Shyamal Premaratne

High- and low-dose superoxide dismutase plus catalase does not reduce myocardial infarct size in a subhuman primate model

Oxygen free radical scavengers have been found to decrease infarct size in dogs subjected to myocardial ischemia-reperfusion injury. A baboon open-chest model was used to determine if superoxide dismutase (SOD), an oxygen free radical scavenger, together with catalase would be equally effective in subhuman primates (baboons). The left anterior descending coronary artery (LAD) was ligated for 2 hours. Before reperfusion, the animals received the following: Group 1 (low-dose SOD/catalase; n = 5) received 15,000 IU/kg of SOD and 55,000 IU/kg of catalase IV over 1 hour, 15 minutes before reperfusion. Group 2 (high-dose human SOD [h-SOD]/catalase; n = 5) received an intraatrial bolus of 400,000 IU of recombinant h-SOD and 27,500 IU/kg of catalase over 30 seconds, followed by 300,000 IU of h-SOD and 55,000 IU/kg of catalase over 1 hour, beginning 15 seconds before reperfusion. Group 3 (n = 8) were control animals. Baboons were put to death 22 hours after reperfusion. Their hearts were excised and sectioned after the perfusion bed distal to the site of ligation was delineated with microvascular dye. The infarct zone was determined histologically. Areas of the perfusion bed and infarct zone were measured by planimetry. Infarct size did not differ significantly between the three groups: control, 66 +/- 7%; low-dose SOD/catalase, 68 +/- 5%; and high-dose h-SOD/catalase, 74 +/- 4%. In this model, high- and low-dose SOD with catalase did not result in any significant reduction in infarct size.

Effects of perfluorocarbon exchange transfusion on reducing myocardial infarct size in a primate model of ischemia-reperfusion injury: a prospective, randomized study.

BACKGROUND This study was undertaken to test the hypothesis that perfluorocarbons were able to reduce myocardial infarct size in a baboon model of ischemia-reperfusion injury. Exchange transfusion of perfluorocarbons has been shown to reduce myocardial infarct size in the dog, who, unlike the baboon, has an extensive collateral circulation. METHODS After 15 minutes of occlusion of the left anterior descending coronary artery, 14 baboons were bled to attain a hematocrit of 24% to 26% and were simultaneously transfused, six with Fluosol-DA 20% emulsion and eight with FC-43 emulsion. After 2 hours of ligation, the coronary arteries were reperfused. Baboons were killed 24 hours after ligation, and the hearts were excised. Microvascular dye was infused into the coronary artery to delineate its perfusion bed. Ratios of the mean volume of infarct to the mean volume of perfusion bed were calculated and compared by use of planimetry. A similar protocol was followed in two other groups of baboons except that lactated Ringers solution was infused into six of them, whereas eight had no exchange transfusions. RESULTS The ratios of the mean volume of infarct to the mean volume of perfusion bed of the four groups were as follows: Fluosol-DA, 38.1% +/- 7.5%; FC-43, 37.7% +/- 8.3%; lactated Ringers, 46.9% +/- 10.5%; controls, 65.6% +/- 6.9%. Statistical significance was reached when comparing both perfluorocarbon-treated groups with the controls (p < 0.05 for both groups) but not significant when comparing them with the Ringers lactate-treated group. CONCLUSIONS Results suggest that the beneficial effects of exchange transfusion with the perfluorocarbons may be primarily due to hemodilution.

Detection of Hydroxyl free Radicals in the Reperfused Primate Heart

Early reperfusion of an ischemic region can result in significant salvage of the area at risk. We show the presence of hydroxyl free radicals at the time of post ischemia reperfusion using electron paramagnetic resonance (EPR) spectroscopy in a macaque model. These free radicals may be formed as a result of reperfusion or may be an un-involved bystander. It is possible that they may be involved in reperfusion injury.

Identification of DNA adducts at specific locations by sequencing techniques

1. A simple procedure for the accurate identification of the positions of adduct formation when viral M13mp18 single stranded DNA is treated with chloroacetaldehyde (CAA) is presented. 2. The normal dideoxy sequencing reaction protocol was employed except no dideoxy nucleotides were used to cause chain termination. 3. Instead, the CAA adducted bases of the template DNA act as points of polymerase fall off causing the appearance of bands of DNA sequencing gel autoradiographs marking locations where adduct formation may have occurred.

