Effects of Cavitation from Extracorporeal Shock Wave Combined with Sulfur Hexafluoride Microbubble on Myocardial Ultrastructure in Rats.

BACKGROUND: In the present study, the effects of extracorporeal cardiac shock waves combined with different concentrations of sulfur hexafluoride ultrasound microbubbles on myocardial ultrastructure in rats were observed. METHODS: Thirty-six rats were randomly divided into 6 groups: control group (N), extracorporeal cardiac shock wave group, and combined group, i.e., extracorporeal cardiac shock wave combined with different concentrations of sulfur hexafluoride microbubble (0.225 mL/kg/min, 0.45 mL/kg/min, 0.9 mL/kg/min, 1.8 mL/kg/min). The combination of extracorporeal cardiac shock wave combined with sulfur hexafluoride microbubbles of different concentrations had no significant effect on hemodynamic indexes and left ventricular function in rats. RESULTS: There were significant differences in cardiac troponin I (cTnI) and nitricoxide among different groups. Histopathology showed that inflammatory cells infiltrated in the shock wave+microbubble 0.9 and shock wave+microbubble 1.8 groups. The myocardial ultrastructural injury score of shock wave+microbubble1.8 group was significantly higher than that of the N group, shock wave group, shock wave+microbubble 0.225 group, and shock wave+microbubble 0.45 group. The score of shock wave+microbubble 0.9 group was higher than that of the control group (P=.009). Western blot results showed that the expression of vascular endothelial growth factor and endothelial nitricoxide synthase (eNOS) protein in the rats treated with extracorporeal cardiac shock wave combined with sulfur hexafluoride microbubbles of different concentrations was higher than that in the N group and shock wave group, with shock wave+microbubble 0.45 group having the strongest expression. CONCLUSION: Myocardial ultrastructure damage occurs when high concentrations of sulfur hexafluoride microbubbles are present, but a proper concentration of sulfur hexafluoride microbubbles could promote the cavitation effect of extracorporeal cardiac shock waves. Thus combination therapy may become a new paradigm in coronary heart disease, especially contributing to the treatment of refractory angina. Combination therapy may change coronary heart disease treatment, especially for refractory angina.

A comparative study of sono-urethrography using saline, agitated saline, and an ultrasound contrast agent in normal beagles.

Sono-urethrography is a technique used to evaluate the integrity of the urethra utilizing fluid dilation of the urethral lumen. The purpose of this prospective, method comparison, pilot study was to investigate the feasibility of sono-urethrography in male dogs and to compare the quality of the images obtained using three different contrast solutions. The prostatic, membranous, and penile urethra was evaluated using saline, agitated saline, and ultrasound contrast agent (Sonovue) in 10 adult, male Beagles. Visibility of the urethral wall was better with sono-urethrography than with conventional ultrasonography, and the conspicuity of urethra could be assessed using all solutions. Hyperechoic lines created by agitated saline and Sonovue were more useful than anechoic saline in allowing identification of the urethra. Visibility scores for the internal margin of the urethral wall using sono-urethrography were significantly higher with saline and one-minute post agitated saline injection. However, the individual layers of the urethral wall could not be observed, regardless of the contrast solution used. Shadowing created by the pelvic bone deteriorated the window through which the urethra could be visualized, and this could not be overcome using sono-urethrography. The results of this study indicated that sono-urethrography is a feasible option for the visualization of the male urethra in dogs. The authors recommend sono-urethrography using saline or agitated saline infusion to evaluate the urethral wall and lumen. Sono-urethrography using ultrasound contrast agent can be applied to assess the integrity of the urethra by improving its conspicuity.

Contrast-enhanced ultrasound can guide the therapeutic strategy by improving the detection of colorectal liver metastases.

