Robin S. Smith

Magnesium reduces free radicals in an in vivo coronary occlusion-reperfusion model

OBJECTIVE This study demonstrated that magnesium (Mg) reduces free radicals after a brief coronary occlusion-reperfusion sequence. BACKGROUND Magnesium has been shown to reduce infarct size in patients with acute myocardial infarction. We hypothesized that this action of Mg occurs through its action on free radicals. METHODS Eighteen mongrel dogs were studied (nine control, nine receiving Mg). Catheters were placed into the coronary sinus for continuous blood withdrawal. A Varian E-4 electron paramagnetic resonance spectrometer was used to monitor the ascorbate free radical (AFR) signal in the coronary sinus blood; AFR is a measure of total oxidative stress. Occlusion of the left anterior descending coronary artery for 20 min was followed by reperfusion. The study animals received 4 g Mg intravenously starting at 15 min of occlusion (5 min before reperfusion) and continuing during reperfusion. RESULTS Results are presented as percent change from baseline +/- SEM. Magnesium blunted the peak AFR increase: at 4 min of reperfusion there was a 4.7 +/- 3.3% increase in AFR signal in the dogs receiving Mg versus an 18.2 +/- 3.3% increase in the control animals (p < 0.05). Total radical flux was reduced during reperfusion by 53% in the Mg dogs compared with controls (p < 0.05). CONCLUSIONS Magnesium attenuates AFR increase after an occlusion-reperfusion sequence. To our knowledge this is the first in vivo real-time demonstration of Mgs impact on free radicals.

Direct current shocks to the heart generate free radicals: An electron paramagnetic resonance study

OBJECTIVES We sought to demonstrate that direct current (DC) shocks to the heart generate free radicals. BACKGROUND Although it is a lifesaving maneuver, defibrillation is known to have myocardial toxicity. The mechanism of this toxicity is unknown. If DC shocks generate free radicals, free radicals could be a mechanism of myocardial injury. METHODS In a canine model, DC shocks of 10 to 100 J were delivered to the epicardium of both beating and fibrillating hearts, and 200-J transthoracic shocks were administered in dogs with beating hearts. Ascorbate free radical (AFR) concentration was measured in arterial blood and blood continuously withdrawn from the coronary sinus. In some dogs, the antioxidant enzymes superoxide dismutase (15,000 U/kg) and catalase (55,000 U/kg) (SOD/Cat) were administered before shocks. RESULTS Ascorbate free radicals were generated by DC shocks. A peak AFR increase of 14 +/- 2% (mean +/- SEM) was seen 5 to 6 min after 100-J epicardial shocks. A peak AFR increase of 7 +/- 5% occurred after transthoracic shocks. There was a significant linear relation between the shock energy and peak percent AFR increase: %AFR increase = 0.18 (Shock energy) + 2.9 (r = 0.73, p < 0.0001). Shocks delivered to hearts in ventricular fibrillation (30 s) resulted in generation of AFR equal to but not greater than that observed during similar shocks delivered to beating hearts in sinus rhythm. Multiple successive shocks (100 J delivered twice or five times) did not result in a greater AFR increase than single 100-J shocks, indicating that peak, not cumulative, energy is the principal determinant of AFR increase. Animals receiving SOD/Cat before shock administration showed significant attenuation of the AFR increase. CONCLUSIONS Direct current epicardial and transthoracic shocks generate free radicals; antioxidant enzymes reduce the free radical generation by shocks.

