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The influence of megadose methylprednisolone on experimental myocardial infarct size
Abstract:
Prior work in our laboratory demonstrated a significant reduction of infarct size following early or late administration of 30 mg/kg of methylprednisolone sodium succinate (MP). This study was designed to determine the influence of larger doses of MP on infarct volume. Healthy anesthetized mongrel dogs with similar cardiac anatomy underwent ligation of the distal third of the LAD coronary artery. Following ligation, animals were randomly placed into control or treatment groups. Treated dogs received an IV bolus of either 50 mg/kg MP at 15 minutes (MP-50) or 30 mg/kg MP at 15 minutes and 1 hour later (2MP-30). Animals were then monitored for 6 hours, sacrificed, and the heart removed. The left ventricle was dissected from the heart, weighed, sectioned, and incubated in nitro-blue tetrazolium solution, an LDH stain. Unstained tissue (infarct) was dissected from the slices and weighed, and infarct volume was calculated. Among 20 untreated animals the infarct size was 14.5% +/- 4.3% of the left ventricle. Treatment with 2MP-30 or MP-50 significantly reduced infarct volume to a similar degree (9.1%-9.6%). There was no difference in the effect on infarct size by "megadose" MP compared to previous results with one injection of 30 mg/kg MP. Therefore, the early use of MP at doses above 30 mg/kg confers no additional protection to the ischemic myocardium.
Insights
Higher doses of methylprednisolone sodium succinate (MP) do not further reduce infarct size in myocardial infarction models. Early administration of MP at doses exceeding 30 mg/kg offers no additional cardioprotection.
Area of Science:
- Cardiology
- Pharmacology
- Experimental Medicine
Background:
- Previous studies showed methylprednisolone sodium succinate (MP) reduces infarct size.
- The current study investigates if higher MP doses provide enhanced cardioprotection.
Purpose of the Study:
- To determine the effect of increased methylprednisolone sodium succinate (MP) doses on myocardial infarct volume.
- To compare the efficacy of MP "megadoses" against established therapeutic levels in a canine model of myocardial infarction.
Main Methods:
- Mongrel dogs underwent LAD coronary artery ligation to induce myocardial infarction.
- Animals received either a single 50 mg/kg MP dose (MP-50) or two 30 mg/kg MP doses (2MP-30).
- Infarct volume was quantified using nitro-blue tetrazolium staining and weighing of unstained tissue.
Main Results:
- Untreated control animals exhibited an average infarct size of 14.5% +/- 4.3%.
- Both MP-50 and 2MP-30 treatments significantly reduced infarct size to 9.1%-9.6%.
- No significant difference in infarct reduction was observed between "megadose" MP and previously established 30 mg/kg MP doses.
Conclusions:
- Early administration of methylprednisolone sodium succinate (MP) at doses above 30 mg/kg does not provide additional protection against myocardial infarction.
- Current therapeutic strategies using MP for acute myocardial infarction should adhere to established dosage guidelines.