BACKGROUND & AIMS: CT may miss up to 30% of cases of colorectal liver metastases (CRLMs). We assessed the impact of contrast-enhanced ultrasound (CEUS) on the detection of CRLMs and on changes to the therapeutic strategy; additionally, we assessed the accuracy of CEUS in differentiating unclear focal liver lesions (FLLs) compared to staging-CT. METHODS: We prospectively analyzed all patients with newly diagnosed and histologically confirmed colorectal cancer (CRC) at our tertiary gastroenterological center between December 2015 and May 2019. CEUS was performed in a total of 296 patients without CRLMs after staging-CT using the contrast agent (SonoVue®). Standard of reference was obtained by MRI or histology to diagnose CRLMs missed by CT. Benign FLLs were confirmed by MRI or follow-up CT (mean follow-up interval: 18 months). RESULTS: Eight additional CRLMs were detected by CEUS (overall 2.7%; sensitivity 88.9%, specificity 99.0%, positive predictive value 100%, negative predictive value 99.6%). All patients with CRLMs detected only by CEUS were in tumor stage T3/T4 (4.0% additionally detected CRLMs). The number needed to screen to detect 1 additional CRLM by CEUS was 37 in all patients and 24.5 in T3/T4-patients. When results were reviewed by a board-certified radiologist and oncologist, the therapeutic strategy changed in 6 of these 8 patients. Among the 62 patients (20.9%) with unclear FLLs after staging-CT, CEUS determined the dignity (malignant vs. benign) of 98.4% of the FLLs. CONCLUSION: Overall, CEUS detected 2.7% additional CRLMs (including 4.0% in tumor stage T3/T4) with a significant impact on the oncological therapeutic strategy for 75% of these patients. Patients with tumor stage T3/T4 would particularly benefit from CEUS. We propose CEUS as the first imaging modality for CT-detected lesions of unknown dignity. LAY SUMMARY: In patients with newly diagnosed colorectal cancer, contrast-enhanced ultrasound (CEUS) detected additional liver metastases after computed tomography (CT). In the majority of these patients, the oncological therapy was changed after obtaining the CEUS results. After staging-CT, 21% of hepatic lesions remained unclear. In these cases, CEUS was accurate to either reveal or exclude liver metastasis in nearly all patients and could reduce costs (e.g., number of MRI scans).

Contrast-enhanced Ultrasound (CEUS) vs contrast-enhanced computed tomography for multilocular cystic renal neoplasm of low malignant potential: A retrospective analysis for diagnostic performance study.

Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) might be benefited from nephron-sparing surgery. Contrast-enhanced computed tomography is used for the diagnosis of MCRNLMP but contrast-enhanced ultrasound has lack of nephrotoxicity and several advantages over contrast-enhanced computed tomography and contrast-enhanced magnetic resonance. The purpose of the study was to compare diagnostic parameters of preoperative contrast-enhanced ultrasound against contrast-enhanced computed tomography for the detection of MCRNLMP in patients who faced curative surgery for complex cystic renal mass.Data regarding contrast-enhanced ultrasound, contrast-enhanced computed tomography, and clinicopathological results of 219 patients who underwent curative surgery for complex cystic renal mass (Bosniak classification III or IV) were retrospectively collected and analyzed. Bosniak classification for imaging modality and the 2016 WHO criteria for clinic pathology were used for detection of MCRNLMP.Contrast-enhanced ultrasound, contrast-enhanced computed tomography, and clinicopathology were detected 68, 66, and 67 as a MCRNLMP respectively. Contrast-enhanced ultrasound and contrast-enhanced computed tomography had 30.37% and 29.27% sensitivities for the detection of MCRNLMP. While 60% and 50% specificities respectively. Bosniak classification III (P = .045) and lower mean Hounsfield unit (P = .049) were associated with the prevalence of MCRNLMP. Contrast-enhanced computed tomography was detected 6 and 7, while contrast-enhanced ultrasound detected 3 and 2 complex cystic renal mass as false positive and false negative MCRNLMP respectively. A contrast-enhanced ultrasound had 0.011 to 1.0 diagnostic confidence and contrast-enhanced computed tomography had 0.045 to 0.983 diagnostic confidence for decision making of nephron-sparing surgeries.Contrast-enhanced ultrasound may have better visualization of MCRNLMP than contrast-enhanced computed tomography.Level of Evidence: III.

