Anthony Fernandez

Retrograde-delivered cardioplegia is not distributed equally to the right ventricular free wall and septum

Right ventricular myocardial protection during cardiac surgery continues to be a challenge. Retrograde delivery of cardioplegia has been shown to perfuse left ventricular regions subtended by critical coronary stenosis and not adequately protected by antegrade delivery. However, the distribution of cardioplegia from the coronary sinus to the right ventricle remains in question. A reliable means for assessing such flow distribution intraoperatively is provided by contrast echocardiography. It was hypothesized that conventional use of coronary sinus catheters for retrograde cardioplegia delivery does not reliably perfuse the myocardial region subtended by the right coronary artery. Six patients scheduled to undergo elective coronary artery bypass surgery were evaluated with contrast echocardiography to determine the distribution of retrograde-delivered cardioplegia into the right ventricle. Sonicated Renografin-76 (Squibb Diagnostics, Princeton, NJ) was injected during retrograde delivery of cold crystalloid cardioplegia solution and continuous two-dimensional ultrasound imaging of the heart. On-line videodensitometric analysis was performed with a digital ultrasound system. The area under the curve and peak pixel intensity were determined for the anterior septum, the posterior septum, and the right ventricular free wall for each contrast injection. Recorded VHS videotape images of contrast-enhanced perfusion patterns were also reviewed and scored. On-line acoustic-densitometric analysis showed that right ventricular posterior and anterior septal peak pixel intensities were 4.8 ± 3.2 and 7.3 ± 1.5, respectively, compared with only 1.6 ± 1.2 ( P ≤ 0.05) in the right ventricular free wall. Visual assessment of contrast enhancement within the identical regions of interest showed similar results. It is concluded that retrograde-delivered cardioplegia through a balloon-tip coronary sinus catheter does not reliably perfuse the right ventricular free wall. If right ventricular protection is a clinical priority, other techniques should be employed to ensure optimal preservation during ischemic arrest.

Interference Between the PHA-4 and PEB-1 Transcription Factors in Formation of the Caenorhabditis elegans Pharynx

PHA-4 is a forkhead/winged helix transcription factor that acts as an organ identity factor in the development of the Caenorhabditis elegans pharynx. PEB-1 is a novel DNA-binding protein also involved in pharyngeal morphogenesis. PHA-4 and PEB-1 bind at overlapping sites on the C183 sequence element that controls pharynx-specific expression of the C. elegans myo-2 gene. It has been suggested that PHA-4 and PEB-1 act cooperatively on the C183 sequence. In this study, we test this model and assess the C183-dependent transcriptional activity of PHA-4 and PEB-1, both individually and in combination. We show that PHA-4 and PEB-1 are both modest transcriptional activators in yeast but that co-expression of the two factors does not result in significantly increased expression of a C183-regulated reporter gene. Electrophoretic mobility-shift assays provide no evidence for the formation of a PHA-4/PEB-1 complex in vitro but rather show that PHA-4 and PEB-1 cannot bind C183 simultaneously. As we have reported previously, ectopic expression of PHA-4 in C. elegans causes ectopic expression of a C183-regulated reporter gene. We show that ectopic expression of PEB-1 cannot cause ectopic expression of the same reporter but rather ectopic PEB-1 inhibits reporter gene activation by PHA-4. Overall, our results do not support a model in which PHA-4 and PEB-1 synergize in vivo but rather support a model in which PEB-1 may negatively modulate PHA-4s ability to activate transcription through C183 during formation of the C. elegans pharynx.

Optimizing Albunex in the left ventricle: An analysis of the technical parameters of four ultrasound systems in canines and humans

Albunex, an intravascular ultrasound contrast agent, has been used clinically to enhance echocardiographic images. The purpose of this study if (1) to determine whether varying the settings on commercially available ultrasound machines has an effect on left ventricular opacification after intravenously administered Albunex and if there is an effect on left ventricular opacification and (2) to determine the ideal settings for each ultrasound scanner. Six canine hearts were imaged with 1 ml injections of intravenously administered Albunex while varying the transducer frequency, preprocessing curves, postprocessing curves, and dynamic range on a variety of ultrasound units. Subsequently 50 human subjects underwent imaging with the various machines while the dynamic range and transducer frequencies were altered. All subjects received two or three intravenous injections of 10 ml Albunex. The opacification of the left ventricular cavitary images in both parts of the study were interpreted visually on a scale of 0 to 4 (0 = none, 1 = trace, 2 = moderate, 3 = dense, and 4 = ideal) by four observers. The maximum compression and transducer frequency of 3.5 MHz showed significant improvement of left ventricular opacification in both canines and humans. These studies have shown that (1) varying the ultrasound units parameters affects the quality of left ventricular imaging when Albunex is used to enhance the image, and (2) higher compression and a transducer frequency of 3.5 MHz tend to enhance Albunex images of canine and human hearts.