Atrial fibrillation and flutter following coronary artery bypass graft surgery: A retrospective study and review

Introduction and objectives Atrial fibrillation is a common arrhythmia following coronary artery bypass graft surgery. Its incidence can range from 10 to 60% of patients undergoing coronary artery bypass graft. This rhythm can result in shorter or longer intervals between beats. Methods Medical records of 143 patients from the Queen’s Medical Center, Kuakini Medical Center, Saint Francis Medical Center, and Straub Hospital and Clinic, all of which are located in Honolulu, Hawaii were reviewed. An additional 39 records of patients who did not develop these complications were also reviewed as a control group. Patients were selected according to the ICD codes for atrial fibrillation/flutter and coronary artery bypass graft. Both anomalies can lead to increased health care costs, morbidity, and mortality. In this study, possible predisposing factors to these complications were investigated. The time of onset, weight gain, elapsed time, fluid status (in/out), hematocrit, and drug regimens were compared between the two groups. Results The differences in weight gain, fluid status, and hematocrit between the groups were not significant. There were a total of 17 different drugs prescribed to the group as a whole but not every patient received the same regimen. Conclusions Atrial fibrillation and flutter were found to be more common in males, particularly between the ages of 60 and 69 years. There were no other significant findings.

An Evaluation of Streptokinase Therapy in Early Coronary Reperfusion in a Primate Model

Efficacy of streptokinase (SK) administered beyond the period of coronary occlusion with regard to ultimate infarct size and the extent of hemorrhagic infarction was assessed in primates. Eleven macaques underwent coronary occlusion for two hours and were then reperfused. Five of them were given a 2,000 U IV bolus of SK followed by a 10,000 U IV infusion over ninety minutes. The remaining 6 served as controls. Macaques were sacrificed seven days postocclusion. The left ventricle was sectioned parallel to the minor axis, and these were examined histologically for infarct size and hemorrhage. Multiplying the planimetric values by the thickness of the sections yielded the total volumes of left ventricle, infarction, and hemorrhage. The mean percentage of left ventricle involved in infarction in the treated group was not significantly different from the controls (14.06 ± 6.35 versus 16.50 ± 4.67, P > 0.10). SK-treated animals had a significantly greater volume of infarct involved with hemorrhage as compared with controls (27.1 ± 10.8 versus 4.0 ± 1.4, P < 0.05). SK infusions done concurrently with reperfusion following a two-hour occlusion did not result in a significant reduction or increase in the size of infarct. However, SK infusions resulted in a significant increase in the amount of hemorrhagic infarction.

A rare case of hepatic duct injury from blunt abdominal trauma

Background: A 25 year-old male was brought to the emergency room following an apparent suicide attempt by jumping from the fourth floor. Case Report: Patient had a large abdominal laceration in the right upper quadrant (RUQ). CT scan showed a sub-scapular hematoma of the liver. Due to the repeated episodes of hypotension, a laporotomy was performed and the left hepatic artery was ligated while the ductal injury was managed with a Roux-en-Y left hepatic jejunostomy and stent. Bile leakage was resolved post-operatively by day 5 and the patient was discharged home on day 13 after clearance from psychiatry. Conclusions: While non-iatrogenic extrahepatic biliary trauma is rare, a high degree of suspicion is essential, especially in cases like the one discussed in this report. Diagnosis can be difficult in patients undergoing observation.

CHARACTERIZATION OF THE REACTION OF CHLOROACETALDEHYDE WITH SINGLE AND DOUBLE STRANDED DNA

Abstract Chloroacetaldehyde reacts with viral M13mp18 single and double stranded DNA to form the highly fluorescent adducts, etheno-AMP and etheno-CMP. Absorbance and fluorescence spectroscopy can be used to monitor and characterize these reactions. Both single and double stranded DNA showed increases in the absorbance following reaction with the aldehyde. The fluorescence also increased in these two groups and continued to rise with increasing time of incubation until a point of saturation was reached. The fluorescence of the double stranded moiety was considerably enhanced following reaction with the aldehyde while that of the single stranded population was not, making this method appropriate for the separation of small quantities of the two populations of DNA.

Detection of small quantities of double stranded DNA by enhanced fluorescence of substituted aldehyde modified polydeoxynucleotide-ethidium bromide complexes

A method for the detection of small amounts of double stranded DNA by a simple incubation procedure involving the reaction of the nucleotide bases in DNA with chloroacetaldehyde is described. Following incubation, the presence of DNA may be visualized by the orange fluorescence emitted when ethidium bromide (EtBr) is added. Alternatively, the aldehyde/DNA mixture may be separated by agarose gel electrophoresis and individual double stranded DNA visualized by exposing the gel to ethidium bromide and observing the orange ultraviolet light induced fluorescence of the aldehyde modified double stranded ethidium bromide complex (Waring, M.J. (1965) J. Mol. Biol. 13, 269-282). At least a 20-fold increase in the detection of double stranded DNA is possible by this procedure. An important aspect of this method is that the visualization of single stranded DNA is not enhanced.