Contrast-enhanced voiding urosonography: A new, radiation-free, alternative method for imaging of urinary bladder and urethra in healthy dogs.

Contrast-enhanced voiding urosonography (CE-VUS) has been generally considered as a promising tool to diagnose vesicoureteral reflux and abnormalities in lower urinary tract in human patients, especially in children. The purpose of this prospective study is to evaluate the quality of images of the urinary bladder and urethra obtained by CE-VUS using a second-generation ultrasound contrast agent (SonoVue®) in healthy dogs and to investigate the safety profile of SonoVue® after intravesical administration. Eighty-four CE-VUS examinations with SonoVue® were successfully performed in both unsedated (39/84) and sedated (45/84) dogs. Contrast-enhanced voiding urosonography examination of urinary bladder was technically successful in all (84/84) dogs. The image quality was not considered adequate in five (5/84) dogs including three dogs in whom layering of contrast media during filling phase was observed and two dogs with premature destruction of microbubbles. In these five dogs, the problem was readily recognized and corrected such that the procedure was still successfully undertaken. The assessment of the urethra during spontaneous micturition was successfully performed in all (84/84) dogs in whom voiding was elicited during the examination. No side effects were observed after intravesical application of SonoVue®. This study demonstrates that CE-VUS is a feasible and valuable technique to evaluate low urinary tract morphology and function in dogs. Based on our review of the literature, there are no published reports about the use of this method in dogs.

miR­378 in combination with ultrasonic irradiation and SonoVue microbubbles transfection inhibits hepatoma cell growth.

Ultrasonic microbubbles in combination with microRNA (miRNAs/miRs) exhibited promising effects on cancer treatments. The aim was to investigate the role of miR­378 in hepatoma cells and the efficiency of it in combination with ultrasonic irradiation and SonoVue® microbubbles method for cell transfection. HuH­7, Hep3B and SK­Hep1 cells were transfected with an miR­378 mimic using only Lipofectamine® 3000 or combined with SonoVue microbubbles and ultrasonic irradiation at 0.5 W/cm2 for 30 sec. mRNAs and protein levels of Cyclin D1, Bcl­2, Bax, Akt, p53 and Survivin were detected by reverse transcription­quantitative PCR and western blotting, respectively. Cell survival rate, proliferation, cell cycle and apoptosis were determined by Cell Counting Kit­8, cell double cytochemical staining and flow cytometry, respectively. It was found that using a combination of ultrasonic irradiation and the SonoVue microbubbles method increased the effectiveness of miR­378 transfection into hepatocellular carcinoma (HCC) cells, and increased the inhibition of cell survival and proliferation. Moreover, miR­378 increased the rate of apoptosis and upregulated the expression of Bax and p53, and suppressed the cell cycle and downregulated the expression of Cyclin D1, Bcl­2, Akt, ß­catenin and Survivin much more effectively in the HCC cell line by applying the combined method. Thus, miR­378 was shown to be a suppressive factor to reduce proliferation and increase apoptosis in HCC cells. Additionally, the combination of ultrasonic irradiation and SonoVue microbubbles method was more efficient in the transfection of miRNA.

Duration of room air tamponade after vitrectomy.

PURPOSE: To evaluate the duration of room air tamponade and its associated factors. STUDY DESIGN: Retrospective cohort study METHODS: The present study reviewed the medical records of patients who received room air tamponade after vitrectomy between Jun 2015 and Dec 2016. The room air duration was assessed by patient interviews 2 weeks after surgery. Relationships between the variables and tamponade duration were determined using logistic regression analysis. The remaining air level was determined from medical records. RESULTS: The room air tamponade had dissipated by 11.1 ± 1.3 days after surgery. The duration was 11.2 ± 1.3 days for eyes with a spared posterior capsule, longer than the duration in other eyes (10.1 ± 0.9 days). Increased axial length was correlated with increased duration. Axial length and a spared posterior capsule were significantly correlated with tamponade duration. Its half-life was presumed about 3.3 days. The room air seems to be absorbed at a constant rate. CONCLUSION: The data suggest that room air tamponade remains in the vitreous cavity for an average of 11.1 days. Axial length and posterior capsule status were associated with duration.