Intracardiac echocardiographic imaging of the left ventricle from the right ventricle: Quantitative experimental evaluation

PURPOSE Our purpose was to demonstrate that intracardiac ultrasound imaging from a transducer placed in the right ventricle can be used to quantitatively image the left ventricle in a swine model. BACKGROUND The left ventricles and right ventricles of dogs and human beings have been studied with intracardiac echocardiography. Usually intracardiac echocardiography has been performed with the ultrasound catheter in the chamber being studied because of limited depth of field. Thus left ventricular imaging required that the ultrasound catheter be placed intra-arterially and manipulated into the left ventricle. The availability of lower frequency ultrasound catheters may allow left ventricular imaging from the right ventricle--a more clinically attractive approach. METHODS In 10 closed chest swine, a 10F, 10-MHz ultrasound catheter was placed into the right ventricle through an introducer sheath placed in the right internal jugular vein. Two-dimensional transthoracic echo images were obtained for comparison. Two protocols were used to image global left ventricular function and regional wall motion during pharmacologic challenge. In protocol 1 (n = 4) we evaluated global left ventricular performance in response to interventions: dobutamine, halothane (a myocardial depressant), nitroprusside, and volume loading. In protocol 2 (n = 6) we evaluated regional contraction abnormalities induced by coronary arterial balloon inflation and deflation (reperfusion) and dobutamine. At baseline and after each intervention, global function of the right ventricle and left ventricle was measured as cross-sectional end-diastolic area and end-systolic area, and regional contraction was evaluated as the percentage of left ventricular circumference with a wall motion abnormality. Intracardiac pressures and cardiac output were also measured for comparison. Left ventricular cross-sectional area ejection fractions (area EF) were calculated for both intracardiac and transthoracic echo images as (end-diastolic cross-sectional area - end-systolic cross-sectional area)/end-diastolic cross-sectional area. RESULTS The 10F, 10-MHz intracardiac ultrasound catheter successfully imaged the left ventricle from the right ventricle in all 10 swine. In protocol 1, dobutamine increased area EF from a baseline of 0.60 +/- 0.03 to 0.87 +/- 0.04 (P < .05). When dobutamine was added to the myocardial depressant halothane, left ventricular area EF increased from a baseline of 0.55 +/- 0.03 to 0.68 +/- 0.04. In protocol 2, coronary occlusion resulted in a detectable regional wall motion abnormality (circumferential percentage) of 23% +/- 3%. After reperfusion and during dobutamine stimulation, the wall abnormality decreased to 12% +/- 4%. Transthoracic echocardiography correlated well with these intracardiac findings. CONCLUSIONS The left ventricle can be quantitatively imaged from the right ventricle with the use of a 10F, 10-MHz intracardiac catheter in swine. This system can detect changes in global and regional left ventricular systolic function. This technique warrants evaluation in clinical applications.

Intracardiac Versus Transthoracic Echocardiographic Imaging of Translation and Rotation of Left Ventricular Center of Cavity Area in Dogs

Motion of the left ventricular cavity center during the cardiac cycle was compared using transthoracic and intracardiac echocardiography. Rotation was comparable for the 2 methods, however, translation of the left ventricular cavity area center was greater with intracardiac echocardiography.

Is transthoracic impedance arrhythmia specific? Experimental studies

Transthoracic impedance (TTI) is a major determinant of current flow in defibrillation, and it is therefore important to understand the factors that determine TTI. Our purpose was to evaluate the effect of atrial and ventricular arrhythmias on TTI. In anesthetized, closed-chest dogs we measured TTI by means of a technique previously validated by us, which did not require administration of actual shocks. Measurements were made at baseline (sinus rhythm) and during rapid atrial pacing (atrial fibrillation), rapid ventricular pacing, and electrically induced ventricular fibrillation (VF) with respiration discontinued. TTI was unchanged by rapid atrial or ventricular pacing. When VF was induced and respiration was discontinued, TTI fell immediately from 51.6 +/- 4.3 ohms to 45.6 +/- 4.7 ohms (p < 0.01) and did not change thereafter. The drop in TTI was probably due to respiratory arrest and decreased chest size with full exhalation; when VF was induced but respiration was continued TTI did not change, whereas discontinuing respiration caused TTI to fall even if VF was not induced. We conclude that TTI is not altered by arrhythmias.