Diastole and end systole were represented by separate elastic finite element models with different unloaded shapes and nonlinear material properties. Left ventricular (LV) end-systolic elastance (E(ES)), diastolic compliance (DC), and Starling relationships were calculated. DC was varied by changing Ogden material property alpha(i) from 12 (compliant) to 20 (stiff). PV was simulated at 20% LV mass reduction. The slope of the Starling relationship increased from 1.82 to 1.21 as alpha(i) increased from 12 to 20. Partial ventriculectomy increased the Starling relationship in each case from 1.34 to 1.01 respectively. However, the net result in each case is a decrement in the Starling relationship with resection, and the smallest decrement was associated with the highest diastolic stiffness (alpha(i) = 20). Partial ventriculectomy depressed the Starling relationship for all values of diastolic compliance. It is expected that patients with a higher diastolic stiffness should do better.

Objective: The success of left ventricular aneurysm plication depends on how the procedure affects both end-systolic elastance and diastolic compliance and how those changes affect ventricular function (stroke work/end-diastolic volume [PRSW] and stroke volume/end-diastolic pressure [Starling] relationships)., Methods: Five male Dorsett sheep were surgically instrumented with coronary artery snares, an inferior vena caval occluder, and an ascending aortic ultrasonic flow probe. One week later an anteroapical myocardial infarction was produced by tightening the coronary snares. Ten weeks after myocardial infarction, the left ventricular aneurysm was plicated. Absolute left ventricular volume was measured by long-axis transdiaphragmatic echocardiography, and relative changes in left ventricular volume were measured with a conductance catheter. End-systolic elastance, diastolic compliance, PRSW, and Starling relationships were measured immediately before myocardial infarction, 10 weeks after myocardial infarction (immediately before plication), and immediately after and 6 weeks after aneurysm plication., Results: After plication, end-diastolic and end-systolic left ventricular volumes return to preinfarction values. The slopes of end-systolic elastance, diastolic compliance, and PRSW decrease 10 weeks after myocardial infarction, increase with aneurysm plication, and then decrease 6 weeks after aneurysm plication. The Starling relationship undergoes a downward parallel shift with aneurysm plication., Conclusion: Aneurysm plication abruptly decreases left ventricular volume and diastolic compliance, increases end-systolic elastance and PRSW, but decreases the Starling relationship. The net effect on left ventricular function is mixed. Furthermore, left ventricular remodeling 6 weeks after aneurysm plication causes left ventricular volume, end-systolic elastance, diastolic compliance, PRSW, and the Starling relationship to return to preplication values.

Background: Nitric oxide-dependent factors (serotonin, activated platelets, acetylcholine) cause vasodilation in normal coronary arteries but vasoconstrict atherosclerotic vessels. This experiment tested the hypothesis that intravenous systemic infusions of L-arginine, a precursor for nitric oxide production, dilate the coronary vascular bed of patients undergoing coronary artery bypass graft surgery., Methods: Twenty patients scheduled for coronary artery bypass graft surgery surgery were studied in a prospective, blinded, randomized clinical trial. Saphenous vein graft blood flow was measured with a transit time flow probe, and coronary vascular resistance was calculated. After weaning from bypass, patients were given a venous infusion (placebo or 10% arginine hydrochloride [30 g]) over 15 min. Arterial blood samples for the determination of L-arginine and L-citrulline levels were drawn before, 10 min after starting infusion, and 10 min after end of infusion., Results: The placebo group experienced an increase in mean arterial pressure and coronary vascular resistance and a decrease in graft blood flow. Patients in the L-arginine group maintained their baseline values. Mean arterial pressure (L-arginine, 88+/-17 to 92+/-13 mmHg vs. placebo, 80+/-12 to 92+/-9 mmHg, P = 0.021), coronary vascular resistance (L-arginine, 97,000+/-60,000 to 99,600+/-51,000 dynes x s x cm(-5) vs. placebo, 81,000+/-69,000 to 117,000+/-64,000 dynes x s x cm(-5), P = 0.05), and graft blood flow (L-arginine, 55+/-25 to 50+/-19 ml/min vs. placebo, 60+/-34 to 46+/-18, P = 0.05) remained more stable in the L-arginine-treated patients., Conclusions: Systemic L-arginine infusion reduced postbypass coronary vasoconstriction. There were no adverse events associated with the drug infusion.