Use of contrast-enhanced ultrasonography in the diagnosis of a liver lobe torsion in a rabbit (Oryctolagus cuniculus).

A 1-year-old male French Lop rabbit (Oryctolagus cuniculus) was presented with a sudden onset of hyporexia. Physical examination revealed cranial abdominal discomfort. Liver enzymes were elevated on serum biochemistry profile. Abdominal radiographs showed diffusely gas-dilated small intestinal loops. On abdominal ultrasound, a lobe in the right aspect of the liver was hypoechoic with rounded margins and was surrounded by hyperechoic fat and anechoic fluid. Contrast-enhanced ultrasonography showed complete lack of perfusion in the abnormal right liver lobe. Exploratory laparotomy revealed torsion of the quadrate liver lobe. Diffuse coagulation necrosis was noted on histopathologic examination. The rabbit fully recovered after surgery.

Clinical utility, dose determination, and safety of ocular contrast-enhanced ultrasonography in horses: A pilot study.

OBJECTIVE: To determine efficacy of contrast-enhanced ultrasonography (CEUS) using different sulfur hexafluoride (SF6) doses to assess blood flow and perfusion in equine eyes and to evaluate safety of SF6 in horses. PROCEDURES: Ocular B-mode and contrast-enhanced ultrasonography were performed bilaterally in nine sedated university-owned horses. Intravenous SonoVue® bolus injections of 5, 10, 15, 20, 25, and 30 mL were administered for 2/18, 5/18, 6/18, 3/18, 1/18, and 1/18 eyes, respectively. Doses were increased based on ascending bodyweight. Each eye within one horse was examined utilizing a different dose. Qualitative blood flow and quantitative perfusion were analyzed. Heart and respiratory rates were monitored nonsedated, sedated, and during first and second minutes of CEUS. RESULTS: Qualitative contrast enhancement (CE) was visible in 7/9 animals. Quantitative CE was measurable bilaterally in four horses, unilaterally in three individuals, and not detected in two animals. In all horses with unilateral CE, the positive eye received the higher dose. Fifteen mL dose resulted in significantly shorter time to peak than 10 mL (P < .05). Peak intensity, maximum signal increase, and corresponding area under the curve were significantly higher for 15 and 20 mL doses compared with 10 mL (P < .05). Uveal and retinal tissues were enhanced frequently. Twenty-five and 30 mL doses revealed no CE. Only sedation reduced heart rates significantly (P < .05). Clinically relevant changes in respiratory rates or adverse reactions following SF6 application were not observed. CONCLUSIONS: Contrast enhancement was in most instances dose-dependent. Fifteen mL appeared appropriate to assess equine ocular perfusion. The reliability in horses remains questionable; however, CEUS was well-tolerated.

[Use of contrast-enhanced ultrasound for assessment of the state of femoropopliteal bypass graft anastomoses]. / Primenenie kontrastnoi sonografii dlia otsenki sostoianiia anastomozov bedrenno-podkolennykh shuntov.

Analysed herein is the experience of the first eight ultrasonographic studies of peripheral arteries with dynamic contrast enhancement using sulphur hexafluoride («SonoVue¼) carried out in patients after previously performed femoropopliteal bypass grafting with a synthetic prosthesis (in seven cases the distal anastomosis of the bypass graft was located below the fissure of the knee joint and in one case - above the fissure of the knee joint). Contrast-enhanced ultrasonography was performed averagely 12.5±4.0 months after the operation, according to the technique recommended by the manufacturer of the contrast agent. It was demonstrated that control ultrasonic scanning of lower-limb arteries using contrast enhancement in the remote period after bypass operations proved more informative in relation to detection of stenoses of the distal anastomosis of the femoropopliteal bypass graft, trifurcation of the popliteal artery and near-ostium segments of tibial arteries than a study with no contrast medium.

Effects of RNA interference combined with ultrasonic irradiation and SonoVue microbubbles on expression of STAT3 gene in keratinocytes of psoriatic lesions.

