Michelle A. Rieder

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.

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.

Comparison of Different Regimens of Electrical Stimulation Applied to Nonmobilized and Newly Mobilized Latissimus Dorsi Muscle

Abstract We investigated the possibility of preventing further aggravation of muscle ischemia and necrosis in newly mobilized, unconditioned latissimus dorsi muscle (LDM) by utilizing short increments of stimulation with intervening rest periods. Adult St. Croix sheep (N = 12) weighing 30 ± 8 kg were used in this study. Fatigue tests (30 min) using different stimulation regimens before and after LDM mobilization were performed on all animals; the length of time to return to baseline levels was also measured. Our investigation yielded results that contradict the conventional wisdom that any electrical stimulation damages newly mobilized LDM and will cause a considerable decrease in contractile force (CF). Stimulation regimens using continuous contractions at 30 and 60 contractions per minute (CPM) for 30 minutes were damaging to the LDM. CF also dropped significantly and returned slowly to baseline values: at 60 CPM, CF dropped to 50 ± 4% and did not return to baseline even after 90 minutes of rest; at 30 CPM, CF dropped to 61 ± 4% and baseline was restored after 80 minutes of rest. Electrical stimulation using continuous contractions at a slower rate (15 CPM) was tolerable, although a 23% decrease in CF was noted (p < 0.05 when compared to 60 CPM). These results did not satisfy us that such a regimen would be useful for cardiac assistance immediately after cardiomyoplasty. The work‐rest regimen at 30 CPM also gave poor results: CF decreased to 75 ± 2% and baseline was restored after 80 minutes of rest. Promising results were seen when utilizing a work‐rest regimen at 15 CPM. The newly mobilized LDM showed no visible signs of fatigue: CF decreased minimally to 92 ± 3% (p < 0.05 when compared to 30 CPM), and light microscopic analysis of biopsies revealed no morphological damage exceeding that typically seen after subtotal mobilization. Such results open avenues for future investigations: beginning electrical stimulation immediately after cardiomyoplasty (using a single impulse and a slow rate of contraction); decreasing the length of time necessary to obtain full cardiac assistance; and beginning partial cardiac assistance immediately after cardiomyoplasty (if needed) for approximately 30 minutes several times a day.

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.

Age related skeletal muscle response to electrical stimulation.

We hypothesized that the conditioned muscles of elderly and growing organisms have different responses to electrical stimulation from that of young adult organisms. Five day old lambs, 1 year old sheep, and 8 year old elderly sheep were used for this investigation. The latissimus dorsi muscle (LDM) was partially mobilized and left in situ. Two electrodes were implanted and electrical stimulation (ES) was begun for 8 weeks; it was then stopped for 2 weeks. Biopsies were taken before ES, after 8 weeks of ES, and after the 2 week delay period. The LDM of old sheep has less fatigue resistance than the LDM of younger animals. Conditioned LDM of the lamb continued to be fatigue resistant after a 2 week delay compared with adult sheep. In all animals, lactate dehydrogenase (LDH) fraction five decreased and LDH-1 + 2 fractions increased after ES. After a 2 week delay, the data returned to baseline values only in adult animals. The percentage area occupied by mitochondria in old sheep was less after ES than in younger animals. In all animals, the mitochondrial area increased after ES and reverted to baseline values after the delay. The number of nuclei and fibers considerably increased after ES. Only in the lamb did the number of nuclei and fibers continue to be elevated after the delay. There are more changes in young skeletal muscle than in adult (1 year or 8 year old) muscle during ES, and they “remember” these properties. Elderly skeletal muscle does not convert to a fatigue resistant state as completely as adult skeletal muscle during a conventional 8 week ES protocol. It is necessary to change and prolong the ES protocol for elderly patients.

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.