Objectives: Ventricular volume reduction surgery has been proposed by Batista to improve cardiac function in patients with dilated cardiomyopathy. However, limited clinical data exist to determine the efficacy of this operation. A finite element simulation is therefore used to determine the effect of volume reduction surgery on left ventricular end-systolic elastance, diastolic compliance, stroke work/end-diastolic volume (preload recruitable stroke work), and stroke work/end-diastolic pressure (Starling) relationships., Methods: End-diastole and end-systole were represented by elastic finite element models with different unloaded shapes and nonlinear material properties. End-systolic elastance, diastolic compliance, preload recruitable stroke work, and Starling relationships, as well as energy expenditure per gram of unresected myocardium, were calculated. Two different types of volume reduction surgery (apical and lateral) were simulated at 10% and 20% left ventricular mass reduction., Results: Ventricular volume reduction surgery causes diastolic compliance to shift further to the left on the pressure-volume diagram than end-systolic elastance. Volume reduction surgery increases the slope of the preload recruitable stroke work relationship (dilated cardiomyopathy 0.006 J/mL; 20% lateral volume reduction surgery 0.009 J/mL) but decreases the slope of the Starling relationship (dilated cardiomyopathy 0.028 J/mm Hg; 20% lateral volume reduction 0.023 J/mm Hg). For a given amount of resection, lateral volume reduction has a greater effect than apical volume reduction. Ten-percent and 20% lateral volume reduction reduces energy expenditure by 7% and 17%, respectively., Conclusion: Ventricular volume reduction surgery shifts end-systolic elastance and diastolic compliance to the left on the pressure-volume diagram. The net effect on ventricular function is mixed. Volume reduction surgery increases the slope of preload recruitable stroke work, but increased diastolic compliance causes a small decrease in the Starling relationship (3 mm Hg difference between dilated cardiomyopathy and volume reduction surgery at stroke work = 0.5 J).

The direct effects of vasopressin on the resistance and capacitance properties of the pulmonary and systemic vasculature were studied in nine aneural dogs on systemic and pulmonary bypass. The systemic and pulmonary pressure-flow, the systemic and pulmonary arterial pressure-volume, and the systemic and pulmonary venous pressure-volume relationships were determined for five levels of infused vasopressin. Vasopressin levels of approximately 10, 30, 150, 300, and 500 pg/ml were achieved by intravenous infusions. Samples of venous blood were drawn before and after each set of pressure-flow and pressure-volume relationships for the determination of vasopressin level by radioimmunoassay. A linear relationship was found between vasopressin level and systemic vascular resistance. Systemic vascular resistance increased 0.072 +/- 0.011 mmHg.kg.min.ml-1 for a change in vasopressin level of 100 pg/ml. Vasopressin did not affect pulmonary vascular resistance or any vascular compliance. High doses of infused arginine vasopressin were necessary to elicit substantial vasoconstriction.

Aflatoxin B 1 was detected, and its identity confirmed, in hypoallergenic milk substitutes composed, among other things, of the following ingredients susceptible to possible aflatoxin contamination: soya protein isolate, soy and coconut oils, cornstarch, and corn syrup. Except for one determination all findings were under 1 ng of aflatoxin/ml of formula at drinking concentration. Manufacturers' reserve samples of soya protein isolate, the ingredient thought to be the most likely source of the aflatoxin, were found to be uncontaminated. Reserve samples of other ingredients were not examined. Because hypoallergenic formula may be the major nutrient of an individual with a metabolic defect at infancy, a vulnerable stage of life, available control measures should be used to avoid aflatoxin-contaminated ingredients.

To study the interference by mycotoxins in protein measurements, solutions of various concentrations of aflatoxin B 1 , citrinin, cytochalasin B, ochratoxin A, patulin, penicillic acid, rubratoxins A and B, T-2 toxin and zearalenone were tested for a positive copper-Folin reaction. Except for T-2 toxin, all mycotoxins tested developed a blue color, characteristic of proteins, in the copper-Folin solution. The Lowry reaction for the mycotoxins was linear over the concentration range of 20-100 μg/ml for most of these toxins. Aflatoxin B 1 and citrinin at 2 μg/ml and zearalenone at 0.5 mg/ml developed a blue color in the copper-Folin solution. The linear relationship between color development and toxin concentration plus high sensitivity makes the copper-Folin reaction a potential analytical method for these toxins but only in the absence of protein or other copper-Folin positive materials.