The most effective sequence of small interfering RNA (siRNA) silencing STAT3 of psoriatic keratinocytes (KCs) was screened out, and the effects of the most effective siRNA combined with ultrasonic irradiation and SonoVue microbubbles on the expression of STAT3 of KCs and the dose- and time-response were investigated. Three chemically-synthetic siRNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs, and the effects on STAT3 expression were detected, then the most effective siRNA was selected for the subsequent experiments. The negative controls of siRNA (siRNA-NC) labeled with Cy3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles were transfected into KCs, then the optimal parameters of ultrasonic irradiation were determined. The most effective siRNA carried by Li-pofectamine 3000 combined with ultrasonic irradiation at the optimal parameters and SonoVue microbubbles was transfected into KCs, and the dose- and time-response of RNA interference was determined. The effect of RNA interference by the most effective siRNA at the optimal time and dose carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group) was compared with that only carried by Li-pofectamine 3000 (L group). The results showed that siRNA-3 achieved the highest silencing efficacy. 0.5 W/cm2 and 30 s were selected as the parameters of ultrasonic irradiation. The siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles could effectively knock down the STAT3 expression at mRNA and protein levels in dose- and time-dependent manners determined at 100 nmol/L with maximum downregulation on mRNA at 48 h, and on protein at 72 h after transfection. The LUS group achieved the highest silencing efficacy. It was concluded that siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles could effectively knock down the STAT3 expression in psoriatic KCs, and the optimized transfection condition and the sequence of siRNA-3 could serve for further research on gene therapy of psoriasis.

The combined effect of subcutaneous granulocyte- colony stimulating factor and myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride on post-infarction left ventricular function, the RIGENERA 2.0 trial: study protocol for a randomized controlled trial.

BACKGROUND: Several clinical trials and recent meta-analyses have demonstrated that administration of recombinant human granulocyte-colony stimulating factor (G-CSF) is safe and, only in patients with large acute myocardial infarction (AMI), is associated with an improvement in left ventricular ejection fraction. Moreover, the mobilization and engraftment of the bone marrow-derived cells may differ significantly among patients, interfering with the restoration of left ventricular function after treatment. Therefore, the clinical potential application of the G-CSF has not yet been fully elucidated. METHODS/DESIGN: The RIGENERA 2.0 trial is a multicenter, phase II, placebo-controlled, randomized, open-label, with blinded evaluation of endpoints (PROBE) trial in which 120 patients with an acute ST-elevation myocardial infarction (STEMI) undergoing successful revascularization but with residual myocardial dysfunction will be enrolled. In cases where there is a left ventricular ejection fraction (LVEF) ≤ 45% the patient will be electronically randomized (1:1 ratio) to receive either subcutaneous recombinant human G-CSF (group 1) or placebo (group 2) both added on top of optimal standard of care. Both groups will undergo myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride (MCE) whilst undergoing the echocardiogram. The primary efficacy endpoint is the evaluation of the LVEF at 6 months after AMI assessed by cardiac magnetic resonance. Secondary efficacy endpoints are the evaluation of LVEF at 6 months after AMI assessed by echocardiography, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) assessed by cardiac magnetic resonance and echocardiography at 6 months, together with the incidence of major adverse clinical events (MACE) defined as death, myocardial infarction, sustained cardiac arrhythmias, cardiogenic shock, stroke and re-hospitalization due to heart failure at 1 year. DISCUSSION: The RIGENERA 2.0 trial will test whether G-CSF administration and MCE, through the enhancement of the bone marrow-derived cells homing in the myocardium, determines an improvement in regional and global contractile function, myocardial perfusion and infarct extension in patients with large AMI. The results of the present study are expected to envision routine clinical use of this safe, affordable and reproducible approach in patients with successful revascularization after AMI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02502747 (29 June 2015); EudraCT: 2015-002189-21 (10 July 2015).

Combined effect of ultrasound/SonoVue microbubble on CD4(+)CD25(+) regulatory T cells viability and optimized parameters for its transfection.