Assessing Myocardial Perfusion With Albunex During Coronary Artery Bypass Surgery: Technical Considerations and Safety of Aortic Root Injections

OBJECTIVE To test the safety and report on limiting technical considerations, including optimal dosing of Albunex (Molecular Biosystems, Inc, Mallinckrodt Medical, St. Louis, MO) for myocardial opacification after intra-aortic root injections during cardiac surgery. DESIGN This was a prospective randomized study with a control group who did not receive Albunex and a group who received intra-aortic root injections of Albunex. SETTING Multicenter (two) independent university hospitals. PARTICIPANTS 32 patients scheduled for elective coronary artery bypass surgery were evaluated after individual informed consent was obtained. INTERVENTIONS 2 to 8 mL of Albunex were injected before and after coronary revascularization. MEASUREMENTS AND MAIN RESULTS Quality of enhancement in each of four regions of the left ventricle was assessed from a short-axis mid-papillary ultrasound image by three experienced observers blinded to dose. Electrocardiogram (ECG), creatine phosphokinase (CPK) (MB fraction), and hemodynamics were evaluated at baseline and throughout the study period for up to 72 hours. No differences were noted between groups with respect to preoperative and postoperative CPK enzymes (CPK-MB fraction), ECG changes, hemodynamics, requirements for separation from CPB, need for postoperative inotropes, time to extubation, and time to discharge from the intensive care unit. The average total dose of Albunex injected was 19 mL +/- 4 (0.25 mL/kg). A single dose of 4.2 +/- 1.2 mL (0.05 mL/kg) appeared to offer optimal enhancement of contrast effect for myocardial perfusion assessment. CONCLUSION Albunex is safe and easy to use for myocardial opacification when administered via an antegrade cardioplegia catheter into the aortic root during CPB.

Retrograde-Delivered Cardioplegia Is Not Distributed Equally to the Right Ventricular Free Wall and Septum

Right ventricular myocardial protection during cardiac surgery continues to be a challenge. Retrograde delivery of cardioplegia has been shown to perfuse left ventricular regions subtended by critical coronary stenosis and not adequately protected by antegrade delivery. However, the distribution of cardioplegia from the coronary sinus to the right ventricle remains in question. A reliable means for assessing such flow distribution intraoperatively is provided by contrast echocardiography. It was hypothesized that conventional use of coronary sinus catheters for retrograde cardioplegia delivery does not reliably perfuse the myocardial region subtended by the right coronary artery. Six patients scheduled to undergo elective coronary artery bypass surgery were evaluated with contrast echocardiography to determine the distribution of retrograde-delivered cardioplegia into the right ventricle. Sonicated Renografin-76 (Squibb Diagnostics, Princeton, NJ) was injected during retrograde delivery of cold crystalloid cardioplegia solution and continuous two-dimensional ultrasound imaging of the heart. On-line videodensitometric analysis was performed with a digital ultrasound system. The area under the curve and peak pixel intensity were determined for the anterior septum, the posterior septum, and the right ventricular free wall for each contrast injection. Recorded VHS videotape images of contrast-enhanced perfusion patterns were also reviewed and scored. On-line acoustic-densitometric analysis showed that right ventricular posterior and anterior septal peak pixel intensities were 4.8 +/- 3.2 and 7.3 +/- 1.5, respectively, compared with only 1.6 +/- 1.2 (p < or = 0.05) in the right ventricular free wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound Densitometric Analysis: Comparison Between an Online Digital Acquisition Acoustic Program and an Offline Analog Program.

Videodensitometric analysis of myocardial contrast echocardiography is traditionally performed off line. Recently, an online contrast ultrasound analysis system, Acoustic Densitometry (Hewlett‐Packard), was introduced. We compared pixel intensities acquired with Acoustic Densitometry to pixel intensities derived from videodensitometry. A tissue phantom was imaged in phase I using three transducer frequencies (2.5, 3.5, and 5.0 MHz). In phase II, an in vitro flowing tube model with various concentrations of Albunex®was imaged at two flow rates, 0.6 and 1.2 m/sec, and at two transducer frequencies, 2.5 and 3.5 MHz. The relationship between pixel intensities yielded by the two systems for identical ultrasound signals was determined with linear regression. Intensities derived with Acoustic Densitometry strongly correlated with those derived from the offline videodensitometry system. The intensities were related by a predictive multiplicative factor based on display characteristics of the two systems. These results suggest that semiquantitative, online perfusion analysis with Acoustic Densitometry is as sensitive as analysis offline with videodensitometry.