Carl W. Christensen

Magnesium Sulfate Reduces Myocardial Infarct Size When Administered Before but Not After Coronary Reperfusion in a Canine Model

BACKGROUND The role of magnesium in treating acute myocardial infarction (AMI) has been controversial. Several small clinical trials indicate that magnesium may have a role in treating AMI early, whereas the other results suggest that magnesium is of questionable benefit. METHODS AND RESULTS We looked at the effect of magnesium on infarct size (IS) when given during a coronary occlusion and after reperfusion. Magnesium sulfate (6-mEq bolus plus 2 mEq/h for 5 hours) was given at 15 or 45 minutes of coronary occlusion or 15 minutes of reperfusion. The left anterior descending coronary artery was occluded for 90 minutes, followed by 300 minutes of reperfusion. IS to area at risk (IS/AR) was measured by planimetry after triphenyltetrazolium chloride staining. Collateral myocardial blood flow was measured with radioactive microspheres. The IS/AR ratio in the control group was 52.3 +/- 19.6% compared with 20.5 +/- 11.7% and 21.3 +/- 6.5% at 15 and 45 minutes of occlusion, respectively (P < .05). There were no significant differences in the reduction in IS at 15 and 45 minutes of occlusion. Although there was a reduction in the IS when magnesium was administered during reperfusion (38.2 +/- 13.4%), it was not statistically significant. There was no significant difference in the AR relative to the total left ventricular weight between the four groups. CONCLUSIONS The data suggest that magnesium infusion during a coronary occlusion has a significant benefit in reducing the IS in this model. Magnesium may have a beneficial clinical role in AMI, especially if administered before reperfusion as a bolus followed by a constant infusion.

Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism.

To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood flow and mechanical function and group 2 (n = 18) for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1 ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows were determined at control (predrug) and maximal coronary flow using radiolabeled microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic parameters were also measured at these times. Both drugs produced comparable increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to 4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon infusion into the left anterior descending coronary artery. Papaverine produced significant (p less than 0.05) changes in subendocardial ST segment electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine phosphate (47% decrease), and coronary sinus serum lactate (277% increase) compared with control. In addition, intracoronary papaverine induced an abnormal contractile pattern. No significant changes in any of these parameters (i.e., ST segment, QT prolongation, myocardial creatine phosphate level, or lactate level) were observed with intracoronary adenosine infusions. We conclude that intracoronary adenosine is comparable to papaverine for maximizing coronary blood flow without the deleterious properties observed with intracoronary papaverine.

Regional myocardial blood flow with areperfusion catheter and an autoperfusion balloon catheter during total coronary occlusion

We investigated the ability of two new coronary perfusion catheters to maintain regional myocardial blood flow throughout a 90-minute period of occlusion. In 21 dogs (group I = total occlusion control; group II = reperfusion catheter; group III = autoperfusion balloon catheter) we studied regional blood flow, distal coronary perfusion pressure, infarct size, and red blood cell hemolysis after placement of either catheter into the left anterior descending coronary artery. Regional (microsphere) blood flow showed a reduction in transmural blood flow during occlusion in comparison to baseline values (1.07 +/- 0.12 to 0.81 +/- 0.11 and 1.01 +/- 0.16 to 0.73 +/- 0.08 ml/min subendocardial perfusion for groups II and III, respectively). Comparable changes in blood flow were observed in the subepicardial and midmyocardial regions. Distal coronary perfusion pressures were reduced by 26% and 28% for groups II and III, respectively. Both catheters prevented significant infarction and maintained adequate regional myocardial blood flow throughout the 90-minute period of occlusion without significant complications of clotting or destruction of erythrocytes.

Inadequate subendocardial oxygen delivery during perfluorocarbon perfusion in a canine model of ischemia

Perfusion of the coronary artery distal to an occlusion was performed in 16 canine preparations to compare the mechanical perfusion of autologous blood to the perfluorocarbon fluosol DA, 20% emulsion (FDA-20). Both substances were perfused under similar conditions (30, 60, and 80 ml/min) and regional electrograms, contractility, and coronary perfusion were measured relative to native coronary perfusion. Autologous blood (60 and 80 ml/min) produced a significant increase in regional (epicardial, midmyocardial, and endocardial) and transmural flow, but not in the endocardial/epicardial perfusion ratio. No other significant changes were observed during autologous blood perfusion. In contrast, FDA-20 perfusion resulted in significant ST depression (-1.8 +/- 0.2, -1.7 +/- 0.2, and -1.3 +/- 0.3 mm) at 30, 60, and 80 ml/min, respectively. FDA-20 also induced a significant decrease in distal diastolic coronary pressure and resistance, a significant decrease in the endocardial/epicardial perfusion ratio at all three perfusion rates, and a significant reduction in delivery of O2 to the subendocardium. These results indicate that autologous blood perfusion of the distal coronary artery during occlusion preserves myocardial function to a better degree than does FDA-20.