The purpose of this study was to investigate the combined effect of ultrasound and SonoVue microbubble on CD4(+)CD25(+) regulatory T cells (Tregs) viability and to explore the appropriate parameters for Tregs transfection. Tregs were separated from peripheral venous blood of patients with hepatocellular carcinoma and seeded in 96-well plates. The optimal ultrasound exposure time and optimal SonoVue microbubble concentration for Tregs were measured by mechanical index (MI) of 1.2 or 1.4, exposure time of 0, 30, 60, 90, 120, 150, 180s, and 0, 10, 20, 30, 40, 50µL/100µL microbubble per well, respectively. In addition, the combined effect of ultrasound and microbubble on Tregs viability was evaluated according to the following parameters: MI 1.2/1.4+exposure time of 120, 150, 180s+0, 10, 20, 30, 40, 50µL/100µL microbubble per well. Tregs viability investigations were performed in order to explore the optimal transfection condition. The efficiency of plasmid transfer was determined by detection of luciferase activity on the microscopic examinations. The proliferation of Tregs could be promoted by ultrasound exposures, while being decreased with the increasing concentration of microbubbles. Under the current experimental conditions, the optimal ultrasound parameters were MI=1.4 and exposure time=150/180s. The optimal microbubble concentration was 10µL/100µL. Compared with treatment with ultrasound or microbubbles alone, the transfection efficiency of Tregs improved 50% by combining ultrasound and microbubble. The results indicate that both ultrasound and microbubble could affect the Tregs proliferation and the optimal Treg transfection rate was obtained by treating with 10% microbubbles and ultrasound exposure for 150/180s under ultrasound MI of 1.4.

Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model.

To elucidate the effects of streaming flow on ultrasound contrast agent (UCA)-assisted drug delivery, streaming velocity fields from sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model. At the beginning of ultrasound sonication, the UCA bubbles formed clusters and translated in the direction of the ultrasound field. Bubble cluster formation and translation were faster with 2.25MHz sonication, a frequency close to the resonance frequency of the UCA. Translation of bubble clusters induced streaming jet flow that impinged on the vessel wall, forming symmetric vortices. The maximum streaming velocity was about 60mm/s at 2.25MHz and decreased to 15mm/s at 1.0MHz for the same acoustic pressure amplitude. The effect of the ultrasound frequency on wall shear stress was more noticeable. Maximum wall shear stress decreased from 0.84 to 0.1Pa as the ultrasound frequency decreased from 2.25 to 1.0MHz. The maximum spatial gradient of the wall shear stress also decreased from 1.0 to 0.1Pa/mm. This study showed that streaming flow was induced by bubble cluster formation and translation and was stronger upon sonication by an acoustic wave with a frequency near the UCA resonance frequency. Therefore, the secondary radiant force, which is much stronger at the resonance frequency, should play an important role in UCA-assisted drug delivery.

Contrast-enhanced ultrasonography of the pancreas in healthy cats.

BACKGROUND: This study describes the pattern of ultrasonographic contrast enhancement of the pancreatic body and left lobe using a second-generation commercial contrast medium (Sonovue) in 10 clinically healthy cats. RESULTS: Following contrast medium administration, microbubbles were observed within the splenic artery. This was followed by an inflow of contrast medium into the pancreatic capillary beds, providing a uniformly contrast-enhanced pancreas at peak intensity (PI). At the time of PI, a replenishment of the splenic and portal veins started and increased progressively during the wash-out phase. During the wash-out phase, the echogenicity of the pancreatic parenchyma decreased progressively. Perfusion parameters included arrival time (4.69 ± 1.26 s), time to peak from injection (7.52 ± 1.88 s), time to peak from initial rise (2.84 ± 0.88 s), peak intensity (6.58 ± 2.66 a.u.), and wash-in rate (2.11 ± 1.79 a.u./s). CONCLUSIONS: This perfusion pattern of normal pancreatic parenchyma may be useful for characterising cats with exocrine pancreatic disorders.

Increased normalized pulmonary transit times and pulmonary blood volumes in cardiomyopathic cats with or without congestive heart failure.