In vitro assessment of the Milwaukee heart and right to left balance

A new, electrically powered, total artificial heart, the Milwaukee Heart, has been developed. This device is undergoing testing in vitro. The unidirectional motion of the brushless DC motor (BDCM) affords easier motor control and reduces energy demand. Motors with a unidirectional motion have a longer life than those with bidirectional motion. This device requires less power due to the highly efficient mechanical design. It consumes 6.5 W of power at an average flow of 5 L/min into 100 mmHg of mean aortic pressure and 20 mmHg of mean pulmonary pressure. Pumping at 8 L/min it requires 9.6 W of power. The maximum pump flow is 10 L/min and overall efficiency is 20%. A slotted optocoupler is used to determine the position of the pusher plate at the start of left systole. The number of revolutions that the BDCM makes is counted from this position. There are 50 revolutions of the BDCM per stroke (using a 50:1 gear reducer connected to the motor). The position of the pusher plate is determined from the number of BDCM revolutions. Based on where the pusher plate encounters resistance from the bladder, the force on the left pump is increased or decreased. Left to right balance has been achieved by reducing the size of the right pusher plate in conjunction with varying right stroke volume. In vitro tests show that this new, electrically powered artificial heart provides reliable performance and satisfactory hemodynamic results.

Is it possible to perform immediate cardiac assist using untrained latissimus dorsi muscle in a work-rest regimen?

The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.

Intracoronary echo-contrast agents: Abnormalities in myocardial function in a normal and reduced coronary perfusion model in dogs☆

Two-dimensional echocardiography using echo-contrast enhancing agents is a promising technique for evaluating myocardial perfusion. However, the potential deleterious effects of injection of echo-enhancing agents into the coronary circulation have not been well evaluated. We utilized two experimental canine models in which the left anterior descending coronary artery was cannulated and perfused continuously by the left common carotid at normal and reduced coronary flows. Analysis of myocardial function included regional left ventricular systolic function by ultrasonic crystals, subendocardial ST segment shifts, left ventricular dP/dr analysis and measurements of coronary blood flow. One ml of each echo-contrast agent was injected into the left anterior descending coronary artery during normal coronary flow. Echo-enhancing agents included: sonicated 70% sorbitol, 50% dextrose, and 6% dextran, hand-agitated Renografin-saline, and unagitated 0.15% hydrogen peroxide, 20% fat emulsion and oxygenated Oxypherol, a perfluorocarbon compound. Two-dimensional echocardiography determined that all echo-enhancing agents except for 20% fat emulsion and Oxypherol produced good myocardial enhancement. All echo-enhancing agents which produced a good contrast effect did so at the expense of significant reversible contractile abnormalities. Each produced more than a 50% reduction in percent segment shortening. Sorbitol and hydrogen peroxide produced the most severe contractile disturbances. In the normal flow model, sorbitol produced systolic bulging and hydrogen peroxide an 83% reduction in percent segment shortening. Hydrogen peroxide induced systolic bulging in the reduced coronary flow model. Other abnormalities induced by echo-enhancing agents included ST segment shifts and malignant ventricular arrhythmias. Six percent dextran produced a good contrast effect with the least harmful myocardial consequences.

A study of the contractile force and fatigue resistance of the latissimus dorsi muscle of growing lambs

In adult organisms, when stimulation of skeletal muscle is stopped, all changes revert to control after 10–14 days. This is the reason that training of the skeletal muscle before cardiomyoplasty is not done. We hypothesized that the muscle of a growing organism would not revert during a delay. Four lambs received 8 weeks of electrical stimulation of the left latissimus dorsi muscle (LDM) with the right LDM as control. Contractility force and positive and negative dF/dt were measured after 8 weeks conditioning, 2 weeks delay, and control. Conditioned muscle during a 30-minute fatigue test had decreased contractile force on an average of 7±2%; control muscle had decreased contractile force on an average of 39±4%; and after 2 weeks delay, there was a decrease in the contractile force of 12±2%. A stronger fatigue test was performed after 10 minutes of rest. Conditioned muscle lost an average of 15±5% of their contractile force, 16±2% positive dF/dt, and 14±2% negative dF/dt. Control muscle lost 40±3%, 39±4%, and 42±5%, respectively. After 2 weeks delay, previously conditioned muscle showed the following decreases: contractile force 21±3%, positive dF/dt 19±3%, and negative dF/dt 16±3%. Skeletal muscle biopsies were also taken and levels of lactate dehydrogenase (LDH) fractions were measured. LDH fractions one and two (LDH-1 + 2) after 8 weeks conditioning consisted of 6.7±1.9% (p<0.05 vs control) of total LDH, 7.2±1.5% (p<0.05 vs control) after 2 weeks delay, and 2.5±0.9% in control muscle. LDH-5 levels decreased to 77±8%, 68±3%, and 91±5%, respectively. Percent of mitochondrial area on conditioned muscle increased and remained elevated after the delay. There was good correlation between fatigue resistance in conditioned and delay muscles with decreasing total units LDH, decreasing LDH-5, and increasing LDH-1 + 2 levels (compared with control muscle). Contractile force, LDH, and mitochondrial data in the delay muscle more closely resemble conditioned muscle than control. This may be very useful for clinical congenital heart surgery.

Echocardiographic Contrast in Two-Dimensional Echocardiography: New Applications for an Old Technique?

Although Gramiak and Shah1 first introduced the technique of using contrast enhanced two‐dimensional echocardiography in 1968, it has seen a resurgence of new and varied applications. Three of the areas of interest are in the use of microbubble enhanced contrast agents to evaluate: (1) regional myocardial blood flow; (2) regional myocardial function; and (3) myocardial ischemic areas and infarct size. Whether these new approaches will have applications and value in the clinical laboratory is still a matter of conjecture. The objective of this review is to briefly summarize the potential uses and the advantages and disadvantages of each application.