OBJECTIVES: To estimate heart rate-normalized pulmonary transit times (nPTTs) in cardiomyopathic cats with or without congestive heart failure (CHF). To assess potential associations of echocardiographic variables and nPTT and to evaluate nPTT as a test for the presence of CHF. ANIMALS: Forty-eight privately owned cats. METHODS: nPTT was measured using echocardiography and the ultrasound contrast media SonoVue(®) in 3 groups of cats: healthy cats (group 1), cats with cardiomyopathy (CM) but without CHF (group 2), and cats with CM and CHF (group 3). Interrelations between pulmonary blood volume (PBV), nPTT, stroke volume (SV), and echocardiographic variables were investigated by means of linear univariate and multivariate analysis. RESULTS: Median nPTT values in group 1, group 2, and group 3 were 3.63 (interquartile range [IQR], 3.20-4.22), 6.09 (IQR, 5.0-7.02), and 8.49 (IQR, 7.58-11.04), respectively. Values were significantly different between all 3 groups. Median PBVs in group 1, group 2, and group 3 were 27.94 mL (IQR, 21.02-33.17 mL), 42.83 mL (IQR, 38.46-50.36 mL) and 49.48 mL (IQR, 38.84-64.39 mL). SV, PBV, and shortening fraction <30% were significant predictors of nPTT. nPTT and left atrial to aortic root (LA:AO) ratio, not SV, were the main predictors of PBV. CONCLUSION: nPTT may be useful as a test for the presence of CHF in cats with CM and as a measure of cardiac performance. nPTT and LA:AO ratios predict CHF with equal accuracy. Increased PBV is significantly associated with higher nPTT and LA:AO ratios.

Lens subluxation after plasmin and SF6 injections in rabbit eyes.

PURPOSE: To investigate the rate of lens subluxation following plasmin and/or SF6 injections in eyes, and whether a subsequent elevated level of vascular endothelial growth factor (VEGF) and vitreous tap would aggravate subluxation. METHODS: Four groups of rabbits were used. Group 1 received an intravitreal injection (IVI) of plasmin and SF6 in the right eye; group 2 received an IVI of plasmin in the right eye; group 3 received an IVI of SF6 in the right eye; and group 4 received an IVI of balanced salt solution in the right eye. After treatment, IVIs of VEGF were given and vitreous tap was performed three times, followed by clinical observation of lens subluxation and scanning electronic microscope evaluation of the zonular fibers. RESULTS: After IVIs of plasmin and SF6, and VEGF and vitreous tap had been performed one to three times, lens subluxation was noted in 0%, 43%, 71%, 71%, and 86% of the eyes in group 1. After IVIs of plasmin, VEGF, and vitreous tap had been performed one to three times, lens subluxation was noted in 11%, 22%, 44%, 44%, and 67% of the eyes in group 2. The eyes in group 3 and 4 did not show signs of lens subluxation after VEGF IVIs and vitreous tap. Histology confirmed zonular fiber damage in the eyes treated with plasmin. CONCLUSIONS: The incidence of lens subluxation increased following plasmin injections in the eyes, and this was aggravated by the subsequent high VEGF level in the eyes and vitreous tapping. Zonular fibers were disrupted following plasmin treatment. These effects should be kept in mind when using plasmin enzymes in patients with vitreoretinal abnormalities.

Electron spin changes during general anesthesia in Drosophila.

We show that the general anesthetics xenon, sulfur hexafluoride, nitrous oxide, and chloroform cause rapid increases of different magnitude and time course in the electron spin content of Drosophila. With the exception of CHCl3, these changes are reversible. Anesthetic-resistant mutant strains of Drosophila exhibit a different pattern of spin responses to anesthetic. In two such mutants, the spin response to CHCl3 is absent. We propose that these spin changes are caused by perturbation of the electronic structure of proteins by general anesthetics. Using density functional theory, we show that general anesthetics perturb and extend the highest occupied molecular orbital of a nine-residue α-helix. The calculated perturbations are qualitatively in accord with the Meyer-Overton relationship and some of its exceptions. We conclude that there may be a connection between spin, electron currents in cells, and the functioning of the nervous system.